Ursolic acid and its isomer oleanolic acid are responsible for the anti-dementia effects of Ocimum sanctum in olfactory bulbectomized mice,Journal of Natural Medicines

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Ursolic acid and its isomer oleanolic acid are responsible for the anti-dementia effects of Ocimum sanctum in olfactory bulbectomized mice
Journal of Natural Medicines ( IF 2.5 ) Pub Date : 2022-02-26 , DOI: 10.1007/s11418-022-01609-2
Hien Thu Nguyen ₁ , Xoan Thi Le ₁ , Tai Van Nguyen ₂ , Hoa Nhu Phung ₂ , Hang Thi Nguyet Pham ₁ , Khoi Minh Nguyen ₂ , Kinzo Matsumoto ₃

Affiliation

This study aims to clarify the bioactive constituents responsible for the anti-dementia effects of Ocimum sanctum Linn. ethanolic extract (OS) using olfactory bulbectomized (OBX) mice, an animal model of dementia. The effects of OS or its extract further fractionated with n-hexane (OS-H), ethyl acetate (OS-E), and n-butanol (OS-B) on the spatial cognitive deficits of OBX mice were elucidated by the modified Y-maze tests. The effects of the major constituents of the most active OS fraction were also elucidated using the reference drug donepezil. The administration of OS and OS-E ameliorated the spatial cognitive deficits caused by OBX, whereas OS-H or OS-B had no effect. Two major constituents, ursolic acid (URO) and oleanolic acid (OLE), and three minor constituents were isolated from OS-E. URO (6 and 12 mg/kg) and OLE (24 mg/kg) attenuated the OBX-induced cognitive deficits. URO (6 mg/kg) and donepezil reversed the OBX-induced down-regulation of vascular endothelial growth factor (VEGF) and choline acetyltransferase expression levels in the hippocampus. URO inhibited the ex vivo activity of acetylcholinesterase with similar efficacy to donepezil. URO inhibited the in vitro activity of acetylcholinesterase (IC₅₀ = 106.5 μM), while the effects of OS, OS-E, and other isolated compounds were negligible. These findings suggest that URO and OLE are responsible for the anti-dementia action of OS extract, whereas URO possesses a more potent anti-dementia effect than its isomer OLE. The effects of URO are, at least in part, mediated by normalizing the function of central cholinergic systems and VEGF protein expression.

Graphical abstract

中文翻译：

熊果酸及其异构体齐墩果酸是圣罗勒对嗅球切除小鼠的抗痴呆作用的原因

本研究旨在阐明圣罗勒抗痴呆作用的生物活性成分。使用嗅球切除 (OBX) 小鼠（一种痴呆动物模型）提取乙醇提取物 (OS)。 OS 或其提取物进一步与正己烷 (OS-H)、乙酸乙酯 (OS-E) 和正丁醇 (OS-B) 分离对 OBX 小鼠空间认知缺陷的影响通过改良的 Y 阐明-迷宫测试。还使用参考药物多奈哌齐阐明了最活跃的 OS 部分主要成分的作用。 OS和OS-E的施用改善了OBX引起的空间认知缺陷，而OS-H或OS-B则没有效果。从 OS-E 中分离出两种主要成分：熊果酸 (URO) 和齐墩果酸 (OLE)，以及三种次要成分。 URO（6 和 12 毫克/公斤）和 OLE（24 毫克/公斤）减轻了 OBX 引起的认知缺陷。 URO (6 mg/kg) 和多奈哌齐逆转了 OBX 诱导的海马血管内皮生长因子 (VEGF) 和胆碱乙酰转移酶表达水平的下调。 URO 抑制乙酰胆碱酯酶的离体活性，其功效与多奈哌齐相似。 URO 抑制乙酰胆碱酯酶的体外活性 (IC ₅₀ = 106.5 μM)，而 OS、OS-E 和其他分离化合物的影响可以忽略不计。这些研究结果表明，OS提取物的抗痴呆作用是由URO和OLE负责的，而URO比其异构体OLE具有更有效的抗痴呆作用。 URO 的作用至少部分是通过使中枢胆碱能系统功能和 VEGF 蛋白表达正常化来介导的。

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更新日期：2022-02-26

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