Advanced Science
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2023
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IF 15.1
Yanfei Li,Lihang Chen,Yu Xu,Sihui Li,Huijia Yan,Tao Chen,Ziqi Hua,Di Wu,Runan Zhao,Jiangning Hu
Oral delivery of antidiabetic active components promises to free millions of people from daily suffering who require routine injections. However, oral insulin (Ins) and other short-acting compounds such as nateglinide (NG) in harsh gastrointestinal tract still face great challenging, including low bioavailability, and rapid elimination. In this study, inspired by the self-assembly of phenylalanine-based peptides in nature, it is showed that NG a small phenylalanine derivative, assembles into left-handed helical nanofibers in the presence of Ca 2+ . These helical NG nanofibers functioned as a coating layer on the surface of Ca 2+ -linked alginate (Alg) microgels for the effective encapsulation of Ins. As expected, the sustained release and prolonged circulation of Ins and NG from the Ins-loading Alg/NG microgels (Ins@Alg/NG) in the intestinal tract synergistically maintain a relatively normal blood glucose level in streptozotocin-induced diabetic mice after oral administration of Ins@Alg/NG. This further confirms that Ins@Alg/NG ameliorated Ins resistance mainly through activating Insreceptor substrate 1 (IRS1), protein kinase B (AKT), and AMP-activated protein kinase (AMPK), as well as by repressing glycogen synthase kinase-3β (GSK-3β). The strategy of using the assembly of NG as a coating achieves the oral delivery of insulin and showcases a potential for the treatment of diabetes.
研究领域:
药学
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纳米技术
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药物递送系统
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糖尿病研究
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
Journal of Bioresources and Bioproducts
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2025
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IF 13
Shuang Qi,Hui Yang,Tian Fang,Tingwei Zhang,Bo Jiang,Sehrish Manan,Chaofeng Zhang,Peng Wang,Caoxing Huang,Wenjuan Wu,Yongcan Jin
Lignin, a natural and renewable aromatic biopolymer, has gained attention in various biomedical applications due to its diverse structure, excellent biocompatibility, and antioxidant activity. However, the effects of lignin with tailored molecular weight on treating type 2 diabetes mellitus (T2DM) remain largely unexplored. In this study, a series of heterogeneous natural phenolic kraft lignin (KL) with tailored molecular weights, derived through an anti-sugar strategy, were prepared by continuous fractionation. The lignin fractions were categorized as F1, F2, and F3, corresponding to high, medium, and low molecular weights, respectively. Their therapeutic effects on T2DM were evaluated using a fractionated lignin culture cell model and intravenous injection into the tail vein of diabetic rats. The results demonstrated that lignin's protective effects in attenuating T2DM progression were molecular weight-dependent. Specifically, F3 reduced fasting blood glucose, reversed insulin resistance, and improved insulin sensitivity by mitigating oxidative stress and inflammatory responses. Mechanistic investigations revealed that F3 positively regulated glucose and lipid metabolism, inhibited hepatic gluconeogenesis, and enhanced hepatic glycogen synthesis by activating the insulin receptor substrate 1/phosphoinositide 3-kinase/protein kinase B (IRS1/PI3K/AKT) signaling pathway. Results revealed that lignin exerts its therapeutic effects on T2DM in a molecular weight-dependent manner, with IRS1/PI3K/AKT signaling as a potential underlying mechanism. This highlights lignin with a defined molecular weight as a promising candidate for T2DM treatment.
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产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
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2021
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IF 6.475
Suwen Liu,Jincheng Yu,Mengfan Fu,Xinfang Wang,Xuedong Chang
Hawthorn polyphenol extract (HPE) is beneficial for patients with type 2 diabetes (T2D). However, the mechanism underlying its beneficial effects remains unclear. We investigated the inhibitory effects and mechanisms of HPE on insulin resistance, inflammation, and aortic injury in T2D rats, using metformin (MF) as a positive control. High-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (HPLC-ESI-MS/MS) was used to determine the primary polyphenols in HPE. Hematoxylin & Eosin (H&E) staining was used to evaluate pathological conditions of the skeletal muscle, liver, and aorta vessels in each group. The levels of serum and intestinal tissue oxidative stress, tumor necrosis factor α (TNF-α), and inflammatory interleukin-6 (IL-6) were also assessed. Western blotting was used to evaluate protein expression levels in the associated molecular pathway. Volatile organic compounds (VOCs) from colon contents were determined using headspace-gas chromatography-ion mobility chromatography. Our results showed that supplementation with 300 mg HPE/kg body weight over four weeks significantly improved total cholesterol (TC), total triglyceride (TG), insulin, and lipopolysaccharide (LPS) levels in diabetic rats ( p < 0.01). The lesions of skeletal muscle, liver, and aorta in diabetic rats were significantly improved. HPE supplementation also significantly downregulated the inflammatory factors (IL-6, TNF-α, and MCP-1) in the liver of diabetic rats via the SIRT1/AMPK/NF-κB signaling pathway. Furthermore, HPE significantly reduced insulin resistance in T2D rats by upregulating the phosphorylation of glucose absorption protein (GLUT4) and insulin resistance-associated proteins, p-IRS1, p-AKT, and p-PI3K, in the rat liver ( p < 0.01). The findings show that HPE could also alleviate aortic injury by activating SIRT1 and regulating the NF-κB and Wnt2/β-catenin signaling pathways. Overall, the results of this study suggest that both HPE and MF have similar inhibitory effects on T2D in rats and that HPE could be used as a functional food component in the adjuvant treatment of T2D.
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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营养学
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产品关联
DOI
PubMed
高影响因子
Food Science and Human Wellness
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2024
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IF 5.6
Chunlan Yan,Zhihao Zhang,Liqun Ma,Xinyi Xu,Muhammad Azhar,Xianju Huang,Jianxun Shi,Jun Li
Our previous research studies have shown that Veratrilla baillonii Franch, a food supplement used by ethnic minorities in Southwest China, has multiple pharmacological activities, such as detoxification, anti-inflammatory, antioxidant, and anti-insulin resistance. However, the detailed signal pathways for its salutary effect on damages in multiple organs due to type 2 diabetes mellitus (T2DM) remains unclear. The current study is to evaluate the therapeutic effects of V . baillonii on T2DM rats and to explore the underlying mechanisms. The T2DM rat model was successfully established by a high-sugar and high-fat diet (HFD) combination with intraperitoneal injection of a small dose of streptozotocin (STZ, 35 mg/kg). Biochemical analysis and histopatholgical examinations were conducted to evaluate the anti-diabetic potential of water extracts of V. baillonii (WVBF). The results showed that the WVBF treatment can improve hyperglycemia and insulin resistance, ameliorate the liver, kidney and pancreas injuries via decreasing inflammatory cytokines such as IL-6 and TNF-α, and oxidative damages. Further investigation suggested that WVBF modulates the signal transductions of the IRS1/PI3K/AKT/GLUT4 and AMPK pathways. These findings demonstrate potentials of WVBF in the treatment of T2DM and possible mechanisms for its hepatoprotective activities.
研究领域:
药理学
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内分泌学
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糖尿病研究
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分子生物学
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传统中药
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产品关联
DOI
高影响因子
FOOD RESEARCH INTERNATIONAL
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2023
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IF 8.1
Qiannan Zhao,Jinyi Yang,Jiahui Li,Lei Zhang,Xiaohai Yan,Tianli Yue,Yahong Yuan
Phenolics of mulberry ( Morus alba L.) leaves (MLs) have potential anti-diabetic effects, but they may be chemically modified during gastrointestinal digestion so affect their biological activity. In this study, an in vitro digestion model coupled with Caco-2 monolayer and Caco-2/insulin-resistant HepG2 coculture model were used to study the transport and hypoglycemic effects of phenolics in raw MLs (U-MLs) and solid-fermented MLs (F-MLs). The results of LC-MS/MS analysis showed that the Papp (apparent permeability coefficient, 10 –6 cm/s) of phenolics in digested MLs ranged from 0.002 ± 0.00 (quercetin 3- O -glucoside) to 60.19 ± 0.67 (ferulic acid), indicating higher phenolic acids absorbability and poor flavonoids absorbability. The Papp values of phenolic extracts of F-MLs in Caco-2 monolayer were significantly higher (p > 0.05) than that of U-MLs. Digested phenolic extracts inhibited the activities of sucrase (60.13 ± 2.03%) and maltase (82.35 ± 0.78%) and decreased 9.28 ± 0.84% of glucose uptake in Caco-2 monolayer. Furthermore, a decrease in the mRNA expression of glucose transporters SGLT1 (0.64 ± 0.18), GLUT2 (0.14 ± 0.02) and the sucrase-isomaltase (0.59 ± 0.00) was observed. In Caco-2/insulin-resistant HepG2 co-culture model, phenolic extracts regulated glucose metabolism by up-regulating the mRNA expressions of IRS1 (9.32-fold), Akt (17.07-fold) and GYS2 (1.5-fold), and down-regulating the GSK-3β (0.22-fold), PEPCK (0.49-fold) and FOXO1 (0.10-fold) mRNA levels. Both U-MLs and F-MLs could improve glucose metabolism, and the partial least squares (PLS) analysis showed that luteoforol and p -coumaric acid were the primary phenolics that strongly correlated with the hypoglycemic ability of MLs. Results suggested that phenolics of MLs can be used as dietary supplements to regulate glucose metabolism.
研究领域:
药理学
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营养学
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生物化学
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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
Drug Discoveries and Therapeutics
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2024
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IF 1.9
Jing Wang,Lisha Li,Jing Zhou,Xinyao Pan,Qing Qi,Hongmei Sun,Ling Wang
Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disorder characterized by a complex pathogenesis and limited treatment options. Yishen Huatan and Huoxue decoction (YHHD), as a traditional Chinese Medicine formula, has shown effectiveness in treating PCOS. However, the specific mechanisms by which YHHD exerts its therapeutic effects remain unclear. In this study, we performed to investigate the therapeutic effects of YHHD and quercetin on dehydroepiandrosterone-induced PCOS mice, and examine the effect of quercetin on the decidualization of T-HESCs under hyperinsulinemic conditions. The results showed that YHHD could reduce early miscarriage rates in PCOS patients and significantly improved glucose metabolism disorders, sex hormone levels, and the estrous cycles in PCOS mice. Quercetin could alleviate effect of high insulin levels and restore the low expression of insulin receptor substrate1/2 (IRS1/2) and glucose transporte 4 (GLUT4) in T-HESCs, demonstrating its potential to mitigate hyperinsulin-induced decidualization dysfunction via the GLUT4 signaling pathway mediated by IRS1/2. This study provides valuable molecular insights of YHHD and highlight the therapeutic potential of quercetin in treating decidualization dysfunction in PCOS.
研究领域:
妇科学
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内分泌学
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中医药学
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分子生物学
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药理学
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产品关联
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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