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This study investigated the effect of sesamin on myocardial fibrosis in spontaneously hypertensive rats (SHRs) and the possible mechanisms involved. Twenty-eight male SHRs were randomly allocated to SHR group, Ses160 group (sesamin 160 mg/kg), Ses80 group (sesamin 80 mg/kg) and Cap30 group (captopril 30 mg/kg). Seven male WKY rats were used as control. Sesamin and captopril were administered intragastrically for 12 weeks. Captopril significantly reduced systolic blood pressure and angiotensin II (Ang II) levels in SHRs, accompanied by a marked attenuation of left ventricular hypertrophy (LVH) and collagen deposition (P <0.05 or P <0.01). Though sesamin had no significant influence on Ang II levels, and the hypotensive effect was also significantly inferior to that of captopril (P <0.05 or P <0.01), however, the improvement of LVH and collagen deposition was similar to that in captopril group. Sesamin markedly reduced transforming growth factor-β1 (TGF-β1) content in cardiac tissues, with Smad3 phosphorylation decreased and Smad7 protein expression increased notably (P <0.05 or P <0.01). Protein expression of type I collagen and type III collagen, target genes of Smad3, was down-regulated markedly by sesamin (P <0.05 or P <0.01). In addition, sesamin significantly increased total antioxidant capacity and superoxide dismutase protein in cardiac tissues (P <0.05 or P <0.01), while the expression of NADPH oxidase subunit p47phox and malondialdehyde content were reduced markedly (P <0.05 or P <0.01). In vitro studies also demonstrated that sesamin was able to suppress Ang II induced phosphorylation of Smad3 and secretion of TGF-β1 and type I and type III collagen in cultured rat cardiac fibroblasts. These data suggest that sesamin is capable of attenuating hypertensive myocardial fibrosis through, at least partly, suppression of TGF-β1/Smad signaling pathway.

BackgroundDanzhi Jiangtang Capsule (DJC), a Chinese medicinal formula, has been clinically used for treatment of diabetes for many years. Previous studies have demonstrated that DJC was able to improve pancreatic islet function in diabetes, but the underlying mechanisms remained unclear.MethodsStreptozotocin (STZ) induced type 1 diabetic rats were treated with DJC for 6 weeks. Fasting plasma insulin and fasting plasma glucose were determined at the end of experiment. Antioxidant status was evaluated by measuring total antioxidant capacity, superoxide dismutase activity and malondialdehyde content in plasma and pancreas. Paraffin sections of pancreas were subjected to H&E staining, TUNEL staining and immunohistochemical examination. Protein levels of Bcl-2, Bax and pancreatic duodenal homeobox-1 (PDX-1) were measured by western blot analysis. Activities of Caspase-3 and Caspase-9 were determined with commercially available kits.ResultsSupplementation with DJC resulted in a significant amelioration of type 1 diabetes as manifested by reduced blood glucose, increased fasting plasma insulin and improved body weight gains. The atrophy and reduction of pancreatic islets were also alleviated in DJC supplemented groups. DJC markedly reduced pancreatic beta cell apoptosis, with Bax protein down-regulated and Bcl-2 protein up-regulated significantly. The activities of caspase-3 and caspase-9 in pancreas were decreased evidently by DJC treatment. DJC effectively ameliorated oxidative stress in type 1 diabetic rats, with the expression of PDX-1 protein increased markedly.ConclusionsDJC was capable of attenuating STZ induced type 1 diabetes in rats, which might be attributed to the suppression of pancreatic beta cell apoptosis. This study would provide further evidence for clinical use of DJC in the management of diabetes.

Instant dark tea (IDT) is a new product gaining increasing attention because it is convenient and can endow significant health benefit to consumers, which is partially attributed to its high concentration of functional ingredients. However, the molecular mechanism underlying its regulatory effect on hyperlipidaemia is rarely studied. In this study, we performed omics and molecular verification in high-fat diet (HFD)-fed rat, aiming to reveal the mechanism and provide molecular evidence. The results showed that the major bioactive components in IDT were 237.9 mg/g total polysaccharides, 336.6 mg/g total polyphenols, and 46.9 mg/g EGCG. Rats fed with IDT (0.27–0.54 g/kg for 12 weeks) significantly reduced the body weight and TC, TG, LDL-C, blood glucose, and MDA and induced the level of serum HDL-C and also the levels of liver SOD, CAT, GSH-Px, and Nrf2, compared to HFD group. For molecular mechanism study, HIDT feeding had significant impact on the gene expressions of biomarkers in lipogenesis (FABP, CD36, SCD1, Cyp4a1, and Kcnn2), lipid oxidation (PPARγ), and glucose glycolysis (Gck and ENO2) in liver tissue. Moreover, gut microbiome study found that rats fed with IDT dramatically modified the gut microbial species at the family level, such as suppressing the increase abundance of Proteobacteria and Firmicutes induced by HFD. HIDT significantly boosted the relative composition of beneficial bacterium Akkermansia and Rikenellaceae_RC9_gut_group and decreased the relative abundance of the harmful bacterium Ruminococcaceae_UCG-005 and Ruminiclostridium_9, compared to HFD (p &lt; 0.01). Correlation analysis between microbiome and animal indicators found that seven genera including Akkermansia, Clostridiales, Lachnospiraceae, Lachnospiraceae_UCG-010, Ruminiclostridium_9, Ruminococaceae-UCG-005, and Ruminocuccus_1 were found as potential biomarkers that were strongly correlated with oxidative stress and metabolism genes. For instance, Ruminococcaceae_UCG-005 was significantly correlated with body weight, TG, HDL-C, Nfr2, FABP3, SCD1, Cyp4a1, and Kcnn2. Collectively, the above data obtained in this study had provided the primary molecular evidence for the molecular mechanism and brought in novel insights based on omics for the regulatory effect of IDT on hyperlipidaemia.