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胶红丸通过调节丝裂原活化蛋白激酶/核因子 κB 通路减轻神经炎症和淀粉样β蛋白诱导的认知功能障碍。

Jiaohong pills attenuate neuroinflammation and amyloid-β protein-induced cognitive deficits by modulating the mitogen-activated protein kinase/nuclear factor kappa-B pathway.

机构信息

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.

出版信息

Animal Model Exp Med. 2024 Jun;7(3):222-233. doi: 10.1002/ame2.12369. Epub 2024 Jan 4.

Abstract

BACKGROUND

Jiaohong pills (JHP) consist of Pericarpium Zanthoxyli (PZ) and Radix Rehmanniae, two herbs that have been extensively investigated over many years due to their potential protective effects against cognitive decline and memory impairment. However, the precise mechanisms underlying the beneficial effects remain elusive. Here, research studies were conducted to investigate and validate the therapeutic effects of JHP on Alzheimer's disease.

METHODS

BV-2 cell inflammation was induced by lipopolysaccharide. AD mice were administered amyloid-β (Aβ). Behavioral experiments were used to evaluate learning and memory ability. The levels of nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-10 (IL-10) were detected using enzyme-linked immunosorbent assay (ELISA). The protein expressions of inducible nitric oxide synthase (iNOS) and the phosphorylation level of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) were detected using Western blot. Nissl staining was used to detect neuronal degeneration.

RESULTS

The results demonstrated that an alcoholic extract of PZ significantly decreased the levels of NO, IL-1β, TNF-α, and iNOS; increased the expression level of IL-10; and significantly decreased the phosphorylation levels of MAPK and NF-κB. These inhibitory effects were further confirmed in the AD mouse model. Meanwhile, JHP improved learning and memory function in AD mice, reduced neuronal damage, and enriched the Nissl bodies in the hippocampus. Moreover, IL-1β and TNF-α in the cortex were significantly downregulated after JHP administration, whereas IL-10 showed increased expression.

CONCLUSIONS

It was found that JHP reduced neuroinflammatory response in AD mice by targeting the MAPK/NF-κB signaling pathway.

摘要

背景

焦红丸(JHP)由两面针(PZ)和熟地黄组成,这两种草药由于具有预防认知能力下降和记忆力减退的潜在保护作用,多年来一直受到广泛研究。然而,其有益作用的确切机制仍难以捉摸。在这里,进行了研究以研究和验证 JHP 对阿尔茨海默病的治疗作用。

方法

用脂多糖诱导 BV-2 细胞炎症。给 AD 小鼠注射淀粉样蛋白-β(Aβ)。采用行为学实验评估学习和记忆能力。用酶联免疫吸附试验(ELISA)检测一氧化氮(NO)、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)和白细胞介素-10(IL-10)的水平。用 Western blot 检测诱导型一氧化氮合酶(iNOS)的蛋白表达和丝裂原激活蛋白激酶(MAPK)和核因子 kappa-B(NF-κB)的磷酸化水平。用尼氏染色检测神经元变性。

结果

结果表明,PZ 的醇提物显著降低了 NO、IL-1β、TNF-α和 iNOS 的水平;增加了 IL-10 的表达水平;并显著降低了 MAPK 和 NF-κB 的磷酸化水平。这些抑制作用在 AD 小鼠模型中得到了进一步证实。同时,JHP 改善了 AD 小鼠的学习和记忆功能,减少了神经元损伤,并丰富了海马的尼氏体。此外,JHP 给药后皮质中的 IL-1β和 TNF-α明显下调,而 IL-10 则表达增加。

结论

研究发现,JHP 通过靶向 MAPK/NF-κB 信号通路减少 AD 小鼠的神经炎症反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4888/11228096/559eb4d7b065/AME2-7-222-g002.jpg

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