Early intervention with Didang decoction delays macrovascular lesions in diabetic rats through regulating AMP-activated protein kinase signaling pathway

• Published in: Chinese journal of natural medicines Vol. 15; no. 11; pp. 847 - 854
• Main Authors: REN, Dan-Dan, LI, Jing, CHANG, Bai, LI, Chun-Shen, YANG, Ju-Hong
• Format: Journal Article
• Language: English
• Published: China Elsevier B.V 01.11.2017
• Subjects: Adenosine Triphosphate - metabolism; AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Aorta - drug effects; Aorta - metabolism; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - prevention & control; Caspase 3 - metabolism; Caspase-3; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Didang decoction; Diptera; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Energy Metabolism - drug effects; Leeches; Mitochondria - drug effects; Mitochondria - metabolism; Nitric Oxide Synthase Type III - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; PGC-1α; Phytotherapy; Proto-Oncogene Proteins c-bcl-2 - metabolism; Prunus persica; Rats, Sprague-Dawley; Rheum; Signal Transduction; AMPK; PGC-1α; Caspase-3; Didang decoction; Endothelial cells
• ISSN: 1875-5364; 1875-5364
• DOI: 10.1016/S1875-5364(18)30018-9

The study aimed to investigate the intervening role of Didang decoction (DDD) at different times in macrovascular endothelial defense function, focusing on its effects on the AMP-activated protein kinase (AMPK) signaling pathway. The effects of DDD on mitochondrial energy metabolism were also investigated in rat aortic endothelial cells (RAECs). Type 2 diabetes were induced in rats by streptozotocin (STZ) combined with high fat diet. Rats were randomly divided into non-intervention group, metformin group, simvastatin group, and early-, middle-, late-stage DDD groups. Normal rats were used as control. All the rats received 12 weeks of intervention or control treatment. Western blots were used to detect the expression of AMP-activated protein kinase α1 (AMPKα1) and peroxisome proliferator-activated receptor 1α (PGC-1α). Changes in the intracellular AMP and ATP levels were detected with ELISA. Real-time-PCR was used to detect the mRNA level of caspase-3, endothelial nitric oxide synthase (eNOS), and Bcl-2. Compared to the diabetic non-intervention group, a significant increase in the expression of AMPKα1 and PGC-1α were observed in the early-stage, middle-stage DDD groups and simvastatin group (P < 0.05). The levels of Bcl-2, eNOS, and ATP were significantly increased (P < 0.05), while the level of AMP and caspase-3 were decreased (P < 0.05) in the early-stage DDD group and simvastatin group. Early intervention with DDD enhances mitochondrial energy metabolism by regulating the AMPK signaling pathway and therefore may play a role in strengthening the defense function of large vascular endothelial cells and postpone the development of macrovascular diseases in diabetes.