Department of Food Science, Faculty of Food Science and Technology, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
Natural Medicines and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, 43400, Serdang, Selangor, Malaysia.
J Ethnopharmacol. 2024 Jan 10;318(Pt B):117015. doi: 10.1016/j.jep.2023.117015. Epub 2023 Aug 10.
Ardisia elliptica Thunb. (AE) (Primulaceae) is a medicinal plant found in the Malay Peninsula and has been traditionally used to treat diabetes. However, limited studies to date in providing scientific evidence to support the antidiabetic efficacy of this plant by in-vitro and in-vivo models.
To investigate the anti-hyperglycemic potential of AE through in-vitro enzymatic activities and streptozotocin-nicotinamide (STZ-NA) induced diabetic rat models using proton-nuclear magnetic resonance (H-NMR)-based metabolomics approach.
Anti-α-amylase and anti-α-glucosidase activities of the hydroethanolic extracts of AE were evaluated. The absolute quantification of bioactive constituents, using ultra-high performance liquid chromatography (UHPLC) was performed for the most active extract. Three different dosage levels of the AE extract were orally administered for 4 weeks consecutively in STZ-NA induced diabetic rats. Physical assessments, biochemical analysis, and an untargeted H-NMR-based metabolomics analysis of the urine and serum were carried out on the animal model.
Type 2 diabetes mellitus (T2DM) rat model was successfully developed based on the clear separation observed between the STZ-NA induced diabetic and normal non-diabetic groups. Discriminating biomarkers included glucose, citrate, succinate, allantoin, hippurate, 2-oxoglutarate, and 3-hydroxybutyrate, as determined through an orthogonal partial least squares-discriminant analysis (OPLS-DA) model. A treatment dosage of 250 mg/kg body weight (BW) of standardized 70% ethanolic AE extract mitigated increase in serum glucose, creatinine, and urea levels, providing treatment levels comparable to that obtained using metformin, with flavonoids primarily contribute to the anti-hyperglycemic activities. Urinary metabolomics disclosed that the following disturbed metabolism pathways: the citrate cycle (TCA cycle), butanoate metabolism, glycolysis and gluconeogenesis, pyruvate metabolism, and synthesis and degradation of ketone bodies, were ameliorated after treatment with the standardized AE extract.
This study demonstrated the first attempt at revealing the therapeutic effect of oral treatment with 250 mg/kg BW of standardized AE extract on chemically induced T2DM rats. The present study provides scientific evidence supporting the ethnomedicinal use of Ardisia elliptica and further advances the understanding of the fundamental molecular mechanisms affected by this herbal antidote.
椭圆紫金牛（AE）（报春花科）是一种在马来半岛发现的药用植物，传统上用于治疗糖尿病。然而，迄今为止，只有有限的研究通过体外和体内模型为这种植物的抗糖尿病功效提供科学证据。
通过基于质子核磁共振（H-NMR）的代谢组学方法，研究 AE 的抗高血糖潜力，采用体外酶活性和链脲佐菌素-烟酰胺（STZ-NA）诱导的糖尿病大鼠模型。
评估 AE 水乙醇提取物的抗α-淀粉酶和抗α-葡萄糖苷酶活性。使用超高效液相色谱（UHPLC）对最活跃的提取物进行生物活性成分的绝对定量。AE 提取物的三个不同剂量水平连续口服 4 周，用于 STZ-NA 诱导的糖尿病大鼠。对动物模型进行物理评估、生化分析和非靶向 H-NMR 基于代谢组学的尿液和血清分析。
根据 STZ-NA 诱导的糖尿病和正常非糖尿病组之间观察到的明显分离，成功建立了 2 型糖尿病（T2DM）大鼠模型。通过正交偏最小二乘判别分析（OPLS-DA）模型确定的鉴别生物标志物包括葡萄糖、柠檬酸盐、琥珀酸盐、尿囊素、马尿酸盐、2-氧戊二酸和 3-羟基丁酸。250mg/kg 体重（BW）的标准化 70%乙醇 AE 提取物剂量可减轻血清葡萄糖、肌酐和尿素水平的升高，提供与二甲双胍相当的治疗水平，黄酮类化合物主要有助于抗高血糖活性。尿代谢组学显示，以下受干扰的代谢途径：柠檬酸循环（TCA 循环）、丁酸盐代谢、糖酵解和糖异生、丙酮酸代谢以及酮体的合成和降解，在用标准化 AE 提取物治疗后得到改善。
本研究首次揭示了口服 250mg/kg BW 标准化 AE 提取物对化学诱导的 T2DM 大鼠的治疗效果。本研究提供了科学证据，支持椭圆紫金牛的民族医学用途，并进一步深入了解这种草药解毒剂影响的基本分子机制。
