Curcuma comosa-Derived Diarylheptanoid Ameliorates Ulcerative Colitis by Inhibiting JNK/NF-κB and Activating AMPK/Nrf2 Pathways

Abstract

Ulcerative colitis (UC) is a persistent inflammatory condition affecting the mucosal layer of the colon, with limited treatment options available. Diarylheptanoids, bioactive secondary metabolites found in Curcuma plants, possess diverse anti-inflammatory and antioxidant properties. However, the biological activities of 1,7-diphenyl-(6E)-6-hepten-3-ol (DPHP), a linear diarylheptanoid derived from Curcuma comosa rhizomes, remain largely unexplored. This study was conducted to investigate the antioxidant and anti-inflammatory mechanisms of DPHP in dextran sodium sulfate (DSS)-induced colitis mice and lipopolysaccharide (LPS)-treated RAW 264.7 macrophages. The results showed that DPHP supplementation considerably alleviated the severity of DSS-induced colitis by reducing the disease activity index, minimizing colon damage and neutrophil infiltration, and preventing body weight loss and colon shortening. DPHP inhibited inflammation in both DSS-induced colitis mice and LPS-treated macrophages by suppressing the c-Jun N-terminal kinases/nuclear factor kappa B pathway. Additionally, DPHP treatment effectively reduced reactive oxygen species formation and oxidative damage by upregulating the expression of antioxidant enzymes, likely via regulation of the adenosine monophosphate-activated protein kinase/nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway. Moreover, the antioxidant and anti-inflammatory effects of DPHP were significantly abrogated upon blocking Nrf2/heme oxygenase-1 activation. Overall, these findings shed light on the protective effects of DPHP against oxidative stress and inflammation through coordinated Nrf2 and nuclear factor-kappa B (NF-κB) pathway modulation, underscoring its potential as a therapeutic agent for preventing and treating UC.