Abstract

Context

Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones.

Objective

This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents.

Materials and methods

Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078–10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays.

Results

Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC₅₀: 1464.32 μg/mL; DPP-4 IC₅₀: 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF₁–CF₄) whereby CF₃ showed the highest antidiabetic activity (α-amylase IC₅₀: 397.68 μg/mL; DPP-4 IC₅₀: 37.16 μg/mL) and resulted in β-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2–4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC₅₀: 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC₅₀: 911.44 μM).

Discussion and conclusions

The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

中文翻译：

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阔叶楝树皮提取物的 α-淀粉酶和二肽基肽酶 4 (DPP-4) 抑制作用以及使用体外和计算机方法鉴定生物活性成分

 抽象的

 语境

据报道， Melicope latifolia (DC.) TG Hartley（芸香科）含有多种植物化学物质，包括香豆素、类黄酮和苯乙酮。

 客观的

本研究调查了阔叶木树皮提取物、级分和分离成分的抗糖尿病和抗氧化作用。

 材料和方法

对宽叶白栉提取物（己烷、氯仿和甲醇）、级分和不同浓度（0.078–10 mg/mL）的分离成分进行体外α-淀粉酶和二肽基肽酶 4 (DPP-4) 抑制测定。进行分子对接以研究活性化合物与α-淀粉酶和DPP-4酶的结合机制。通过 2,2-二苯基-1-三硝基苯肼 (DPPH) 自由基清除和 β-胡萝卜素漂白测定来测定M. latifolia组分和化合物的抗氧化活性。

 结果

宽叶白楝氯仿提取物显示出最高的抗糖尿病活性（α-淀粉酶 IC ₅₀ ：1464.32 μg/mL；DPP-4 IC ₅₀ ：221.58 μg/mL）。氯仿提取物分级分离得到四个主要组分 (CF ₁ –CF ₄ )，其中 CF ₃显示出最高的抗糖尿病活性（α-淀粉酶 IC ₅₀ ：397.68 μg/mL；DPP-4 IC ₅₀ ：37.16 μg/mL）并产生 β -谷甾醇 ( 1 )、哈夫丁 ( 2 )、对香豆酸甲酯( 3 ) 和原儿茶酸 ( 4 )。首次报道从该物种中分离出化合物2 – 4及其 DPP-4 抑制作用。化合物2表现出最高的α-淀粉酶(IC ₅₀ : 197.53 μM)和β-胡萝卜素(88.48%)抑制作用，并与α-淀粉酶的关键氨基酸残基形成最多数量的分子相互作用。化合物3表现出最高的DPP-4抑制作用（IC ₅₀ ：911.44 μM）。

讨论与结论

体外和计算机分析表明M. latifolia作为 α-淀粉酶和 DPP-4 抑制剂的替代来源的潜力。建议对这些化合物进行进一步的药理学研究。