Palachai Nut, Supawat Araya, Kongsui Ratchaniporn, Klimaschewski Lars, Jittiwat Jinatta
Faculty of Medicine, Mahasarakham University, Mahasarakham 44000, Thailand.
Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
Int J Mol Sci. 2025 Feb 21;26(5):1847. doi: 10.3390/ijms26051847.
The rising incidence of ischemic stroke poses significant health and healthcare burdens. Given the limitations of current therapeutic options, there is increasing interest in exploring the potential of galangin, a natural flavonoid compound, as a treatment for ischemic stroke. This study aimed to evaluate the neuroprotective effects and underlying mechanisms of galangin in mitigating oxidative stress, inflammation, and apoptosis in a rat model of permanent cerebral ischemia. Sixty male Wistar rats were divided into six groups: control; right middle cerebral artery occlusion (Rt.MCAO) with vehicle; Rt.MCAO with piracetam, a synthetic compound known as a cognitive enhancer; and Rt.MCAO with galangin administered at doses of 25, 50, and 100 mg/kg body weight. Neurological deficit scores, brain edema, neuronal density, and microglial morphology were assessed along with the activity of myeloperoxidase (MPO), a marker of inflammation, and superoxide dismutase (SOD). Additionally, the expression of key markers for inflammation and apoptosis, cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), Bcl-2-associated X protein (Bax), B-cell lymphoma-extra large (Bcl-XL), and caspase-3, was analyzed to elucidate potential mechanisms. The results demonstrated that galangin treatment significantly improved neurological deficit scores, reduced brain edema, enhanced neuronal density, attenuated microglial activation, decreased MPO activity, and increased SOD activity in both the cortex and hippocampus, highlighting its neuroprotective potential. These effects were linked to the modulation of inflammatory and apoptotic pathways. Specifically, galangin significantly reduced the expression of IL-6, COX-2, Bax, and caspase-3 while increasing the levels of the anti-apoptotic protein Bcl-XL. In conclusion, galangin demonstrates significant promise as a neuroprotective agent for ischemic stroke by suppressing inflammation and apoptosis, thereby improving neurological outcomes. However, clinical trials are required to validate these preclinical findings and confirm galangin's therapeutic efficacy in humans.
缺血性中风发病率的上升带来了重大的健康和医疗负担。鉴于当前治疗选择的局限性,人们越来越有兴趣探索天然黄酮类化合物高良姜素作为缺血性中风治疗方法的潜力。本研究旨在评估高良姜素在减轻永久性脑缺血大鼠模型中的氧化应激、炎症和细胞凋亡方面的神经保护作用及其潜在机制。将60只雄性Wistar大鼠分为六组:对照组;右侧大脑中动脉闭塞(Rt.MCAO)加赋形剂组;Rt.MCAO加吡拉西坦组(吡拉西坦是一种已知的认知增强合成化合物);以及Rt.MCAO加高良姜素组,高良姜素的给药剂量分别为25、50和100mg/kg体重。评估神经功能缺损评分、脑水肿、神经元密度和小胶质细胞形态,以及炎症标志物髓过氧化物酶(MPO)和超氧化物歧化酶(SOD)的活性。此外,分析炎症和细胞凋亡关键标志物环氧合酶-2(COX-2)、白细胞介素-6(IL-6)、Bcl-2相关X蛋白(Bax)、B细胞淋巴瘤-特大号(Bcl-XL)和半胱天冬酶-3的表达,以阐明潜在机制。结果表明,高良姜素治疗显著改善了神经功能缺损评分,减轻了脑水肿,提高了神经元密度,减弱了小胶质细胞激活,降低了MPO活性,并增加了皮质和海马中的SOD活性,突出了其神经保护潜力。这些作用与炎症和凋亡途径的调节有关。具体而言,高良姜素显著降低了IL-6、COX-2、Bax和半胱天冬酶-3的表达,同时增加了抗凋亡蛋白Bcl-XL的水平。总之,高良姜素通过抑制炎症和细胞凋亡,从而改善神经功能结局,显示出作为缺血性中风神经保护剂的巨大前景。然而,需要进行临床试验来验证这些临床前研究结果,并确认高良姜素在人类中的治疗效果。