ophiopogonin-d and Body-Weight

Ophiopogonin D (OP-D) is a steroidal saponin extracted from Ophiopogon japonicus (Thunb.) Ker Gawl. (Liliaceae), that has been traditionally used to treat cough, sputum, and thirst in some Asian countries. Recently, various pharmacological roles of OP-D have been identified, including anti-inflammatory, cardioprotective, and anti-cancer effects. However, whether OP-D can prevent diabetic myocardial injury remains unknown.. In this study, we aimed to observe the effects of OP-D on the diabetic myocardium.. Leptin receptor-deficient db/db mice were used as an animal model for type 2 diabetes. The effects of OP-D on blood glucose, blood lipids, myocardial ultrastructure, and mitochondrial function in mice were observed after four weeks of intragastric administration. Palmitic acid was used to stimulate cardiomyocytes to establish a myocardial lipotoxicity model. Cell apoptosis, mitochondrial morphology, and function were observed.. Blood glucose and blood lipid levels were significantly increased in db/db mice, accompanied by myocardial mitochondrial injury and dysfunction. OP-D treatment reduced blood lipid levels in db/db mice and relieved mitochondrial injury and dysfunction. OP-D inhibited palmitic acid induced-mitochondrial fission and dysfunction, reduced endogenous apoptosis, and improved cell survival rate in H9C2 cardiomyocytes. Both in vivo and in vitro models showed increased phosphorylation of DRP1 at Ser-616, reduced phosphorylation of DRP1 at Ser-637, and reduced expression of fusion proteins MFN1/2 and OPA1. Meanwhile, immunofluorescence co-localization analysis revealed that palmitic acid stimulated the translocation of DRP1 protein from the cytoplasm to the mitochondria in H9C2 cardiomyocytes. The imbalance of mitochondrial dynamics, protein expression, and translocation of DRP1 were effectively reversed by OP-D treatment. In isolated mice ventricular myocytes, palmitic acid enhanced cytoplasmic Ca. Our findings indicate that OP-D intervention could alleviate lipid accumulation and mitochondrial injury in diabetic mouse hearts and palmitic acid-stimulated cardiomyocytes. The cardioprotective effect of OP-D may be mediated by the regulation of mitochondrial dynamics.

Topics: Animals; Apoptosis; Blood Glucose; Body Weight; Calcineurin; Calcium; Cardiotonic Agents; Cell Line; Cell Survival; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Disease Models, Animal; Dynamins; Lipids; Liver; Male; Mice; Mitochondria; Mitochondrial Dynamics; Myocytes, Cardiac; Palmitic Acid; Rats; Saponins; Spirostans

Gut dysbiosis is believed to play a critical role in the pathogenesis of metabolic diseases, including obesity. Ophiopogonin D (OP-D), a steroidal glycoside and an active component extracted from the root of the plant Ophiopogon japonicus (also known as radix ophiopogonis), can regulate multiple physiologic processes. Here we show that OP-D administration reduces body weight, hyperglycemia, hyperlipidemia, and insulin resistance in male mice fed a high-fat diet (HFD). Pyrosequencing of the V4 regions of 16S rRNA genes in mouse feces revealed a deviation of the gut microbiota in response to OP-D treatment. In particular, the decreased Firmicutes-to- Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels indicated that OP-D reversed HFD-induced gut dysbiosis. More importantly, the effects of OP-D on modulation of obesity and microbiota were transferable via horizontal feces transfer from OP-D-treated mice to HFD-fed mice. Taken together, our results suggest that OP-D may be used as a prebiotic agent to treat obesity-associated gut dysbiosis and metabolic syndrome.-Chen, S., Li, X., Liu, L., Liu, C., Han, X. Ophiopogonin D alleviates high-fat diet-induced metabolic syndrome and changes the structure of gut microbiota in mice.

Topics: Animals; Body Weight; Diet, High-Fat; Dysbiosis; Gastrointestinal Microbiome; Hyperglycemia; Hyperlipidemias; Insulin Resistance; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Saponins; Spirostans