Dietary capsaicin attenuates aortic dissection by inhibiting M1 macrophage polarisation and modulating the gut microbiota

  • Phytomedicine. 2026 Jul:156:158269. doi: 10.1016/j.phymed.2026.158269.
Wanqi Lan  1 ,  Heng Yang  2 ,  Wu Liu  3 ,  Congcong Li  3 ,  Chao Luo  3 ,  Yonggang Shi  3 ,  Juesheng Yang  3 ,  Haiyan Xiang  3 ,  Yongqin Li  3 ,  Yuqi Yi  3 ,  Jing Wei  4 ,  Yanhua Tang  5 ,  Tingtao Chen  6
Affiliations
  • 1. Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, China; The Second Clinical Medical College of Nanchang University, Nanchang 330008, China; Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330036, China.
  • 2. Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, China; The Second Clinical Medical College of Nanchang University, Nanchang 330008, China; Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, China.
  • 3. Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, China; The Second Clinical Medical College of Nanchang University, Nanchang 330008, China.
  • 4. The Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330036, China.
  • 5. Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, China; The Second Clinical Medical College of Nanchang University, Nanchang 330008, China. Electronic address: [email protected].
  • 6. Department of Cardiovascular Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330008, China; The Second Clinical Medical College of Nanchang University, Nanchang 330008, China; Jiangxi Province Key Laboratory of Bioengineering Drugs, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang 330036, China; The Institute of Translational Medicine, Jiangxi Medical College, Nanchang University, Nanchang 330036, China. Electronic address: [email protected].
PMID: 42102790 DOI: 10.1016/j.phymed.2026.158269
Abstract

Background: Aortic dissection (AD) is a fatal cardiovascular emergency for which effective pharmacological treatments are lacking. Increasing evidence suggests that spicy diets exert beneficial effects on cardiovascular diseases. However, whether a spicy diet can attenuate AD, and the mechanisms by which it might do so, remain unclear.

Purpose: This study was performed to investigate the role of dietary capsaicin in AD and to elucidate its underlying mechanisms.

Methods: Fifty patients with AD (AD group) and 50 volunteers with risk factors for AD (NP group) were enrolled to examine associations among spicy food consumption, serum capsaicin levels, and AD. In addition, a β-aminopropionitrile-induced AD mouse model and a lipopolysaccharide-induced M1 macrophage polarisation model were established to investigate the impact of capsaicin on AD and elucidate its underlying mechanisms.

Results: Patients with AD exhibited lower spicy food consumption, reduced serum capsaicin concentrations, and gut microbiota dysbiosis compared with the NP group. Dietary capsaicin attenuated AD pathogenesis in mice, suppressed M1 macrophage polarisation, and restored gut microbiota homeostasis. Mechanistically, in vitro transcriptomic Sequencing and small interfering RNA experiments demonstrated that capsaicin activates TRPV1 to suppress TLR4/MyD88/NF-κB signalling, thereby inhibiting M1 macrophage polarisation. Importantly, the TRPV1 antagonist capsazepine abrogated the protective effects of capsaicin in vivo, confirming TRPV1 dependence.

Conclusions: These findings elucidate the mechanistic basis of the protective effects of dietary capsaicin against AD and provide the first evidence that dietary capsaicin attenuates AD by inhibiting M1 macrophage polarisation, an effect accompanied by the restoration of gut microbiota homeostasis and improved intestinal barrier function. Collectively, this work supports dietary capsaicin as a promising therapeutic strategy for AD.

Keywords
Aortic dissection; Capsaicin; Gut microbiota; Macrophage polarization; TRPV1.
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