Department of Botany, Magadh University, Bodh Gaya, Bihar, India.
Department of Botany, Thakur Prasad Singh College (Patliputra University), Patna, Bihar, India.
Curr Pharm Biotechnol. 2020;21(15):1674-1687. doi: 10.2174/1389201021666200702152000.
Metal Nanoparticles (NPs) have been widely used for various applications in biomedical sciences, including in drug delivery, and as therapeutic agents, but limited owing to their toxicity towards the healthy tissue. This warrants an alternative method, which can achieve the desired activity with much reduced or no toxicity. Being a biological product, Withania somnifera (W. somnifera) is environment friendly, besides being less toxic as compared to metal-based NPs. However, the exact mechanism of action of W. somnifera for its antibacterial activities has not been studied so far.
To develop "silver nanoparticles with root extract of W. somnifera (AgNPs-REWS)" for antimicrobial and anticancer activities. Furthermore, the analysis of their mechanism of action will be studied.
Using the in-silico approach, the molecular docking study was performed to evaluate the possible antibacterial mechanism of W. somnifera phytochemicals such as Anaferine, Somniferine, Stigmasterol, Withaferin A, Withanolide- A, G, M, and Withanone by the inhibition of Penicillin- Binding Protein 4 (PBP4). Next, we utilized a bottom-up approach for the green synthesis of AgNPs- REWS, performed an in-detail phytochemical analysis, confirmed the AgNPs-REWS by SEM, UVvisible spectroscopy, XRD, FT-IR, and HPLC. Eventually, we examined their antibacterial activity.
The result of molecular docking suggests that WS phytochemicals (Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone) possess the higher binding affinity toward the active site of PBP4 as compared to the Ampicillin (-6.39 kcal/mol) reference molecule. These phytochemicals predicted as potent inhibitors of PBP4. Next, as a proof-of-concept, AgNPs- REWS showed significant antibacterial effect as compared to crude, and control; against Xanthomonas and Ralstonia species.
The in-silico and molecular docking analysis showed that active constituents of W. somnifera such as Somniferine, Withaferin A, Withanolide A, Withanolide G, Withanolide M, and Withanone possess inhibition potential for PBP4 and are responsible for the anti-bacterial property of W. somnifera extract. This study also establishes that AgNPs via the green synthesis with REWS showed enhanced antibacterial activity towards pathogenic bacteria.
金属纳米粒子（NPs）已广泛应用于生物医学科学的各种领域，包括药物输送和治疗剂，但由于其对健康组织的毒性而受到限制。这就需要一种替代方法，该方法可以在降低或消除毒性的情况下实现所需的活性。作为一种生物制品，南非醉茄（W. somnifera）对环境友好，而且毒性比基于金属的 NPs 小。然而，W. somnifera 发挥其抗菌作用的确切机制尚未得到研究。
开发“载有 W. somnifera 根提取物的银纳米粒子（AgNPs-REWS）”，用于抗菌和抗癌活性。此外，还将研究其作用机制。
使用计算机模拟方法，进行分子对接研究，评估 W. somnifera 植物化学物质（如 Anaferine、Somniferine、Stigmasterol、Withaferin A、Withanolide-A、Withanolide-G、Withanolide-M 和 Withanone）通过抑制青霉素结合蛋白 4（PBP4）发挥抗菌作用的可能机制。接下来，我们采用自下而上的方法进行 AgNPs-REWS 的绿色合成，进行详细的植物化学分析，通过 SEM、UV-可见光谱、XRD、FT-IR 和 HPLC 对 AgNPs-REWS 进行确认。最后，我们检查了它们的抗菌活性。
分子对接的结果表明，与 Ampicillin（-6.39 kcal/mol）参考分子相比，WS 植物化学物质（Somniferine、Withaferin A、Withanolide A、Withanolide G、Withanolide M 和 Withanone）对 PBP4 的活性位点具有更高的结合亲和力。这些植物化学物质被预测为 PBP4 的有效抑制剂。接下来，作为概念验证，与粗提物和对照物相比，AgNPs-REWS 对黄单胞菌和罗尔斯顿菌属的物种表现出显著的抗菌作用。
计算机模拟和分子对接分析表明，W. somnifera 的活性成分，如 Somniferine、Withaferin A、Withanolide A、Withanolide G、Withanolide M 和 Withanone，对 PBP4 具有抑制潜力，是 W. somnifera 提取物具有抗菌特性的原因。这项研究还表明，通过与 REWS 进行绿色合成的 AgNPs 对致病菌表现出增强的抗菌活性。
