Alserhani Gharam Saad, Mohamed Maged E, Younis Nancy Safwat
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, 31982, Al-Ahsa, Saudi Arabia.
Pharmaceutical Care Management, Aljouf Health Cluster, Aljouf, Saudi Arabia.
Naunyn Schmiedebergs Arch Pharmacol. 2025 Mar 18. doi: 10.1007/s00210-025-04042-w.
Cyclophosphamide (CP) is associated with detrimental side effect including hepatic and renal toxicities. Linalool (LIN), acyclic monoterpene alcohol, is acquired from several plants' essential oils. Rats were disseminated into four groups. Group 1: Normal and Cyclophosphamide (CP) groups in which rats were given normal saline or CP intraperitoneally (200 mg/kg, ip on 12nd). Group 3 and 4 (LIN 50 + CP and LIN 100 + CP) groups in which rats were administered LIN (50 or 100 mg/kg) orally for 14 days and CP (200 mg/kg, ip on 12nd). Assessment of hepatic and renal function tests and histopathological examination were performed. Oxidative stress indicators, inflammatory mediators, and apoptosis markers in hepatic and renal homogenates were assessed. JAK2/STAT3/NFκB gene expression was measured. The network pharmacology study suggests JAK2 as one the targets so molecular docking of LIN against JAK2 was accomplished. LIN administration with CP resulted in a significant reduction in liver function test including ALT, AST, LDL, bilirubin, and γGTT1 and in renal function markers including BUN, creatinine, uric acid, Kim-1, NGAL, and CysC. Also, LIN increases in antioxidant ability via enhancing GST, GSH-Px, GSH-R, SOD, and catalase as well as a declining NO, MDA levels. Furthermore, LIN significantly diminished JAK2/STAT3/NFκB gene expressions with subsequent reduction in the inflammatory markers including TNF-α, MPO, ICAM-1, IL-6, and IL-1β levels and the apoptotic markers Bax and cleavage caspase-3 and 9. LIN protected the hepatic and renal tissues from ROS damage and mitigated JAK2/STAT3/NFκB with subsequent anti-inflammatory and anti-apoptotic properties.
环磷酰胺（CP）具有包括肝毒性和肾毒性在内的有害副作用。芳樟醇（LIN）是一种无环单萜醇，可从多种植物的精油中获得。将大鼠分为四组。第1组：正常组和环磷酰胺（CP）组，其中大鼠腹腔注射生理盐水或CP（200mg/kg，第12天腹腔注射）。第3组和第4组（LIN 50 + CP和LIN 100 + CP），其中大鼠口服LIN（50或100mg/kg）14天，并于第12天腹腔注射CP（200mg/kg）。进行肝功能和肾功能测试评估以及组织病理学检查。评估肝和肾匀浆中的氧化应激指标、炎症介质和凋亡标志物。检测JAK2/STAT3/NFκB基因表达。网络药理学研究表明JAK2是靶点之一，因此完成了LIN与JAK2的分子对接。LIN与CP联合给药导致肝功能测试指标（包括ALT、AST、LDL、胆红素和γGTT1）以及肾功能标志物（包括BUN、肌酐、尿酸、Kim-1、NGAL和CysC）显著降低。此外，LIN通过增强GST、GSH-Px、GSH-R、SOD和过氧化氢酶提高抗氧化能力，同时降低NO、MDA水平。此外，LIN显著降低JAK2/STAT3/NFκB基因表达，随后降低包括TNF-α、MPO、ICAM-1、IL-6和IL-1β水平在内的炎症标志物以及凋亡标志物Bax和裂解的半胱天冬酶-3和9。LIN保护肝和肾组织免受ROS损伤，并减轻JAK2/STAT3/NFκB的作用，随后具有抗炎和抗凋亡特性。
