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菠萝蛋白酶在阿尔茨海默病小鼠模型中的药理学评价。

Pharmacological evaluation of bromelain in mouse model of Alzheimer's disease.

机构信息

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara 144411, Punjab, India.

出版信息

Neurotoxicology. 2022 May;90:19-34. doi: 10.1016/j.neuro.2022.02.009. Epub 2022 Feb 24.

Abstract

The current study elucidates pharmacological evaluation of bromelain as a bioactive compound obtain from pineapple stem belongs to family Bromeliaceae in AlCl and D - galactose induced mice. In mice, co-administration of AlCl at dose 5 mg/kg b.w., via the oral route, and D - galactose at dose 60 mg/kg b.w., via intraperitoneal route for 90 days resulted in cognitive impairment, spatial learning, and memory deficits, as well as neurotoxicity. However, 30 consecutive days, treatments via an intraperitoneal route with bromelain low dose (Brm L) at dose 10 mg/kg b.w., bromelain high dose (Brm H) at dose 20 mg/kg b.w., donepezil (Dnpz) at dose 2 mg/kg b.w., and Brm L + Dnpz at doses 10, 2 mg/kg b.w. were considerably reversed the effect of AlCl and D - galactose induced AD mice. Consequences of behavioral parameters (Morris water maze, elevated plus maze and locomotor), biochemical estimation (MDA, GSH, SOD, CAT, Nitrite and AChE), and ELISA tests (mouse BACE, Aβ, TNF-α, IL-6, and BDNF) confirmed significant (p < 0.05) neuroprotective effect of treatments in AlCl and D - galactose induced mice. Additionally, hematoxylin and eosin staining of the cerebral cortex and the hippocampus exposed eosinophilic lesions and hyperchromatic nuclei in AD mice, but these neurodegenerative effects were eliminated by Brm L, Brm H, Dnpz, and Brm L + Dnpz treatments. Thus, bromelain alone and in combination with donepezil prevent AlCl and D - galactose induced spatial learning and memory deficits, as well as cognitive impairment, by increasing cholinergic activity and synaptic plasticity, as well as reducing oxidative damage, neuroinflammation, Aβ aggregations, and histopathological damage, according to our findings. The present study consequences indicate that bromelain alone and in combination with donepezil appears to have neuroprotective properties. Henceforward, this may be a promising treatment option for Alzheimer's disease.

摘要

本研究阐明了菠萝茎中提取的生物活性化合物菠萝蛋白酶作为一种药物的药理评价,属于凤梨科。在小鼠中,通过口服途径给予 5mg/kg b.w. 的 AlCl 和通过腹腔途径给予 60mg/kg b.w. 的 D-半乳糖 90 天可导致认知障碍、空间学习和记忆缺陷以及神经毒性。然而,连续 30 天通过腹腔途径给予低剂量(Brm L)10mg/kg b.w.、高剂量(Brm H)20mg/kg b.w.、多奈哌齐(Dnpz)2mg/kg b.w. 和 Brm L+Dnpz 剂量为 10、2mg/kg b.w.,可显著逆转 AlCl 和 D-半乳糖诱导的 AD 小鼠的作用。行为参数(Morris 水迷宫、高架十字迷宫和运动)、生化评估(MDA、GSH、SOD、CAT、亚硝酸盐和 AChE)和 ELISA 测试(小鼠 BACE、Aβ、TNF-α、IL-6 和 BDNF)的结果证实了治疗在 AlCl 和 D-半乳糖诱导的小鼠中的显著神经保护作用(p<0.05)。此外,大脑皮质和海马的苏木精和伊红染色显示 AD 小鼠有嗜酸性病变和核深染,而 Brm L、Brm H、Dnpz 和 Brm L+Dnpz 治疗消除了这些神经退行性效应。因此,根据我们的研究结果,菠萝蛋白酶单独使用和与多奈哌齐联合使用可通过增加胆碱能活性和突触可塑性以及减少氧化损伤、神经炎症、Aβ 聚集和组织病理学损伤来预防 AlCl 和 D-半乳糖诱导的空间学习和记忆缺陷以及认知障碍。本研究结果表明,菠萝蛋白酶单独使用和与多奈哌齐联合使用具有神经保护作用。因此,这可能是治疗阿尔茨海默病的一种有前途的治疗选择。

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