A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology
Abstract Background 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...
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BMC
2020-03-01
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| Series: | BMC Complementary Medicine and Therapies |
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| Online Access: | http://link.springer.com/article/10.1186/s12906-020-2871-3 |
| _version_ | 1828388329170665472 |
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| author | Le Wang Nana Tan Huan Wang Jingbo Hu Wenbo Diwu Xiaoling Wang |
| author_facet | Le Wang Nana Tan Huan Wang Jingbo Hu Wenbo Diwu Xiaoling Wang |
| author_sort | Le Wang |
| collection | DOAJ |
| description | Abstract Background 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. Methods 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. Results The n-butanol part of ethanol extract from RS showed a strong α-glucosidase inhibition activity (90.55%, IC50 0.551 mg/mL) against positive control acarbose (90.59%, IC50 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 d = 0.165, C b = 0.232, C c = 0.401), ACACB (C d = 0.155, C b = 0.184, C c = 0.318), NFKB1 (C d = 0.233, C b = 0.161, C c = 0.431), and PGH2 (C d = 0.194, C b = 0.157, C 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. Conclusions 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. |
| first_indexed | 2024-12-10T06:11:09Z |
| format | Article |
| id | doaj.art-7ad821b755cb445c92961d8a86991b3f |
| institution | Directory Open Access Journal |
| issn | 2662-7671 |
| language | English |
| last_indexed | 2024-12-10T06:11:09Z |
| publishDate | 2020-03-01 |
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| series | BMC Complementary Medicine and Therapies |
| spelling | doaj.art-7ad821b755cb445c92961d8a86991b3f2022-12-22T01:59:33ZengBMCBMC Complementary Medicine and Therapies2662-76712020-03-0120111710.1186/s12906-020-2871-3A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacologyLe Wang0Nana Tan1Huan Wang2Jingbo Hu3Wenbo Diwu4Xiaoling Wang5Shaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and SciencesShaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and SciencesCollege of Computer Science and Technology, Baoji University of Arts and SciencesCollege of Electronic and Electrical Engineering, Baoji University of Arts and SciencesShaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and SciencesShaanxi Key Laboratory of Phytochemistry, College of Chemistry and Chemical Engineering, Baoji University of Arts and SciencesAbstract Background 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. Methods 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. Results The n-butanol part of ethanol extract from RS showed a strong α-glucosidase inhibition activity (90.55%, IC50 0.551 mg/mL) against positive control acarbose (90.59%, IC50 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 d = 0.165, C b = 0.232, C c = 0.401), ACACB (C d = 0.155, C b = 0.184, C c = 0.318), NFKB1 (C d = 0.233, C b = 0.161, C c = 0.431), and PGH2 (C d = 0.194, C b = 0.157, C 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. Conclusions 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.http://link.springer.com/article/10.1186/s12906-020-2871-3Radix scutellariaeFlavonoidsα-Glucosidase inhibitorsUltrafiltrationLC-MSNetwork pharmacology |
| spellingShingle | Le Wang Nana Tan Huan Wang Jingbo Hu Wenbo Diwu Xiaoling Wang A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology BMC Complementary Medicine and Therapies Radix scutellariae Flavonoids α-Glucosidase inhibitors Ultrafiltration LC-MS Network pharmacology |
| title | A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology |
| title_full | A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology |
| title_fullStr | A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology |
| title_full_unstemmed | A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology |
| title_short | A systematic analysis of natural α-glucosidase inhibitors from flavonoids of Radix scutellariae using ultrafiltration UPLC-TripleTOF-MS/MS and network pharmacology |
| title_sort | systematic analysis of natural α glucosidase inhibitors from flavonoids of radix scutellariae using ultrafiltration uplc tripletof ms ms and network pharmacology |
| topic | Radix scutellariae Flavonoids α-Glucosidase inhibitors Ultrafiltration LC-MS Network pharmacology |
| url | http://link.springer.com/article/10.1186/s12906-020-2871-3 |
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