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仙人掌水醇提取物对脂多糖(LPS)诱导的炎症和认知障碍的影响:来自体内和体外研究的证据。

The effects of hydro-ethanolic extract of Capparis spinosa (C. spinosa) on lipopolysaccharide (LPS)-induced inflammation and cognitive impairment: Evidence from in vivo and in vitro studies.

机构信息

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.

Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Neurology, Kashan University of Medical Sciences, Kashan, Iran.

出版信息

J Ethnopharmacol. 2020 Jun 28;256:112706. doi: 10.1016/j.jep.2020.112706. Epub 2020 Feb 25.

DOI:10.1016/j.jep.2020.112706
PMID:32109547
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Capparis spinose (C. spinosa) belonging to Capparaeae, originates from dry areas in the west or central Asia and Mediterranean basin. For thousands of years, C. spinosa has been reported to be used as a therapeutic traditional medicine to relieve various ailments including rheumatism, pain and inflammatory diseases.

AIM OF THE STUDY

There are several studies mentioning that systemic inflammation results in learning and memory impairments through the activation of microglia. The objective of this study was to investigate the effect of C. spinosa on both in vivo and in vitro models of neuroinflammation and cognitive impairment using lipopolysaccharide (LPS).

MATERIALS AND METHODS

In vivo: 40 male rats were used in the present study. Cognitive impairment was induced using LPS (1 mg/kg/d; i.p.) for 4 weeks. Treatment with C. spinosa (100 and 300 mg/kg/d; p.o.) was performed 1 h before LPS administration. At the end of the experiment, rats were undergone for behavioral and biochemical analysis. In vitro: Primary microglia isolated from mouse was used in the present study. The cells were pretreated with C. spinosa extract (10-300 μg/ml) and then stimulated with LPS (1 μg/ml). The expression levels of inflammatory and anti-inflammatory cytokines were elucidated using Real-Time PCR and ELISA methods.

RESULTS

The escape latency in the Morris water maze test in the LPS group was significantly greater than the control group (p < 0.001), while, in extract-treated groups, it was less than the LPS group (p < 0.001). Additionally, we found that the levels of IL-1β, TNF-α, and iNOS/Arg-1 ratio was also significantly lower in extract-treated groups than the LPS group (p < 0.001). The results revealed that C. spinosa extract significantly reduced the levels of TNF-α, iNOS, COX-2, IL-1β, IL-6, NO and PGE2, and the ratios of iNOS/Arg-1 and NO/urea, following the LPS-induced inflammation in microglia (p < 0.001).

CONCLUSIONS

Our finding provides evidence that C. spinosa has a neuroprotective effect, and might be considered as an effective therapeutic agent for the treatment of neurodegenerative diseases that are accompanied by microglial activation, such as AD.

摘要

民族药理学相关性

尖瓣木(Capparis spinosa)属于尖瓣木科,原产于西亚和地中海盆地的干旱地区。几千年来,尖瓣木被报道作为一种治疗传统药物,用于缓解各种疾病,包括风湿、疼痛和炎症性疾病。

研究目的

有几项研究表明,系统性炎症通过激活小胶质细胞导致学习和记忆障碍。本研究的目的是使用脂多糖(LPS)研究尖瓣木对体内和体外神经炎症和认知障碍模型的影响。

材料和方法

体内:本研究使用了 40 只雄性大鼠。使用 LPS(1mg/kg/d;腹腔注射)诱导 4 周认知障碍。在 LPS 给药前 1 小时给予尖瓣木(100 和 300mg/kg/d;口服)进行治疗。实验结束时,对大鼠进行行为和生化分析。体外:本研究使用从小鼠分离的原代小胶质细胞。用尖瓣木提取物(10-300μg/ml)预处理细胞,然后用 LPS(1μg/ml)刺激。使用实时 PCR 和 ELISA 方法阐明炎症和抗炎细胞因子的表达水平。

结果

在 LPS 组,水迷宫测试中的逃避潜伏期明显大于对照组(p<0.001),而在提取物处理组,其潜伏期小于 LPS 组(p<0.001)。此外,我们发现,在提取物处理组中,IL-1β、TNF-α 和 iNOS/Arg-1 比值也明显低于 LPS 组(p<0.001)。结果表明,尖瓣木提取物显著降低了 LPS 诱导的小胶质细胞炎症模型中 TNF-α、iNOS、COX-2、IL-1β、IL-6、NO 和 PGE2 的水平,以及 iNOS/Arg-1 和 NO/urea 的比值(p<0.001)。

结论

我们的发现提供了证据表明尖瓣木具有神经保护作用,并且可能被认为是治疗伴有小胶质细胞激活的神经退行性疾病的有效治疗剂,例如 AD。

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