Aulifa Diah Lia, Adnyana I Ketut, Sukrasno Sukrasno, Levita Jutti
Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang, 45363, Indonesia.
Department of Pharmacology and Toxicology, School of Pharmacy, Bandung Institute of Technology, Bandung, 40132, Indonesia.
Heliyon. 2022 May 21;8(5):e09501. doi: 10.1016/j.heliyon.2022.e09501. eCollection 2022 May.
In Indonesia, the sap Koidzumi has been utilized traditionally as a blood-sugar reducer, nonetheless, its molecular mechanism still needs to be studied. This study aimed to isolate xanthoangelol (XA) from the yellow sap of planted in Mount Rinjani, Indonesia, and to investigate its mechanism by and methods towards α-glucosidase and dipeptidyl peptidase-IV (DPP-IV). The dried yellow sap was macerated using ethanol, subjected to liquid-liquid extraction using a different polarity of solvents, further gradient-eluted with column chromatography. The isolated compound, formed as yellow crystals, melting point 114-114.4 °C, λ 368 nm, 393.20 [M + H], was confirmed as XA. Acarbose, an α-glucosidase inhibitor, and sitagliptin, a DPP-IV inhibitor, respectively, were employed as the reference drugs for both the and studies. XA interacts with essential amino acid residues 232-237 in the -terminal -loop of α-glucosidase by forming a hydrogen bond with Ala234, a salt-bridge with Asp232, and 9 hydrophobic interactions (binding energy -7.81 kcal/mol; Ki = 1.99 μM). These binding modes resemble those of acarbose. Moreover, XA forms hydrogen bonds with Glu205 and Glu206 in the subsite S2 and π-π interaction with Phe357 in the extensive subsite S2 of DPP-IV (binding energy -8.34 kcal/mol; Ki = 0.873 μM), which are similar to those of sitagliptin. XA inhibits both α-glucosidase (IC XA = 14.45 μM; IC acarbose = 207 μM) and DPP-IV (IC XA = 10.49 μM; IC sitagliptin = 0.87 μM). Taken together, XA isolated from the yellow sap of Koidzumi might possess the potential to be further developed as an inhibitor of α-glucosidase and DPP-IV.
在印度尼西亚，小泉黄皮树汁传统上被用作降血糖剂，然而，其分子机制仍有待研究。本研究旨在从印度尼西亚林贾尼山种植的小泉黄皮树的黄色汁液中分离出黄皮香豆素（XA），并通过体外和计算机模拟方法研究其对α-葡萄糖苷酶和二肽基肽酶-IV（DPP-IV）的作用机制。将干燥的黄色汁液用乙醇浸渍，使用不同极性的溶剂进行液-液萃取，再用柱色谱进行梯度洗脱。分离得到的化合物为黄色晶体，熔点114 - 114.4℃，λ 368 nm， 393.20 [M + H]，经确认为XA。分别使用α-葡萄糖苷酶抑制剂阿卡波糖和DPP-IV抑制剂西他列汀作为体外和计算机模拟研究的参考药物。XA通过与Ala234形成氢键、与Asp232形成盐桥以及9种疏水相互作用（结合能-7.81 kcal/mol；Ki = 1.99 μM），与α-葡萄糖苷酶N末端β-环中的必需氨基酸残基232 - 237相互作用。这些结合模式与阿卡波糖的相似。此外，XA在DPP-IV的S2亚位点与Glu205和Glu206形成氢键，并在广泛的S2亚位点与Phe357形成π-π相互作用（结合能-8.34 kcal/mol；Ki = 0.873 μM），这与西他列汀的相似。XA同时抑制α-葡萄糖苷酶（IC XA = 14.45 μM；IC阿卡波糖 = 207 μM）和DPP-IV（IC XA = 10.49 μM；IC西他列汀 = 0.87 μM）。综上所述，从小泉黄皮树黄色汁液中分离出的XA可能具有进一步开发成为α-葡萄糖苷酶和DPP-IV抑制剂的潜力。
