The total iridoid glycoside extract of Lamiophlomis rotata Kudo induces M2 macrophage polarization to accelerate wound healing by RAS/ p38 MAPK/ NF-?B pathway

作者全名："Lei, Lei; Wan, Guoguo; Geng, Xiaoyu; Sun, Jianguo; Zhang, Yi; Wang, Jianwei; Yang, Congwen; Pan, Zheng"

作者地址："[Lei, Lei; Wan, Guoguo; Geng, Xiaoyu; Sun, Jianguo; Wang, Jianwei; Yang, Congwen; Pan, Zheng] Chongqing Med Univ, Chongqing, Peoples R China; [Zhang, Yi] Chengdu Univ Tradit Chinese Med, Chengdu 611130, Peoples R China; [Pan, Zheng] Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing, Peoples R China"

通信作者："Pan, Z (通讯作者)，Chongqing Med Univ, Coll Tradit Chinese Med, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, 1 Yixueyuan Rd, Chongqing, Peoples R China."

来源：JOURNAL OF ETHNOPHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000971517100001

JCR分区：Q1

影响因子：4.8

年份：2023

卷号：307

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Lamiophlomis rotata; Iridoid glycoside; M2 macrophage; Wound healing

摘要："Ethnopharmacological relevance: Lamiophlomis rotata (Benth.) Kudo (L. rotata), a Tibetan medicinal plant, is used to treat ""yellow-water diseases"", such as skin disease, jaundice and rheumatism. Our previous study showed that the iridoid glycoside extract of L. rotata (IGLR) is the major constituent of skin wound healing. However, the role of IGLR in the biological process of trauma repair and the probable mechanism of the action remain largely unknown.Aim of the study: To investigate the role of IGLR in the biological process of trauma repair and the probable mechanism of the action. Materials and methods: The role of IGLR in wound healing was investigated by overall skin wound in mice with Hematoxylin and Eosin (H&E) and Masson trichrome staining. The anti-inflammatory, angiogenesis-promoting and fibril formation effects of IGLR were visualized in wound skin tissue by immunofluorescence staining, and the proinflammatory factors and growth factors were assayed by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Macrophages, dermal fibroblasts, and endothelial cells were cultured to measure the direct/indirect interaction effects of IGLR on the proliferation and migration of cells, and flow cytometry was employed to assess the role of IGLR on macrophage phenotype. Network pharmacology combined with Western blot experiments were conducted to explore possible mechanisms of the actions.Results: IGLR increased the expression of CD206 (M2 markers) through the RAS/p38 MAPK/NF-kappa B signaling pathway during wound injury in vivo and in vitro. IGLR suppressed the inflammatory cytokines iNOS, IL-1 beta and TNF-alpha in the early stage of wound healing. During the proliferation step of wound repair, IGLR promoted angiogenesis and fibril formation by increasing the expression of VEGF, CD31, TGF-beta and alpha-SMA in wound tissue, and similar results were verified by RT-PCR and ELISA. In a paracrine mechanism, the extract promoted the proliferation of dermal fibroblasts, and endothelial cells were founded by the conditioned medium (CM). Conclusion: IGLR induced M2 macrophage polarization in the early stage of wound healing; in turn, IGLR played a key role in the transition from inflammation to cell proliferation during the biological process of wound healing."

基金机构：National Natural Science Foundation of China [81973567]; Chongqing talent program [cstc2022ycjh-bgzxm0010]

基金资助正文："This work was supported by the National Natural Science Foundation of China (grant number: 81973567) , and Chongqing talent program (cstc2022ycjh-bgzxm0010) ."