Yan Zhao1,
Jie Chen1,
Yi Xu1,
Geling Liu1,
Jia Cui1,
Liping Liu1,
Jie Gao2
1Ward 1, Department of Endocrinology, Tangshan Gongren Hospital, Tangshan 063000, China;
2Tangshan Maternal and Child Health Hospital, Tangshan 063000, China.
For correspondence:- Jie Gao
Email: gtcp6j@163.com
Accepted: 29 July 2022
Published: 28 August 2022
Citation:
Zhao Y, Chen J, Xu Y, Liu G, Cui J, Liu L, et al.
Combined administration of Gegen Yinlian decoction and metformin ameliorates liver metabolic disorder in rats by regulating miR-195-5p/IRS1/PI3K/AKT axis. Trop J Pharm Res 2022; 21(8):1647-1653
doi:
10.4314/tjpr.v21i8.10
© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..
Abstract
Purpose: To investigate the effect of Gegen Yinlian decoction (GYD), made from lobed kudzuvine root, baicalensis, huanglian and liquorice, and metformin on liver metabolism dysfunction in type 2 diabetes mellitus (T2DM) rats.
Methods: Wistar rats were treated with high-fat diet and a single intraperitoneal streptozotocin (STZ) injection to establish T2DM model. Thereafter, the T2DM-rats were treated with GYD and metformin (GYD/metformin). Serum triglyceride (TG), TC, LDL, and HDL levels, as well as glucose and insulin tolerance of the rats were evaluated. Furthermore, the effects of GYD/metformin treatment on the expressions of the related genes were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunoblot assay.
Results: After GYD-metformin treatment, the metabolic indicators in T2DM rats significantly improved (p < 0.05). However, there was decrease in t liver miR-1955p expressions. Silencing miR-195-5p improved glucose consumption and triglyceride levels of palmitate (PA)-induced pathological state in ALM12 cells (p < 0.05). Furthermore, miR-195-5p targeted insulin receptor substrate 1 (IRS1). Suppression of IRS1 partly annulled the impact of miR-195-5p silencing on ALM12 cell model. Moreover, IRS1 downregulation significantly mitigated the impact of the silencing on PI3K/AKT pathway activity (p < 0.05).
Conclusion: Combination of GYD with metformin ameliorated dysfunctional liver metabolism via control of miR-195-5p/IRS1/PI3K/AKT axis.
Keywords: MiR-195-5p, IRS1, PI3K/AKT, Gegen Yinlian decoction, Metformin, Liver metabolism dysfunction, Diabetes mellitus type 2