Formulation of category-2 hypoglycemic Improved Traditional Medicines from selected Cameroonian medicinal plants: Mangifera indica, Persea americana and Ageratum conyzoides

G. Shu, Denis Zofou, A. A. Ufuan, Gisele Etame Loe, J. Foba-Tendo, Ebane Ndode Mesue, Mukete Patrick Dioh, C. T. Mofor, F. P. T. Manfo, J. N. Assob, Vincent P.K. Titanji
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Abstract

Diabetes mellitus is the fourth leading cause of death worldwide, and constitutes a major public health crisis. Management of the adverse  condition relies mostly on synthetic drugs such as metformin, glibenclamide and insulin. However, treatment with synthetic  drugs is challenged by side effects and high cost especially to patients in low-income countries like Cameroon. This study set out to  formulate Improved Traditional Medicines (ITMs) in the form of capsules from lyophilized aqueous leaf extracts of Ageratum conyzoides,  Mangifera indica and Persea americana, in combination, coded as ITM-1, and leaf extract of Mangifera indica alone, referred to as ITM-2.  Phytochemical profiling of individual extracts was carried out using standard methods, while their antioxidant activity was evaluated in  vitro by the 2,2-diphenyl-1-picryhadrazyl reducing (DPPH) assay and the Ferric (Iron) reducing antioxidant power assay (FRAP). Capsule  formulation was guided by findings from prior Physicochemical and pharmacotechnical analysis of individual extracts and their  combination. Safety studies were carried out both in vitro (cytotoxicity testing in Vero cells); and in vivo (acute toxicity tests using the  mouse model). Preliminary evaluation of the antidiabetic potential of the formulated ITMs was achieved through determination of their  acute hypoglycemic and antihyperglycemic properties in Wistar rats (Oral Glucose Tolerance Test). Major classes of phytochemicals detected were alkaloids, phenols, tannins, flavonoids, anthocyanins, tri-terpenes and anthraquinones. The DPPH and FRAP assays showed  dose-dependent antioxidant activity for ITM-1 and ITM-2. Both ITMs showed no toxic effects, be it in vitro, (Cytotoxic  Concentration 50% - CC50>1000 µg/mL in cells) or in vivo. At the dose of 25 mg/Kg, both ITMs exhibited significant hypoglycemic effects  in Wistar rats. The ITM-2 capsules completely suppressed post-prandial glucose peak in rats as compared to the negative control (distilled  water), ITM-1 capsule was able to cause restoration of the glucose levels to normal levels after 120 minutes  
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从选定的喀麦隆药用植物中提炼 2 类降血糖改良传统药物:Mangifera indica、Persea americana 和 Ageratum conyzoides
糖尿病是全球第四大死因,也是一个重大的公共卫生危机。治疗糖尿病主要依靠合成药物,如二甲双胍、格列本脲和胰岛素。然而,使用合成药物治疗面临着副作用大、费用高的挑战,尤其是对喀麦隆等低收入国家的患者而言。这项研究的目的是用冻干的芒果叶水溶液提取物(Ageratum conyzoides)、芒果叶水溶液提取物(Mangifera indica)和芒果叶水溶液提取物(Persea americana)配制胶囊形式的改良传统药物(ITMs),其中芒果叶水溶液提取物组合称为 ITM-1,芒果叶水溶液提取物单独称为 ITM-2。 各提取物的植物化学成分分析采用标准方法进行,而其抗氧化活性则通过 2,2-二苯基-1-苦嗪还原法(DPPH)和铁(铁)还原抗氧化力测定法(FRAP)进行体外评估。胶囊配方以之前对单个提取物及其组合进行的物理化学和药物技术分析结果为指导。在体外(Vero 细胞的细胞毒性测试)和体内(使用小鼠模型的急性毒性测试)进行了安全性研究。通过测定 Wistar 大鼠的急性降血糖和抗高血糖特性(口服葡萄糖耐量试验),对配制的 ITMs 的抗糖尿病潜力进行了初步评估。检测到的主要植物化学物质有生物碱、酚类、单宁、黄酮类、花青素、三萜类和蒽醌类。DPPH 和 FRAP 试验表明,ITM-1 和 ITM-2 具有剂量依赖性抗氧化活性。无论是在体外(细胞毒性浓度 50% - CC50>1000 µg/mL)还是在体内,这两种 ITM 都没有显示出毒性作用。当剂量为 25 毫克/千克时,两种 ITM 对 Wistar 大鼠都有明显的降血糖作用。与阴性对照组(蒸馏水)相比,ITM-2 胶囊能完全抑制大鼠餐后血糖峰值,ITM-1 胶囊则能使血糖水平在 120 分钟后恢复到正常水平。
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