ORCID Profile
0000-0003-4022-0000
Current Organisation
Monash University
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Publisher: International Journal of Pharmaceutical Sciences and Research
Date: 10-2017
Publisher: Springer Science and Business Media LLC
Date: 31-07-2020
Publisher: Hindawi Limited
Date: 23-03-2022
DOI: 10.1155/2022/6814901
Abstract: This study was aimed to determine the antibacterial activity of root bark, leaves, and pericarp extract of Diploknema butyracea and to evaluate the prospective antioxidant activity, total flavonoid, polyphenol, and carbohydrate content. The plant parts were collected and extracted by cold maceration, using hexane, ethyl acetate, methanol, and distilled water. Phytochemical screening of different s les of D. butyracea in different solvents revealed the presence of varied extent of alkaloid, saponin, terpenoid, anthraquinones, tannin, cardiac glycoside, flavonoid, carbohydrate, polyphenol, protein and amino acid, resin, and phytosterol. Our study showed that methanolic root bark extract exhibited the potent antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis, and Klebsiella pneumonia with an average zone of inhibition of 17.33 mm, 14.33 mm, and 13.0 mm, respectively. Surprisingly, all of the extracts were insensitive to Escherichia coli. The lowest minimum bactericidal concentration (MBC), 4.6 mg/ml, was observed with the aqueous pericarp extract against S. epidermidis and the highest was of 50 mg/ml shown by ethyl acetate pericarp against K. pneumonia. Our results showed that both the polar and nonpolar components present in the different parts of D. butyracea exhibit prominent antibacterial activities against different bacterial strains. The in vitro 2,2′-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity showed that the methanol extract of root barks displayed the most potent antioxidant activity (IC50 : 6.1 µg/ml). The total polyphenol content of the plant part extracts was observed between 19.48 ± 0.23 and 123.48 ± 1.84 µg gallic acid equivalent/mg of dry extract weight. Likewise, flavonoid content ranged from 40.63 ± 1.28 µg to 889.72 ± 3.40 μg quercetin equivalent/mg of dry extract weight and total carbohydrate content ranged from 11.92 ± 0.60 µg to 174.72 ± 0.60 µg glucose equivalent per/mg dry extract weight. Overall, our study showed that the root bark, pericarp, and leaves extract of D. butyracea evinced prominent antibacterial properties against various pathogenic bacterial strains.
Publisher: Sciencedomain International
Date: 18-10-2019
DOI: 10.9734/MRJI/2019/V29I230158
Abstract: Background: Cow urine has been widely used as therapeutic or additive agents in different parts of Nepal, mainly to treat infections, cuts, burns, etc. Cow urine has been considered as sacred and holy water and used in many rituals and worshipping purposes. Apart from therapeutic and rituals ceremony cow urines are also used in purification and disinfecting the houses. Objective: The aim of the study was to investigate the in-vitro antioxidant and antibacterial activity of cow urine from different altitudes across Nepal. Materials and Methods: Antioxidant activity of cow urines was carried out by using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) as free radicals. The antibacterial activity of cow urines was tested by the agar disc diffusion method against Escherichia coli (gram-negative) and Staphylococcus aureus (gram-positive). Results: The urine s le from Muktinath (Subalpine region) showed the highest 44.8±0.21% inhibition against DPPH free radicals. The urine s les from Jajarkot and Marpha (Temperate zone) showed 39.70±0.43% and 37.30±0.15% inhibition against DPPH free radicals respectively. The urine s les from Palpa and Shyangja (Subtropical region) showed 30.00±0.24 and 34.4±0.01 percent inhibition of DPPH radicals. The s les from Butwal and Dhangadhi (Tropical region) showed the least percentage inhibition of 23.9±0.08 and 21.12±0.1 respectively. Amongst the entire s le, the subalpine region of cow urine (Muktinath 3710m) made known the highest inhibition zone such as 10.56±0.05mm against S. aureus and 7.46±0.15 against E.coli. Conclusion: Our study has concluded that cow urines have the antibacterial and antioxidant activities and vary in potency according to altitudinal and climatic differences. Hence cow urine from the subalpine zone has better antibacterial and antioxidant activity than that of lower altitudinal climatic zones.
Publisher: Elsevier BV
Date: 10-2022
Publisher: Hindawi Limited
Date: 22-06-2021
DOI: 10.1155/2021/6678059
Abstract: This study aimed to evaluate and compare the in vivo chronic anti-inflammatory efficacy, from the ethyl acetate and ethanolic extracts of Artemisia vulgaris leaves, grown at three different altitudes in Nepal, by formalin-induced paw edema in Swiss albino mice. Edema was induced on the mice paw by administering 0.2% of formalin injection. Indomethacin was used as a standard drug at the concentration of 5 mg/kg of body weight. Ethyl acetate and ethanolic leaves extract, at the concentration of 200 mg/kg and 400 mg/kg, were used as test drugs. Standard drug and all the extracts were administered 30 min before formalin injection. The paw thickness was measured at 0, 1, 2, 3, 24, 48, and 72 hours after formalin injection, using a Vernier caliper. It was observed that both ethyl acetate and ethanolic extract from all the altitudes exhibited significant inhibition of paw edema ( p 0.05 ) induced by formalin. Maximum activity was shown by 400 mg/kg of the plant leaf extract taken from the temperate zone, with 54.05% of paw edema inhibition, and it is almost similar to the inhibition of standard drug (56.75%). Moreover, the ethanolic extract was found to be more effective than ethyl acetate extract in all the plant s les. The results suggested that the anti-inflammatory effect of A. vulgaris leaves increases with an increase in altitudes and this plant can be used as a useful source of medicine to treat chronic inflammation.
Publisher: Research Square Platform LLC
Date: 25-01-2023
DOI: 10.21203/RS.3.RS-2472929/V1
Abstract: Chemokines, the key regulators of leukocyte trafficking, are attractive targets for anti-inflammatory therapy. Evasins are anti-inflammatory, chemokine-binding proteins found in tick saliva, with important therapeutic potential. However, therapeutic application of evasins will require manipulation of their chemokine target selectivity. Here we describe a new family of evasins, class A3 evasins, that is unique to the tick genus Amblyomma and distinguished from “classical” class A1 evasins by an additional disulfide-bonded pair of cysteine residues near the chemokine recognition interface. The class A3 evasin EVA-AAM1001 (EVA-A) bound to CC chemokines and inhibited their receptor activation. However, unlike class A1 evasins, EVA-A did not utilise N- and C-terminal regions to differentiate chemokine targets. Instead, structures of EVA-A bound to four chemokines revealed a deep hydrophobic pocket, unique to class A3 evasins, that interacts with the residue immediately following the CC motif of the chemokine (the “CC+1” residue). The preference of EVA-A for chemokines with aliphatic CC+1 residues results from negative selection against binding of aromatic CC+1 residues into this pocket. Consequently, mutations to alleviate this negative selection yielded broad-spectrum chemokine inhibitors. This study illustrates that class A3 evasins are an excellent platform for engineering proteins with targeted chemokine binding selectivity for applications in research, diagnosis or anti-inflammatory therapy.
Publisher: EManuscript Technologies
Date: 2020
DOI: 10.4103/PR.PR_27_20
Publisher: Springer Science and Business Media LLC
Date: 14-07-2023
DOI: 10.1038/S41467-023-39879-3
Abstract: Chemokines are key regulators of leukocyte trafficking and attractive targets for anti-inflammatory therapy. Evasins are chemokine-binding proteins from tick saliva, whose application as anti-inflammatory therapeutics will require manipulation of their chemokine target selectivity. Here we describe subclass A3 evasins, which are unique to the tick genus Amblyomma and distinguished from “classical” class A1 evasins by an additional disulfide bond near the chemokine recognition interface. The A3 evasin EVA-AAM1001 (EVA-A) bound to CC chemokines and inhibited their receptor activation. Unlike A1 evasins, EVA-A was not highly dependent on N- and C-terminal regions to differentiate chemokine targets. Structures of chemokine-bound EVA-A revealed a deep hydrophobic pocket, unique to A3 evasins, that interacts with the residue immediately following the CC motif of the chemokine. Mutations to this pocket altered the chemokine selectivity of EVA-A. Thus, class A3 evasins provide a suitable platform for engineering proteins with applications in research, diagnosis or anti-inflammatory therapy.
Publisher: World Journal of Pharmacy and Pharmaceutical Sciences
Date: 06-2017
Publisher: Codon Publications
Date: 19-04-2023
Abstract: This study aims to evaluate the standard physicochemical parameters, such as iodine value, acid value, saponification value, ester value, refractive index, peroxide value, and viscosity, of Prinsepia utilis (P. utilis) seed oil (PUSO) obtained as hexane extract from seeds, and to formulate ketoconazole soap (2% w/w) by using extracted oil as a base. The quality control standards of the final ketoconazole soap complied with the standards specified in Indian Pharmacopeia. Pharmaceutical soap was obtained by treating PUSO with potassium hydroxide (KOH), undergoing basic saponification. All physicochemical parameters, such as acid value (21.78 mg KOH/g), saponification value (194.13 mg KOH/g), iodine value (99.7 g I2/100 g), ester value (172.35 mg KOH/g), refractive index (1.464), and viscosity (192 centipoises [cps]), conformed to industrial standards, except the peroxide value (19.23 milliequivalent KOH/g). Besides, evaluation of quality control parameters of pharmaceutical soap suggested that its various parameters, such as pH (7.3), foam-forming ability (14.5 cm), foam retention time (15 min), total fatty matter (69.31%), moisture content (10.35%), and drug content (99.37%), were within the acceptable limit. Overall, our study showed that P. utilis base was physicochemically stable and suitable for manufacturing cosmetic products, soaps, and sh oo in an economical manner, rather than using expensive chemical additives, in the pharmaceutical and cosmeceutical industry. Further, this study suggested that therapeutically and commercially successful ketoconazole soap, with all the required quality control parameters, could be manufactured by using naturally available oil at a low cost.
Publisher: Innovare Academic Sciences Pvt Ltd
Date: 24-05-2020
DOI: 10.22159/IJPPS.2020V12I7.37783
Abstract: Objective: Because of adverse side effects, caused by NSAIDs, tolerance, and dependence induced by opiates, the use of these analgesic agents has not been successful in all cases. Therefore, alternative analgesic drugs from plant sources are the new target now days. The objective of this study was to evaluate the analgesic activity of ethanolic extracts of stem barks and leaves of Ficus religiosa. Methods: The analgesic activity of ethanolic extract of stem barks and leaves was evaluated in the Swiss albino mice model using acetic acid-induced writing response and Eddy’s hot plate method. Analgesic activity was demonstrated with the percentage inhibition of acetic acid induced writings and the percentage increased in latency time of paw licking. The potency of test extracts was compared with standard drug, Diclofenac. Results: Ethanolic extract of leaves and bark of F. religiosa showed potential analgesic activity from both methods. From Eddy’s hot plate model, it was observed that the percentage of increased latency time at 90 min by ethanolic extract of leaves and stem bark was found to be 70.81 % (8.54 min) and 70.78 % (8.53 min) respectively at a dose of 400 mg/kg. Both of these results are statistically significant (p .05) as compared to the test group. Furthermore, both of these extracts showed the dose-dependent and time-dependent increased in latency time and these results are compared to that of standard drug Diclofenac. Similarly, ethanolic extract of leaves and stem at 400 mg/kg significantly inhibited the number of writhings induced by acetic acid. The percentage inhibition of writhings by ethanolic extract of leaves at a dose of 400 mg/kg was 68.47 % which was similar to that of standard drug Diclofenac (68.47 %). However, ethanolic extract of bark showed relatively lower percentage inhibition (60.79 %) as compared to leaf extract and standard, but the result was significant as compared to that of the test group (p .05). Conclusion: Ethanolic extracts of F. religiosa stem bark and leaf possess both central and peripheral analgesic properties and these effects may be beneficial for the management of pain.
Publisher: Proceedings of the National Academy of Sciences
Date: 25-02-2022
Abstract: Inflammatory diseases collectively account for numerous deaths and morbidity worldwide. New treatment approaches are needed. A central feature of inflammatory diseases is the recruitment of leukocytes to the affected tissues, which is stimulated by secreted proteins called chemokines. Effective suppression of leukocyte recruitment could be achieved by simultaneously targeting multiple chemokines, a natural molecular strategy used by tick salivary proteins called evasins. Here, we describe the structural and molecular features of a tick evasin that control its ability to bind and block a limited set of chemokines. By modifying these features, we demonstrate that evasins can be engineered to alter the array of chemokines that they target. Thus, this study establishes a structure-based paradigm for the development of antiinflammatory therapeutics.
Publisher: Hindawi Limited
Date: 16-11-2021
DOI: 10.1155/2021/6612135
Abstract: The fat obtained from the ripened seeds of Diploknema butyracea is widely used as a vegetable oil in rural areas of Nepal. This study was aimed for the physicochemical evaluation (acid value, iodine value, saponification value, peroxide value, ester value, pH, and liquefaction point) of the Diploknema butyracea seed extract (chyuri fat) and the formulation of 2% w/w ketoconazole ointment by using it as a base. All the physicochemical parameters were determined quantitatively by using the method of Indian Pharmacopoeia (IP), volume-I. By fusion method, 3 different formulations F-A, F-B, and F-C were prepared, in which different proportions of chyuri fat, polyethylene glycol 6000 (PEG 600), Tween 80, and propylene glycol were used as an ointment base. Various quality parameters such as spreadability, extrudability, viscosity, smoothness, pH, average fill weight, assay, content uniformity, accelerated stability, and drug release profiles were determined. HPLC was used for the determination of ketoconazole content in the ointment formulations. Physicochemical evaluation of the chyuri fat ensured its suitability for industrial purpose. The active ingredient release profile of formulations F-A (87.71%), F-B (88.89%), and F-C (91.09%) after 5 hours were within acceptable range along with other parameters. Assay of the formulations F-A, F-B, and F-C were reported to be 103.01, 107.9, and 102.45%, respectively. Overall, evaluation of the formulation F-A, prepared by using chyrui fat only, gave satisfactory results and most of the parameters were statistically similar ( p 0.05 ) to the F-B and F-C formulated by incorporating a certain proportion of synthetic base. Thus it can be concluded that chyuri fat can be the best alternative to replace the expensive synthetic base.
Publisher: Springer Science and Business Media LLC
Date: 26-03-2020
Publisher: MDPI AG
Date: 20-09-2019
Abstract: Background: Pogostemon benghalensis leaves have traditionally been utilized for relieving body aches, headaches and fever. Based on its uses, the present study was designed to investigate the antinociceptive, antipyretic and anti-edematogenic activities from P. benghalensis leaves’ methanol extract (PBME) in Wister rats. Methods: The thermal (hot plate) and chemical (acetic acid-induced writhing and formalin test) models for antinociceptive effects, and the Brewer's yeast induced hyperthermia test for antipyretic action and rat paw edema by carrageenan for anti-edematogenic activity, were applied for PBME at different dose levels. The acute toxicity of PBME through the oral route was performed to determine the lethal dose. Results: PBME significantly and dose-dependently reduced pyrexia and diminished edema volume, which depicted its antipyretic and anti-edematogenic effects respectively. The inhibition of writhing reflex, increased reaction latency and reduced frequency of licking indicated that PBME has significant dose-dependent antinociceptive activity. P. benghalensis methanol extract at 4000 mg/kg shows no sign of toxicity, which is a considerable, good margin of safety. Conclusions: The study illustrated the antipyretic, antinociceptive and anti-inflammatory potential of P. benghalensis leaf extract with a safety margin, and validated its traditional use to alleviate fever, pain, and inflammation.
Publisher: Innovare Academic Sciences Pvt Ltd
Date: 17-07-2020
DOI: 10.22159/IJCPR.2020V12I4.39085
Abstract: Objective: The systematic study of effective alternative anti-diabetic drugs has great importance to manage diabetes as well as other oxidative stress-related diseases. According to previous research, root and bark of Mussaenda macrophylla plant has anti-microbial, anti-coagulant, anti-inflammatory, and hepatoprotective activity. Ethnomedicinal data shows that Mussaenda macrophylla is used to treat diabetes as well as oxidative stress. The objective of this research is to investigate in vitro anti-diabetic and anti-oxidant activity of root extract of Mussaenda macrophylla. Methods: DPPH free radical scavenging assay was used to detect anti-oxidant potency of ethanol and methanol root extract of the plant and expressed as % of radicle inhibition. Anti-diabetic activity was determined by the glucose diffusion method using a glucose oxidase kit and results were expressed as mean±SD. Results: The ethanol root extract at the concentration of 50 mg/ml and 100 mg/ml showed better glucose diffusion inhibition than that of methanol extract at the same concentration on increasing time interval. Ethanol extract at the concentration 100 µg/ml displayed better DPPH scavenging activity (89.83±0.19 %) than that of methanol extract (86.61±0.75%). Conclusion: This study concluded that ethanol and methanol root extract of Mussenda macrophylla have potent anti-diabetic as well as anti-oxidant activity but further advance research is necessary in the animal model.
Publisher: Hindawi Limited
Date: 27-04-2021
DOI: 10.1155/2021/6649574
Abstract: Garugapinnata Roxb. (Burseraceae) is a medium-sized tree widely available all over the tropical regions of Asia. Bryophyllum pinnatum (Lam) Oken. (Crassulaceae) is an indigenous and exotic plant grown in tropical regions. Both plants have been used for their anti-inflammatory, antioxidant, anticancer, wound healing, antidiabetic activities, etc. This investigation was designed to explore the result shown by methanolic extract of Garuga pinnata bark and Bryophyllum pinnatum leaves, on cognitive power and retention of the memory in experimental mice along with quantification of phenolic compounds and DPPH radicals neutralizing capacity. The memory-enhancing activity was determined by the elevated plus-maze method in Scopolamine-induced amnesic mice, using Piracetam as allopathic and Shankhpushpi as ayurvedic standard drugs. Two doses (200 and 400 mg/kg p.o.) of both extracts were administered to mice up to 8 consecutive days transfer latency of in idual group was recorded after 45 minutes and memory of the experienced things was examined after 1 day. DPPH assay method and the Folin–Ciocalteu method were employed to determine antioxidant potency and total phenol amount, respectively. 400 mg/kg of the methanolic B. pinnatum bark extract significantly improved memory and learning of mice with transfer latency (TL) of 32.75 s, which is comparable to that of standard Piracetam (21.78 s) and Shankhpushpi (27.83 s). Greater phenolic content was quantified in B. pinnatum bark extract (156.80 ± 0.33 µg GAE/mg dry extract) as well as the antioxidant potency (69.77% of free radical inhibition at the 100 µg/mL concentration). Our study proclaimed the scientific evidence for the memory-boosting effect of both plants.
Publisher: Wiley
Date: 11-09-2014
DOI: 10.1111/FEBS.12969
Abstract: Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer properties in several human carcinomas, but its molecular mechanisms of action remain unclear. Here, we show that baicalein leads to human cancer cell death by inducing autophagy rather than apoptosis, because cell death induced by baicalein was completely reversed by suppressing the expression levels of key molecules in autophagy such as Beclin 1, vacuolar protein sorting 34 (Vps34), autophagy-related (Atg)5 and Atg7, but not by pan-caspase inhibitor. Our data revealed that baicalein significantly increased the number of green fluorescence protein-cytosol-associated protein light chain 3 (GFP-LC3)-containing puncta and LC3B-II expression levels, which were further enhanced by chloroquine treatment. Furthermore, a luciferase-based reporter assay showed that the ratio of RLuc-LC3wt/RLuc-LC3G120A was greatly reduced. The data suggested that baicalein induced not only autophagosome formation, but also autophagic flux. Experiments using short interfering RNAs and pharmacological inhibitors revealed that Beclin 1, Vps34, Atg5, Atg7 and UNC-51 (Caenorhabditis elegans)-like kinase 1 (ULK1) play pivotal roles in mediating baicalein-induced autophagy. Moreover, baicalein activated AMP-activated protein kinase (AMPK)α, leading to ULK1 activation through phosphorylation at Ser555, whereas both protein and mRNA levels of mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and autophagy, were markedly downregulated by baicalein. Our data suggest that the anticancer effects of baicalein are mainly due to autophagic cell death through activation of the AMPK/ULK1 pathway and inhibition of mTOR/Raptor complex 1 expression. These results provide new mechanistic insights into the anticancer functions of autophagy inducers, such as baicalein, which may be used as potential therapeutics for cancer treatment.
No related grants have been discovered for Pramod Aryal.