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

doi:10.1016/j.heliyon.2023.e22007

Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway

Heliyon. 2023 Nov 8;9(11):e22007. doi: 10.1016/j.heliyon.2023.e22007. eCollection 2023 Nov.

Authors

Shuting Zhuang¹, Xian Zhou², Xiaowen Yang¹, Dennis Chang², Tao Chen³, Yibin Sun³, Chenxiang Wang³, Chutian Zhang¹, Jichao Jiang¹, Yong Chen¹, Xiaohui Lin¹, Xiaoning Wang¹, Wenzhen Yu¹, Xinjun Lin¹, Caigu He¹, Yanfang Zheng³, Jieping Zhang¹, Hong Shi¹

Affiliations

¹ College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China.
² NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2006, Australia.
³ College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China.

Abstract

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.

Keywords: AGE/RAGE/Akt signaling; Apoptosis; Autophagy; Dendrobium mixture; Inflammation; Liver steatosis; Type 2 diabetes mellitus.