INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2021
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IF 6.953
Huashan Gao,Linlin Ding,Rui Liu,Xinhua Zheng,Xichao Xia,Fuan Wang,Jinxu Qi,Weishuang Tong,Yuanhao Qiu
Anoectochilus roxburghii is a traditional herb in China that can be potentially used to treat diabetes. A novel polysaccharide ARLP-W was isolated from Anoectochilus roxburghii by chromatography on DEAE-52 cellulose. Chemical analysis indicated that ARLP-W (8.1 × 10 4 Da) was mainly composed of mannose and glucose. The main linkages of glycosidic bonds of ARLP-W were β-1, 4-Manp and α-1, 4-Glcp. The terminal Glcp was connected to Manp-via O-3. RT-qPCR and western blotting analysis showed that ARLP-W caused a significant reduction in the levels of the key gluconeogenesis enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) in the liver. The results of the insulin resistance tests indicated that ARLP-W increased glucose absorption. These results indicate that ARLP-W has a good therapeutic effect on type 2 diabetes and can assist with further development and application treatment of diabetes.
研究领域:
药理学
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生物化学
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糖尿病研究
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DOI
PubMed
高影响因子
FITOTERAPIA
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2024
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IF 2.5
Li Wang,Yi-Xiao Chen,Xin-Jing Meng,Hai-Yang Liang,Ya-Dan Zhang,Hui-Hui Zhou,Yu-Hang Liu,Xiao-Yu Chen,Zhen-Hua Liu,Shi-Ming Li,Wen-Yi Kang
Patrinia punctiflora is a medical and edible Chinese herb with high nutritional and medicinal value. The continuing study of its chemical constituents led to the isolation of six iridoids, which were previously unreported compounds, patriscabioins P U ( 1–6 ). Their structures were characterized and confirmed with NMR (1D & 2D), HRMS, IR and UV. Among them, compound 5 was screened to evaluate its insulin resistance activity on an IR-HepG-2 cell model. Compound 5 had no cytotoxicity compared with the control group and could promote glucose uptake in IR-HepG-2 cells. Through further mechanism studies, the undescribed compound 5 could increase the expression levels of PI-3 K, p -AKT, GLUT4 and p -GSK3 β proteins. Moreover, the expression of PEPCK and G6Pase proteins, which are key gluconeogenic enzymes, was also inhibited. Thus, compound 5 promotes the transfer of GLUT4 to the plasma membrane by activating the PI-3 K/AKT signaling pathway, at the same time, promotes glycogen synthesis and inhibits the onset of gluconeogenesis, which in turn ameliorates insulin resistance.
研究领域:
药理学
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
Food Science & Nutrition
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2022
·Vol. 10
·期 7
·2455-2469
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IF 3.553
Xiaoyu Chen,Hongyuan Zhao,Fanqiang Meng,Libang Zhou,Xinyi Pang,Zhaoxin Lu,Yingjian Lu
Surfactin, produced by Bacillus amyloliquefaciens fmb50, was used to treat insulin-resistant (IR) hepatocyte. It was found that surfactin increased glucose consumption in insulin-resistant HepG2 (IR-HepG2) cells and ameliorated IR by increasing glucose transporter 4 (GLUT4) protein expression and AMP-activated protein kinase (AMPK) mRNA expression, promoting GLUT4 translocation and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) in IR-HepG2 cells. Meanwhile, surfactin downregulated protein expression of phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase), further inhibiting hepatic gluconeogenesis. In addition, surfactin played important roles in eliminating reactive oxygen species (ROS), improving mitochondrial dysfunction, and inhibiting proinflammatory mediators. We observed that surfactin promoted glucose consumption, meanwhile increased translocation and protein expression of GLUT4 in Caco-2 cells. These results confirmed the conclusion in hepatic cells. Furthermore, surfactin supplement decreased body weight, food intake, and fasting blood glucose of type 2 diabetes mellitus (T2DM) mice induced by streptozotocin (STZ)/high-fat diet (HFD). Our data indicated that surfactin ameliorated insulin resistance and lowered blood glucose in intro and in vivo.
研究领域:
药理学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2015
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IF 6.332
Lushan Yu,Zhangting Wang,Minmin Huang,Yingying Li,Kui Zeng,Jinxiu Lei,Haihong Hu,Baian Chen,Jing Lu,Wen Xie,Su Zeng
The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis . In this study, we investigated the effects of two evodia alkaloids, rutaecarpine ( Rut ) and evodiamine ( Evo ), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo . The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors : New Tricks for An Old Dog, edited by Dr. Wen Xie.
研究领域:
药理学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
JOURNAL OF FOOD BIOCHEMISTRY
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2021
·Vol. 45
·期 7
·e13771
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IF 2.72
Chao Xin,Mengya Zhao,Jiahui Wang,Zhenyu Wang
Hawthorn berry has been proved hypoglycemic effect due to the presence of some α-glucosidase inhibitors. Herein, screening and identifying of α-glucosidase inhibitors from hawthorn berry were conducted, and the results showed polyphenols mainly containing quercetin (74.58%) and hyperioside (9.58%) were responsible for its bioactivity. In order to enhance the hypoglycemic effect, the combined glucose-lowering complex (DEH) consisting of hawthorn polyphenols, D-chiro-inositol (DCI), and epigallocatechin gallate (EGCG) was prepared, where three ingredients exerted the synergistic hypoglycemic effect to enhance glucose consumption and glycogen levels and inhibit hepatic gluconeogenesis in IR-HepG2 cells. In STZ/HFD-induced mice, DEH effectively improved insulin resistance, reduced fasting blood glucose (FBG) and hepatic gluconeogenesis, and increased hepatic glycogen synthesis and storage via down-regulation of PI3K/Akt/FOXO1-mediated PEPCK and G6Pase and up-regulation of PI3K/Akt/GSK3-mediated GS activation in the liver. In summary, these findings indicate that DEH is a potential novel strategy for the treatment of type 2 diabetes. Practical applications Glucose-lowering complex (DEH) with superior hypoglycemic effect, can effectively improve the insulin resistance, reduce the fasting blood glucose, hepatic gluconeogenesis and increase the hepatic glycogen synthesis and storage in mice, which represents a potential novel strategy for the treatment of type 2 diabetes.
研究领域:
药理学
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糖尿病研究
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分子生物学
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PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2017
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IF 3.154
Jiarui Nie,Yaning Chang,Yujia Li,Yingjun Zhou,Jiawen Qin,Zhen Sun,Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated for the ameliorative effects on insulin resistance and the mechanisms were identified, using non-insulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5 weeks of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Proinflammatory cytokines in serum and the expressions of tumor necrosis factor-alpha (TNF-α) mRNA in tissues were markedly downregulated from CAPE-treated mice. In vitro, CAPE supplement significantly improved glucose consumption, glucose uptake, glycogen content, and oxidative stress and decreased expression of glucose-6-phosphatase (G6Pase) mRNA in cells. Both in vivo and in vitro, CAPE enhanced p-Akt (Ser473) and p-insulin receptor substrate (IRS)-1 (Tyr612), but inhibited p-JNK (Thr183/Tyr185), p-NF-κB p65 (Ser536), and nuclear translocation of p-NF-κB p65 (Ser536). In summary, CAPE can ameliorate insulin resistance through modulation of JNK and NF-κB signaling pathway in mice and HepG2 cells.
研究领域:
药理学
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内分泌学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2022
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IF 5.988
Sa Yang,Shijie Cao,Congyu Li,Jichao Zhang,Chang Liu,Feng Qiu,Ning Kang
Non-alcoholic fatty liver disease (NAFLD) is a major public health problem in many countries. Berberine (BBR) is an effective therapeutic agent in alleviating NAFLD. Berberrubine (BRB) is one of the main active metabolites of BBR, which shows significant anti-obesity and antihypoglycemic effects. However, whether BRB is responsible for the in vivo therapeutic effect and the underlying mechanism of BRB on NAFLD have not been elucidated. In this study, the ability of BRB to ameliorate NAFLD, together with its molecular mechanism, was investigated. The results showed that BRB treatments could significantly improve hepatic steatosis and insulin resistance in high-fat diet (HFD)-fed mice and oleic acid (OA)-treated HepG2 cells. Meanwhile, BBR and BRB treatment similarly prevented lipid accumulation by regulating the protein expression of ATGL, GK, PPARα, CPT-1, ACC1, FAS, and CD36. In addition, compared with BBR, BRB could maintain glucose homeostasis via GLUT2, GSK3β, and G6Pase in HFD-fed mice. Furthermore, the components of the gut microbiota in mice were analyzed by 16S rRNA gene sequencing. BBR and BRB treatment could greatly modify the structure and composition of gut microbiota. At the genus level, BBR and BRB treatment decreased Lactobacillus and Romboutsia , while BBR increased beneficial bacteria, such as Akkermansia and Bacteroides , and BRB increased beneficial bacteria, such as Ileibacterium and Mucispirillum . Altogether, both BRB and BBR were active in alleviating NAFLD in vivo and BRB might be used as a functional material to treat NAFLD clinically.
研究领域:
药理学
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代谢学
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胃肠病学
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微生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2022
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IF 5.195
Xu-guang Zhang,Ai-xia Liu,Yu-xin Zhang,Ming-yan Zhou,Xiang-yi Li,Ming-hai Fu,Yi-peng Pan,Jian Xu,Jun-qing Zhang
Ethnopharmacological relevance Alpinia officinarum Hance, a perennial natural medicine-food herb, has been traditionally used to treat colds, stomachache, and diabetes for thousands of years. 1,7-Diphenyl-4E-en-3-heptanone (DPH5), a diarylheptanoid isolated from the rhizome of A. officinarum has been reported to be safe and to have antioxidant and hypoglycemic effects, suggesting its potential in the treatment of insulin resistance (IR). Aim of the study : Aim of to investigate the protective effect of DPH5 on IR and elucidate its underlying mechanism of action. Materials and methods HepG2 cells were used as the research objects. Glucose uptake and reactive oxygen species (ROS) levels in high glucose–induced insulin-resistant HepG2 cells were assessed using flow cytometry. Glucose consumption and the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were analyzed using the corresponding assay kits. The expression of mRNA and proteins related to insulin signaling, glucose metabolism, and antioxidant factor, including insulin receptor substrate-1 (IRS1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), translocation of glucose transporter-4, glycogen synthase kinase-3β (GSK3β), glucokinase (GCK), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), nuclear factor-erythroid 2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), NADPH quinoneoxidoreductase (NQO1), and glutathione peroxidase (GSH-Px) was determined using real-time quantitative polymerase chain reaction and western blotting . Furthermore, molecular docking was performed to determine the spatial mechanism of DPH5 on the key targets PI3K, AKT, Nrf2 , and GSK3β. Results DPH5 could improve IR that manifested as increased glucose uptake and glucose consumption in insulin-resistant HepG2 cells. Moreover, DPH5 could enhance antioxidant capacity by activating Nrf2/HO-1 elements, including increasing Nrf2, HO-1, SOD, NQO1, and GSH-Px expression and reducing MDA, ROS, and JNK levels, thereby improving oxidative stress and ultimately alleviating IR. Additionally, DPH5 could promote the expression of IRS1, PI3K, AKT, GSK3β, GCK, and PK, and downregulate the expression of PEPCK and G6pase, thereby accelerating glucose utilization and enhancing insulin sensitivity. The mechanism underlying the effect of DPH5 in alleviating IR was related to the PI3K/AKT- and Nrf2/HO-1-mediated regulation of the GSK3β signaling pathway, and the results were further confirmed using the specific inhibitors LY294002 and ML385. Results from molecular docking indicated that there were different regulatory sites and interacting forces between DPH5 and PI3K, AKT, Nrf2, and GSK3β; however, the binding force was relatively strong. Conclusions DPH5 improved oxidative stress and glucose metabolism via modulating the PI3K/AKT-Nrf2-GSK3β pathway, thereby ameliorating IR. Overall, our findings suggest the potential of DPH5 as a natural medicine to treat type-2 diabetes mellitus.
研究领域:
药理学
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细胞生物学
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分子生物学
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内分泌学
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糖尿病
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DOI
PubMed
高影响因子
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