Wang Ye, Ji Xingming, Wang Xinyi, Sun Mengyu, Li Cheng, Wu Dongmei
Key Laboratory of Microecology-Immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, People's Republic of China.
Department of Gastroenterology, Tianjin First Central Hospital, Tianjin, People's Republic of China.
J Inflamm Res. 2025 Jan 2;18:1-15. doi: 10.2147/JIR.S485007. eCollection 2025.
The aim of this study is to investigate the protective effect of Cannabidiol (CBD) on DSS-induced colitis in C57BL/6 mice and its related pathways.
A mouse model of ulcerative colitis (US) was induced by DSS. Enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase-chain reaction (qRT-PCR), Western blot (WB) and immunofluorescence (IF) were used to identify the key factors involved in inflammatory response, oxidative stress and intestinal fibrosis. In addition, we transfected si-RNA into CCD-18Co cells.
The research suggests that CBD significantly improves intestinal inflammation by up-regulating the nuclear factor erythroid 2-related factor 2 (Nrf2) expression, inhibiting the classical Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κb) pathway, and inhibiting the release of IL-6 (Interleukin), IL-1β, Tumor Necrosis Factor-α (TNF-α) and other factors. At the same time, CBD plays an antioxidant role by regulating Nrf2/ HO-1 (Heme Oxygenase-1) pathway and activating HO-1 activity. On the other hand, CBD may regulate Transforming growth factor beta (TGF-β)/SMADs signaling pathway by inhibiting the expression of TGF-β1, thereby inhibiting the expression of α-SMA, Collagen1, TIMP1 and other factors, thus playing an anti-fibrotic role. Notably, when Nrf2 is inhibited or lacking, CBD loses the above protective effect against DSS-induced colon injury.
CBD affects the classical NF-κb pathway, Nrf2/ Heme Oxygenase-1 (HO-1) pathway, and Transforming growth factor beta (TGF-β)/SMAD pathway by regulating Nrf2, thereby reducing colonic inflammation and oxidative stress and improving the progression of colonic fibrosis.
本研究旨在探讨大麻二酚（CBD）对葡聚糖硫酸钠（DSS）诱导的C57BL/6小鼠结肠炎的保护作用及其相关通路。
用DSS诱导建立溃疡性结肠炎（UC）小鼠模型。采用酶联免疫吸附测定（ELISA）、定量逆转录聚合酶链反应（qRT-PCR）、蛋白质免疫印迹法（WB）和免疫荧光法（IF）鉴定参与炎症反应、氧化应激和肠道纤维化的关键因子。此外，我们将小干扰RNA转染至人正常结肠成纤维细胞（CCD-18Co）中。
研究表明，CBD通过上调核因子红细胞2相关因子2（Nrf2）的表达、抑制经典的活化B细胞核因子κB（NF-κb）通路以及抑制白细胞介素6（IL-6）、白细胞介素1β、肿瘤坏死因子-α（TNF-α）等因子的释放，显著改善肠道炎症。同时，CBD通过调节Nrf2/血红素加氧酶-1（HO-1）通路并激活HO-1活性发挥抗氧化作用。另一方面，CBD可能通过抑制转化生长因子β（TGF-β）1的表达来调节TGF-β/信号转导分子和转录激活因子（SMADs）信号通路，从而抑制α-平滑肌肌动蛋白（α-SMA）、胶原蛋白1、基质金属蛋白酶组织抑制因子1（TIMP1）等因子的表达，进而发挥抗纤维化作用。值得注意的是，当Nrf2被抑制或缺失时，CBD对DSS诱导的结肠损伤失去上述保护作用。
CBD通过调节Nrf2影响经典的NF-κb通路、Nrf2/血红素加氧酶-1（HO-1）通路以及转化生长因子β（TGF-β）/SMAD通路，从而减轻结肠炎症和氧化应激，改善结肠纤维化进程。
