Cytochrome P450-mediated herb-drug interaction (HDI) of Polygonum multiflorum Thunb. based on pharmacokinetic studies and in vitro inhibition assays

Xing, Yanchao; Qiao, Yu; Zhou, Lin; Cui, Wen; Zhang, Yuxin; Bi, Yajuan; Zhang, Youcai; Fu, Zhifei; Han, Lifeng

doi:10.1016/j.phymed.2023.154710

Cited by 5 publications

(1 citation statement)

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“…Cytochrome P450 enzymes are a family of enzymes responsible for metabolizing a wide range of drugs and other xenobiotics (foreign substances) in the body. Inhibiting specific CYP enzymes can enhance drug bioavailability, extend half-life, and mitigate drug-drug interactions (Chatterjee et al 2022 ; He et al 2023 ; Xing et al 2023 ). Each of the compounds demonstrated substantial gastrointestinal absorption, suggesting a pronounced capacity for absorption within the human intestinal tract (Table 2 ).…”

Section: Resultsmentioning

confidence: 99%

Network pharmacology and molecular docking: combined computational approaches to explore the antihypertensive potential of Fabaceae species

Shahzadi,

Yousaf,

Anjum

et al. 2024

Bioresour. Bioprocess.

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Hypertension is a major global public health issue, affecting quarter of adults worldwide. Numerous synthetic drugs are available for treating hypertension; however, they often come with a higher risk of side effects and long-term therapy. Modern formulations with active phytoconstituents are gaining popularity, addressing some of these issues. This study aims to discover novel antihypertensive compounds in Cassia fistula, Senna alexandrina, and Cassia occidentalis from family Fabaceae and understand their interaction mechanism with hypertension targeted genes, using network pharmacology and molecular docking. Total 414 compounds were identified; initial screening was conducted based on their pharmacokinetic and ADMET properties, with a particular emphasis on adherence to Lipinski's rules. 6 compounds, namely Germichrysone, Benzeneacetic acid, Flavan-3-ol, 5,7,3',4'-Tetrahydroxy-6, 8-dimethoxyflavon, Dihydrokaempferol, and Epiafzelechin, were identified as effective agents. Most of the compounds found non-toxic against various indicators with greater bioactivity score. 161 common targets were obtained against these compounds and hypertension followed by compound-target network construction and protein–protein interaction, which showed their role in diverse biological system. Top hub genes identified were TLR4, MMP9, MAPK14, AKT1, VEGFA and HSP90AA1 with their respective associates. Higher binding affinities was found with three compounds Dihydrokaempferol, Flavan-3-ol and Germichrysone, −7.1, −9.0 and −8.0 kcal/mol, respectively. The MD simulation results validate the structural flexibility of two complexes Flavan-MMP9 and Germich-TLR4 based on no. of hydrogen bonds, root mean square deviations and interaction energies. This study concluded that C. fistula (Dihydrokaempferol, Flavan-3-ol) and C. occidentalis (Germichrysone) have potential therapeutic active constituents to treat hypertension and in future novel drug formulation. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%