OBJECTIVE To investigate the potential therapeutic effects and underlying mechanisms of total alkaloids derived from processed Aconitum carmichaelii Debx(ACA)on ulcerative colitis(UC)in mice.METHODS The chemical composition of AC A was analyzed using liquid chromatography-mass spectrometry.A mouse model of UC was induced using dextran sodium sulfate(DSS)to assess the effects of continuous administration of salicylazosulfapyridine(SASP)(200 mg·kg-1)and ACA(10 and 20 mg·kg-1)over seven days,evaluating parameters such as body weight,disease activity index,colon length,and pathological damage to the colon.The anti-inflammatory activity and mechanisms of ACA were investigated through in vitro experiments,enzyme-linked immunosorbent assay,and Western blotting.RESULTS ACA is primarily composed of various characteristic monomeric alka-loids.Treatment with ACA(10 and 20 mg/kg)significantly mitigated weight loss,disease index elevation,colon shortening,and pathological damage induced by DSS in the mice.Additionally,ACA reduced the levels of inflammatory factors,including IL-1β,IL-18,and IL-6,elevated by DSS in colitis.The in vitro inflammatory model further demonstrated that ACA functions as a specific inhibi-tor,MCC950,similar to the NLRP3 inflammasome,which suppresses the secretion of the aforementioned inflammatory factors in the supernatant of LPS-and Nigericin-induced THP-1 cells.Protein expression analysis suggested that this effect may be linked to the inhi-bition of the NLRP3 signaling pathway.CONCLUSION ACA contains multiple structurally similar monomeric alkaloids that exhibit anti-UC activity in mice,potentially exerting anti-inflammatory effects through the inhibition of the NLRP3 inflammasome.
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