Ginsenoside Rh1 Treats Diabetes in Mice by Boosting GLP-1 Through Gut Bacteria and Bile Acid Reprogramming | Research

The takeaway

Ginsenoside Rh1 improved diabetes in mice by reshaping gut microbiota and bile acid profiles to activate TGR5 and suppress FXR signaling, ultimately enhancing L-cell differentiation and GLP-1 secretion.

Complete pathway mapped
From ginsenoside → liver enzymes → gut bacteria → bile acids → FXR/TGR5 → L-cells → GLP-1: a fully characterized mechanism

What the researchers found

Rh1 upregulated CYP27A1/CYP7B1, reshaped gut microbiota BSH/bai genes, increased ileal T-β-MCA (FXR suppression) and LCA (TGR5 activation), promoting L-cell differentiation and GLP-1 secretion via CREB/cAMP/GCG/PCSK1 pathway.

Why it matters

Understanding how natural compounds boost GLP-1 through specific gut-liver-hormone pathways could lead to nutraceuticals that complement pharmaceutical GLP-1 therapy.

How the study worked

HFD/STZ-induced T2DM mouse model treated with 60 mg/kg/day ginsenoside Rh1 for 4 weeks, with 16S rRNA sequencing, targeted bile acid metabolomics, Western blotting, gene expression, and enzyme activity assays.

What this study cannot tell us

Mouse model. 4-week treatment is short. The specific ginsenoside Rh1 epimers may have different activities. Human gut microbiome responses may differ.

How to read the evidence

Well-designed preclinical study with comprehensive pathway analysis. Strong mechanistic evidence needing human validation.

When this study was published

Published in 2025.

The bigger picture

This maps a complete molecular pathway from a natural compound through gut bacteria and bile acids to GLP-1 secretion—providing a framework for developing precision nutraceuticals.

Questions still open

Would ginsenoside Rh1 enhance pharmaceutical GLP-1 RA effects?
Can the FXR/TGR5 signaling pathway be directly targeted for GLP-1 enhancement?
Does human gut microbiota respond similarly to Rh1 treatment?

Common questions

How does ginseng help with diabetes?

This study shows a specific ginseng compound (Rh1) works by reprogramming gut bacteria and bile acids to boost natural GLP-1 release—the same hormone targeted by drugs like Ozempic—through a fully characterized molecular pathway.

Could ginseng supplements replace GLP-1 drugs?

Unlikely to replace them, but could complement them. Understanding the specific pathway through which ginseng boosts GLP-1 could lead to targeted nutraceuticals that enhance pharmaceutical therapy.

Read the original research

20(S/R)-ginsenoside Rh1 improves type 2 diabetes via gut microbiota-modulated bile acid signaling and FXR/TGR5-dependent GLP-1 enhancement.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 195, 118997

View on PubMed ↗Publisher’s paper ↗

Citation

Gao, Ge; Wang, Enyu; Yang, Ge; Gao, Yansong; Zhao, Zijian; Zhao, Yujuan; Kang, You; Zhao, Lei; Li, Shengyu. (2026). 20(S/R)-ginsenoside Rh1 improves type 2 diabetes via gut microbiota-modulated bile acid signaling and FXR/TGR5-dependent GLP-1 enhancement.. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 195, 118997. https://doi.org/10.1016/j.biopha.2026.118997