Basic Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2022; 28(43): 6131-6156
Published online Nov 21, 2022. doi: 10.3748/wjg.v28.i43.6131
Salvia miltiorrhiza extract may exert an anti-obesity effect in rats with high-fat diet-induced obesity by modulating gut microbiome and lipid metabolism
Zi-Li Ai, Xian Zhang, Wei Ge, You-Bao Zhong, Hai-Yan Wang, Zheng-Yun Zuo, Duan-Yong Liu
Zi-Li Ai, Xian Zhang, Department of Postgraduate, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Wei Ge, Department of Proctology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang 330006, Jiangxi Province, China
You-Bao Zhong, Laboratory Animal Research Center for Science and Technology, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Hai-Yan Wang, Zheng-Yun Zuo, Duan-Yong Liu, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China
Author contributions: Ai ZL and Zhang X contributed equally to this work; Zhong YB and Ge W performed the experiments; Liu DY, Wang HY, and Zuo ZY contributed reagents/materials/analytical tools; Liu DY and Ge W analyzed the data; Ai ZL and Liu DY wrote the paper; Zuo ZY and Wang HY conceived and designed the experiments.
Supported by the National Natural Science Foundation of China, No. 82060836; Jiangxi Province Graduate Student Innovation Special Fund Project, No. YC2021-B146; and Jiangxi University of Chinese Medicine Science and Technology Innovation Team Development Program, No. CXTD22008.
Institutional review board statement: The study was reviewed and approved by the Jiangxi University of Chinese Medicine (Formula-Pattern Research Center).
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Jiangxi University of Chinese Medicine Animal Care and Use Committee (Approval No. JZLLSC2021-236).
Conflict-of-interest statement: There are no conflicts of interest to report.
Data sharing statement: No additional unpublished data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Hai-Yan Wang, PhD, Associate Professor, Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Meiling Avenue 1688, Nanchang 330004, Jiangxi Province, China. 378278287@qq.com
Received: August 25, 2022
Peer-review started: August 25, 2022
First decision: September 2, 2022
Revised: September 21, 2022
Accepted: October 31, 2022
Article in press: October 31, 2022
Published online: November 21, 2022
Processing time: 83 Days and 1.3 Hours
Abstract
BACKGROUND

Studies have shown that a high-fat diet (HFD) can alter gut microbiota (GM) homeostasis and participate in lipid metabolism disorders associated with obesity. Therefore, regulating the construction of GM with the balance of lipid metabolism has become essential for treating obesity. Salvia miltiorrhiza extract (Sal), a common traditional Chinese medicine, has been proven effective against atherosclerosis, hyperlipidemia, obesity, and other dyslipidemia-related diseases.

AIM

To investigate the anti-obesity effects of Sal in rats with HFD-induced obesity, and explore the underlying mechanism by focusing on GM and lipid metabolism.

METHODS

Obesity was induced in rats with an HFD for 7 wk, and Sal (0.675 g/1.35 g/2.70 g/kg/d) was administered to treat obese rats for 8 wk. The therapeutic effect was evaluated by body weight, body fat index, waistline, and serum lipid level. Lipid factors (cAMP, PKA, and HSL) in liver and fat homogenates were analyzed by ELISA. The effect of Sal on GM and lipid metabolism was assessed by 16S rRNA-based microbiota analysis and untargeted lipidomic analysis (LC-MS/MS), respectively.

RESULTS

Sal treatment markedly reduced weight, body fat index, serum triglycerides (TG), total cholesterol (TC), low-density lipoprotein, glucose, free fatty acid, hepatic lipid accumulation, and adipocyte vacuolation, and increased serum high-density lipoprotein (HDL-C) in rats with HFD-induced obesity. These effects were associated with increased concentrations of lipid factors such as cAMP, PKA, and HSL in the liver and adipose tissues, enhanced gut integrity, and improved lipid metabolism. GM analysis revealed that Sal could reverse HFD-induced dysbacteriosis by promoting the abundance of Actinobacteriota and Proteobacteria, and decreasing the growth of Firmicutes and Desulfobacterita. Furthermore, LC-MS/MS analysis indicated that Sal decreased TGs (TG18:2/18:2/20:4, TG16:0/18:2/22:6), DGs (DG14:0/22:6, DG22:6/22:6), CL (18:2/ 18:1/18:1/20:0), and increased ceramides (Cers; Cer d16:0/21:0, Cer d16:1/24:1), (O-acyl)-ω-hydroxy fatty acids (OAHFAs; OAHFA18:0/14:0) in the feces of rats. Spearman’s correlation analysis further indicated that TGs, DGs, and CL were negatively related to the abundance of Facklamia and Dubosiella, and positively correlated with Blautia and Quinella, while OAHFAs and Cers were the opposite.

CONCLUSION

Sal has an anti-obesity effect by regulating the GM and lipid metabolism.

Keywords: Salvia miltiorrhiza extract; Obesity; Gut microbiota; Lipid metabolism; High fat diet

Core Tip: Obesity is a major public health issue today and an obesity-related change in gut microbiota composition and its metabolite profile has been demonstrated. As a commonly used traditional Chinese medicine, Salvia miltiorrhiza extract (Sal) has many pharmacological effects, including anticoagulant, anti-inflammation, antioxidation, anti-fibrosis, anti-tumor, and organ protection. Although it has not been documented, Sal has a regulatory effect on obesity, which may be related to the gut microbiota. In the present study, we found that Sal plays a role in weight loss, lowering serum lipid levels, regulating the gut microbiota, and improving intestinal fecal metabolites in obese rats.