INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2022
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IF 6.51
Xianbin Wang,Wenjun Cao,Chuanfen Sun,Yutie Wang,Mingyu Wang,Jiarong Wu
Rheumatoid arthritis (RA) is a chronic and symmetrical autoimmune disease that primarily characterized with articular synovial hyperplasia, joint swelling, cartilage and bone destruction. The in-depth understanding of the role of immune signaling pathway inhibitors provides inspiration for the construction of new and more effective strategy for RA therapy. In this study, by loading methotrexate (MTX) into an acetalated dextran biopolymer, AcDEX, we developed a pH-sensitive, MTX-loaded and molecularly targeted nanodrug [email protected] NPs) to decrease the toxicity of MTX and simultaneously enhance its therapeutic effect. The resultant [email protected] NPs showed the spherical morphology and notable pH-responsiveness with high drug loading of 88.32%. As demonstrated in vitro and in vivo , the reduced cytotoxicity of both RAW264.7 cells and LPS-activated RAW264.7 cells treated with [email protected] NPs was found compared to free MTX. Upon intravenous administration into adjuvant-induced arthritis (AIA) rat model, the nanodrug had potent pharmacokinetic and pharmacodynamic profiles, which can accumulate in RA lesions and release MTX inhibitors for regulating the JAK-STAT pathways. As a result, the [email protected] NPs achieved the cartilage and bone protective and a better anti-inflammatory effect with negligible systemic toxicity, suggesting the strong potential of safe and effective nanodrug for RA therapy as well as other autoimmune diseases.
研究领域:
药学
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纳米技术
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免疫学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2025
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IF 5.7
Kaiwen Yin,Zheng Liu,Chenyu Liao,Jiawei Li,Hao Wang,Kunhua Yang,Li Zhang,Yunfeng Li
The potential for persistent and controllable delivery of osteoprotegerin (OPG) under osteoporotic conditions has become an essential property of bone implants to promote osseointegration and osteogenesis. Herein, a microenvironment-responsive surface coating for titanium (Ti) implants by immobilizing metal-organic frameworks (MOFs) loaded with OPG onto alkali heat-treated Ti surfaces via gelatin (Gel) (AHT-MOF@OPG-GEL) was successfully fabricated. In weakly acidic environment, MOF@OPG can achieve responsive degradation and slow release of zinc ions (Zn2+) and OPG, which not only inhibits osteoclast activity and osteoclastic biomarker expressions, but also potentiates osteoblast proliferation and differentiation in vitro. Moreover, alkali heat treatment was favorable for the hydrophilicity and cell adhesion of the Ti surface. In addition, in vivo experiments in the osteoporotic bone defect model confirmed that the MOF-based functional coating could promote the generation of new bone around the implant, thereby enhancing the bonding strength between the implant and the surrounding bone tissue, and effectively facilitating the osseointegration of the implant with the bone tissue. In conclusion, this study is expected to provide new ideas for improving the osseointegration of implants in osteoporotic conditions.
研究领域:
生物医学工程
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骨科研究
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材料科学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2015
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IF 2.998
Hui-Hui Xiao,Quan-Gui Gao,Ming-Xian Ho,Yan Zhang,Ka-Chun Wong,Yi Dai,Xin-Sheng Yao,Man-Sau Wong
Ethnopharmacological relevance Sambucus williamsii Hance (SWH), which belongs to the Caprifoliaceae family distributed in various regions of China, Korea and Japan, has been used as a folk medicine for treatment of bone and joint diseases in China for thousands of years. In previous studies, SWH was shown to possess anti-osteoporosis, healing fracture, anti-inflammatory and analgesic activities. Our previous studies showed that SWH extract effectively suppressed ovariectomy-induced increase in bone turnover and improved bone mineral density and bone biomechanical strength in rats as well as in mice. An 8- O -4′ norlignan, (7 R ,8 S )-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol (PPD) was previously isolated and identified as the bioactive ingredient in SWH. The present study aimed to characterize the bone protective effects as well as its mechanism of actions in osteoblasts. Materials and methods Bone protective actions of PPD on different cells were determined by proliferation assay, alkaline phosphatase (ALP) activity assay, calcium deposition as well as real-time reverse transcriptase-polymerase chain reaction (RT-PCR). In addition, estrogen receptor (ER) antagonist ICI182,780 and mitogen-activated protein kinase kinase (MEK) inhibitor U0126 blocking assays, competitive ER radioligand binding assay, ERE-dependent luciferase reporter assay and immunoblotting were used to determine if PPD activated ER and if the effects of PPD on osteoblastic functions were ER dependent. Results PPD exerted anabolic effects in osteoblasts and its effects were abolished by co-incubation with ICI182,780 or U0126. PPD induced mRNA expressions of Runx2, ALP, osteocalcin, and increased the ratio of osteoprotegerin/receptor activator of nuclear factor κB (OPG/RANKL). PPD failed to bind to either ERα or ERβ and did not activate ERE-luciferase activity via ER. PPD induced the phosphorylation of extracellular regulated kinases (ERK) and its effect was completely abolished by U0126. It also induced the phosphorylation of ERα at serine 118. Conclusion These data show that PPD is a bioactive compound in SWH that exerts oestrogen-like actions in osteoblast-like cells via ligand-independent, estrogen response element (ERE)-independent and mitogen-activated protein (MAP) Kinase-mediated rapid nongenomic ER signaling pathway.
研究领域:
民族药理学
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分子生物学
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骨代谢研究
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2025
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IF 6.5
Kaifeng Gan,Jie Li,Xuyang Zhang,Zhenhua Feng,Junhui Liu,Fengdong Zhao
Introduction Osteoarthritis (OA) is a common chronic joint disease that severely affects patients’ quality of life. Quercetin, a natural flavonoid, exhibits chondroprotective effects, though its bioavailability through regular oral consumption is limited. In this study, we employed two-dimensional MXene nanosheets as a nanocarrier to facilitate targeted intracellular delivery of quercetin, aiming to enhance its therapeutic efficacy against OA.Methods Methods: Porous Ti₃C₂Tₓ MXene nanosheets were synthesized via selective etching and then loaded with quercetin through physical adsorption. Material characterization was performed using transmission electron microscopy (TEM), scanning electron microscopy (SEM), ultraviolet–visible spectroscopy (UV–Vis), dynamic light scattering (DLS), and in vitro release assays. For in vitro evaluation, IL-1β-stimulated primary mouse articular chondrocytes (ACs) were treated with free quercetin or MXene-loaded quercetin, followed by assessments of cell viability, apoptosis, cell cycle progression, migration, oxidative stress markers, and ferroptosis-related protein expression. For in vivo validation, a destabilization of the medial meniscus (DMM) mouse model of OA was established to assess cartilage morphology, ferroptosis markers, and histological changes after intra-articular injection of treatments.Results MXene-loading significantly enhanced quercetin’s protective effects in IL-1β-induced primary mouse ACs, including improved cell viability and proliferation, reduced apoptosis, alleviated oxidative stress, and suppression of ferroptosis. In OA mice, MXene–quercetin treatment more effectively preserved cartilage integrity and inhibited ferroptosis compared with free quercetin.Conclusion These findings suggest that MXene can serve as a biocompatible carrier to improve quercetin delivery in osteoarthritis models, supporting its potential for further preclinical evaluation.
研究领域:
骨科学
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纳米医学
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药剂学
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分子生物学
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转化医学
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风湿病学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Mingmei Xiao,Jiuhua Zhang,Jiajin Wu,Ning Yuan,Tao Liu,Chunzhi Tang,Nenggui Xu,Qingxin Li,Jinchuan Wu,Shijie Li,Zhuoyue Song
3-Acetylaconitine (AAC) is a commercially analgesic drug for arthritis, however, due to its narrow safety range, its clinical application is limited. The objective of the study was to investigate the combined effect of Cucumaria frondosa polysaccharide (CFP) and AAC in microneedles on knee osteoarthritis (KOA). The characterization of microneedles was conducted and a rat model of monosodium iodoacetate (MIA)-induced KOA was established to evaluate the anti-inflammatory and analgesic activity in this study. The inhibitory effects on cartilage degradation and synovial inflammation were determined by morphological observation of the knee joint, pathological and imaging results. The von Frey pain threshold and hind limb weight bearing test were used to evaluate the effect of microneedles on pain relief. The results showed that microneedles had the mechanical strength to penetrate the skin and dissolved well in the skin for drug delivery within 30 min after patch administration. Furthermore, AAC-MN and CFP-AAC-MN both played roles in relieving pain, reducing cartilage degeneration and inhibiting synovial inflammation in KOA. In summary, CFP combined with AAC loading into microneedles exhibited higher skin penetration and more advantages in inhibiting cartilage damage and inflammation compared to AAC alone.
研究领域:
医学
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药理学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Pham Thi Nhat Trinh,Tong Thanh Danh,Do Chiem Tai,Phung Van Trung,Luu Hong Truong,Dang Thi Le Hang,Truong Minh Dung,Le Tien Dung
Ethnopharmacological relevance Traditional medicine in Vietnam has long utilized Caryota mitis Lour fruit peel to relieve joint pain, back pain, and inflammation. Despite its widespread use, scientific validation of its therapeutic effects remains limited. The application of the fruit peel in disease treatment is largely based on anecdotal evidence, highlighting the need for rigorous scientific research to substantiate its efficacy and elucidate its mechanisms of action. Aim of the study This study aimed to investigate the immunomodulatory effects, including anti-xanthine oxidase activity, reactive oxygen species (ROS) inhibition, and anti-inflammatory properties, alongside cartilage-protective effects such as in vitro chondrocyte proliferation, chondrogenic activity, and in vivo osteoarthritis treatment. Furthermore, phytochemical profiling was conducted to identify bioactive compounds in the fruit peel extract. Methods Active compounds were extracted using various chromatographic techniques. Cytotoxicity and chondrogenic assays were performed on human chondrocytes to assess cellular responses. A model of LPS-induced RAW264.7 macrophages was used to evaluate nitric oxide (NO), interleukin-6 (IL-6), and interleukin-10 (IL-10) secretion, as well as ROS inhibition. Xanthine oxidase inhibition assays were conducted to assess the impact on uric acid production. In vivo efficacy was examined using a CFA-induced osteoarthritis mouse model, with histological analysis and biomarker quantification to assess cartilage regeneration and anti-inflammatory effects. The phytochemical profile was analysed using LC-MS/MS and molecular networking, while the chemical structures of isolated compounds were confirmed through spectral analysis. Results All extracts—including crude ethanol (CME), hexane (CMH), chloroform (CMC), ethyl acetate (CMEA), and methanol (CMM)—significantly enhanced chondrocyte proliferation at concentrations below 1 μg/mL. At 0.1 μg/mL, CME, CMC, and CMEA strongly promoted cartilage formation. Additionally, CME, CMH, and CMEA exhibited potent immunomodulatory effects by reducing intracellular ROS, inhibiting xanthine oxidase activity, and suppressing inflammatory mediators such as NO and IL-6. In vivo, osteoarthritis-induced mice treated with CME exhibited significant cartilage regeneration, as evidenced by Safranin O staining and histopathological evaluation. The extract reduced ankle joint swelling, suppressed inflammatory cytokines, and improved cartilage integrity, demonstrating comparable efficacy to diclofenac treatment. Phytochemical analysis identified 18 bioactive compounds, primarily flavonoids and anthraquinones, in the fruit peel. Among them, emodin and esculetin, isolated from the CMEA fraction, demonstrated significant anti-inflammatory and xanthine oxidase inhibitory activities. Conclusion This study provides the first pharmacological validation of Caryota mitis fruit peel in joint disease management. The extracts exhibited immunomodulatory effects, cartilage-protective properties, and xanthine oxidase inhibition, supporting their potential role as a natural alternative to NSAIDs for osteoarthritis and gout. These findings underscore the need for further clinical research to facilitate the integration of Caryota mitis into modern phytotherapy.
研究领域:
药理学
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传统医学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Journal of Traditional and Complementary Medicine
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2019
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IF 0
Tijjani Rabiu Giaze,Ahmad Nazrun Shuid,Ima Nirwana Soelaiman,Norliza Muhammad,Jamia Azdina Jamal,Mh Busra Fauzi,Norazlina Mohamed
Background Marantodes pumilum var. alata ( MPva ), popularly known as Kacip Fatimah, is widely used to maintain female reproductive health , facilitate post-partum recovery and manage symptoms of menopause and osteoporosis in South-East Asia. This study aims to further evaluate the osteoprotective potential of MPva in view of reports of its bone-protective properties in postmenopausal condition. Methods Thirty female Sprague-Dawley rats were sorted into 5 groups (n = 6) namely: MPv (leaf treatment); MPr (root treatment); ERT (estrogen treatment); OVXC (untreated ovariectomized control) and Sham (untreated sham-operated control). All rats (except the Sham) were ovariectomized to induce a state of estrogen deficiency that simulates menopause. Two weeks after ovariectomy , the rats were treated for 8 weeks with oral gavages of estrogen and plant extracts. The ERT group received 64.5 μg/kg/day dose of estrogen while MPv and MPr groups received 20 mg/kg/day dose of leaf and root extracts , respectively. At the end of treatment , left femora were excised from euthanized rats and investigated for changes in bone micro-architecture, mineral density , and biomechanical properties. Results Bone volume fraction, degree of anisotropy and structure-model-index of bone were significantly improved ( p < 0.05) in the MPv group compared to OVXC. Breaking force and maximum stress of bone were also significantly higher ( p < 0.05) in the MPv group compared to the OVXC. Conclusion Treatment with MPva leaf protected bone microarchitecture and density against osteoporosis-related changes in postmenopausal rats. Similar to estrogen, the protective effects of MPva leaf translated into better-enhanced bone mechanical properties compared to the root treatment.
研究领域:
药理学
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骨生物学
✓ 已验证
DOI
PubMed
Journal of Inflammation Research
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2025
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IF 4.1
Ya Li,Peizhi Lu,Haoyu Yao,Shuo Yang,Bizhi Tu,Lingchao Kong,Rende Ning
Background Knee osteoarthritis (KOA) is a degenerative joint disease characterized by cartilage degradation, synovial inflammation, and joint pain. The infrapatellar fat pad (IFP) has been suggested to play a role in modulating the inflammatory processes in KOA. Excision of the IFP is considered a potential therapeutic approach to reduce inflammation and slow disease progression.Methods A mouse model of KOA was used to evaluate the impact of IFP excision on inflammation. Mice were divided into five groups: sham (control), unexcised IFP, quarter excision, partial excision, and complete excision of the IFP. Knee joints were collected at early, middle, and late stages of KOA. Gait analysis, micro-computed tomography (micro-CT), HE staining, Safranin O-Fast Green staining, and immunohistochemistry (IHC) were performed to assess joint stability, bone changes, and inflammatory markers (MMP-3, IL-6, TNF-α, COL-2). qRT-PCR was conducted for cartilage tissue analysis.Results Partial IFP excision significantly improved joint stability, particularly in the middle and late stages of KOA. Micro-CT analysis showed increased bone volume fraction (BV/TV) and trabecular thickness (Tb.Th) in excised groups, with the most significant effects in the partial and complete excision groups. IHC and qRT-PCR indicated reduced MMP-3, IL-6, and TNF-α levels in excised groups, particularly in the partial and complete excision groups, suggesting reduced inflammation. COL-2 expression was higher in excised groups, particularly in late-stage KOA, indicating cartilage protection. The partial excision group exhibited the most balanced reduction in inflammation and improved cartilage integrity across all disease stages.Conclusion IFP excision, especially partial excision, significantly modulates the inflammatory response in KOA. Partial excision showed the most effective and balanced impact on joint stability, bone integrity, and cartilage protection, offering potential as a therapeutic approach for KOA.
研究领域:
医学
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病理学
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骨科
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2022
·Vol. 23
·期 15
·8468
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IF 6.208
Innocent U. Okagu,Timothy P. C. Ezeorba,Rita N. Aguchem,Ikenna C. Ohanenye,Emmanuel C. Aham,Sunday N. Okafor,Carlotta Bollati,Carmen Lammi
The drugs used for treating bone diseases (BDs), at present, elicit hazardous side effects that include certain types of cancers and strokes, hence the ongoing quest for the discovery of alternatives with little or no side effects. Natural products (NPs), mainly of plant origin, have shown compelling promise in the treatments of BDs, with little or no side effects. However, the paucity in knowledge of the mechanisms behind their activities on bone remodeling has remained a hindrance to NPs’ adoption. This review discusses the pathological development of some BDs, the NP-targeted components, and the actions exerted on bone remodeling signaling pathways (e.g., Receptor Activator of Nuclear Factor κ B-ligand (RANKL)/monocyte/macrophage colony-stimulating factor (M-CSF)/osteoprotegerin (OPG), mitogen-activated protein kinase (MAPK)s/c-Jun N-terminal kinase (JNK)/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Kelch-like ECH-associated protein 1 (Keap-1)/nuclear factor erythroid 2–related factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1), Bone Morphogenetic Protein 2 (BMP2)-Wnt/β-catenin, PhosphatidylInositol 3-Kinase (PI3K)/protein kinase B (Akt)/Glycogen Synthase Kinase 3 Beta (GSK3β), and other signaling pathways). Although majority of the studies on the osteoprotective properties of NPs against BDs were conductedex vivoand mostly on animals, the use of NPs for treating human BDs and the prospects for future development remain promising.Keywords:bioactive compounds;bone diseases;bone remodeling;natural products;osteoprotective properties;bone signaling pathways
研究领域:
医学
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生物学
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DOI
PubMed
高影响因子
ACS Biomaterials Science & Engineering
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2024
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IF 5.4
Linlin Zhao,Liangxiao Li,Yingyu Zhang,Ziye He,Xin Chen,Yingying Liu,Bin Shi,Yajun Liu
Osteoarthritis (OA) is a chronic joint disease highly associated with an imbalance in the network of inflammatory factors and typically characterized by oxidative stress and cartilage damage. Moreover, the specificity of the joint structure makes it difficult for drugs to achieve good penetration and effective enrichment in the joint cavity. Therefore, therapeutic strategies that increase the specific targeting of drugs to inflammatory joint and incorporate antioxidative stress effects are important to improve the efficacy of OA. Here, we developed a folic acid-modified liposomal nanoparticle (AST@Lip-FA) loaded with the antioxidant astaxanthin (AST) to enhance the water solubility and stability of AST and to target the delivery of AST to the site of OA, leading to a significant improvement in therapeutic efficacy. In vitro experiments demonstrated that, due to the recognition by FA of the receptor folate receptor β on the surface of activated macrophages, the cellular uptake efficiency of AST@Lip-FA was increased. Meanwhile, intracellularly overexpressed inflammatory mediators such as reactive oxygen species and nitric oxide were efficiently removed by AST@Lip-FA. In addition, in the ACLT-induced OA mouse model, AST@Lip-FA was precisely enriched in the inflamed joints and achieved long-term retention, fully utilizing the anti-inflammatory, antioxidant, and cartilage-protecting effects of AST to effectively alleviate the progression of OA. In summary, AST@Lip-FA has an important prospect as a potential and effective therapeutic strategy for OA.
研究领域:
药理学
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纳米技术
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风湿病学
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骨科
✓ 已验证
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
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2023
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IF 7.5
Wanwu Dai,Pan Jin,Xingyan Li,Jinmin Zhao,Ying Lan,Hongmian Li,Li Zheng
Osteoarthritis (OA) is considered to be the most common joint disorder. Exogenous drug intervention is one of the effective means for OA treatment. Clinical applications of numerous drugs are restricted owing to the short retention as well as rapid clearance in the joint cavity. A wide variety of carrier-based nanodrugs have been developed, but additional carriers may bring unexpected side effects or even toxicity. Herein, by exploiting the spontaneous fluorescence of Curcumin, we designed a new carrier-free self-assembly nanomedicine Curcumin (Cur)/icariin (ICA) nanoparticles with adjustable particle size, which is composed of two small-molecule natural drugs assembled via π–π stacking interaction. Experimental results revealed that Cur/ICA NPs endowed with little cytotoxicity, high cellular uptake and sustained drug release, could inhibit secretion of inflammatory cytokines and reduce cartilage degeneration. Moreover, both the in vitro and in vivo experiments showed the NPs exerted superior synergism effects in anti-inflammatory and cartilage protection than either Cur or ICA alone, and self-monitored its retention by autofluorescence. Thus, the new self-assembly nano-drug combining Cur and ICA represents a new strategy for the treatment of osteoarthritis.
研究领域:
药学
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纳米技术
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Translational Research
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2021
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IF 4.06
Jinlong Chen,Yishan Yang
Objective: To determine whether long-chain non-coding RNA (lncRNA) HAGLR can regulate BMP2 by absorbing microRNA-214-3p (miR-214-3p), and to explore its role and mechanism in tibial fracture (TF) healing. Methods: The HAGLR, miR-214-3p, and BMP2 expression levels in TF and in adjacent normal tissues were measured using quantitative real-time polymerase chain reaction (qRT-PCR). MC3T3-E1 osteoblasts were used to construct the in vitro model. HAGLR was localized subcellularly through RNA-fluorescence in situ hybridization (FISH). A dual-luciferase report experiment confirmed that miR-214-3p has a targeted relationship with HAGLR and BMP2. It was then divided into a HAGLR over-expression group, an miR-214-3p mimic group, a HAGLR+miR-214-3p mimic group, an sh-HAGLR group, a BMP over-expression group, an sh-HAGLR+over-expression BMP2 group, and a negative control group. The proliferation and apoptosis of the MC3T3-E1 osteoblasts were examined using MTT assays and flow cytometry. A TF model was established in male C57BL/6J mice. The serum alkaline phosphatase (ALP) and osteoprotegerin (OPG) levels in the sham group, the TF group, and the TF group that were injected with HAGLR were compared using ELISA. Hematoxylin-eosin (HE) staining was used to confirm the fracture healing in the mouse model. Results: Compared with the adjacent normal tissues in the TF patients, the HAGLR and BMP2 expressions decreased but the miR-214-3p expressions increased in the TF tissues ( P <0.05). HAGLR, an endogenous sponge, absorbed the miR-214-3p, and the BMP2 expression was directly regulated by miR-214-3p. HAGLR increased the proliferative activity of the osteoblasts and decreased the apoptosis rate. The over-expression of miR-214-3p partly reversed the effect of HAGLR on the cells, decreased the proliferative activity, and increased the apoptosis rate (all P <0.05). The sh-HAGLR decreased the proliferative activity and increased the apoptosis rate. But after the over-expression of BMP2, the proliferative activity of the cells was higher, and the apoptosis rate was lower than it was in the sh-HAGLR group (all P <0.05). The over-expression of HAGLR can up-regulate the ALP and OPG levels in mouse models ( P <0.05). Conclusion: lncRNA HAGLR can regulate BMP2 to play a protective role in TF by absorbing miR-214-3p, and it is related to promoting the osteoblast proliferation, inhibiting apoptosis, and up-regulating the serum ALP and OPG levels to accelerate bone healing.
研究领域:
分子生物学
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骨科
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再生医学
✓ 已验证
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）