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PNGL reduces lipotoxicity in diabetic cardiomyopathy and activates the adiponectin pathway
Jialu Wang1, Hongna Tong1, Chenyang Zhang1
1Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of New Drug Discovery Based on Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China; Key Laboratory of Efficacy Evaluation of Chinese Medicine against Glycolipid Metabolic Disorders, State Administration of Traditional Chinese Medicine, Beijing, China; NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China.
Aims:
To investigate the effect of Notoginseng leaf triterpenes (PNGL) on diabetic cardiomyopathy by suppressing lipotoxicity, and to explore the possible underlying mechanisms. To study the potential mechanism by which PNGL decrease lipotoxicity and hence affect diabetic cardiomyopathy.
Methods:
For 8 weeks, diabetic db/db mice were given either a high-dose (100 mg/kg daily) or low-dose (50 mg/kg daily) of PNGL intragastrially. Body weight, blood glucose, body fat, iWAT weight, BAT weight level, serum lipids, hormones involved in the metabolism of glucose and lipids, inflammatory variables, and antioxidant factors were among the many parameters that were assessed. In addition, cardiac function and myocardial enzyme levels were examined. Cardiac pathological structure, cardiomyocyte apoptosis levels and lipid accumulation were detected. To look into the potential mechanism and function of PNGL in diabetic cardiomyopathy (DCM).
Results:
PNGL treatment improved obesity, serum lipids, glucose and lipid metabolism, antioxidant function, and reduced inflammation and cardiomyocyte apoptosis in db/db mice. Cardiac function and myocardial enzyme levels were also improved by PNGL. In addition, PNGL alleviated cardiac histopathology, myocardial fibrosis and lipid accumulation in cardiomyocytes. Further research demonstrated that PNGL may play a protective role in diabetic cardiomyopathy by alleviating lipid metabolism.
Conclusions:
PNGL protects cardiac structure and function in diabetic cardiomyopathy by inhibiting lipotoxicity, and the mechanism is partially related to the adiponectin pathway activation.
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