PLoS One
·
2013
·Vol. 8
·期 1
·e54198
·
IF 3.73
Hao Gong,Xin Zhang,Biao Cheng,Yue Sun,Chuanzhou Li,Ting Li,Ling Zheng,Kun Huang
Bisphenol A (BPA) is a chemical compound widely used in manufacturing plastic products. Recent epidemiological studies suggest BPA exposure is positively associated with the incidence of type 2 diabetes mellitus (T2DM), however the mechanisms underlying this link remain unclear. Human islet amyloid polypeptide (hIAPP) is a hormone synthesized and secreted by the pancreatic β-cells. Misfolding of hIAPP into toxic oligomers and mature fibrils can disrupt cell membrane and lead to β-cell death, which is regarded as one of the causative factors of T2DM. To test whether there are any connections between BPA exposure and hIAPP misfolding, we investigated the effects of BPA on hIAPP aggregation using thioflavin-T based fluorescence, transmission electronic microscopy, circular dichroism, dynamic light scattering, size-exclusion chromatography,fluorescence-dye leakage assay in an artificial micelle system and the generation of reactive oxygen species in INS-1 cells. We demonstrated that BPA not only dose-dependently promotes the aggregation of hIAPP and enhances the membrane disruption effects of hIAPP, but also promotes the extent of hIAPP aggregation related oxidative stress. Taken together, our results suggest that BPA exposure increased T2DM risk may involve the exacerbated toxic aggregation of hIAPP.
研究领域:
毒理学
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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
RSC Advances
·
2016
·Vol. 6
·期 9
·7239-7248
·
IF 3.289
Lizi Huang,Mingyan Liao,Xin Yang,Hao Gong,Liang Ma,Yudan Zhao,Kun Huang
Bisphenols (BPs) are a group of chemicals with two hydroxyphenyl functionalities. BPs analogues including bisphenol A (BPA), bisphenol B (BPB), bisphenol F (BPF), bisphenol S (BPS), bisphenol AF (BPAF), bisphenol AP (BPAP), tetrabromobisphenol A (TBBPA) and tetrachlorobisphenol A (TCBPA) are widely used in the production of plastic materials. There has been a growing concern worldwide about environmental BPs exposure due to their potential adverse effects on human health. Deposition of β-cell toxic misfolded human islet amyloid polypeptide (hIAPP), a hormone biosynthesized and secreted by the pancreatic β-cells, is a cardinal finding in type 2 diabetes mellitus (T2DM). Epidemiological studies suggest BPA exposure is positively associated with the incidence of T2DM, which may be due to the exacerbated toxic aggregation of hIAPP induced by BPA as we previously reported. Here, we demonstrate that bisphenol analogues showed different effects on hIAPP amyloid formation. Unlike the accelerating effects of BPA, four BPs analogues (BPAF, BPAP, TBBPA and TCBPA) showed inhibitory effects on hIAPP aggregation and decreased the membrane disruption capacity of hIAPP. Our results also explained a possible relationship between the spatial structure and the inhibitory capacities of BPs analogues.
研究领域:
环境科学
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毒理学
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分子生物学
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内分泌学
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Jia-Lin Yu,Zhen-Yang Zhang,Sheng-Ping Liu,Hong-Ping Long,Ting-Ting Wang,Feng-Qing Huang,Jia Guo,Wei-Long Xu,Fei Li
Ethnopharmacological relevance Type 2 diabetes mellitus (T2DM) poses significant threats to public health. In Traditional Chinese Medicine (TCM), the Phellodendri Chinensis Cortex-Anemarrhenae Rhizoma (PCC/AR) herb pair has long been used for T2DM treatment, although its specific anti-diabetic mechanisms remain unclear. Aim of the study This study aimed to elucidate the relationship between metabolomics of T2DM patients and the anti-diabetic effects of PCC/AR herb pair in mice through clinical metabolomics and both in vitro and in vivo experiments. Materials and methods In this study, a T2DM mouse model was established via high-fat feeding (HFD) and streptozotocin (STZ) injection. The effects of PCC/AR on blood glucose, lipid metabolism, and inflammatory markers were evaluated. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was performed for metabolomics analysis of T2DM patients. Results Serum metabolomics analysis identified significant alterations in metabolites linked to the biosynthesis of unsaturated fatty acids and purine metabolism in T2DM patients, with elevated 2-hydroxyvaleric acid (2HB) levels. In T2DM mice, PCC/AR intervention normalized FBG, GHbA1c, TC, TG, LDL-C, HDL-C, TNF-α and IL-1β levels, while improving insulin sensitivity and pancreatic β-cell function in T2DM mice. Notably, PCC/AR reduced key enzymes in gluconeogenesis and fatty acid synthesis, PEPCK and ACC1. Conclusion PCC/AR herb pair exerts an anti-diabetes effect in T2DM mice by regulating 2HB through ACC1 inhibition, thereby reducing FFA and TG synthesis. Additionally, PCC/AR may also exert its effects by modulating glucose and lipid metabolism and reducing inflammation. These results support further investigation into the PCC/AR herb pair as a complementary therapy for T2DM.
研究领域:
中药学
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代谢组学
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糖尿病研究
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DOI
PubMed
高影响因子
Diabetology & Metabolic Syndrome
·
2023
·Vol. 15
·期 1
·1-13
·
IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
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PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Hong Yang,Yong-xin Chen,Ke-gang Linghu,Peng-yan Ren,Yu-ting Yao,Feng Jiang,Guo-ping Wu,Ting-ting Chen,Ling Tao,Qian-yun Sun,Yue Li,Xiang-chun Shen
Background Type 2 diabetes mellitus (T2DM) is primarily attributed to impaired insulin secretion caused by β cell dysfunction. 1,8-Cineole is a key bioactive compound in the essential oil extracted from Fructus Alpiniae Zerumbet , which possesses anti-inflammatory and antioxidant properties. Nevertheless, it remains elusive about the protective effect and precise mechanisms of 1,8-Cineole against the β cell deterioration in DM. Purpose To investigate the effect of 1,8-Cineole on β cell dysfunction in T2DM and the potential mechanism of its action. Methods A mouse model of T2DM and a β cell model of high glucose induction were generated to analyze the pharmacological properties of 1,8-Cineole. Proteomic and network pharmacological analyses were conducted to identify the crucial pathways involved in T2DM. Resveratrol [a Sirtuin1 (Sirt1) agonist] and Sirt1 knockdown were used to ascertain the mechanism of 1,8-Cineole in T2DM. The binding affinity of 1,8-Cineole to Sirt1 was assessed with molecular docking, surface plasmon resonance, immunoprecipitation assay, and cellular thermal shift assay. Results First, dysregulated crucial pathways in T2DM were screened out, including redox imbalance and mitochondrial dysfunction. Subsequently, 1,8-Cineole was found to activate Sirt1 and nuclear factor E2-related factor 2 (Nrf2) to repress oxidative stress in both T2DM mice and high glucose-induced β cells, thereby relieving mitochondrial dysfunction and apoptosis. Furthermore, 1,8-Cineole specifically targeted Sirt1 and favored the direct interaction between Sirt1 and Nrf2, ultimately restoring β cell function. Conclusions Our findings provide the first evidence that 1,8-Cineole directly binds to Sirt1 protein and enhances its stability, therefore rectifying impaired oxidative homeostasis, and then suppressing mitochondrial dysfunction and apoptosis in T2DM, indicating that 1,8-Cineole may be a potential candidate drug for DM treatment.
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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PubMed
高影响因子
JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
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2022
·
IF 1.61
Wei-Wei Ye,Xiang-Ying Meng,Qian Zhao,Jian-Yang Chen,Cong Liu,Feng Chen,Yong Zhou,Yi Wang
Echinacoside (ECH) is the main compound of Cistanche deserticola, which possesses antioxidant, antitumor, antifatigue, and anti-inflammatory properties. The present study investigated the protective effects of echinacoside on type 2 diabetes mellitus (T2DM)-induced injury in T2DM injury db/db mice model and insulin-resistant LO2 cell model. The results demonstrated that ECH probably alleviated T2DM-induced injury by mediating the AKT pathway, which provided a new direction for the treatment of T2DM-induced injury.
研究领域:
药理学
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糖尿病研究
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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
ORAL DISEASES
·
2023
·
IF 3.8
Sitong Hu,Yihui Zhu,Shujia Yu,Yanchuan Guo,Yihu Wang,Menghao Lv,Wei Bai,Pan Ma
Objective The aim of this study was to investigate the effect of IL-10 on the phenotype polarization of macrophages and osteogenesis in diabetes mellitus type 2 (T2DM) rat jaw defects. Methods Lipopolysaccharide (LPS) and interleukin-10 (IL-10) were chosen to induce the polarization of macrophages. In vitro assessment included wound-healing assay, western blotting, and alizarin red staining after co-culture of the bone marrow-derived mesenchymal stem cells (BMSCs) and induced macrophages. For in vivo study, IL-10 was loaded on GelMA-Heparin and applied to bone defects of the alveolar ridge in diabetic rats, while Bio-Oss Collagen, simple GelMA-Heparin, and blank control groups were set for contrast experiment. The mandibles of rats were processed for micro-computed tomography, histology, and immunohistochemistry 1 week and 4 weeks after the operation. Results IL-10 induced expression of arginase 1, TGF-β1, EGR2, and Mannose Receptor (CD206), whereas LPS induced expression of iNOS, TNF-α, IL-6, CD80. The BMSCs co-cultured with macrophages induced by IL-10 showed increased migration, osteogenic differentiation, and mineralization in vitro. Notably, the IL-10-laden GelMA-Heparin group showed quicker new bone formation and a higher M2/M1 ratio of macrophages in the jawbone defect area compared with the control groups. Conclusions IL-10 can stably induce macrophages to M2 type, thereby influencing BMSCs and improving the osteogenesis of jaw bone defects.
研究领域:
免疫学
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骨科
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再生医学
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口腔科学
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DOI
PubMed
高影响因子
Nutrients
·
2022
·Vol. 14
·期 19
·3980
·
IF 6.706
Shan-Shan Zhang,Yu-Fei Hou,Shao-Jing Liu,Sen Guo,Chi-Tang Ho,Nai-Sheng Bai
Forty compounds were isolated and characterized fromA. tenuissimumflower. Among them, twelve flavonoids showed higher α−glucosidase inhibition activities in vitro than acarbose, especially kaempferol. The molecular docking results showed that the binding of kaempferol to α−glucosidase (GAA) could reduce the hydrolysis of substrates by GAA and reduce the glucose produced by hydrolysis, thus exhibiting α−glucosidase inhibition activities. The in vivo experiment results showed that flavonoids−richA. tenuissimumflower could decrease blood glucose and reduce lipid accumulation. The protein expression levels of RAC−alpha serine/threonine−protein kinase (AKT1), peroxisome proliferator activated receptor gamma (PPARG), and prostaglandin G/H synthase 2 (PTGS2) in liver tissue were increased. In addition, the Firmicutes/Bacteroidetes (F/B) ratio was increased, the level of gut probioticsBifidobacteriumwas increased, and the levels ofEnterobacteriaceaeandStaphylococcuswere decreased. The carbohydrate metabolism, lipid metabolism, and other pathways related to type 2 diabetes mellitus were activated. This study indicating flavonoids−richA. tenuissimumflower could improve glycolipid metabolic disorders and inflammation in diabetic mice by modulating the protein expression and gut microbiota.Keywords:A. tenuissimumflower flavonoids;network pharmacology;molecular docking;gut microbiota;type 2 diabetes mellitus
研究领域:
药理学
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分子生物学
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微生物学
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糖尿病研究
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Haihui Jiang,Shibo Feng,Panpan Zhang,Jiaojiao Wang,Yi Jiang,Huawei Zhang,Xiaomei Song,Wenli Huang,Yundong Xie,Chong Deng
Ethnopharmacological relevance Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. Aim of the study This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. Materials and methods GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. Results Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group ( P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. Conclusions The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.
研究领域:
药理学
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民族药理学
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糖尿病研究
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微生物组研究
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代谢组学
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DOI
PubMed
高影响因子
Nutrients
·
2025
·Vol. 17
·期 20
·3249
·
IF 5
Ting Xia,Zhenjie Liu,Wenya Ding,Liting Deng,Xinyang Ning,Jianfang Feng
Background/Objectives:Achyranthes bidentata(AB), recognized as a food and traditional Chinese medicine, exhibits notable biological activity. Our previous study showed the hypoglycemic effect ofAchyrantha bidentata polysaccharide(ABP). The properties and digestion process of polysaccharides affect their pharmacological activities. The digestion characteristics of ABP are unclear. In this study, we aimed to explore the characteristics of ABP’s simulated digestion and its prebiotic properties and hypoglycemic effects.Methods: We used simulated digestion methods to investigate the alterations in ABP levels in the process of digestion and fermentation. Animal experiments were used to compare the effects of the prebiotic properties of ABP on normal control (NC) and type 2 diabetes mellitus (T2DM) mice. Then, in order to further verify the hypoglycemic effect of ABP after fermentation (ABPF), α-glucosidase activity and glucose uptake in Caco-2 cells were examined.Results: The results showed that ABP was anti-digestive and mainly degraded by the intestinal flora. Moreover, ABP showed a stronger promoting advantage against beneficial bacteria and inhibited harmful bacteria in the T2DM mice. Compared with NC mice, after ABP treatment, T2DM mice showed a higher increase in levels of short-chain fatty acids (SCFAs). Additionally, the glucose uptake and α-glucosidase activity of Caco-2 cells were significantly decreased after treatment with ABPF.Conclusions: These results underscore the potential of ABP as a prebiotic candidate for gut health promotion and T2DM alleviation.
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PubMed
高影响因子
TISSUE & CELL
·
2026
·
IF 3.1
Yang Li,Xinchang Feng,Lingpeng Zheng
Type 2 diabetes mellitus (T2DM) has become a leading cause of chronic liver disease worldwide. Farrerol has been demonstrated to ameliorate multiple metabolic disorders. However, the role of farrerol in hepatic insulin resistance (IR) in T2DM, as well as the underlying mechanism, remain unclear. The present study aims to elucidate these issues. A rat model of T2DM was used to evaluate the effect of farrerol on IR in vivo. BRL 3 A cells were stimulated with palmitic acid to obtain an in vitro model of IR to further determine the role and mechanism of farrerol in hepatic IR. The involvement of the AMPK pathway was investigated using a selective and ATP-competitive AMPK inhibitor Compound C and specific siRNA targeting AMPKα1. The present study demonstrated that farrerol administration reduced HOMA-IR index, ameliorated dyslipidemia, and regulated glucose tolerance in diabetic rats. Additionally, farrerol administration alleviated hepatic damage, inflammation and oxidative stress accompanied by restored the AMPKα1/mTOR/SREBP-1 pathway in the liver of diabetic rats. Furthermore, in an in vitro model, farrerol enhanced glucose uptake, inhibited lipid accumulation, restored the membrane translocation of GLUT-2, suppressed inflammation and oxidative stress, and regulated the AMPKα1/mTOR/SREBP-1 pathway in palmitic acid-induced BRL 3 A cells. However, incubation with AMPK inhibitor or AMPKα1 knockdown reversed the protective effects of farrerol in vitro . Our findings demonstrate that farrerol ameliorates hepatic IR and associated metabolic dysfunctions by regulating the AMPKα1/mTOR/SREBP-1 pathway. Farrerol may be a promising therapeutic target for the treatment of IR in T2DM.
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PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Wen-lin Li,Ke Li,Wen-guang Chang,Hui Shi,Wen-xuan Zhang,Zi Wang,Wei Li
Background Although our previous work confirmed 20(R)-ginsenoside Rg3 (R-Rg3), which is an active ingredient in the Panax Ginseng C.A. Meyer, to have good anti-diabetic activity, its beneficial effect on diabetic retinal injury was found to be limited. Purpose This study aims to investigate the protective effects of R-Rg3 on diabetes-induced retinal injury and the associated molecular mechanisms of action. Methods Diabetic retinal injury was induced in mice using a combination of a high-fat diet (HFD) and intraperitoneal injection of streptozotocin (STZ). R-Rg3 (10 and 20 mg/kg) was subsequently administered for 6 weeks. The human retinal endothelial cells (HRECs) were subjected to high glucose (HG)-induced injury for the in vitro analysis and treated with R-Rg3 (4, 8, 16 μM), antioxidant N-Acetylcysteine (NAC, 1 mM) and Nrf2 inhibitor ML385 (5 μM). The mice retinas then underwent functional and histopathological analysis. Expression levels of proteins related to the Nrf2/HO-1 axis, tight junction proteins, endoplasmic reticulum (ER) stress and the apoptosis in retinal tissue and HRECs were determined by western blot. Expressions of ZO-1 and Nrf2 in the retina and HRECs were assessed by immunofluorescence. Additional evaluations included measuring body weights, fasting blood glucose (FBG), lipid levels and oxidative markers. Results The results showed 6 weeks of R-Rg3 treatment significantly restored the functional changes and redox system imbalance that was induced by HFD/STZ in mice. R-Rg3 was also found to significantly reduce retinal barrier damage and thickness changes resulting from hyperglycaemia exposure. At the same time, R-Rg3 also protected HRECs from HG-induced damage. R-Rg3 could also activate Nrf2/HO-1 axis and inhibit endoplasmic reticulum stress as a means of alleviating retinal endothelial cells apoptosis. The molecular docking results also demonstrated that R-Rg3 had a good binding ability with Nrf2. Conclusion Our study suggested Nrf2/HO-1 axis might be crucial for the ability of R-Rg3 to prevent diabetic retinal injury.
研究领域:
药理学
·
糖尿病
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眼科学
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分子生物学
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细胞生物学
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PubMed
高影响因子
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