Oroxin A from Oroxylum indicum improves disordered lipid metabolism by inhibiting SREBPs in oleic acid-induced HepG2 cells and high-fat diet-fed non-insulin-resistant rats
Tianqi Cai,
Xiaoxue Xu,
Ling Dong,
Shufei Liang,
Meiling Xin,
Tianqi Wang,
Tianxing Li,
Xudong Wang,
Weilong Zheng,
Chao Wang,
Zhengbao Xu,
Meng Wang,
Xinhua Song,
Lingru Li,
Jingda Li,
Wenlong Sun
Affiliations
Tianqi Cai
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Xiaoxue Xu
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Ling Dong
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Shufei Liang
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Meiling Xin
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Tianqi Wang
College of Life Science, Yangtze University, Jingzhou, Hubei, 434000, People's Republic of China
Tianxing Li
National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100000, People's Republic of China
Xudong Wang
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, Zhejiang 310000, People's Republic of China
Weilong Zheng
Institute of Biomass Resources, Taizhou University, Taizhou, Zhejiang, 317700, People's Republic of China
Chao Wang
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Zhengbao Xu
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Meng Wang
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Xinhua Song
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China
Lingru Li
National Institute of TCM Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, 100000, People's Republic of China; Corresponding author.
Jingda Li
College of Life Science, Yangtze University, Jingzhou, Hubei, 434000, People's Republic of China; Corresponding author.
Wenlong Sun
School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China; Corresponding author. Institute of Biomedical Research, School of Life Sciences, Shandong University of Technology, Zibo, Shandong, 255000, People's Republic of China.
Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.
