Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
J Ethnopharmacol. 2013 Jan 30;145(2):530-5. doi: 10.1016/j.jep.2012.11.025. Epub 2012 Nov 23.
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.
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.
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 N(G)-nitro-L-arginine methyl ester (L-NAME), N-ethylmaleimide (NEM) and indomethacin.
Investigation of the acute toxicity revealed that infusions of the leaves and stem-barks of both Hintonia species were not toxic to mice (LD(50)>5000 mg/kg in all cases). HLSB, HSSB, HLL and HSL provoked a significant gastroprotective effect [80.5±3.35% (ED(50)=184.7 mg/kg), 80.26±3.96%, 75.1±7.26% (ED(50)=109.1 mg/kg), 76.85±3.17% (ED(50)=149.7 mg/kg) of gastroprotection respectively]. Compounds 1 and 2, present in all the extracts, were also active [68.85±8.4% (ED(50)=15 mg/kg), 74.04±4.4% (ED(50)=26 mg/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.
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.
Hintonia latiflora 和 Hintonia standleyana 的茎皮,当地称为“copalchi”,用于治疗多种疾病,如糖尿病和胃肠道疾病,包括胃溃疡。尽管已经证明了其降血糖作用,但对其胃保护作用仍未得到探索。
本研究的主要目的是确定 Hintonia latiflora 和 Hintonia standleyana 的水提物和化合物的潜在急性毒性和胃保护活性,以证明它们在墨西哥民间医学中治疗胃溃疡的临床前疗效。
通过浸渍法制备 Hintonia latiflora 和 Hintonia standleyana 的茎皮(HLSB 和 HSSB)和叶(HLL 和 HSL)的水提物。通过 Lorke 法进行急性毒性研究。使用卡波诺醇作为阳性对照,通过常规乙醇诱导的大鼠胃损伤模型评估胃保护作用。还测定了 5-O-[β-D-阿戊呋喃基-(1→6)-β-D-吡喃葡萄糖基]-7-甲氧基-3',4'-二羟基-4-苯基香豆素(1)和绿原酸(2)。使用相同的药理模型,但用 N(G)-硝基-L-精氨酸甲酯(L-NAME)、N-乙基马来酰亚胺(NEM)和吲哚美辛预处理动物,分析了测试化合物的初步作用机制。
急性毒性研究表明,两种 Hintonia 属植物的叶和茎皮提取物对小鼠均无毒性(在所有情况下,LD50>5000mg/kg)。HLSB、HSSB、HLL 和 HSL 均能显著发挥胃保护作用[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)]。所有提取物中存在的化合物 1 和 2 也具有活性[68.85±8.4%(ED50=15mg/kg)、74.04±4.4%(ED50=26mg/kg)],其作用机制涉及非蛋白巯基内源性(NP-SH)化合物,因为只有用 NEM 预处理才能抑制其胃保护作用。
本研究倾向于支持 HLSB、HSSB 用于治疗胃溃疡的民族医学用途。由于 HLL 和 HSL 也具有活性,因此可以替代使用叶子,从自然资源保护的角度来看,这是一个突出的发现,考虑到两种 Hintonia 植物的种群都很稀少,有灭绝的危险。主要有两种化合物(1 和 2)是植物的重要活性成分。