Dendrobium officinale Attenuates Myocardial Fibrosis via Inhibiting EMT Signaling Pathway in HFD/STZ-Induced Diabetic Mice

Biol Pharm Bull. 2020;43(5):864-872. doi: 10.1248/bpb.b19-01073.

Abstract

Cardiac fibrosis is a major contributor for diabetic cardiomyopathy and Dendrobium officinale possessed therapeutic effects on hyperglycemia and diabetic cardiomyopathy. To further investigate the possible mechanisms of the Dendrobium officinale on diabetic myocardial fibrosis in mice. Water-soluble extracts of Dendrobium officinale (DOE) from dry stem was analyzed by HPLC and phenol-sulfuric acid method. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ) (30 mg/kg) for 4 consecutive days after intragastric administration of a high-fat diet (HFD) for 2 weeks. The groups were as follows: control group, model group, DOE low, medium, high dose group (75, 150, 300 mg/kg) and Metformin positive group (125 mg/kg). The results showed that DOE dose-dependently lower serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and grew the high-density lipoprotein cholesterol (HDL-C) after 12 weeks of daily administration with DOE. Hematoxylin-eosin staining and Sirius red staining showed obvious amelioration of cardiac injury and fibrosis. In addition, the result of immunoblot indicated that DOE increased the expression of peroxisome proliferator activated receptor-α (PPAR-α), phosphorylation of insulin receptor substrate 1 (p-IRS1) and E-cadherin and repressed the expression of transforming growth factor β1 (TGF-β1), phosphorylation of c-Jun N-terminal kinase (p-JNK), Twist, Snail1 and Vimentin. The present findings suggested that DOE ameliorated HFD/STZ-induced diabetic cardiomyopathy (DCM). The possible mechanism mainly associated with DOE accelerating lipid transport, inhibiting insulin resistant and suppressing fibrosis induced by epithelial mesenchymal transition (EMT).

Keywords: Dendrobium officinale; diabetic cardiomyopathy; epithelial mesenchymal transition; fibrosis.

MeSH terms

  • Animals
  • Blood Glucose / drug effects
  • Dendrobium*
  • Diabetes Mellitus, Experimental / blood
  • Diabetes Mellitus, Experimental / drug therapy*
  • Diabetes Mellitus, Experimental / metabolism
  • Diet, High-Fat
  • Epithelial-Mesenchymal Transition / drug effects*
  • Fibrosis
  • Insulin Resistance
  • Lipid Metabolism / drug effects
  • Male
  • Mice
  • Myocardium / pathology*
  • Plant Extracts / therapeutic use*
  • Plant Stems
  • Signal Transduction / drug effects

Substances

  • Blood Glucose
  • Plant Extracts