PHYTOTHERAPY RESEARCH
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2022
·Vol. 36
·期 4
·1678-1691
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IF 6.388
Shiquan Chang,Xin Li,Yachun Zheng,Huimei Shi,Di Zhang,Bei Jing,Zhenni Chen,Guoqiang Qian,Guoping Zhao
Switching microglial polarization from the M1 to M2 phenotype is a promising therapeutic strategy for neuropathic pain (NP). Toll-like receptor 4 (TLR4) is activated by lipopolysaccharide (LPS). Uncontrolled activation of TLR4 has been proven to trigger chronic inflammation. Kaempferol, a dietary flavonoid, is known to have anti-inflammatory properties. This study is aimed to investigate the analgesic and anti-inflammatory effects and the underlying mechanisms of kaempferol, which were explored with an NP model in vivo and LPS-induced injury in microglial BV2 cells in vitro. The levels of proinflammatory cytokines were evaluated. H&E staining and immunohistochemistry were used to assess the sciatic nerve condition after chronic constriction injury surgery. Western blotting and immunofluorescence were used to determine whether TLR4/NF-ĸB signaling pathway plays a major role in kaempferol-mediated alleviation of neuroinflammation. Quantitative real-time polymerase chain reaction and flow cytometry were used to examine the modulator effect of kaempferol on microglial M1/M2 polarization. We found that kaempferol treatment can significantly reduce NP and proinflammatory cytokine production. Kaempferol attenuated the activation of TLR4/NF-κB pathways in LPS-activated BV2 cells. The analgesic effects of kaempferol on NP may be due to inhibition of microglia activation and switching the M1 to M2 phenotype.
研究领域:
神经科学
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药理学
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炎症
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疼痛管理
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
·
IF 4.2
Ruyi Zhu,Yaling Zhang,Weitai He,Yanan Sun,Xin Zhao,Yaping Yan,Qian Zhang
Wogonoside (WG) is a natural flavonoid extracted from Scutellariae Radix, recognized for its established anti-inflammatory properties. However, the role of WG in the context of neuroinflammation after spinal cord injury (SCI) remains inadequately elucidated. This study employed in silico , in vitro , and in vivo methodologies to investigate the impact of WG on microglia-mediated neuroinflammation after SCI. In the in silico experiment, we identified 15 potential target genes of WG associated with SCI. These genes were linked to the regulation of inflammatory response and immune defense. Molecular docking maps revealed toll-like receptor 4 as a molecular target for WG, demonstrating binding through a hydrogen bond (Lys263, Ser120). In lipopolysaccharide-stimulated BV2 cells and SCI mice, WG significantly attenuated microglial activation and facilitated a phenotype shift from M1 to M2. This was evidenced by the reversal of the increased expressions of Iba1, GFAP, and iNOS, as well as the decreased expression of Arg1. WG also suppressed the production of pro-inflammatory mediators (NO, TNF-α, IL-6, IL-1α, IL-1β, C1q). WG exerted these effects by suppressing the TLR4/MyD88/NF-κB signaling axis in microglia. Furthermore, by reducing levels of TNF-α, IL-1α, and C1q in supernatant of LPS-induced microglia, WG indirectly induced astrocytes change to A2 phenotype, evidenced by transcriptome sequencing result of primary mouse astrocytes. All these events above collectively created a favorable microenvironment, contributing to a significant alleviation of weight loss and neuronal damage at the lesion site of SCI mice. Our findings substantiate the efficacy of WG in mitigating neuroinflammation after SCI, thereby warranting further exploration.
研究领域:
药理学
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神经科学
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炎症
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2023
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IF 10.3
Y. Wang,Y. Feng,J. Yan,X. Han,P. Song,Y. Wu,X. Wang,Z. Mu,X. Li,H. Zhang
Wound healing is a complex and orchestrated physiological process that involves multiple stages, including hemostasis, inflammation, proliferation, and remodeling stages. Various nanomaterials have been developed to improve the wound healing; however, most of them can only promote an individual stage of this intricate process, lacking hierarchical acceleration for multiple stages. In the present study, spiky gold-palladium heterostructured nanoparticles (AuPd SHs) were designed to possess topographical architectures on the surface of nanoparticles, capable of promoting multistage wound healing in a programmable manner. First, the spiky surface topography of AuPd SHs exhibited the potent nanobridge effect for rapid wound closure, promoting the hemostasis stage. Second, the heterostructures of AuPd SHs realized visible-light-mediated hot electron excitation and electron–hole spatial separation between Au cores and Pd spikes to efficiently generate reactive oxygen species , beneficial for the inflammation stage. Third, the spiky surface topography of AuPd SHs triggered macrophage polarization from M1 to M2 phenotype, promoting the proliferation and maturation stages. Spiky AuPd SHs with simple composition and compact structures exhibit hierarchical acceleration on multiple stages of wound healing.
研究领域:
纳米技术
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生物材料
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生物医学工程
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组织工程
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伤口愈合
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产品关联
DOI
高影响因子
ADVANCED MATERIALS
·
2025
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IF 26.8
Yajun Shuai,Tao Yang,Meidan Zheng,Li Zheng,Jie Wang,Chuanbin Mao,Mingying Yang
Assembling natural proteins into large, strong, bone-mimetic scaffolds for repairing bone defects in large-animal load-bearing sites remain elusive. Here this challenge is tackled by assembling pure silk fibroin (SF) into 3D scaffolds with cortical-bone-like lamellae, superior strength, and biodegradability through freeze-casting. The unique lamellae promote the attachment, migration, and proliferation of tissue-regenerative cells (e.g., mesenchymal stem cells [MSCs] and human umbilical vein endothelial cells) around them, and are capable of developing in vitro into cortical-bone organoids with a high number of MSC-derived osteoblasts. High-SF-content lamellar scaffolds, regardless of MSC inoculation, regenerated more bone than non-lamellar or low-SF-content lamellar scaffolds. They accelerated neovascularization by transforming macrophages from M1 to M2 phenotype, promoting bone regeneration to repair large segmental bone defects (LSBD) in minipigs within three months, even without growth factor supplements. The bone regeneration can be further enhanced by controlling the orientation of the lamella to be parallel to the long axis of bone during implantation. This work demonstrates the power of oriented lamellar bone-like protein scaffolds in repairing LSBD in large animal models.
研究领域:
生物医学工程
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组织工程
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再生医学
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生物材料科学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 52
·2207637
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IF 19.924
Hongbin Yang,Zhenyan Yu,Shuaishuai Ji,Jie Yan,Yan kong,Qiang Huo,Zhijun Zhang,Yimin Niu,Yang Liu
The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra-articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane-coated, quercetin-loaded metal-organic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane-camouflaged nanoparticles containing various natural “eat me” signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macrophages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a “Trojan horse” strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membrane-coated nanoparticles to resolve inflammation by simulating specific inflammatory processes.
研究领域:
骨科
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纳米医学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）