cytellin and masticadienonic-acid

Amphipterygium adstringens (Schltdl.) Standl. (Anacardiaceae) is widely used in traditional Mexican medicine for the treatment of gastritis and ulcers. In this work, we studied the anti-Helicobacter pylori activity of its bark, this Gram-negative bacterium is considered the major etiological agent of chronic active gastritis and peptic ulcer disease, and it is linked to gastric carcinoma. From a bio-guided assay of the fractions obtained form a continuous Soxhlet extraction of the bark, we identified that petroleum ether fraction had significant antimicrobial activity against Helicobacter pylori. From this fraction, we isolated an anacardic acids mixture and three known triterpenes: masticadienonic acid; 3alpha-hydroxymasticadienonic acid; 3-epi-oleanolic; as well as the sterol beta-sitosterol. Only the anacardic acids mixture exhibits a potent dose-dependent antibacterial activity (MIC=10 microg/ml in broth cultures). It is enriched in saturated alkyl phenolic acids (C15:0, C16:0, C17:0 C19:0) which represents a novel source of these compounds with potent anti-Helicobacter pylori activity. The promising use of anacardic acids and Amphipterygium adstringens bark in the development of an integral treatment of Helicobacter pylori diseases is discussed.

Topics: Anacardiaceae; Anacardic Acids; Anti-Bacterial Agents; Dose-Response Relationship, Drug; Helicobacter pylori; Humans; Hydroxybenzoates; Medicine, Traditional; Mexico; Microbial Sensitivity Tests; Oleanolic Acid; Plant Bark; Plant Extracts; Sitosterols; Triterpenes

In this investigation three bioactive compounds, responsible for the gastroprotective property of Amphipterygium adstringens, were purified from an active dichloromethane fraction. These compounds were 3alpha-hydroxymasticadienonic acid, beta-sitosterol and 3- epi-oleanolic acid. The latter was the most active compound (88.8 % of gastroprotection) followed by 3alpha-hydroxymasticadienoic acid and beta-sitosterol (69.8 and 42.5 % of gastroprotection, respectively). Carbenoxolone was used as positive control and it showed 88.4 % of gastroprotection. Masticadienonic acid was also isolated from the active fraction, but it was unable to inhibit the ethanol-induced gastric lesions. The gastroprotection of the methanol extract was completely inhibited by the pretreatment with l-NAME and attenuated by pretreatment with indomethacin and N-ethylmaleimide. These results suggest that endogenous nitric oxide plays an important role in the gastroprotection of A. adstringens methanol extract on ethanol-induced gastric mucosal lesions and that there is partial participation by prostaglandins and endogenous sulfhydryls. The effect of 3alpha-hydroxymasticadienonic acid was attenuated only by pretreatment with N-ethylmaleimide, indicating that endogenous sulfhydryls (thiols) participate in its gastroprotective mechanism. Capsaicin-sensitive afferent neurons do not participate in the gastroprotection of either the methanol extract or 3alpha-hydroxymasticadienoic acid.

Topics: Animals; Capsaicin; Dose-Response Relationship, Drug; Ethanol; Gastric Mucosa; Gastrointestinal Agents; Male; Neurons, Afferent; Nitric Oxide; Oleanolic Acid; Phytotherapy; Plant Extracts; Plant Stems; Plants, Medicinal; Prostaglandins; Rats; Rats, Wistar; Sitosterols; Stomach Ulcer; Sulfhydryl Compounds; Triterpenes