Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Zhou, Shanshan; Ai, Zhongzhu; Li, Weinan; Peng, You; Wu, Caicong; Li, Liang; Hu, Yuanyang; Ba, Yi

doi:10.3389/fphar.2020.00425

Cited by 64 publications

(41 citation statements)

References 58 publications

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“…The liver promotes C-reactive protein production in hepatocytes by excreting circulating triglycerides and free fatty acids and triggering the release of cytokines which play key roles in inflammation ( Zhong et al, 2020 ). The observed diminution in VRC metabolism during inflammation may be explained by the concomitant synthesis of hub targets of the active compounds, namely TNF-α, IL-1β and IL-6 which in turn, alter the expression of specific transcription factors such as NF-κB, leading to a vicious circle of inflammatory response ( Zhou et al, 2020 ). Our results support the concept that disruption of metabolic capacity is accompanied by an increased in liver damage due to inflammation, CRP levels increased with the VRC exposure level.…”

Section: Discussionmentioning

confidence: 99%

Bacteroides Fragilis Polysaccharide A Ameliorates Abnormal Voriconazole Metabolism Accompanied With the Inhibition of TLR4/NF-κB Pathway

Wang

Xun

et al. 2021

Front. Pharmacol.

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The antifungal agent voriconazole (VRC) exhibits extreme inter-individual and intra-individual variation in terms of its clinical efficacy and toxicity. Inflammation, as reflected by C-reactive protein (CRP) concentrations, significantly affects the metabolic ratio and trough concentrations of voriconazole. Bacteroides fragilis (B. fragilis) is an important component of the human intestinal microbiota. Clinical data have shown that B. fragilis abundance is comparatively higher in patients not presenting with adverse drug reactions, and inflammatory cytokine (IL-1β) levels are negatively correlated with B. fragilis abundance. B. fragilis natural product capsular polysaccharide A (PSA) prevents various inflammatory disorders. We tested the hypothesis that PSA ameliorates abnormal voriconazole metabolism by inhibiting inflammation. Germ-free animals were administered PSA intragastrically for 5 days after lipopolysaccharide (LPS) stimulation. Their blood and liver tissues were collected to measure VRC concentrations. PSA administration dramatically improved the resolution phase of LPS-induced hepatic VRC metabolism and inflammatory factor secretion. It reversed inflammatory lesions and alleviated hepatic pro-inflammatory factor secretion. Both in vitro and in vivo data demonstrate that PSA reversed LPS-induced IL-1β secretion, downregulated the TLR4/NF-κB signaling pathway and upregulated CYP2C19 and P-gp. To the best of our knowledge, this study is the first to show that PSA from the probiotic B. fragilis ameliorates abnormal voriconazole metabolism by inhibiting TLR4-mediated NF-κB transcription and regulating drug metabolizing enzyme and transporter expression. Thus, PSA could serve as a clinical adjunct therapy.

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Section: Discussionmentioning

confidence: 99%

Bacteroides Fragilis Polysaccharide A Ameliorates Abnormal Voriconazole Metabolism Accompanied With the Inhibition of TLR4/NF-κB Pathway

Wang

Xun

et al. 2021

Front. Pharmacol.

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“…Network pharmacology is based upon the theories of system biology and multi-directional pharmacology ( Zhou Y. et al, 2020 ). It allows the construction of biological networks and network visualization analysis of bioactive components, hub targets, and signaling pathways to elucidate the complex relationships between drugs and diseases ( Zhou S. et al, 2020 ). Network pharmacology can reveal the mechanisms of action of a TCM formula with multiple components and target characteristics ( Li and Zhang, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

“Fei Yan No. 1” as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study

Zhong-zhu

Zhou

et al. 2020

Front. Pharmacol.

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There has been a large global outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), representing a major public health issue. In China, combination therapy, including traditional Chinese medicine (TCM) as a treatment for COVID-19 has been used widely. “Fei Yan No. 1” (QFDYG) is a formula recommended by the Hubei Government to treat COVID-19. A retrospective study of 84 COVID-19 patients from Hubei Provincial Hospital of TCM and Renmin Hospital of Hanchuan was conducted to explore the clinical efficacy of QFDYG combination therapy. TCMSP and YaTCM databases were used to determine the components of all Chinese herbs in QFDYG. Oral bioavailability (OB) ≥ 30% and drug-like (DL) quality ≥ 0.18 were selected as criteria for screening the active compounds identified within the TCMSP database. The targets of active components in QFDYG were determined using the Swiss TargetPrediction (SIB) and Targetnet databases. The STRING database and the Network Analyzer plugin in Cytoscape were used to obtain protein-protein interaction (PPI) network topology parameters and to identify hub targets. Gene Ontology (GO) enrichment was conducted using FunRich version 3.1.3, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using ClueGO version 2.5.6 software. PPI and compound-pathway (C-T) networks were constructed using Cytoscape 3.6.0. Compared with the control group, combined treatment with QFDYG resulted in a significantly higher rate of patients recovering from symptoms and shorter the time. After 14 days of treatment, QFDYG combined treatment increased the proportion of patients testing negative for SARS-CoV-2 nucleic acid by RT-PCR. Compared with the control group, promoting focal absorption and inflammation as viewed on CT images. GO and KEGG pathway enrichment indicated that QFDYG principally regulated biological processes, such as inflammation, an immune response, and apoptosis. The present study revealed that QFDYG combination therapy offered particular therapeutic advantages, indicating that the theoretical basis for the treatment of COVID-19 by QFDYG may play an antiviral and immune response regulation through multiple components, targets, and pathways, providing reference for the clinical treatment of COVID-19.

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“…In vitro metabolic studies can reasonably predict the in vivo pharmacokinetic behaviour of candidate compounds by using the in vitro metabolic parameters of candidate compounds in the early stage of new drug development [25]. It not only guides the selection of models for later pharmacodynamics, pharmacokinetic and safety evaluations, but also narrows the screening scope of in vivo studies, which has broad application prospects [25][26][27][28][29]. The method of using cell lines to study drug metabolism in vitro can eliminate the interference of many factors in vivo and provide a reliable theoretical basis for the overall experiment.…”

Section: Metabolismmentioning

confidence: 99%

Study on pharmacological properties and cell absorption metabolism of novel daidzein napsylates

Jiao

Peng

et al. 2021

R. Soc. open sci.

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Novel daidzein napsylates (DD4 and DD5) were synthesized by microwave irradiation, according to structural modification of daidzein (DAI) using the principle of pharmacokinetic transformation. The pharmacological properties of DD4 and DD5 were evaluated via high performance liquid chromatography (HPLC) and calculated based on the drug design software C hem A xon 16.1.18. The cell uptake changes of DD4 and DD5 were investigated to analyse the structure–property relationship. The metabolisms of DD4 and DD5 were analysed by HPLC-mass spectrometry in human aortic vascular smooth muscle cells (HAVSMCs) and their possible metabolic pathways were inferred in vivo . The results showed that the solubility of DD4 and DD5 was increased by 2.79 × 10 5 and 2.16 × 10 5 times compared to that of DAI, separately, in ethyl acetate. The maximum absorption rates of DD4 and DD5 were enhanced by 4.3–4.5 times relative to DAI. Preliminary studies on metabolites of DD4 and DD5 in HAVSMCs showed that DD4 and DD5 were hydrolysed into DAI under the action of intracellular hydrolase in two ways, ester hydrolysis or ether hydrolysis. Then, DAI was combined with glucuronic acid to form daidzein monoglucuronate under the action of uridine diphosphate (UDP)-glucuronidase. Meanwhile, it was also found that metabolite M5 of DD5 could undergo glucuronidation under the action of UDP-glucuronosyltransferase and competitive sulphation under the action of sulphotransferase to produce its sulfate conjugate M7. Analysis of structure–property relationships indicated that the absorption and utilization of drugs is closely relative to the physical properties and could be improved by adjusting the liposolubility. The pharmaceutical properties were optimized comprehensively after DAI was modified by naphthalene sulphonate esterification. This indicates that this kind of derivatives may have relatively good absorption and transport characteristics and biological activities in vivo . The research on biological activities of the new derivatives (DD4 and DD5) is ongoing in our laboratory.

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Deciphering the Pharmacological Mechanisms of Taohe-Chengqi Decoction Extract Against Renal Fibrosis Through Integrating Network Pharmacology and Experimental Validation In Vitro and In Vivo

Cited by 64 publications

References 58 publications

Bacteroides Fragilis Polysaccharide A Ameliorates Abnormal Voriconazole Metabolism Accompanied With the Inhibition of TLR4/NF-κB Pathway

Bacteroides Fragilis Polysaccharide A Ameliorates Abnormal Voriconazole Metabolism Accompanied With the Inhibition of TLR4/NF-κB Pathway

“Fei Yan No. 1” as a Combined Treatment for COVID-19: An Efficacy and Potential Mechanistic Study

Study on pharmacological properties and cell absorption metabolism of novel daidzein napsylates

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