Brazilian Medicinal Plant Acts on Prostaglandin Level and Helicobacter pylori

Z.P. Lima,T.R. Calvo,E.F. Silva,C.H. Pellizzon,W. Vilegas,A.R.M.S. Brito,T.M. Bauab,C.A. Hiruma-Lima 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.4

Among the current treatment strategies for the peptic ulcer patient with Helicobacter pylori infection, the method of choice is triple therapy based on the concurrent use of proton inhibitors and two antibiotics. Alchornea triplinervia is a medicinal plant commonly used by people living in the Cerrado region of Brazil to treat gastrointestinal ulcers. In the present work we proposed therapy based on this medicinal plant that presents effective gastroprotective action with antibiotic effects. Oral pretreatment with methanolic extract (ME) of A. triplinervia in rats and mice decreased the gastric injuries induced by ethanol and HCl/ethanol. Increasing the dose reduced the gastroprotective effects of ME on the gastric lesions induced by nonsteroidal anti-inflammatory drug. After pylorus ligature of mice, oral administration of ME induced a decrease not only in total acid but also in the ulcer index. We also observed that ME displayed antibacterial activity against H. pylori. Liquid-liquid separation of ME indicated that active constituents responsible for the gastroprotective action are concentrated in the ethyl acetate fraction (EAF) (50% protection) rather than in the aqueous fraction, which did not induce significant gastroprotection at the same dose (100 mg/kg). EAF induced an increase of gastric mucosa prostaglandin (PG) E2 levels, which remained high even after previous administration of indomethacin. The phytochemical profile of ME revealed that EAF contains mainly flavonoids. In conclusion, all these results suggest that ME did not show acute toxicity, but exhibited an antisecretory property, anti-H. pylori effect, and gastroprotective action. The observed effect did not involve the participation of nitric oxide or endogenous sulfhydryl groups. However, EAF showed a more efficient gastroprotective effect than ME at a lower dose and protected the gastric mucosa by increasing PGE2.

Gastroprotective Effect of Serjania erecta Radlk (Sapindaceae): Involvement of Sensory Neurons, Endogenous Nonprotein Sulfhydryls, and Nitric Oxide

Ana Paula Corrêa Castelo Branco Nappi,Roberta Gomes Coelho,Neli Kika Honda,Catharine Ferrazoli,Arnildo Pott,Clélia Akiko Hiruma-Lima 한국식품영양과학회 2009 Journal of medicinal food Vol.12 No.6

The present study reveals the pharmacological action of Serjania erecta Radlk. (Family Sapindaceae), an important medicinal plant species used in the Brazilian Pantanal against gastric pain. The methanolic (Me) and chloroformic (Se) extracts obtained from leaves of S. erecta were challenged by a very strong necrotizing agent in rodents, absolute ethanol. Se was also confronted with a nitric oxide synthase inhibitor (NG-nitro-l-arginine methyl ester), a capsaicin cation channel transient receptor potential vanilloid type 1 antagonist (ruthenium red), or a sulfhydryl-blocker (N-ethylmaleimide) to evaluate the participation of these cytoprotective factors in gastroprotection. In an in vivo experimental model, Me and Se presented several degrees of gastroprotective action without signs of acute toxicity. The best gastroprotective effect was restricted to all doses of Se. The mechanisms involving the gastroprotective action of Se are related to an augmented defense mechanism of the gastrointestinal mucosa consisting of sensory neurons, nitric oxide, and sulfhydryl groups that prevent and attenuate the ulcer process. The presence of polyisoprenoids in the Se explains the potent gastroprotective action of this medicinal species. Effective gastroprotective action and the absence of acute toxicity indicate this species may be a promising herbal drug against gastric disease.

Healing Actions of Essential Oils from Citrus aurantium and d-Limonene in the Gastric Mucosa: The Roles of VEGF, PCNA, and COX-2 in Cell Proliferation

Thiago Mello Moraes,Ariane Leite Rozza,He´lio Kushima,Claudia Helena Pellizzon,Lucia Regina Machado Rocha,Cle´lia Akiko Hiruma-Lima 한국식품영양과학회 2013 Journal of medicinal food Vol.16 No.12

Previous studies have described the gastroprotective effects of essential oils that are derived from Citrus aurantium (OEC) and its main compound d-limonene (LIM) in a model of chemically induced ulcers in rats. However, these studies do not address the compound’s healing effects on the gastric mucosa. Thus, the aim of this work was to evaluate the healing activity of OEC and LIM in acetic acid-induced gastric ulcers in rats, a model that reproduces human chronic ulcers. The obtained results demonstrated that lower effective doses of OEC (250 mg/kg) and LIM (245 mg/kg) induced gastric mucosal healing with a cure rate of 44% and 56%, respectively, compared with the control group (P < .05). During the 14 days of OEC or LIM treatment, none of the groups demonstrated toxicity in terms of body and organ weight or serum biochemical parameters. Both OEC and LIM treatment promoted an increase in epithelial healing, as confirmed by immunohistochemistry, which was greater in the animals that were treated with the positive control. In addition, both treatments increased cellular proliferation as measured by proliferating cell nuclear antigen and cyclooxygenase 2 expression in the gastric mucosa, vascular endothelial growth factor-mediated blood vessel formation in the margin of the ulcer, and production of gastric mucus, which fortifies the gastric protective barrier. We concluded that OEC and LIM, two common flavoring agents, promote gastric mucosal healing without any apparent toxic effect, resulting in better gastric epithelial organization in the treated rats.

Involvement of Glutathione, Sulfhydryl Compounds, Nitric Oxide, Vasoactive Intestinal Peptide, and Heat-Shock Protein-70 in the Gastroprotective Mechanism of Croton cajucara Benth. (Euphorbiaceae) Essential Oil

Ariane Leite Rozza,Thiago de Mello Moraes,Hélio Kushima,Domingos Sávio Nunes,Clélia Akiko Hiruma-Lima,Cla´udia Helena Pellizzon 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.9

This study aimed to evaluate the gastroprotective mechanism of action of the essential oil of Croton cajucara Benth. (Euphorbiaceae) stem bark in ethanol-induced gastric ulcers and its in vitro anti–Helicobacter pylori activity. The involvement of heat-shock protein-70, vasoactive intestinal peptide, glutathione, nitric oxide, and nonprotein sulfhydryl compounds in the gastroprotective effect was determined in male Wistar rats. The minimum inhibitory concentration against H. pylori was determined in vitro. The results were analyzed by analysis of variance followed by the Dunnett test, and a P value less than 0.05 was considered to represent a statistically significant difference. C. cajucara decreased ethanol-induced ulcer area in 100% of ulcers and decreased the histologic lesions. In the C. cajucara group, the area marked by heat-shock protein-70 was significantly higher than the area in the control group; this finding was not seen for vasoactive intestinal peptide. C. cajucara could not maintain glutathione levels close to those in the sham group. The gastric ulcer area of rats treated with the sulfhydryl compound blocker was decreased, but the ulcer area of rats treated with nitric oxide synthase inhibitor showed no alteration. The minimum inhibitory concentration obtained for C. cajucara was 125 μg/mL. These findings suggest that sulfhydryl compounds and heat-shock protein-70, but not nitric oxide, glutathione, or vasoactive intestinal peptide, are involved in the C. cajucara gastroprotective effect against ethanol-induced gastric ulcers.

Differences in Gastroprotective and Mutagenic Actions Between Polar and Apolar Extracts of Ananas ananassoides

J.S. Silva,M.A. Andreo,F.R. Tubaldini,E.A. Varanda,L.R.M. Rocha,A.R.M.S. Brito,W. Vilegas,C.A. Hiruma-Lima 한국식품영양과학회 2008 Journal of medicinal food Vol.11 No.1

Several plants are used in folk medicine to treat gastrointestinal disorders. Ananas ananassoides(Baker) L.B.Smith (Family Bromeliaceae) is a medicinal plant commonly used in the central region of Brazil against gastric pain. Weevaluated two extracts (methanol [MeOH] and dichloromethane [DCM]) obtained from the leaves of A. ananassoidesfor theirability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% ethanol, absolute ethanol,non-steroidal anti-inflammatory drugs, and pylorus ligation) in mice and rats. The best results were obtained after pretreat-ment with the DCM extract, whereas the MeOH extract did not show any significant anti-ulcerogenic activity but presentedmutagenic action. The mechanism of action of the DCM extract suggested the effective participation of endogenous sulfhydrylgroup in the gastroprotective action. The data, taken together with the absence of acute toxicity and mutagenicity, indicatethe apolar extract, instead of the polar, extract of A. ananassoides as a safe and potential new anti-ulcerogenic drug.