Honokiol and Magnolol Exert an Anti-Inflammatory Effect by Inhibiting JAK2/STAT3/IL17 Signalling in a Rat Model of Ulcerative Colitis: A Combination of Bioinformatics and Experimental Study.

Abstract

Ulcerative colitis (UC) is a chronic, inflammatory bowel disease with limited clinical treatment. Traditional Chinese medicinal ingredients honokiol and magnolol have potential anti-inflammatory and gastrointestinal protective effects. However, their anti-inflammatory potential has not been investigated in UC. This study hypothesized that honokiol and magnolol alleviate UC by targeting key inflammatory signalling pathways. To verify this, we established a 2,4-dinitrobenzenesulfonic acid-induced UC rat model and administered honokiol and magnolol orally. The results showed that the two ingredients significantly reduced the disease activity index and colonic mucosal damage index and downregulated serum levels of pro-inflammatory factors TNF-α, IL-17, and CRP. Histopathological examination showed marked alleviation of colonic mucosal hyperemia, inflammatory infiltration, and ulcerative damage following honokiol and magnolol treatment. Bioinformatics analysis identified 74 UC-related targets for honokiol and 62 for magnolol, which were enriched in inflammatory response and JAK-STAT/IL-17 signalling pathways. A gradient boosting machine model was established to screen 16 shared hub targets, among which IL17A, JAK2, and STAT3 were highly correlated with immune cell infiltration. Molecular docking confirmed that honokiol and magnolol could stably bind to key proteins of the JAK-STAT pathway via noncovalent interactions with low binding energy. Immunohistochemistry and Western blot further verified that both ingredients significantly inhibited the activation of IL17A, JAK2, and STAT3 in the colonic tissues of UC rats. This study demonstrates that honokiol and magnolol exert anti-inflammatory effects in UC rats by inhibiting the JAK2/STAT3/IL17 pathway, providing a mechanistic basis and potential targets for the application of traditional Chinese medicinal ingredients in UC treatment.