Division of Life Science and Applied Life Science (BK21 plus), College of Natural Sciences, Gyeongsang National University, Jinju, 52828, Republic of Korea.
Mol Neurobiol. 2019 Sep;56(9):6293-6309. doi: 10.1007/s12035-019-1512-7. Epub 2019 Feb 12.
Hesperetin is a bioactive flavonoid in the body, produced from hesperidin. No comprehensive studies have shown its protective effects in neurodegenerative disorders. Here, we hypothesized that hesperetin may protect the mice brain against Aβ-induced neurodegeneration. Twenty-four hours after intracerebroventricular injection of Aβ1-42, the treated group was injected hesperetin. For in vitro experiments, HT22 and BV-2 cells were used. Immunoblot, immunofluorescence, and behavioral analyses were used to evaluate the different parameters. Our results indicated that hesperetin significantly attenuated oxidative stress, as assessed by the expression of Nrf2/HO-1 and LPO and ROS assays, in the hippocampus, cortex, and in vitro HT22 cells. Similarly, activated glial cells were regulated by hesperetin, as assessed by the expression of GFAP and Iba-1. Moreover, the expression of TLR4, p-NF-κB, and downstream targets was analyzed; the results showed that hesperetin reinstated the expression of these markers. The effects of hesperetin were further confirmed by using specific TLR4 and p-NF-κB inhibitors in BV-2 cells. Next, we evaluated Aβ pathology in the cortex, hippocampus, and HT22 cells, showing that hesperetin significantly reduced the Aβ pathology. Furthermore, the antiapoptotic effects of hesperetin were assessed, which showed strong antiapoptotic effects. Overall, the neuroprotective effect of hesperetin was found to be a multipotent effect, involving the inhibition of oxidative stress, neuroinflammation, apoptotic cell death, and cognitive consolidation. Given antioxidant, anti-inflammatory, and antiapoptotic potentials against Aβ-induced neurodegeneration and memory impairment, hesperetin may be a promising therapeutic agent for Alzheimer's disease-like neurological disorders.
橙皮素是体内的一种生物活性类黄酮，由橙皮苷产生。目前尚无综合研究表明其对神经退行性疾病有保护作用。在这里，我们假设橙皮素可能对 Aβ 诱导的神经退行性病变有保护作用。在 Aβ1-42 脑室内注射后 24 小时，给予橙皮素处理组进行注射。对于体外实验，使用 HT22 和 BV-2 细胞。通过免疫印迹、免疫荧光和行为分析来评估不同参数。我们的结果表明，橙皮素可显著减轻氧化应激，其标志物为 Nrf2/HO-1 的表达、LPO 和 ROS 测定值，在海马体、大脑皮质和 HT22 细胞中也有相同的作用。同样，通过 GFAP 和 Iba-1 的表达，橙皮素也调节了胶质细胞的激活。此外，还分析了 TLR4、p-NF-κB 和下游靶标的表达；结果表明橙皮素恢复了这些标志物的表达。在 BV-2 细胞中使用特定的 TLR4 和 p-NF-κB 抑制剂进一步证实了橙皮素的作用。接下来，我们评估了皮质、海马体和 HT22 细胞中的 Aβ 病理学，结果表明橙皮素可显著减少 Aβ 病理学。此外，还评估了橙皮素的抗凋亡作用，结果表明其具有很强的抗凋亡作用。总的来说，橙皮素的神经保护作用是一种多效作用，涉及抑制氧化应激、神经炎症、细胞凋亡和认知巩固。鉴于其对 Aβ 诱导的神经退行性病变和记忆损伤具有抗氧化、抗炎和抗凋亡潜力，橙皮素可能是治疗类似阿尔茨海默病的神经退行性疾病的一种有前途的治疗药物。
