PMID- 38034607 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231202 IS - 2405-8440 (Print) IS - 2405-8440 (Electronic) IS - 2405-8440 (Linking) VI - 9 IP - 11 DP - 2023 Nov TI - Dendrobium mixture ameliorates hepatic injury induced by insulin resistance in vitro and in vivo through the downregulation of AGE/RAGE/Akt signaling pathway. PG - e22007 LID - 10.1016/j.heliyon.2023.e22007 [doi] LID - e22007 AB - 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. CI - Crown Copyright (c) 2023 Published by Elsevier Ltd. FAU - Zhuang, Shuting AU - Zhuang S AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Zhou, Xian AU - Zhou X AD - NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2006, Australia. FAU - Yang, Xiaowen AU - Yang X AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Chang, Dennis AU - Chang D AD - NICM Health Research Institute, Western Sydney University, Westmead, NSW, 2006, Australia. FAU - Chen, Tao AU - Chen T AD - College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China. FAU - Sun, Yibin AU - Sun Y AD - College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China. FAU - Wang, Chenxiang AU - Wang C AD - College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China. FAU - Zhang, Chutian AU - Zhang C AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Jiang, Jichao AU - Jiang J AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Chen, Yong AU - Chen Y AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Lin, Xiaohui AU - Lin X AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Wang, Xiaoning AU - Wang X AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Yu, Wenzhen AU - Yu W AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Lin, Xinjun AU - Lin X AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - He, Caigu AU - He C AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Zheng, Yanfang AU - Zheng Y AD - College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, 350100, China. FAU - Zhang, Jieping AU - Zhang J AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. FAU - Shi, Hong AU - Shi H AD - College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fu Zhou, 350100, China. LA - eng PT - Journal Article DEP - 20231108 PL - England TA - Heliyon JT - Heliyon JID - 101672560 PMC - PMC10685200 OTO - NOTNLM OT - AGE/RAGE/Akt signaling OT - Apoptosis OT - Autophagy OT - Dendrobium mixture OT - Inflammation OT - Liver steatosis OT - Type 2 diabetes mellitus COIS- The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/11/30 18:45 MHDA- 2023/11/30 18:46 PMCR- 2023/11/08 CRDT- 2023/11/30 17:36 PHST- 2023/03/20 00:00 [received] PHST- 2023/11/01 00:00 [revised] PHST- 2023/11/01 00:00 [accepted] PHST- 2023/11/30 18:46 [medline] PHST- 2023/11/30 18:45 [pubmed] PHST- 2023/11/30 17:36 [entrez] PHST- 2023/11/08 00:00 [pmc-release] AID - S2405-8440(23)09215-0 [pii] AID - e22007 [pii] AID - 10.1016/j.heliyon.2023.e22007 [doi] PST - epublish SO - Heliyon. 2023 Nov 8;9(11):e22007. doi: 10.1016/j.heliyon.2023.e22007. eCollection 2023 Nov.