Zexie Tang targeting FKBP38/mTOR/SREBPs pathway improves hyperlipidemia.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

Zexie Tang (ZXT), only two consists with Alismatis Rhizoma (AR) and Atractylodes macrocephala Rhizoma (AM), a classical Chinese medicine formula from Synopsis of the Golden Chamber with a history of 2000 years. Clinical observation in recent years has found that ZXT has excellent lipid-lowering effect.

AIM OF THE STUDY:

To explore the potential mechanism of ZXT ameliorates hyperlipidemia based on FKBP38/mTOR/SREBPs pathway.

MATERIALS AND METHODS:

WD-induced hyperlipidemia mice and oleic acid induced cell lipid accumulation model were used to investigate pharmacodynamic. The effect of ZXT on the transcriptional activity of SREBPs was detected by reporter gene assay. Proteins and downstream genes of mTOR/SREBPs pathway were detected in vivo and in vitro. Combined with network pharmacology and HPLC-Q-TOF/MS, the active ingredients were screened and identified. The interaction between active compounds of ZXT and FKBP38 protein were analyzed by docking analysis.

RESULTS:

ZXT decreased TC, TG and LDL-c levels in blood of WD-induced hyperlipidemia mouse model, and improved insulin resistance in vivo. ZXT also reduced TC, TG and lipid accumulation in cells line, and inhibited SREBPs luciferase activity, protein and its target genes expression such as FASN, HMGCR, etc. Meanwhile, ZXT inhibited protein expression levels of p-mTOR, p-S6K, etc in vitro and in vivo. Combined with network pharmacology and HPLC-Q-TOF/MS, 16 active ingredients were screened and identified. Docking results showed that active compounds of ZXT binding to FKBP38 and formed hydrogen bond.

CONCLUSION:

Our findings highlighted that ZXT ameliorates hyperlipidemia, in which FKBP/mTOR/SREBPs pathway might be the potential regulatory mechanism.

• Authors: Zhishen Xie, Er-Wen Li, Gai Gao, Yueyue Du, Mengyao Wang, Hui Wang, Pan Wang, Yonghui Qiao, Yunfang Su, Jiangyan Xu, Xiaowei Zhang, Zhenqiang Zhang
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 290 Pg. 115101 (May 23 2022) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 35151834 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Elsevier B.V. All rights reserved.

Chemical References

• Lipids
• Plant Extracts
• Sterol Regulatory Element Binding Proteins
• TOR Serine-Threonine Kinases
• Tacrolimus Binding Proteins

Topics

• Alismatales
• Animals
• Atractylodes
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Hyperlipidemias (pathology)
• Lipids (blood)
• Male
• Mice
• Mice, Inbred C57BL
• Molecular Docking Simulation
• Network Pharmacology
• Plant Extracts (pharmacology)
• Sterol Regulatory Element Binding Proteins (drug effects)
• TOR Serine-Threonine Kinases (drug effects)
• Tacrolimus Binding Proteins (drug effects)