Abstract
BackgroundTripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases. Nevertheless, its pharmacological and toxicological profiles still remain to be elucidated. In the current study, the network pharmacology approach was applied to identify synergistic interaction and mechanism of efficacy and toxicity for THH from a holistic perspective.MethodsThe compounds from THH were collected using literature retrieval and relevant databases. After the production of putative therapeutic targets for dominant diseases and harmful targets of adverse reactions (ADRs) induced by THH, the protein-protein interactions (PPIs), topological analysis and pathway enrichment were established to distinguish the hub targets and pathways. Additionally, the binding activity of candidate ingredients with core targets were revealed by molecular docking simulation.ResultsA total of eight bioactive components in THH were enrolled, and 633 targets were responsible for rheumatoid arthritis (RA), 1067 targets were corresponding to systemic lupus erythematosus (SLE), 1318 targets of ADRs were obtained. The results of enrichment analysis among THH-RA, THH-SLE and THH-ADR networks indicated that pathway in cancer, hepatitis B, rheumatoid arthritis, and PI3K-Akt signaling pathway might participate in THH for treating RA and SLE. Besides, the mechanism of ADRs that induced by THH were associated with viral carcinogenesis, p53 signaling pathway, PI3K-Akt signaling pathway, and so on. Whereas, these active ingredients of THH exerted the superior binding activities with crucial targets including STAT3, VEGFA, TP53 and MMP9 that functioned synergistically efficacy and toxicity as observed via molecular docking simulation.ConclusionThe present research preliminarily interpreted the synergistic interaction of therapeutic and toxicological mechanisms for THH through the comprehensive analysis of relationship and binding activity between primary components and core targets, providing a feasible and promising approach to facilitate the development of toxic and irreplaceable herbs.
Highlights
Tripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases
With respect to morphologically similar species from Tripterygium genus, THH exhibits the similarity on therapeutic effects, clinical indications and toxicity with Tripterygium wilfordii Hook, besides, it has been widely affirmed in treating chronic autoimmune diseases due to mild pharmaceutical advantages and lasting immunosuppressive effects [5]
Accumulating evidence suggests that THH and its active ingredients could induce severe adverse reactions (ADRs), hepatotoxicity and nephrotoxicity, these side effects can display the higher serum levels of alanine transaminase, aspartate transaminase, serum creatinine and urea nitrogen, and are responsible for inhibiting CYP450 and the transporters [14,15,16,17]
Summary
Tripterygium hypoglaucum Hutch (THH) both has prominent efficacy and unwarranted toxicity in the treatment of autoimmune diseases. Current toxicological studies often focus on acute toxicity, reproductive toxicity and nephrotoxicity for its similar species from Tripterygium genus, Tripterygium wilfordii Hook, or some components from THH [25,26,27,28,29]. With this in mind, the approaches of network pharmacology combined with molecular docking were employed to distinguish bioactive components and predict key targets, for disclosing synergistic interaction of efficacious and toxic mechanisms for THH from a systemic and holistic perspective
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