PMID- 29272757 OWN - NLM STAT- MEDLINE DCOM- 20180302 LR - 20180302 IS - 1873-376X (Electronic) IS - 1570-0232 (Linking) VI - 1073 DP - 2018 Jan 15 TI - Putative identification of components in Zengye Decoction and their effects on glucose consumption and lipogenesis in insulin-induced insulin-resistant HepG2 cells. PG - 145-153 LID - S1570-0232(17)31152-2 [pii] LID - 10.1016/j.jchromb.2017.12.019 [doi] AB - Zengye Decoction (ZYD) is a well-known traditional medicine in China used for treating diseases associated with "Yin deficiency" such as diabetes. However, little information is available on its components, pharmacological effects and underlying mechanisms. This study was designed to identify its active components and evaluate the effects and mechanisms of ZYD on glucose consumption and lipogenesis in insulin-induced insulin-resistant (IR)-HepG2 cells. In this study, 45 compounds of ZYD were putatively identified, in which the iridoid glycosides such as catalpol, aucubin and harpagide were identified as the main components. The insulin-resistant (IR)-HepG2 cell model was established and the effect of ZYD at three doses (0.17, 0.5 and 1.5 mug/mL) on cell growth was evaluated with an IncuCyte live-cell imaging system. The effects of ZYD on glucose consumption and uptake were evaluated by glucose consumption and uptake assay. Meanwhile, the effect of ZYD on lipogenesis was investigated in IR-HepG2 cells by oil red O (ORO) staining. Western blot was applied to observe the changes in some of the key factors involved in glucose metabolism and lipogenesis. It was found that the ZYD at a dose of 1.5 mug/mL exhibited an inhibitory activity on IR-HepG2 cell growth. Besides, ZYD at doses of 0.5 and 1.5 mug/mL accelerated the glucose consumption, glucose uptake and reduced the lipogenesis in the IR-HepG2 cells. Western blot studies revealed that ZYD phosphorylated AMP-activated protein kinase alpha subunits (AMPKalpha), upregulated hexokinase (HK), phosphorylated acetyl-CoA carboxylase alpha (pACC1) and carnitine palmitoyltransferase 1A (CPT1A) in the IR-HepG2 cells. These results indicate ZYD promotes glucose consumption and uptake, and attenuates lipogenesis in IR-HepG2 cells, which may be involved in activating AMPK and regulating its downstream factors including HK, pACC1 and CPT1A. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Liu, Zhenzhen AU - Liu Z AD - School of Medicine, Yangtze University, Jingzhou 434000, China. FAU - Kuang, Wenhua AU - Kuang W AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing 100084, China. FAU - Xu, Xi AU - Xu X AD - School of Medicine, Yangtze University, Jingzhou 434000, China. FAU - Li, Dandan AU - Li D AD - School of Medicine, Yangtze University, Jingzhou 434000, China. FAU - Zhu, Wufu AU - Zhu W AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, China. FAU - Lan, Zhou AU - Lan Z AD - Jiangxi Provincial Key Laboratory of Drug Design and Evaluation, School of Pharmacy, Jiangxi Science and Technology Normal University, Nanchang 330013, China. Electronic address: A83875785@126.com. FAU - Zhang, Xu AU - Zhang X AD - School of Life Sciences, Tsinghua University, Beijing 100084, China. LA - eng PT - Journal Article DEP - 20171212 PL - Netherlands TA - J Chromatogr B Analyt Technol Biomed Life Sci JT - Journal of chromatography. B, Analytical technologies in the biomedical and life sciences JID - 101139554 RN - 0 (Drugs, Chinese Herbal) RN - 0 (Insulin) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - AMP-Activated Protein Kinases/metabolism MH - Drugs, Chinese Herbal/*pharmacology MH - Glucose/*metabolism MH - Glycolysis/drug effects MH - Hep G2 Cells MH - Humans MH - Insulin/*metabolism MH - *Insulin Resistance MH - Lipogenesis/*drug effects OTO - NOTNLM OT - AMPKalpha OT - Glucose consumption OT - Glucose uptake OT - Hexokinase OT - Insulin resistant OT - Zengye Decoction EDAT- 2017/12/23 06:00 MHDA- 2018/03/03 06:00 CRDT- 2017/12/23 06:00 PHST- 2017/07/06 00:00 [received] PHST- 2017/11/29 00:00 [revised] PHST- 2017/12/10 00:00 [accepted] PHST- 2017/12/23 06:00 [pubmed] PHST- 2018/03/03 06:00 [medline] PHST- 2017/12/23 06:00 [entrez] AID - S1570-0232(17)31152-2 [pii] AID - 10.1016/j.jchromb.2017.12.019 [doi] PST - ppublish SO - J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jan 15;1073:145-153. doi: 10.1016/j.jchromb.2017.12.019. Epub 2017 Dec 12.