Taraxacum officinale-derived exosome-like nanovesicles modulate gut metabolites to prevent intermittent hypoxia-induced hypertension

Background: We aimed to investigate whether Taraxacum officinale (T. officinale)-derived exosome-like nanovesicles (ELNs) exerted hypotensive effects in intermittent hypoxia (IH)-induced hypertensive disorders and their potential mechanisms. Results: In this study, we developed T. officinale-derived natural nanoparticles with ideal size and stable negative surface charge, containing large amount of lipids and some functional proteins. We found that ELNs effectively reduced IH-induced hypertension, exhibited local anti-inflammatory effects on intestinal tissues in a rat model of IH-induced hypertension, and reduced intestinal tissue damage, including loss of goblet cells and barrier integrity damage, and ultimately inhibited the systemic inflammatory response. In addition, we evaluated intestinal microbial composition and SCFAs content and found significant changes in the structure and diversity of intestinal microbes, where butyrate was identified as the most important cause of the overall differences in the flora. Therefore, we further evaluated whether butyrate was a key target for ELNs to exert their effects in IH-induced hypertensive disease. We found that butyrate intervention further inhibited systemic inflammatory response and vascular wall remodeling by improving the intestinal microenvironment in IH rats, thereby attenuating IHinduced hypertension. Conclusions: T. officinale-derived ELNs were effective in the treatment of IH-induced hypertensive disease, whereas butyrate played a major role in mediating the effects of ELNs in anti-IH-induced hypertensive disease.