EUROPEAN JOURNAL OF PHARMACOLOGY
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2020
·
IF 3.263
Min Chen,Qiu-Ping Zhang,Ji-Xiao Zhu,Jie Cheng,Qing Liu,Guang-Hui Xu,Cheng-Fu Li,Li-Tao Yi
It has been reported that liquiritin produced an antidepressant-like effect in rodents. However, little information is known regarding its antidepressant activity with the regulation of fibroblast growth factor 2 (FGF-2), a protein maintaining development and maturation of the nervous central system . Therefore, the aim of the present study was to investigate the underlying FGF-2 modulation involved in the antidepressant-like effects of liquiritin. In the present study, mice were orally administrated with liquiritin for 7 days prior to LPS injection. The depressive-like behaviors , levels of FGF-2, number of Iba1 positive cells, expression of proinflammatory cytokines and density of dendritic spines were evaluated. The results showed that liquiritin significantly ameliorated the depressive-like behaviors in mice response to LPS injection. Liquiritin reversed the reduction of FGF-2 levels in the hippocampus of LPS induced mice. In addition, the microglial activation caused by LPS was attenuated by liquiritin, in accordance with downregulation in mRNA levels of proinflammatory cytokines. Moreover, liquiritin also increased the density of dendritic spines in the hippocampus, which was suppressed by LPS. In conclusion, our findings demonstrated that liquiritin exerted the antidepressant-like effects in LPS-induced depression through FGF-2 enhancement by inhibiting neuroinflammation and maintaining synaptogenesis .
研究领域:
药理学
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神经科学
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免疫学
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DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2020
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IF 4.268
Xin Shan,Jing Chen,Shilin Dai,Jie Wang,Zhiheng Huang,Zhiyang Lv,Qian Wang,Qinan Wu
Background Cyanidin (CY) is one of the most abundant anthocyanidins found in red-purple diet sources such as grapes, blueberries and purple corns . CY has been proven to exhibit a wide range of biological functions including antioxidant, antiviral, anticarcinogenic and anti-inflammatory properties. Purpose This study investigated the anti-depressive activity of CY and its related mechanism. Methods In the behavioral tests, CY-related effects on depressive symptoms were evaluated. Then the changes in PI3K/AKT/FOXG1/FGF-2 signaling and adult neurogenesis including doublecortin (DCX+) cell number, dendritic length, secondary and third dendrites number in the hippocampus were investigated by Immunofluorescence and Western blot analyses. PI3K antagonist LY 294,002 was used to verify the unique impact of PI3K/AKT/FoxG1/FGF-2 signaling on CY-related antidepressant efficacy. Results CY grossly reversed CUMS-induced behavioral defects, The DCX+ cell number and protein levels increased in CUMS mice receiving CY administration. LY 294,002 successfully blocked CY-induced improvements in depressive behaviors, neurogenesis, and protein levels in CUMS mice. Conclusion The findings demonstrated that CY was efficacious in alleviating depression-like symptoms, which was dependent on PI3K/AKT/FoxG1/FGF-2 signaling-modulated neurogenesis enhancement.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Jie Cheng,Min Chen,Hui-Qi Wan,Xue-Qin Chen,Cheng-Fu Li,Ji-Xiao Zhu,Qing Liu,Guang-Hui Xu,Li-Tao Yi
Ethnopharmacological relevance Paeonia lactiflora is a famous Traditional Chinese medicine widely used for immunological regulation. Paeoniflorin , the main component of Paeonia lactiflora , exerts neuroprotective and antidepressant-like effects in rodents. Aim of the study Fibroblast growth factor 2 (FGF-2) is essentially required in the central nervous system as it acts as both a neurotrophic factor and an anti-inflammatory factor participating in the regulation of proliferation, differentiation and apoptosis of neurons in the brain. However, it is unclear whether paeoniflorin could exert antidepressant effects via regulating FGF-2. Materials and methods In the present study, the effects of paeoniflorin were evaluated in depressive mice induced by the endotoxin lipopolysaccharide (LPS) injection. Results The results showed that paeoniflorin markedly increased sucrose preference and reduced immobility time in LPS mice, indicating antidepressant effects. Consistent with the results from molecular docking showing paeoniflorin antagonizes TLR4 , NF-κB and NLRP3, the biochemical analysis also indicated paeoniflorin inhibited TLR4/NF-κB/NLRP3 signaling, decreased proinflammatory cytokine levels and microglial activation in the hippocampus of LPS induced mice. In addition, the levels of neuronal FGF-2 and the density of dendritic spine were improved by paeoniflorin. More importantly, the FGFR1 inhibitor SU5402 prevented the antidepressant effects of paeoniflorin and blocked the neuroinflammatory and neurogenic regulatory effects of paeoniflorin, indicating that FGF-2/FGFR1 activation was required for the effects of paeoniflorin. Conclusion Taken together, the results demonstrate that paeoniflorin exhibits neuroprotective and antidepressant effects in mice, which may be mediated by activating neuronal FGF-2/FGFR1 signaling via the inhibition of microglial activation in the hippocampus.
研究领域:
药理学
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神经科学
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免疫学
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中医
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DOI
PubMed
高影响因子
Journal of Materials Chemistry B
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2020
·Vol. 8
·期 43
·9921-9932
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IF 5.344
Min Ge,Yaqi Sheng,Shuyue Qi,Lei Cao,Yan Zhang,Jun Yang
Incorporating poly(lactic-co-glycolic) acid (PLGA) microparticles into human mesenchymal stem cells (hMSC) aggregates has shown promising application prospects. However, the acidic degradation products and burst release of PLGA microparticles still need to be ameliorated. In this study, the PLGA/chitosan–heparin (P/C–h) composite microparticles were successfully fabricated by integrating the double emulsion and microfluidic technology through the precise manipulation of the emulsion composition and flow rate of the two-phase in a flow-focusing chip. The P/C–h microparticles were highly monodispersed with a diameter of 23.45 ± 0.25 μm and shell–core structure of the PLGA encapsulated C–h complex, which were suitable for the fabrication of hMSC aggregates. When the mass ratio of PLGA to the C–h complex was optimized to 2 : 1, the pH of the leach liquor of P/C–h microparticles remained neutral. Compared with those of PLGA microparticles, the cytotoxicity and the initial burst release (loaded FGF-2 and VEGF) were both significantly reduced in P/C–h microparticles. Furthermore, the survival, stemness, as well as secretion and migration abilities of cells in hMSC aggregates incorporating P/C–h microparticles were also enhanced. In summary, the P/C–h composite microparticles prepared by the droplet microfluidic technique support the optimal biological and functional profile of the hMSC aggregates, which may facilitate the clinical applications of MSC-based therapy.
研究领域:
生物医学工程
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组织工程
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干细胞生物学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Zhihong Deng,Lifeng Zhao,Xiuxue Li,Chang-Yun Wang,Yue Zhou,Mengfei Li,Yingfei Li,Xianjun Fu
Appropriate topical dressings for burn treatments are important to accelerate skin wound recovery and prevent external infections. This study aimed to evaluate the effect and investigate the mechanism of folium crataegi ( Crataegus pinnatifida Bge. ) for the treatment of burn wounds, as well as to compare the therapeutic effects of aqueous extracts ( HLW ) and alcoholic extracts ( HLE ) from folium crataegi . The results demonstrated that both HLW and HLE groups exhibited a higher wound contraction rate than the silver sulfadiazine ( SSD ) ointment group. Moreover, HLW showed more significant wound repair effects than HLE . HLW significantly increased levels of EGF and FGF-2 in wound tissue, as well as TGF-β1 , VEGF , CAT and IL-10 in serum. Folium crataegi extract, especially aqueous extracts, exerted good anti-inflammatory, anti-oxidant and anti-bacterial effects by upregulating the expression of lag3 , txn1 and slpi , respectively. Folium crataegi extract significantly inhibits the expression of npas2 , a key gene in the circadian rhythm pathway. In conclusion, this research illustrated that the folium crataegi extract, especially aqueous extracts, had better therapeutic effects on skin burns through multiple ways, possibly including a novel mechanism related to circadian rhythm pathway. These findings suggest that folium crataegi could be a valuable source of compounds for enhancing skin regeneration through multiple ways.
研究领域:
药理学
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烧伤治疗
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伤口愈合
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分子生物学
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免疫学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
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2017
·Vol. 5
·期 11
·2251-2267
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IF 4.21
Jie Wu,Kunxi Zhang,Xi Yu,Jianxun Ding,Lei Cui,Jingbo Yin
The key barrier to the clinical application of tissue engineering scaffolds is the limitation of rapid and sufficient vascularization. Adipose-derived stem cells (ASCs), especially multicellular aggregates, exhibited a promising angiogenic activity. Herein, we designed a series of poly(L-glutamic acid) (PLGA)-based hydrogels with tunable hydration to control the in situ formation of multicellular spheroids. Oligo(ethylene glycol)s (OEGs) were employed to regulate the hydration of hydrogels. The hydrogel cross-linked with ethylene glycol (OEG1) supported the most excellent adhesion and proliferation of human ASCs in vitro. However, as the hydration of hydrogels strengthened, the adherent ASCs were gradually replaced with multicellular spheroids. Moreover, the in situ formation of spheroids was more effective in upregulating hypoxia-adaptive signals (e.g., hypoxia-inducible factor-1α, HIF-1α) and enhancing the secretion of angiogenic factors (e.g., vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2)) compared to adherent cells in OEG1 hydrogels. The hydrogel cross-linked with oligo(ethylene glycol)400 (OEG9) carrying spheroids induced a high angiogenic response of host tissue in vivo, resulting in an improved system vascularization, compared to adherent cells in the OEG1 hydrogel. These features indicated that the PLGA-based hydrogels were expected to be applied toward bone and fat tissue regeneration.
研究领域:
组织工程
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生物材料
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再生医学
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细胞生物学
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血管生成
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DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
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2025
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IF 11.5
Xiaotong Hu,Daping Xie,Yuwei Li,Yiming Niu,Rongwei Tan,Zhending She,Chunming Wang
Artificial dermal matrixes (ADMs) are valuable clinical options for treating large soft tissue defects, but their suboptimal bioactivities compared with the real tissue limit their therapeutic potential. For example, glycosaminoglycan (GAG) polysaccharides in the native skin vitally and differentially regulate endogenous growth factors (GFs) to maintain tissue homeostasis. However, the GAG used in the current ADMs has often lost such delicate regulation. Here, we developed a novel polysaccharide-based ADM that can promote skin tissue repair through selective modulation of specific pro-healing GFs. First, we prepared a plant-derived backbone of glucomannan (named BSP) – representing the two dominant monosaccharide components in the human body – in mass and homogenic quality. Then, we modified this backbone with sulfate and acetyl groups in a controlled manner to yield an optimized BSP derivative (S M A L -BSP) as a main composition to generate a new ADM. In vitro, S M A L -BSP enabled the ADM to selectively sequester pro-angiogenic GFs of VEGF-A and FGF-2 in situ for stimulating endothelial cell growth. Moreover, the addition of the acetyl group induced macrophages to secrete nitric oxide (NO) with antibacterial activities. Further in vivo tests in a rat model of full-thickness skin wounds indicated that S M A L -BSP ADM could sequester GFs in situ to promote angiogenesis and thus tissue regeneration, with superior effects than conventional chondroitin sulfate-based ADM, while showing no adverse effects often associated with animal-derived products. Our study represents a novel strategy for ADM design, targeting selective GF sequestration towards optimal skin tissue regeneration.
研究领域:
组织工程
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生物材料
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伤口愈合
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药剂学
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DOI
PubMed
高影响因子
Stem Cell Research & Therapy
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2022
·Vol. 13
·期 1
·1-16
·
IF 8.079
Cui XiaoLing,Wang XiaoTan,Wen Jie,Li Xiao,Li Nan,Hao XuXiao,Zhao BaoXiang,Wu Xunwei,Miao JunYing
Background Human dermal fibroblasts (HDFs) have the potential to differentiate into vascular endothelial cells (VECs), but their differentiation rate is low and the mechanism involved is not clear. The small molecule pathway controls the phenotype of fibroblasts by activating cellular signaling pathways, which is a more convenient method in the differentiation strategy of HDFs into VECs. Methods In this study, HDFs were treated with the different doses of CPP ((E)-4-(4-(4-(7-(diethylamino)-2-oxo-2H-chromene-3-carbonyl) piperazin-1-yl) styryl)-1-methylpyridin-1-ium iodide), and the mRNA and protein levels of HDFs were detected by qPCR, Western blot, flow cytometry and immunofluorescent staining. The matrigel assays, acetylated-LDL uptake and angiogenesis assays of chick embryo chorioallantoic membrane (CAM) and hindlimb ischemia model of nude mice were performed to evaluate the functions of VECs derived from HDFs. Results Here, we report that the small chemical molecule, CPP, can effectively induce HDFs to differentiate into VECs. First, we observed the morphological changes of HDFS treated with CPP. Flow cytometry, Western blot and qRT-PCR analyses showed that CPP effectively decreased the level of the HDFs-marker Vimentin and increased levels of the VEC-markers CD31, CD133, TEK, ERG, vWF, KDR and CDH5. Detection of the percentage of CD31-positive cells by immunofluorescent staining confirmed that CPP can effectively induce HDFs to differentiate into VECs. The results of Matrigel assays, DiI-ac-LDL uptake, angiogenesis assays on CAM and hindlimb ischemia model of nude mice showed that CPP-induced HDFs have the functions of VECs in vitro and in vivo. Western blot and qRT-PCR analysis showed that CPP induces HDFs to differentiate into VECs by promoting the expression of pro-angiogenic factors (VEGF, FGF-2 and PDGF-BB). Conclusions Our data suggest that the small chemical molecule CPP efficiently induces the differentiation of HDFs into VECs. Simultaneously, this new inducer provides a potential to develop new approaches to restore vascular function for the treatment of ischemic vascular diseases.
研究领域:
细胞生物学
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分子生物学
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血管生物学
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再生医学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）