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中药药对白芍和白术通过抑制丝裂原活化蛋白激酶(MAPK)和核因子κB(NF-κB)信号通路抑制脂多糖(LPS)诱导的炎症反应。

Chinese herb pair Paeoniae Radix Alba and Atractylodis Macrocephalae Rhizoma suppresses LPS-induced inflammatory response through inhibiting MAPK and NF-κB pathway.

作者信息

Zhou Yangyang, Tao Hongxun, Wang Anqi, Zhong Zhangfeng, Wu Xu, Wang Mei, Bian Zhaoxiang, Wang Shengpeng, Wang Yitao

机构信息

State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Avenida da Universidade, Taipa, Macao China.

2Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan China.

出版信息

Chin Med. 2019 Jan 29;14:2. doi: 10.1186/s13020-019-0224-2. eCollection 2019.

Abstract

BACKGROUND

The combination of Radix Paeoniae Alba (RPA) and Rhizoma Atractylodis Macrocephalae (RAM) has long been used as a classic herb pair for the treatment of gynecologic and gastrointestinal diseases, but the underlying mechanisms of the herb pair remain unknown. This study aims to explore the anti-inflammatory potentials of RPA-RAM herb pair and to elucidate the underlying mechanisms.

METHODS

The bioactive parts of RPA-RAM were extracted and screened through the inhibitory effects against nitric oxide (NO) production. The effects of optimized RPA-RAM extracts (OPAE) on inflammation-associated mediators were investigated by Western blotting, real-time quantitative PCR (RT-qPCR), Enzyme-linked immunosorbent (ELISA) and immunofluorescence staining.

RESULTS

OPAE potently suppressed the productions of NO, TNF-α, IL-6 and MCP-1 in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, concentration-dependently inhibited protein level of inducible nitric oxide synthase (iNOS), dramatically downregulated mRNA expression of iNOS, TNF-α, IL-6 and MCP-1. In addition, OPAE significantly prevented phosphorylation and degradation of inhibitory kappa Bα (IκBα) and subsequently restrained the nuclear translocation of NF-κB p65. Pretreatment with OPAE also attenuated the LPS-induced phosphorylation of ERK, JNK and p38.

CONCLUSIONS

Our findings demonstrated that OPAE suppressed inflammatory responses in LPS-stimulated RAW 264.7 macrophages by decreasing critical molecules involved in MAPK and NF-κB pathway, suggesting that the herb pair could be a promising therapeutic candidate for inflammation-related diseases.

摘要

背景

白芍(RPA)与白术(RAM)的组合长期以来一直作为经典药对用于治疗妇科和胃肠道疾病,但其潜在机制仍不清楚。本研究旨在探讨RPA-RAM药对的抗炎潜力并阐明其潜在机制。

方法

通过对一氧化氮(NO)产生的抑制作用提取并筛选RPA-RAM的生物活性成分。通过蛋白质印迹法、实时定量聚合酶链反应(RT-qPCR)、酶联免疫吸附测定(ELISA)和免疫荧光染色研究优化后的RPA-RAM提取物(OPAE)对炎症相关介质的影响。

结果

OPAE能有效抑制脂多糖(LPS)诱导的RAW 264.7巨噬细胞中NO、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和单核细胞趋化蛋白-1(MCP-1)的产生,浓度依赖性地抑制诱导型一氧化氮合酶(iNOS)的蛋白水平,显著下调iNOS、TNF-α、IL-6和MCP-1的mRNA表达。此外,OPAE显著阻止抑制性κBα(IκBα)的磷酸化和降解,随后抑制核因子κB p65(NF-κB p65)的核转位。用OPAE预处理还可减弱LPS诱导的细胞外信号调节激酶(ERK)、应激活化蛋白激酶(JNK)和p38的磷酸化。

结论

我们的研究结果表明,OPAE通过减少丝裂原活化蛋白激酶(MAPK)和NF-κB途径中的关键分子来抑制LPS刺激的RAW 264.7巨噬细胞中的炎症反应,表明该药对可能是炎症相关疾病的一种有前景的治疗候选药物。

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