Exploring the Mechanism of Tripterygium wilfordii Against Cancer Using Network Pharmacology and Molecular Docking

Background: The root of Tripterygium wilfordii(Tripterygii radix), a natural powerful traditional Chinese medicine(TCM) for various diseases treatment, has been used for centuries in the Asian countries as anti-rheumatoid arthritis(RA) agent, antioxidant agent, and anti-inflammatory agent. Its combination with other herbs in treating RA has been explored. The anti-RA effect of T. wilfordii for cancer treatment has been supported by some evidence. Aims and Objectives: To investigate the anticancer mechanism of T. wilfordii, bioinformatics databases were used to identify its active ingredients. Materials and Methods: Target proteins associated with cancer were determined using a network pharmacology analysis platform, and 25 key active compounds and 55 key targets of T. wilfordii were identified in our study. A common potential mechanism of T. wilfordii involvement in cancer was disclosed by in-depth network analysis of diseases, functions, and pathways.Finally, the analysis results of the TCM-disease target protein interaction network revealed 5 potential targets;subsequently, a total of 30targets(these 5 targets, as well as 25 previously identified compounds) were subjected to molecular docking. Results: Our results showed that the therapeutic effect of T. wilfordii in cancer is characterized by multiple components, targets, and pathways. The regulation of signaling pathways such as Kaposi sarcoma-associated herpes virus infection, colorectal cancer, small-cell lung cancer, and prostate cancer may be the important pharmacodynamic basis of anticancer therapy. Conclusion: Triptonoditerpenic acid inhibited proliferation and induced apoptosis in SW480 cells. The mechanism may be related to the downregulation of Bcl-2 expression, upregulation of Bax mRNA expression, and expression inhibition of PTGS2.

Protective Effect of Ginsenoside Rd on Lipopolysaccharide-Induced Acute Lung Injury through its Anti-Inflammatory and Anti-Oxidative Activity

Background:Inflammation and oxidation stress are key factors in the mechanism of acute lung injury(ALI).Therefore,suppression of the inflammatory response and oxidative stress could be a potential strategy to treat lipopolysaccharide(LPS)-induced ALI.Ginsenoside Rd(Rd),a natural Ginseng extract,alleviates inflammation and oxidative stress in several diseases such as Alzheimer’s disease and cerebral ischemia,but its effect on ALI is still unclear.Aims and Objectives:To explore the protective effect of Rd on LPS-induced ALI and explored associated mechanisms.Materials and Methods:Mice were divided into five groups:A sham-operated group,a LPS-induced ALI group,and three LPS groups pretreated with Rd doses of 20,40,and 80 mg/kg,respectively.The pathological changes of lung,collagen deposition,pulmonary edema,inflammatory cytokine,oxidative stress and the expression levels of TLR4 and NF-κB were detected.Results:The oral administration of Rd dose dependently attenuated histopathologic changes in the lung,lung edema,pulmonary collagen deposition,protein concentration in bronchoalveolar lavage fluid(BALF),myeloperoxidase(MPO)activity,and inflammatory cell infiltration.In addition,Rd suppressed the LPS-induced inflammatory cytokines tumor necrosis factor-α,interleukin(IL)-6,and IL-1βin BALF.The productions of oxidative stress-related enzymes(catalase,superoxide dismutase,and glutathione peroxidase)in lung tissue were significantly upregulated by Rd administration.However,malondialdehyde and pulmonary MPO activity was reduced in the Rd-pretreated groups when compared with LPS-induced ALI group.Rd treatment also dose dependently suppressed LPS-induced NF-κB activation and TLR4 expression.Conclusion:Overall,these findings provide evidence that Rd pretreatment inhibits LPS-induced ALI through anti-inflammatory and antioxidative actions,suggesting that it could be a promising protective drug for LPS-induced ALI.