Effects of Cannabidiol on Intestinal Myofibroblast Fibrotic PathwaysPATHWAYS

Abstract

Inflammatory bowel disease (IBD) includes two immune-mediated disorders, Crohn’s disease (CD) and ulcerative colitis (UC). IBD is characterized by recurrent and chronic inflammation of the gastrointestinal tract. IBD is lifelong, and there is no cure. There has been an interest in new advanced medications to decrease inflammation and manage symptoms. Many of these new medications are expensive and depress the immune system, leaving many patients looking for alternatives to current medical therapies. Some IBD patients use medical marijuana to relieve the symptoms of this disease, and cannabidiol (CBD) in particular shows potential for reducing inflammation. This study investigates the potential therapeutic effects of CBD on IBD by examining its impact on fibrotic pathways in human intestinal myofibroblast (InMyoFib) cells.

Cultured InMyoFibs were pre-treated with CBD, followed by transforming growth factor-beta 1 (TGF-β1) to stimulate a pro-fibrotic phenotype and mimic human IBD in the lab. Expression of genes associated with fibrosis, inflammation, and cannabinoid signaling was measured by quantitative polymerase chain reaction (qPCR). Fibrotic protein expression in the culture media was analyzed using enzyme-linked immunosorbent assays (ELISA). CBD pre-treatment before TGF-β1 stimulation significantly reduced the expression of pro-fibrotic genes ACTA2, CCN2, COL1A1, and SERPINH1 compared to cells stimulated with TGF-β1 alone. Additionally, CBD increased the expression of inflammation-related genes IL6 and PTGS2 and the lipid metabolism gene PPARG, known to have anti-fibrotic properties. These findings suggest that CBD may modulate fibrotic and inflammatory signaling pathways, providing a potential therapeutic avenue for IBD treatment.