allylpyrocatechol and Stomach-Ulcer

The gastro-intestinal disorders, induced by the NSAIDs including indomethacin (IND) remain unresolved medical problems. Herein, we disclose allylpyrocatechol (APC) as a potential agent against IND-gastropathy and rationalize its action mechanistically.. Mice were pre-treated with APC for 1h followed by IND (18mgkg(-1)) administration, and the ulcer-prevention capacity of APC was evaluated on the 3rd day by histology. Its effect on the inflammatory (MPO, cytokines, adhesion molecules), ulcer-healing (COX, prostaglandins, growth factors and their receptors) and signaling parameters (NF-κB and MAPKs) were assessed by immunoblots/mRNA, and ELISA at the time points of their maximal changes due to IND administration.. IND induced oxidative stress, triggering mucosal TNF-α that activated NF-κB and JNK MAPK signaling in mice. These increased the pro-inflammatory biochemical parameters, but reduced the healing factors. APC reversed all the adverse effects to prevent gastric ulceration. APC (5mgkg(-1)), trolox (50mgkg(-1)) and NAC (250mgkg(-1)) showed similar protection that was better than that by misoprostol (5μgkg(-1)) and omeprazole (3mgkg(-1)).. The anti-ulcer effect of APC can be primarily attributed to its antioxidant action that helped in controlling various inflammatory parameters and augmenting angiogenesis.. Given that APC is an effective, non-toxic antioxidant with appreciable natural abundance, further evaluation of its pharmacokinetics and dynamics would help in promoting it as a new anti-inflammatory agent.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Anti-Ulcer Agents; Catechols; Disease Models, Animal; Indomethacin; Male; MAP Kinase Signaling System; Mice; Misoprostol; Omeprazole; Oxidative Stress; Piper betle; Stomach Ulcer; Tumor Necrosis Factor-alpha

The role of the ariginine-metabolism in the healing action of the Piper betle phenol, allylpyrocatechol (APC) and omeprazole against indomethacin-induced stomach ulceration in mouse was investigated. Indomethacin (18 mg/kg) was found to induce maximum stomach ulceration in Swiss albino mice on the 3rd day of its administration, which was associated with reduced arginase activity (21.6%, P<0.05), endothelial nitric oxide synthase (eNOS) expression (72%, P<0.001), and IL-4 and TGF-beta levels, along with increased inducible nitric oxide synthase (iNOS) (9.3 folds, P<0.001) expression, nitrite (2.29 folds, P<0.001), IL-1beta and IL-6 generation. Besides providing comparable healing as omeprazole (3 mg/kg x 3 days), APC (5 mg/kg x 3 days) shifted the iNOS/NO axis to the arginase/polyamine axis as revealed from the increased arginase activity (73.1%, P<0.001), eNOS expression (67.8%, P<0.001), and reduced iNOS expression (65.6%, P<0.001) and nitrite level (53.2%, P<0.001). These can be attributed to a favourable anti-/pro-inflammatory cytokines ratio, generated by APC. The healing by omeprazole was however, not significantly associated with those parameters.

Topics: Animals; Anti-Inflammatory Agents; Arginase; Arginine; Catechols; Cytokines; Gene Expression Regulation, Enzymologic; Male; Mice; Mucous Membrane; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Peroxidase; Stomach Ulcer

Indomethacin caused maximum stomach ulceration in mice on the 3rd day, which was associated with reduction of plasma total antioxidant status (TAS), COX-1, COX-2, mucosal PGE(2), VEGF, and vWF, along with an increase in endostatin levels. Treatment with the phytochemical allylpyrocatechol (5 mg/kg, p.o. for 3 days) provided significant ulcer healing by reversing these biochemical parameters, as well as increasing the EGF expression more than that observed due to ulceration. Omeprazole (3 mg/kg, p.o. for 3 days) provided a similar healing by improving TAS and mucin levels, without significantly altering the other parameters.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Catechols; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone; Disease Models, Animal; Dose-Response Relationship, Drug; Indomethacin; Male; Mice; Omeprazole; Oxidative Stress; Plant Extracts; Stomach Ulcer; Vascular Endothelial Growth Factor A; von Willebrand Factor; Wound Healing

To evaluate the protective activity of allylpyrocatechol (APC), the major antioxidant constituent of Piper betel, against the indomethacin-induced stomach ulceration in the rat model and correlates with its antioxidative and mucin protecting properties.. Male Sprague-Dawley rats were divided into five groups. Normal control rats (group I) were given the vehicle oral dose of gum acacia in distilled water (1 mL per rat); ulcerated control and treated rats (groups II-V) were given a single dose of indomethacin (30 mg/kg body wt.); group II rats were sacrificed 4 h after indomethacin administration; groups III-V rats were given the vehicle (1 mL per rat) or APC (2 mg/kg body wt.) or misoprostol (1.43 mug/kg body wt.) once daily by oral intubation for 7 d starting from 4 h after the indomethacin administration. After 7 d, the stomach tissues were excised for histological examination and biochemical analysis.. Treatment with APC (2 mg/kg body wt per day) and misoprostol (1.43 mug/kg body wt per day) for 7 d could effectively heal the stomach ulceration as revealed from the ulcer index and histopathological studies. Compared to the zero day ulcerated group, treatment with APC and misoprostol reduced the ulcer index by 93.4% and 85.4% respectively (P < 0.05). Both APC and misoprostol accelerated ulcer healing observed in natural recovery (P < 0.05), their respective healing capacities not being significantly different. The healing capacities of APC and misoprostol could be attributed to their antioxidant activity as well as the ability to enhance the mucin content of the gastric tissues. Compared to the ulcerated untreated rats, those treated with APC and misoprostol showed near normal MDA levels, while the protein levels were 86% and 78% of the normal value respectively (P < 0.05). Likewise, both APC and misoprostol increased the SOD, catalase, and mucin levels significantly (P < 0.05), the effect of APC being better.. APC can protect indomethacin-induced gastric ulceration due to its antioxidative and mucin protecting properties.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Catalase; Catechols; Disease Models, Animal; DNA; Gastric Mucins; Gastric Mucosa; Hexosamines; Indomethacin; Lipid Peroxidation; Male; Malondialdehyde; Misoprostol; Piper betle; Plant Extracts; Plant Leaves; Proteins; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Superoxide Dismutase; Time Factors; Wound Healing