Gastroprotective and anti-inflammatory effects of Prunus cerasus phytochemicals and their possible mechanisms of action

Prunus cerasus (P. cerasus) is an alternative-medicine used traditionally for amelioration of chronic-ailments marked by elevation in oxidative-stress like neuropathy. The oxidative-stress control was reported to ameliorate the inflammatory-process. This study aimed to phytochemically-investigate P. cerasus most-active phytochemicals utilizing in-vivo biological models to explore their gastroprotective, anti-inflammatory, and antinociceptive potentials and their possible mechanisms of action. Sonication with EtAc was used to extract P. cerasus fruit (Scf), and seed (Scs). The phytochemical-investigation of Scf was performed by RP-HPLC, while that of Scs was explored utilizing GC-FID. A bio-guided-fraction and isolation method was done utilizing column-chromatography, and have shown that cyanidin-3-glucoside (Cy3G) was the most-active constituent in Scf, while linoleic-acid (LA) was the most-active constituent in Scs. Scf, Scs, Cy3G, and LA significantly (p ˂ 0.05) protected the gastric-mucosa against HCl/EtOH-induced gastric-lesions. Scs (200 mg/kg) has shown the most gastroprotective-potentials, and had comparable-results to ranitidine (50 mg/kg). Scf, Scs, Cy3G, and LA have shown significant anti-inflammatory and antinociceptive potentials against carrageenan induced-edema and nociceptive-pain, respectively, where Scs (200 mg/kg) has shown the most anti-inflammatory and antinociceptive potentials, and had comparable results to ibuprofen (100 mg/kg). Scf, Scs, Cy3G, and LA have counter-acted carrageenan-induced oxidative-stress markers, with increased serum-catalase and reduced-glutathione levels, and decreased lipid-peroxidation. Histopathological-studies demonstrated gastroprotective potentials, regeneration and improvement of the spleen-structural architecture when treated with highest doses of Scs and Scf. The reduction of the pro-inflammatory TNF-alpha and IL-6, and elevation the anti-inflammatory factor IL-10 levels, spleen regenerative-capacity and oxidative-stress amelioration might be the main-mechanism responsible for P. cerasus anti-inflammatory potentials. P. cerasus appears to aid in ameliorating the inflammatory process, and reducing pain-thresholds while preserving the stomach.

Keywords: Anti-inflammatory; Antinociceptive effects; Cy3G, Cyanidin 3-glucoside; EtAc, Ethyl acetate; EtOH, ethanol; FID, flame-ionization detector; GSH, reduced glutathione; Gastroprotective; H and E staining, Hematoxylin and Eosin staining; HAc, acetic acid; IL-10, Interleukin 10; IL-6, Interleukin 6; Ib, Ibuprofen; LA, Linoleic acid; LPO, lipid peroxidation; MeOH, methanol; NSAIDs, Non-steroidal anti-inflammatory drugs; Oxidative stress; P. cerasus, Prunus cerasus; PWT, paw withdrawal threshold; Prunus cerasus; Scf, sour cherry fruit ethyl acetate extract; Scs, sour cherry seed ethyl acetate extract; TBARS, Thiobarbituric acid reactive substances; TNF-alpha, Tumor necrosis factor alpha; VEH, vehicle control; e, edema; er, erosions; h, hemorrhage; ic, infiltration of inflammatory cell in the sub-mucosa; mu, mucosa; sm, sub-mucosa.