Neixiao-ruanmai decoction No 2 improves carotid atherosclerosis by modulating gut microbiota and inhibiting TLR4/NF-κB pathway activation

Abstract

Background

Carotid atherosclerosis(CAs) plaques are challenging to reverse. Neixiao-Ruanmai Decoction No 2(NXRMT No 2), a Traditional Chinese Medicine (TCM) decoction, has shown potential in treating CAs. However, while preliminary clinical trials have confirmed the efficacy of NXRMT No 2 in improving CAs, the comparative effectiveness of long-term versus short-term treatment courses remains unclear, and the underlying mechanisms of this decoction are not yet fully understood.

Methods

We conducted clinical trials, animal studies, 16S rRNA sequencing, metabolomics and fecal microbiota transplantation.

Result

Clinical research results indicate that NXRMT No 2(24 weeks of treatment) reduced total plaque area by 22.02%, maximum plaque thickness by 7.91%, and maximum plaque area by 21.29%. NXRMT No 2 improves patients’serum inflammatory levels, with a 24-week treatment course demonstrated superior efficacy compared to the 12-week treatment. Animal experiments demonstrated that NXRMT No 2 improved CAs progression, modulated the gut microbiota, inhibited the intestinal Toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) pathway and activated the expression of intestinal tight junction proteins.

Conclusion

NXRMT No 2 significantly attenuates CAs progression, with its primary mechanism likely related to modulating the gut microbiota to counteract the TLR4/NF-κB pathway and protect the intestinal barrier. This study provides evidence-based support for the use of NXRMT No 2 in treating CAs, offers guidance on optimal treatment duration for patients, and contributes to the development of traditional Chinese medicine formulations that improve CAs by modulating the gut microbiota—a significant advance in the prevention and treatment of CAs.