作者: Yang, Shusheng ; Zhang, Liang ; Zhang, Te ; Xiang, Ke ; Xu, Jiaixin ; Chen, Yunhe ; Guo, Yang ; Liu, Ying ; Ke, Wei ; Liu, Xuewen ; Si, Yuan ; Zhou, Tong ; Yang, Rui

2025-04-01·Journal of Ethnopharmacology

Deciphering the effective components of a TCM formula for atherosclerosis by three-dimensional pattern recognition of exogenous components correlated with endogenous metabolites

Article

作者: Wang, Qi ; Chen, Xuanjing ; Yao, Xinsheng ; Wu, Huanlin ; Zhang, Xinya ; Lin, Yihan ; Lin, Pei ; Xu, Danping ; Yao, Zhihong ; Qin, Zifei ; Guo, Jianwen ; He, Rongrong ; He, Liangliang

ETHNOPHARMACOLOGICAL RELEVANCEThe deciphering of effective components is crucial for understanding the role they play and how they function in traditional Chinese medicine (TCM) formulae. However, this remains a significant challenge for these complex systems with multiple components, targets, and pathways, despite their therapeutic benefits.AIM OF THE STUDYThree-dimensional pattern recognition of exogenous components correlated with endogenous metabolites was proposed to discover the effective components of Gualou-Xiebai-Banxia decoction (GXB), a famous classical TCM formula for effective improvement of atherosclerosis (AS).MATERIALS AND METHODSThe potential effective exogenous components were determined by three-dimensional pattern recognition of abundance, bioavailability and AS-related activity. The efficacy of GXB in attenuating AS was evaluated using an Apolipoprotein E-deficient (ApoE^-/-) mice model subjected to a high-fat diet regimen. Plasma metabolomics was developed to dig out GXB efficacy-related endogenous metabolites. Next, the potential effective exogenous components and GXB efficacy-related endogenous metabolites were combined with AS targets to develop correlation analysis, so as to explore candidate effective components and potential mechanisms of GXB. Further, the effective components were validated by oxidized low-density lipoprotein-induced RAW 264.7 macrophages.RESULTSA total of 30 potential effective exogenous components in GXB were ascertained by three-dimensional pattern recognition after conducting Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) analysis. GXB demonstrated a significant ameliorative effect on atherosclerotic symptoms in ApoE^-/- mice under a high-fat diet, as evidenced by decreasing serum lipid levels, atherosclerotic plaques (aorta and aortic root) and IL-6 content. Subsequently, metabolomics results revealed that it was associated with the regulation of endogenous metabolites, including organic acids, amino acid, fatty acids and glycerophospholipid. Next, the correlation analysis was constructed with AS targets by the network of "potential effective exogenous components-AS targets-endogenous metabolites", tentatively inferring that 18 exogenous components were candidate effective components, and lipid metabolism was the major regulation pathway of GXB. Furthermore, GXB suppressed lipid accumulation in vivo/vitro through increasing expressions of PPAGγ, ABCA1, ABCG1, and SR-B1 related to cholesterol efflux. Cucurbitacin B and 5 (6)-ene-macrostemonoside B were demonstrated as the effective components with inhibitory activity on foam cell formation and lipid accumulation.CONCLUSIONThree-dimensional pattern recognition of exogenous components correlated with endogenous metabolites was proposed and effectively utilized to demystify the effective components of GXB in AS prevention. This strategy also provided a reference for the related studies of other classical TCM formulae.

2025-04-01·Molecular Diversity

From antibiotic to antiviral: computational screening reveals a multi-targeting antibiotic from Streptomyces spp. against Nipah virus fusion proteins

Article

作者: Macalalad, Mark Andrian B ; Odchimar, Nyzar Mabeth O ; Orosco, Fredmoore L

Nipah Virus is a re-emerging zoonotic paramyxovirus that poses a significant threat to both swine industry and human health. The pursuit of potential antiviral agents with both preventive and therapeutic properties holds promise for targeting such viruses. To expedite this search, leveraging computational biology is essential. Streptomyces is renowned for its capacity to produce large and diverse metabolites with promising bioactivities. In the current study, we conducted a comprehensive structure-based virtual screening of 6524 Streptomyces spp. metabolites sourced from the StreptomeDB database to evaluate their potential inhibitory effects on three Nipah virus fusion (NiVF) protein conformations: NiVF pre-fusion 1-mer (NiVF-1mer), pre-fusion 3-mer (NiVF-3mer), and NiVF post-fusion (NiVF-PoF). Prior to virtual screening, the drug-likeness of Streptomyces spp. compounds was profiled using ADMET properties. From the 913 ADMET-filtered compounds, the subsequent targeted and confirmatory blind docking analysis revealed that S896 or virginiamycin M1, a known macrolide antibiotic, showed a maximum binding affinity with the NiVF proteins, suggesting a multi-targeting inhibitory property. In addition, the 200-ns molecular dynamics simulation and MM/PBSA analyses revealed stable and strong binding affinity between the NiVF-S896 complexes, indicating favorable interactions between S896 and the target proteins. These findings suggest the potential of virginiamycin M1, an antibiotic, as a promising multi-targeting antiviral drug. However, in vitro and in vivo experimental validations are necessary to assess their safety and efficacy.

100 项与 Cucurbitacin B 相关的药物交易

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