Effects of luteolin on glucose and lipid metabolism and liver oxidative stress injury in db/db mice based on artificial intelligence assisted drug quality evaluation and pharmacodynamics and its mechanisms
- VernacularTitle:基于人工智能辅助药物质量评价结合药效学研究木犀草素对db/db小鼠糖脂代谢及肝脏氧化应激损伤的作用及机制
- Author:
Qi XU
1
;
Hong-rong ZHANG
;
Nuo-bing RUAN
;
Xi-juan LYU
;
Zhao-hui FANG
Author Information
- Publication Type:Journal Article
- Keywords: type 2 diabetes mellitus; artificial intelli-gence; luteolin; oxidative stress; drug evaluation; Nrf2/HMOX1 pathway
- From: Chinese Pharmacological Bulletin 2025;41(2):323-333
- CountryChina
- Language:Chinese
- Abstract: Aim To study the possibility of luteolin(LUT)as a new drug of traditional Chinese medicine and its improving effect on glucose and lipid metabo-lism and liver oxidative stress injury in db/db mice,and to explore the possible mechanism.Methods AI was used to predict the drug toxicity,evaluate the phys-ical and chemical properties and segment the molecular structure of LUT.Molecular docking was used to verify the binding ability of LUT with Nrf2 and HMOX1;db/m mice were divided into the group C,and db/db mice were randomly divided into the T,L,M,H and P groups.The body weight and FBG changes were ob-served within 12 weeks of intervention.The expres-sions of FBG,HbA1c,Fins,TC,TG,HDL-C,LDL-C were detected.The pathomorphological changes and steatosis of mouse liver were observed by HE and oil red O staining.The expression of MDA,SOD and GSH-Px in liver was detected by Kit.The protein and mRNA expressions of Nrf2 and HMOX1 were detected by immunohistochemistry,WB and qPCR.Results AI algorithm predicted the safety and easy synthesis of LUT.LUT intervention had no significant effect on the body weight of db/db mice.After 12 weeks,compared with the group C,the livers of mice in group T showed disordered structure of hepatic lobules,irregular ar-rangement of hepatocytes,and a large number of fat vacuoles and lipid droplets in the cytoplasm.Compared with the group T,LUT intervention could improve the pathological changes of liver,reduce the expression of FBG,HbA1c,fins,TC,TG,LDL-C,MDA,improve the level of HOMA-IR,and upregulate the activities of SOD and GSH-Px.Molecular docking results showed LUT had strong binding with Nrf2 and HMOX1,and could increase the expression of Nrf2 and HMOX1.Conclu-sion LUT can correct the disorder of glucose and lip-id metabolism in db/db mice,and improve the level of oxidative stress in liver of mice through Nrf2/HMOX1 pathway,which has the development prospect as a new Chinese medicine for the treatment of T2DM.
