# Astragalus membranaceus—Salvia miltiorrhiza Decoction Ameliorates Metabolic Syndrome and Gut Microbiota Dysbiosis Induced by High‐Fat Diet: A Comparative Study

## TL;DR

This study shows that a specific herbal combination, Astragalus membranaceus and Salvia miltiorrhiza, can reduce the effects of a high-fat diet on metabolic syndrome and gut health in rats.

## Contribution

The study identifies the optimal 1:2 ratio of the herbs and links their effects to gut microbiota and metabolite changes.

## Key findings

- ASD-A (1:2 ratio) most effectively reduced obesity, hyperlipidemia, and inflammation in rats.
- ASD-A improved gut microbiota dysbiosis and balanced SCFAs and BAs levels.
- Lactic acid and other metabolites are potential biomarkers for ASD's therapeutic effects.

## Abstract

Astragalus membranaceus (Fisch.) Bunge (AM)—
Salvia miltiorrhiza
Bunge (SM) decoction (ASD) is a herb pair not only widely used in clinic against cardiovascular diseases and metabolic syndrome, but also as key compositions in some functional foods. However, the pairing ratios and potential mechanisms of ASD in preventing metabolic syndrome are still unclear. The present study comprehensively evaluated how the pairing ratios of AM and SM affect the treatment of ASD against high‐fat diet (HFD)‐induced metabolic disorder and investigate the roles of gut microbiota in the biological process. To establish a metabolic syndrome model, thirty SD male rats received a 10‐week HFD. All rats were divided into six groups randomly: ND, HFD, ASD‐A (the quality ratio of 1:2 AM to SM), ASD‐B (the quality ratio of 1:1 AM to SM), ASD‐C (the quality ratio of 2:1 AM to SM), and Simvastatin groups, and treated with corresponding medicine or saline. Biochemical changes and inflammation levels in serum and liver were assessed, while histopathology staining was conducted to evaluate liver and intestinal barrier lesions. Moreover, 16S rRNA sequencing technology was employed to assess the gut microbiota structure, and a targeted metabolomics method was utilized to quantify the fecal content of BAs and SCFAs. Administration of ASDs in three different pairing ratios considerably alleviated obesity, hyperlipidemia, systemic inflammation, liver injury, and intestinal barrier disorder in rats. Among the three decoctions, ASD‐A showed the greatest potential in multi‐aspects. Furthermore, ASD‐A significantly ameliorated gut microbiota dysbiosis and the imbalance of SCFAs and BAs induced by HFD. Especially, correlation analysis results suggested that the levels of lactic acid, 3‐hydroxybutyric acid, and 3‐hydroxypropionic acid are potential therapeutic biomarkers. The research findings indicated that ASDs could effectively prevent HFD‐induced metabolic syndrome, among which ASD‐A, with a quality ratio of 1:2 (AM: SM) exhibited superior effects. ASD‐A also significantly ameliorated gut microbiota disorders induced by HFD and promoted the production of beneficial metabolites.

The optimal pairing ratio of ASDs against hyperlipidemia was systematically investigated. ASD maintains intestinal homeostasis and improves the systemic inflammatory response. A new LC–MS/MS method for the determination of derivatized SCFAs was established. ASD regulates the gut microbiota and its metabolites (SCFAs and BAs). Potential biomarkers of ASD against metabolic syndrome were proposed.