Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and Sciences, High-tech Avenue 1#, Baoji, 721013, China.
College of Computer Science and Technology, Baoji University of Arts and Sciences, Baoji, 721013, China.
BMC Complement Med Ther. 2020 Mar 6;20(1):72. doi: 10.1186/s12906-020-2871-3.
Flavonoids from plant medicines are supposed to be viable alternatives for the treatment of type 2 diabetes (T2D) as less toxicity and side effects. Radix scutellariae (RS) is a widely used traditional medicine in Asia. It has shown great potential in the research of T2D. However, the pharmacological actions remain obscured due to the complex chemical nature of plant medicines.
In the present study, a systematic method combining ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology was developed to screen α-glucosidase inhibitors from flavonoids of RS, and explore the underlying mechanism for the treatment of T2D.
The n-butanol part of ethanol extract from RS showed a strong α-glucosidase inhibition activity (90.55%, IC 0.551 mg/mL) against positive control acarbose (90.59%, IC 1.079 mg/mL). A total of 32 kinds of flavonoids were identified from the extract, and their ESI-MS/MS behaviors were elucidated. Thirteen compounds were screened as α-glucosidase inhibitors, including viscidulin III, 2',3,5,6',7-pentahydroxyflavanone, and so on. A compound-target-pathway (CTP) network was constructed by integrating these α-glucosidase inhibitors, target proteins, and related pathways. This network exhibited an uneven distribution and approximate scale-free property. Chrysin (k = 87), 5,8,2'-trihydroxy-7-methoxyflavone (k = 21) and wogonin (k = 20) were selected as the main active constituents with much higher degree values. A protein-protein interaction (PPI) weighted network was built for target proteins of these α-glucosidase inhibitors and drug targets of T2D. PPARG (C = 0.165, C = 0.232, C = 0.401), ACACB (C = 0.155, C = 0.184, C = 0.318), NFKB1 (C = 0.233, C = 0.161, C = 0.431), and PGH2 (C = 0.194, C = 0.157, C = 0.427) exhibited as key targets with the highest scores of centrality indices. Furthermore, a core subnetwork was extracted from the CTP and PPI weighted network. Type II diabetes mellitus (hsa04930) and PPAR signaling pathway (hsa03320) were confirmed as the critical pathways.
These results improved current understanding of natural flavonoids on the treatment of T2D. The combination of ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology provides a novel strategy for the research of plant medicines and complex diseases.
植物药中的类黄酮被认为是治疗 2 型糖尿病（T2D）的可行替代品，因为它们的毒性和副作用较小。黄芩（RS）是亚洲广泛使用的传统药物。它在 T2D 的研究中显示出巨大的潜力。然而，由于植物药的复杂化学性质，其药理作用仍不清楚。
在本研究中，开发了一种结合超滤 UPLC-TripleTOF-MS/MS 和网络药理学的系统方法，从 RS 中的类黄酮中筛选α-葡萄糖苷酶抑制剂，并探讨其治疗 T2D 的潜在机制。
RS 乙醇提取物的正丁醇部分对阳性对照阿卡波糖（90.59%，IC 0.579mg/mL）表现出强烈的α-葡萄糖苷酶抑制活性（90.55%，IC 0.551mg/mL）。从提取物中鉴定出 32 种类黄酮，并阐明了它们的 ESI-MS/MS 行为。筛选出 13 种类黄酮为α-葡萄糖苷酶抑制剂，包括粘毛菌素 III、2'，3，5，6'，7-五羟基黄酮等。通过整合这些α-葡萄糖苷酶抑制剂、靶蛋白和相关途径，构建了一个化合物-靶-途径（CTP）网络。该网络表现出不均匀的分布和近似无标度的特性。白杨素（k=87）、5,8,2'-三羟基-7-甲氧基黄酮（k=21）和白杨素（k=20）被选为具有更高程度值的主要活性成分。为这些α-葡萄糖苷酶抑制剂的靶蛋白和 T2D 的药物靶标构建了一个蛋白质-蛋白质相互作用（PPI）加权网络。PPARG（C=0.165、C=0.232、C=0.401）、ACACB（C=0.155、C=0.184、C=0.318）、NFKB1（C=0.233、C=0.161、C=0.431）和 PGH2（C=0.194、C=0.157、C=0.427）被认为是具有最高中心性指数得分的关键靶标。此外，从 CTP 和 PPI 加权网络中提取了一个核心子网。2 型糖尿病（hsa04930）和 PPAR 信号通路（hsa03320）被确认为关键通路。
这些结果提高了人们对天然类黄酮治疗 T2D 的认识。超滤 UPLC-TripleTOF-MS/MS 与网络药理学的结合为植物药和复杂疾病的研究提供了一种新策略。
