Frontiers in Pharmacology (Apr 2022)
Co-Crystal of Rosiglitazone With Berberine Ameliorates Hyperglycemia and Insulin Resistance Through the PI3K/AKT/TXNIP Pathway In Vivo and In Vitro
- Qichen He,
- Qichen He,
- Qichen He,
- Bo Chen,
- Bo Chen,
- Bo Chen,
- Gang Wang,
- Gang Wang,
- Gang Wang,
- Duanfang Zhou,
- Duanfang Zhou,
- Duanfang Zhou,
- Hongfang Zeng,
- Hongfang Zeng,
- Hongfang Zeng,
- Xiaoli Li,
- Xiaoli Li,
- Xiaoli Li,
- Yi Song,
- Yi Song,
- Yi Song,
- Xiaoping Yu,
- Xiaoping Yu,
- Xiaoping Yu,
- Wenxin Liang,
- Wenxin Liang,
- Wenxin Liang,
- Huiling Chen,
- Huiling Chen,
- Huiling Chen,
- Xu Liu,
- Xu Liu,
- Xu Liu,
- Qiuya Wu,
- Qiuya Wu,
- Qiuya Wu,
- Lihong Wu,
- Lihong Wu,
- Lihong Wu,
- Limei Zhang,
- Limei Zhang,
- Limei Zhang,
- Huizhen Li,
- Xiangnan Hu,
- Xiangnan Hu,
- Weiying Zhou,
- Weiying Zhou,
- Weiying Zhou
Affiliations
- Qichen He
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Qichen He
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Qichen He
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Bo Chen
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Bo Chen
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Bo Chen
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Gang Wang
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Gang Wang
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Gang Wang
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Duanfang Zhou
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Duanfang Zhou
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Duanfang Zhou
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Hongfang Zeng
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Hongfang Zeng
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Hongfang Zeng
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Xiaoli Li
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Xiaoli Li
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Xiaoli Li
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Yi Song
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Yi Song
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Yi Song
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Xiaoping Yu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Xiaoping Yu
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Xiaoping Yu
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Wenxin Liang
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Wenxin Liang
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Wenxin Liang
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Huiling Chen
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Huiling Chen
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Huiling Chen
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Xu Liu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Xu Liu
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Xu Liu
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Qiuya Wu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Qiuya Wu
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Qiuya Wu
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Lihong Wu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Lihong Wu
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Lihong Wu
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Limei Zhang
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Limei Zhang
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Limei Zhang
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- Huizhen Li
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Xiangnan Hu
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Xiangnan Hu
- Department of Medicinal Chemistry, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Weiying Zhou
- Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, China
- Weiying Zhou
- Chongqing Key Laboratory of Drug Metabolism, Chongqing Medical University, Chongqing, China
- Weiying Zhou
- Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, China
- DOI
- https://doi.org/10.3389/fphar.2022.842879
- Journal volume & issue
-
Vol. 13
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease characterized by insulin resistance and hyperglycemia. This study examined the effect and elucidated the mechanism of improvement of hyperglycemia and insulin resistance by a co-crystal of rosiglitazone with berberine (RB) in high-sugar high-fat diet (HSHFD)-induced diabetic KKAy mice.Methods: Diabetic KKAy mice were randomly divided into seven groups: KKAy model control group (DM control) treated with 3% sodium carboxymethyl cellulose; RB groups, administered daily with RB 0.7 mg/kg (RB-L), 2.11 mg/kg (RB-M), or 6.33 mg/kg (RB-H); positive control groups, administered daily with rosiglitazone 1.04 mg/kg (RSG), berberine 195 mg/kg (BBR), or combination of 1.04 mg/kg RSG and 1.08 mg/kg BBR (MIX). Test compounds were administered orally for 8 weeks. Non-diabetic C57BL/6J mice were used as normal control (NC). Blood glucose, food intake, body weight, glucose-lipid metabolism, and pathological changes in the pancreas and liver were examined. We further evaluated the mechanism of action of RB in C2C12 and HepG2 cells stimulated with high glucose and palmitate.Results: RB treatment improved glucolipid metabolism and insulin resistance in diabetic KKAy mice. RB reduced blood glucose levels, white fat index, plasma triglyceride (TG), low-density lipoprotein (LDL), gastric inhibitory peptide (GIP), and insulin levels, increased the levels of plasma glucagon-like peptide-1 (GLP-1), high-density lipoprotein (HDL), and glycogen content in the liver and muscle; and improved oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and pathological changes in the pancreas and liver of KKAy mice. Moreover, RB upregulated p-PI3K and p-AKT levels and reduced TXNIP expression in KKAy mice and in HepG2 and C2C12 cells.Conclusion: These data indicate that RB ameliorates insulin resistance and metabolic disorders, and the mechanism might be through regulating the PI3K/AKT/TXNIP signaling pathway . Thus, the co-crystal drug RB may be considered as a potential antidiabetic agent for future clinical therapy.
Keywords
