Materials Today Communications
·
2026
·
IF 4.9
Jia Ning,Zhen Wang,Xin Zhang,Changyi Li,Zhimin Zhou
Periodontitis is a chronic inflammatory disease that progressively destroys periodontal tissues and alveolar bone, posing a significant challenge for clinical regeneration. Tissue engineering strategies integrating stem cells, biomaterials, and bioactive agents hold promise for overcoming the limitations of current periodontal regenerative approaches. In this study, we developed an injectable PLGA composite microscaffold-based co-delivery system with a porous architecture for the combined delivery of icariin (ICA) and bone marrow-derived mesenchymal stem cells (BMSCs). ICA-loaded PLGA composite microscaffolds (ICA-PLGA) were fabricated by a double emulsion–solvent evaporation method, followed by fibrinogen (Fg) surface modification via electrostatic layer-by-layer assembly to generate ICA-PLGA-Fg microscaffolds with improved cell-adhesive properties. These porous microscaffolds exhibited sustained ICA release for up to 28 days and enhanced BMSC adhesion and spreading. In vitro, ICA-PLGA-Fg supported favorable cytocompatibility and enhanced osteogenic differentiation of BMSCs under inflammatory conditions. In vivo, BMSC-seeded ICA-PLGA-Fg constructs implanted into rat periodontitis-related alveolar bone defects achieved markedly greater bone regeneration compared with both periodontitis and PLGA-only controls. Collectively, this co-delivery platform integrates sustained ICA release with a bioactive, cell-supportive microscaffold interface, promotes osteogenic responses in vitro, and shows therapeutic promise for enhancing periodontal bone repair in vivo.
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高影响因子
COMPOSITES PART B-ENGINEERING
·
2021
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IF 9.078
Kun Li,Yingnan Zhang,Junwei Xu,Jingxi Wang,Xuenan Gu,Ping Li,Yubo Fan
The electrospun fibrous scaffold has shown a great potential due to an extracellular matrix-mimicking structure of nanofibers , however, a three-dimensional (3D) fibrous scaffold, much similar to in vivo environment, still remains challenging in fabrication. The magnetic nanoparticles (MNPs) have been explored to promote bone-related cells activity under static magnetic field (SMF). Herein, via electrospinning, Fe 3 O 4 MNPs and icariin (ICA) from traditional Chinese medicine were introduced into polycaprolactone (PCL) fibers to manufacture two-dimensional (2D) membranes (PCL/Fe 3 O 4 /ICA), which were then expanded to 3D scaffold by depressurization of subcritical CO 2 fluid. The expanding behavior was more remarkable for the membrane collected from rotary collector than that on plate collector, especially after the addition of Fe 3 O 4 MNPs. Co-cultured with pre-osteoblasts, PCL/Fe 3 O 4 /ICA 3D scaffold induced a higher cell proliferation viability than that in 2D membrane in later period, and the combined utilization with SMF group showed the highest cell viability. When implanted subcutaneously, 3D scaffold exhibited better cell infiltration , internal collagen deposition and angiogenesis due to the enhanced porosity and the action of ICA. This highly porous magnetic PCL/Fe 3 O 4 /ICA 3D scaffold provided a new idea for the design and application of magnetic scaffold in the bone tissue engineering .
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JOURNAL OF CELLULAR PHYSIOLOGY
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2020
·Vol. 236
·期 3
·1889-1902
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IF 5.546
Wenhui Yao,Kai Wang,Xiniao Wang,Xinran Li,Jieyan Dong,Yusheng Zhang,Xuansheng Ding
Icariin (ICA), as a flavonoid glycoside, is associated with the improvement of vascular complications in diabetes. However, its protective mechanisms remain to be well-established. Here, we tested the hypothesis that ICA attenuates vascular endothelial dysfunction by inhibiting endoplasmic reticulum (ER) stress in type 1 diabetes. In streptozotocin-induced diabetic rats, ICA positively affected acetylcholine-induced vasodilation and phenylephrine-induced vasoconstriction in aortas. ICA treatment significantly attenuated ER stress in diabetic rats and high-glucose induced human umbilical vein endothelial cells. Incubation with ICA in vitro attenuated vascular reactivity in diabetic rats, which was blocked by the ER stress inducer, and peroxisome proliferator-activated receptor α (PPARα), sirtuin1 (Sirt1), or AMP-activated protein kinase-α (AMPKα) inhibitors. Western blot showed that ICA activated the PPARα/Sirt1/AMPKα pathway, which contributed to reducing ER stress and activating endothelial nitric oxide synthase in vivo and vitro. Our results implicate that ICA normalizes ER stress to attenuate endothelial dysfunction by the regulation of the PPARα/Sirt1/AMPKα pathway.
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高影响因子
International Journal of Biological Sciences
·
2019
·
IF 4.067
Haotian Li,Xinran Zhang,Xi Qi,Xu Zhu,Liming Cheng
Endoplasmic reticulum (ER) stress-induced neuronal apoptosis is a crucial pathological process of spinal cord injury (SCI). In our previous study, icariin (ICA) showed neuroprotective effects in SCI. However, the relationships between ER stress and ICA in SCI are unclear yet. Therefore, whether ICA could ameliorate SCI via attenuating ER stress was investigated in vitro and in vivo . Adult mice were established SCI model and received vehicle solution or ICA by gavage once per day in vivo . The primary cultured cells were treated with or without thapsigargin (TG), ICA or LY294002 to induce ER stress in vitro . Motor dysfunction, neuronal apoptosis, tissue damage and inhibition of PI3K/AKT pathway were induced by ER stress after SCI. But ICA administration significantly enhanced motor recovery and protected spinal cord tissues against infraction and hemorrhage, etc. post injury. Meanwhile, the expression of ER stress markers ATF6, IRE1α, GRP78, XBP1 and eIF2α was decreased, while the level of p-AKT/AKT was increased by ICA. Furthermore, ICA significantly inhibited the expression of ER stress apoptotic proteins caspase-12, CHOP, Bax/Bcl-2, caspase-9 and caspase-3. Moreover, immunofluorescence double staining indicated that ICA reduced GRP78, CHOP and TUNEL positive neurons following SCI. However, this beneficial effect of ICA was abolished by PI3K/AKT inhibitor LY294002 in vitro . Finally, ICA preserved the ultra-structure of ER by transmission electron microscope histologically. This study suggested that the neuroprotective effect of ICA on motor recovery and neuronal survival was related to attenuating ER stress via PI3K/AKT signaling pathway after SCI.
研究领域:
神经科学
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药理学
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分子生物学
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病理生理学
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International Journal of Nanomedicine
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2019
·
IF 4.471
Yuanlong Xie,Wenchao Sun,Feifei Yan,Huowen Liu,Zhouming Deng,Lin Cai
Objective Icariin (IC) promotes osteogenic differentiation, and it may be a potential small molecule drug for local application in bone regeneration. Icariin-loaded hydroxyapatite/alginate (IC/HAA) porous composite scaffolds were designed in this study for the potential application of the sustainable release of icariin and subsequent bone regeneration.Methods An icariin-loaded hydroxyapatite/alginate porous composite scaffold was prepared and characterized by SEM and HPLC for morphology and release behavior, respectively. The mechanical properties, degradation in PBS and cytotoxicity on BMSCs were also evaluated by MTT assay, compression strength and calculation of weight remaining ratio, respectively. Rabbit BMSCs were cocultured with IC/HAA scaffolds, and ALP activity and Alizarin Red staining were performed to evaluate osteogenic differentiation induction. The mRNA and protein expression level of an osteogenic gene was detected by RT-PCR and Western blotting, respectively. In vivo animal models of critical bone defects in the radius of rabbit were used. Four and 12 weeks after the implantation of IC/HAA scaffolds in the bone defect, radiographic images of the radius were obtained and scored by using the Lane and Sandhu X-ray scoring system. Tissue samples were also evaluated using H&E and Masson staining, and an osteogenic gene and Wnt signaling pathway genes were detected.Results A hydroxyapatite/alginate (HAA) porous composite scaffold-loaded icariin was fabricated using a freeze-drying method. Our data indicated that the icariin was loaded in alginate scaffold without compromising the macro/microstructure or mechanical properties of the scaffold. Notably, the IC/HAA promoted the proliferation of rBMSCs without exerting cytotoxicity on rBMSCs. In vivo, rabbit radius bone defect experiments demonstrated that the IC/HAA scaffold exhibited better capacity for bone regeneration than HAA, and IC/HAA upregulated the relative expression levels of an osteogenic gene and the Wnt signaling pathway genes. Most notably, the IC/HAA scaffold also inhibited osteoclast activity in vivo.Conclusion Our data suggests a promising application for the use of HAA scaffolds to load icariin and promote bone regeneration in situ through mediation of the coupling processes of osteogenesis induction and osteoclast activity inhibition.
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JOURNAL OF CELLULAR BIOCHEMISTRY
·
2019
·Vol. 120
·期 8
·13121-13132
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IF 3.448
Xiaoxiao Liang,Zhiqiang Hou,Yuanlong Xie,Feifei Yan,Sisi Li,Xiaobin Zhu,Lin Cai
Osteoporosis (OP) results from the impaired function of endogenous bone marrow mesenchymal stem cells (BMSCs). Icariin (ICA) has shown potential osteoprotective effects. However, the molecular mechanism for the anabolic action of ICA remains largely unknown. The objective of the present study is to investigate whether ICA prevents bone loss by acting on BMSCs via affecting the level of autophagy after ovariectomy (OVX). The BMSCs were extracted from BALB/c mice treated with ICA, chloroquine (CQ, an autophagy inhibitor) or ICA + CQ. The OVX mice were injected with ICA, CQ, or ICA + CQ for 1 month. We performed Alizarin Red staining and alkaline phosphatase staining to detect osteogenic differentiation of BMSCs. Micro-CT, hematoxylin and eosin staining, Oil Red O staining, and tartrate-resistant acid phosphatase staining were used to assess the bone mass, lipid droplets and osteoclasts in femurs. Autophagy activity in BMSCs from different groups was evaluated by Western blot analysis. The osteogenic differentiation of BMSCs from OVX-induced OP mice was decreased. Treatment with ICA reduced bone loss and formation of osteoclasts and increased osteogenic differentiation of BMSCs in vitro and vivo. In addition, autophagy was enhanced in BMSCs of OVX mice treated with ICA. Our results indicate that ICA prevents OVX-induced bone loss possibly by strengthening the osteogenic differentiation of BMSCs via increasing autophagic activity.
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INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
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IF 4.8
Hanxiao Zheng,Limin Qu,Lei Yang,Xianmin Xie,Ling Song,Qiuen Xie
Knee osteoarthritis (KOA) is a chronic disease characterized by joint wear and cartilage degeneration. Current clinical treatments are based on symptomatic relief and are not effective in regenerating cartilage, and inflammation-induced cartilage damage accelerates the progression of osteoarthritis, making the protection of articular cartilage important for controlling the development of knee osteoarthritis. In this study, a biodegradable hydrogel (HA-Ca-Alg@Ica) loaded with Icariin (Ica) was prepared by in situ cross-linking of hyaluronic acid-calcium complex (HA-Ca) and sodium alginate (Alg-Na) for local sustained delivery of Ica. The hydrogel promoted chondrocyte proliferation and inhibited the degradation of cartilage matrix by regulating key factors (Wnt3a, β-catenin and GSK-3β) in the Wnt/β-catenin signaling pathway. In addition, the hydrogel reduced the expression of inflammatory factors, including IL-1β, IL-6, TNF-α, COX-2, and MMP13, leading to a reduction in inflammation and pain relief. In summary, this hydrogel containing Icariin has shown significant effects in reducing chondrocyte degradation and promoting chondrocyte proliferation, which can play a role in delaying osteoarthritis by protecting chondrocytes. These findings offer innovative prospects for the therapeutic management of knee osteoarthritis.
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Molecular Catalysis
·
2025
·
IF 4.9
Haoyu Jia,Jinyue Hu,Le Zhao,Xiaoke Zheng,Weisheng Feng
Baohuoside I, a valuable flavonoid derivative of Herba Epimedii , exhibits superior bioactivities compared to its precursor, icariin. The conversion of icariin to baohuoside I using β-glucosidase (β-G) is an efficient approach for industrial production. Herein, β-G was successfully immobilized into a porous materials metal-organic frameworks (MOFs) via a simple one-pot coprecipitation method. The β-G@MOF biocomposite exhibited high encapsulation efficiency and excellent tolerance to extreme pH, high temperature, organic solvent and glucose. Remarkably, β-G@MOF retained its full initial activity even at 200 mM glucose. The β-G@MOF has a lower K m value compared with the free β-G, indicating enhanced substrate affinity. A conversion of 99.8 % was achieved in the hydrolysis of icariin to baohuoside I within 2 h. Additionally, β-G@MOF exhibited significantly reusability, maintaining 70.5 % yield after eight cycles at 60 °C. This study provides a simple, efficient, and sustainable approach for industrial production of baohuoside I and has potential for hydrolyzing other poorly soluble flavonoids.
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Asian Journal of Pharmaceutical Sciences
·
2024
·
IF 10.7
Boyu Xiong,Xinxin Shao,Guangxu Fang,Mengmeng Dong,Haobo Han,Quanshun Li
Herein, porous poly(lactic-co-glycolic acid) (PLGA) microspheres were prepared to load icariin and miR-23b for the treatment of metastatic lung cancer. The microspheres exhibited desirable aerodynamic diameter, high drug loading and encapsulation efficiency, as well as a favorable drug release profile, which was beneficial for the deposition and exposure of drugs in the lung tissues. The release solution from microspheres exhibited a favorable anti-proliferative effect by inducting cell apoptosis and arresting the cell cycle at G1 phase, and meanwhile inhibited the migration and invasion of cancer cells. More importantly, the microspheres could be effectively inhaled and accumulated in the lung tissues to trigger the in situ apoptosis of tumor cells and suppress metastasis, using mice bearing melanoma-metastatic lung cancer as a model. Furthermore, inhalation of the microspheres showed good favorable biocompatibility, barely causing tissue damage. Overall, porous PLGA microspheres provide a promising platform for the inhalable co-delivery of drugs and genes to obtain ideal therapeutic efficacy in lung cancer and other pulmonary diseases.
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Materials Today Bio
·
2025
·
IF 10.2
Yongbin Wang,Han Zhang,Zhili Xu,Weihang Zhu,Sheng Chang,Jiahao Wei,Shuqing Chen,Yong Liu,Weiqing Kong,Jianwei Guo
Large bone defects present significant clinical challenges due to limitations of current treatments including immune rejection, infection, and poor osteoinductive capacity. This study developed a novel biomimetic piezoelectric scaffold system combining 3D-printed potassium sodium niobate/nano-hydroxyapatite/polylactic acid (KNN/nHA/PLA) scaffolds with icariin-loaded gelatin methacryloyl hydrogel (ICA@G/NHP) to synergistically promote bone regeneration and immunomodulation. The composite scaffolds demonstrated excellent mechanical properties and stable piezoelectric output under ultrasonic activation. In vitro studies revealed that ultrasonic stimulation was essential for activating piezoelectric effects, significantly enhancing osteogenic differentiation of bone marrow mesenchymal stem cells through upregulation of ALP, RUNX2, and COL1 expression. The incorporated icariin effectively promoted endothelial cell migration and induced M2 macrophage polarization via C-type lectin receptor signaling pathway, creating a pro-regenerative immune microenvironment. In vivo validation using rat cranial and rabbit femoral condyle defect models demonstrated superior bone regeneration with enhanced bone mineral density, bone volume fraction, and mature trabecular architecture compared to controls. Immunofluorescence analysis confirmed sustained M2 macrophage dominance and suppressed inflammatory responses. RNA sequencing identified PI3K/Akt as the central mechanotransduction pathway mediating scaffold effects. This integrated platform addresses dual challenges of osteogenesis and immune regulation, offering a promising therapeutic strategy for critical-sized bone defect repair through ultrasound-activated piezoelectric stimulation combined with targeted immunomodulation.
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Chinese Journal of Natural Medicines
·
2024
·
IF 4
Wenhui YAO,Rongpin TAO,Kai WANG,Xuansheng DING
ABSTRACT Icariin, a flavonoid glycoside, is extracted from Epimedium . This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1β, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation.
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Biomaterials Advances
·
2026
·
IF 6.7
Changxu Wang,Shenghao Shi,Fei Wang,Chong Yuan,Di Liu,Yifei Liu
Osteoporosis is a prevalent metabolic bone disorder characterized by an imbalance between bone resorption and formation. Current therapeutic options are constrained by side effects and low bioavailability. Icariin (ICA), a naturally derived osteotropic flavonoid, exhibits osteogenic and anti-osteoclastogenic properties; however, its clinical application is limited due to poor solubility and low oral bioavailability. This study introduces β-cyclodextrin-modified gold nanoclusters (CGNCs) as a nanocarrier for efficient delivery of ICA. The synthesized ICA-loaded CGNCs (ICA-CGNCs) have a hydrodynamic diameter of approximately 2.16 nm, demonstrating excellent dispersity, sustained release kinetics, and storage stability. In vitro, ICA-CGNCs showed good cytocompatibility in both MC3T3-E1 pre-osteoblasts and RAW264.7 macrophages. In MC3T3-E1 cells, ICA-CGNCs promoted osteogenic differentiation, as indicated by increased ALP activity, enhanced mineralization, and upregulated osteogenic genes (ALP, BMP2, RUNX2, and COL1A1 ); immunofluorescence further showed elevated nuclear β-catenin and RUNX2 signals, supporting the involvement of osteogenic pathway-associated events in this cell model. In RAW264.7 cells, ICA-CGNCs suppressed RANKL-induced osteoclastogenesis by reducing TRAP-positive multinucleated osteoclast formation, disrupting F-actin ring organization, and downregulating osteoclast markers ( TRAP, CTSK, MMP9, and NFATc1 ), which was supported by decreased bone resorption pit formation and attenuated nuclear accumulation of NF-κB p65 and NFATc1·In a glucocorticoid-induced zebrafish osteoporosis model, ICA-CGNCs effectively promoted cranial and vertebral bone mineralization without systemic toxicity, outperforming both free ICA and CGNCs alone. This study establishes the ICA-CGNC platform as a dual-action nanotherapeutic strategy with significant potential for osteoporosis treatment and bone regeneration.
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