PDF(Pubmed)
Abstract：
The search for bioactive compounds in natural products holds promise for discovering new pharmacologically active molecules. This study explores the anti-inflammatory potential of açaí (Euterpe oleracea Mart.) constituents against the NLRP3 inflammasome using high-throughput molecular modeling techniques. Utilizing methods such as molecular docking, molecular dynamics simulation, binding free energy calculations (MM/GBSA), and in silico toxicology, we compared açaí compounds with known NLRP3 inhibitors, MCC950 and NP3-146 (RM5). The docking studies revealed significant interactions between açaí constituents and the NLRP3 protein, while molecular dynamics simulations indicated structural stabilization. MM/GBSA calculations demonstrated favorable binding energies for catechin, apigenin, and epicatechin, although slightly lower than those of MCC950 and RM5. Importantly, in silico toxicology predicted lower toxicity for açaí compounds compared to synthetic inhibitors. These findings suggest that açaí-derived compounds are promising candidates for developing new anti-inflammatory therapies targeting the NLRP3 inflammasome, combining efficacy with a superior safety profile. Future research should include in vitro and in vivo validation to confirm the therapeutic potential and safety of these natural products. This study underscores the value of computational approaches in accelerating natural product-based drug discovery and highlights the pharmacological promise of Amazonian biodiversity.
摘要：
在天然产物中寻找生物活性化合物有望发现新的药理活性分子。这项研究探讨了açaí（EuterpeoleraceaMart。)使用高通量分子建模技术对抗NLRP3炎性体的成分。利用分子对接等方法，分子动力学模拟,结合自由能计算(MM/GBSA)，在硅毒理学中，我们将açaí化合物与已知的NLRP3抑制剂进行了比较，MCC950和NP3-146（RM5）。对接研究揭示了açaí成分与NLRP3蛋白之间的显着相互作用，而分子动力学模拟表明结构稳定。MM/GBSA计算证明了儿茶素的有利结合能，芹菜素,还有表儿茶素,虽然略低于MCC950和RM5。重要的是,与合成抑制剂相比，硅毒理学预测açaí化合物的毒性较低。这些发现表明，açaí衍生的化合物是开发针对NLRP3炎性体的新型抗炎疗法的有希望的候选人。结合疗效与优越的安全性。未来的研究应包括体外和体内验证，以确认这些天然产物的治疗潜力和安全性。这项研究强调了计算方法在加速基于天然产品的药物发现中的价值，并强调了亚马逊生物多样性的药理前景。
