Steaming reduces Polygonum multiflorum hepatotoxicity by modulating gut microbiota-bile acid-FXR/NF-κB signaling in the gut-liver axis.
Processing Polygonum multiflorum, especially with black bean decoction, significantly reduces liver toxicity in a mouse model, but the implications for human health require further investigation.
Where it sits
this study against the rest of the lixisenatide corpusSummary and findings
This study investigated the hepatotoxicity of Polygonum multiflorum (PM) and the effects of its processed forms, specifically steaming with black bean decoction (PPM), in a mouse model. The results indicated that PPM treatment reduced serum alanine aminotransferase (ALT) levels by 82% compared to PM. The study aimed to elucidate the mechanisms involved in the modulation of the gut-liver axis.
Abstract
<h4>Background</h4>Polygonum multiflorum Thunb. (PM) can induce hepatotoxicity, particularly with prolonged use. Traditional processing methods, notably steaming (SPM) and steaming with black bean decoction (PPM), are recognized for their ability to mitigate this toxicity; however, the underlying mechanisms, especially from the gut-liver axis perspective, remain poorly understood.<h4>Purpose</h4>This study aims to clarify the mechanism by which processing reduces PM-induced hepatotoxicity, with a particular focus on the regulation of the gut-liver axis.<h4>Methods</h4>We employed a comprehensive approach integrating histopathological examination, multi-omics analyses (including 16S rRNA sequencing, transcriptomics, and metabolomics), and molecular analysis to investigate the distinct effects of PM, SPM, and PPM in a mouse model.<h4>Results</h4>PM caused significant liver injury, characterized by elevated serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and severe pathological damage. This damage was marked by intestinal barrier disruption (decreased tight junction protein-1 (ZO-1) and occludin), systemic inflammation (elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels), and activation of the hepatic nuclear factor-kappa B (NF-κB) pathway. Multi-omics analysis revealed that PM induced severe GM dysbiosis (e.g., reduction in the Lactobacillus and a significant increase in the unclassified_f_Oscillospiraceae), a marked decrease in short-chain fatty acids (SCFAs) (e.g., a 72% reduction in butyrate), and disruption of the hepatic bile acid profile. Notably, the two processed products, particularly PPM, significantly reversed these alterations. Compared to the PM group, PPM treatment reduced serum ALT by 82% and exerted extensive protective effects. It restored beneficial bacteria, increased SCFAs levels, normalized bile acid metabolism, and suppressed the hepatic fibrogenic/NF-κB inflammatory axis. This detoxifying effect may be associated with reduced systemic exposure to toxic stilbene glycosides and anthraquinones in the processed PM groups compared to the PM group.<h4>Conclusion</h4>This study suggests that processing, particularly with black bean decoction (PPM), can alleviate PM-induced hepatotoxicity by reshaping the GM, restoring its metabolic products (SCFAs), normalizing bile acid signaling, and downregulating the FXR/NF-κB inflammatory axis within the gut-liver axis. These findings provide a mechanistic basis for the clinical preference for processed PM products and highlight the importance of stringent quality control, while also underscoring that residual risk may persist, particularly in susceptible populations.
Background
The study addresses the hepatotoxicity associated with prolonged use of Polygonum multiflorum (PM), a traditional herbal remedy. Previous research has indicated that processing methods like steaming can mitigate this toxicity, but the mechanisms involved, particularly regarding the gut-liver axis, remain unclear. Understanding these mechanisms is crucial for ensuring the safe use of PM in clinical settings.
Methods
The study utilized a mouse model to assess the effects of PM, steamed PM (SPM), and steamed PM with black bean decoction (PPM). Histopathological examinations, multi-omics analyses (including 16S rRNA sequencing, transcriptomics, and metabolomics), and molecular analyses were employed. Specific outcomes measured included serum ALT and AST levels, intestinal barrier integrity, and inflammatory markers.
Results
PM caused significant liver injury, with elevated serum ALT and AST levels indicating hepatotoxicity. PPM treatment resulted in an 82% reduction in serum ALT compared to the PM group. Additionally, PM led to a 72% reduction in butyrate levels and increased systemic inflammation, evidenced by elevated TNF-α and IL-6 levels.
Interpretation
The findings suggest that processing PM, particularly with black bean decoction, may effectively reduce hepatotoxicity through modulation of gut microbiota and restoration of metabolic products. While the study demonstrates significant statistical findings, the clinical relevance of these results in human populations remains uncertain. Confounding factors include the use of a mouse model and the potential for residual risks in certain populations.
Key findings
- PM caused significant liver injury, characterized by elevated serum ALT and AST levels.
- PPM treatment reduced serum ALT by 82% compared to the PM group.
- PM induced a 72% reduction in butyrate levels.
- PPM restored beneficial bacteria and increased SCFAs levels.
- PM resulted in systemic inflammation with elevated TNF-α and IL-6 levels.
Limitations
- Conducted in a mouse model, limiting human applicability.
- Potential residual risk in susceptible populations.
- Short duration of study may not capture long-term effects.