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

作　　者：Zainab Shahzadi Zubaida Yousaf Irfan Anjum Muhammad Bilal Hamna Yasin Arusa Aftab Anthony Booker Riaz Ullah Ahmed Bari 

机构地区：[1]Department of Botany,Lahore College for Women University,Lahore,Pakistan [2]Department of Basic Medical Sciences,Shifa College of Pharmaceutical Sciences,Shifa Tameer-e-Millat University,Islamabad,Pakistan [3]Centers for Applied Molecular Biology,University of the Punjab,Lahore,Pakistan [4]Research Centre for Optimal Health,School of Life Sciences,College of Liberal Arts and Sciences,University of Westminster,115 New Cavendish Street,London W1W 6UW,UK [5]Research Group‘Pharmacognosy and Phytotherapy’,UCL School of Pharmacy,Univ.London,29-39 Brunswick Sq.,London WC1N 1AX,UK [6]Department of Pharmacognosy,College of Pharmacy King,Saud University,Riyadh,Saudi Arabia [7]Department of Pharmaceutical Chemistry,College of Pharmacy King,Saud University,Riyadh,Saudi Arabia.

出　　处：《Bioresources and Bioprocessing》2024年第1期721-744,共24页生物资源与生物加工(英文)

基　　金：Researchers supporting Project number RSP2024R346,King Saud University Riyadh Saudi Arabia.

摘　　要：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.

关 键 词：Hypertension Herbal medicine PHYTOCHEMICALS FABACEAE Cassia species Network pharmacology Molecular docking 

分 类 号：R54[医药卫生—心血管疾病]