The protective effects of rutaecarpine on gastric mucosa injury in rats

Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects gastric mucosa against injury induced by acetylsalicylic acid (ASA) and that rutaecarpine activates vanilloid receptors to evoke CGRP release. In the present study, we examined the protective effects of rutaecarpine on gastric mucosa injury, and explored whether the protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors in rats. In an ASA-induced ulceration model, gastric mucosal ulcer index, pH value of gastric juice and plasma concentrations of CGRP were determined. ASA significantly increased the gastric mucosal ulcer index and the back-diffusion of H+ through the mucosa. Rutaecarpine at the doses of 100 or 300 microg/kg (i.v.), and 300 or 600 microg/kg (intragastric, i.g.) reduced the ulcer index and back-diffusion of H+, which was abolished by pretreatment with capsaicin (50 mg/kg, s.c.) or capsazepine (3 mg/kg, i.v.), a competitive vanilloid receptor antagonist. Rutaecarpine significantly increased the plasma concentration of CGRP, which was also abolished by capsazepine. In a stress-induced ulceration model, rutaecarpine reduced gastric mucosal damages, which was abolished by capsazepine (5 mg/kg, i.p.). These results suggest that rutaecarpine protects the gastric mucosa against injury induced by ASA and stress, and that the gastroprotective effect of rutaecarpine is related to a stimulation of endogenous CGRP release via activation of the vanilloid receptor.     

Protective effects of rutaecarpine in cardiac anaphylactic injury is mediated by CGRP

Previous investigations have indicated that rutaecarpine activates the vanilloid receptor to evoke calcitonin gene-related peptide (CGRP) release. CGRP has been shown to alleviate cardiac anaphylactic injury. In the present study, the effect of rutaecarpine on cardiac anaphylaxis was examined. Challenge of presensitized guinea-pig hearts with a specific antigen caused marked decreases in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/- dp/dt(max)), an increase in heart rate, and prolongation of the P-R interval. Rutaecarpine (0.3 or 1 microM) markedly increased the content of calcitonin gene-related peptide (CGRP) in the coronary effluent and decreased the content of tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues concomitantly with a significant improvement of cardiac function and alleviation of the extension of the P-R interval. Rutaecarpine at the concentration of 1 microM also inhibited the sinus tachycardia. The protective effects of rutaecarpine on cardiac anaphylaxis were abolished by CGRP (8-37), a selective CGRP receptor antagonist. These results suggest that the protective effects of rutaecarpine on cardiac anaphylactic injury are related to inhibition of TNF-alpha production by stimulation of CGRP release.     

The cardioprotection of rutaecarpine is mediated by endogenous calcitonin related-gene peptide through activation of vanilloid receptors in guinea-pig hearts

Previous investigations have shown that calcitonin gene-related peptide (CGRP) protects against myocardial ischemia-reperfusion injury and that rutaecarpine activates vanilloid receptors to evoke CGRP release. In the present study, we examined whether rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts, and whether the protective effects of rutaecarpine are related to stimulation of endogenous CGRP release via activating vanilloid receptors. The isolated guinea-pig heart was arrested using St. Thomas Hospital solution, and then reperfused with normothermic Krebs-Henseleit solution for 30 min after a 4-h hypothermic ischemic period. Hypothermic ischemia caused a decline in cardiac function (left ventricular pressure, +/-dp/dt(max), heart rate and coronary flow) and an increased release of creatine kinase during reperfusion. Rutaecarpine at the concentration of 1.0 microM significantly improved the recovery of cardiac function and reduced the release of creatine kinase during reperfusion after hypothermic ischemia. Rutaecarpine at the concentration of 3.0 microM significantly reduced the release of creatine kinase and increased the coronary flow, but only caused a slight improvement of left ventricular pressure, +/-dp/dt(max), heart rate during reperfusion. The cardioprotective effects of rutaecarpine were abolished by capsazepine, a competitive vanilloid receptor antagonist, or by CGRP (8-37), a selective CGRP receptor antagonist. Rutaecarpine at the concentration of 1.0 or 3.0 microM significantly increased the release of CGRP, which was also abolished by capsazepine. These results suggest that rutaecarpine enhances preservation with cardioplegia in guinea-pig hearts and that the protective effects of rutaecarpine are due to stimulation of endogenous CGRP release via activating vanilloid receptors.     

The depressor and vasodilator effects of rutaecarpine are mediated by calcitonin gene-related peptide

Previous studies have shown that rutaecarpine has depressor and vasodilator effects, and activates vanilloid receptors to evoke calcitonin gene-related peptide (CGRP) release. In the present study, we examined whether the depressor and vasodilator effects of rutaecarpine are related to the stimulation of endogenous CGRP release via activation of vanilloid receptors in rats. Rutaecarpine (30, 100, or 300 microg/kg, i. v.) caused a depressor effect concomitantly with an increase in the plasma concentrations of CGRP in a dose-dependent manner, and the effects of rutaecarpine were abolished by pretreatment with capsaicin (50 mg/kg, s. c.) which depletes neurotransmitters in sensory nerves. In aortic and superior mesenteric arterial rings, rutaecarpine (10 (-7)-10(-5) M) or capsaicin (3 x 10(-9)-3 x 10(-6) M) caused a concentration-dependent vasodilator response, which was significantly attenuated by capsazepine (10(-5) M), a competitive vanilloid receptor antagonist, or by CGRP-(8-37) (10(-6) M), a selective CGRP receptor antagonist. After pretreatment with capsaicin (10(-5) M) for 20 min, vasodilator responses to rutaecarpine were also markedly attenuated. Similarly, pretreatment with rutaecarpine (10(-5) M) for 20 min also attenuated vasodilator responses to capsaicin. These results suggest that the depressor and vasodilator effects of rutaecarpine are related to stimulation of endogenous CGRP release via activation of vanilloid receptors in rats.     

Solid dispersion of rutaecarpine improved its antihypertensive effect in spontaneously hypertensive rats

It was reported previously that rutaecarpine produced a hypotensive effect in phenol‐induced and 2‐kidney, 1‐clip hypertensive rats. However, the same dose of crude rutaecarpine did not produce significant hypotensive effects when applied to spontaneously hypertensive rats (SHR). In the present study, a different dose of rutaecarpine solid dispersion was administered intragastrically to SHR. The systolic blood pressure was monitored by the tail‐cuff method with an electro‐sphygmomanometer. The plasma concentration of rutaecarpine, calcitonin gene‐related peptide (CGRP) and the mRNA levels of CGRP in dorsal root ganglion were determined. The results showed that administration of the solid dispersion significantly increased the blood concentration of rutaecarpine, accompanied by significant hypotensive effects in SHR in a dose‐dependent manner. The levels of plasma CGRP were also elevated significantly, concomitantly with the increased mRNA levels in the dorsal root ganglion in a dose‐dependent manner. It was concluded that a change of the dosage from the crude drug to solid dispersion could improve significantly the efficiency of rutaecarpine absorption and increase its plasma concentration. The anti‐hypertensive effect exerted by rutaecarpine solid dispersion in SHR is mediated by CGRP. Copyright © 2008 John Wiley & Sons, Ltd.     

Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats

Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O₂, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP_8–37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway.     

CALCITONIN GENE-RELATED PEPTIDE MEDIATES THE CARDIOPROTECTIVE EFFECTS OF RUTAECARPINE AGAINST ISCHAEMIA–REPERFUSION INJURY IN SPONTANEOUSLY HYPERTENSIVE RATS

• 1 It has been shown that calcitonin gene‐related peptide (CGRP) plays an important role in mediating the cardioprotection exerted by rutaecarpine in normal animals. The aim of the present study was to determine whether rutaecarpine is able to decrease the susceptibility of hypertensive animals to ischaemia–reperfusion injury by stimulating CGRP release.
• 2 Spontaneously hypertensive rats (SHR) were pretreated with rutaecarpine (20 or 40 mg/kg per day, i.g.) for 18 days and then the heart and thoracic aorta were isolated for cardiac function and vascular relaxation analysis. Blood samples and coronary effluent were collected to measure CGRP levels and creatine kinase activity, respectively. The effect of 10 or 30 µmol/L rutaecarpine on CGRP release was also examined in isolated aortic rings set up in a homeothermal organ bath.
• 3 Rutaecarpine treatment resulted in a hypotensive effect in SHR concomitant with increases in plasma CGRP levels. In addition, rutaecarpine significantly stimulated the release of CGRP from aortic rings. Twenty minutes ischaemia and 30 min reperfusion resulted in a marked decrease in myocardial function and a significant increase in the release of creatine kinase in normal control (Wistar‐Kyoto) rats, an effect that was exacerbated in SHR. Similarly, the decreased vasodilator response to acetylcholine (3 ? 10^?9 to 10^?6 mol/L) in isolated aortic rings from Wistar‐Kyoto rats was also aggravated in SHR. Both cardiac function and vasodilator responses were significantly improved in SHR after pretreatment with rutaecarpine.
• 4 The results of the present study suggest that the increased cardiac susceptibility to ischaemia–reperfusion injury in SHR is related to decreased plasma CGRP levels and that antihypertensive therapy with rutaecarpine reverses cardiac susceptibility to reperfusion injury by stimulating CGRP release.

     

胡椒碱抗实验性胃溃疡的作用

目的：研究胡椒碱抗大鼠或小鼠实验性胃溃疡的作用。方法：实验性胃溃疡是由应激、吲哚美辛、盐酸和幽门结扎引起,实验前5h ig胡椒碱。结果：胡椒碱25、50、100mg/kg能抑制大鼠或小鼠胃粘膜损伤,对应激性型胃粘膜损伤,抑制率分别为16．9％,36．0％,48．3％;吲哚美辛型胃粘膜损伤为4．4％,51．1％,64．4％;盐酸型胃粘膜损伤为19．2％,41．5％,59．6％;对幽门结扎型胃粘膜损伤为4．8％,11．9％,26．2％;胃液分泌减少;胃酸、胃蛋白酶活性降低。结论：胡椒碱具有抗实验性胃溃疡作用。     

The positive inotropic and chronotropic effects of evodiamine and rutaecarpine, indoloquinazoline alkaloids isolated from the fruits of Evodia rutaecarpa, on the guinea-pig isolated right atria: possible involvement of vanilloid receptors

Cardiotonic effects of evodiamine and rutaecarpine, constituents of the fruits of Evodia rutaecarpa Bentham Rutaceae, were evaluated on guinea pig isolated atria. Comparison with capsaicin, a vanilloid receptor agonist, revealed similar positive inotropic and chronotropic activity, as judged from antagonistic effects of the competitive vanilloid receptor (capsaicin receptor) antagonist capsazepine, the non-competitive vanilloid receptor antagonist ruthenium red, the calcitonin gene related peptide antagonist CGRP(8-37), the P2X purinoceptor antagonist PPADS, and various desensitization studies. Evodiamine and rutaecarpine produced transient positive inotropic and chronotropic effects on the guinea-pig isolated atria, followed by a desensitizing effect to additional administration. Dose-response relationships for evodiamine, rutaecarpine and capsaicin were obtained. All the compounds evoked positive inotropic and chronotropic effects in a concentration-dependent manner. Maximal contractions for evodiamine, rutaecarpine and capsaicin were observed at concentrations of 1 microM, 3 microM and 0.3 microM, respectively. The cardiotonic responses evoked by both evodiamine and rutaecarpine were shifted to the right by capsazepine, an established antagonist of vanilloid receptor (capsaicin-receptor). The effects of both evodiamine (1 microM) and rutaecarpine (3 microM) were abolished by pretreatment with a desensitizing dosage of capsaicin (1 microM), developing cross-tachyphylaxis between these compounds. The effects of evodiamine (1 microM), rutaecarpine (3 microM) and capsaicin (0.3 microM) were also significantly reduced by pretreatment with ruthenium red (10 microM) and CGRP (8-37) (10 microM). The effects of evodiamine, rutaecarpine and capsaicin were not affected by pretreatment with PPADS (100 microM), a highly selective P2X purinoceptor antagonist, and the possibility of the involvement of the P2X purinoceptor was excluded. These results suggest that the positive inotropic and chronotropic effects on the guinea-pig isolated right atria induced by both evodiamine and rutaecarpine could be attributed to their interaction with vanilloid receptors and the resultant release of CGRP, a cardiotonic neurotransmitter, from capsaicin-sensitive nerves as with capsaicin.     

Role of central and peripheral ghrelin in the mechanism of gastric mucosal defence

Ghrelin, identified in the gastric mucosa, has been involved in the control of food intake and growth hormone (GH) release, but whether this hormone influences the gastric secretion and gastric mucosal integrity has been little elucidated. We compared the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of ghrelin on gastric secretion and gastric lesions induced in rats by 75% ethanol or 3.5 h of water immersion and restraint stress (WRS) with or without suppression of nitric oxide (NO)-synthase or functional ablation of afferent sensory nerves by capsaicin. The number and the area of gastric lesions was measured by planimetry, the GBF was assessed by the H₂-gas clearance method and blood was withdrawn for the determination of the plasma ghrelin and gastrin levels. In addition, the gastric mucosal expression of mRNA for CGRP, the most potent neuropeptide released from the sensory afferent nerves, was analyzed in rats exposed to WRS with or without ghrelin pre-treatment. Ghrelin (5–80 μg/kg i.p. or 0.6–5 μg/kg i.c.v.) increased gastric acid secretion and attenuated gastric lesions induced by ethanol and WRS. This protective effect was accompanied by a significant rise in the gastric mucosal blood flow (GBF), luminal NO concentration and plasma ghrelin and gastrin levels. Ghrelin-induced protection was abolished by vagotomy and significantly attenuated by L-NNA and deactivation of afferent nerves with neurotoxic dose of capsaicin. The signal for CGRP mRNA was significantly increased in gastric mucosa exposed to WRS as compared to that in the intact gastric mucosa and this was further enhanced in animals treated with ghrelin. We conclude that central and peripheral ghrelin exerts a potent protective action on the stomach of rats exposed to ethanol or WRS, and these effects depend upon vagal activity and hyperemia mediated by the NOS-NO system and CGRP released from sensory afferent nerves.     

颈交感神经干离断减轻鼠急性胃黏膜损伤

目的 探讨颈交感神经干离断(TCST)对大鼠急性胃黏膜损伤的保护作用.方法 30只雄性SD大鼠,随机分为假手术(A)组、假手术后浸水(B)组和TCST后浸水(C)组,每组10只.B、c组大鼠垂卣浸水至剑突水平6h,测各组大鼠胃黏膜血流量(GMBF),评定黏膜溃疡指数(UI).采用放免法检测胃黏膜组织降钙素基因相关肽(CGRP)含量,硝酸还原酶法测定胃黏膜组织中一氧化氮合酶(NOS)含量.结果 B、C组胃黏膜见出血性溃疡,B组损伤较重.B组GMBF、CGRP降低及UI、NOS明显高于C组(P<0.05或P<0.01).结论 TCST对大鼠急性胃黏膜损伤有保护作用,其机制可能与调节胃黏膜组织CGRP及NOS含量有关.     

Sulphasalazine and experimental stress ulcers

The effects of sulphasalazine on gastric ulceration induced by restraint at 4 degrees C (stress) for 2 h were studied in rats. Doses of 63 or 125 mg/kg s.c., which had no effect on stomach wall prostaglandin E2 (PGE2) levels, prevented stress ulceration but not the lesions produced by indomethacin. Stress significantly increased gastric glandular mucosal PGE2 levels. Indomethacin pretreatment (20 mg/kg, p.o.) markedly reduced PGE2 levels in the same region of the stomachs, and worsened stress-induced lesion formation. Pretreatment with sulphasalazine of animals given indomethacin and then subjected to stress did not appear to affect the indomethacin component of indomethacin-stress ulceration. Oral administration of PGE2 200 micrograms/kg significantly elevated gastric PGE2 levels, but had no effect on stress ulceration. It appears that neither the antiulcer activity of sulphasalazine nor stress-induced ulceration is associated with gastric tissue PGE2 increase or decrease, respectively. The protective mechanism may result from the ability of sulphasalazine to inhibit lipoxygenase activity.     

Calcitonin gene-related Peptide-mediated depressor effect and inhibiting vascular hypertrophy of rutaecarpine in renovascular hypertensive rats

Calcitonin gene-related peptide (CGRP), the predominant neurotransmitter in capsaicin-sensitive sensory nerves, is a potent vasodilator and inhibits proliferation of vascular smooth muscle cells. Previous investigations have demonstrated that the hypotensive effect of rutaecarpine (Rut) is associated to stimulation of CGRP synthesis and release via activation of the vanilloid receptor subtype 1 (VR1) in the phenol-induced hypertensive rat. This study tested whether the depressor effect and inhibiting vascular hypertrophy of Rut is mediated by endogenous CGRP in 2-kidney, 1-clip (2K1C) hypertensive rats. Systolic blood pressure (SBP) was measured by tail-cuff method in conscious. Mesenteric arteries were isolated for examination of morphological changes. The concentration of CGRP in the plasma and the expression of CGRP mRNA in dorsal root ganglia (DRG) were measured. Chronic administration of Rut (10, 20, or 40 mg/kg/day, respectively) for 4 weeks caused a depressor effect and significantly regressed the lumen diameter and decreased the medium thickness of mesenteric arteries in hypertensive rats concomitantly with an increase in the plasma concentration of CGRP and the expression of CGRP mRNA in DRG. In conclusion, chronic administration of Rut can reduce blood pressure and relieve mesenteric artery hypertrophy in the 2K1C hypertensive rats, and the effects of Rut may be related to stimulation of CGRP synthesis and release.     

Cholinergic-mediated gastric mast cell degranulation with subsequent histamine H1-and H2-receptor activation in stress ulceration in rats.

The effects of atropine, mepyramine, metiamide or NaHCO3 on gastric ulceration, gastric secretion and gastric mast cell degranulation were studied in stressed pylorus-occluded rats. The influence of dexamethasone pretreatment on stress ulcers in animals without pylorus occlusion (intact rats) was also examined. Stress produced a high glandular lesion incidence and ulcer index, and markedly lowered gastric secretion and glandular wall mast cell counts. Injected 0.5 h before stress, atropine, mepyramine or metiamide strongly antagonised ulceration. Atropine or metiamide, but not mepyramine, reduced gastric secretion. Only atropine prevented stress-induced mast cell changes. NaHCO3, given intragastrically before stress, did not prevent ulceration or mast cell degranulation despite complete neutralisation of gastric acid. Dexamethasone-induced gastric mucosal mast cell depletion could reduce stress ulceration. The findings show that stress degranulates stomach mast cells via a cholinergic pathway; released histamine from this source is largely responsbile for gastric ulceration through H1- and H2-receptor effects. Histamine H2-receptor-mediated gastric acid may play only a small contributory role in stress ulcers in rats. The antiulcer mechanisms of histamine H1- and H2-receptor blockade are discussed.     

The influence of chronic or acute nicotine pretreatment on ethanol-induced gastric ulceration in the rat

The effects in rats of chronic or acute nicotine pretreatment were studied on three gastric parameters: ethanol-induced ulceration, gastric wall mucus content and gastric acid secretion, under basal or histamine-stimulated conditions. Oral administration of ethanol (40%, 10 ml kg-1) depleted gastric wall mucus and produced ulceration in the gastric glandular mucosa. Ten-day nicotine pretreatment (15 or 25 micrograms ml-1 drinking water) worsened the adverse effects of ethanol on mucosal ulceration and mucus content, potentiated the gastric secretory action of histamine, but did not affect basal acid secretion. Single oral doses of nicotine (2 or 4 mg kg-1, given 1 h beforehand) prevented ulceration and mucus depletion in ethanol-treated animals; however, they did not influence either basal or histamine-stimulated gastric acid output. It is concluded that chronic nicotine administration aggravates ethanol ulceration, possibly by decreasing gastric wall mucus content and sensitizing the stomach to the acid secretory action of histamine. On the other hand, an acute oral dose of nicotine preserves the mucus content and prevents ethanol-induced ulcer formation.     

栀子总苷对幽门结扎大鼠胃溃疡保护作用的实验研究

目的：研究栀子总苷（TGZ）对幽门结扎模型大鼠胃溃疡的影响,初步探讨其抗溃疡作用的机制。方法：采用大鼠幽门结扎的方法建立大鼠胃溃疡模型,收集胃液测定胃液游离酸和总酸、胃蛋白酶活性以及观察胃黏膜损伤指数。结果：TGZ灌胃70或140mg/kg5d能显著抑制幽门结扎大鼠胃溃疡的发生,抑制胃液量,降低胃液中游离酸度与总酸度,有效降低胃液中胃蛋白酶活性。结论：栀子总苷对幽门结扎所致的大鼠胃溃疡具有明显的保护作用,与其抑制胃酸分泌和胃蛋白酶的活性有关。     

雷尼替丁、兰索拉唑和氢氧化镁铝抗实验性胃溃疡的比较研究

目的 :比较雷尼替丁、兰索拉唑和氢氧化镁铝抗 3种实验性胃溃疡模型的作用。方法 :采用 3种实验性胃溃疡模型 :小鼠水浸应激性胃溃疡、大鼠幽门结扎型胃溃疡、大鼠乙酸烧灼型胃溃疡 ,以溃疡抑制率来比较三药的治疗效果。结果 :3种模型中兰索拉唑有明显的抑制溃疡形成的作用 (P <0 .0 5 ) ,溃疡指数是最低的 ,溃疡抑制率也均高于其他两药。结论 :兰索拉唑对于实验性胃溃疡的作用优于氢氧化镁铝、雷尼替丁     

Zinc deficiency: its role in gastric secretion and stress-induced gastric ulceration in rats

The effects of zinc deficiency on gastric secretion and on cold-restraint stress-induced ulceration in rat stomachs have been studied. Administration of graded zinc deficient diets for 5 weeks significantly depressed the serum zinc concentration and decreased body weight gain in the rats. These diets significantly increased the gastric secretory volume, acid and pepsin. Zinc deficiency produced or aggravated the formation of glandular ulceration in the absence or presence of stress, respectively; it also decreased the mast cell count in the gastric glandular mucosa. It is concluded that zinc deficiency adversely affects the rats by reducing the body weight gain and producing ulceration which is probably mast cell-mediated. On the other hand, it increases gastric secretory functions.     

Anti-Ulcerogenic Evaluation of the Persian Tooth Brush Tree (Salvadora Persica)

The effect of the lyophilized decoction of Salvadora persica on ulceration induced by ethanol, indomethacin and cold restraint stress was investigated in rats. Pre-treatment tests in rats revealed that the extract possessed significant protective action against ulcers induced by ethanol or stress. The protective effect was not altered by indomethacin, administered as a prostaglandin biosynthesis inhibitor. Salvadora persica shows some increase in gastric mucus with a certain diminution in the ulcer index in cold stress-induced ulcers. However, the drug failed to heal ethanol and indomethacin-induced ulcers.     

Beneficial effects of capsiate on ethanol-induced mucosal injury in rats are related to stimulation of calcitonin gene-related Peptide release

Capsiate is a non-pungent analogue of capsaicin from CH-19 Sweet peppers. Capsaicin is reported to trigger calcitonin gene-related peptide (CGRP) release through activation of transient receptor potential vanilloid subfamily member 1 (TRPV1) and produces beneficial effects on gastric mucosa. This study aimed to investigate whether capsiate is able to produce beneficial effects on gastric mucosa and whether the protective effects of capsipate occur through a mechanism involving the activation of TRPV1 and CGRP release. A rat model of gastric mucosal injury was established by the oral administration of acidified ethanol. Gastric tissues were collected for analysis of the gastric ulcer index, cellular apoptosis, activities of caspase-3, catalase and superoxide dismutase (SOD), and levels of CGRP, TNF-α, and malondialdehyde (MDA). Our results show that the acute administration of ethanol significantly increased the gastric ulcer index concomitantly with an increase in cellular apoptosis, caspase-3 activity, and TNF-α and MDA levels, as well as a decrease in the activities of catalase and SOD. Pretreatment with 1 mg/kg capsiate attenuated ethanol-induced gastric mucosal injury and cellular apoptosis accompanied by an increase in CGRP level, catalase, and SOD activities, and a decrease in caspase-3 activity, and TNF-α and MDA levels. The effects of capsiate were inhibited by capsazepine, an antagonist of TRPV1. These results suggest that capsiate is able to produce beneficial effects on ethanol-induced gastric mucosal injury. These effects are related to the stimulation of CGRP release through the activation of TRPV1.