Quercetin Promotes Diabetic Wound Healing via Switching Macrophages From M1 to M2 Polarization

被引:107
作者
Fu, Jia [1 ,2 ,3 ]
Huang, Jingjuan [1 ,2 ,3 ]
Lin, Man [1 ,2 ,3 ]
Xie, Tingting [1 ,2 ,3 ]
You, Tianhui [1 ,2 ,3 ]
机构
[1] Guangdong Pharmaceut Univ, Sch Nursing, Guangzhou 510310, Guangdong, Peoples R China
[2] Guangdong Pharmaceut Univ, Guangzhou Key Lab Construct & Applicat New Drug S, Guangzhou, Guangdong, Peoples R China
[3] Guangdong Pharmaceut Univ, Key Lab New Drug Discovery & Evaluat Ordinary Uni, Guangzhou, Guangdong, Peoples R China
关键词
Wound healing; Quercetin; Macrophage; Inflammation; Diabetic rats; HEME OXYGENASE-1; INJURY; DIFFERENTIATION; INFLAMMATION; PLASTICITY; INDUCTION; INSULIN; REPAIR;
D O I
10.1016/j.jss.2019.09.011
中图分类号
R61 [外科手术学];
学科分类号
摘要
Background: For patients with diabetes mellitus, excessive and long-lasting inflammatory reactions at the wound site commonly lead to the delayed refractory wound healing. The polarization of macrophages in terms of M1 and M2 phenotypes is closely related to the production of inflammatory cytokines. Quercetin is traditionally recognized to have anti-inflammatory effect; however, whether quercetin modulates macrophage polarization from M1 to M2 and thus promotes diabetic wound healing remain unknown. Materials and methods: Wounded male diabetic rats were equally divided into five groups: model group, solvent control group (10% DMSO), and three drug groups treated with quercetin (Q) at concentrations of 10 mg/mL (Q-LD [low dose]), 20 mg/mL (Q-MD [medium dose]), and 40 mg/mL (Q-HD [high dose]), respectively. The anti-inflammatory effect of quercetin on diabetic wounds was observed. Immunohistochemistry and quantificational real-time polymerase chain reaction were applied to test the changes in macrophage polarization and inflammatory responses. Results: The wound contraction was fastest in Q-HD group. Hematoxylin and eosin (H&E) and Masson's trichrome staining revealed that fibroblast distribution and collagen deposition in quercetin-treated groups were significantly higher than those in the model group. Immunohistochemistry tests showed more CD206-positive cells and less iNOS-positive cells in quercetin-treated groups. Furthermore, the levels of proinflammatory factors in quercetin-treated groups were lower than those in the model group, whereas the levels of the anti-inflammatory factors and angiogenesis-related factors were relatively higher. Conclusions: In short, quercetin inhibits inflammatory reactions via modulating macrophage polarization switching from M1 to M2 phenotype, thereby accelerating the diabetic wound repair. (C) 2019 Published by Elsevier Inc.
引用
收藏
页码:213 / 223
页数:11
相关论文
共 42 条
  • [1] Hypoglycemic, Hypolipidemic, and Wound Healing Potential of Quercetin in Streptozotocin-Induced Diabetic Rats
    Ahmad, Mahrukh
    Sultana, Mudasir
    Raina, Rajinder
    Pankaj, Nrip Kishore
    Verma, Pawan Kumar
    Prawez, Shahid
    [J]. PHARMACOGNOSY MAGAZINE, 2017, 13 (51) : S633 - S639
  • [2] Quercetin and low level laser therapy promote wound healing process in diabetic rats via structural reorganization and modulatory effects on inflammation and oxidative stress
    Ahmed, Osama M.
    Mohamed, Tarek
    Moustafa, Hala
    Hamdy, Hany
    Ahmed, Rasha R.
    Aboud, Ebtsam
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2018, 101 : 58 - 73
  • [3] Effect of Clausena excavata Burm. f. (Rutaceae) leaf extract on wound healing and antioxidant activity in rats
    Albaayit, Shaymaa Fadhel Abbas
    Abba, Yusuf
    Rasedee, Abdullah
    Abdullah, Noorlidah
    [J]. DRUG DESIGN DEVELOPMENT AND THERAPY, 2015, 9 : 3507 - 3518
  • [4] Anti-inflammatory actions of the heme oxygenase-1 pathway
    Alcaraz, MJ
    Fernandez, P
    Guillén, MI
    [J]. CURRENT PHARMACEUTICAL DESIGN, 2003, 9 (30) : 2541 - 2551
  • [5] [Anonymous], 2016, REV ENDOCR METAB DIS
  • [6] Effect of Topical Insulin on Second-Degree Burns in Diabetic Rats
    Azevedo, F.
    Pessoa, A.
    Moreira, G.
    Dos Santos, M.
    Liberti, E.
    Araujo, E.
    Carvalho, C.
    Saad, M.
    Lima, M. H.
    [J]. BIOLOGICAL RESEARCH FOR NURSING, 2016, 18 (02) : 181 - 192
  • [7] Pseudomonas aeruginosa infection alters the macrophage phenotype switching process during wound healing in diabetic mice
    Chen, Sinuo
    Li, Renren
    Cheng, Chun
    Xu, Jing-Ying
    Jin, Caixia
    Gao, Furong
    Wang, Juan
    Zhang, Jieping
    Zhang, Jingfa
    Wang, Hong
    Lu, Lixia
    Xu, Guo-Tong
    Tian, Haibin
    [J]. CELL BIOLOGY INTERNATIONAL, 2018, 42 (07) : 877 - 889
  • [8] PEGylated graphene oxide-mediated quercetin-modified collagen hybrid scaffold for enhancement of MSCs differentiation potential and diabetic wound healing
    Chu, Jing
    Shi, Panpan
    Yan, Wenxia
    Fu, Jinping
    Yang, Zhi
    He, Chengmin
    Deng, Xiaoyuan
    Liu, Hanping
    [J]. NANOSCALE, 2018, 10 (20) : 9547 - 9560
  • [9] Quercetin disrupts tyrosine-phosphorylated phosphatidylinositol 3-kinase and myeloid differentiation factor-88 association, and inhibits MAPK/AP-1 and IKK/NF-κB-induced inflammatory mediators production in RAW 264.7 cells
    Endale, Mehari
    Park, Seung-Chun
    Kim, Suk
    Kim, Seung-Hyung
    Yang, Yanyan
    Cho, Jae Youl
    Rhee, Man Hee
    [J]. IMMUNOBIOLOGY, 2013, 218 (12) : 1452 - 1467
  • [10] Topical vascular endothelial growth factor accelerates diabetic wound healing through increased angiogenesis and by mobilizing and recruiting bone marrow-derived cells
    Galiano, RD
    Tepper, OM
    Pelo, CR
    Bhatt, KA
    Callaghan, M
    Bastidas, N
    Bunting, S
    Steinmetz, HG
    Gurtner, GC
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2004, 164 (06) : 1935 - 1947