Herb pair Danggui-Honghua has been frequently used for treatment of blood stasis syndrome (BSS) in China, one of the most common clinical pathological syndromes in traditional Chinese medicine (TCM). However, its therapeutic mechanism has not been clearly elucidated. In the present study, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the mechanisms of this herb pair. Thirty-one active ingredients of Danggui-Honghua possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 42 BSS-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as HMOX1, NOS2, NOS3, HIF1A and PTGS2 were mainly involved in TNF signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway and neurotrophin signaling pathway. The contribution index of every active ingredient also indicated six compounds, including hydroxysafflor yellow A, safflor yellow A, safflor yellow B, Z-ligustilide, ferulic acid, and Z-butylidenephthalide, as the principal components of this herb pair. These results successfully explained the polypharmcological mechanisms underlying the efficiency of Danggui-Honghua for BSS treatment, and also probed into the potential novel therapeutic strategies for BSS in TCM.
The rapidly increasing diabetes mellitus (DM) is becoming a major global public health issue. Traditional Chinese medicine (TCM) has a long history of the treatment of DM with good efficacy. Huangqi and Huanglian are one of the most frequently prescribed herbs for DM, and the combination of them occurs frequently in antidiabetic formulae. However, the synergistic mechanism of Huangqi (Radix Astragali) and Huanglian (Rhizoma Coptidis) has not been clearly elucidated. To address this problem, a feasible system pharmacology model based on chemical, pharmacokinetic and pharmacological data was developed via network construction approach to clarify the synergistic mechanisms of these two herbs. Forty-three active ingredients of Huangqi (mainly astragalosides and isoflavonoids) and Huanglian (primarily isoquinoline alkaloids) possessing favorable pharmacokinetic profiles and biological activities were selected, interacting with 50 DM-related targets to provide potential synergistic therapeutic actions. Systematic analysis of the constructed networks revealed that these targets such as GLUT2, NOS2, PTP1B, and IGF1R were mainly involved in PI3K-Akt signaling pathway, insulin resistance, insulin signaling pathway, and HIF-1 signaling pathway, and were mainly located in retina, pancreatic islet, smooth muscle, immunity-related organ tissues, and whole blood. The contribution index of every active ingredient also indicated five compounds, including berberine (BBR), astragaloside IV (AIV), quercetin, palmatine, and astragalus polysaccharides, as the principal components of this herb combination. These results successfully explained the polypharmcological and synergistic mechanisms underlying the efficiency of Huangqi and Huanglian for the treatment of DM and its complications.
This review summarized the botany, traditional uses, phytochemistry and pharmacology ofCudrania tricuspidata, and the limitations of the studies on this species were also discussed so as to serve as the basis for further research and development of this medicinal plant.
Currently, DNA topoisomerase I (Topo I) inhibitors constitute a family of antitumor agents with demonstrated clinical effects on human malignancies. However, the clinical uses of these agents have been greatly limited due to their severe toxic effects. Therefore, it is urgent to find and develop novel low toxic Topo I inhibitors. In recent years, during our ongoing research on natural antitumor products, a collection of low cytotoxic or non-cytotoxic compounds with various structures were identified from marine invertebrates, plants, and their symbiotic microorganisms. In the present study, new Topo I inhibitors were discovered from low cytotoxic and non-cytotoxic natural products by virtual screening with docking simulations in combination with bioassay test. In total, eight potent Topo I inhibitors were found from 138 low cytotoxic or non-cytotoxic compounds from coral-derived fungi and plants. All of these Topo I inhibitors demonstrated activities against Topo I-mediated relaxation of supercoiled DNA at the concentrations of 5–100 µM. Notably, the flavonoids showed higher Topo I inhibitory activities than other compounds. These newly discovered Topo I inhibitors exhibited structurally diverse and could be considered as a good starting point for the development of new antitumor lead compounds.
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