MOLECULES
·
2022
·Vol. 27
·期 14
·4535
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IF 4.927
Zhimin Xu,Yidan Sun,Huanyan Dai,Yujie Ma,Han Bing
The skull defects are challenging to self-heal, and autologous bone graft repair has numerous drawbacks. The scaffolds for the rapid and effective repair of skull defects have become an important research topic. In this study, polyvinyl alcohol (PVA)/β-tricalcium phosphate(β-TCP) composite scaffolds containing icariin (ICA) were prepared through direct-ink three-dimensional (3D) printing technology. β-TCP in the composite scaffold had osteoconductive capability, and the ICA molecule had osteoinductive capacity. The β-TCP and ICA components in the composite scaffold can enhance the capability to repair skull defects. We show that ICA exhibited a slow-release behaviour within 80 days. This behaviour helped the scaffold to continuously stimulate the formation of new bone. The results of in vitro cell compatibility experiments showed that the addition of ICA molecules contributed to the adhesion and proliferation of MC-3T3-E1 cells. The level of alkaline phosphatase secretion demonstrated that the slow release of ICA can promote the osteogenic differentiation of MC-3T3-E1 cells. The introduction of ICA molecules accelerated the in situ bone regeneration in in vivo. It is concluded that the 3D-printed PVA scaffold with β-TCP and ICA has a wide range of potential applications in the field of skull defect treatment.Keywords:three-dimensional printing;polyvinyl alcohol;icariin;β-tricalcium phosphate;skull base defects
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Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Zhou Mengyang,Guo Min,Shi Xincui,Ma Jie,Wang Shutao,Wu Shuo,Yan Weiqun,Wu Feng,Zhang Peibiao
Multifunctionality has becoming essential for bone tissue engineering materials, such as drug release. In this study, icariin (ICA)-incorporated poly(glycolide-co-caprolactone) (PGCL) porous microcarriers were fabricated and then coated with decellularized extracellular matrix (dECM) which was derived from bone marrow mesenchymal stem cells (BMSC). The porous structure was generated due to the soluble gelatin within the microcarriers. The initial released ICA in microcarriers regulated osteogenic ECM production by BMSCs during ECM formation. The dECM could further synergistically enhance the migration and osteogenic differentiation of BMSCs together with ICA as indicated by the transwell migration assay, ALP and ARS staining, as well as gene and protein expression. Furthermore, in vivo results also showed that dECM and ICA exhibited excellent synergistic effects in repairing rat calvarial defects. These findings suggest that the porous microcarriers loaded with ICA and dECM coatings have great potential in the field of bone tissue engineering.
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PHYTOMEDICINE
·
2024
·
IF 6.7
Wang Haoyue,Sun Kexiang,Tan Wei Shan,Gao Jiamin,Yuan Luyun,Wen Junkai,Deng Wanli
Background A controlled type of cell death called ferroptosis is linked to increased reactive oxygen species (ROS), lipid peroxidation, and iron buildup. Furthermore, evidence indicates that ferroptosis may act as an immunogenic form of cell death with potential physiological functions in tumors and immunosuppression. Inducing ferroptosis in tumor cells may have the potential to complement cancer immunotherapy strategies. The development of colorectal cancer (CRC) and the poor efficacy of immunotherapy are associated with the crosstalk of cellular ferroptosis. Currently, Icariin (ICA), the main bioactive component extracted from Epimedium , has been shown to inhibit a variety of cancers. However, the specific role and potential mechanism of ICA in regulating ferroptosis in CRC remains unclear. Purpose The aim of this investigation was to clarify the mechanism underlying the anti-CRC cancer properties of ICA and how it induces ferroptosis to enhance immunotherapy. Methods To evaluate cell viability, the Cell Counting Kit-8 (CCK-8) test was utilized. The transwell test and the wound healing assay were used to assess cell migration. A subcutaneous graft tumor model was constructed with C57BL/6 mice using MC38 colorectal cancer cell lines. The inhibitory effect of ICA on CRC, ferroptosis level and immunomodulatory effects were detected by serum biochemical assay, cytokine assay, hematoxylin-eosin (H&E) staining, immunofluorescence staining, CyTOF mass spectrometry flow screening and Western blotting. Western blotting, proteomics, molecular docking and microscale thermophoresis (MST) were used to forecast and confirm ICA's binding and interaction with HMGA2, STAT3, and HIF-1α. Moreover, the levels of lipid peroxidation and ferroptosis were assessed through the use of the C11-BODIPY fluorescent probe, the FerroOrange fluorescent probe, the iron level, the malondialdehyde (MDA) and reduced glutathione (GSH) assay kit, and Western blotting analysis. To assess alterations in mitochondrial structure and membrane potential, transmission electron microscopy (TEM) and JC-1 immunofluorescence were employed. Results It was demonstrated in the current study that ICA treatment inhibits CRC and enhances anti-PD-1 therapy efficacy by inciting ferroptosis. As shown in vitro, ICA inhibits CRC cell proliferation, migration, and apoptosis. As demonstrated in vivo, ICA has a dose-dependent tumor suppressor effect when combined with anti-PD-1, it can significantly inhibit tumor growth, increase the expression of serum TNF-α, IFN-γ, and granzyme B, and promote CD69 + CD8 + T, CD69 + CD8 + Tem, CD69 + CD8 + Teff, TCRβ + CD8 + T, TCRβ + CD8 + T, TCRβ + CD8 + Tem, TCRβ + CD8 + Teff. The inhibitory effect of ICA on CRC was associated with the binding of HMGA2, STAT3, and HIF-1α proteins, which inhibited CRC by increasing the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), promoting the accumulation of iron (Fe 2+ ), depletion of reduced glutathione (GSH), inhibiting SLC7A11 and GPX4 expressions, thereby inducing ferroptosis in CRC. As a consequence of ICA-induced ferroptosis, mitochondria are dysfunctional, with increased ROS production, membrane potential depolarization (MMP), and ATP production reduced. This process can be efficiently reversed by the mitochondria-targeted antioxidant Mito-Q. It is noteworthy that the ferroptosis inhibitor liproxstatin-1 (lip-1), anti-CD8, and anti-IFN-γ exhibited a significant inhibitory effect on the level of ferroptosis and antitumor capacity of ICA combined with anti-PD-1. This finding suggests that the antitumor immunopotentiating effect of ICA on anti-PD-1 is dependent on the secretion of IFN-γ-induced ferroptosis of CRC cells by the CD8 + T cell. Conclusion Our study represents the inaugural demonstration of the mechanism whereby ICA exerts anti-CRC effects and synergistically enhances the efficacy of anti-PD-1, inducing mitochondrial damage and leading to ferroptosis. ICA promotes ferroptosis of CRC cells by inducing mitochondrial dysfunction, and ICA combined with anti-PD-1 significantly promotes CD69, TCRβ signalling, activates effector CD8 + T cells to secrete IFN-γ, and achieves immunopotentiation by promoting ferroptosis of CRC cells, thus inhibiting CRC development. This study is built upon existing research into the pharmacodynamic mechanisms of ICA in the context of CRC, and offers a novel therapeutic approach in addressing the issue of CRC immunotherapy potentiation.
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American Journal of Translational Research
·
2016
·
IF 3.146
Zhisheng Wei,Mengxia Wang,Mingfan Hong,Shengpeng Diao,Aiqun Liu,Yeqing Huang,Qingyun Yu,Zhongxing Peng
Background: Estrogen exerts neuroprotective and anti-inflammatory effects in EAE and multiple sclerosis (MS), but its clinical application is hindered due to side effects and risk of tumor. Phytoestrogen structurally or functionally mimics estrogen with fewer side effects than endogenous estrogen. Icariin (ICA), an active component of Epimedium extracts, demonstrates estrogen-like neuroprotective effects. However, it is unclear whether ICA is effective in EAE and what are the underlying mechanisms. Objective: To determine the therapeutic effects of ICA in EAE and explore the possible mechanisms. Methods: C57BL/6 EAE mice were treated with Diethylstilbestrol, different dose of ICA and mid-dose ICA combined with ICI 182780. The clinical scores and serum Interleukin-17 (IL-17), Corticosterone (CORT) concentrations were then analyzed. Western blot were performed to investigate the expressions of glucocorticoid receptor (GR), estrogen receptor alpha (ERα) and ERβ in the cerebral white matter of EAE mice. Results: High dose ICA is equally effective in ameliorating neurological signs of EAE as estrogen. Estrogen and ICA has no effects on serum concentrations of IL-17 in EAE. While the CORT levels were decreased by ICA at mid or high doses, the expressions of GR, ERα and ERβ were up-regulated by estrogen or different doses of ICA in a dosedependent manner. Estrogen induced the elevation of ERα more markedly than ICA. In contrast, ICA at mid and high doses promoted ERβ more significantly than estrogen. Conclusion: ICA exerts estrogen-like activity in ameliorating EAE via mediating ERβ, modulating HPA function and up-regulating the expression of GR in cerebral white matter. ICA may be a promising therapeutic option for MS.
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APOPTOSIS
·
2023
·Vol. 28
·期 3
·607-626
·
IF 7.2
Yu Li-Ming,Dong Xue,Huang Tao,Zhao Ji-Kai,Zhou Zi-Jun,Huang Yu-Ting,Xu Yin-Li,Zhao Qiu-Sheng,Wang Zhi-Shang,Jiang Hui,Yin Zong-Tao,Wang Hui-Shan
Ferroptosis contributes to the pathogenesis of atrial fibrillation (AF), although the mechanisms are still largely uncovered. The current study was designed to explore the pharmacological effects of icariin against ethanol-induced atrial remodeling, if any, and the mechanisms involved with a focus on SIRT1 signaling. Excessive ethanol-treated animals were administered with Ferrostatin-1, Erastin or icariin to evaluate the potential effects of icariin or ferroptosis. Then, the underling mechanisms was further explored in the in vitro experiments using HL-1 atrial myocytes. Excessive ethanol administration caused significant atrial damage as evidenced by increased susceptibility to AF, altered atrial conduction pattern, atrial enlargement, and enhanced fibrotic markers. These detrimental effects were reversed by Ferrostatin-1 or icariin treatment, while Erastin co-administration markedly abolished the beneficial actions conferred by icariin. Mechanistically, ethanol-treated atria exhibited markedly up-regulated pro-ferroptotic protein (PTGS2, ACSL4, P53) and suppressed anti-ferroptotic molecules (GPX4, FTH1). Icariin treatment inhibited ethanol-induced atrial ferroptosis by reducing atrial mitochondrial damage, ROS accumulation and iron overload. Interestingly, the in vivo and in vitro data showed that icariin activated atrial SIRT1-Nrf-2-HO-1 signaling pathway, while EX527 not only reversed these effects, but also abolished the therapeutic effects of icariin. Moreover, the stimulatory effects on GPX4, SLC7A11 and the suppressive effects on ACSL4, P53 conferred by icariin were blunted by EX527 treatment. These data demonstrate that ferroptosis plays a causative role in the pathogenesis of ethanol-induced atrial remodeling and susceptibility to AF. Icariin protects against atrial damage by inhibiting ferroptosis via SIRT1 signaling. Its role as a prophylactic/therapeutic drug deserves further clinical study.
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PHYTOMEDICINE
·
2024
·
IF 6.7
Huizhen Tian,Qigang Pan,Jianfeng Wu,Juanjuan Liao,Yuwei Wan,Ke Pei,Qiong Liu,Lingbing Zeng,Yanli Cao,Qiaofa shi,Nanzhen Kuang,LiJuan Sun,Xiaomin Yu,Xiaotian Huang
Background Coxsackievirus B3 (CVB3) is a leading cause of viral myocarditis and is currently lacking specific pharmacological treatments, highlighting the critical need for therapeutic development. Icariin (ICA), a prenylated flavonol glycoside, was previously found to exhibit several pharmacological effects, but its potential to combat CVB3 remains uninvestigated. Purpose This study aimed to elucidate the anti-CVB3 efficacy of ICA and elucidate its molecular mechanisms. Methods CVB3-infected HeLa cells, H9C2 cells and neonate rat ventricular cardiomyocytes (NRVCs) were selected as in vitro models, and were treated with ICA at 1 and 10 μM. Additionally, BALB/c mice that were infected with CVB3 via intraperitoneal injection were chosen as in vivo model and were treated with ICA or ribavirin over 3 days. The effect of ICA against CVB3 was determined by Cell Counting Kit-8 (CCK-8) assay, western blot, real-time fluorescence quantitative PCR (RT–qPCR), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) and flow cytometry. Results In this study, it was found that ICA is capable of reducing CVB3 viral load both in vitro and in vivo . Mechanistic studies suggested that ICA prevents cardiomyocyte apoptosis by attenuating the S100 calcium binding protein A6 (S100A6)/β-catenin/c-Myc signaling pathway. Additionally, ICA inhibits the secretion of proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and CXC motif chemokine ligand 2 (CXCL2) in heart tissue, thereby mitigating CVB3-induced myocarditis. Moreover, ICA also regulates the immune response of CD4 + T, CD8 + T and Treg cells by changing the cells numbers in spleen tissue. Lastly, ICA can reduce the load of other enteroviruses (such as CVA6, CVA16 and EV71) in rhabdomyosarcoma (RD) cells as well. Conclusion Our findings indicate that ICA provides significant protection against CVB3 infection by modulating the S100A6/β-catenin/c-Myc signaling pathway, suggesting its potential use as a novel drug against CVB3 infection in clinical application.
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JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Rong Ma,Yuge Zhou,Weifan Huang,Xiaoni Kong
Ethnopharmacological relevance Epimedium Tourn. ex L. is a traditional Chinese medicine used for thousands of years in China to treat forgetfulness. Icariin is a principal component of the genus Epimedium . Aim of the study The metabolic mechanism of icariin treating forgetfulness is explored. Materials and methods A D-galactose-induced senescent mouse model was employed. The cognitive performance of mice was assessed in the fear conditioning test. Hippocampal pathology was assessed in the immunohistochemistry assay. Plasma metabolome was analyzed using GC-MS method, and the differential metabolites were further identified by UPLC-MS/MS or GC-MS method. The liver function, including ALT and AST, was assessed by enzyme reaction. Icariin was administered intraperitoneally at 50 and 100 mg/kg. Mice were administered five consecutive days per week for 8 weeks. Results Icariin treatment improved hippocampus-related fear memory but not amygdala-related memory, whereas Pexidartinib (PLX3397), a microglial scavenger, did not. Icariin treatment maintained the TMEM119-positive microglial population and decreased the accumulation of the senescent biomarker p16 in the dorsal hippocampus in senescent mouse brains, whereas PLX3397 did not. Notably, p16 in the CA2 subregion significantly decreased in icariin-treated mice than the other hippocampal subregions. The senescent mice exhibited the circulating metabolic characteristics of mild ketoacidosis, active tricarboxylic acid (TCA) cycle, lactic acidosis, hyperglycemia, active detoxification, active cis-oleic acid metabolism, and inhibitory GABA shut. R-3-hydroxybutyric acid primarily produced in the liver was selectively and robustly decreased by icariin treatment, which was not observed with PLX3397. The TCA cycle was rescued in senescent mice by icariin treatment. Icariin also protected liver function (plasma ALT) in D-gal-induced senescent mice. Conclusions Icariin may protect mouse hippocampal cognition from D-gal-induced senescence by protecting microglial homeostasis, and facilitating the utilization of R-3-hydroxybutyric acid is one of the underpins.
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BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
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2019
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IF 4.328
Wenbin Hua,Shuai Li,Rongjin Luo,Xinghuo Wu,Yukun Zhang,Zhiwei Liao,Yu Song,Kun Wang,Kangcheng Zhao,Shuhua Yang,Cao Yang
Intervertebral disc degeneration (IVDD) is a well-known cause of lower back pain. Icariin has been shown to exert a protective effect on human nucleus pulposus (NP) cells and accordingly has implications for the prevention and treatment of IVDD; however, the molecular mechanisms underlying its action are not fully established. In this study, the mechanisms underlying its protection against hydrogen peroxide (H 2 O 2 )-induced oxidative stress injury were investigated. In vitro, we demonstrated that icariin inhibits H 2 O 2 -induced mitochondria-mediated apoptosis. It upregulates oxidative stress mediators, i.e., reactive oxygen species, and downregulates mitochondrial membrane potential. Nuclear factor erythroid 2-related factor 2 (Nrf-2) is a key factor involved in the regulation of the endogenous defense system. It was proved that icariin could activate the Nrf-2 signaling pathway, upregulate the protein expression of nuclear respiratory factor-1 and the mitochondrial transcription factor, promoting mitochondrial biogenesis in human NP cells. An Nrf-2 agonist and inhibitor promoted or partly abolished the protective effects of icariin on mitochondrial homeostasis. Moreover, it was demonstrated that the Nrf-2 signaling pathway could be inhibited by the phosphatidylinositol 3-Kinase/AKT pathway. In vivo, icariin ameliorated IVDD in a rat model by promoting Nrf-2 activity, and preserving extracellular matrix in NP cells. These data suggest that icariin could ameliorate IVDD in rat models in vivo. In summary, the protective effects of icariin on human NP cells may suppress the pathogenesis of IVDD via the Nrf-2 signaling pathway. Our findings suggest that the Nrf-2 signaling pathway is a novel therapeutic target for the treatment of IVDD.
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POLYMER SCIENCE SERIES B
·
2022
·Vol. 64
·期 4
·487-499
·
IF 1.023
Zhen Hua,Cheng Jian,Shi Dong-jian,Chen Ji-wei,Peng Hong-cheng,Liu Ming-ming
Abstract The delivery of cytokines and Chinese medicines using biodegradable microspheres may promote bone regeneration. We designed a sustained-release microcapsule containing bone morphogenetic protein-2 (BMP2) and icariin (ICA) and evaluated its effects on osteogenic differentiation in MC3T3-E1 cells. ICA was preloaded onto sodium alginate-grafted phenylboronic acid (Alg-PBA) particles. Alg-PBA-ICA was used to coat the surface of SiO 2 -NH 2 colloids by electrostatic interaction, and then SiO 2 colloids were etched using HF. The Alg-PBA-ICA vesicles were immersed in a BMP2 solution, and Alg-PBA-ICA/BMP2 microcapsules were obtained. The optimal concentration of ICA and BMP2 for osteogenic differentiation induction was selected. We evaluated the microcapsules' osteogenic differentiation capacity. The microcapsules displayed intact morphology without obvious broken debris. The size of Alg-PBA-ICA@SiO 2 microcapsules was 210 ± 2 nm; the surface charge was –15.70 ± 2.12 mV. BMP2 (100 ng/mL) combined with 10 nM ICA had the strongest effect on cell behavior. The osteo-inductive effect at this concentration was stronger than that of the other combinations. The mRNA and protein expression levels of osteogenic genes increased after treatment with the microcapsules following 7 days of stimulation. This new drug delivery system has powerful osteo-inductive effects on MC3T3-E1 cells.
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ACS Applied Materials & Interfaces
·
2026
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IF 7.8
Yuhui Liu,Ning Zhou,Yumeng Luo,Xinyue Guan,Wenxin Meng,Xing Yu,Quanli Li,Qunlin Zhang,Xianwen Wang,Guomin Wu
This study aims to fabricate a scaffold based on natural herbal active substances, achieving antibacterial, anti-inflammatory, and osteogenic activities by graded and sustained drug release, overcoming the high cost and instability of growth factors in conventional bone defect scaffolds. Coaxial electrospinning was employed to construct a scaffold with silk fibroin (SF)/polycaprolactone (PCL)/kaempferol (KAE) as the shell and icariin (ICA) as the core, preparing nanofibrous scaffolds (ICA@SF/PCL/KAE). Comprehensive characterizations confirmed the co-axial structure of the nanofibers and successful drug loading and favorable release profiles of KAE and ICA, as well as the significantly enhanced mechanical performance. The KAE-loaded scaffold exerted outstanding antibacterial activity, while all of the drug-containing scaffolds maintained excellent cytocompatibility. In LPS-induced inflammatory environments, macrophages co-cultured on KAE-containing scaffolds exhibited markedly reduced reactive oxygen species and nitric oxide production, along with a decreased M1 macrophage ratio and an increased M2 macrophage ratio. RT-PCR results demonstrated that KAE-loaded scaffolds downregulated pro-inflammatory gene expression and upregulated anti-inflammatory gene expression. In vitro osteogenic induction revealed that the incorporation of KAE and ICA, especially ICA, remarkably enhanced osteogenic activity of the nanofibrous scaffolds. Under inflammatory conditions, KAE-containing scaffolds exhibited superior regulation of the osteogenic immune microenvironment compared with ICA-containing scaffolds. Notably, the ICA@SF/PCL/KAE scaffold containing both components achieved the optimal performance in all of the above in vitro experiments. Finally, rat cranial defect experiments further verified the excellent osteogenic efficacy of ICA@SF/PCL/KAE in vivo. Collectively, the ICA@SF/PCL/KAE core-shell nanofibrous scaffold offers an innovative approach for clinical bone defect treatment and expands the application potential of natural herbal active substances.
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Neuropsychiatric Disease and Treatment
·
2022
·
IF 2.989
Ting Zhang,Keli Dong,Lan Xiao,Guangcheng Li,Zhanwei Zhang
Objective We investigated the effect of icariin (ICA) combined with Panax notoginseng saponins (PNS) on intestinal microbiota and hippocampal protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) transgenic mice, a model of Alzheimer’s disease (AD).Methods Transgenic mice were treated with icariin and PNS. The Morris water maze (MWM) was used to assess spatial memory, and the gut microbiota and differential protein expression in the hippocampus were investigated using high-throughput screening techniques. Differential protein expression was confirmed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting.Results The MWM results showed that the mice treated with the medium dose of ICA+PNS spent significantly more time in the target quadrant compared with the AD group. Bacterial diversity was the lowest in the AD group, with significantly greater diversity in the ICA + PNS treatment group. Three proteins were selected for proteomic analysis, and qRT-PCR and Western blot were used to detect the expression of 2ʹ-5ʹ-oligoadenylate synthetase ubiquitin like 1 (Oasl1), trichoplein keratin filament-binding protein (TCHP), and tumor necrosis factor receptor associated 3-interacting protein 1 (MIPT3). Compared with control mice, MIPT3 expression was increased and Oasl1 and TCHP were reduced in the AD group. These abnormal protein expressions tended to normalization after treatment with medium dose of ICA and PNS.Conclusion Treatment with ICA and PNS ameliorated memory impairment in an AD mouse model. The mechanisms may be related to modulation of the intestinal microbiota and expression of Oasl1, TCHP, and MIPT3.
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Feng Sa,Liu Linyan,Cheng Yuelin,Zhou Mengmeng,Zhu Haoqiang,Zhao Xinyan,Chen Ziyu,Kan Shunli,Fu Xuanhao,Hu Wei,Zhu Rusen
Objective: The limited ability to regenerate axons after spinal cord injury (SCI) is influenced by factors such as astrocyte activation, reactive proliferation, and glial scar formation. The TGF-β/Smad (transforming growth factor-β/mothers against decapentaplegic homolog) pathway, associated with astrocytic scarring, plays a crucial role in recovery post-injury. This study aims to investigate how icariin (ICA) interacts with reactive astrocytes in the treatment of spinal cord injury.Methods: A rat SCI model was constructed, and the recovery of motor function was observed after treatment with ICA.HE staining, LFB staining, immunofluorescence staining, and Western blotting were employed to assess ICA's ability to inhibit astrocyte proliferation in rats following spinal cord injury by modulating YAP, as well as to evaluate the reparative effects of ICA on the injured spinal cord tissue. Primary astrocytes were isolated and cultured. Immunoprecipitation-Western Blot (IP-WB) ubiquitination and cytoplasm-nuclear separation were employed to assess PPM1B ubiquitination and nuclear translocation.Results: The CatWalk XT gait analysis, BBB (Basso, Beattie, and Bresnahan) score, electrophysiological measurements, HE staining, and LFB staining collectively demonstrated that ICA promotes motor function and tissue recovery following spinal cord injury in rats. Immunofluorescence staining and Western Blot analyses revealed that ICA inhibits astrocyte proliferation in rats post-spinal cord injury by suppressing YAP activity. Furthermore, the activation of YAP by XMU-MP-1 was shown to compromise the efficacy of ICA in these rats after spinal cord injury. Additional immunofluorescence staining and Western Blot experiments confirmed that ICA inhibits TGFβ1-induced astrocyte activation through the regulation of YAP. The knockdown of PPM1B (protein phosphatase, Mg2+/Mn2+-dependent 1B) in astrocytes was found to inhibit TGFβ signaling. Additionally, YAP was shown to regulate PPM1B ubiquitination and nuclear translocation through immunoprecipitation-Western blot analysis, along with the segregation of cytoplasm and nucleus.Conclusion: Icariin promotes functional recovery in rats after spinal cord injury by inhibiting YAP and regulating PPM1B ubiquitination to inhibiting the activation of reactive astrocytes.
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