Ayaz Muhammad, Sadiq Abdul, Mosa Osama F, Zafar Tariq Abdalla, Eisa Hamdoon Alashary Adam, Elkhalifa Modawy Elnour Modawy, Elawad Mohammed Ahmed, Ahmed Alshebli, Ullah Farhat, Ghufran Mehreen, Kabra Atul
Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara 18000, Dir (L), KP, Pakistan.
Public Health Department Health Sciences College at Lieth, Umm Al Qura University, Makkah, Saudi Arabia.
Evid Based Complement Alternat Med. 2022 Apr 14;2022:6705810. doi: 10.1155/2022/6705810. eCollection 2022.
Natural products are among the most useful sources for the discovery of new drugs against various diseases. Keeping in view the ethnobotanical relevance ethnopharmacological significance of Polygonaceae family in diabetes, the current study was designed to isolate pure compounds from L. leaves and evaluate their and antidiabetic potentials.
Six compounds were isolated from the chloroform-ethyl acetate fractions using gravity column chromatography and were subjected to structure elucidation process. Structures were confirmed using H-NMR, C-NMR, and mass spectrometry techniques. Isolated phytochemicals were subjected to antidiabetic studies, including -glucosidase, -amylase inhibition, and DPPH, and ABTS antioxidant studies. Furthermore, the binding mode of these compounds in the target enzymes was elucidated via MOE-Dock software.
The isolated compounds revealed concentration-dependent inhibitions against -glucosidase enzyme. Ph-1 and Ph-2 were most potent with 81.84 and 78.79% enzyme inhibitions at 1000 g·mL, respectively. Ph-1 and Ph-2 exhibited ICs of 85 and 170 g·mL correspondingly. Likewise, test compounds showed considerable -amylase inhibitions with Ph-1 and Ph-2 being the most potent. Tested compounds exhibited considerable antioxidant potentials in both DPPH and ABTS assays. Molecular simulation studies also revealed top-ranked confirmations for the majority of the compounds in the target enzymes. Highest observed potent compound was Ph-1 with docking score of -12.4286 and formed eight hydrogen bonds and three H-pi linkages with the Asp 68, Phe 157, Phe 177, Asn 241, Glu 276, His 279, Phe 300, Glu 304, Ser 308, Pro 309, Phe 310, Asp 349, and Arg 439 residues of -glucosidase binding packets. Asp 68, Glu 276, Asp 349, and Arg 439 formed polar bonds with the 3-ethyl-2-methylpentane moiety of the ligand.
The isolated compounds exhibited considerable antioxidant and inhibitory potentials against vital enzymes implicated in T2DM. The docking scores of the compounds revealed that they exhibit affinity for binding with target ligands. The enzyme inhibition and antioxidant potential of the compounds might contribute to the hypoglycemic effects of the plant and need further studies.
天然产物是发现针对各种疾病的新药的最有用来源之一。鉴于蓼科植物在糖尿病方面的民族植物学相关性和民族药理学意义，本研究旨在从L.叶中分离纯化合物，并评估它们的抗糖尿病潜力。
使用重力柱色谱法从氯仿 - 乙酸乙酯馏分中分离出六种化合物，并进行结构解析。使用氢核磁共振（H-NMR）、碳核磁共振（C-NMR）和质谱技术确认结构。对分离出的植物化学物质进行抗糖尿病研究，包括α-葡萄糖苷酶、α-淀粉酶抑制以及二苯基苦味酰基自由基（DPPH）和2,2'-联氮-双-3-乙基苯并噻唑啉-6-磺酸（ABTS）抗氧化研究。此外，通过分子操作环境（MOE）-对接软件阐明这些化合物在靶标酶中的结合模式。
分离出的化合物对α-葡萄糖苷酶表现出浓度依赖性抑制作用。Ph-1和Ph-2最有效，在1000μg·mL时酶抑制率分别为81.84%和78.79%。Ph-1和Ph-2的半数抑制浓度（IC）分别为85和170μg·mL。同样，测试化合物对α-淀粉酶有显著抑制作用，其中Ph-1和Ph-2最有效。测试化合物在DPPH和ABTS测定中均表现出相当的抗氧化潜力。分子模拟研究还揭示了大多数化合物在靶标酶中的顶级确认结果。观察到的最有效化合物是Ph-1，对接分数为 -12.4286，与α-葡萄糖苷酶结合口袋的天冬氨酸68（Asp 68）、苯丙氨酸157（Phe 157）、苯丙氨酸177（Phe 177）、天冬酰胺241（Asn 241）、谷氨酸276（Glu 276）、组氨酸279（His 279）、苯丙氨酸300（Phe 300）、谷氨酸304（Glu 304）、丝氨酸308（Ser 308）、脯氨酸309（Pro 309）、苯丙氨酸310（Phe 310）、天冬氨酸349（Asp 349）和精氨酸439（Arg 439）残基形成八个氢键和三个氢-π键。天冬氨酸68、谷氨酸276、天冬氨酸349和精氨酸439与配体的3-乙基-2-甲基戊烷部分形成极性键。
分离出的化合物对2型糖尿病（T2DM）中涉及的重要酶表现出相当的抗氧化和抑制潜力。化合物的对接分数表明它们对与靶标配体结合具有亲和力。化合物的酶抑制和抗氧化潜力可能有助于该植物的降血糖作用，需要进一步研究。
