In Silico ADME and Molecular Simulation Studies of Pharmacological Activities of Phytoconstituents of Annona muricata (L.) Fruit

Iseoluwa Isaac Ajayi, T. Fatoki, Ayodele Sunday Alonge, C. D. Famusiwa, I. Saliu, O. S. Akinlolu, C. Onodugo, Rachel Temitop Ojo
{"title":"In Silico ADME and Molecular Simulation Studies of Pharmacological Activities of Phytoconstituents of Annona muricata (L.) Fruit","authors":"Iseoluwa Isaac Ajayi, T. Fatoki, Ayodele Sunday Alonge, C. D. Famusiwa, I. Saliu, O. S. Akinlolu, C. Onodugo, Rachel Temitop Ojo","doi":"10.31665/jfb.2024.18374","DOIUrl":null,"url":null,"abstract":"Annona muricata Lin is known for its ethnomedicinal uses as food, decoctions, or infusions to address various conditions like skin infections, fever, diabetes, insomnia, malaria, hypertension, nervous disorders, diarrhea, and cancer. The study aimed to analyze the phytochemicals such as acetogenins, alkaloids, cyclopeptides, and flavonoids, present in A. muricata fruit, evaluate their pharmacokinetics, and understand binding dynamics with key molecular targets relevant to human well-being. Results indicated a mix of high and low gastrointestinal absorption (GIA) among A. muricata phytochemicals, with some demonstrating blood-brain barrier (BBB) permeability. Molecular target prediction highlighted frequent interactions with Programmed cell death protein 4 (PDCD4). Protein-protein interaction analysis revealed central connectivity of tyrosinase (TYR), Tyrosine 3-monooxygenase (TH), interleukin 2 (IL2), and others. Molecular docking results identified Luteolin 3´7-di-O-glucoside with the highest binding affinity for PDCD4 (-7.65 kcal.mol-1), followed by Annonaine (-7.294 kcal.mol-1); meanwhile, Dexamethasone (standard compound) exhibited a binding affinity of -6.682 kcal.mol-1. Molecular dynamic simulation indicated a stable binding energy ΔGbind (Total) for the Annonaine - PDCD4 complex (-11.240 kcal.mol-1) and Dexamethasone - PDCD4 complex (-18.909 kcal.mol-1). In conclusion, this study suggests potential anticancer properties of A. muricata based on modulation of PDCD4 protein, influencing the CDK/Akt/STAT3 pathway. Further in vivo investigations are necessary to validate these findings.","PeriodicalId":15882,"journal":{"name":"Journal of Food Bioactives","volume":"11 5","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Food Bioactives","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.31665/jfb.2024.18374","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

Abstract

Annona muricata Lin is known for its ethnomedicinal uses as food, decoctions, or infusions to address various conditions like skin infections, fever, diabetes, insomnia, malaria, hypertension, nervous disorders, diarrhea, and cancer. The study aimed to analyze the phytochemicals such as acetogenins, alkaloids, cyclopeptides, and flavonoids, present in A. muricata fruit, evaluate their pharmacokinetics, and understand binding dynamics with key molecular targets relevant to human well-being. Results indicated a mix of high and low gastrointestinal absorption (GIA) among A. muricata phytochemicals, with some demonstrating blood-brain barrier (BBB) permeability. Molecular target prediction highlighted frequent interactions with Programmed cell death protein 4 (PDCD4). Protein-protein interaction analysis revealed central connectivity of tyrosinase (TYR), Tyrosine 3-monooxygenase (TH), interleukin 2 (IL2), and others. Molecular docking results identified Luteolin 3´7-di-O-glucoside with the highest binding affinity for PDCD4 (-7.65 kcal.mol-1), followed by Annonaine (-7.294 kcal.mol-1); meanwhile, Dexamethasone (standard compound) exhibited a binding affinity of -6.682 kcal.mol-1. Molecular dynamic simulation indicated a stable binding energy ΔGbind (Total) for the Annonaine - PDCD4 complex (-11.240 kcal.mol-1) and Dexamethasone - PDCD4 complex (-18.909 kcal.mol-1). In conclusion, this study suggests potential anticancer properties of A. muricata based on modulation of PDCD4 protein, influencing the CDK/Akt/STAT3 pathway. Further in vivo investigations are necessary to validate these findings.
关于鼠李子(Annona muricata (L.))果实中植物成分药理活性的 In Silico ADME 和分子模拟研究
Annona muricata Lin因其作为食物、煎剂或输液的民族药用而闻名,可用于治疗各种疾病,如皮肤感染、发烧、糖尿病、失眠、疟疾、高血压、神经紊乱、腹泻和癌症。该研究旨在分析A. muricata果实中的植物化学物质,如乙酰甙元、生物碱、环肽和黄酮类化合物,评估它们的药代动力学,并了解与人类健康相关的关键分子靶点的结合动态。结果表明,鼠李果植物化学物质的胃肠道吸收率(GIA)有高有低,其中一些具有血脑屏障(BBB)渗透性。分子靶标预测强调了与程序性细胞死亡蛋白 4 (PDCD4) 的频繁相互作用。蛋白质-蛋白质相互作用分析表明了酪氨酸酶(TYR)、酪氨酸 3-单氧化酶(TH)、白细胞介素 2(IL2)等的中心连接性。分子对接结果表明,木犀草素 3´7-di-O- 葡萄糖苷与 PDCD4 的结合亲和力最高(-7.65 kcal.mol-1),其次是安诺那因(-7.294 kcal.mol-1);而地塞米松(标准化合物)的结合亲和力为-6.682 kcal.mol-1。分子动力学模拟表明,安诺那因-PDCD4 复合物(-11.240 kcal.mol-1 )和地塞米松-PDCD4 复合物(-18.909 kcal.mol-1 )的稳定结合能ΔGbind (Total)。总之,这项研究表明,A. muricata 具有潜在的抗癌特性,其基础是调节 PDCD4 蛋白,影响 CDK/Akt/STAT3 通路。要验证这些发现,还需要进一步的体内研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信