Ophiopogonin D alleviates diabetic myocardial injuries by regulating mitochondrial dynamics.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: In this study, we aimed to observe the effects of OP-D on the diabetic myocardium. MATERIALS AND METHODS: 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. RESULTS: 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 Ca2+ levels and suppressed contractility in ventricular myocytes, accompanied by activation of calcineurin, a key regulator of DRP1 dephosphorylation at Ser-637. OP-D reversed the changes caused by palmitic acid. CONCLUSIONS: 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.

Shengmai San Alleviates Diabetic Cardiomyopathy Through Improvement of Mitochondrial Lipid Metabolic Disorder.

BACKGROUND/AIMS: Shengmai San (SMS), prepared from Panax ginseng, Ophiopogon japonicus, and Schisandra chinensisin, has been widely used to treat ischemic disease. In this study, we investigated whether SMS may exert a beneficial effect in diabetic cardiomyopathy through improvement of mitochondrial lipid metabolism. METHODS: A leptin receptor-deficient db/db mouse model was utilized, and lean age-matched C57BLKS mice served as non-diabetic controls. Glucose and lipid profiles, myocardial structure, dimension, and function, and heart weight to tibial length ratio were determined. Myocardial ultrastructural morphology was observed with transmission electron microscopy. Protein expression and activity of oxidative phosphorylation (OXPHOS) complex were assessed using western blotting and microplate assay kits. We also observed cellular viability, mitochondrial membrane potential, OXPHOS complex activity, and cellular ATP level in palmitic acid-stimulated H9C2 cardiomyocytes. Changes in the sirtuin (SIRT1)/AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) pathway and mitochondrial uncoupling signaling were assessed using western blotting and quantitative real-time PCR. RESULTS: Leptin receptor-deficient db/db mice exhibit obesity, hyperglycemia, and hyperlipidemia, accompanied by distinct myocardial hypertrophy and diastolic dysfunction. SMS at a dose of 3 g/kg body weight contributed to a recovery of diabetes-induced myocardial hypertrophy and diastolic dysfunction. SMS administration led to an effective restoration of mitochondrial structure and function both in vivo and in vitro. Furthermore, SMS markedly enhanced SIRT1 and p-AMPKα protein levels and decreased the expression of acetylated-PGC-1α and uncoupling protein 2 protein. SMS also restored the depletion of NRF1 and TFAM levels in diabetic hearts and H9C2 cardiomyocytes. CONCLUSION: The results indicate that SMS may alleviate diabetes-induced myocardial hypertrophy and diastolic dysfunction by improving mitochondrial lipid metabolism.

Buyanghuanwu Decoction alleviated pressure overload induced cardiac remodeling by suppressing Tgf-ß/Smads and MAPKs signaling activated fibrosis.

Buyanghuanwu Decoction (BHD), a traditional Chinese medicine recipe, is a representative prescription for the treatment of qi-deficiency and blood-stasis syndrome. In this study, the effect of BHD on pressure overload induced cardiac remodeling was investigated and possible mechanism underlying was explored. Rats were randomly divided into four groups: sham, transverse aorta constriction (TAC) with saline, TAC with telmisartan (TAC+Tel), and TAC with BHD (TAC+BHD) for 16 weeks (n=6∼8 in each group). Cardiac morphological and functional changes were evaluated by echocardiography and histological methods, the molecular alterations were detected by western blotting. Our results revealed that pressure overload prominently induced cardiac dysfunction, dilated and atrophied left ventricle, decreased cardiomyocyte cross sectional area, and fibrosis. However, BHD, similar to Tel, greatly reversed cardiac dysfunction, left ventricular dilation, and fibrosis, together with increased left ventricular wall thickness and size of cardiomyocyte. Furthermore, activated classical pro-fibrotic signaling of Tgf-ß/Smads and MAPKs after TAC was dramatically suppressed by BHD or Tel treatment. Taken together, it was demonstrated in this study that BHD exerted a cardioprotective effect against pressure overload induced cardiac remodeling via inactivation of Tgf-ß/Smads and MAPKs signaling triggered fibrosis.

Isolation and characterization of xanthan-degrading Enterobacter sp. nov. LB37 for reducing the viscosity of xanthan in petroleum industry.

A Gram-negative, straight rod and facultative anaerobic bacterium was isolated from soil sample. It exhibits the phenotypic characteristics consistent with its classification in the genus Enterobacter. The isolate ferment glucose to acid and gas. Arginine dihydrolase, ornithin decarboxylase and gelatinase but not deoxyribonuclease was produced by this isolate. There was no hydrogen sulfide production. On the basis of the phenotypic data, together with phylogenetic analysis based on 16S rDNA gene sequences, this strain should represent a novel species of the genus Enterobacter and was designated as LB37. The strain LB37 could degrade xanthan molecules resulting in the rapid decrease of the viscosity of xanthan solution used in oil drilling process. Endoxanthanase activity was also detected in the culture supernatant. To our knowledge, it is the first report on the microbes being involved in the xanthan degradation for oil industry. The isolate LB37 would be useful for potential application in enhanced oil recovery and oil drilling field.