Erigeron bonariensis is widely distributed throughout the world's tropics and subtropics. In folk medicine, E. bonariensis has historically been used to treat head and brain diseases. Alzheimer’s disease (AD) is the most widespread form of dementia initiated via disturbances in brain function. Herein, the neuroprotective effect of the chemically characterized E. bonariensis ethanolic extract is reported for the first time in an AD animal model. Chemical profiling was conducted using UPLC–ESI-MS analysis. Female rats underwent ovariectomy (OVX) followed by 42 days of D-galactose (D-Gal) administration (150 mg/kg/day, i.p) to induce AD. The OVX/D-Gal-subjected rats received either donepezil (5 mg/kg/day) or E. bonariensis at 50, 100, and 200 mg/kg/day, given 1 h prior to D-Gal. UPLC–ESI-MS analysis identified 42 chemicals, including flavonoids, phenolic acids, terpenes, and nitrogenous constituents. Several metabolites, such as isoschaftoside, casticin, velutin, pantothenic acid, xanthurenic acid, C18-sphingosine, linoleamide, and erucamide, were reported herein for the first time in Erigeron genus. Treatment with E. bonariensis extract mitigated the cognitive decline in the Morris Water Maze test and the histopathological alterations in cortical and hippocampal tissues of OVX/D-Gal-subjected rats. Moreover, E. bonariensis extract mitigated OVX/D-Gal-induced Aβ aggregation, Tau hyperphosphorylation, AChE activity, neuroinflammation (NF-κBp65, TNF-α, IL-1β), and apoptosis (Cytc, BAX). Additionally, E. bonariensis extract ameliorated AD by increasing α7-nAChRs expression, down-regulating GSK-3β and FOXO3a expression, and modulating Jak2/STAT3/NF-ĸB p65 and PI3K/AKT signaling cascades. These findings demonstrate the neuroprotective and memory-enhancing effects of E. bonariensis extract in the OVX/D-Gal rat model, highlighting its potential as a promising candidate for AD management.

Graphical Abstract

中文翻译：

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使用 UPLC/MS 揭示灯盏草乙醇提取物对雌性大鼠卵巢切除/D-半乳糖诱导的记忆障碍的神经保护潜力与其代谢物指纹相关

灯盏花广泛分布于世界热带和亚热带地区。在民间医学中，博纳里桉历史上曾被用来治疗头部和脑部疾病。阿尔茨海默病 (AD) 是最常见的痴呆症，由大脑功能紊乱引起。在此，首次报道了在 AD 动物模型中化学表征的E. bonariensis乙醇提取物的神经保护作用。使用 UPLC-ESI-MS 分析进行化学分析。雌性大鼠接受卵巢切除术 (OVX)，随后给予 42 天的 D-半乳糖 (D-Gal)（150 mg/kg/天，腹膜内注射）以诱导 AD。OVX/D-Gal 组大鼠在D-Gal 治疗前 1 小时接受多奈哌齐（5 mg/kg/天）或 50、100 和 200 mg/kg/天的博纳利埃里希菌。UPLC-ESI-MS 分析鉴定出 42 种化学物质，包括类黄酮、酚酸、萜烯和含氮成分。灯盏花属中的几种代谢产物，如异夏夫糖苷、蓖麻素、绒毛素、泛酸、黄嘌呤酸、C18-鞘氨醇、亚油酰胺和芥酸酰胺，均为首次报道。用博纳里埃里希提取物治疗可减轻莫里斯水迷宫测试中的认知能力下降以及 OVX/D-Gal 实验大鼠皮质和海马组织的组织病理学改变。此外，E. bonariensis提取物还可减轻 OVX/D-Gal 诱导的 Aβ 聚集、Tau 过度磷酸化、AChE 活性、神经炎症（NF-κBp65、TNF-α、IL-1β）和细胞凋亡（Cytc、BAX）。此外，E. bonariensis提取物通过增加 α7-nAChRs 表达、下调 GSK-3β 和 FOXO3a 表达以及调节 Jak2/STAT3/NF-ĸB p65 和 PI3K/AKT 信号级联反应来改善 AD。这些发现证明了E. bonariensis提取物在 OVX/D-Gal 大鼠模型中的神经保护和记忆增强作用，突显了其作为 AD 治疗的有希望的候选者的潜力。

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