Epigallocatechin-3-gallate (EGCG) possesses anti-fibrotic potential in diverse tissues; however, the molecular mechanisms underlying the impacts of EGCG on diabetes-induced myocardial fibrosis remain unclear. This present study aimed to unravel the anti-fibrotic effects of EGCG on the heart in type 2 diabetic rats and investigate its molecular mechanisms. Rats were randomly assigned to the following four groups: Normal (NOR), diabetic cardiomyopathy (DCM), DCM + 40 mg/kg EGCG, and DCM + 80 mg/kg EGCG groups. After 8 weeks of EGCG treatment, fasting blood glucose, left ventricular hemodynamic indices, heart index, and myocardial injury-related parameters were measured. Hematoxylin and eosin staining and Sirius Red staining were used to evaluate myocardial pathological alterations and collagen accumulation. The contents of myocardial hydroxyproline, collagen-I, collagen-III, transforming growth factor (TGF)-β1, matrix metalloprotease (MMP)-2, and MMP-9 were measured. The gene expression levels of myocardial TGF-β1, MMP-2, and MMP-9 were detected. Autophagic regulators, including adenosine 5’-monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), and autophagic markers, including microtubule-associated protein-1 light chain 3 and Beclin1 were estimated. The results indicated that diabetes significantly decreased cardiac contractile function and aggravated myocardial hypertrophy and injury. Furthermore, diabetes repressed the activation of autophagy in myocardial tissue and promoted cardiac fibrosis. Following ingestion with different doses of EGCG, myocardial contractile dysfunction, hypertrophy and injury were ameliorated; myocardial autophagy was activated, and myocardial fibrosis was alleviated in the EGCG treatment groups. In conclusion, these findings suggested that EGCG could attenuate cardiac fibrosis in type 2 diabetic rats, and its underlying mechanisms associated with activation of autophagy via modulation of the AMPK/mTOR pathway and then repression of the TGF-β/MMPs pathway.

Epigallocatechin-3-gallate (EGCG), an essential polyphenolic constituent found in tea leaves, possesses various potent biological activities. This research was undertaken to investigate the impact of EGCG against endoplasmic reticulum (ER) stress-mediated inflammation and to clarify the underlying molecular mechanism in type 2 diabetic kidneys. The male rats were randomized into four groups: normal, diabetic, low-dose EGCG, and high-dose EGCG. In type 2 diabetic rats, hyperglycemia and hyperlipidemia noticeably caused renal structural damage and dysfunction and aggravated ER stress. Meanwhile, sustained ER stress activated the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and then upregulated the contents of inflammatory cytokines in the diabetic kidney. Following supplementation with 40 mg/kg and 80 mg/kg EGCG, hyperglycemia, hyperlipidemia, and renal histopathological alterations and dysfunction were noticeably ameliorated; renal ER stress, NLRP3 inflammasome, and inflammatory response were markedly repressed in the EGCG treatment groups. In summary, the current study highlighted the renoprotective effects of EGCG in type 2 diabetes and its mechanisms are mainly associated with the repression of ER stress-mediated NLRP3 inflammasome overactivation.

Diabetes mellitus has been shown to impair respiratory function. The diaphragm is an important skeletal muscle involved in respiration. Hydrogen sulfide (H₂S) is one of the three endogenous gas messengers in mammals, which exhibits anti-fibrotic activity in some types of diabetes-related complications. However, whether and how H₂S exerts its anti-fibrotic activity on the diabetic diaphragmatic muscle remains unclear. In this study, we explored the anti-fibrotic activity of exogenous H₂S on the diaphragm using a streptozotocin (STZ)-induced diabetic rat model. The results showed that diaphragmatic biomechanical parameters were decreased, whereas the levels of inflammatory cytokines, collagen, and nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-related protein expression were increased in diabetic diaphragms. This implies that diabetes causes fibrosis of the diaphragm muscle through activation of NLRP3 inflammasome. After supplementation with exogenous H₂S, the diaphragmatic biomechanical and pathological alterations were ameliorated and activation of NLRP3 inflammasome was inhibited, followed by a decline in diaphragm muscle inflammation and fibrosis. These results demonstrate for the first time that exogenous H₂S effectively attenuates STZ-induced diabetic diaphragm muscle fibrosis, and that the underlying mechanism may be associated with suppression of the NLRP3 inflammasome-mediated inflammatory reaction. Impact statement: Diabetes mellitus is a group of chronic metabolic disorders, which causes serious damage to a variety of organs, such as the retina, heart, and skeletal muscle. The diaphragm is an important skeletal muscle involved in respiration in mammals. Fibrosis of the diaphragm muscle affects its contractility, which in turn impairs respiratory function. Accumulating evidence suggests that exogenous hydrogen sulfide (H₂S) exhibits anti-fibrotic activity in diabetes mellitus, but whether and how H₂S exerts this anti-fibrotic effect in the diabetic diaphragm remains unclear. The current work for the first time reveals that exogenous H₂S attenuates hyperglycemia-induced fibrosis of the diaphragm muscle and strengthens diaphragmatic biomechanical properties in diabetes mellitus, and the mechanism may involve the alleviation of collagen deposition by suppression of the nucleotide-binding oligomerization domain-like receptor protein (NLRP) 3 inflammasome-mediated inflammatory reaction. Therefore, H₂S supplementation could be used as an efficient targeted therapy against the NLRP3 inflammasome in the diabetic diaphragm.

Genistein (GEN) exhibits diverse biological activities. This study is conducted to explore the effect of GEN on metabolic dysfunction-associated steatotic liver disease (MASLD) mice. MASLD was induced in mice by a high-fat diet (HFD). The results indicated that GEN significantly reduced HFD-induced body weight and improved lipid homeostasis and glucose tolerance in HFD-fed mice. Furthermore, GEN intervention markedly ameliorated hepatic pathological changes, hepatic dysfunction, and macrophage polarization. Meanwhile, GEN had a beneficial significant impact on colonic pathological changes and the expression of tight junction-related proteins. The results of gut microbiota showed that high-dose GEN intervention was able to down-regulate Firmicutes and Proteobacteria and increase Bacteroidota at the phylum level. At the genus level, GEN intervention increased Lactobacillus , Muribaculum , and Muribaculaceae_unclassified in MASLD mice, and decreased Ruminococcus , Allobaculum , and Helicobacter . In conclusion, GEN attenuated lipid metabolism disorders and hepatic inflammatory reaction via regulating the composition of the gut microbiota and hepatic macrophage polarization in MASLD mice.