BIOMEDICINE & PHARMACOTHERAPY
·
2017
·
IF 2.759
QiuShi Wei,MinCong He,MeiHui Chen,ZhenQiu Chen,Fan Yang,HaiBin Wang,Jin Zhang,Wei He
Icariin, the major ingredient of Herba Epimedii, promotes the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and exerts protective effects against bone loss and increases bone regeneration, but the underlying signaling pathway by which icariin affects osteogenic differentiation remain unclear. Transcriptional coactivator with PDZ-binding motif (TAZ) is a transcriptional modulator of the Hippo signaling pathway, which plays an important role in the osteogenic differentiation of BMSCs by activating Runx2 gene during the terminal osteogenic differentiation. In this study, we found that 0.1 μM icariin markedly promoted the proliferation, calcium depositions, and osteogenic genes expression of rBMSCs. Icariin (0.1 μM) upregulated TAZ, Runx2, β-catenin, Osteopotin, and Dlx5 expression mainly at the early stage of osteogenic differentiation, and increased osteocalcin expression at the late stage. Our result further demonstrated that knockdown TAZ expression by lentivirus-mediated TAZ shRNA inhibited the icariin-induced osteogenic differentiation. Moreover, ICI 182780 (the estrogen receptor alpha inhibitor) or DKK1 (the Wnt/β-catenin pathway inhibitor), inhibited the icariin-induced increase in TAZ expression. Furthermore, icariin stimulated the activation of TAZ as evidenced by increased total TAZ protein and nuclear translocation, but these effects of icariin were blocked by ICI 182780 or DKK1. Taken together, our results demonstrate that icariin promotes the osteogenic differentiation of rBMSCs by increasing TAZ expression, and that the increased TAZ expression induced by icariin is mostly mediated by the ERα and Wnt/β-catenin pathway.
研究领域:
药理学
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细胞生物学
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分子生物学
·
骨再生
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
·
2024
·
IF 5.4
Xunmeng Tang,Yawen Wang,Na Liu,Xinyuan Deng,Ziyi Zhou,Chenghao Yu,Yuanfei Wang,Kuanjun Fang,Tong Wu
Bone defects typically result in bone nonunion, delayed or nonhealing, and localized dysfunction, and commonly used clinical treatments (i.e., autologous and allogeneic grafts) have limited results. The multifunctional bone tissue engineering scaffold provides a new treatment for the repair of bone defects. Herein, a three-dimensional porous composite scaffold with stable mechanical support, effective antibacterial and hemostasis properties, and the ability to promote the rapid repair of bone defects was synthesized using methacrylated carboxymethyl chitosan and icariin-loaded poly-l-lactide/gelatin short fibers (M-CMCS-SFs). Icariin-loaded SFs in the M-CMCS scaffold resulted in the sustained release of osteogenic agents, which was beneficial for mechanical reinforcement. Both the porous structure and the use of chitosan facilitate the effective absorption of blood and fluid exudates. Moreover, its superior antibacterial properties could prevent the occurrence of inflammation and infection. When cultured with bone mesenchymal stem cells, the composite scaffold showed a promotion in osteogenic differentiation. Taken together, such a multifunctional composite scaffold showed comprehensive performance in antibacterial, hemostasis, and bone regeneration, thus holding promising potential in the repair of bone defects and related medical treatments.
研究领域:
生物医学工程
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组织工程
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生物材料
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骨科
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Xue Li,Jian Huang,Yan-Ming Zhou,Xue Chen,Qin-Wei Dong,Yuan-Lu Cui,Yi-Bing Chen
Excessive reactive oxygen species (ROS)-induced nigrostriatal dopaminergic neuron degeneration is a cardinal pathological feature of Parkinson’s disease (PD). Although icariin, a natural antioxidant capable of scavenging ROS, shows therapeutic potential, it remains underutilized in clinical settings. This translational gap primarily stems from two pharmacological limitations: (1) inadequate blood–brain barrier (BBB) penetration that prevents effective delivery of icariin to the brain, and (2) the lack of targeted drug release at pathological sites, thereby diminishing its local neuroprotective efficacy against ROS-mediated neurodegeneration. To overcome these challenges, we developed a ROS-responsive selenocysteamine-alginate nanogel (ASeNG-ICA) that bypasses the BBB via nose-to-brain delivery and enables pathology-triggered drug release through diselenide bond cleavage in the high-ROS microenvironments characteristic of PD. In vitro studies demonstrated that the nanogels undergo ROS-responsive disintegration, resulting in sustained icariin release under oxidative conditions. Following intranasal administration in mice, ASeNG-ICA achieved rapid brain biodistribution. In a PD mouse model, this delivery system significantly reduced striatal malondialdehyde (MDA) levels, regulated antioxidant enzymes (HO-1, SOD) expression, alleviated oxidative stress and improved behavioral disorders, surpassing conventional free icariin therapy. Overall, ASeNG-ICA resolves critical delivery barriers in PD therapy, offering a new paradigm for neurodegenerative disease treatment.
研究领域:
纳米医学
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神经药理学
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药物递送
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活性氧(ROS)
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神经退行性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Artificial Cells Nanomedicine and Biotechnology
·
2025
·
IF 4.5
Shiyao Liao,Kai Zhou,Yao Kang,Tingxiao Zhao,Yicheng Lin,Jun Lv,Danjie Zhu
Cartilage repair remains challenging due to limited self-healing, poor biocompatibility, and insufficient mechanical properties of current materials. To overcome these issues, we developed a multifunctional composite hydrogel by integrating gelatine methacrylate (GelMA) with magnesium-doped bioactive glass (Mg-BG) and icariin (ICA). SEM analysis revealed that pure GelMA exhibited a highly porous yet loosely organized structure, whereas the addition of Mg-BG and ICA produced a denser, more interconnected porous network that enhances cell adhesion and nutrient diffusion. In vitro, the ICA/Mg-BG/GelMA hydrogel achieved a swelling ratio up to 430% and maintained cell viability above 80% over 5 days. Moreover, qRT-PCR and immunohistochemical analyses demonstrated that the composite hydrogel upregulated chondrogenic markers (SOX9, ACAN, and COL2A1) compared with GelMA alone. Specifically, it downregulates M1 pro-inflammatory markers (CCR7, iNOS, CD86) and upregulates M2 anti-inflammatory markers (ARG1, CD163, CD206), thereby creating a regenerative microenvironment. These results indicate that the synergistic combination of GelMA, Mg-BG, and ICA not only improves the scaffold’s mechanical support but also enhances its biological functionality, offering a promising strategy for cartilage repair. Future studies will focus on in vivo validation to further assess its clinical potential.
研究领域:
组织工程
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再生医学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2021
·
IF 7.658
Xiaoang Li,Imran Khan,Wenrui Xia,Guoxin Huang,Liang Liu,Betty Yuen Kwan Law,Lin Yin,Weilin Liao,Waikit Leong,Ruixuan Han,Vincent Kam Wai Wong,Chenglai Xia,Xiaoling Guo,W.L. Wendy Hsiao
We previously reported the neuroprotective effects of icariin in rat cortical neurons. Here, we present a study on icariin's anti-aging effect in 24-month aged mice by treating them with a single daily dose of 100 mg/kg of icariin for 15 consecutive days. Icariin treatment improved motor coordination and learning skills while lowered oxidative stress biomarkers in the serum, brain, kidney, and liver of the aged mice. In addition, icariin improved the intestinal integrity of the aged mice by upregulating tight junction adhesion molecules and the Paneth and goblet cells, along with the reduction of iNOS and pro-inflammatory cytokines (IL-1β, TNF-α, IL-2 and IL-6, and IL-12). Icariin treatments also significantly upregulated aging-related signaling molecules, Sirt 1 , 3 & 6, Pot1α, BUB1b, FOXO1, Ep300, ANXA3 , Calb1 , SNAP25 , and BDNF in old mice. Through gut microbiota (GM) analysis, we observed icariin-associated improvements in GM composition of aged mice by reinstating bacteria found in the young mice, while suppressing some bacteria found in the untreated old mice. To clarify whether icariin's anti-aging effect is rooted in the GM, we performed fecal microbiota transfer (FMT) from icariin-treated old mice to the old mice. FMT-recipients exhibited similar improvements in the rotarod score and age-related biomarkers as observed in the icariin-treated old mice. Equal or better improvement on the youth-like features was noticed when aged mice were FMT with feces from young mice. Our study shows that both direct treatments with icariin and fecal transplant from the icariin-treated aged mice produce similar anti-aging phenotypes in the aged mice. We prove that GM plays a pivotal role in the healing abilities of icariin. Icariin has the potentials to be developed as a medicine for the wellness of the aged adults.
研究领域:
药理学
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衰老研究
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微生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
CURRENT PHARMACEUTICAL BIOTECHNOLOGY
·
2021
·Vol. 22
·期 1
·168-175
·
IF 2.837
Sun Lin-Jun,Li Chong,Wen Xiang-hao,Guo Lu,Guo Zi-Fen,Liao Lan-qing,Guo Yu
Background: Icariin (ICA), one of the main effective components isolated from the traditional Chinese herb Epimedium brevicornu Maxim., has been reported to possess extensive pharmacological actions, including enhanced sexual function, immune regulation, anti-inflammation, and antiosteoporosis.
Methods: Our study was designed to investigate the effect of ICA on cell proliferation and differentiation and the molecular mechanism of OPG/RANKL mediated by the Estrogen Receptor (ER) in hFOB1.19 human osteoblast cells. Results: The experimental results show that ICA can stimulate
cell proliferation and increase the activity of Alkaline Phosphatase (ALP), Osteocalcin (BGP) and I Collagen (Col I) and a number of calcified nodules. Furthermore, the mRNA and protein expression of OPG and RANKL and the OPG/ RANKL mRNA and protein expression ratios were upregulated by ICA.
The above-mentioned results indicated that the optimal concentration of ICA for stimulating osteogenesis was 50ng/mL. Subsequent mechanistic studies comparing 50ng/mL ICA with an estrogen receptor antagonist demonstrated that the effect of the upregulated expression is connected with the estrogen
receptor. In conclusion, ICA can regulate bone formation by promoting cell proliferation and differentiation and upregulating the OPG/RANKL expression ratio by the ER in hFOB1.19 human osteoblast cells.
研究领域:
药理学
·
细胞生物学
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分子生物学
·
内分泌学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2022
·Vol. 49
·期 7
·719-730
·
IF 2.963
Jie Zheng,Yuling Liao,Yuanyuan Xu,Zhentao Mo
Ischaemic stroke possesses the characteristics of high incidence, high disability and high mortality. Icariin (ICA) is a flavonoid extracted from the traditional Chinese medicine Epimedium . The protective effect of ICA on ischaemic stroke is worthy of further study. In this study, male Sprague–Dawley rats were randomly divided into the following seven groups: sham, model, ICA low-dose (10 mg/kg), ICA medium-dose (20 mg/kg), ICA high-dose (40 mg/kg), positive control drug (12 mg/kg nimodipine) and endoplasmic reticulum stress induction (0.16 mg/kg tunicamycin) groups. The model of cerebral ischaemia–reperfusion injury in the rats, including 2 h ischaemia and 24 h reperfusion, was accomplished by applying the method of transient middle cerebral artery occlusion (MCAO). At 24 h reperfusion, neurological deficits, brain water content, pathological damage of brain tissues, the expression of inflammation-related targets, and the signal pathway-related proteins were explored. Compared with the model group, ICA significantly improved neurological deficits, brain oedema and pathological damage after MCAO. In addition, ICA increased neuron survival, reduced microglial activation and expression of IL-1β, alleviating the inflammatory damage caused by ischaemic stroke. Moreover, ICA suppressed the expressions of glucose-regulated protein 78 (GRP78), inositol requiring enzyme-1 α (IRE1α), phospho-IRE1α (p-IRE1α), protein kinase RNA-like ER kinase (PERK), phospho-PERK (p-PERK), spliced XBP1 (XBP1s), unspliced XBP1 (XBP1u), thioredoxin-interacting protein (TXNIP), NLRP3, and caspase-1. These results suggested that ICA offers neuroprotection against ischaemic stroke by inhibiting ER stress-mediated inflammation.
研究领域:
神经科学
·
药理学
·
病理学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Orthopaedic Surgery and Research
·
2025
·Vol. 20
·期 1
·1-12
·
IF 2.8
He Zhenhong,Zeng Shengqiang,Qin Bo,Liu Gang,Liu Huan,Bao Dingsu
ObjectiveTendon injury is a common and frequent disease in the field of sports medicine, and tendon repair after injury is a common clinical difficulty. Repair strategy based on tendon stem cells (TDSCs) therapy is considered a promising therapeutic option for the treatment of tendon injuries. Icariin (ICA) has been shown to be an effective herbal monomer for the treatment of tendon-bone healing and may be effective in the repair of tendon injuries.Methods In vitro, TDSCs isolated from C57 mice were treated with ICA (0.01–100 µM) to assess proliferation (CCK-8 assay) and tendonogenic differentiation (qRT-PCR). In vivo, 42 C57 mice with surgically induced patellar tendon defects were randomized into three groups (n = 14/group): (1) 20 mg/kg ICA, (2) 40 mg/kg ICA, and (3) control group (DMSO), administered intraperitoneally for 14 days. Half of each group (n = 7) underwent histopathological (hematoxylin-eosin staining, Masson staining) and molecular (qRT-PCR) analyses at 2 and 4 weeks post-surgery.Results In vitro, after 7 days of ICA intervention in TDSC, the expression of Mohawk (MKX), Scleraxis (SCX), fibromodulin (FMOD), and Tenomodulin (TNC) were higher in the ICA group than in the control group. In vivo, the expression of MKX, SCX, FMOD, and TNC was higher in the 20 mg/kg ICA group and 40 mg/kg ICA group than in the control group at 2 and 4 weeks after surgery. Histological evaluation revealed superior tendon repair in both ICA-treated groups compared to controls at both 2 and 4 weeks postoperative intervals. The 20 mg/kg ICA group demonstrated a significant enhancement in tissue continuity and collagen fiber organization, exhibiting greater defect filling, fewer interstitial gaps, and reduced vascular infiltration. In contrast, control specimens exhibited disorganized collagen architecture with prominent interstitial gaps. The 40 mg/kg ICA group showed intermediate repair outcomes between the 20 mg/kg ICA and control groups.Conclusion ICA can improve tendon injury repair by enhancing tendonogenic differentiation of TDSC.
研究领域:
运动医学
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再生医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF SPORTS MEDICINE
·
2019
·
IF 6.093
Cheng Zheng,Hongbin Lu,Yifu Tang,Zhanwen Wang,Haozhe Ma,Haixia Li,Huabin Chen,Yang Chen,Can Chen
Background:Tendon-bone interface (TBI) injuries are common in sports activities. Owing to the limited regenerative ability of the TBI, its functional healing remains a difficulty in clinical practice. Icariin (ICA) provides strong stimulation for osteogenesis. Platelet-rich plasma (PRP) can be used as a carrier for bioactive molecules, although its ability to provide sustained release for such molecules needs improvement.Hypothesis:Freeze-dried PRP (FD-PRP) as a carrier for ICA can provide sustained release of ICA into the tendon-bone (T-B) healing site, thus accelerating T-B healing.Study Design:Controlled laboratory study.Methods:A total of 84 New Zealand rabbits with partial patellectomy in the hindlimb were randomly allocated into 3 different treatments: ICA incorporated with FD-PRP (ICA/FD-PRP), FD-PRP alone (FD-PRP), or saline control (CTL). The rabbit patella–patellar tendon (PP) interfaces were postoperatively harvested at postoperative week 8 or 16 for gross, radiological, histological, and mechanical evaluations.Results:Our results showed that FD-PRP can act as a carrier for sustained release of ICA into the T-B healing site. Macroscopically, no signs of infection or osteoarthritis were shown in the regenerated PP interfaces, and the area of cartilaginous metaplasia in the FD-PRP and ICA/FD-PRP groups at postoperative week 16 was significantly larger than that of the CTL group (P < .05 for all). Radiologically, micro–computed tomography showed that new bone which formed at the healing site in the ICA/FD-PRP group was significantly increased, remodeled, and mineralized in comparison with the CTL group (P < .05 for all). Histologically, the ICA/FD-PRP group exhibited a significant native PP interface, as shown by the enlargement and remodeling of new bone, well-organized collagen fibers, and robust production of proteoglycans in the regenerated fibrocartilage. The mechanical strength of the regenerated PP interface was significantly improved in the ICA/FD-PRP group. Significantly higher failure load and stiffness were shown in the ICA/FD-PRP group compared with the CTL and FD-PRP groups, respectively (P < .05 for all).Conclusion:FD-PRP is a suitable sustained-release carrier for ICA, and ICA/FD-PRP can provide sustained release of ICA into the T-B healing site, thus effectively accelerating T-B healing.Clinical Relevance:Findings of this study demonstrate the feasibility of using FD-PRP as a carrier for ICA to improve T-B healing and provide a foundation for future clinical application.
✓ 已验证
DOI
高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Li Song,Yue Li,Wenjing Li,Bingfeng Lin,Wenlong Xiao,Yuzhen Xia,Feida Wang,Mingli Ye,Wei Wang,Nani Wang
Background Sarcopenia is a prevalent disorder among postmenopausal women, representing a debilitating condition with limited treatment options. Icariin (ICA), a prenylated flavonol glycoside, is commonly used in conditions associated with estrogen deficiency; however, its efficacy and mechanism in postmenopausal sarcopenia remain undefined. Purpose This study aimed to evaluate the therapeutic effect of ICA on postmenopausal sarcopenia and to elucidate its underlying mechanism, with a focus on the estrogen receptor α/fatty acid transport protein 1 (ERα/FATP1) pathway. Study design An integrated approach was employed, combining in vivo pharmacological evaluation, multi-omics analyses, and in vitro mechanistic validation. Methods The in vivo therapeutic effect of oral ICA was assessed by evaluating muscle function, histology, and senescence markers. Human muscle transcriptome datasets and mouse single-cell RNA sequencing data were analyzed. In vitro validation was performed in D-galactose-induced senescent C2C12 myoblasts. Target engagement was confirmed by molecular docking, cellular thermal shift assay, and surface plasmon resonance, and mechanistic validation was performed via FATP1 knockdown. Results Oral administration of ICA significantly improved muscle mass, function, and fiber cross-sectional area, while attenuating lipid deposition and cellular senescence. Single-cell RNA sequencing revealed a diminished myoblast pool with downregulated ERα in aged muscle. This finding aligns with human transcriptome data, linking reduced ERα/FATP1 signaling and dysregulated fatty acid metabolism to sarcopenia. Metabolomic analysis identified FATP1 as a critical transporter of eicosapentaenoic acid and docosapentaenoic acid, which activated the protein kinase B/ mammalian target of rapamycin pathway to promote myogenesis. Importantly, ICA functioned as a dual-target agonist, directly binding to and upregulating both ERα and FATP1, thereby elevating eicosapentaenoic/ docosapentaenoic acid levels and reactivating the protein kinase B/ mammalian target of rapamycin/ myogenic differentiation 1 axis. The specificity of this pathway was confirmed, as FATP1 knockdown completely abrogated the protective effects of ICA. Conclusion This study identifies the ERα/FATP1 axis as a pivotal therapeutic target for sarcopenia. ICA, acting as a first-in-class dual agonist of this pathway, represents a promising candidate for sarcopenia treatment by synchronously modulating estrogen signaling and fatty acid metabolism. Download: Download high-res image (181KB) Download: Download full-size image
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2020
·Vol. 72
·期 9
·1152-1164
·
IF 2.571
Wang Jinwu,Zhu Gaosheng,Wang Xingyu,Cai Jie,Xie Linzhen,Zheng Wenhao,Feng Yongzeng,Guo Qiang,Chen Hua,Cai Leyi
ObjectivesIcariin, extracted from Epimedium, is a kind of flavonoid and possesses osteogenesis and antioxidant. This study aimed to evaluate the therapeutic effects of icariin liposome on acute blunt skeletal muscle injury in rats.MethodsIcariin liposome was prepared by the thin-film dispersion method. After muscle injury, the corresponding treatment measures were given every day for two weeks. Recovery and mechanism of muscle injury were evaluated by QRT-PCR, HE, immunohistochemistry, malondialdehyde, superoxide dismutase and serological tests.Key findingsThe particle size, polydispersity index, zeta potential, encapsulation efficiency and drug loading of icariin liposomes were 171.37 ± 38.23 nm, 0.27 ± 0.01, −5.59 ± 1.36 mV, 78.15 ± 2.04% and 15.62%, respectively. The QRT-PCR showed that icariin liposome significantly promoted the expression of MHCIIB and vimentin. Through HE, immunohistochemistry, ELISA and serological tests, we found that icariin liposome effectively promoted desmin expression, reduced collagen I expression and inhibited the production of pro-inflammatory factors, including TNF-α and IL-6. Icariin liposome therapy significantly reduced the level of malondialdehyde and increased the activity of superoxide dismutase.ConclusionsIcariin liposome has excellent therapeutic effects on acute blunt muscle injury in rats by improving immunity, repairing cytoskeleton and cellular integrity, anti-inflammation, anti-fibrosis and antioxidant stress.
研究领域:
药理学
·
肌肉骨骼系统
·
药物递送系统
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2017
·
IF 5.401
Haiyun Zhai,Haihang Wang,Shiqiao Wang,Zuanguang Chen,Shumei Wang,Qing Zhou,Yufang Pan
A novel Au-Ag nanoparticles (NPs) on multi-walled carbon nanotubes/sulfonated graphene sheets modified glassy carbon electrode (Au-AgNPs/MWNTs-SGSs/GCE) was prepared to determine mangiferin (MIN) and icariin (IIN) by electrochemical methods Scanning electron microscopy and energy-dispersive spectroscopy showed that Au-AgNPs were electrodeposited on drape and tubular structure of MWNTs-SGSs/GCE successfully. The modified electrode had high electroactivities against both MIN and IIN. The anodic peak currents of MIN and IIN on the GCE modified by Au-AgNPs/MWNTs-SGSs were much higher than those on the bare GCE. Differential pulse voltammetry showed a wide detection range of 0.05 ∼ 500.0 μM for MIN and 0.05 ∼ 100.0 μM for IIN, with low detection limits (0.017 μM both) as well as high sensitivity, selectivity and repeatability. Au-AgNPs/MWNTs-SGSs/GCE was successfully applied to simultaneously detect MIN and IIN in Rhizoma anemarrhenae and to independently determine MIN in Artemisia capillaris Herba and IIN in the leaves of Epimedium macranthum .
研究领域:
分析化学
·
药理学
·
纳米材料科学
✓ 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）