We examined the modulatory activity of β-caryophyllene (CA) and gene expression in colitic colon tissues in a dextran sulfate sodium (DSS)-induced colitis model. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. CA (30 or 300 mg/kg) was administered orally once a day together with DSS. CA administration attenuated the increases in the disease activity index, colon weight/length ratio, inflammation score, and myeloperoxidase activity in DSS-treated mice. Microarray analysis showed that CA administration regulated the expression in colon tissue of inflammation-related genes including those for cytokines and chemokines (Ccl2, Ccl7, Ccl11, Ifitm3, IL-1β, IL-28, Tnfrsf1b, Tnfrsf12a); acute-phase proteins (S100a8, Saa3, Hp); adhesion molecules (Cd14, Cd55, Cd68, Mmp3, Mmp10, Sema6b, Sema7a, Anax13); and signal regulatory proteins induced by DSS. CA significantly suppressed NF-κB activity, which mediates the expression of a different set of genes. These results suggest that CA attenuates DSS-induced colitis, possibly by modulating the expression of genes associated mainly with colon inflammation through inhibition of DSS-induced NF-κB activity.
Keywords: CA, β-caryophyllene; CD, crohn disease; Cebpb, CCAAT/enhancer-binding protein β Colitis; DSS, dextran sulfate sodium; Dextran sulfate sodium; Gene expression; Hp, haptoglobin; IBD, inflammatory bowel disease; IL, interleukin; Inflammation; IκB, inhibitor κB; MPO, myeloperoxidase; NF-κB, nuclear factor-kappa B; S100a8, S100 calcium binding protein a8; SAL, sulfasalazine; Saa3, serum amyloid A3; TNF-α, tumor necrosis factor-α; UC, ulcerative colitis; β-Caryophyllene (PubChem CID5281515).