Study on the mechanism of Yishen tongluo formula improving abnormal lipid metabolism based on SREBPs pathway
- VernacularTitle:基于SREBPs通路的益肾通络方改善脂质代谢异常作用机制研究
- Author:
Liang ZHAO
1
;
Xiaowei ZHANG
1
;
Zhishen XIE
1
;
Shixie XIANG
1
;
Yafei DUAN
1
;
Gai GAO
1
;
Pan WANG
1
;
Huifen MA
1
;
Yiran SUN
1
;
Jie CHEN
2
;
Jiangyan XU
1
;
Zhenqiang ZHANG
1
Author Information
1. Academy of Chinese Medical Sciences，Henan University of Chinese Medicine，Zhengzhou 450046，China
2. International Academic Affairs Department，Management and Science University，Selangor Darul Ehsan Shah Alam 47300，Malaysia
- Publication Type:Journal Article
- Keywords:
Yishen tongluo formula;
abnormal lipid metabolism;
sterol regulatory element binding proteins;
lipid accumulation
- From:
China Pharmacy
2023;34(23):2835-2840
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the mechanism of Yishen tongluo formula （YSTLF） in improving abnormal lipid metabolism based on the sterol regulatory element binding proteins （SREBPs） pathway. METHODS Using C57BLKS/J （db/db） mice as model and C57BLKS/J （db/m） mice as normal control， the mechanism of 1， 2.5 and 5 g/kg YSTLF improving abnormal lipid metabolism of db/db mice was investigated by determining the liver coefficient， the contents of serum total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL） and high-density lipoprotein （HDL）， observing steatosis and lipid accumulation in liver tissue of mice， detecting the protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription levels of Srebp- 1c， Srebp-2 and their downstream lipid metabolism-related target genes （Fasn， Acc1， Scd5， Fads1， Hmgcr， Dhcr24， Insig-1， Fdps） in liver tissue of mice. Using low-fat cultured human liver cancer cell HepG2 as an in vitro cell model for abnormal lipid metabolism， and 25-HC （SREBPs inhibitor， 10 μmol/L） as the control， the effects of 125， 250 and 500 μg/mL YSTLF on protein expressions of SREBP-1 and SREBP-2 as well as mRNA transcription of SREBP-1c， SREBP-2 and their downstream lipid metabolism-related target genes were investigated to verify the mechanism in vitro. RESULTS 1， 2.5， 5 g/kg YSTLF significantly reduced the levels of TC， TG and LDL， the percentage of lipid droplet-positive region in liver tissue and liver coefficient， significantly down-regulated protein expressions of Pre-SREBP-1， n-SREBP-1， Pre-SREBP-2 and n-SREBP-2， and mRNA transcription of Srebp-1c， Srebp-2 and their downstream target genes in liver tissue， while significantly increased HDL level， with statistical significance （P＜0.05 or P＜0.01）. In the cell experiment in vitro， the expressions of the above-mentioned proteins and genes in the cells treated with YSTLF at 125， 250 and 500 μg/mL for 24 hours were consistent with those in the animal experiment； there was no significant difference in the expressions of the above-mentioned proteins and genes between inhibitor control group and 250， 500 μg/mL YSTLF groups （P＞0.05）. CONCLUSIONS YSTLF can regulate the expression of transcription factor SREBPs， so as to inhibit the high expression of fatty acid and cholesterol synthesis-related genes， promote the degradation of TC and TG， improve the abnormality of lipid metabolism and inhibit lipid accumulation， thus playing the role of lipid-lowering.
