Open Access Research article

Isoquercitrin activates the AMP–activated protein kinase (AMPK) signal pathway in rat H4IIE cells

Jingxin Zhou1, Hisae Yoshitomi2, Tonghua Liu1*, Boxin Zhou3, Wen Sun1, Lingling Qin1, Xiangyu Guo1, Liansha Huang4, Lili Wu1 and Ming Gao2*

Author Affiliations

1 Beijing University of Chinese Medicine, 11 North 3rd-ring East Road, Beijing, Chaoyang District 100029, People’s Republic of China

2 School of Pharmaceutical Sciences, Mukogawa Women’s University, 11-68 Koshien Kyuban-cho, Nishinomiya, Hyogo 663-8179, Japan

3 Sanshui Hospital affiliated to Guangdong Medical college, 16 Guanghai West Road, Foshan, Guangdong 528000, People’s Republic of China

4 Shenzhen TCM Hospital, 1 Fuhua Road, Shenzhen, Guangdong, Futian District 518000, People’s Republic of China

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BMC Complementary and Alternative Medicine 2014, 14:42  doi:10.1186/1472-6882-14-42

Published: 3 February 2014



Isoquercitrin, a flavonoid compound that is widely distributed in medicinal and dietary plants, possesses many biological activities, including inhibition of adipocyte differentiation. In this study, we investigated the effect of isoquercitrin on lipid accumulation and its molecular mechanisms in rat hepatoma H4IIE cells.


To investigate the effect of isoquercitrin on lipid accumulation, H4IIE cells were induced by FFA and the total lipid levels were detected by Oil Red O staining. Furthermore, The protein levels of AMPK and acetyl-CoA carboxylase (ACC), the gene expressions of transcriptional factor, lipogenic genes, and adiponectin receptor 1 (AdipoR1) were analyzed by Western blotting and quantitative real-time PCR. To further confirm the pathway of isoquercitrin-mediated hepatic lipid metabolism, H4IIE cells were treated with an AMPK inhibitor and AdipoR1 siRNA.


Isoquercitrin significantly enhances AMPK phosphorylation, downregulates sterol regulatory element binding protein transcription factor 1 (SREBP-1) and fatty acid synthase (FAS) gene expressions. Pretreatment with AMPK inhibitor, significantly decreased the AMPK phosphorylation and increased FAS expression stimulated by isoquercitrin. Isoquercitrin might also upregulate the expression of AdipoR1 dose-dependently via AMPK in the presence of an AMPK inhibitor and AdipoR1 siRNA.


Isoquercitrin appears to regulate AMPK activation, thereby enhancing AdipoR1 expression, suppressing SREBP-1 and FAS expressions, and resulting in the regulation of lipid accumulation. These results suggest that isoquercitrin is a novel dietary compound that can be potentially be used to prevent lipid metabolic disorder and nonalcoholic fatty liver disease.

Isoquercitrin; H4IIE cells; AMPK; AdipoR1