Capsaicin alleviates acute alcohol-induced pyroptosis by activating ESCRT-III-dependent cell membrane repair in hepatocytes.

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  • Additional Information
    • Source:
      Publisher: Royal Society of Chemistry Country of Publication: England NLM ID: 101549033 Publication Model: Electronic Cited Medium: Internet ISSN: 2042-650X (Electronic) Linking ISSN: 20426496 NLM ISO Abbreviation: Food Funct Subsets: MEDLINE
    • Publication Information:
      Original Publication: Cambridge : Royal Society of Chemistry
    • Subject Terms:
      Pyroptosis*/drug effects ; Capsaicin*/pharmacology ; Capsaicin*/analogs & derivatives ; Endosomal Sorting Complexes Required for Transport*/metabolism ; Hepatocytes*/drug effects ; Hepatocytes*/metabolism ; Cell Membrane*/drug effects ; Cell Membrane*/metabolism ; TRPV Cation Channels*/metabolism; Animals ; Mice ; Humans ; Male ; Mice, Inbred C57BL ; Ethanol ; Liver Diseases, Alcoholic/drug therapy ; Liver Diseases, Alcoholic/metabolism
    • Abstract:
      Capsaicin (CAP), the active ingredient in hot chilli peppers, has anti-inflammatory and hepatoprotection effects. Acute alcoholic liver injury (AALI) is liver damage caused by acute alcohol abuse, which can lead to severe liver lesions and even be life-threatening. Pyroptosis is inflammation-related programmed cell death characterized by membrane rupture and plays a key role in AALI. The endosomal sorting complexes required for transport (ESCRT) proteins can gather at damaged areas of the membrane to facilitate the process of sealing the membrane. In this study, we found that CAP could relieve acute alcohol-induced pyroptosis of hepatocytes in vitro and in vivo . Mechanically, we found that CAP could alleviate acute alcohol-induced pyroptosis by activating the ESCRT-III-dependent membrane repair machinery. Furthermore, the data showed that CAP induced ESCRT-III protein expression by activating transient receptor potential vanilloid member 1 (TRPV1) on the cell membrane and Ca 2+ influx. TRPV1 inhibitor capsazepine (CPZ) inhibited the relief effect of CAP on acute alcohol-induced pyroptosis. Overall, these results showed that CAP might activate ESCRT-III-dependent membrane repair machinery through Ca 2+ influx, which is regulated by TRPV1 calcium channels, therefore mitigating acute alcohol-induced pyroptosis. Our research provides a new perspective on a naturally active food product to promote cell repair and relieve AALI.
    • Accession Number:
      S07O44R1ZM (Capsaicin)
      0 (Endosomal Sorting Complexes Required for Transport)
      0 (TRPV Cation Channels)
      3K9958V90M (Ethanol)
    • Publication Date:
      Date Created: 20240722 Date Completed: 20240812 Latest Revision: 20240812
    • Publication Date:
      20240813
    • Accession Number:
      10.1039/d4fo00806e
    • Accession Number:
      39036891