Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan.
Faculty of Pharmacy, Abasyn University, Peshawar, 25000, Pakistan.
Naunyn Schmiedebergs Arch Pharmacol. 2022 Feb;395(2):195-215. doi: 10.1007/s00210-021-02192-1. Epub 2022 Jan 7.
In the present study, poncirin was evaluated against paracetamol-induced liver injury using in vivo and computational approaches. Paracetamol was administered intraperitoneally (i.p,) to establish liver injury in mice and, subsequently, to investigate the hepatoprotective effect of poncirin (administered intraperitoneally) on liver injury. The effect of poncirin was evaluated against the liver injury markers and inflammatory cytokines. Similarly, in the present study, the antioxidants and oxidative stress parameters were also assessed following paracetamol-induced liver injury. The histological studies following liver injury were also assessed using H and E staining, Masson's trichrome staining, and periodic acid-Schiff staining. Similarly, the computational approach was used to assess the pharmacokinetic parameters of poncirin and its interaction with various protein targets. Poncirin markedly improved the antioxidant enzymes while attenuated the oxidative stress markers and inflammatory cytokines. Poncirin also markedly improved hematological parameters. Furthermore, poncirin treatment significantly improved the histological parameters using H and E staining, Masson's trichrome, and PAS staining compared to the control. Poncirin treatment also improved the liver function tests and liver synthetic activity compared to paracetamol treated group. The immunohistochemistry analysis revealed significant decrease in the inflammatory signaling protein such as nuclear factor kappa light chain enhancer of activated B cells (NF-κB), Jun N-terminal kinase (JNK), and cyclooxygenase-2 (COX-2) expression level compared to the paracetamol treated group. Computational analysis (molecular docking and molecular dynamic simulation) showed significant binding affinity of poncirin with the NF-κB, JNK, COX-2, IL-1β, IL-6, and TNF-α via multiple hydrophilic and hydrophobic binds. Similarly, the SwissADME software revealed that poncirin follows various drug-likeness rules and exhibited better pharmacokinetic parameters. Poncirin improved the sign and symptoms associated with liver injury using both in vivo and computational approaches.
在本研究中，采用体内和计算方法评估了朴西林对乙酰氨基酚诱导的肝损伤的作用。通过腹腔内（i.p.）给予对乙酰氨基酚来建立小鼠肝损伤模型，然后研究朴西林（腹腔内给予）对肝损伤的保护作用。评估了朴西林对肝损伤标志物和炎症细胞因子的影响。同样，在本研究中，还评估了朴西林对乙酰氨基酚诱导的肝损伤后的抗氧化剂和氧化应激参数。肝损伤后的组织学研究也使用 H 和 E 染色、马松三色染色和过碘酸希夫染色进行评估。同样，计算方法用于评估朴西林的药代动力学参数及其与各种蛋白质靶标的相互作用。朴西林显著改善了抗氧化酶，同时减轻了氧化应激标志物和炎症细胞因子。朴西林还显著改善了血液学参数。此外，与对照组相比，朴西林治疗显著改善了 H 和 E 染色、马松三色和 PAS 染色的组织学参数。朴西林治疗还改善了肝功能试验和肝合成活性，与乙酰氨基酚治疗组相比。免疫组织化学分析显示，与乙酰氨基酚治疗组相比，炎症信号蛋白如核因子 kappa 轻链增强子的活性 B 细胞（NF-κB）、Jun N-末端激酶（JNK）和环氧化酶-2（COX-2）的表达水平显著降低。计算分析（分子对接和分子动力学模拟）显示，朴西林与 NF-κB、JNK、COX-2、IL-1β、IL-6 和 TNF-α具有显著的结合亲和力，通过多种亲水和疏水结合。同样，SwissADME 软件显示，朴西林遵循各种类药性规则，并表现出更好的药代动力学参数。朴西林通过体内和计算方法改善了与肝损伤相关的症状和体征。
