Guangxi Key Laboratory of Plant Functional Phytochemicals and Sustainable Utilization, Guangxi Institute of Botany, Guangxi Zhuang Autonomous Region and Chinese Academy of Sciences, Guilin 541006, China.
Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials, College of Chemistry and Bioengineering, Guilin University of Technology, Guilin 541004, China.
Int J Mol Sci. 2023 Jun 15;24(12):10178. doi: 10.3390/ijms241210178.
The discovery of bioactive compounds from medicinal plants has played a crucial role in drug discovery. In this study, a simple and efficient method utilizing affinity-based ultrafiltration (UF) coupled with high-performance liquid chromatography (HPLC) was developed for the rapid screening and targeted separation of α-glucosidase inhibitors from roots. First, an active fraction of roots (SGR2) was prepared, and 17 potential α-glucosidase inhibitors were identified based on UF-HPLC analysis. Second, guided by UF-HPLC, a combination of MCI gel CHP-20P column chromatography, high-speed counter-current countercurrent chromatography, and preparative HPLC were conducted to isolate the compounds producing active peaks. Sixteen compounds were successfully isolated from SGR2, including two lignans and fourteen cucurbitane-type triterpenoids. The structures of the novel compounds (, , , , , and ) were elucidated using spectroscopic methods, including one- and two-dimensional nuclear magnetic resonance spectroscopy and high-resolution electrospray ionization mass spectrometry. Finally, the α-glucosidase inhibitory activities of the isolated compounds were verified via enzyme inhibition assays and molecular docking analysis, all of which were found to exhibit certain inhibitory activity. Compound exhibited the strongest inhibitory activity, with an IC value of 430.13 ± 13.33 μM, which was superior to that of acarbose (1332.50 ± 58.53 μM). The relationships between the structures of the compounds and their inhibitory activities were also investigated. Molecular docking showed that the highly active inhibitors interacted with α-glucosidase through hydrogen bonds and hydrophobic interactions. Our results demonstrate the beneficial effects of roots and their constituents on α-glucosidase inhibition.
从药用植物中发现生物活性化合物在药物发现中发挥了关键作用。在这项研究中，开发了一种利用基于亲和性的超滤（UF）与高效液相色谱（HPLC）相结合的简单而有效的方法，用于从 根中快速筛选和靶向分离α-葡萄糖苷酶抑制剂。首先，制备 根的活性部分（SGR2），并根据 UF-HPLC 分析鉴定出 17 种潜在的α-葡萄糖苷酶抑制剂。其次，根据 UF-HPLC 指导，采用 MCI 凝胶 CHP-20P 柱层析、高速逆流色谱和制备 HPLC 相结合的方法，分离产生活性峰的化合物。从 SGR2 中成功分离出 16 种化合物，包括两种木脂素和十四种葫芦烷型三萜。利用光谱学方法，包括一维和二维核磁共振波谱和高分辨率电喷雾电离质谱，阐明了这些新化合物（、、、、和 ）的结构。最后，通过酶抑制测定和分子对接分析验证了分离化合物的α-葡萄糖苷酶抑制活性，发现它们均表现出一定的抑制活性。化合物 表现出最强的抑制活性，IC 值为 430.13 ± 13.33 μM，优于阿卡波糖（1332.50 ± 58.53 μM）。还研究了化合物结构与抑制活性之间的关系。分子对接表明，高活性抑制剂通过氢键和疏水相互作用与α-葡萄糖苷酶相互作用。我们的结果表明 根及其成分对α-葡萄糖苷酶抑制具有有益作用。
