Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3β and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.

啤酒花，来自Humulus lupulus的干燥雌簇L.，传统上被用作治疗失眠、神经痛和更年期障碍的民间药物。然而，尚未研究其对铁过载引起的神经损伤的药理作用。本研究旨在评估啤酒花提取物 (HLE) 及其活性成分黄腐酚 (XAN) 在体内外对铁过载诱导的神经损伤的保护作用，并探讨其潜在机制。结果表明，HLE和XAN显着改善了铁过载小鼠的记忆障碍，主要表现为潜伏期缩短，跨平台次数和自发交替率增加，相关蛋白表达增加。此外，HLE 和 XAN 显着增加超氧化物歧化酶 (SOD) 和谷胱甘肽过氧化物酶 (GSH-PX) 活性，并显着降低海马体中的丙二醛 (MDA) 水平。此外，HLE 和 XAN 明显降低了右旋糖酐铁 (ID) 诱导的 PC12 细胞的活性氧 (ROS) 含量，并改善了氧化应激水平。此外，HLE 和 XAN 显着上调核因子 E2 相关因子 (Nrf2)、NAD(P)H 醌氧化还原酶 (NQO1)、血红素加氧酶-1 (HO-1)、SOD、磷酸化 AKT (p-AKT) 的表达, 和磷酸化 GSK3海马和 PC12 细胞中的β (p-GSK3 β )。这些发现证明了 HLE 和 XAN 对铁诱导的记忆障碍的保护作用，这归因于其通过激活 AKT/GSK3 β和 Nrf2/NQO1 通路的抗氧化特性。此外，有人提出啤酒花可能是铁过载相关神经系统疾病治疗的潜在候选者。