ORCID Profile
0000-0002-4812-8957
Current Organisations
Kansas State University Department of Agronomy
,
University of Health Sciences, Lahore
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Publisher: Springer Science and Business Media LLC
Date: 12-08-2019
DOI: 10.1007/S10753-019-01066-2
Abstract: Curcumin is well known for possessing anti-inflammatory properties and for its beneficial effects in the treatment of asthma. Current study investigates the immunomodulatory and anti-inflammatory effects of curcumin using mouse model of ovalbumin-induced allergic asthma. BALB/c mice were immunized with ovalbumin on day 0 and 14 to induce allergic asthma. Animals were treated with two different doses of curcumin (20 mg/kg and 100 mg/kg) and methylprednisolone from day 21 to 28. Mice were also daily challenged intranasally with ovalbumin during treatment period, and all groups were sacrificed at day 28. Histopathological examination showed amelioration of allergic asthma in treated groups as evident by the attenuation of infiltration of inflammatory cells, goblet cell hyperplasia, alveolar thickening, and edema and vascular congestion. Curcumin significantly reduced total and differential leukocyte counts in both bronchoalveolar lavage fluid and blood. Reverse transcription polymerase chain reaction analysis showed significantly suppressed mRNA expression levels of IL-4 and IL-5 (pro-inflammatory cytokines), TNF-α, TGF-β (pro-fibrotic cytokines), eotaxin (chemokine), and heat shock protein 70 (marker of airway obstruction) in treated groups. Attenuation of these pro-inflammatory markers might have led to the suppression of airway inflammation. The expression levels of aquaporin-1 (AQP) and AQP-5 were found significantly elevated in experimental groups which might be responsible for reduction of pulmonary edema. In conclusion, curcumin significantly ameliorated allergic asthma. The anti-asthmatic effect might be attributed to the suppression of pro-inflammatory cytokines, and elevation of aquaporin expression levels, suggesting further studies and clinical trials to establish its candidature in the treatment of allergic asthma.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.BIOPHA.2017.08.101
Abstract: The gut microbiota has a crucial effect on human health and physiology. Hypothyroid Hashimoto's thyroiditis (HT) is an autoimmune disorder manifested with environmental and genetic factors. However, it is hypothesized that intestinal microbes might play a vital role in the pathogenesis of HT. The aim of current was to investigate and characterize the gut microbial composition of HT patients both quantitatively and qualitatively. The fecal s les from 29 HT patients and 12 healthy in iduals were collected. The PCR-DGGE targeted V3 site of 16S rRNA gene and real time PCR for Bifidobacterium Lactobacillus, Bacteroides vulgatus and Clostridium leptum were performed. Pyrosequencing of 16S rRNA gene with V4 location was performed on 20 randomly selected s les. The comparative analysis of ersity and richness indices revealed ersification of gut microbiota in HT as compared to control. The statistical data elucidate the alterations in phyla of HT patients which was also affirmed at the family level. We observed the declined abundance of Prevotella_9 and Dialister, while elevated genera of the diseased group included Escherichia-Shigella and Parasutterella. The alteration in gut microbial configuration was also monitored at the species level, which showed an increased abundance of E. coli in HT. Therefore, the current study is in agreement with the hypothesis that HT patients have intestinal microbial dysbiosis. The taxa statistics at species-level along with each gut microbial community were modified in HT. Thus, the current study may offer the new insights into the treatment of HT patients, disease pathway, and mechanism.
Publisher: Informa UK Limited
Date: 23-12-2016
DOI: 10.1080/09513590.2016.1261103
Abstract: Present study was designed to find out whether leptin is a predictor of bone mass density (BMD) in premenopausal women (PMW) and postmenopausal osteoporotic women (PMOPW) or it has no association with BMD. One hundred and ninety two women (98 PMOPW and 94 PMW) were recruited for this study. The control group was BMI matched with osteoporotic subjects. BMD assessment was done on calcaneus by peripheral ultrasound bone densitometry and T scores were determined. Serum leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). Serum leptin and BMD values were significantly different in both groups (leptin, 18.56 ± 8.65 ng/ml versus 21.64 ± 9.80 ng/ml, p = 0.02) and (BMD, -0.70 ± 0.19 versus -3.17 ± 0.59, p = 0.000), respectively. In PMOPW serum leptin and BMD were considerably correlated with weight (lep, r = 0.53, p = <0.001 BMD, r = -0.21, p = 0.02), BMI (lep, r = 0.52, p = <0.001 BMD, r = -0.27, p = 0.005), waist circumference (lep, r = 0.61, p = <0.001 BMD, r = 0.18, p = 0.04), hip circumference (lep, r = 0.58, p = <0.001). Multivariate linear stepwise regression analysis showed that weight and BMI in PMW and PMOPW were independent predictors of BMD. Serum leptin level was not found to be the predictor of BMD in both groups. The present results indicate that body weight and BMI have an impact on BMD while serum leptin is not associated with BMD in PMW and PMOPW.
Publisher: Springer Science and Business Media LLC
Date: 22-08-2020
DOI: 10.1186/S13063-020-04697-1
Abstract: An amendment to this paper has been published and can be accessed via the original article.
Publisher: Springer Science and Business Media LLC
Date: 11-03-2020
Publisher: Informa UK Limited
Date: 25-11-2014
DOI: 10.3109/13880209.2014.920396
Abstract: Ginger has been used commonly in the traditional system of medicine for the treatment of respiratory disorders. The present study investigates the immunosuppressive activity of ginger by using the mouse model of ovalbumin-induced allergic asthma. Treatment with ethanol extract (500 mg/kg) and aqueous extract (720 mg/kg) of rhizomes, and methylprednisolone (5 mg/kg) was initiated 1 week after second sensitization of mice with ovalbumin and continued for 7 d. RT-PCR followed by gel electrophoresis and ELISA were used for the evaluation of mRNA expression levels and protein levels of Th2 type markers, respectively. Lung tissue histopathology was conducted by using H&E and PAS staining. We observed significant reduction in goblet cell hyperplasia (0.83 ± 0.17 and 1.0 ± 0.26), infiltration of inflammatory cells in airways (0.67 ± 0.33 and 1.0 ± 0.37), and edema with vascular congestion (1.0 ± 0.26 and 1.2 ± 0.17) by both ethanol and aqueous extracts, respectively. A highly significant reduction of total and differential count of eosinophils and neutrophils in BALF, and eosinophil count in blood were also observed. Both extracts significantly inhibited Th2-mediated immune response, which is evident by a decrease in mRNA expression levels of IL-4 and IL-5. Protein levels of IL-4 and IL-5 in BALF, along with total serum IgE levels, were also significantly suppressed by both extracts. Our study validated the traditional use of ginger in respiratory disorders and suggests that ginger reduces allergic airway inflammation, possibly by the suppression of Th2-mediated immune response.
Publisher: MDPI AG
Date: 30-10-2023
Publisher: Ivyspring International Publisher
Date: 2022
DOI: 10.7150/JCA.66816
Publisher: Bentham Science Publishers Ltd.
Date: 03-08-2016
DOI: 10.2174/1389450116666150907104742
Abstract: Oxidative stress plays a key role in the pathogenesis of various diseases. Antioxidants protect the cells and tissues from oxidative stress by scavenging free radicals and reactive oxygen species. These antioxidants may be endogenous or exogenous. Plants are considered as potential and powerful exogenous source of antioxidants. Astragalus species (spp.), especially Astragalus membranaceus, have a long history of medicinal use in traditional Chinese medicine. Specifically, constituents of the dried roots of Astragalus spp. (Radix Astragali) provide significant protection against heart, brain, kidney, intestine, liver and lung injury in various models of oxidative stress-related disease. Different isolated constituents of Astragalus spp., such as astragalosides, flavonoids and polysaccharides also displayed significant prevention of tissue injury via antioxidant mechanisms. In this article, the antioxidant benefits of Astragalus spp. and its isolated components in protecting tissues from injury are reviewed, along with identification of the various constituents that possess antioxidant activity.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.BIOPHA.2018.12.002
Abstract: Oxyresveratrol, an active ingredient of Artocarpus lakoocha, is known to possess anti-inflammatory and immunomodulatory properties. Current study investigates the immunomodulatory effect of oxyresveratrol in mouse model of ethanol-induced ulcer. Anti-ulcer effect was determined using histopathological evaluation (H&E staining) and different tests like, gastric ulcer scoring, ulcer index, total acid secretion, and gastric pH. The mRNA expression levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nuclear factor-kappaB (NF-ĸB), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and trefoil factor 2 (TFF-2) were evaluated using reverse transcription polymerase chain reaction (RT-PCR). The data showed marked percentage inhibition of erosion, hemorrhage, fibrinoid necrosis, inflammatory infiltrate, and ulcer in low (30 mg/kg b.w.) and high dose (50 mg/kg b.w.) groups of oxyresveratrol. Treatment with oxyresveratrol inhibited ulcer score and ulcer index as compared with disease control group. Oxyresveratrol significantly increased gastric pH (P < 0.001) and attenuated total acid (P < 0.001) secretion. RT-PCR analysis showed significant suppression in the mRNA expression levels of IL-6 (P < 0.001), TNF-α (P < 0.01), NF-ĸB (P < 0.001), and COX-2 (P < 0.05) in oxyresveratrol treated groups, while COX-1 expression levels were found unaltered. Treatment with oxyresveratrol significantly elevated (P < 0.01) the expression levels of cytoprotective TFF-2 levels. Similar Immunomodulatory and anti-ulcer effects were found with ranitidine treatment, which was used as a reference drug. In conclusion, oxyresveratrol possess significant anti-ulcer property which might be attributed to attenuated expression levels of IL-6, TNF-α, NF-ĸB, and COX-2 and elevated expression levels of TFF-2.
Publisher: Medknow
Date: 2016
Publisher: Wiley
Date: 28-06-2019
DOI: 10.1002/MGG3.775
Abstract: Insulin resistance (IR), known to reduce the response to insulin action, develops with obesity leading to type 2 diabetes mellitus (T2DM). The PC‐1 gene has been associated with dyslipidemia, polycystic ovarian disease and T2DM in different regions of the world. The objective of the present study was to investigate the genetic association of PC‐1 rs1044498 polymorphism with insulin resistance in type 2 diabetes in the Punjabi population of Pakistan. This s tudy was carried out on 161 healthy controls and 161 patients of T2DM with insulin resistance. Whole blood was collected for DNA extraction and molecular studies. PCR‐RFLP with AvaII was performed to determine the genotype in cases and controls. Chi‐square and Hardy Weinberg analyses were carried out. Statistical analysis was performed by SPSS software. The demographic data of cases and controls showed significant differences for different parameters like glucose, insulin, Homeostatic model assessment‐insulin resistance (HOMA‐IR) and lipid profiles ( p 0.000). Different statistical models revealed that all the dominant models were found associated in between alleles for disease risk ( p 0.001) while no association of PC‐1 rs1044498 (K121Q) polymorphism was found with insulin‐resistant parameters in T2DM cases. Overall, the results indicate that the K121Q polymorphism was not found associated with insulin resistance in type 2 diabetes in a Pakistani Punjabi population. This is the first‐ever report about the genotype of PC‐1 gene in this population.
Publisher: Medknow
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 06-11-2019
Publisher: Springer Science and Business Media LLC
Date: 17-03-2022
DOI: 10.1007/S11033-022-07311-6
Abstract: Carica papaya L. (C. papaya) is used as a folk medicine for the treatment of various diseases throughout the world. Recently, papaya leaves decoction has been effectively used for the prevention and treatment of thrombocytopenia. The current study was undertaken to evaluate the thrombopoietic and immunomodulatory activities of C. papaya leaves in the mouse model of carboplatin induced myelosuppression. Myelosuppression was induced by a single intraperitoneal injection of carboplatin (125 mg/kg b. w.). Aqueous extract of C. papaya leaves (15 mg/kg b. w.) was given orally by feeding tube from day 0-18 to preventive group to see the preventive effect and from day 6-18 to treatment group for treatment effect. The results showed that the C. papaya leaves extract significantly decreased the fall in platelet count in preventive and treatment groups. Extract significantly prevented the fall in total WBCs count on day 12 and 18 in the preventive group, whereas it significantly elevated the WBCs count in treatment group on day 18. Significantly increased RBCs count in both groups was observed on day 18 after treatment with C. papaya leaves extract. Treatment with C. papaya leaves extract significantly upregulated the mRNA expression levels of thrombopoietic cytokine IL-11 in both preventive and treatment groups. It is also observed that restoration of normal platelet count might have been resulted owing to the synergistic effect of upregulated IL-11 which ultimately led to a significantly diminished TPO expression. Our data suggest that aqueous extract of C. papaya leaves possesses significant preventive and curative properties against thrombocytopenia.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BIOPHA.2017.10.162
Abstract: Traditionally, Citrullus lanatus is known to have protective properties in kidney diseases and for having the ability to clear urine. Current study aims to validate the traditional uses of C. lanatus by evaluation of anti-urolithiatic and diuretic activities using in vivo and in vitro experiments. Male Wistar rats were used for in vivo anti-urolithiatic and diuretic activities. Supersaturated solution of calcium and oxalate was used for in vitro crystallization study. Hematoxylin & eosin staining was used for histopathological evaluation of kidney. In the in vivo rat model of urolithiasis, the pulp extract reduced calcium oxalate (CaOX) crystal count in both kidney and urine. The pulp extract also increased the urinary pH and output, and prevented the weight loss. Serum analysis showed elevation in creatinine clearance and reduction in urea and creatinine levels. Urinary analysis demonstrated that pulp extract restored altered phosphate, calcium, oxalate, and citrate levels. In the in vivo rat model of diuresis the pulp extract produced diuresis, reduced serum chloride levels, and elevated urinary sodium and chloride levels. In the in vitro crystallization experiment, pulp extract inhibited the aggregation phase. Seed extract failed to show any convincing results. GC-MS analysis revealed the presence of steroids and alkanes as the major constituents of pulp extract, which might be responsible for anti-urolithiatic activity however, further studies are required for isolation and identification of active constituents. Current study validated the traditional uses of watermelon and demonstrated that pulp extract possessed significant anti-urolithiatic and diuretic activities.
Publisher: Ivyspring International Publisher
Date: 2018
DOI: 10.7150/IJBS.24151
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.RESP.2019.04.005
Abstract: Ziziphora clinopodioides has been frequently used as an anti asthmatic plant in traditional medication. Recent work explores the anti-asthmatic activity of Z. clinopodioides in allergen-induced asthmatic mice. Intraperitoneal sensitization followed by intranasal challenge were given with ovalbumin (allergen) to develop allergic asthma. Investigational groups of animals were administered with drug methylprednisolone (MP) (15 mg/kg body weight), n-hexane fraction, ethylacetate fraction, and methanolic extract of Z. clinopodioides extract (500 mg/kg b.w.) for successive 07 days. Hematoxyline and eosin (H&E) and periodic acid-Schiff (PAS) stains were used to evaluate histopathological parameters on lung tissues. As an index of lungs tissues edema, wet/dry weight ratio of lungs was determined. Evaluation of expression levels of AQP1, AQP5, IL4, and IL5 was conducted by using RT-PCR. The data exhibited that both Z. clinopodioides and MP attenuated differential and total leukocyte counts in hematological examination i.e. in BALF and blood. Treatment with Z. clinopodioides also caused suppression of inflammatory cell infiltration and expression levels of IL4 and IL5, the later could have caused attenuation of pulmonary inflammation. The study also found decline in lung wet/dry ratio and goblet cellh hyperplasia in treated groups which indicates amelioration of lung edema. Treatment with Z. clinopodioides significantly increased the expression levels of aquaporin-1 and -5, which could have led to reduction in lung edema. The treatment with MP showed comparable results to Z. clinopodioides. Current investigation revealed that Z. clinopodioides possessed anti-asthmatic property which might be accredited to upregulagted AQP1 and AQP5 levels and downregulated IL4 and IL5 levels.
Publisher: Springer Science and Business Media LLC
Date: 16-11-2018
DOI: 10.1007/S10787-018-0543-4
Abstract: Clematis orientalis Linn has long been used as ethnopharmacy for the treatment of arthritis. This study is intended to evaluate the curative efficacy of Clematis orientalis in treating polyarthritis in rats. Aqueous ethanolic extract and fractions (hexane, butanol and aqueous) were administered orally at 200 mg/kg for 28 days after CFA immunization. Paw swelling, paw diameter, arthritic score, body weight, hematological parameters, radiographic and histological analysis of ankle joints were evaluated. Moreover, levels of various inflammatory markers through RT-PCR and ELISA were measured. DPPH and reducing power assays were used to appraise antioxidant capacity. Qualitative phytochemical analysis, determination of total phenolic and flavonoid contents were also carried out. Aqueous ethanolic extract and fractions significantly (p < 0.001) reduced paw volume, paw thickness and arthritic score and considerably prevented decrease in body weight along with anomalous alterations in hematological parameters in comparison with arthritic control. X-ray and histological examination revealed no significant structural changes in ankle joints of treated rats. Expression levels of IL-1β, TNF-α, IL-6, COX-2 and NF-Kβ were significantly (p < 0.05-0.001) suppressed as well as noteworthy increase in the levels of IL-4 and IL-10 among treated animals has been detected. Overproduction of TNF-α and PGE2 was substantially prevented in animals given different treatments. Aqueous ethanol extract and its fractions demonstrated significant and concentration-dependent antioxidant potential. In general, among fractions aqueous fraction exhibited a greater anti-arthritic effect. Phytochemical analysis of aqueous fraction confirmed the presence of flavonoids and glycosides, 215.29 mgGAE/ml phenolic content and 633.03 μgQE/ml flavonoid content. Thus, we suggest Clematis orientalis as a potent strategy for the treatment of rheumatoid arthritis.
Publisher: Elsevier BV
Date: 06-2019
DOI: 10.1016/J.JEP.2019.03.019
Abstract: The roots of Ribes orientale (Family Grossulariaceae) have long been used as a folk remedy to treat rheumatism and joints pain in Northern Areas of Pakistan. The purpose of study was to observe the preventive efficacy of roots of Ribes orientale (RO) aqueous ethanolic extract (30:70) and its aqueous and n-butanol fractions in treating rheumatoid arthritis and to determine its possible mechanism of action. Arthritis was evaluated in vitro using heat induced bovine serum albumin and egg albumin denaturation and membrane stabilizing assays at 50-6400 μg/ml concentration of extract/fractions whereas, in vivo arthritis was evaluated at 50, 100, 200 mg/kg doses of extract/fractions in formaldehyde model by measuring rat paw volume/diameter. Moreover, highest effective dose (200 mg/kg) of extract/fractions was evaluated in Freünd complete adjuvant (FCA) model. Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. RO extract/fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) whereas, PGE2 and TNF-α levels in serum s les were measured by Enzyme linked immunosorbent assay (ELISA). Furthermore, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. The anti-oxidant activity of plant extract and fractions was evaluated using DPPH and reducing power assays. In addition, phytochemistry, total phenolic and flavonoid contents, and HPLC analysis of most active fraction (aqueous fraction) were performed. Results showed that RO extract and fractions (notably aqueous fraction) significantly reduced protein denaturation and protected erythrocyte membrane in concentration dependent manner. Similarly, extract/fractions induced dose-dependent decrease in paw volume/diameter in the formaldehyde model. Plant extract and fractions significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, RO extract/fractions downregulated gene expression levels of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α whereas, upregulated those of IL-4 and IL-10, compared with FCA control rats. The radiographic and histopathologic improvement in joint architecture was also observed in RO treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of flavonoids and polyphenols. Results indicated that suppression of pro-inflammatory enzymes/cytokines, inhibition of protein denaturation, lysosomal membrane stabilizing abilities, and redox/free radical scavenging properties of RO extract and fractions support anti-arthritic and immunomodulatory property of Ribes orientale that might be due to its polyphenolic and flavonoid constituents. This suggests that Ribes orientale roots may be used as a therapeutic agent for treating human arthritis.
Publisher: Springer Science and Business Media LLC
Date: 30-12-2023
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BIOPHA.2017.11.118
Abstract: Ziziphora clinopodioides has been used in traditional medicine for its anti-inflammatory properties. Current study is believed to first time report the potential of Z. clinopodioides extracts to ameliorate joint inflammation using model of chronic joint inflammation (FCA-induced rheumatoid arthritis). The study further investigates the effects on joint inflammation using acute inflammatory paw edema models. The anti-inflammatory effects were also supported by using xylene-induced ear edema model. Results showed that Z. clinopodioides significantly ameliorated rheumatoid arthritis as indicated by the inhibition of arthritic development and paw edema. Histopathological examination showed significant attenuation in pannus formation, bone erosion, and joint inflammation. Treatment with the plant extracts also nearly normalized counts of RBCs, platelets, and total leukocytes along with hemoglobin (Hb) content. Biochemical analysis (AST, ALT, urea, and creatinine) showed that plant extracts did not possess hepatotoxic or nephrotoxic effects. Water displacement plethysmometric analysis showed that Z. clinopodioides significantly attenuated carrageenan-induced paw edema. To evaluate the mechanism, anti-inflammatory effects were further evaluated using histamine- and serotonin-induced inflammatory paw edema models. Z. clinopodioides significantly suppressed paw edema induced by both histamine and serotonin, and also caused the inhibition of xylene-induced ear edema. This suggested the inhibition of autacoids as one of the mechanisms of anti-inflammatory effects of plant. GC-MS analysis showed that the plant is rich in essential oils, including terpenoids, esters, alcohols, furans, cyclic ketones, epoxides, oxanes, and acyclic hydrocarbons. In conclusion, current study demonstrated that Z. clinopodioides possessed significant anti-arthritic and anti-inflammatory properties which might be attributed to the inhibition of autacoids.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.CYTO.2015.09.013
Abstract: Oxyresveratrol is known to possess anti-inflammatory property. Current study investigates the immunosuppressive effect of oxyresveratrol by using mouse model of ovalbumin (OVA)-induced allergic airway inflammation. BALB/c mice were randomly ided into five groups having 8 mice in each group. Treatment with low dose (7 mg/kg) and high dose (15 mg/kg) of oxyresveratrol, and methylprednisolone (15 mg/kg standard drug) was started 2 week after immunization of mice with ovalbumin and continued for 7d. Ovalbumin was also injected into pinna of right ear 24h before sacrificing the mice to evaluate delayed type hypersensitivity (DTH). H&E and PAS staining were used for histopathological evaluation of lungs. Reverse transcription polymerase chain reaction followed by gel electrophoresis were used for evaluation of mRNA expression levels of IL-4, IL-5, and IL-13. Oxyresveratrol significantly reduced total leucocyte count in both blood and bronchoalveolar lavage fluid (BALF). Treatment with oxyresveratrol normalized altered eosinophil and neutrophil counts in both blood and BALF. OVA-specific T-cell response was also significantly inhibited by oxyresveratrol. A significant attenuation of inflammatory cell infiltration and goblet cell hyperplasia was observed after treatment with oxyresveratrol. Data showed that oxyresveratrol significantly suppressed Th2 (T helper cells) type immune response which was obvious by the reduction in mRNA expression levels of IL-4, IL-5, and IL-13. Similarly, treatment with methylprednisolone also significantly reduced all the immunomodulatory and inflammatory parameters. Our study demonstrates that oxyresveratrol ameliorates allergic asthma. The anti-asthmatic activity might in part occur via the down regulation of IL-4, IL-5, and IL-13 expression levels.
Publisher: MDPI AG
Date: 12-10-2022
Abstract: The application of polyploidy in sustainable agriculture has already brought much appreciation among researchers. Polyploidy may occur naturally or can be induced in the laboratory using chemical or gaseous agents and results in complete chromosome nondisjunction. This comprehensive review described the potential of polyploidization on plants, especially its role in crop improvement for enhanced production and host-plant resistance development against pests and diseases. An in-depth investigation on techniques used in the induction of polyploidy, cytogenetic evaluation methods of different ploidy levels, application, and current research trends is also presented. Ongoing research has mainly aimed to bring the recurrence in polyploidy, which is usually detected by flow cytometry, chromosome counting, and cytogenetic techniques such as fluorescent in situ hybridization (FISH) and genomic in situ hybridization (GISH). Polyploidy can bring about positive consequences in the growth and yield attributes of crops, making them more tolerant to abiotic and biotic stresses. However, the unexpected change in chromosome set and lack of knowledge on the mechanism of stress alleviation is hindering the application of polyploidy on a large scale. Moreover, a lack of cost–benefit analysis and knowledge gaps on the socio-economic implication are predominant. Further research on polyploidy coupling with modern genomic technologies will help to bring real-world market prospects in the era of changing climate. This review on polyploidy provides a solid foundation to do next-generation research on crop improvement.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.LFS.2021.119825
Abstract: This article has been retracted: please see Elsevier Policy on Article Withdrawal (bout/our-business olicies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief. A reader reported that Figure 9 of the above paper contains similar section with Figure 4 of another article authored by the same group in Inflammopharmacology, 29, (2021) 1119-1129, 0.1007/s10787-021-00840-9, and part of the Figure 9 of the above paper is used in Figure 9 of another article authored by the same group in Inflammopharmacology, 29, (2021) 673–682, 0.1007/s10787-021-00804-z. The journal requested the authors to explain the repeated use of the image and provide the raw data. However, the authors were not able to fulfill this request and therefore the Editor-in-Chief has decided to retract the article.
Publisher: Frontiers Media SA
Date: 09-02-2022
DOI: 10.3389/FPHAR.2022.822671
Abstract: Osteoporosis is a condition in which bone mineral density is reduced due to altered bone microstructure, which results in increased skeletal fragility and incidence of various types of fractures. Adipokines such as chemerin, vaspin, omentin-1 and osteoprotegerin are involved in bone remodeling. The current study was designed to determine the changes in circulating chemerin, vaspin, omentin-1, and osteoprotegerin levels after treatment with oral ibandronate 150 mg in postmenopausal osteoporotic females. The present study enrolled 107 postmenopausal osteoporotic females from a tertiary care hospital in Faisalabad, Pakistan, based on stringent inclusion and exclusion criteria. Sixty-six healthy postmenopausal, non-osteoporotic females with no systemic illness were chosen from the general population. The assessment of bone mineral density (BMD) was done using a DEXA scan. Serum levels of chemerin, vaspin, omentin-1 and osteoprotegerin were estimated using commercially available enzyme-linked immunosorbent assay kits. The collected data were analyzed with the Statistical Package for Social Sciences (SPSS) version 24. Following 6 months of ibandronate treatment, there was a significant decrease of 24.24% ( p & .033) in serum chemerin levels, as well as a significant increase in serum vaspin levels 343.32% ( p & .001) and osteoprotegerin levels 19.57% ( p & .001), with no significant change in omentin-1 levels. Thus, an increase in serum chemerin levels and a decrease in serum vaspin and osteoprotegerin levels could be implicated in osteoporosis.
Publisher: MDPI AG
Date: 29-08-2023
DOI: 10.3390/PHARMACEUTICS15092228
Abstract: Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the treatment of this disease due to the large number of side-effects caused by commercial medicines. In the current study, the antiarthritic potential of methanolic extract (AM-metha), n-hexane (AM-hexa) fraction, and ethyl acetate (AM-etha) fraction of the bark of A. modesta against a complete Freund’s adjuvant rat model was evaluated. Evaluation using a digital plethysmometer, macroscopic evaluation, and histopathological evaluation were conducted to determine the paw volume and arthritic scoring. ELISA was performed to assess the PGE2 levels. RT-PCR was used to evaluate the expression levels of MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF. Biochemical and hematological analyses were also conducted. GC/MS was also carried out to analyze the presence of medicinal compounds. The data revealed a marked reduction in the paw volume, arthritic scoring, and histopathological parameters, indicating the anti-arthritic potential of the plant. Treatment with plant extracts and fractions markedly down-regulated MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF levels. Similarly, PGE2 levels were also found to be ameliorated in the treatment groups, indicating the immunomodulatory property of plant bark. Plant treatment nearly normalized hematological parameters such as counts of WBCs, RBCs, and platelets, along with Hb content, thereby validating the anti-arthritic activity. GC/MS analysis disclosed the presence of strong anti-inflammatory compounds such as lupeol, oleic acid, and squalene. The study showed that A. modesta possesses anti-arthritic and immunomodulatory potential linked to significant down-regulation of pro-inflammatory and inflammatory biomarkers.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.PHYMED.2017.04.009
Abstract: Natural products have a prime importance as an essential source for new drug discovery. Carica papaya leaves (CPL) have been used to treat inflammation in traditional system of medicine. Current study evaluates the anti-inflammatory and immunomodulatory effects of CPL extract using mouse model of ovalbumin- (OVA) induced allergic asthma. All the mice were intraperitoneally sensitized and subsequently given intranasal challenge with OVA except the control group. Group-III and -IV were treated for seven consecutive days with CPL extract and methylprednisolone (MP), respectively. At the end of study, histopathological examination of the lungs was performed and inflammatory cell counts were done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS were measured using reverse transcription polymerase chain reaction (RT-PCR). Results showed significant attenuation of lung infiltration of inflammatory cells, alveolar thickening, and goblet cell hyperplasia after treatment with CPL extract. We also found significant suppression of total and differential leukocyte counts in both blood and BALF s les of CPL extract treated group. CPL extract also alleviated the expression levels of IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS. Similarly, treatment with MP, used as a reference drug, also significantly ameliorated all the pro-inflammatory markers. Current study shows that CPL extract possesses anti-inflammatory effect in mouse model of allergic airway inflammation by down-regulating IL-4, IL-5, eotaxin, TNF-α, NF-ĸB, and iNOS expression levels.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2022
DOI: 10.1007/S10787-022-00930-2
Abstract: Rheumatoid arthritis is primarily associated with inflammation and increased level of proinflammatory cytokines which are released by immune cells, macrophages or activation of arachidonic acid metabolism. The expression of these cytokines, oxidative free radicals and the activation of COX-2 enzymes are crucial targets for chronic inflammation. On the basis of established anti-inflammatory efficacy of nerolidol, the primary study was further appraised to determine its approach against Freund's complete adjuvant (CFA) rheumatoid model. Arthritis was induced by inoculation of 0.1 mL CFA injection into the left hind footpad of rats. Anti-arthritic potential of nerolidol (at 200, 400 and 800 mg/kg doses) was assessed by measuring the paw volume, body weight, serum analysis, histopathological and radiographs of ankle joints. Expressions of cytokine's panels such as IL-10, IL-4, COX-2, NF-kB, TNF-α, IL-6, PGE-2 and IL-1β were determined by real-time qPCR. Antioxidant enzyme analyses were conducted by measuring the SOD, POD and catalase activity from serum and equated with arthritic control group. Nerolidol prevented body weight loss, stabilized biochemical and haematological homeostasis and significantly reduced the paw volume. Furthermore, X-ray and histopathological assessment of ankle joints showed an improvement in the joint structure of rats treated with nerolidol. Besides that, overexpression of gene pointers like TNF-α, IL-1β, IL-6, NF-kB, PGE-2 and COX-2 in CFA-treated control rats were also reversed with nerolidol. This anti-arthritic mechanism was further supported by the increased level of IL-10, IL-4 and serum antioxidant activity. The present findings demonstrate that nerolidol reduced adjuvant arthritis by downregulating the proinflammatory cytokines and upregulating the aforementioned anti-inflammatory cytokines and may be used as a therapeutic substance for the management of human rheumatoid arthritis.
Publisher: American Chemical Society (ACS)
Date: 08-09-2022
Publisher: Pakistan Journal of Medical Sciences
Date: 13-05-2022
Abstract: Background & Objective: This study aimed to assess the clinical effectiveness of Hydroxychloroquine Sulfate (200 mg orally 8 hourlies thrice a day for 5 days), oseltamivir (75 mg orally twice a day for 5 days), and Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in seven groups). Methods & Analysis: An adaptive design is deployed, set within a comprehensive cohort study, to permit flexibility in fast-changing clinical and public health scenario. Primary outcomes include turning the test negative for coronavirus nucliec acid and in bringing about clinical improvement on day 7 of follow-up on a seven-point ordinal scale. The randomized study will recruit participants of either gender above 18 years of age who will test positive for SARS-CoV-2 on Quantitative Reverse Transcription Polymerase Chain Reaction (PCR). Pregnant or lactating females, and those with severe respiratory distress, or with serious comorbidities will be excluded. Randomization will be done maintaining concealment of allocation sequence using a computer-generated random number list. The s le size will be subjected to periodic reviews by National Data Safety and Monitoring Board. Ethics and Dissemination: The trial is approved by the National Bioethics Committee (No.4-87/NBC-471-COVID-19-05/20/) and institutional Ethical Review Committee. This clinical trial conducted under Good Clinical Practice is expected to inform patients clinical guidelines for the use of these drugs in newly diagnosed with SARS-CoV-2. Trial Registration: The trial was prospectively registered on April 08, 2020 at clinicaltrials.gov with ID: NCT04338698 doi: 0.12669 jms.38.5.5512 How to cite this:Azhar S, Akram J, Shahzad M, Latif W, Khan KS. Protocol of Pakistan randomized and observational trial to evaluate coronavirus treatment among newly diagnosed patients with COVID-19: Azithromycin, Oseltamivir, and Hydroxychloquine. Pak J Med Sci. 2022 (5):---------. doi: 0.12669 jms.38.5.5512 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (icenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Hindawi Limited
Date: 05-04-2022
DOI: 10.1155/2022/1695701
Abstract: Juglans regia has been used to treat inflammatory and arthritic disorders in traditional medicine. The present study aimed to investigate the antiarthritic and anti-inflammatory potential of ethanolic leaves extract of J. regia. Arthritis was induced in rodents with Freund’s complete adjuvant. J. regia treatment was started on 8th day of arthritis induction and sustained for 20 days. Acute inflammatory models were developed using carrageenan, histamine, serotonin, and dextran. Qualitative and GC-MS analyses were also performed. Arthritis was determined using an arthritis scoring index and histopathological examination of ankle joints. RT-PCR was performed to determine the expression of pro-inflammatory markers (TNF-α, NF-κB, IL-6, IL-1β, and COX-2) and anti-inflammatory IL-4. PGE2 levels were evaluated using an ELISA. Blood and biochemical parameters were also determined. Paw edema was measured using a digital plethysmometer. Treatment with extracts inhibited arthritic development and attenuated paw edema along with all histopathological parameters. The expression levels of pro-inflammatory cytokines and COX-2 were downregulated, while IL-4 was upregulated. PGE2 levels were also reduced in extract-treated groups. Blood and biochemical parameters were nearly normalized in the treatment groups. Both extracts significantly inhibited carrageenan, histamine, serotonin, and dextran-induced paw edema. Qualitative phytochemical screening and GC-MS analysis confirmed that extracts possessed potential medicinal compounds. In conclusion, ethanol and n-hexane extracts of J. regia leaves have immunomodulatory and anti-inflammatory effects that ameliorate experimentally induced arthritis and edema. The inhibition of autacoids may also be one of the mechanisms inducing the immunomodulatory effect.
Publisher: Elsevier BV
Date: 11-2014
DOI: 10.1016/J.JEP.2014.09.039
Abstract: Various medicinal plants have protective properties against the toxicities of the venom of cobra snake (Naja species). They may be used as local first aid for the treatment of snakebite victims, and can significantly inhibit lethality, cardio-, neuro-, nephro- and myotoxicity, hemorrhage, and respiratory paralysis induced by the cobra snake venom. The plants or their extracts may also complement the benefits of conventional anti-serum treatment. This review provides information on the protective, anti-venom, properties of medicinal plants against snakebites from cobras. In addition, it identifies knowledge gaps and suggests further research opportunities. The literature was searched using databases including Google Scholar, PubMed, ScienceDirect, Scopus and Web of Science. The searches were limited to peer-reviewed journals written in English with the exception of some books and a few articles in foreign languages. The plants possess neutralization properties against different cobra venom enzymes, such as hyaluronidase, acetylcholinesterase, phospholipase A2 and plasma proteases. Different active constituents that show promising activity against the effects of cobra venom include lupeol acetate, β-sitosterol, stigmasterol, rediocides A and G, quercertin, aristolochic acid, and curcumin, as well as the broad chemical groups of tannins, glycoproteins, and flavones. The medicinal plants can increase snakebite victim survival time, decrease the severity of toxic signs, enhance diaphragm muscle contraction, block antibody attachment to venom, and inhibit protein destruction. In particular, the cardiovascular system is protected, with inhibition of blood pressure decline and depressed atrial contractility and rate, and prevention of damage to heart and vessels. The designs of experimental studies that show benefits, or otherwise, of use of medicinal plants have some limitations: deficiency in identification and isolation of active constituents responsible for therapeutic activity lack of comparison with reference drugs and little investigation of the mechanism of anti-venom activity. Despite some current deficiencies in experimental or clinical analysis, medicinal plants with anti-venom characteristics are effective and so are candidates for future therapeutic agents. We suggest that emphasis on identification and testing of active ingredients in research in the future will assist better understanding of their anti-venom activity.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JEP.2018.06.018
Abstract: The whole plant, roots and stems of Ephedra gerardiana (Family Ephedraceae) have long been used as a folk remedy to treat rheumatism and painful joints in Northern Areas of Pakistan. The purpose of study was to observe the preventive efficacy of Ephedra gerardiana (EG) aerial parts in treating rheumatoid arthritis using Freund's complete adjuvant (FCA) induced arthritis in rat model and to determine its possible mechanism of action. Arthritis was induced in Sprague Dawley rats by immunization with 0.1 ml FCA in left footpad. EG aqueous ethanolic extract (30:70) and its aqueous, n-butanol and ethyl acetate fractions at 200 mg/kg were orally administered from day 0, 30 min prior to adjuvant injection and sustained for 28 days. Paw volume/diameter, arthritic score, body weight, and hematological (WBC, RBC, ESR, Hb and Platelet count) and biochemical (AST, ALT, ALP, urea, creatinine, CRP and RF) parameters were observed. The mRNA expression levels of COX-2, IL-1β, IL-6, NF-kB, TNF-α, IL-4 and IL-10 were measured by real time reverse transcription polymerase chain reaction (RT-PCR) while, PGE2 and TNF-α levels in serum s les were measured by Enzyme linked immunosorbent assay (ELISA). Moreover, radiographs of hind paws and histological changes in ankle joint were analyzed in adjuvant injected rats. In addition, anti-oxidant activity of plant extract and fractions was also evaluated using DPPH and reducing power assays. Also, preliminary phytochemistry and total phenolic and flavonoid contents were investigated in most active fraction (aqueous fraction). EG extract and fractions (notably aqueous fraction) significantly suppressed paw swelling and arthritic score, prevented cachexia and remarkably ameliorated hematological and biochemical changes. Furthermore, the overproduction of PGE2, COX-2, IL-1β, IL-6, NF-kB and TNF-α were remarkably attenuated in all EG treated rats, however, IL-4 and 10 were markedly increased. The radiographic and histopathologic improvement in joint architecture was also observed in EG treated rats. Piroxicam, used as reference drug, also significantly suppressed arthritis. Additionally, plant exhibited notable anti-oxidant activity and phytochemical analysis revealed the presence of alkaloids, flavonoids, phenols, tannins, saponins and glycosides. These results indicate that EG extract and fractions significantly attenuated adjuvant arthritis in rats by decreasing the levels of aforementioned pro-inflammatory and increasing the levels of anti-inflammatory mediators. This suggests that Ephedra gerardiana aerial parts might be used as a therapeutic agent for treating human arthritis.
Publisher: Springer Science and Business Media LLC
Date: 04-09-2019
DOI: 10.1007/S10787-019-00636-Y
Abstract: In our article entitled "Moringa rivae leaf extracts attenuate Complete Freund's adjuvant-induced arthritis in Wistar rats via modulation of inflammatory and oxidative stress biomarkers", we described the anti-arthritic effects of the plant leaves from Pakistan that we referred to as Moringa rivae (Saleem et al. 2019). Unfortunately, the identity of the plant material was incorrect. In fact, the plant leaves under study were later identified as belonging to wild type Moringa oleifera Lam. rather than Moringa rivae Chiov.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.JEP.2015.12.027
Abstract: Astragalus membranaceus either alone or in combination with Angelica sinensis has been used traditionally for kidney disease in East Asia and China for thousands of years. Previous studies using in vivo animal models have shown the benefits of these medicinal herbs in kidney diseases that involve oxidative stress. However, the mechanisms by which these medicinal herbs protect kidney cells remain largely unknown. To investigate the mechanisms by which ethanol, methanol and aqueous crude extracts of roots of A. membranaceus and A. sinensis afford protection to human kidney proximal tubular epithelial cells, using an in vitro model of oxidative stress. Ethanol, methanol and aqueous extracts of roots of A. membranaceus and A. sinensis were prepared by a three-solvent sequential process. HK2 human kidney proximal tubular epithelial cells were treated with H2O2 alone (0.5mM) or in combination with different concentrations of extracts. Cell mitosis and death (microscopy) and cell viability (MTT assay) were compared. Western immunoblot was used to study expression of apoptosis-related proteins (pro-apoptotic Bax andanti-apoptotic Bcl-XL), and cell survival (NFκB subunits p65 and p50), pro-inflammatory (TNF-α) and protective (TGFβ1) proteins. H2O2-induced oxidative stress significantly increased apoptosis and reduced cell survival upregulated pro-apoptotic and down-regulated Bcl-XL increased NFκB (p65, p50) increased TNFα and decreased TGFβ1. All changes indicated kidney damage and dysfunction. All were modulated by all extracts of both plant species, except for NFκB which was only modulated by extracts of A. membranaceus. In conclusion, in a model of oxidative stress that might occur after nephrotoxicity, the plant extracts were protective via anti-apoptotic and anti-inflammatory mechanisms.
Publisher: Springer Science and Business Media LLC
Date: 05-03-2020
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.MOLIMM.2018.07.013
Abstract: Atopic dermatitis (AD) or atopic eczema is a skin disease characterized with itching, increased serum level of immunoglobulin E, and peripheral eosinophilia. Thymoquinone (TQ) is an important ingredient of Nigella sativa seeds having antioxidant and anti-inflammatory effects. Present study investigates the immunomodulatory effects of Thymoquinone (TQ) in mice model of atopic dermatitis. Ear pinnas of mice were sensitized and challenged with DNCB (2-4 di nitro chloro benzene) to induce AD-like lesions. The mice were then treated with TQ and tacrolimus, both orally and topically. Ear thickness and weight were measured along with gross changes. Total and differential leukocyte counts were measured in blood. Total serum IgE levels were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expression levels of IL-4, IL-5, and IFN-γ in ear tissue were measured using reverse transcription polymerase chain reaction (RT-PCR). Both oral and topical thymoquinone showed the potential to improve atopic dermatitis by significantly reducing the inflammatory cells infiltration in the blood (p < 0.001) and improving the dermatitis score (p < 0.001). Significant reduction in ear thickness (p < 0.001) and IgE levels (p < 0.001) were also observed. TQ and tacrolimus also significantly attenuated mRNA expression levels of IL-4, IL-5 and IFN-γ (p < 0.001). Taken together, our results showed that oral and topical application of thymoquinone exerts immunomodulatory effects in animal model of atopic dermatitis, suggesting further studies and clinical trials to establish it as a candidate nutraceutical for the treatment of AD.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
DOI: 10.1007/S10787-019-00596-3
Abstract: Moringa rivae is widely used as a traditional remedy against arthritis. The present research was designed to evaluate the anti-arthritic potential of Moringa rivae extracts. Treatment of rats with adjuvant-induced arthritis with methanolic and aqueous extracts of M. rivae (150, 300 or 600 mg/kg), and piroxicam (10 mg/kg) was started orally at day 8 post-administration of complete Freund's adjuvant and continued till 28th day. The therapeutic effect of the plant extracts was assessed in arthritic rats by arthritic index, body weight, and haematological and biochemical parameters. Furthermore, the modulatory effect on gene expression (I-κB, IL-4 and IL-10, COX-2, IL-1β and IL-6, NF-κB, and TNF-α) in the blood was determined using qRT-PCR, while ELISA assay was used to find PGE2 and TNF-α concentrations in the serum. Oxidative stress parameters in the liver and ankle joint histopathology were also evaluated. Moreover, the most effective methanolic extract was further characterized by GC-MS for the presence of phytochemicals. Treatment with the plant extracts significantly restored arthritic index, change in the body weight and immune organ weight, and the histopathological indices. Both extracts significantly (p < 0.05) reduced the serum concentration of rheumatoid factor, C-reactive protein, PGE2, and TNF-α in arthritic rats. The extracts persuasively down-regulated the COX-2, PGE2, IL-1β, IL-6, NF-κB, and TNF-α, and up-regulated the mRNA expression of I-κB, IL-4, and IL-10. Both extracts increased the activities of CAT and SOD while reducing the formation of MDA in a dose- dependent manner in the liver. Histopathological evaluation showed that treatment with the plant extracts significantly (p < 0.05) reduced joint inflammation, pannus formation, and bone erosion in treatment groups in comparison to arthritic control. Phytochemicals detected by GC-MS in the methanolic extract included esters, alcohols, ketones, fatty acids, and vitamin E. These findings provide evidence of the anti-arthritic potential of M. rivae extracts in chronic polyarthritis model.
Publisher: Informa UK Limited
Date: 16-11-2012
DOI: 10.3109/13880209.2012.717228
Abstract: Cucumis melo Linn. (Cucurbitaceae) and Citrullus lanatus Thunb. (Cucurbitaceae) are desert vegetables popular for their nutritional value and year round availability. The pulp and seeds of these plants are used for dietary purposes or as medications for certain ailments in the folk medicinal system. Peels of the fruit are either wasted or used as feed of grazing animals. A detailed investigation regarding the chemical constituents and antioxidative analyses of the peel extract of fully ripened fruits from different cultivars of the two vegetables was carried out here for the first time. Chemical constituents of the peel extracts of C. melo and C. lanatus cultivars in methanol, 1-butanol, chloroform and n-hexane were analysed by gas chromatography-mass spectrometry (GC-MS) and the antioxidative properties were evaluated using standard in vitro antioxidative assays. The results demonstrated large variation in the chemical constituents of the extracts including alkanes, saturated and unsaturated fatty acids and their esters, cyclic ketones, aldehydes, phenolic compounds and anthocyanin derivatives. Total phenolic content ranged from 2.96-0.85 mg/L gallic acid equivalents for different extracts. Employing GC-MS analyses and standard in vitro antioxidative assays, the data presented here clearly demonstrate the potency of C. melo and C. lanatus extracts as antioxidant and radical scavenger plants which may be used as good sources of natural antioxidants. The peels of both the plants can be added to the diet at various stages to compensate food shortage and dietary deficiency problems of living beings.
Publisher: Pakistan Journal of Medical Sciences
Date: 03-02-2021
Abstract: Objectives: To investigate the association of serum chemerin with calcium, alkaline phosphatase and bone mineral density in postmenopausal non-osteoporotic and osteoporotic females. Methods: This cross-section analysis was carried out at the orthopedic department of Madina Teaching Hospital, Faisalabad, Pakistan, in the year 2017-2019. Postmenopausal females were ided into two groups according to their bone mineral density (BMD). All osteoporotic females had a T-score of -2.5 or less. Data were analyzed on SPSS-24. Results: A total of 140 women were included in our study (80 osteoporotic and 60 non-osteoporotic). Non significant difference in age and BMI was observed between osteoporotic and non-osteoporotic subjects (p=0.152) and (p=0.291) respectively. There was a significant difference found in total BMD, serum chemerin levels between osteoporotic and non-osteoporotic subjects p .001 in both parameters. No significant correlation of serum chemerin was found with serum calcium, serum alkaline phosphatase and BMD in postmenopausal osteoporotic females (p=0.907), (p=0.318) (p=0.664) respectively. A significant negative correlation was found between serum alkaline phosphatase levels and total BMD in postmenopausal osteoporotic females (p=- 0.039). Linear regression analysis of serum alkaline phosphatase levels with total BMD showed no association between BMD and serum alkaline phosphatase levels (p=0.869). Conclusion: There is no association of serum chemerin with calcium, ALP and bone mineral density in non-osteoporotic and osteoporotic postmenopausal females. doi: 0.12669 jms.37.2.3907 How to cite this:Tariq S, Tariq S, Shahzad M. Association of serum chemerin with calcium, alkaline phosphatase and bone mineral density in postmenopausal females. Pak J Med Sci. 2021 (2):384-388. doi: 0.12669 jms.37.2.3907 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (icenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2019
DOI: 10.1007/S11033-019-05041-W
Abstract: Insulin resistance (IR), a pathological condition of type 2 diabetes mellitus (T2DM) is characterized by an inability of body's tissue to respond the secreted or administered insulin, a necessary step for cellular glucose transportation. The prevalence of insulin resistance progresses with age, especially in overweight people with central obesity. Insulin receptor substrates (IRS) are important molecular proteins in the insulin signalling pathway, where IRS-1 plays a key function in cells insulin sensitivity. The common mutation (rs1801278 r.2963G > A: Gly972Arg) of the IRS-1 gene occurs when residue glycine changes to arginine at codon 972. The objective of this study was to detect the genetic association of rs1801278 polymorphism of the IRS-1 gene with insulin resistance in type 2 diabetes from the Lahore region of Pakistan. A total of 322 subjects (161 cases and 161 healthy in iduals) were included. DNA was isolated for detection of the genotype distribution and allele frequencies by PCR-RFLP. The results showed a significant difference in the genotype distribution and allele frequency between the T2DM cases and controls for single nucleotide polymorphism (SNP) rs1801278 (OR 17.61, 95% CI 8.06-38.4, p < 0.001). In conclusion, association between rs1801278 polymorphism of the IRS-1 gene and insulin resistance in T2DM has been established in a Pakistani population.
Publisher: ResearchersLinks Ltd
Date: 2018
Publisher: MDPI AG
Date: 12-04-2023
DOI: 10.3390/PHARMACEUTICS15041225
Abstract: Chrysin (5,7-dihydroxyflavone) has many pharmacological properties including anti-inflammatory actions. The objective of this study was to evaluate the anti-arthritic activity of chrysin and to compare its effect with the non-steroidal anti-inflammatory agent, piroxicam, against complete Freund’s adjuvant (CFA)-induced arthritis in a pre-clinical model in rats. Rheumatoid arthritis was induced by injecting CFA intra-dermally in the sub-plantar region of the left hind paw of rats. Chrysin (50 and 100 mg/kg) and piroxicam (10 mg/kg) were given to rats with established arthritis. The model of arthritis was characterized using an index of arthritis, with hematological, biological, molecular, and histopathological parameters. Treatment with chrysin significantly reduced the arthritis score, inflammatory cells, erythrocyte sedimentation rate, and rheumatoid factor. Chrysin also reduced the mRNA levels of tumor necrosis factor, nuclear factor kappa-B, and toll-like recepter-2 and increased anti-inflammatory cytokines interleukin-4 and -10, as well as the hemoglobin levels. Using histopathology and microscopy, chrysin reduced the severity of arthritis in joints, infiltration of inflammatory cells, subcutaneous inflammation, cartilage erosion, bone erosion, and pannus formation. Chrysin showed comparable effects to piroxicam, which is used for the treatment of rheumatoid arthritis. The results showed that chrysin possesses anti-inflammatory and immunomodulatory effects that make it a potential drug for the treatment of arthritis.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2021
DOI: 10.1007/S10787-021-00804-Z
Abstract: Pseudoephedrine (substituted phenethylamine) is well known as psychotic and bronchodilator. Numerous studies on phenethylamine derivatives indicated that these agents have the potential to abolish inflammatory responses in the non-biological and biological systems. These facts provided the basis to conduct a study on pseudoephedrine to explore its therapeutics in Complete Freund's Adjuvant (CFA)-induced arthritis. Furthermore, existing treatment approaches for RA associated with limited effect on chronic immunological models. Real-time polymerase chain reaction (q-PCR) was performed to execute the expression of pro and anti-inflammatory cytokines in treated and non-treated arthritic rats. These findings were further co investigate by histological observations. The paw volume, paw diameter, weight variations and arthritic score were determined at specific days throughout the experiment of 28 days. Pseudoephedrine at all doses significantly (p < 0.001) suppressed the expression of PGE2, TNF-α, IL-1β and IL-6. Moreover, pseudoephedrine (20 and 40 mg/kg) caused significant augmentation of IL-4 and IL-10. Similarly, the drug expressed a significant anti-arthritic effect by reducing the paw volume, paw diameter and arthritic score. Similarly, it also reverts the reduction in body weight of arthritic rats at all above-mentioned doses. These findings supported the anti-arthritic potential of pseudoephedrine and recommended it for clinical trials.
Publisher: Springer Science and Business Media LLC
Date: 09-04-2009
DOI: 10.1007/S00011-009-0027-5
Abstract: Aim of this study is to explore the expression stability of 12 commonly used housekeeping genes in inflammation condition. Two rat models, pristane-induced arthritis (PIA) and antigen-induced pulmonary inflammation (AIPI) were established and reverse transcription-PCR was performed from rat spleens and inguinal lymph nodes. The reference gene expression fluctuated in the immune-associated tissues and 18S rRNA expression from the various inflammatory conditions was the most stably in all examined gene expression. Besides, peptidylprolyl isomerase A and beta-glucuronidase in PIA spleens, beta-actin and GAPDH in PIA inguinal lymph nodes, and peptidylprolyl isomerase A and beta-actin in AIPI spleens, expressed more stably than others. These results were further confirmed by expression study of TNF-alpha in PIA rat inguinal lymph nodes. We suggest that the stable gene mentioned above or geometric mean of three best references in each experimental condition should be used as the reference and the variable ones should be avoided in similar study designs.
Publisher: Springer Science and Business Media LLC
Date: 08-08-2020
DOI: 10.1186/S13063-020-04616-4
Abstract: To evaluate the effectiveness of Hydroxychloroquine Phosphate/Sulfate (200 mg orally 8 hourly thrice a day for 5 days), versus oseltamivir (75 mg orally twice a day for 5 days), and versus Azithromycin (500 mg orally daily on day 1, followed by 250 mg orally twice a day on days 2-5) alone and in combination (in all seven groups), in clearing the coronavirus (COVID-19) nucleic acid from throat and nasal swab and in bringing about clinical improvement on day 7 of follow-up (primary outcomes). An adaptive design, set within a comprehensive cohort study, to permit flexibility in this fast-changing clinical and public health scenario. The randomized study will be a multicenter, multiarm, multistage, randomized controlled trial with a parallel design. An observation only cohort will emerge from those not consenting to randomization. Eligible will be newly diagnosed patients, either hospitalized or in self-isolation, without any comorbidities or with controlled chronic medical conditions like diabetes mellitus and hypertension. Participants of any gender or age group having tested positive for COVID-19 on Real-Time qRT-PCR (Quantitative Reverse Transcription PCR) will be invited to take part in study at twelve centers across eight cities in Pakistan. Those pregnant or lactating, severely dyspneic or with respiratory distress, already undergoing treatment, and with serious comorbidities like liver or kidney failure will be excluded. There will be a total of seven comparator groups: Each drug (Hydroxychloroquine Phosphate/Sulfate, Oseltamivir and Azithromycin) given as monotherapy (three groups) combinations of each of two drugs (three groups) and a final group on triple drug regimen. The laboratory-based primary outcome will be turning the test negative for COVID-19 on qRT-PCR on day 7 of follow-up. The clinical primary outcome will be improvement from baseline of two points on a seven-category ordinal scale of clinical status on day 7 of follow-up. Participants will be randomized, maintaining concealment of allocation sequence, using a computer-generated random number list of variable block size into multiple intervention groups in the allocation ratio of 1:1 for all groups. This is an open label study, neither physician nor participants will be blinded. This is an adaptive design and parameters for formal s le size calculation in a new disease of a previously unknown virus are not available. Thus, the final s le size will be subjected to periodic reviews at each stage of adaptive design and subsequent advice of National Data Safety & Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. Protocol Version 1.7 dated July 5, 2020. By July 03, 2020, the trial had recruited a total of about 470 participants across 12 centers after approval from the National Bioethics Committee and Drug Regulatory Authority of Pakistan. Recruitment started on April 20, 2020. The recruitment is expected to continue for at least three months subject to review by the National Data Safety and Management Board (NDSMB) notified by Drug Regulatory Authority of Pakistan. Prospectively registered on 8 April 2020 at clinicaltrials.gov ID: NCT04338698 The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2 ).
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JEP.2019.02.025
Abstract: Ribes alpestre Decne has been commonly used in the treatment of joint complaints. The present study was undertaken to evaluate the antiarthritic potential of ethanolic extract and fractions of Ribes alpestre and to explore its probable mechanism of action. Complete Freunds adjuvant induced arthritis in Sprague Dawley rats was used to assess antiarthritic activity of aqueous ethanol extract, butanol and aqueous fractions at 200 mg/kg oral dose for 28 days. Paw volume and diameter, arthritic index, body weight, hematological and biochemical parameters, radiographic and histological analysis of ankle joints were carried out. An array of pro-inflammatory mediators (IL-1β, IL-6, NF-Kβ, TNF-α, COX-2, IL-4, IL-10 and PGE2) were estimated by RT-PCR and enzyme linked immunosorbent assay. Antioxidant capacity was assessed using DPPH and reducing power assays. Qualitative phytochemical screening, total phenolic and flavonoid content and HPLC analysis of aqueous fraction of Ribes alpestre were also carried out. Significant (p < 0.001) reduction in paw volume and thickness and arthritic score by aqueous ethanolic extract and its fractions has been found. Aqueous ethanolic extract and fractions in particular aqueous fraction considerably prevented decrease in body weight, alterations in hematological parameters. Radiographic and histological examination revealed no significant architectural changes in joints of treated rats. Significant (p < 0.05-0.001) down regulation of pro-inflammatory genes IL-1β, TNF-α, IL-6, COX-2, PGE2 and NF-Kβ alongwith noteworthy increase in levels of IL-4 and IL-10 was recorded among treated animals. Aqueous ethanol extract and its fractions demonstrated notable and concentration dependent (50-6400 μg/ml) antioxidant potential. Qualitative phytochemical analysis of active fraction (aqueous) displayed presence of flavonoids, alkaloids, tannins and glycosides. Besides total phenolic and flavonoid contents has been found to be 179.3 mg GAE/ml and 389.40 μg QE/ml in aqueous fraction of Ribes alpestre respectively. HPLC profile demonstrated presence of quercitin, chlorogenic acid, vanillic acid and cinamic acid in aqueous fraction. Present communication suggests Ribes alpestre a potent antiarthritic therapy by ameliorating adjuvant arthritis in rats by downregulating proinflammatory mediators with up regulation of anti-inflammatory cytokines.
Publisher: American Chemical Society (ACS)
Date: 14-01-2021
Publisher: Pakistan Journal of Medical Sciences
Date: 22-05-2019
Abstract: Background & Objective: The “silent thief” of bone osteoporosis is associated with various modifiable factors, identifying these factors is important in decreasing the prevalence of this highly prevalent disease. Therefore, this study was planned to identify these risk factors for osteoporosis in premenopausal and postmenopausal Pakistani women. Methods: A total of 1205 pre and postmenopausal females between the age of 20 to 80 years were selected. Detailed history about the socio-demographic characteristics including age, education, profession, marital and resident status was recorded. Medical and gynecological history was also taken after informed consent Bone health of females was assessed using calcaneal ultrasound bone densitometer. SPSS 22.0 was used to analyze data. Results: Univariate analysis showed that age (30-39 yrs, and 60-69 yrs), occupation (housewives) and education (secondary and primary education, illiterate) were significantly associated with low bone mass density (LBMD). Multivariate analysis showed that age 30-39 years (OR=0.25 95%CI 0.13 – 0.49), age 40-49 years (OR=0.30 95%CI 0.15 – 0.59), age 50-59 years (OR=0.42 95%CI 0.22 – 0.79), primary education (OR=3.83, 95%CI 2.30 - 6.38) and illiteracy (OR=3.83 95%CI 2.52 – 5.82), were significantly associated with LBMD. The prevalence of osteopenia and osteoporosis was 29.8%, 27.2%, respectively, while 43% of subjects had normal BMD. Conclusion: It is concluded that within Pakistani population, the prevalence of osteopenia is high even at an early age group and the odds of having LBMD are more in less educated or illiterate women. doi: 0.12669 jms.35.3.551 How to cite this:Tariq S, Baig M, Tariq S, Shahzad M. Status of bone health and association of socio-demographic characteristics with Bone Mineral Density in Pakistani Females. Pak J Med Sci. 2019 (3):812-817. doi: 0.12669 jms.35.3.551 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (icenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Springer Science and Business Media LLC
Date: 25-08-2016
DOI: 10.1007/S10753-016-0427-Y
Abstract: The anti-inflammatory activities of benzothiazine and pyrazole derivatives are well documented. A series of novel N'-arylmethylidene-2-(3,4-dimethyl-5,5-dioxidopyrazolo(4,3 c)(1,2) benzothiazin-2(4H)yl) acetohydrazide compounds were previously synthesized by combining benzothiazine and pyrazole moieties into a single nucleus. The current study investigates the anti-arthritic potential of 3-ethoxy-4-hydroxyphenyl derivative (EHP) and its possible mechanism in arthritic rat model. Sprague-Dawley rats were induced rheumatoid arthritis with Freund's complete adjuvant and treated with EHP and piroxicam. At the end of the study, arthritic score was calculated, and ankle joint histopathology was performed using hematoxylin and eosin staining. Real-time reverse transcription polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to determine mRNA expression and protein levels of various inflammatory markers, respectively. In vitro concanavalin A (ConA)-stimulated splenocyte proliferation was measured. Serum levels of C-reactive protein (CRP), urea, creatinine, aspartate aminotransferase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) were also determined. EHP significantly attenuated macroscopic arthritic score, joint histopathological lesions, and CRP levels. Treatment with EHP significantly reduced pro-inflammatory tissue necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-кB), interleukin-17 (IL-17), and prostaglandin-E2 (PGE2) levels and increased the levels of anti-inflammatory interleukin-4 (IL-4) and interleukin-10 (IL-10). ConA-stimulated splenocyte proliferation was also significantly suppressed by treatment with EHP. Normalizing all hematological markers and ALP levels, EHP did not display any sign of nephrotoxicity and hepatotoxicity as determined by urea, creatinine, ALT, and AST levels. In conclusion, EHP possesses significant anti-arthritic property which may be attributed to its anti-inflammatory and immunomodulatory effects.
Publisher: Elsevier BV
Date: 12-2017
DOI: 10.1016/J.BIOPHA.2017.10.061
Abstract: Hyperlipidemia is a metabolic disorder that is caused by high levels of triglycerides and cholesterol in blood. Using of plants for the treatment of various ailments is a traditional practice in developing countries. The main objective of the study is to analyse the nutritional composition of Pistacia khinjuk and to assess its anti-hyperlipidemic activity. In the present study, the ethanolic extract of Pistacia khinjuk leaves was evaluated for antihyperlipidemic activity. 40 adult albino rats were ided into five groups. Hyperlipidemia was induced using high fat diet for 60days. Pistacia khinjuk extract of 150mg/kg body weight and 300mg/kg of body weight was administered to the rats for 28days. Proximate analysis of Pistacia khinjuk was also performed. Proximate analysis of Pistacia khinjuk leaves showed 6.8% ash content, 12.8% crude fiber and only 6.85% fat content. Findings of present study revealed that both doses of Pistacia khinjuk extract improved the serum lipid profile in albino rats by reducing total lipids, total cholesterol, triglycerides and low density lipoprotein, and increasing high density lipoprotein levels in Pistacia khinjuk treated groups. Body weight findings showed significant increase in body weight of all groups from zero day to 60th day. But before sacrifice, there was a decrease in hyperlipidemic and high dose Pistacia khinjuk while increase in control and low dose Pistacia khinjuk group respectively. From the results of the present study, it is concluded that Pistacia khinjuk extract has curative effect against hyperlipidemia.
Publisher: Hindawi Limited
Date: 09-11-2020
DOI: 10.1155/2020/8869484
Abstract: Anacardium occidentale (cashew) has been used in the traditional system of medicine for curing many inflammatory disorders. The present study investigates the antiarthritic effects of cashew leaves extract using the rat model of FCA-induced rheumatoid arthritis. Arthritic rats were treated with 100 and 200 mg/kg b.w. ethanolic extract of cashew leaves. Animals were sacrificed at day 23, and before sacrificing the animals, gross pathological changes were observed. Histopathology of ankle joint was evaluated with hematoxylin and eosin staining, whereas the serum levels of C-reactive protein (CRP) were evaluated by the agglutination method. Inflammatory cells and other hematological parameters were assessed by employing an automated hemocytometer and chemistry analyzer. Rheumatoid factor (Rf) and lysosomal enzymes levels were determined in blood. Results indicated that A. occidentale significantly decreased the CPR levels, macroscopic arthritic score, and rheumatoid factor as compared to the diseased group. Histopathological evaluation showed significant attenuation in bone erosion, joint inflammation, and pannus formation by plant extract. Treatment with A. occidentale significantly suppressed the levels of acid phosphatase, β-galactosidase, β-glucuronidase, N-acetylglucosaminidase, and collagenase. Moreover, A. occidentale significantly raised the HB levels and RBCs counts which were found depleted in the diseased group. The raised counts of total leukocytes, platelets, neutrophils, lymphocytes, and monocytes were also significantly decreased by treatment with plant extract. Comparative analysis showed that higher dose of A. occidentale demonstrated superior amelioration of rheumatoid arthritis as compared to low dose. In conclusion, A. occidentale possesses significant antiarthritic potential, which may be attributed to the suppression of lysosomal enzymes and collagenase levels.
Publisher: Hindawi Limited
Date: 12-12-2020
DOI: 10.1155/2020/8836080
Abstract: The genus of Trigonella has long been used for the treatment of arthritis and inflammatory disorders. This study was aimed to investigate the immunomodulatory activities of ethanol and n-hexane extracts of T. gharuensis in the rat model of rheumatoid arthritis. Freund’s complete adjuvant (FCA) model was used to induce arthritis in rats. Arthritis was induced on day 0, while treatment which was started on day 8 continued for twenty days. Arthritic development and paw edema were determined using an arthritic scoring index and plethysmometer, respectively. Histopathology was evaluated using H& E staining. RNA extraction, reverse transcription, and polymerase chain reaction (RT-PCR) were performed to determine expression levels of proinflammatory markers such as TNF-α, NF-ĸB, IL-6, IL-1β, COX2, and anti-inflammatory cytokine IL-4. Prostaglandin E2 level (PGE2) was evaluated using ELISA. Blood analysis and biochemical parameters were also determined. The significance level was set as P 0.05 . Treatment with extracts reduced paw edema, arthritic progression, and histopathological parameters. Expression levels of abovementioned proinflammatory cytokines and COX2 were downregulated, while IL-4 was upregulated. PGE2 levels were found reduced with extract treatment. Blood parameters were nearly normalized in treatment groups. Extract treatment did not alter biochemical parameters. Both extracts had effects comparable with piroxicam. In conclusion, extracts of T. gharuensis ameliorated experimentally induced arthritis that may be ascribed to its immunomodulatory effects.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 04-2022
Publisher: Wiley
Date: 25-02-2022
DOI: 10.1002/JMV.27648
Abstract: Human immunodeficiency virus (HIV) infection is fast becoming widespread in the world with 37.7 million people living with HIV in 2020. Antiretroviral therapy involving chemical drugs has declined acquired immunodeficiency syndrome (AIDS)‐related mortality and improved the life quality of AIDS/HIV sufferers. However, the emergence of drug resistance and side effects are the main obstacles for the long‐term use of these chemicals as antiretroviral therapy. Recently, a lot of emphasis is being put on finding naturally occurring drug candidates that show activity against HIV and can be potentially used as antiretroviral therapy. In this study, different medicinal plants, Pistacia khinjuk, Teucrium stocksianum, Uncaria tomentosa, Pistacia integerrima, Trigonella gharuensis, and Artocarpus lakoocha , were explored for their anti‐HIV potential. Syncytium and p24 assays were performed to determine antiviral activity, while the MTT assay was used to determine cytotoxicity. Results showed that extracts from all six plants inhibited HIV replication in vitro. Also, extracts from Pistacia khinjuk , Teucrium stocksianum , Uncaria tomentosa , and Pistacia integerrima showed low cytotoxicity with a 50% cytotoxicity concentration value of μM. Results of this study indicate that there is potential in these natural extracts to become candidate drugs to be used as complementary and alternative medicine for HIV infection.
Publisher: Springer Science and Business Media LLC
Date: 30-01-2013
DOI: 10.1007/S12031-013-9968-9
Abstract: Oxidative stress leading to retinal nerve cells (RNCs) apoptosis is a major cause of neurodegenerative disorders of the retina. 17β-Estradiol (E2) has been suggested to be a neuroprotective agent in the central nervous system however, at present, the underlying mechanisms are not well understood, and the related research on the RNCs is less reported. Here, in order to investigate the protective role and mechanism of E2 against oxidative stress-induced damage on RNCs, the transmission electron microscopy and annexin V-FITC ropidium iodide assay were applied to detect the RNCs apoptosis. Western blot and real-time PCR were used to determine the expression of the critical molecules in Bcl-2 and caspase family associated with apoptosis. The transmission electron microscopy results showed that H(2)O(2) could induce typical features of apoptosis in RNCs, including formation of the apoptosome. E2 could, however, suppress the H(2)O(2)-induced morphological changes of apoptosis. Intriguingly, we observed E2-mediated phagocytic scavenging of apoptosome. In response to H(2)O(2)-induced apoptosis, Bax, acting as one of the pivotal pro-apoptotic members of Bcl-2 family, increased significantly, which directly resulted in an increased ratio of Bax to anti-apoptotic protein Bcl-2 (Bax/Bcl-2). Additionally, caspases 9 and 3, which are the critical molecules of the mitochondrial apoptosis pathway, were activated by H(2)O(2). In contrast, E2 exerted anti-apoptotic effects by reducing the expression of Bax to decrease the ratio of Bax/Bcl-2 and impeded the caspases 9/3 activation. Moreover, LY294002, a phosphatidylinositol 3-kinase (PI3K) inhibitor, could sharply block the effect of E2 in reducing the percentage of apoptotic cells resistance to H(2)O(2). And the attenuation of Bax, the reduced activities of caspases 9/3 and the impeded release of mitochondrial cytochrome c mediated by E2 resistance to H(2)O(2) damage were significantly retrieved by LY294002 administration. Taken together, E2 protects the RNCs against H(2)O(2)-induced apoptosis by significantly inhibiting the Bax-involved mitochondrial apoptosis via the activation of PI3K/Akt signal pathway.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EJPHAR.2014.05.045
Abstract: Benzothiazine and pyrazole derivatives possess anti-inflammatory properties. Previously, synergism of both heterocyclic moieties into a single nucleus has shown to produce biologically active N'-arylmethylidene-2-(3,4-dimethyl-5,5-dioxidopyrazolo(4,3-c)(1,2)benzothiazin-2(4H)yl)acetohydrazides) compound. Present study investigates the anti-arthritic effect and possible mechanism of 2,4-dihydroxyphenyl derivative (DHP) in Freund's complete adjuvant-induced arthritic rat model. Ankle joint histopathology was performed with Hematoxylin & Eosin staining, while serum C-reactive protein (CRP) levels were measured by agglutination method. mRNA expression levels and protein levels of proinflammatory markers were measured by real time reverse transcription polymerase chain reaction and Enzyme linked immunosorbent assay (ELISA), respectively. in vitro Concanavalin A (ConA)-stimulated splenocyte proliferation was also measured by ELISA reader. DHP treatment reduced the macroscopic arthritic score, CRP levels, synovial inflammation, bone erosion and pannus formation. Levels of cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), Prostaglandin-E2 (PGE2), and 5-lipoxygenase (5-LOX), were significantly attenuated by DHP. It also significantly decreased the levels of toll-like receptor 2, nuclear factor-kappaB (NF-ĸB), and tissue necrosis factor-α (TNF-α) and non-significantly elevated interleukin-4 (IL-4) levels. Piroxicam, used as reference drug, significantly reduced the levels of COX-1, COX-2, PGE2, NF-ĸB, and TNF-α, but did not show reduction in 5-LOX and toll-like receptor 2 levels. However piroxicam significantly enhanced the levels of IL-4. Both DHP and piroxicam suppressed ConA-stimulated splenocyte proliferation. DHP normalized all altered hematological markers and did not show any sign of hepatotoxicity or nephrotoxicity as determined by alanine transaminase, aspartate aminotransferase, urea, and creatinine levels. Results showed that DHP possesses significant anti-arthritic activity which may be attributed to its immunomodulatory and anti-inflammatory effects.
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.BIOPHA.2019.01.006
Abstract: Thymoquinone (TQ), the most important active principle of Nigella sativa is known to have anti-inflammatory, analgesic, antimicrobial and antioxidant properties. The present study was designed to see the anti-arthritic effect of TQ in rat model of arthritis. In the current research, anti-arthritic effect of TQ was determined in Freund's Complete Adjuvant (FCA)-induced arthritic rats by measuring TLRs expression levels. The mRNA expression levels of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), interleukin-1 (IL-1), nuclear factor-kappa B (NFκB) and tissue necrosis factor-α (TNF-α) were measured by reverse-transcription polymerase chain reaction. Arthritic signs were observed by macroscopic criteria. Hematoxylin and Eosin staining was used to perform ankle joint histopathology and agglutination method was used for measuring C-reactive protein (CRP) levels. Rheumatoid factor, alanine transaminase, aspartate aminotransferase, urea and creatinine were also determined in serum. TQ treatment reduced the macroscopic arthritic score, levels of CRP, synovial inflammation, pannus formation and bone erosion. It also reduced the mRNA levels of TLR2, TLR4, IL-1, NFκB and TNF-α. Methotrexate, used as a reference drug also significantly decreased their expression levels. TQ also normalized the hematological markers and did not depict any signs of hepatotoxicity and nephrotoxicity as determined by serum levels of alanine transaminase, aspartate aminotransferase, urea and creatinine. Our results showed that TQ possesses significant anti-arthritic activity which can be due to its anti-inflammatory and immunomodulatory effects. Results indicate that TQ has got the potential to ameliorate rheumatoid arthritis by downregulating TLR2, TLR4, TNF-α, IL-1, and NFκB expression levels.
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.INTIMP.2022.108990
Abstract: Psoriasis is a chronic skin disease with 2-4% of prevalence worldwide conferring a major burden on health systems. It is assumed that the prevalence might increase due to climatic change and deterioration of protective ozone barrier. With the chances of increasing prevalence, newer and specific treatment options need to be explored. Skin is a constant target of oxidative stress owing to continuous exposure to ultraviolet radiations. Oxidative stress is considered to have a central role in dermatological diseases, including psoriasis. This study was designed to explore the role of Humanin analogue (S14-G HNG) as an important anti oxidant for psoriasis like condition in BALB/c mice as till date the commomly used drugs for this disease are corticosteroids which have a dissatisfactory adverse effect profile in terms of chronic use. Imiquimod 5% was used to induce Psoriasis like condition in mice, and the role of HNG was assessed through the histological examination, protein expressions and markers of oxidative stress. Two doses (low and high) of HNG were used and results were compared with an established drug methylprednisolone. Significant improvement was seen on histology, PASI scoring, protein expression and oxidative stress by the use of intraperitoneal injections of S14-G HNG and the results were comparable to those obtained through peritoneal injections of methylprednisolone. S14G-HNG can be considered as a suitable option for treatment of Psoriasis after clinical trials and it might prove to have lesser side effects as compared to other drugs employed for the treatment of psoriasis being an innate anti oxidant and anti apoptotic compound.
Publisher: Wiley
Date: 16-08-2023
DOI: 10.1002/JCB.30459
Abstract: Glabridin, a polyphenolic flavonoid derived from Glycyrrhiza glabra (licorice) roots, has shown anti‐inflammatory and antioxidant properties. The current study sought to investigate glabridin's immunomodulatory effect in ovalbumin induced allergic asthma. Healthy male Wistar rats were ided into five groups. Group I served as a control group. Asthma was induced in groups II– IV. Groups III and IV were treated with glabridin (40 mg/kg) and methylprednisolone (15 mg/kg), respectively. Inflammatory cells counts were determined in blood and bronchoalveolar lavage fluid (BALF). Serum IgE levels and levels of catalase, superoxide dismutase and glutathione peroxidase in lung homogenate were measured. The levels of mRNA expression of pro‐inflammatory, anti‐inflammatory and oxidative stress markers were analysed. Delayed type hypersensitivity (DTH) and acute toxicity of glabridin were also checked. Glabridin significantly decreased inflammatory cells in the blood and BALF. It increased the concentration of antioxidant enzymes catalase, superoxide dismutase and glutathione peroxidase. Glabridin markedly decreased serum IgE levels and DTH when compared to asthmatic rats. It significantly alleviated the expression of TNF‐α, IL‐4, IL‐5, CXCL1, iNOS, and NF‐κB. Administering 10 times the therapeutic dose of glabridin did not show any signs of acute toxicity. Findings suggest that glabridin has the potential to ameliorate allergic asthma and its effects are comparable to those of methylprednisolone. The immunomodulatory effect of glabridin might be contributed by the suppression of pro‐inflammatory cytokines, oxidative stress markers, IgE antibodies, and elevation of antioxidant enzymes, suggesting future study and clinical trials to propose it as a candidate to treat allergic asthma.
Publisher: Elsevier BV
Date: 06-2018
Publisher: Frontiers Media SA
Date: 16-09-2022
DOI: 10.3389/FPHAR.2022.986802
Abstract: Carbapenem resistant Acinetobacter baumannii has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant A. baumannii infections. Therefore, resistance to colistin is considered as a serious medical threat. The purpose of this study was to assess the current status of colistin resistance in Pakistan, a country where carbapenem resistant A. bumannii infections are endemic, to understand the impact of colistin resistance on virulence in mice and to assess alternative strategies to treat such infections. Out of 150 isolates collected from five hospitals in Pakistan during 2019–20, 84% were carbapenem resistant and 7.3% were additionally resistant to colistin. There were two isolates resistant to all tested antibiotics and 83% of colistin resistant isolates were susceptible to only tetracycline family drugs doxycycline and minocycline. Doxycycline exhibited a synergetic bactericidal effect with colistin even in colistin resistant isolates. Exposure of A. baumannii 17978 to sub inhibitory concentrations of colistin identified novel point mutations associated with colistin resistance. Colistin tolerance acquired independent of mutations in lpxA, lpxB, lpxC , lpxD , and pmrAB supressed the proinflammatory immune response in epithelial cells and the virulence in a mouse infection model. Moreover, the oral administration of water extract of Saussuria lappa, although not showing antimicrobial activity against A. baumannii in vitro , lowered the number of colonizing bacteria in liver, spleen and lung of the mouse model and also lowered the levels of neutrophils and interleukin 8 in mice. Our findings suggest that the S. lappa extract exhibits an immunomodulatory effect with potential to reduce and cure systemic infections by both opaque and translucent colony variants of A. baumannii.
Publisher: Pakistan Journal of Medical Sciences
Date: 22-01-2019
Abstract: Objective: To assess the glycemic response of metformin in patients with Type-2 Diabetes Mellitus (T2DM) as well as to see its association with reductions in BMI and GIT intolerance. Methods: This Quasi, Experimental study was conducted at Jinnah-Allama Iqbal Institute of Diabetes and Endocrinology (JAIDE) Jinnah Hospital, Lahore from 1st March 2016 to 30th September 2016. Newly diagnosed T2DM patients were given metformin for duration of three months and later on they were categorized into Responders and Non-Responders on the basis of HbA1c (A1C) reductions, which were estimated by Hemoglobin (A1C) analyzer (TD4611A TAIDoc Tech. Taiwan) through photometry. Similarly, baseline BMI and BMI after three months therapy with metformin was also recorded. Results: Among total of 200 patients, 40.5% of the patients were classified as Non-Responders whereas 59.5% of the patients as Responders. The baseline BMI (26.09 kg/m2) was also decreased significantly after metformin therapy (25.40 kg/m2). It was found that metformin reduced the A1C in all the patients. However, the glycemic control was much better in patients with higher baseline A1C (1.13% ± 0.08) as compared to lower baseline levels (0.61% ± 0.07). Regarding GIT intolerance, 140 patients lacked the symptoms, out of which 60.7% were responders and 39.3% were non-responders. Conclusions: Metformin lead to improvement in glycemic control in 59.5% of newly diagnosed T2DM patients after taking metformin for three months but in 40.5% it did not which may be because of combined effects of various gene polymorphisms and their interaction with non-genetic factors. Metformin reduced the BMI in all the patients however, BMI lowering activity of metformin was same regardless of its effect on HbA1C. Moreover, the signs and symptoms of GIT intolerance did not differ between the two groups. How to cite this:Rashid M, Shahzad M, Mahmood S, Khan K. Variability in the therapeutic response of Metformin treatment in patients with type 2 diabetes mellitus. Pak J Med Sci. 2019 (1):71-76. doi: 0.12669 jms.35.1.100 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (icenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher: Informa UK Limited
Date: 19-05-2022
Publisher: Wiley
Date: 13-06-2022
DOI: 10.1002/JCB.30296
Abstract: The Hedgehog (Hh) pathway has emerged as a potential target for effectual hepatic repair based on convincing clinical and preclinical evidence that proves its significance in regulating hepatic damage. The purpose of this study is to probe the effect of quercetin on liver fibrosis through the modulation of the Hh pathway. Healthy male Wistar rats were ided into four groups ( n = 10). The control group was treated with saline, rats in the remaining three groups received twice a week intoxication with intraperitoneal injections of thioacetamide (200 mg/kg) for the induction of hepatic fibrosis for 6 weeks. After 28 days of quercetin and silymarin treatment, histological changes, serum biochemical index, antioxidant enzyme activity, key mediators of Hh pathway and inflammation were analyzed. Serological analysis showed statistically improved cholesterol, H.D.L‐Cholesterol, and L.D.L‐Cholesterol in the treatment groups. Superoxide dismutase and glutathione levels were found to be increased after the treatment with quercetin and silymarin. mRNA expression of important mediators of the Hh signaling, and inflammation including Shh, Ihh, Ptch‐1, Smo, Hhip, Gli‐3, TNF‐α, NFκ‐β, and Socs‐3 were significantly downregulated after the use of quercetin and silymarin. Quercetin also minimized the thioacetamide‐induced histopathological changes, as confirmed by a lower degree of hepatic lobule degeneration, the intralobular occurrence of inflammatory cells, and a lower degree of hepatocytic necrosis. Sudan Black B staining showed remarked lipids improvements in the treatment groups. Taken together, these findings demonstrate that quercetin could ameliorate hepatic fibrosis by antagonizing the hedgehog pathway and also suggest the hedgehog pathway as a potential therapeutic target for the treatment of liver fibrosis.
Publisher: Springer Science and Business Media LLC
Date: 14-05-2021
Publisher: Informa UK Limited
Date: 19-02-2010
DOI: 10.3109/02770900903483808
Abstract: Nitric oxide (NO) is considered as a hallmark for allergic airway inflammation in asthmatics and animal models. But the correlation between NO and antigen-induced pulmonary inflammation (AIPI), a rat model for asthma, in varying genetic background population has not been completely understood. The objective in this study is to observe the different responsiveness to AIPI in two commonly used inbred rat strains and verify the correlation between NO from different sources and pathological parameters of AIPI by using Dark Agouti (DA), E3, F1 (E3 x DA), and F2 rat populations. AIPI was induced by systemically immunizing and intranasally challenging E3, DA, F1 (DA x E3), and F2 rats with ovalbumin (OVA). Pathological changes and mucus secretion in lungs were observed after hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining, whereas eosinophils in bronchoalveolar lavage fluid (BALF) were counted after Giemsa staining. Delayed-type hyperresponsiveness was determined by subcutaneous injection of OVA in ear. Total immunoglobulin E (IgE) and OVA-specific IgG1 were detected with enzyme-linked immunosorbent assay (ELISA). NO concentration was measured by the Griess method. DA rats were unresponsive to OVA treatment, whereas E3 rats were susceptible to AIPI. F1 rats manifested the same responsiveness to OVA treatment as DA rats, and in idual F2 rats showed the variable severity of AIPI. NO concentration in BALF and serum was significantly elevated in E3 rats but not in DA and F1 rats after OVA treatment. In F2 rats, NO concentration in serum was positively correlated with eosinophils in BALF, total IgE, and pathological scores, whereas NO concentration in BALF correlated only with eosinophils in BALF and total IgE. DA and F1 rats are resistant, whereas E3 rats are sensitive, to AIPI. NO in serum can represent the severity of allergic inflammation and pathological changes in lungs in F2 population.
Publisher: Springer Science and Business Media LLC
Date: 02-05-2020
Publisher: SMW Supporting Association
Date: 07-12-2010
Abstract: Black seed oil (BSO) is widely used as a traditional medicine for asthma and other inflammatory diseases. The aim of this study is to evaluate the effects of BSO on ovalbumin (OVA) induced acute lung remodelling in E3 inbred rats. Rats were ided into three groups Control, OVA and BSO. The rats were intraperitoneally sensitised and challenged intranasally with OVA and treated intraperitoneally with pure BSO for seven days. The collagen deposition and other pathological alteration were determined by Masson's trichrome, PAS and HE staining. Activity of arginase, ornithine decarboxylase (ODC) and proline level was determined by spectrophotometry, and polyamine by HPLC. The mRNA expression of arginase І, endothelin1 (Edn1), matrix metallopeptidase 3 (MMP3) and growth factors was determined by real time RT-PCR. Massive inflammation and characteristics of lung remodelling including collagen deposition, goblet cell hyperplasia and proline level were observed in the lungs of OVA exposed rats. Administration of BSO in the OVA exposed rats suppressed the inflammatory cells infiltration, goblet cell hyperplasia and collagen deposition. The activity of total arginase and ODC proline and polyamine level was decreased in the lung homogenate of BSO treated rats. Furthermore, BSO abrogated the mRNA expression of Edn1, MMP3, transforming growth factor beta (TGF-β), fibroblast growth factor 2 (FGF2) and vascular epidermal growth factor (VEGF) in the lungs of OVA challenged rats. Administration of BSO significantly reduced the level of allergen induced lung remodelling. The effect of BSO on lung remodelling is probably mediated by the inhibition of arginase pathways and the expression of Edn1, MMP3 and growth factors. Our findings suggest that BSO might have useful implications in the treatment and future research into allergen-induced lung remodelling.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.PHYMED.2016.04.006
Abstract: Natural products are considered as an essential source for the search of new drugs. Pistacia integerrima galls (PI) have been used for the treatment of asthma and cough in traditional system of medicine. Current study investigates the immunomodulatory and anti-inflammatory activities of P. integerrima in mouse model of ovalbumin-induced allergic asthma. Mice were intraperitoneally sensitized and subsequently challenged intranasally with ovalbumin to induce allergic asthma. Experimental group mice were treated with methanol extract of P. integerrima extract (200mg/kg b. w.) and Methylprednisolone (MP) (15mg/kg b. w.) for 07 consecutive days, alongside intranasal challenge. Lung tissues were stained with Hematoxyline and Eosin (H & E), and Periodic Acid-Schiff (PAS) stains for histopathological evaluation. Lung wet/dry weight ratio was measured as an index of lung tissue edema. Albumin was injected in the right ear 24h before sacrificing the mice and difference of weight was taken as a degree of delayed type hypersensitivity (DTH). mRNA expression levels of TNF-α, IL-4, IL-5, Aquaporin-1 (AQP1), and AQP5 were evaluated using reverse transcription polymerase chain reaction (RT-PCR) followed by gel electrophoresis. The data showed both PI extract and MP significantly alleviated DTH and nearly normalized total leukocyte count and differential leukocyte count in both blood and BALF. We found significantly suppressed goblet cell hyperplasia and inflammatory cell infiltration after treatment with both PI extract and MP. Expression levels of TNF-α, IL-4, and IL-5 were also found significantly reduced after treatment with both PI extract and MP, which might have resulted in the amelioration of airway inflammation. Current study displayed that both PI extract and MP significantly decreased lung wet/dry ratio, suggesting reduction in pulmonary edema. RT-PCR analysis showed significant increase in AQP1 and AQP5 expression levels after treatment with both PI extract and MP, which might have caused the alleviation of pulmonary edema. Our study displays that P. integerrima possesses significant anti-asthmatic activity which may be attributed to reduction in TNF-α, IL-4, and IL-5 expression levels, and increase in AQP1 and AQP5 expression levels.
Publisher: Springer Science and Business Media LLC
Date: 08-05-2019
DOI: 10.1007/S10787-019-00597-2
Abstract: Oleanolic acid (OA) is a hydroxyl pentacyclic triterpene acid (HTAs) used in various ailments. Inflammatory diseases may be profoundly influenced by iron (Fe) and zinc (Zn) status. We studied the anti-asthmatic effects of two metal complexes (Fe and Zn) of OA in the ovalbumin (OVA)-induced rat model. Delayed type hypersensitivity (DTH) was measured. Total and differential leucocyte count was done in blood as well as bronchoalveolar lavage fluid (BALF). The mRNA expression levels of pro-inflammatory cytokines were measured in lung tissue by reverse transcription polymerase chain reaction. The levels of cyclooxygenase-2 (COX-2), immunoglobulin E (IgE) and 5-lipoxygenase (5-LOX) were estimated by enzyme linked immunosorbent assay. Splenocyte proliferation was performed through BrdU uptake method and nitric oxide levels were measured by colorimetric assay kit. The acute toxicity study was also done for the complexes. The asthmatic group developed allergic airway inflammation shown by increased DTH and inflammatory markers in blood and BALF. OA + Fe and OA + Zn displayed significant decrease in DTH, NO, expression of IL-4, 5, 13, 17, toll-like receptor-2, nuclear factor-kappa B and tumor necrosis factor-α serum IgE, COX-2, and 5-LOX. The metal complexes also attenuated OVA-stimulated splenocyte proliferation. While no hepatotoxic or nephrotoxic potential was shown by OA + Fe and OA + Zn. Our findings indicate that both OA + Fe and OA + Zn possess significant anti-asthmatic effect which may be ascribed to its immunomodulatory and anti-inflammatory features.
Publisher: Elsevier BV
Date: 02-2009
DOI: 10.1016/J.PUPT.2008.11.006
Abstract: The black seeds, from the Ranunculaceae family, have been traditionally used by various cultures as a natural remedy for several ailments. In this study, we examined the effect of black seed oil as an immunomodulator in a rat model of allergic airway inflammation. Rats sensitized to ovalbumin and challenged intranasally with ovalbumin to induce an allergic inflammatory response were compared to ovalbumin-sensitized, intranasally ovalbumin-exposed rats pretreated with intraperitoneally administered black seed oil and to control rats. The levels of IgE, IgG1 and ova-specific T-cell proliferation in spleen were measured by ELISA. The pro-inflammatory cytokine IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression levels were measured by reverse transcription polymerase chain reaction. The intraperitoneal administration of black seed oil inhibited the Th2 type immune response in rats by preventing inflammatory cell infiltration and pathological lesions in the lungs. It significantly decreased the nitric oxide production in BALF, total serum IgE, IgG1 and OVA-specific IgG1 along with IL-4, IL-5, IL-6 and TGF-beta1 mRNA expression. Black seed oil treatment resulted in decreased T-cell response evident by lesser delayed type hypersensitivity and lower T-cell proliferation in spleen. In conclusion, black seed oil exhibited a significant reduction in all the markers of allergic inflammation mainly by inhibiting the delayed type hypersensitivity and T-cell proliferation. The data suggests that inhibition of T-cell response may be responsible for immunomodulatory effect of black seed oil in the rat model of allergic airway inflammation.
Publisher: Springer Science and Business Media LLC
Date: 15-02-2022
Location: United States of America
No related grants have been discovered for Muhammad Shahzad.