针对不同表型的巨噬细胞：天然产物治疗炎症性骨和关节疾病的一种潜在策略。

Targeting different phenotypes of macrophages: A potential strategy for natural products to treat inflammatory bone and joint diseases.

机构信息

Graduate School, Heilongjiang University of Chinese Medicine, 24 Heping Road, Xiangfang District, Harbin, Heilongjiang 150040, China.

The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang 150000, China.

出版信息

Phytomedicine. 2023 Sep;118:154952. doi: 10.1016/j.phymed.2023.154952. Epub 2023 Jul 12.

DOI:10.1016/j.phymed.2023.154952

PMID:37506402

Abstract

BACKGROUND

Macrophages, a key class of immune cells, have a dual role in inflammatory responses, switching between anti-inflammatory M2 and pro-inflammatory M1 subtypes depending on the specific environment. Greater numbers of M1 macrophages correlate with increased production of inflammatory chemicals, decreased osteogenic potential, and eventually bone and joint disorders. Therefore, reversing M1 macrophages polarization is advantageous for lowering inflammatory factors. To better treat inflammatory bone disorders in the future, it may be helpful to gain insight into the specific mechanisms and natural products that modulate macrophage polarization.

OBJECTIVE

This review examines the impact of programmed cell death and different cells in the bone microenvironment on macrophage polarization, as well as the effects of natural products on the various phenotypes of macrophages, in order to suggest some possibilities for the treatment of inflammatory osteoarthritic disorders.

METHODS

Using 'macrophage polarization,' 'M1 macrophage' 'M2 macrophage' 'osteoporosis,' 'osteonecrosis of femoral head,' 'osteolysis,' 'gouty arthritis,' 'collagen-induced arthritis,' 'freund's adjuvant-induced arthritis,' 'adjuvant arthritis,' and 'rheumatoid arthritis' as search terms, the relevant literature was searched using the PubMed, the Cochrane Library and Web of Science databases.

RESULTS

Targeting macrophages through different signaling pathways has become a key mechanism for the treatment of inflammatory bone and joint diseases, including HIF-1α, NF-κB, AKT/mTOR, JAK1/2-STAT1, NF-κB, JNK, ERK, p-38α/β, p38/MAPK, PI3K/AKT, AMPK, AMPK/Sirt1, STAT TLR4/NF-κB, TLR4/NLRP3, NAMPT pathway, as well as the programmed cell death autophagy, pyroptosis and ERS.

CONCLUSION

As a result of a search of databases, we have summarized the available experimental and clinical evidence supporting herbal products as potential treatment agents for inflammatory osteoarthropathy. In this paper, we outline the various modulatory effects of natural substances targeting macrophages in various diseases, which may provide insight into drug options and directions for future clinical trials. In spite of this, more mechanistic studies on natural substances, as well as pharmacological, toxicological, and clinical studies are required.

摘要

背景

巨噬细胞是一类重要的免疫细胞，在炎症反应中具有双重作用，根据特定的环境在抗炎 M2 和促炎 M1 亚型之间转换。更多数量的 M1 巨噬细胞与炎症化学物质的产生增加、成骨潜能降低以及最终的骨骼和关节疾病相关。因此，逆转 M1 巨噬细胞极化有利于降低炎症因子。为了更好地治疗未来的炎症性骨疾病，深入了解调节巨噬细胞极化的特定机制和天然产物可能会有所帮助。

目的

本综述探讨了程序性细胞死亡和骨微环境中的不同细胞对巨噬细胞极化的影响，以及天然产物对各种巨噬细胞表型的影响，以期为炎症性骨关节炎疾病的治疗提供一些可能性。

方法

使用“巨噬细胞极化”“M1 巨噬细胞”“M2 巨噬细胞”“骨质疏松症”“股骨头坏死”“溶骨性骨病”“痛风性关节炎”“胶原诱导性关节炎”“弗氏完全佐剂诱导性关节炎”“佐剂性关节炎”和“类风湿性关节炎”作为检索词，通过 PubMed、Cochrane 图书馆和 Web of Science 数据库检索相关文献。

结果

通过不同的信号通路靶向巨噬细胞已成为治疗炎症性骨和关节疾病的关键机制，包括 HIF-1α、NF-κB、AKT/mTOR、JAK1/2-STAT1、NF-κB、JNK、ERK、p-38α/β、p38/MAPK、PI3K/AKT、AMPK、AMPK/Sirt1、STAT TLR4/NF-κB、TLR4/NLRP3、NAMPT 通路，以及程序性细胞死亡自噬、细胞焦亡和 ERS。