Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF‐kB‐p65, pro‐IL‐1β, cleaved IL‐1β, metalloproteinase‐9, Tissue Inhibitory Factor‐1 (TIMP‐1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF‐kB‐p65, pro, and cleaved IL‐1β, MMP‐9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro‐IL‐1β in the striatum while they augmented TIMP1 and reduced MMP‐9 amounts in both regions. AAs reversed rotenone‐induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro‐IL‐1β and MMP‐9 levels in both regions, NF‐kB‐p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.

中文翻译：

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纯化的漆树酸在帕金森病农药模型中发挥多种神经保护作用：体内和计算机分析

由环境毒素诱发的帕金森病 (PD) 涉及多因素级联的有害因素，因此促使人们寻找能够作用于最多分子靶标的治疗剂。本研究评估了从腰果壳液中分离的 50 mg/kg 纯化漆树酸 (AAs) 对黑质 (SN) 和纹状体中鱼藤酮诱导的氧化应激和炎症的多个步骤的功效。成年小鼠分为四组：对照组、鱼藤酮、AAs+鱼藤酮和单独的AAs。评估了脂质过氧化、一氧化氮 (NO) 水平和还原型谷胱甘肽 (GSH)/氧化型谷胱甘肽 (GSSG) 的比率。NF-kB-p65, pro-IL-1β, 裂解的 IL-1β, 金属蛋白酶-9, 组织抑制因子-1 (TIMP-1), 酪氨酸羟化酶 (TH), 通过蛋白质印迹评估胶质纤维酸性蛋白（GFAP）水平。还使用 SwissADME 网络工具进行了计算机模拟研究。鱼藤酮增加了脂肪过氧化和 NO 的产生，并降低了 SN 和纹状体中的 TH 水平和 GSH/GSSG 比率。与对照组和 AA 组相比，它还增强了 NF-kB-p65、pro 和裂解的 IL-1β、MMP-9、GFAP 水平。单独的 AA 减少了纹状体中的 pro-IL-1β，同时它们增加了 TIMP1 并减少了两个区域的 MMP-9 量。AA 可以逆转鱼藤酮对脂质过氧化、NO 产生和 GSH/GSSG 比率的影响，以及增加 TH 和减弱两个区域的 pro-IL-1β 和 MMP-9 水平，SN 中的 NF-kB-p65 和 GFAP纹状体。总之，体内和计算机分析增强了 AA 的多个和明确的分子靶点，