Shengxian Decoction improves cardiac function and gut barrier integrity by modulating microbiota in chronic heart failure rats
Background
Chronic heart failure (CHF) is a debilitating syndrome with high morbidity and mortality, posing a significant global health burden. Current treatments often fall short, highlighting the need for novel therapeutic strategies. Traditional Chinese Medicine (TCM) formulations like Shengxian Decoction (SXT) have shown promise in CHF treatment, but their precise mechanisms, particularly concerning the increasingly recognized gut-heart axis and gut microbiota modulation, remain largely unexplored. Understanding how SXT impacts gut microbiota could reveal new therapeutic pathways for CHF.
Study Design
Researchers established a CHF model in rats via transverse aortic constriction (TAC) surgery. The study identified 147 components in Shengxian Decoction (SXT) using LC-MS. Rats were treated with SXT, with a specific focus on a high-dose group. Cardiac function was assessed by echocardiography, and serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), lipopolysaccharide (LPS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were analyzed. Myocardial and colonic histopathology were examined via H&E and Masson's trichrome staining. Intestinal barrier function was evaluated using immunohistochemistry (IHC), Western blotting, and RT-qPCR. Fecal 16S rRNA gene sequencing and UPLC-MS metabolomics characterized gut microbiota and metabolites.
Results
Shengxian Decoction (SXT) treatment significantly improved cardiac function in CHF rats. It also reduced serum levels of key biomarkers: NT-proBNP, LPS, TNF-α, and IL-6, indicating reduced cardiac stress and systemic inflammation. Furthermore, SXT ameliorated pathological alterations observed in both myocardial and colonic tissues. The treatment restored the expression of tight junction proteins, occludin and ZO-1, in colonic tissue, suggesting improved intestinal barrier integrity. The high-dose SXT group demonstrated the most prominent therapeutic effects across these measures. 16S rRNA sequencing revealed that SXT effectively ameliorated gut microbiota dysbiosis, identifying 17 differentially abundant bacterial genera. Among these, SXT increased the abundance of genera capable of producing beneficial metabolites, although the abstract text was truncated at 'prod'.
Key Findings
- Shengxian Decoction (SXT) improved cardiac function in rats with chronic heart failure.
- SXT reduced serum levels of inflammatory markers:
NT-proBNP,LPS,TNF-α, andIL-6. - SXT ameliorated myocardial and colonic pathological alterations, restoring tight junction proteins occludin and ZO-1.
- High-dose SXT showed the most prominent therapeutic effects.
- SXT modulated gut microbiota, increasing the abundance of 17 differentially abundant bacterial genera.
Why It Matters
This study provides compelling evidence that Shengxian Decoction (SXT) offers a multi-faceted therapeutic approach for chronic heart failure (CHF), extending beyond direct cardiac effects to include gut microbiota modulation and intestinal barrier restoration. For those exploring integrative or complementary therapies, SXT emerges as a promising candidate, particularly for its potential to address the gut-heart axis, a critical but often overlooked aspect of CHF pathology. While this is a preclinical animal study, the findings suggest a novel mechanism for SXT's efficacy, potentially paving the way for future human trials. Understanding the specific microbial shifts and metabolites involved could inform the development of targeted pre/probiotic interventions or refined SXT formulations for better clinical outcomes in CHF patients.
shengxian-decoction
chronic-heart-failure
gut-microbiota
inflammation
intestinal-barrier
tcm