Flavonoid compound from Agrimonia pilosa Ledeb improves adipose insulin resistance by alleviating oxidative stress and inflammation.
Tingwang Guo, Yun Pan, Lin Yang, Gang Chen, Jia Deng, Liancai Zhu
Author Information
Tingwang Guo: Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China.
Yun Pan: Department of Gastroenterology, Children's Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing Key Laboratory of Pediatrics, Chongqing, China. panyun0617@163.com.
Lin Yang: College of Environment and Resources, Chongqing Technology and Business University, Chongqing, China.
Gang Chen: College of Environment and Resources, Chongqing Technology and Business University, Chongqing, China.
Jia Deng: College of Environment and Resources, Chongqing Technology and Business University, Chongqing, China.
Liancai Zhu: Key Laboratory of Biorheological Science and Technology, Ministry of Education, College of Bioengineering, Chongqing University, Chongqing, China. zhuliancai75@126.com.
BACKGROUND: Researches and practice of traditional Chinese medicine indicated that Agrimonia pilosa Ledeb could improve insulin resistance (IR) and treat type 2 diabetes (T2DM). To reveal its underling mechanisms, we isolated Flavonoid component (FC) from Agrimonia pilosa Ledeb and elucidated its effects on glucose metabolism to improve IR by suppressing oxidative stress and inflammation. METHODS: Adipocytes or mice IR model was established with overdosed glucose and insulin or high-fat diet. The uptake of 2-NBDG and glucose consumption were measured to verify insulin sensitivity in vitro and vivo. Reactive oxidative species (ROS) were detected by flow cytometry, and superoxide dismutase (SOD) activity as well as the malondialdehyde (MDA) content were also measured. Meanwhile, factors associated with insulin signal pathway including PPARγ, insulin receptor substrate-1 (IRS-1), GLUT4, and oxidative stress including NF-E2-related factor 2 (Nrf2), as well as the related inflammatory cytokines such as NF-κB, IL-1β, IL-6 and TNF-α were tested. Furthermore, the JNK/PI3K/Akt signal pathway was also explored. RESULTS: FC extracted from Agrimonia pilosa Ledeb ameliorated the impaired glucose metabolism significantly. Further study indicated that FC could regulate the insulin signal pathway to improve insulin resistance. Moreover, it could upregulate PPARγ with the similar efficacy as pioglitazone (Piog) straightway. FC also decreased the endogenous ROS and MDA content, increased SOD activity and Nrf2 expression to facilitate oxidative homeostasis. It attenuated expression and secretion of inflammatory cytokines obviously. At last, our results indicated JNK/PI3K/Akt pathway was regulated by FC in adipocytes and adipose tissue. CONCLUSION: FC could ameliorate glucose metabolism and improve IR. It exerted these effects by suppressing oxidative stress and inflammation. FC from Agrimonia pilosa Ledeb has a good prospect to be drugs or functional foods for IR and T2DM.
