Inandiklioglu Nihal, Onat Taylan, Raheem Kayode Yomi, Kaya Savas
Faculty of Medicine, Department of Medical Biology, Yozgat Bozok University, 66200 Yozgat, Türkiye.
Faculty of Medicine, Department of Obstetrics and Gynecology, Yozgat Bozok University, 66200 Yozgat, Türkiye.
Life (Basel). 2024 Sep 24;14(10):1214. doi: 10.3390/life14101214.
In recent years, significant progress has been made in understanding the biological and molecular pathways that regulate the effects of ischemia-reperfusion (I/R) injuries. However, despite these developments, various pharmacological agents are still being tested to either protect against or mitigate the damage caused by the IR's harmful consequences. JWH133 is a CB2R-selective agonist and belongs to the class of Δ8-tetrahydrocannabinol. The present study aimed to determine the in vivo effect of JWH-133 on uterine IR injury via the TLR4/NF-κB, pathway. Female Wistar albino rats (n = 40) were randomly divided into five groups. Three different doses of JWH-133 (0.2, 1, and 5 mg/kg) were administered to the rats. RNA was isolated from uterine tissue samples, and gene expression was measured by RT-PCR using specific primers. The interaction energies and binding affinities of JWH-133 with IL-1β, IL-6, NF-κB, TLR-4, and TNF-α were calculated through molecular docking analysis. The expression analysis revealed that JWH-133 administration significantly reduced the expression levels of IL-1β, IL-6, NF-κB, TLR-4, and TNF-α ( < 0.05). Notably, in the 1 mg/kg JWH-133 group, all of the gene expression levels decreased significantly ( < 0.05). The molecular docking results showed that JWH-133 formed hydrogen bonds with GLU64 of IL-1β, SER226 of IL-6, and SER62 of TNF-α. This study highlights the molecular binding affinity of JWH-133 and its potential effects on inflammation in IR injury. These results pave the way for future research on its potential as a therapeutic target.
近年来，在理解调节缺血再灌注（I/R）损伤效应的生物学和分子途径方面取得了重大进展。然而，尽管有这些进展，仍在测试各种药理剂以预防或减轻I/R有害后果所造成的损害。JWH133是一种CB2R选择性激动剂，属于Δ8-四氢大麻酚类。本研究旨在通过TLR4/NF-κB途径确定JWH-133对子宫I/R损伤的体内作用。将雌性Wistar白化大鼠（n = 40）随机分为五组。给大鼠施用三种不同剂量的JWH-133（0.2、1和5 mg/kg）。从子宫组织样本中分离RNA，并使用特异性引物通过RT-PCR测量基因表达。通过分子对接分析计算JWH-133与IL-1β、IL-6、NF-κB、TLR-4和TNF-α的相互作用能和结合亲和力。表达分析显示，施用JWH-133显著降低了IL-1β、IL-6、NF-κB、TLR-4和TNF-α的表达水平（<0.05）。值得注意的是，在1 mg/kg JWH-133组中，所有基因表达水平均显著下降（<0.05）。分子对接结果表明，JWH-133与IL-1β的GLU64、IL-6的SER226和TNF-α的SER62形成氢键。本研究突出了JWH-133的分子结合亲和力及其对I/R损伤炎症的潜在影响。这些结果为其作为治疗靶点的潜力的未来研究铺平了道路。
