ORCID Profile
0009-0007-0306-9221
Current Organisation
Washington University in St. Louis
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Publisher: Informa UK Limited
Date: 12-2015
DOI: 10.2147/DDDT.S79388
Publisher: Hindawi Limited
Date: 31-05-2018
DOI: 10.1155/2018/8903849
Abstract: Total flavones of Rhododendron simsii Planch flower (TFR) have a significant protective effect against cerebral ischemia-reperfusion injury. However, its mechanism is unclear. This study investigated the protection of TFR against cerebral ischemia-reperfusion injury via cystathionine- γ -lyase- (CSE-) produced H 2 S mechanism. CSE -/- mice and CSE-siRNA-transfected rat were used. Relaxation of cerebral basilar artery (CBA), H 2 S, and CSE mRNA were measured. TFR significantly inhibited cerebral ischemia-reperfusion-induced abnormal neurological symptom and cerebral infarct in the normal rats and the CSE +/+ mice, but not in the CSE -/- mice, and the inhibition was markedly attenuated in CSE-siRNA-transfected rat TFR elicited a significant vasorelaxation in rat CBA, and the relaxation was markedly attenuated by removal of endothelium or CSE-siRNA transfection or coapplication of NO synthase inhibitor L-NAME and PGI 2 synthase inhibitor Indo. CSE inhibitor PPG drastically inhibited TFR-evoked vasodilatation resistant to L-NAME and Indo in endothelium-intact rat CBA. TFR significantly increased CSE mRNA expression in rat CBA endothelial cells and H 2 S production in rat endothelium-intact CBA. The increase of H 2 S production resistant to L-NAME and Indo was abolished by PPG. Our data indicate that TFR has a protective effect against the cerebral ischemia-reperfusion injury via CSE-produced H 2 S and endothelial NO and/or PGI 2 to relax the cerebral artery.
Publisher: American Physiological Society
Date: 11-2022
DOI: 10.1152/AJPENDO.00109.2022
Abstract: Adipose tissue blood flow plays a key role in postprandial nutrient storage. People at-risk of type 2 diabetes have impaired postmeal adipose tissue blood flow. Impaired adipose tissue blood flow is associated with altered fat oxidation. Risk of type 2 diabetes may be elevated by poor adipose tissue blood flow.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.EJPHAR.2014.04.050
Abstract: Artemisinin has been used to treat malaria for centuries in the context of traditional Chinese medicine. In the present study, the effects of artemisinin on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in inflammatory bowel disease were investigated. LS174T cells exposed to artemisinin at various concentrations and for different periods of time were examined with respect to the specific induction of CYP3A4 and PXR mRNA expression. Transient transfection experiments showed transcriptional activation of the CYP3A4 gene through artemisinin to be PXR-dependent. An electrophoretic-mobility shift assay (EMSA) showed that artemisinin activates the DNA-binding capacity of the PXR for the CYP3A4 element. These results indicate that the induction of CYP3A4 by artemisinin is mediated through the activation of PXR. Using animal models, it was demonstrated that artemisinin abrogates dextran sulfate sodium (DDS)-induced intestinal inflammation. Preadministration of artemisinin ameliorated the clinical hallmarks of colitis in DSS-treated mice as determined by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Artemisinin was found to prevent or reduce the severity of colonic inflammation by inducing CYP3A expression by activation of PXR.
Publisher: Springer Science and Business Media LLC
Date: 29-09-2022
DOI: 10.1007/S00125-021-05572-7
Abstract: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in in iduals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal. In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+ i.e. a parent with type 2 diabetes n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC. Despite normal blood glucose concentrations, FH+ in iduals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH- p < 0.05) during the MMC. The MMC increased forearm muscle microvascular blood volume in both the FH- (1.3-fold, p < 0.01) and FH+ (1.3-fold, p < 0.05) groups but not in participants with type 2 diabetes. However, the MMC increased MBF (1.9-fold, p < 0.01), brachial artery diameter (1.1-fold, p < 0.01) and brachial artery blood flow (1.7-fold, p < 0.001) and reduced vascular resistance (0.7-fold, p < 0.001) only in FH- participants, with these changes being absent in FH+ and type 2 diabetes. Participants with type 2 diabetes displayed significantly higher vascular stiffness (p < 0.001) compared with those in the FH- and FH+ groups however, vascular stiffness did not change during the MMC in any participant group. Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC.
Publisher: Elsevier BV
Date: 07-2015
DOI: 10.1016/J.JEP.2015.04.006
Abstract: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated. LS174T cells and C57BL/6J mice were treated by the piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis. Data indicated that treatment of LS174T cells with piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via piperine was PXR-dependent. Data show that pre-administration of piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA). Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2015
DOI: 10.1007/S11655-015-2282-3
Abstract: To evaluate the rationality and compatibility of Shenfu Formula (, SFF), a typical Chinese medicine (CM) comprised of Panax ginseng and Aconitum carmichaeli. Caco-2 cells were used to study the permeability of Aconitum carmichaeli marker compounds when the CM preparation was combined with Panax ginseng. P-glycoprotein (P-gp) activity and protein as well as multidrug resistance 1 (MDR1) mRNA were analyzed with rhodamine123 efflflux, western blot and real time quantitative polymerase chain reaction. Aconitine (AC), mesaconitine (MA), hypaconitine (HA) and fifive other active alkaloids in Aconitum carmichaeli were selected as marker compounds. Panax ginseng inhibited intestinal absorption of highly toxic AC, MA and HA from Aconitum carmichaeli in Caco-2 cells. P-gp and breast cancer resistance protein (BCRP) were observed to be involved in AC, MA and HA efflflux. Panax ginseng induced P-gp activity in Caco-2 cells via increased MDR1/P-gp expression. Thus, Panax ginseng facilitated P-gp-mediated efflflux of toxic Aconitum carmichaeli alkaloids and restricted their intestinal absorption without inflfluencing other active components. Future studies to elucidate mechanism of reduced toxicity of Aconitum carmichaeli when combined with Panax ginseng will guide future formula optimization.
Publisher: Wiley
Date: 27-12-2017
Abstract: Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes. Either of these responses (myocyte and/or vascular) may be impaired in insulin resistance, and both impairments are apparent in type 2 diabetes, resulting in diminished glucose disposal by muscle. The aim of this review is to report on the growing body of literature suggesting that insulin-mediated control of skeletal muscle perfusion is an important regulator of muscle glucose uptake and that impairment of microvascular insulin action has important physiological consequences early in the pathogenesis of insulin resistance. This work was discussed at the 2015 Australian Physiological Society Symposium "Physiological mechanisms controlling microvascular flow and muscle metabolism".
Publisher: American Diabetes Association
Date: 07-07-2017
DOI: 10.2337/DC16-2750
Abstract: Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin’s microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. Seventeen (11 male and 6 female 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.
Publisher: Springer US
Date: 2023
Publisher: Elsevier BV
Date: 2021
Publisher: American Physiological Society
Date: 08-2018
DOI: 10.1152/AJPENDO.00448.2017
Abstract: Skeletal muscle microvascular (capillary) blood flow increases in the postprandial state or during insulin infusion due to dilation of precapillary arterioles to augment glucose disposal. This effect occurs independently of changes in large artery function. However, acute hyperglycemia impairs vascular function, causes insulin to vasoconstrict precapillary arterioles, and causes muscle insulin resistance in vivo. We hypothesized that acute hyperglycemia impairs postprandial muscle microvascular perfusion, without disrupting normal large artery hemodynamics, in healthy humans. Fifteen healthy people (5 F/10 M) underwent an oral glucose challenge (OGC, 50 g glucose) and a mixed-meal challenge (MMC) on two separate occasions (randomized, crossover design). At 1 h, both challenges produced a comparable increase (6-fold) in plasma insulin levels. However, the OGC produced a 1.5-fold higher increase in blood glucose compared with the MMC 1 h postingestion. Forearm muscle microvascular blood volume and flow (contrast-enhanced ultrasound) were increased during the MMC (1.3- and 1.9-fold from baseline, respectively, P 0.05 for both) but decreased during the OGC (0.7- and 0.6-fold from baseline, respectively, P 0.05 for both) despite a similar hyperinsulinemia. Both challenges stimulated brachial artery flow (ultrasound) and heart rate to a similar extent, as well as yielding comparable decreases in diastolic blood pressure and total vascular resistance. Systolic blood pressure and aortic stiffness remained unaltered by either challenge. Independently of large artery hemodynamics, hyperglycemia impairs muscle microvascular blood flow, potentially limiting glucose disposal into skeletal muscle. The OGC reduced microvascular blood flow in muscle peripherally and therefore may underestimate the importance of skeletal muscle in postprandial glucose disposal.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.JEP.2015.01.047
Abstract: Tanshinone IIA (Tan IIA) is one of the main natural active ingredients purified from Salvia miltiorrhiza radix, which has long been used in clinical practice in China to treat diseases including liver fibrosis, Alzheimer׳s disease, and cardiovascular diseases. Tan IIA has hepatoprotective properties, and is an efficacious PXR agonist. Our study was designed to observe the function and mechanism of the hepatoprotective properties of Tan IIA. HepG2 cells were used to investigate the vitrol effects of Tan IIA on PXR and CYP3A4. Gut-formed LCA is hepatotoxic, and has been implicated in the pathogenesis of cholestatic diseases. To further investigate the hepatoprotective mechanisms of Tan IIA against LCA-induced cholestasis in vivo, we choose the normal mice and siRNA-treated mice. The in vitro study demonstrated that the effect of Tan IIA on CYP3A4 was mediated by transactivation of PXR in a dose- and time-dependent manner. The in vivo experiments using PXR siRNA revealed that Tan IIA could protect against LCA-induced hepatotoxicity and cholestasis in a dose-dependent manner. These effects were partially caused by the upregulation of PXR, as well as Cyp3a11, Cyp3a13, and Mdr1, which are the enzymes responsible for LCA metabolism. This is the first report showing that the hepatoprotective effects of Tan IIA are partly mediated by PXR.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2018
DOI: 10.1161/CIRCIMAGING.117.007074
Abstract: In obesity and type 2 diabetes mellitus (T2D), adipose tissue expansion (because of larger adipocytes) results in reduced microvascular density which is thought to lead to adipocyte hypoxia, inflammation, and reduced nutrient delivery to the adipocyte. Adipose tissue microvascular responses in humans with T2D have not been extensively characterized. Furthermore, it has not been determined whether impaired microvascular responses in human adipose tissue are most closely associated with adiposity, inflammation, or altered metabolism. Overnight-fasted healthy controls (n=24, 9 females/15 males) and people with T2D (n=21, 8 females/13 males) underwent a body composition scan (dual-energy X-ray absorptiometry), an oral glucose challenge (50 g glucose) and blood analysis of clinical chemistries and inflammatory markers. Abdominal subcutaneous adipose tissue microvascular responses were measured by contrast-enhanced ultrasound at baseline and 1-hour post-oral glucose challenge. Adipose tissue microvascular blood volume was significantly elevated in healthy subjects 1-hour post-oral glucose challenge however, this effect was absent in T2D. Adipose tissue microvascular blood flow was lower in people with T2D at baseline and was significantly blunted post-oral glucose challenge compared with controls. Adipose tissue microvascular blood flow was negatively associated with truncal fat (%), glucoregulatory function, fasting triglyceride and nonesterified fatty acid levels, and positively associated with insulin sensitivity. Truncal fat (%), systolic blood pressure, and insulin sensitivity were the only correlates with microvascular blood volume. Systemic inflammation was not associated with adipose tissue microvascular responses. Impaired microvascular function in adipose tissue during T2D is not conditionally linked to systemic inflammation but is associated with other characteristics of the metabolic syndrome (obesity, insulin resistance, hyperglycemia, and dyslipidemia).
Publisher: American Physiological Society
Date: 12-2018
DOI: 10.1152/AJPENDO.00234.2018
Abstract: The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood s led for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.
Publisher: Bioscientifica
Date: 11-2019
DOI: 10.1530/JOE-19-0067
Abstract: Insulin stimulates glucose disposal in skeletal muscle in part by increasing microvascular blood flow, and this effect is blunted during insulin resistance. We aimed to determine whether metformin treatment improves insulin-mediated glucose disposal and vascular insulin responsiveness in skeletal muscle of insulin-resistant rats. Sprague–Dawley rats were fed a normal (ND) or high-fat (HFD) diet for 4 weeks. A separate HFD group was given metformin in drinking water (HFD + MF, 150 mg/kg/day) during the final 2 weeks. After the intervention, overnight-fasted (food and metformin removed) anaesthetised rats underwent a 2-h euglycaemic–hyperinsulinaemic cl (10 mU/min/kg) or saline infusion. Femoral artery blood flow, hindleg muscle microvascular blood flow, muscle glucose disposal and muscle signalling (Ser 473 -AKT and Thr 172 -AMPK phosphorylation) were measured. HFD rats had elevated body weight, epididymal fat pad weight, fasting plasma insulin and free fatty acid levels when compared to ND. HFD-fed animals displayed whole-body and skeletal muscle insulin resistance and blunting of insulin-stimulated femoral artery blood flow, muscle microvascular blood flow and skeletal muscle insulin-stimulated Ser 473 -AKT phosphorylation. Metformin treatment of HFD rats reduced fasting insulin and free fatty acid concentrations and lowered body weight and adiposity. During euglycaemic-hyperinsulinaemic cl , metformin-treated animals showed improved vascular responsiveness to insulin, improved insulin-stimulated muscle Ser 473 -AKT phosphorylation but only partially restored (60%) muscle glucose uptake. This occurred without any detectable levels of metformin in plasma or change in muscle Thr 172 -AMPK phosphorylation. We conclude that 2-week metformin treatment is effective at improving vascular and metabolic insulin responsiveness in muscle of HFD-induced insulin-resistant rats.
Location: United States of America
No related grants have been discovered for Donghua Hu.