Antiulcer Effect of Bark Extract of Tabebuia avellanedae: Activation of Cell Proliferation in Gastric Mucosa During the Healing Process

Tabebuia avellanedae (syn. Handroanthus impetiginosus) is popularly known as ‘ipê‐roxo’ and has been used in folk medicine as anti‐inflammatory and in the treatment of ulcers, bacterial and fungal infections. This study evaluated the gastric ulcer healing property of the ethanolic extract (EET) of barks from Tabebuia avellanedae and investigated the mechanisms that may underlie this effect. Rats were treated with EET (twice a day for 7 days) after induction of chronic gastric ulcers by 80% acetic acid. Following treatment, histological and immunohistochemical analysis were performed in gastric ulcer tissues. Oral administration of EET (100 and 300 mg/kg) significantly reduced the gastric lesion induced by acetic acid in 44 and 36%, respectively. Histopathological evaluation demonstrated a contraction of gastric ulcer size, increase of mucus layer (periodic acid‐Schiff stained mucin‐like glycoproteins) and cell proliferation (proliferating cell nuclear antigen immunohistochemistry) in animals treated with EET (100 and 300 mg/kg). The results demonstrate that EET significantly accelerates healing of acetic acid induced gastric ulcer in rats through increase of mucus content and cell proliferation, indicating a potential usefulness for treatment of peptic ulcer diseases. Copyright © 2012 John Wiley & Sons, Ltd.     

Cytoprotective and Anti‐secretory Effects of Azadiradione Isolated from the Seeds of Azadirachta indica (neem) on Gastric Ulcers in Rat Models

Azadirachta indica is well known medicinal plant mentioned in ancient herbal texts. It has been extensively used in Ayurvedic, Unani and Homoeopathic medicine and has become a luminary of modern medicine. As part of our drug discovery program we isolated azadiradione from the ethanolic extract of seeds of A. indica and evaluated for in‐vivo antiulcer activity in cold restraint induced gastric ulcer model, aspirin induced gastric ulcer model, alcohol induced gastric ulcers model and pyloric ligation induced ulcer model. Azadiradione exhibited potent antiulcer activity through the inhibition of H+ K+‐ATPase (proton pump) activity via its cytoprotective effect and also via its antisecretory effect. This combined effect has valuable potential in the future treatment of peptic ulceration. Copyright © 2015 John Wiley & Sons, Ltd.     

The protective effect and action mechanism of Vaccinium myrtillus L. on gastric ulcer in mice

Vaccinium myrtillus L. anthocyanoside (VMA) is used as a folk medicine to treat diseases related to gastric ulcers in northern Europe. However, the effects of VMA and its detailed mechanism on gastric ulcer have not been investigated sufficiently. Therefore, the aim of the present study was to investigate the protective effects of VMA on gastric mucosal damage in a murine gastric ulcer model. First the effects of VMA on ethanol‐induced gastric ulcers in mice were investigated. Then, the levels of lipid peroxide in murine stomach homogenates were measured to investigate the antioxidative effects of VMA. In addition, the free radical scavenging activity of VMA and its main anthocyanidins were evaluated by electron spin resonance measurement. Oral administration of VMA (10, 30 and 100 mg/kg) significantly protected gastric mucosa against HCl/ethanol‐induced gastric ulcers. Furthermore, VMA inhibited lipid peroxide levels in a concentration‐dependent manner and showed high scavenging activity against the superoxide anion radical (·O₂^‐) and the hydroxyl radical (·OH). Anthocyanidins also showed scavenging activity against the ·O₂^‐, while only delphinidin showed high scavenging activity against the ·OH. These findings indicate that the protective effects of VMA on HCl/ethanol‐induced gastric mucosal injury may be partially due to the antiperoxidative effects of anthocyanidins. Copyright © 2011 John Wiley & Sons, Ltd.     

dl-四氢巴马汀抗大鼠胃溃疡作用

 目的研究dl-四氢巴马汀(dl-THP)对大鼠急、慢性溃疡的保护作用,并初步分析其机制。方法胃黏膜损伤由吲哚美辛、束缚应激、结扎幽门和胃浆膜下注入醋酸引起。dl-THP15,30,45mg·kg^-1灌胃,1日2次,共5次。测定大鼠胃溃疡数目、面积、胃酸分泌、胃蛋白酶活性以及胃黏膜血流。结果dl-THP15,30,45mg·kg^-1能抑制大鼠胃黏膜损伤,且呈剂量依赖性;dl-THP30mg·kg^-1对大鼠慢性胃溃疡的抑制率为75.8%,与雷尼替丁30mg·kg^-1的67.7%相仿。dl-THP可增加胃黏膜血流,但对胃酸和胃蛋白酶分泌无影响。结论dl-THP具有明显抗实验性胃溃疡作用,可能与其增加胃黏膜血流有关,亦可能部分通过阻滞胃黏膜DA受体而发挥作用。     

Protective effects of astaxanthin from Paracoccus carotinifaciens on murine gastric ulcer models

The purpose of this study was to investigate the effect of astaxanthin extracted from Paracoccus carotinifaciens on gastric mucosal damage in murine gastric ulcer models. Mice were pretreated with astaxanthin for 1 h before ulcer induction. Gastric ulcers were induced in mice by oral administration of hydrochloride (HCl)/ethanol or acidified aspirin. The effect of astaxanthin on lipid peroxidation in murine stomach homogenates was also evaluated by measuring the level of thiobarbituric acid reactive substance (TBARS). The free radical scavenging activities of astaxanthin were also measured by electron spin resonance (ESR) measurements. Astaxanthin significantly decreased the extent of HCl/ethanol‐ and acidified aspirin‐induced gastric ulcers. Astaxanthin also decreased the level of TBARS. The ESR measurement showed that astaxanthin had radical scavenging activities against the 1,1‐diphenyl‐2‐picrylhydrazyl radical and the superoxide anion radical. These results suggest that astaxanthin has antioxidant properties and exerts a protective effect against ulcer formation in murine models. Copyright © 2011 John Wiley & Sons, Ltd.     

Cytoprotective effects of Bergenia ciliata Sternb, extract on gastric ulcer in rats

Bergenia ciliata is used for the treatment of stomach disorders in the folk medicine of some areas of South East Asia. This study was designed to evaluate its gastroprotective effects on ethanol/HCl, indomethacin and pylorus ligation-induced gastric ulcers in rats. Doses of 15, 30 and 60 mg/kg b/w of the aqueous and methanol extracts of the rhizome were administered 1 h after ulcerogenic treatment. The animals were killed 3 h later, their stomachs removed and the mean area of ulcer lesion was determined. The weight of mucus and gastric acidity were also measured. The aqueous extract decreased the ulcer lesion (p < 0.05) in all models to a greater extent than the methanol extract, but at the higher doses the effect was reduced. In addition, the antiulcer activity appears to be mediated via cytoprotective effects conferred by enhancement of the mucosal barrier, rather than by prevention of gastric acid secretion or the lowering of pH and acidity.     

乙酰谷氨酰胺锌抗实验性胃溃疡的作用研究

 目的 研究新化合物乙酰谷氨酰胺锌(Zn-GL)对大鼠实验性胃溃疡的防治作用及机制。方法 分别采用大鼠水浸应激性胃溃疡,无水乙醇、吲哚美辛和慢性醋酸诱导的胃溃疡为实验模型。以胃黏膜损伤程度,溃疡指数及胃壁结合黏液含量为观察指标。结果 100或150 mg·kg^-1 Zn-GL灌胃给药对4种大鼠急慢性胃黏膜损伤均有明显的预防或治疗作用,胃溃疡指数显著降低,胃液分析显示该化合物能显著升高胃壁结合黏液含量,光镜下观察未见胃黏膜组织炎性细胞浸润。结论 该化合物具有较强的抗溃疡作用,这一作用依赖于内源性的PGE₂,并与加强胃黏液屏障防御功能,促进溃疡愈合有关。     

蒙药验方溃疡散对实验性大鼠胃溃疡的作用

目的:观察蒙药验方溃疡散对大鼠应激性胃溃疡、乙醇导致的胃溃疡及幽门结扎术的胃溃疡等实验性胃溃疡的影响。方法:将150只健康Wistar大鼠分为3个实验组,每个实验组分别分为模型组、溃疡散高、中、低3个剂量组(2.26,1.13,0.56 g.kg-1)和雷尼替丁组(0.15 g.kg-1)或胶体果胶铋组(0.25 g.kg-1)等5个组,每组10只。各给药组每天灌胃1次,连续灌胃7 d,末次给药后各组动物以相应方法致溃疡模型。各组大鼠处死后通过肉眼观察溃疡点状;采用图像分析软件ipWin计算溃疡面积;测定胃液中总酸度和胃蛋白酶活性,观察溃疡散对各型溃疡的影响。结果:溃疡散对应激性胃溃疡面积具有明显的抑制作用(P<0.05或P<0.01);溃疡散对乙醇导致的胃溃疡溃疡点数和溃疡面积均有明显的抑制作用(P<0.05或P<0.01);溃疡散对幽门结扎致胃溃疡大鼠胃液中胃酸总浓度和胃蛋白酶的活性具有一定的抑制作用(P<0.05)。结论:溃疡散对大鼠实验性胃溃疡具有预防作用和胃黏膜保护作用。     

Antiulcer Activity in Rats by Flavonoids of Erica andevalensis Cabezudo-Rivera

Oral treatment with the ether fraction of the flavonoid extract of Erica andevalensis (62.5, 125 and 250 mg/kg) was found to be effective in the prevention of gastric ulceration induced by cold-restraint stress in rats. Statistically significant ulcer index values with respect to the control group were observed. Mucus content was not increased although it was accompanied by an increase in proteins and hexosamines. In pyloric-ligated animals flavonoids showed a significant reduction in the severity of the ulcers, however, it did not significantly alter the gastric secretion volume or acidity compared with the control. Gastric ulcers induced by oral administration of absolute ethanol were reduced by pretreatment with the highest dose of the ether fraction of the flavonoid extract (250 mg/kg), however it did not induce significant changes in the amount and glycoprotein content of gastric mucus.     

Effect of garlic oil on ethanol induced gastric ulcers in rats

Garlic oil was evaluated for gastroprotective activity against ethanol induced ulcers. Reactive oxygen species are involved in the pathogenesis of these ulcers. The possible involvement of garlic oil in restraining the oxidation process produced in gastric tissue was also investigated. The ulcer index, lipid peroxidation and antioxidant enzyme activity (GPx, catalase, SOD) were determined. Pretreatment with garlic oil in doses of 0.25 and 0.5 mg/kg, 30 min before administration of ethanol (1 mL of 100%) caused a decrease in ulcer index and lipid peroxidation and ameliorated the decrease in antioxidant enzyme levels caused by ethanol. The result suggests that garlic oil possesses antioxidant properties and provides protection against ethanol induced gastric injury.     

平溃散对急性胃溃疡及胃黏膜损伤的保护作用

目的:研究平溃散(绞股蓝,沙棘等)对抗急性溃疡的作用.方法:采用组织胺和消炎痛法建立大鼠实验模型,测量溃疡面积和胃黏液的量.结果:平溃散对组胺引起的急性溃疡有一定的抑制作用,对消炎痛引起的胃黏膜分泌的减少有一定的抑制作用.结论:平溃散具有抗溃疡、保护胃黏膜的作用.     

Effects of TDEYA from Atractylodes rhizome on experimental gastric ulcer

The administration of (6E, 12E)-tetradecadiene-8, 10-diyne-1, 3-diol diacetate (TDEYA), isolated from Atractylodes rhizome, promoted the transit of charcoal in the small intestine of mice at a dose of 250 mg/kg. TDEYA prevented lesion formation induced by HCl-ethanol or ethanol in a dose-dependent manner. This action was still evident following intraperitoneal administration and previous treatment with indomethacin. The protective effect of TDEYA against gastric lesion caused by necrotizing agents would thus appear not to be mediated by endogenous prostaglandins. TDEYA did not inhibit gastric ulcers induced by pyloric ligation nor did it reduce gastric juice output or pepsin activity. TDEYA significantly increased hexosamine content in gastric juice and the mucosa. The effect of TDEYA on HCl-ethanol or ethanol-induced gastric lesions may thus be exerted through its protective action on the stomach by secreting mucus and by not reducing gastric juice secretion or pepsin activity.     

愈疡散的药效学研究

目的:研究愈疡散(獐芽菜、象皮、白及等)抗实验性胃溃疡的作用.方法:采用乙酸烧灼型溃疡模型、应激性溃疡模型、乙醇致胃粘膜损伤模型、幽门结扎型胃溃疡模型观察愈疡散对各型溃疡及胃液量、胃液酸度、胃蛋白酶活性的影响.结果:与空白组相比,愈疡散可抑制溃疡的形成,降低大鼠胃溃疡指数,促进溃疡的愈合,抑制胃液分泌,降低胃液酸度,有降低胃蛋白酶活性的趋势.结论:实验结果与该药临床用于治疗胃溃疡的功效相吻合.     

胃溃宁抗胃溃疡的研究

目的:研究胃溃宁的抗胃溃疡及抑酸作用。方法:分别采用皮下注射利血平法、shay氏结扎幽门法、乙酸烧灼法等建立大鼠胃溃疡模型,随机分组,模型对照组灌胃给予0.5%羧甲基纤维素钠10ml/kg、药物治疗组分别灌胃给予雷尼替丁50mg/kg、胃康胶囊1.8g/kg和不同剂量的胃溃宁(4.0g/kg,2.0g/kg,1.0g/kg),观察胃溃宁对大鼠胃溃疡面积、胃液分泌量、胃液总酸度及胃蛋白酶活性的影响。结果:胃溃宁4.0g/kg,2.0g/kg,1.0g/kg能明显抑制各型胃溃疡的形成,并有效减小胃溃疡面积,与模型对照组比较,有显著性差异(P<0.01或P<0.05);胃溃宁4.0g/kg,2.0g/kg对于幽门结扎型溃疡,能有效减少胃液分泌量,降低胃液分泌总酸度,抑制胃蛋白酶活性,与模型对照组比较,有明显差异(P<0.01或P<0.05)。结论:胃溃宁对大鼠胃溃疡模型有明显的抗胃溃疡作用。     

Gastroprotective effect of essential oil from Croton cajucara Benth. (Euphorbiaceae)

The gastroprotective activity of the essential oil from the bark of Croton cajucara Benth (Euphorbiaceae) was assessed in three different models of experimentally induced gastric ulcer in mice. At oral dose of 100 mg/kg the essential oil reduced gastric lesions induced by hypothermic restraint stress and HCl/ethanol significantly. In the HCl/ethanol model a dose-dependent gastroprotective effect was found. Moreover, significant changes in gastric parameters such as pH, secretion rate and total gastric acid were found after intraduodenal administration of essential oil under ligated pylorus (Shay) conditions. The acute toxicity of essential oil was assessed in mice. The LD50 values were 9.3 and 680 mg/kg for oral and intraperitoneal administrations, respectively. The cytotoxicity of essential oil was studied also. A dose-dependent cell viability inhibition was found in V79 fibroblast cell cultures with an IC50 of 22.9 microg/ml. Our results support the pharmacological study of this essential oil.     

一贯煎对四种实验性胃溃疡的防治作用

以一贯煎煎剂10g/kg的剂量给动物灌胃,对四种实验性胃溃疡(慢性醋酸型、消炎痛型、利血平型和幽门结扎型)有明显的保护作用。研究表明一贯煎在不影响胃液分泌的情况下,可能通过多种机制发挥抗溃疡的作用。     

胃疡宁丸抗实验性胃溃疡的药效及机制研究

目的:研究胃疡宁丸抗实验性胃溃疡的药效及其机制.方法:采用大鼠醋酸注射法、水浸应激性、阿司匹林诱发及幽门结扎性胃溃疡模型,观察胃疡宁丸抗胃溃疡的作用并考察其对血清NO,EGF含量,胃黏膜血流量,PGE2含量,及对胃液分泌、胃酸含量、胃蛋白酶活性的影响.结果:胃疡宁丸能够降低各种胃溃疡模型的溃疡指数,升高NO,EGF含量,PGE2含量及胃黏膜血流量,抑制胃液分泌和胃酸含量及降低胃蛋白酶活性.结论:胃疡宁丸具有明显的抗实验性胃溃疡的作用,该作用与其减少胃黏膜损伤因子(胃酸、胃蛋白酶),增加胃黏膜屏障的功能,增强胃黏膜修复作用(NO,EGF,PGE2,胃黏膜血流量)有关.     

Evaluation of the antipeptic ulcer activity of the leaf extract of Plantago lanceolata L. in rodents

The effect of the leaf extract of Plantago lanceolata L. (Plantaginaceae) on gastric secretion and cytoprotection was evaluated using different models of gastroduodenal ulcer, including acetic acid induced chronic gastric ulcer, indomethacin induced gastric ulcer, cysteamine induced duodenal ulcer and pylorus ligation induced gastric ulcer. The aqueous extract was administered at 200 mg/kg and 400 mg/kg and 140 mg/kg and 280 mg/kg for mice and rats, respectively, and compared with vehicle or the standard, ranitidine (50 or 70 mg/kg) or misopristol (280 μg/kg). In addition, activity of the mucilage (172 mg/kg) was also evaluated in acetic acid induced chronic gastric ulcer. Administration was done orally except in pylorus ligation, where the intraduodenal route was used. In all cases, higher doses of the extract provided better protection than lower doses and the mucilage, hinting at a dose‐dependent effect. Whilst higher doses of the extract showed a better healing of the ulcer as well as protection in indomethacin and pylorus ligation models, activities of lesser magnitude than ranitidine were noted in the cysteamine model. Together these findings indicate that higher doses used in the present study provided an overall better protection against gastroduodenal ulcers than the standard drugs employed through antisecretory and cytoprotective mechanisms. Copyright © 2011 John Wiley & Sons, Ltd.     

附子的温中止痛药理研究

本文观察附子水煎剂能显著对抗小鼠水浸应激型和大鼠盐酸损伤性溃疡。附子煎剂能显著对抗蓖麻油和番泻叶引起的小鼠药物性腹泻。在热板法和乙酸扭歪试验中它有明显镇痛效应。认为这是附子温中止痛的药理学基础。     

Analysis of propolis from Baccharis dracunculifolia DC. (Compositae) and its effects on mouse fibroblasts

This paper confirms Baccharis dracunculifolia DC. (Compositae) as the main botanical source of the propolis from southeastern Brazil (state of São Paulo) investigated to ascertain specific biological activity in relation to mouse NIH-3T3 fibroblasts, skin cells directly involved in the cicatrization processes. Flavonoid and total phenolic compounds were determined by spectrophotometry, and chemical composition by HPLC; the chromatographic profile, characterized largely by flavonoids and aromatic acids, was found to be qualitatively similar to that of Baccharis dracunculifolia DC. The adsorption of phenolic compounds in the propolis to skin powder was also investigated, and 68% of these compounds adsorbed to the skin powder. At concentrations from 0.12 to 7.81 μg/ml, the propolis revealed no statistical significant differences from its control solutions; however, at concentrations of 31.25 μg/ml or more, the propolis was toxic to NIH-3T3 cells. Thus, the propolis from Baccharis dracunculifolia DC. (Compositae) presents an in vitro concentration-dependent toxicity on mouse NIH-3T3 fibroblasts.