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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 ACA 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 alkaloids. 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 inhibitor, 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 inhibition 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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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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