Beneficial Effects of Camellia Oil (Camellia oleifera Abel.) on Ketoprofen-Induced Gastrointestinal Mucosal Damage through Upregulation of HO-1 and VEGF

Abstract

Nonsteroidal anti-inflammatory drugs, such as ketoprofen, are generally used to treat pain and inflammation and as pyretic agents in clinical medicine. However, the usage of these drugs may lead to oxidative injury to the gastrointestinal mucosa. Camellia oil ( Camellia oleifera Abel.) is commonly used in Taiwan and China as cooking oil. Traditional remedies containing this oil exert beneficial health effects on the bowel, stomach, liver, and lungs. However, the effects of camellia oil on ketoprofen-induced oxidative gastrointestinal mucosal lesions remain unknown. The objective of this study was to evaluate the effect of camellia oil on ketoprofen-induced acute gastrointestinal ulcers. The results showed that treatment of Int-407 cells with camellia oil (50-75 μg/mL) not only increased the levels of heme oxygenase-1 (HO-1), glutathione peroxidase (GPx), and superoxide dismutase (SOD) mRNA expression but also increased vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) protein secretion, which served as a mucosal barrier against gastrointestinal oxidative injury. Moreover, Sprague-Dawley (SD) rats treated with camellia oil (2 mL/kg/day) prior to the administration of ketoprofen (50 mg/kg/day) successfully inhibited COX-2 protein expression, inhibited the production of interleukin-6 (IL-6) and nitrite oxide (NO), reversed the impairment of the antioxidant system, and decreased oxidative damage in the gastrointestinal mucosa. More importantly, pretreatment of SD rats with camellia oil strongly inhibited gastrointestinal mucosal injury induced by ketoprofen, which was proved by the histopathological staining of gastrointestinal tissues. Our data suggest that camellia oil exerts potent antiulcer effects against oxidative damage in the stomach and intestine induced by ketoprofen.

Beneficial Effects of Camellia Oil (<i>Camellia oleifera</i> Abel.) on Hepatoprotective and Gastroprotective Activities

“…The increased level of VEGF and PGs is an important mechanism for mucosal healing and regeneration. Furthermore, administration of camellia oil (1-4 mL/kg body weight) also dose-dependently reversed the impairment of the antioxidant system of GPx, GR, GST, catalase and SOD in intestinal mucosa after treatment with ketoprofen in vivo (17). Therefore, camellia oil potentially suppressed ketoprofen-caused oxidative injury by means of the upregulation of vital antioxidant enzymes, especially HO-1.…”

“…Camellia oil is reported to be rich in oleic acid and similar to olive oil, and it protects against NSAIDs-induced damage of the gastrointestinal mucosa (17). Moreover, the mRNA levels of GPx, SOD, and HO-1 expression were markedly increased by camellia oil in human intestinal epithelial Int-407 cells.…”

“…, which exhibit powerful antioxidant activity as determined by 1,1-diphenyl-2-picrylhydrazyl (DPPH), trolox equivalent antioxidant capacity (TEAC) and oxygen radical absorbance capacity (ORAC), respectively (5,17). In an in vivo study, treatment with camel-S101 lia oil (150 g/kg diet) suppressed CCl4-induced acute hepatotoxicity in rats through its protective action (16).…”

“…Moreover, the mRNA levels of GPx, SOD, and HO-1 expression were markedly increased by camellia oil in human intestinal epithelial Int-407 cells. Camellia oil also promoted secretions of vascular endothelial growth factor (VEGF) and prostaglandin E2 (PGE2) levels to enhance Int-407 cell migration and served as barrier to exhibit an inhibitory effect of gastrointestinal mucosal oxidative injury and a promotion of mucosal repair in vitro (17), which is in agreement with the previous studies (24)(25)(26). Since VEGF and prostaglandins (PGs) have been reported to be critical cytokines for gland reconstruction or tissue regeneration in ulcer areas (24,25), an upregulation of PGE2 effectively prevents indomethacin-and ethanolinduced gastrointestinal damage (26).…”

“…Administration of lansoprazole prevents gastric mucosal injury by indomethacin, piroxicam or ketoprofen by reducing cyclooxygenase-2 (COX-2) mRNA expression in SD rats (29). Cheng et al (17) further observed that administration of camellia oil reduced COX-2 mRNA expression and NO production in ketoprofen-induced SD rats. Morikawa et al (30) indicated that treatment with the saponin fraction from the seeds of Camellia sinensis and its principal constituents, theasaponins, was found to show a potent protective effect on ethanol-or indomethacin-induced damage to the gastric mucosa of SD rats.…”