Erdoğan Mehmet Mustafa, Erdoğan Esra, Kocaman Nevin, Telo Selda, Biçen Hakan, Erdoğdu Hamza, Yerlikaya Kavak Songül, Karakuzulu Fatma Tuba
Histology and Embryology Department, Şanlıurfa Training and Research Hospital, Şanlıurfa, Türkiye.
Faculty of Pharmacy, Basic Pharmaceutical Sciences Department, Harran University, Şanlıurfa, Türkiye.
Mol Biol Rep. 2025 Jul 18;52(1):734. doi: 10.1007/s11033-025-10842-3.
Oxidative stress and inflammation are pivotal in pathogenesis of brain ischemia-reperfusion (I/R) injury. This study evaluated neuroprotective effects of nerolidol (NRD) on asprosin (ASP), spexin (SPX), and DARS2 expressions in myocardial infarction (MI) induced cerebral I/R injury, and systemic inflammatory responses by measuring serum cytokine levels.
Twenty-eight Wistar rats were divided into: Control, MI (200 mg/kg isoproterenol), NRD (100 mg/kg/day), and MI + NRD groups. After 14 days, brain cortex tissues were analyzed histopathologically and immunohistochemically, while serum TAS, TOS, and cytokines were measured via ELISA. Histopathological examination revealed severe cortical damage in MI rats, which was significantly attenuated by NRD treatment. Immunohistochemistry showed marked upregulation of ASP, SPX, and DARS2 in the MI group, with NRD normalizing SPX/DARS2 and partially reducing ASP. Serum analysis revealed comprehensive therapeutic effects of NRD, effectively counteracting the metabolic and inflammatory disturbances caused by MI. The treatment completely restored depleted Metrnl levels to normal values, demonstrating its metabolic regulatory capacity. NRD also showed potent anti-inflammatory action, significantly lowering elevated levels of key pro-inflammatory cytokines while maintaining a balanced immune response. Furthermore, it effectively corrected the oxidative imbalance characteristic of I/R injury, normalizing both oxidant and antioxidant markers to near-control levels. NRD effectively reduces cerebral I/R injury after MI by combining antioxidant, anti-inflammatory, and metabolic regulatory actions. It normalizes Metrnl, cytokines, and oxidative stress markers while modulating ASP/SPX/DARS2 pathways, suggesting their role in both injury and recovery.
These findings highlight the potential of NRD in preventing post-MI brain damage and the need for further research on optimal dosing and mechanistic pathways.
氧化应激和炎症在脑缺血再灌注（I/R）损伤的发病机制中起关键作用。本研究通过测量血清细胞因子水平，评估了橙花叔醇（NRD）对心肌梗死（MI）诱导的脑I/R损伤中脂联素（ASP）、刺鼠肽基因相关肽（SPX）和天冬酰胺-tRNA合成酶2（DARS2）表达的神经保护作用，以及全身炎症反应。
将28只Wistar大鼠分为：对照组、MI组（200mg/kg异丙肾上腺素）、NRD组（100mg/kg/天）和MI + NRD组。14天后，对大脑皮质组织进行组织病理学和免疫组织化学分析，同时通过酶联免疫吸附测定法检测血清总抗氧化能力（TAS）、总氧化应激（TOS）和细胞因子。组织病理学检查显示MI大鼠存在严重的皮质损伤，而NRD治疗可使其明显减轻。免疫组织化学显示MI组中ASP、SPX和DARS2明显上调，NRD使SPX/DARS2恢复正常，并部分降低ASP。血清分析显示NRD具有综合治疗作用，可有效对抗MI引起的代谢和炎症紊乱。该治疗将耗尽的Metrnl水平完全恢复到正常值，证明了其代谢调节能力。NRD还显示出强大的抗炎作用，显著降低关键促炎细胞因子的升高水平，同时维持平衡的免疫反应。此外，它有效纠正了I/R损伤特有的氧化失衡，使氧化剂和抗氧化剂标志物均恢复到接近对照水平。NRD通过结合抗氧化、抗炎和代谢调节作用，有效减轻MI后的脑I/R损伤。它使Metrnl、细胞因子和氧化应激标志物恢复正常，同时调节ASP/SPX/DARS2途径，表明它们在损伤和恢复中均起作用。
这些发现突出了NRD在预防MI后脑损伤方面的潜力，以及对最佳剂量和作用机制途径进行进一步研究的必要性。
