Frontiers in Pharmacology
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2025
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IF 4.8
Jue Bai,Si-Yuan Yang,Shao-Mei Yu,Ying Cao,Chang-Han Ma,Xuan-Yi Hu,Xiong Chen,Ying-Nan Song,Hong-Jin Chen
Background: Myocardial ischemia/reperfusion injury (MIRI) is a critical problem in cardiovascular medicine, often occurring after coronary revascularization procedures or cardiopulmonary bypass. The characters of MIRI are both energy metabolism disturbances and severe myocardium insulin resistance (IR), which exacerbated myocardial damage and cell death. Isoliquiritigenin (ISL), a flavonoid derived from licorice roots (Glycyrrhiza spp.), has demonstrated protective effects on MIRI. However, the potential cardio-protective effects and mechanism of ISL in MIRI remain unclear.Propose: In this study, we aimed to investigate ISL’s therapeutic effects on MIRI. Moreover, we elucidate the underlying mechanisms of ISL regulated myocardium insulin resistance in vivo and in vitro.Methods: In vivo, SD rats underwent left anterior descending coronary artery ligation/reperfusion to induce MIRI. Chest echocardiography was performed to monitor cardiac function post-reperfusion, followed by measurement of myocardial injury and IR markers. In vitro, H9C2 cardiomyocytes subjected to oxygen-glucose deprivation/reperfusion (OGD/R). Markers associated with myocardial injury and IR were assessed. Then, we identified potential therapeutic targets IGFBP5 for MIRI by network pharmacology and molecular docking analysis. Finally, lentivirus were used to silence or over-express IGFBP5 to elucidate the role of IGFBP5 in regulating the therapeutic effects of ISL on IR in MIRI.Results: In the present study, In vivo experiments demonstrated that ISL attenuated myocardial infarct size, decreased serum markers of myocardial injury, improved left ventricular systolic function, and enhanced insulin sensitivity. In vitro data revealed that ISL ameliorated glucose uptake and cell survival rate. Furthermore, ISL increased AKT phosphorylation and upregulated membrane-bound GLUT4 (M-GLUT4) protein expression levels. These effects of ISL are mediated by the induction of IGFBP5, as demonstrated using gene-specific shRNA or overexpression for IGFBP5.Conclusion: Our results reveal that ISL protects against myocardial damage caused by MIRI through the regulation of IR via the IGFBP5/AKT/GLUT4 pathway.
研究领域:
心血管医学
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药理学
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分子生物学
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Yong-Yu Yang,Jing-Jing Qi,Si-Yi Jiang,Ling Ye
Ethnopharmacological relevance Cortex fraxini (also known as qinpi)—the bark of Fraxinus rhynchophylla Hance (Oleaceae)—is widely used as a Chinese traditional medicinal for its anti-inflammatory and anti-hyperuricemic activities. Aim of the study Obesity-induced insulin resistance (IR) is driving the rising incidence of type 2 diabetes mellitus and is related to pathological adipose tissue remodeling. Esculin, a major active component of Cortex fraxini , has anti-diabetic effects. However, whether esculin improves obesity-induced IR by regulating adipose tissue remodeling is unclear. The aims of the present study were to assess the effects of esculin on obesity-induced IR and to explore the underlying mechanisms. Materials and methods Obese IR C57BL/6J mice were treated with esculin (40 or 80 mg/kg/day) for 4 weeks. Oral glucose tolerance tests were used to assess insulin sensitivity. Histological analyses were performed to analyze the number and size distribution of adipocytes. Glucose uptake was assessed using 2-NBDG. Results Esculin had no effect on body weight gain but reduced fasting blood glucose, improved oral glucose tolerance, and increased insulin sensitivity. Esculin reduced adipocyte size and the expression levels of collagen 4A1 and tumor necrosis factor α and increased the number of adipocytes and the expression of vascular endothelial growth factor A. Esculin promoted the differentiation of 3T3-L1 cells and upregulated the mRNA expression of CCAAT/enhancer-binding protein α and peroxisome proliferator-activated receptor-γ, activated the insulin receptor substrate 1 (IRS1)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, and enhanced the translocation of glucose transporter type 4 (GLUT4) and glucose uptake in adipocytes treated with palmitic acid. Conclusions These data suggest that esculin increases insulin sensitivity by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway.
研究领域:
药理学
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内分泌学
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代谢
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中药
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PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2026
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IF 6.8
Xiang Chen,Mengting Li,Miaomiao Xia,Yumeng Yang,Rui Liu,Ling Ma,Mao Luo
Ethnopharmacological relevance Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Aurantio-obtusin (AO), a bioactive anthraquinone compound, exhibits diverse pharmacological activities, derived from Cassiae Semen, a traditional herb used for metabolic disorders; however, its protective efficacy against prediabetes remains poorly understood. Aim of the study This study aimed to investigate the effects of AO on prediabetes and to elucidate the underlying mechanisms, with particular emphasis on gut microbiota-mediated regulation of metabolic homeostasis. Materials and methods Mice were subjected to prediabetes by a combination of a high-fat diet and streptozotocin. Metabolic parameters, liver function, oxidative stress, inflammatory responses, insulin signaling, and gut microbiota composition were assessed. Fecal microbiota transfer and models simulating antibiotic-induced germ-free conditions were utilized to investigate the function of gut microbiota. Results AO exhibited a marked improvement in glucose tolerance, lipid profiles, and insulin sensitivity among prediabetic mice. Furthermore, AO demonstrated a protective effect against liver damage, as suggested by the notable reductions in serum levels of alanine aminotransferase and aspartate aminotransferase. Oxidative stress was markedly suppressed, as indicated by decreased malondialdehyde levels, along with enhanced antioxidant defenses, including superoxide dismutase, catalase, and reduced glutathione. Additionally, AO preserved intestinal barrier integrity, reduced endotoxemia, and suppressed Toll-like receptor 4-mediated inflammatory signaling, accompanied by restoration of the PI3K/Akt/GLUT4 pathway. Notably, depletion of gut microbiota completely abolished the metabolic benefits of AO. Conclusion Collectively, this study substantiates the ethnomedical value of Cassiae Semen, demonstrating that AO improves prediabetes through the regulation of intestinal barrier function, oxidative stress, inflammation, and insulin signaling, which is dependent on gut microbiota.
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PubMed
高影响因子
MOLECULES
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2024
·Vol. 29
·期 9
·1998
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IF 4.2
Pengshou Li,Yunlu Wang,Xiaoting Wang,Rui Li,Kaihui Wang,Yu Jiang,Mingyuan Zhang,Chuhan Huang,Qixiang Ma,Jian Sun,Jianye Quan
This study synthesized a novel oatβ-glucan (OBG)-Cr(III) complex (OBG-Cr(III)) and explored its structure, inhibitory effects on α-amylase and α-glucosidase, and hypoglycemic activities and mechanism in vitro using an insulin-resistant HepG2 (IR-HepG2) cell model. The Cr(III) content in the complex was found to be 10.87%. The molecular weight of OBG-Cr(III) was determined to be 7.736 × 104Da with chromium ions binding to the hydroxyl groups of OBG. This binding resulted in the increased asymmetry and altered spatial conformation of the complex along with significant changes in morphology and crystallinity. Our findings demonstrated that OBG-Cr(III) exhibited inhibitory effects on α-amylase and α-glucosidase. Furthermore, OBG-Cr(III) enhanced the insulin sensitivity of IR-HepG2 cells, promoting glucose uptake and metabolism more efficiently than OBG alone. The underlying mechanism of its hypoglycemic effect involved the modulation of the c-Cbl/PI3K/AKT/GLUT4 signaling pathway, as revealed by Western blot analysis. This research not only broadened the applications of OBG but also positioned OBG-Cr(III) as a promising Cr(III) supplement with enhanced hypoglycemic benefits.
研究领域:
药学
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营养学
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生物化学
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细胞生物学
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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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高影响因子
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