Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation

Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils (Rosaceae), is also known as "GU-GONG-GUO", the root of which has been recognized as common ethnodrug from the Yi nationality for treating inflammatory bowel disease. The aim of the present study was to investigate the preventive and curative effects of extract from the fruits of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils (FOE) in vitro and in vivo as well as elucidate the potential mechanisms of the action involved.Male Wistar rats were applied to ethanol-induced gastric ulcer model. They were divided into six groups: control, model (GU), positive (Magnesium aluminate chewable tablets, 125 mg/kg), FOE low (125 mg/kg), middle (250 mg/kg) and high (500 mg/kg) doses groups. Histopathology observation of gastric tissues was detected by hematoxylin and eosin (H&E) staining. The expression of Nrf2, HO-1, Keap1, NF-κB p65 and IKKα/β in gastric tissues were evaluated by immunohistochemistry (IHC). The levels of cytokines in serum and tissues were measured by Enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, Keap1, NF-κB p65, IKKα/β, PCNA and COX2 proteins were ulteriorly assessed by Western blotting to elucidate the molecular mechanism of FOE's protective effect on gastric ulcer.MTT detection showed that LPS reduced RAW264.7 cell survival, and FOE blocked the inhibition of RAW264.7 cell growth induced by LPS. When RAW264.7 cells were treated with both FOE (100 μg mL-1) and LPS (5 μg mL-1) for 24 h, compared with the model group, the level of NO, TNF-α, IL-6, IL-1β and MDA significantly decreased, and the activity of SOD was significantly reduced. Obvious pathological injuries in the GU model group were observed, which was improved after treatments with FOE. The contents of pro-inflammatory factors in serum and tissues were decreased by 25% whereas prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were increased by 30% in a dose-dependent manner after FOE (500 mg/kg) treatments. In addition to the promotion effects of superoxide dismutase (SOD), FOE (500 mg/kg) also attenuated the levels of nitric oxide (NO) and malondialdehyde (MDA) by 20%. Likewise, the expression of NF-κB p65, IKKα/β and Keap1 were suppressed after treatments with FOE whereas Nrf2 and HO-1 showed the opposite trend, which mechanisms were found to be associated with Nrf2/NF-κB signaling pathways.The study demonstrated that FOE is able to protect against GU via inhibiting NF-κB signaling pathway and activating Nrf2 signaling pathway, which might provide a stronger theoretical basis for the treatment of GU.