Gastroprotective effect of Hintonia latiflora and Hintonia standleyana aqueous extracts and compounds

ETHNOPHARMACOLOGICAL RELEVANCE: The stem-barks of Hintonia latiflora and Hintonia standleyana, locally known as “copalchi”, are used for treating several maladies such as diabetes and gastrointestinal complaints, including gastric ulcers. Although the antidiabetic properties have been demonstrated, the gastroprotective action remains unexplored. AIM OF THE STUDY: The main goals of this study were to establish the potential acute toxicity and the gastroprotective activity of aqueous extracts and compounds from Hintonia latiflora and Hintonia standleyana in order to demonstrate their preclinical efficacy for the treatment of gastric ulcers in Mexican folk medicine. MATERIALS AND METHODS: The aqueous extracts from the stem-barks (HLSB and HSSB) and leaves (HLL and HSL) from Hintonia latiflora and Hintonia standleyana were prepared by infusion. Investigation of the acute toxicity was accomplished by the Lorke method. The gastroprotective effect was assessed by means of a conventional ethanol-induced gastric injury model in rats using carbenoxolone as positive control. 5-O-[β-d-apiofuranosyl-(1→6)-β-d-glucopyranosyl]-7-methoxy-3′,4′-dihydroxy-4-phenylcoumarin (1) and chlorogenic acid (2) were also assayed. Preliminary mechanism of action of the tested compounds was analyzed using the same pharmacological models but pretreating the animals with Nᴳ-nitro-l-arginine methyl ester (l-NAME), N-ethylmaleimide (NEM) and indomethacin. RESULTS: Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD₅₀>5000mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED₅₀=184.7mg/kg), 80.26±3.96%, 75.1±7.26% (ED₅₀=109.1mg/kg), 76.85±3.17% (ED₅₀=149.7mg/kg) of gastroprotection respectively]. Compounds 1 and 2, present in all the extracts, were also active [68.85±8.4% (ED₅₀=15mg/kg), 74.04±4.4% (ED₅₀=26mg/kg) of gastroprotection respectively] and their mode of action involved non-protein sulfhydryl endogenous (NP-SH) compounds, since only pretreatment with NEM inhibited their gastroprotective action. CONCLUSIONS: The present investigation tends to support the ethnomedical use of HLSB, HSSB for treating gastric ulceration. Since HLL and HSL were also active, the leaves could be use alternatively, which in terms of natural resources conservation is an outstanding finding, considering that the plant populations of both Hintonia are scarce and in danger of extinction. Mainly two compounds (1 and 2) are important active principles of the plants.