Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway
Shuting Zhuang,
Xian Zhou,
Xiaowen Yang,
Dennis Chang,
Tao Chen,
Yibin Sun,
Chenxiang Wang,
Chutian Zhang,
Jichao Jiang,
Yong Chen,
Xiaohui Lin,
Xiaoning Wang,
Wenzhen Yu,
Xinjun Lin,
Caigu He,
Yanfang Zheng,
Jieping Zhang,
Hong Shi
Affiliations
Shuting Zhuang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Xian Zhou
NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2006, Australia
Xiaowen Yang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Dennis Chang
NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2006, Australia
Tao Chen
College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China
Yibin Sun
College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China
Chenxiang Wang
College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China
Chutian Zhang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Jichao Jiang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Yong Chen
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Xiaohui Lin
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Xiaoning Wang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Wenzhen Yu
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Xinjun Lin
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Caigu He
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China
Yanfang Zheng
College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China; Corresponding author.
Jieping Zhang
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China; Corresponding author.
Hong Shi
College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China; Corresponding author. No.1 Huatuo Road, Shangjie University Town, Fuzhou, Fujian Province, China.
Dendrobium mixture (DM) is a patented Chinese herbal medicine which has been shown to ameliorate type 2 diabetes mellitus (T2DM) with non-alcoholic fatty liver disease (NAFLD) in vivo and in vitro. We aimed to investigate the underlying mechanism of DM as a therapeutic agent in attenuating liver steatosis in relation to type 2 diabetes mellitus (T2DM).DM (16.2 g/kg/d) was administered to db/db mice for 4 weeks. The db/m mice and db/db mice in the control and model groups were given normal saline. Additionally, DM (11.25 g/kg/d) was administered to Sprague-Dawley (SD) rats, and the serum was collected and used in an experiment involving palmitic acid (PA)-induced human liver HepG2 cells with abnormal lipid and glucose metabolism.In db/db mice, the administration of DM significantly alleviated liver steatosis, including histological damage and cell apoptosis. DM was found to prevent the upregulation of the RAGE and AKT1 proteins in liver tissues. The underlying mechanism of DM was further studied in PA-induced HepG2 cells. Post-DM administration serum from SD rats reduced lipid accumulation and regulated glucose metabolism in HepG2 cells. Consequently, it inhibited RAGE/AKT signaling and restored autophagy activity. The upregulated autophagy was associated with the mTOR-AMPK signaling pathway. Furthermore, post-DM administration serum reduced apoptosis of hepatocytes in PA-induced HepG2 cells. Our study supports the potential use of DM as a therapeutic agent for the treatment of NAFLD in T2DM. The mechanism underlying this therapeutic potential is associated with the downregulation of the AGE/RAGE/Akt signaling pathway.
