The present study investigates the neuro-protective ability of nordihydroguaretic acid (NDGA) in the experimental paradigm of autism spectrum disorders (ASD) and further decipher the nitric oxide pathway’s role in its proposed action. An intracerebroventricular infusion of 4 μl of 1 M PPA was given in the lateral ventricle’s anterior region to induce autism-like phenotype in male rats. Oral administration of NDGA (5, 10 & 15 mg/kg) was initiated from the 3^rd day lasting till the 28th day. L-NAME (50 mg/kg) and L-Arginine (800 mg/kg) were also given individually and combined to explore NDGA’s ability to act via the nitric oxide pathway. Behavior tests for sociability, stereotypy, anxiety, depression, novelty, repetitive and perseverative behavior were carried out between the 14th and 28th day. On the 29th day, animals were sacrificed, and mitochondrial complexes and oxidative stress parameters were evaluated. We also estimated the levels of neuroinflammatory and apoptotic markers such as TNF-α, IL-6, NF-κB, IFN-γ, HSP-70, and caspase-3. To assess the involvement of the nitric oxide pathway, levels of iNOS and homocysteine were estimated. Treatment with NDGA significantly restored behavioral, biochemical, neurological, and molecular deficits. Hence, NDGA can be used as a neurotherapeutic agent in ASD. Targeting nitric oxide pathway mediated oxidative & nitrosative stress responsible for behavioral, biochemical, and molecular alterations via modulating nitric oxide pathway. The evaluation of iNOS and homocysteine levels conclusively establishes the nitric oxide pathway’s role in causing behavioral, biochemical & molecular deficits and NDGA’s beneficial effect in restoring these alterations.

本研究在自闭症谱系障碍 (ASD) 的实验范式中研究去甲二氢胍酸 (NDGA) 的神经保护能力，并进一步破译一氧化氮途径在其拟议作用中的作用。在侧脑室前区给予 4 μl 1 M PPA 的脑室内输注，以诱导雄性大鼠出现自闭症样表型。^从第3天开始口服 NDGA（5、10 和 15 mg/kg）一天持续到第28天。L-NAME (50 mg/kg) 和 L-精氨酸 (800 mg/kg) 也分别给予并结合以探索 NDGA 通过一氧化氮途径发挥作用的能力。在第 14 天和第 28 天之间进行了社交能力、刻板印象、焦虑、抑郁、新奇、重复和坚持行为的行为测试。第29天，处死动物，评估线粒体复合物和氧化应激参数。我们还估计了 TNF-α、IL-6、NF-κB、IFN-γ、HSP-70 和 caspase-3 等神经炎症和凋亡标志物的水平。为了评估一氧化氮途径的参与，估计了 iNOS 和同型半胱氨酸的水平。NDGA 治疗显着恢复了行为、生化、神经和分子缺陷。因此，NDGA 可用作 ASD 的神经治疗剂。靶向一氧化氮途径介导的氧化和亚硝化应激通过调节一氧化氮途径导致行为、生化和分子改变。iNOS 和同型半胱氨酸水平的评估最终确定了一氧化氮途径在引起行为、生化和分子缺陷中的作用以及 NDGA 在恢复这些改变中的有益作用。