A Network Pharmacology-Based Investigation to the Pharmacodynamic Material Basis and Mechanisms of the Anti-Inflammatory and Anti-Viral Effect of Isatis indigotica

• Published in: Drug design, development and therapy development and therapy, 2021-01, Vol.15, p.3193-3206
• Main Authors: Deng, Jiuling, Ma, Ying, He, Yuqiong, Yang, Hong, Chen, Yanhong, Wang, Liang, Huang, Doudou, Qiu, Shi, Tao, Xia, Chen, Wansheng
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; AKT1 protein; Analysis; Animals; Anti-Inflammatory Agents - pharmacology; Anti-inflammatory drugs; Antiviral agents; Antiviral Agents - pharmacology; bioassay analysis; Bioflavonoids; Cell proliferation; Flavones; Flavonoids; Gas flow; Herbs; IL-1β; Immune system; Immunosuppressive agents; Indigo; Indoles; Inflammation; Inflammatory response; Influenza; Ingredients; Interleukin 2; Investigations; Isatis - chemistry; Isatis indigotica; Lignans; Lipopolysaccharides; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Mice; network analysis; Network Pharmacology; Original Research; Pharmacodynamics; Pharmacokinetics; Pharmacology; Proteins; Quadrupoles; Questions and answers; RAW 264.7 Cells; Signal transduction; Signal Transduction - drug effects; Signaling; Tumor necrosis factor-α; uplc-q-tof-ms
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S316701

( ) is a cruciferous herb that is widely distributed in China, and its roots and leaves have been used in two renowned antipyretic detoxicate crude drugs in Chinese Pharmacopoeia, ( ) and ( ) . However, the pharmacodynamic material basis and underlying mechanisms of the herbal efficacy remained to be elucidated. Ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was adopted for the chemical profiling of and . The active ingredients were screened out through the prediction of gastrointestinal absorption and druglikeness analysis using SwissADME. A herb-ingredient-target network was constructed through target prediction of the herbal active ingredients and anti-inflammation or anti-viral properties, followed by protein-protein interaction analysis. Then, the potential relevant signaling pathways were predicted by pathway enrichment. Finally, for verification, RAW 264.7 cell line was adopted to examine the anti-inflammatory and anti-viral activities of 6 representative ingredients in . Seventy-three compounds have been identified from through UPLC-Q-TOF-MS. A total of 17 potential active ingredients were screened through pharmacokinetics and drug-likeness evaluation using SwissADME. It was shown that key targets might include TNF, AKT1, SRC, IL2, CASP9, and CASP3 in our herb-ingredient-target network, and isovitexin, a flavonoid, tended to participate in the inflammatory response, indoles were more likely to affect the cell proliferation processes, and lignans might have a broader affinity to key targets than the other active ingredients, such as regulating immune system (targeting IL-2) and PI3K-Akt signaling pathway. In vitro, indigo and secoisolariciresinol diglucoside markedly reduced TNF-α expression in Poly (I: C)-incubated cells. Isovitexin significantly inhibited TNF-α expression, and isatin treatment markedly reduced IL-1β expression in LPS-incubated cells. As the pharmacodynamics material basis of , indoles, lignans, and flavonoids are believed to confer beneficial properties through various cellular aspects with multiple signaling pathways involved.