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Abstract：
The present study predicts the molecular targets and druglike properties of the phyto-compound piperine (PIP) by in silico studies including molecular docking simulation, druglikeness prediction and ADME analysis for prospective therapeutic benefits against diabetic complications. PIP was encapsulated in biodegradable polymer poly-lactide-co-glycolide (PLGA) to form nanopiperine (NPIP) and their physico-chemical properties were characterized by AFM and DLS. ∼ 30 nm sized NPIP showed 86.68% encapsulation efficiency and - 6 mV zeta potential, demonstrated great interactive stability and binding with CT-DNA displaying upsurge in molar ellipticity during CD spectroscopy. NPIP lowered glucose levels in peripheral circulation by > 65 mg/dL compared to disease model and improved glucose influx in alloxan-induced in vivo and in vitro diabetes models concerted with 3-folds decrease in ROS production, ROS-induced DNA damage and 27.24% decrease in nuclear condensation. The 25% increase in % cell viability and inhibition in chromosome aberration justified the initiation of p53 and PARP DNA repairing protein expression and maintenance of Hsp90. Thus, the experimental study corroborated well with in silico predictions of modulating the p53/PARP-1/Hsp90 axis, with predicted dock score value of - 8.72, - 8.57, - 8.76 kcal/mol respectively, validated docking-based preventive approaches for unravelling the intricacies of molecular signalling and nano-drug efficacy as therapeutics for diabetics.
摘要：
本研究通过包括分子对接模拟在内的计算机模拟研究预测了植物化合物胡椒碱（PIP）的分子靶标和药物性质，糖尿病并发症的前瞻性治疗益处的药物相似度预测和ADME分析。将PIP封装在可生物降解的聚合物聚丙交酯-共-乙交酯（PLGA）中以形成纳米perine（NPIP），并通过AFM和DLS表征其物理化学性质。30nm大小的NPIP显示86.68%的封装效率和-6mV的zeta电位，在CD光谱学过程中，显示出很好的相互作用稳定性和与CT-DNA的结合显示出摩尔椭圆率的激增。与疾病模型相比，NPIP可降低外周循环中的葡萄糖水平>65mg/dL，并改善四氧嘧啶诱导的体内和体外糖尿病模型中的葡萄糖流入，同时ROS产生减少3倍。ROS诱导的DNA损伤和27.24%的核缩合减少。25％的细胞活力和染色体畸变的抑制增加了25％，证明了p53和PARPDNA修复蛋白表达的启动和Hsp90的维持。因此，实验研究证实了调节p53/PARP-1/Hsp90轴的计算机预测，预测码头评分值分别为-8.72、-8.57、-8.76kcal/mol，经过验证的基于对接的预防方法，可揭示分子信号和纳米药物作为糖尿病患者治疗方法的复杂性。
