Investigation of the protective effect of beta caryophyllene against indomethacin-induced gastric ulcer in rats: in vivo and in vitro study

Abstract

Abstract In this study, the protective and healing effects of beta-caryophyllene (BCP) on gastric mucosa in indomethacin (INDO)-induced gastric ulcer model were investigated. In the study, 116 male Sprague–Dawley rats were used. In in vivo experiments, rat was administered doses of 50–100–200 mg/kg BCP and 5 mg/kg omeprazole for 14 days, and indomethacin (100 mg/kg) was given on the last day. In in vitro experiments, the effects of BCP (250–500–1000 µg/ml) on gastric motility and acid secretion were examined by isolated organ bath method. It was found that INDO treatment increased MDA level in gastric tissue, but decreased GPx and SOD activities. Nrf2 and HO-1 levels were decreased in INDO-treated groups. INDO increased TNF-α, IL-1β, and NF-κB levels and iNOS activity, but decreased COX-1 activity and PGE2 levels. INDO induced ER stress and increased GRP78, ATF4, ATF6, p-IRE1, sXBP1, eIF2-α, and CHOP expression levels in gastric tissue. Bax, caspase-3, and caspase-12 levels increased in INDO group, while Bcl-2 level decreased. BCP showed protective activity in gastric tissue and brought these parameters closer to normal levels. In vitro studies revealed that BCP decreased ACh and KCl-induced gastric contractions. Again, BCP decreased gastric acid secretion via M3 receptor pathway but not via H2 and CCK2 receptor pathways. This study revealed that BCP showed healing effects by protecting gastric mucosa from oxidative stress, inflammation, ER stress, and apoptosis in INDO-induced gastric ulcer model. In addition, it was revealed that BCP affects gastric motility by regulating gastric acid secretion via M3 receptor pathway.