N- p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3β pathway

Yuechang Huang; Xingmin Zhang; Qian Li; Wende Zheng; Panpan Wu; Rihui Wu; Wen-Hua Chen; Chen Li

doi:10.3389/fphar.2024.1396641

N- p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3β pathway

Front Pharmacol. 2024 Apr 25:15:1396641. doi: 10.3389/fphar.2024.1396641. eCollection 2024.

Authors

Yuechang Huang^#^{1

2

3}, Xingmin Zhang^#^{1

2

3}, Qian Li^{1

2

3}, Wende Zheng^{1

2

3}, Panpan Wu^{1

2

3}, Rihui Wu^{1

2

3}, Wen-Hua Chen^{1

2

3}, Chen Li^{1

2

3}

Affiliations

¹ School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, China.
² International Healthcare Innovation Institute (Jiangmen), Jiangmen, China.
³ Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, Wuyi University, Jiangmen, China.

^# Contributed equally.

Abstract

Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic β-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N-p-coumaroyloctopamine (N-p-CO) in vitro and in vivo. N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3β proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3β signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.

Keywords: N-p-coumaroyloctopamine; diabetes; hyperglycemia; mechanism of action; oxidative stress.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the National Natural Science Foundation of China (Nos 81803390 and 22077020), Natural Science Foundation of Guangdong Province, China (No. 2021A1515010221), Guangdong and Macao Cooperation Project from the Department of Science and Technology of Guangdong Province and Jiangmen Science and Technology Bureau (2022A0505020026) and Department of Education of Guangdong Province, China (Nos 2021ZDZX4041 and 2020KZDZX1202) and Jiangmen Science and Technology Plan Project (No. 2021030102620004497), the Science and Technology Planning Project of Guangdong Province, China (2021B1212040016).