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13 pages, 4625 KB  
Article
Formulation, Optimization, and Evaluation of Transferosomes Co-Loaded with Methotrexate and Sorafenib for Anti-Arthritic Activity
by Muhammad Adnan, Lateef Ahmad, Muhammad Junaid Dar, Humzah Jamshaid, Muhammad Noman and Muhammad Faheem
Pharmaceutics 2025, 17(9), 1196; https://doi.org/10.3390/pharmaceutics17091196 - 15 Sep 2025
Viewed by 404
Abstract
Purpose: This study was designed to develop a nanoparticle-based methotrexate (MTX) and sorafenib (SRF)-loaded transferosome (MTX-SRF-TFS) for effective management of arthritis through the transdermal route. Methods: For the preparation of MTX-SRF-TFS, the thin-film hydration technique was selected and optimized using Box–Behnken Design. The [...] Read more.
Purpose: This study was designed to develop a nanoparticle-based methotrexate (MTX) and sorafenib (SRF)-loaded transferosome (MTX-SRF-TFS) for effective management of arthritis through the transdermal route. Methods: For the preparation of MTX-SRF-TFS, the thin-film hydration technique was selected and optimized using Box–Behnken Design. The particle size of the nanoparticles was determined using a Malvern Zeta sizer and electron microscopy. An in vivo skin retention and penetration study was also conducted to evaluate the designed delivery system. Furthermore, the therapeutic response of MTX-SRF-TFS was determined using the CFA-induced mouse model. Results: The optimized MTX-SRF-TFS formulation (F4), having an average particle size (PS) of 162.20 ± 2.89 nm and percent entrapment efficiency (%EE) of MTX and SRF of 92.16 ± 4.95 and 81.54 ± 3.23, respectively, was selected for further assessment. Due to the deformable nature of MTX-SRF-TFS, MTX and SRF penetrate more deeply into the cutaneous layers, exhibiting an enhanced transdermal effect, as shown by the results of ex vivo skin permeation and retention studies. Furthermore, in vivo anti-arthritic studies have shown the superior pharmacodynamic response of MTX and SRF when incorporated into transferosomes, as it caused a marked reduction in arthritic score and paw diameter in CFA-induced arthritis in BALB/c mice. Histopathology analysis and X-ray radiography also confirmed the findings that MTX-SRF-TFS has improved anti-arthritic response in contrast to plain MTX-SRF gel. Conclusions: The MTX-SRF-TFS is highly effective in managing CFA-induced arthritis, and the designed delivery system should be further evaluated on pharmacokinetic grounds to progress towards clinical studies. Full article
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11 pages, 1307 KB  
Article
Prospective Comparison of Short-Term Outcomes in Kinematic and Mechanical Alignment Total Knee Arthroplasty
by Ofir Vinograd, Ahmad Essa, Netanel Steinberg, Ilan Y. Mitchnik, Dana Avraham, Inon Rotem, Adi Vinograd, Yiftah Beer, Noam Shohat and Yaron Bar-Ziv
Clin. Pract. 2025, 15(9), 162; https://doi.org/10.3390/clinpract15090162 - 31 Aug 2025
Viewed by 695
Abstract
Background: While mechanical alignment total knee arthroplasty (TKA) has long been the conventional surgical technique in patients with advanced osteoarthritis, kinematic alignment TKA has emerged as a promising alternative, designed to restore the knee’s native pre-arthritic anatomy. Since superiority of either technique remains [...] Read more.
Background: While mechanical alignment total knee arthroplasty (TKA) has long been the conventional surgical technique in patients with advanced osteoarthritis, kinematic alignment TKA has emerged as a promising alternative, designed to restore the knee’s native pre-arthritic anatomy. Since superiority of either technique remains inconclusive, we aimed to compare immediate and short-term postoperative outcomes of kinematic versus mechanical alignment TKA. Methods: This prospective cohort study was conducted at a tertiary care centre between January 2020 and August 2022, enrolling kinematic and mechanical alignment TKA patients. Outcomes were assessed during hospitalization and at 14 days postoperatively. Data collected included patient-reported outcome measures (PROMs), functional performance evaluations, pain scores, discharge disposition and hospital length of stay. Both univariate and multivariate regression analyses were conducted, adjusting for potential confounders. Results: The study included 103 patients, with 77 who underwent kinematic alignment and 26 mechanical alignment TKA. Patients in the kinematic alignment group demonstrated statistically significant better postoperative outcomes compared to those in the mechanical alignment group. Kinematic alignment TKA patients demonstrated superior functional performance on the Timed Up and Go test immediately postoperatively and were more frequently discharged home rather than to a rehabilitation facility. Hospital stay length and short-term PROMs also favoured the Kinematic alignment TKA group, showing statistically significant higher scores in the Oxford Knee Score, short form-12 Mental Component Summary, and the Knee Injury and Osteoarthritis Outcome Score Symptoms subscale. Conclusions: Kinematic alignment TKA offers superior immediate and short-term outcomes compared to mechanical alignment TKA, with benefits in functional recovery, hospitalization duration, and discharge disposition. This evidence supports kinematic alignment TKA as a viable alternative, aiding in patient and surgeon decision-making. Full article
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19 pages, 6713 KB  
Article
In Vitro Enzymatic and Computational Assessments of Pyrazole–Isatin and Pyrazole–Indole Conjugates as Anti-Diabetic, Anti-Arthritic, and Anti-Inflammatory Agents
by Ahmed M. Naglah, Abdulrahman A. Almehizia, Mohammed Ghazwani, Asma S. Al-Wasidi, Abdelrahman A. Naglah, Wael M. Aboulthana and Ashraf S. Hassan
Pharmaceutics 2025, 17(3), 293; https://doi.org/10.3390/pharmaceutics17030293 - 23 Feb 2025
Cited by 4 | Viewed by 1506
Abstract
Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to the various biomedical applications of pyrazole, isatin, and indole derivatives. Accordingly, cooperation will continue [...] Read more.
Background/Objectives: Recently, the prevalence of diseases such as diabetes, arthritis, and inflammatory diseases, along with their complications, has become a significant health problem. This is in addition to the various biomedical applications of pyrazole, isatin, and indole derivatives. Accordingly, cooperation will continue between chemistry scientists, pharmaceutical scientists, and human doctors to produce hybrid compounds from pyrazole with isatin or indole possessing biological activities as anti-diabetic, anti-arthritic, and anti-inflammatory agents. Methods: The two series of pyrazole–isatin conjugates 12ah and pyrazole–indole conjugates 14ad were prepared from our previous works via the direct reaction of 5-amino-pyrazoles 10ad with N-alkyl isatin 11a,b, and 1H-indole-3-carbaldehyde (13), respectively, using the previously reported procedure. The potential biological activities of 12ah and 14ad as anti-diabetic, anti-arthritic, and anti-inflammatory agents were assessed through estimated inhibition percentage (%) and the median inhibitory concentrations (IC50) using methods described in the literature. Further, the computational assessments of 12ah and 14ad such as toxic doses (the median lethal dose, LD50), toxicity classes, drug-likeness model scores (DLMS), molecular lipophilicity potential (MLP) maps, polar surface area (PSA) maps, and topological polar surface area (TPSA) values were predicted using available free websites. Results: The in vitro enzymatic assessment results showed that pyrazole–indole conjugate 14b possesses powerful activities against (i) α-amylase (% = 65.74 ± 0.23, IC50 = 4.21 ± 0.03 µg/mL) and α-glucosidase (% = 55.49 ± 0.23, IC50 = 2.76 ± 0.01 µg/mL); (ii) the protein denaturation enzyme (% = 49.30 ± 0.17) and against the proteinase enzyme (% = 46.55 ± 0.17) with an IC50 value of 6.77 ± 0.01 µg/mL; (iii) the COX-1, COX-2, and 5-LOX enzymes with an IC50 of 5.44 ± 0.03, 5.37 ± 0.04, and 7.52 ± 0.04, respectively, which is almost close to the IC50 of the indomethacin and zileuton drugs. Also, the computational assessment results showed (i) the conjugate 14b possesses lipophilic surface properties thus can cross cell membranes, and is effective for treatment; (ii) all the conjugates possess a TPSA value of more than 140 Å2 thus possess good intestinal absorption. Conclusions: The two series of pyrazole–isatin conjugates 12ah and pyrazole–indole conjugates 14ad were synthesized from our previous works. The results of these in vitro enzymatic and computational assessments concluded that the pyrazole–indole conjugate 14b possesses powerful activities against various studied enzymes and possesses good computational results. In the future, our research team will present in vitro, in vivo biological, and computational assessments to hopefully obtain effectual agents such as anti-diabetic, anti-arthritic, and anti-inflammatory. Full article
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31 pages, 5127 KB  
Article
Quantum Health Accelerator® Ameliorates CFA-Induced Animal Model of Rheumatoid Arthritis: Investigating the Role of Immunomodulatory and Anti-Oxidative Effects
by Ali Akbar Mohaddes, Mohammad Ali Saatchi, Marziyeh Afshari Chamanabadi, Saeed Saatchi, Sadra Rostami and Vahid Reza Askari
Brain Sci. 2025, 15(3), 232; https://doi.org/10.3390/brainsci15030232 - 23 Feb 2025
Viewed by 1592
Abstract
Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory and autoimmune disease characterized by joint swelling, pain, damage to the cartilage, and disability. In the present study, we aimed to evaluate the anti-oxidant, anti-inflammatory, and immune-modulatory properties of Quantum Health Accelerator® as water [...] Read more.
Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory and autoimmune disease characterized by joint swelling, pain, damage to the cartilage, and disability. In the present study, we aimed to evaluate the anti-oxidant, anti-inflammatory, and immune-modulatory properties of Quantum Health Accelerator® as water enriched with vital bio-quantum information/energy (EW) following complete Freund’s adjuvant (CFA)-induced RA in rats. Methods: Forty adult male Wistar rats (180–220 g) were divided into five groups. Arthritis was induced on day one using a single subcutaneous injection of CFA into the left hind footpad of the rat. Rats were assigned to receive methotrexate (MTX, 2 mg/kg/week, intraperitoneally), EW (orally, instead of normal water ad libitum), or their combination for 29 days. The anti-RA activities were determined by paw edema, joint diameter, arthritis score, and several nociceptive behavioral tests (thermal hyperalgesia, cold allodynia, and tactile allodynia). The levels of inflammatory (TNF-α, CRP, RF, and anti-CCP), anti-inflammatory (IL-10), and oxidative stress (NO, MDA, and GSH) markers were measured in serum. In addition, the levels of IFN-γ, IL-4, IL-17, and TGF-β were assessed in the spleen-isolated lymphocytes. Results: We found that treatment with MTX, EW, and their combination remarkably ameliorated thermal hyperalgesia, cold allodynia, and tactile allodynia results following CFA-induced RA in rats. In addition, EW also notably attenuated arthritis score, joint diameter, inflammatory cytokines, and oxidative markers while propagating anti-inflammatory and anti-oxidative mediators. Conclusions: We reveal that EW possesses anti-arthritic effects, possibly through anti-oxidative, anti-inflammatory, and immunomodulatory properties. Collectively, EW may be a promising therapeutic agent for treating RA. Full article
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20 pages, 26775 KB  
Article
Inhibitory Effects of Heat-Processed Gynostemma pentaphyllum Extract (Actiponin®) and Its Components on Cartilage Breakdown in Osteoarthritis
by Seul Ah Lee, Chan Hwi Lee, Sun Hee Lee, Eunju Do, Do Kyung Kim, Tae-Lin Huh and Chun Sung Kim
Int. J. Mol. Sci. 2025, 26(4), 1728; https://doi.org/10.3390/ijms26041728 - 18 Feb 2025
Cited by 2 | Viewed by 2167
Abstract
Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), [...] Read more.
Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), a perennial herb of the Cucurbitaceae family, has been used since the Ming dynasty as a medicinal material to treat various ailments, such as rheumatism, liver disease, and diabetes. In this study, we investigated the anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin (AP)) and its derivatives, damulin A (DA) and damulin B (DB), using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems. Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001). In addition, cartilage thickness and chondrocytes were reduced in the DMM group, but were restored in the AP-administered group. Furthermore, the von Frey analysis results showed that the pain threshold of the DMM group was considerably low (54.5 g at 8 weeks), whereas that of the AP group was dose-dependently increased (65.5, 69.5, 70.3, and 71.8 at 8 weeks for 30, 50, 100, and 200 mg/kg, respectively). In vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. Collectively, these results suggest that AP is a potential therapeutic agent for mitigating OA progression and chondroprotection. Full article
(This article belongs to the Section Bioactives and Nutraceuticals)
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27 pages, 9670 KB  
Article
Application of Microsponge Drug Platform to Enhance Methotrexate Administration in Rheumatoid Arthritis Therapy
by Noemi Fiaschini, Patrizia Nadia Hanieh, Daniela Ariaudo, Rita Cimino, Carlo Abbate, Elena Romano, Francesca Cavalieri, Mariano Venanzi, Valeria Palumbo, Manuel Scimeca, Roberta Bernardini, Maurizio Mattei, Alberto Migliore and Antonio Rinaldi
Pharmaceutics 2024, 16(12), 1593; https://doi.org/10.3390/pharmaceutics16121593 - 13 Dec 2024
Viewed by 1645
Abstract
Background/Objectives: This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation [...] Read more.
Background/Objectives: This study aimed to develop a novel nanotechnological slow-release drug delivery platform based on hyaluronic acid Microsponge (MSP) for the subcutaneous administration of methotrexate (MTX) in the treatment of rheumatoid arthritis (RA). RA is a chronic autoimmune disease characterized by joint inflammation and damage, while MTX is a common disease-modifying antirheumatic drug (DMARD), the conventional use of which is limited by adverse effects and the lack of release control. Methods: MSP were synthesized as freeze-dried powder to increase their stability and allow for a facile reconstitution prior to administration and precise MTX dosing. Results: A highly stable and rounded-shaped micrometric MSP, characterized by an open porosity inner structure, achieved both a high MTX loading efficiency and a slow release of MTX after injection. Our drug release assays indeed demonstrated a characteristic drug release profile consisting of a very limited burst release in the first few hours, followed by a slow release of MTX sustained for over a month. By means of a preclinical rat model of RA, the administration of MTX-loaded MSP proved to nearly double the therapeutic efficacy compared to sole MTX, according to a steep reduction in arthritic score compared to control groups. The preclinical study was replicated twice to confirm this improvement in performance and the safety profile of the MSP. Conclusions: This study suggests that the MSP drug delivery platform holds significant potential for clinical use in improving RA therapy by enabling the sustained slow release of MTX, thereby enhancing therapeutic outcomes and minimizing side effects associated with conventional burst-release drug administration. Full article
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15 pages, 918 KB  
Systematic Review
No Effect of Cigarette Smoking in the Outcome of Arthroscopic Management for Femoroacetabular Impingement: A Systematic Review
by Ludovico Lucenti, Nicola Maffulli, Tommaso Bardazzi, Gennaro Pipino, Gaetano Pappalardo and Filippo Migliorini
J. Clin. Med. 2024, 13(23), 7214; https://doi.org/10.3390/jcm13237214 - 27 Nov 2024
Cited by 2 | Viewed by 1198
Abstract
Background: The impact of smoking in arthroscopic surgery for femoroacetabolar impingement (FAI) is controversial. This systematic review updates and discusses current evidence on the influence of cigarette smoking on the outcome of arthroscopic management of FAI. The outcomes of interest were to compare [...] Read more.
Background: The impact of smoking in arthroscopic surgery for femoroacetabolar impingement (FAI) is controversial. This systematic review updates and discusses current evidence on the influence of cigarette smoking on the outcome of arthroscopic management of FAI. The outcomes of interest were to compare patient-reported outcome measures (PROMs) and complications. Methods: The present systematic review followed the PRISMA guidelines. Embase, Web of Science, and PubMed were accessed in June 2024 without additional filters or temporal constraints. All the clinical investigations comparing smokers versus nonsmokers in patients who underwent arthroscopic management for FAI were considered. The risk of bias in nonrandomised controlled trials was assessed using the Risk of Bias in Nonrandomised Studies of Interventions (ROBINS-I). Results: Data from 368 patients were retrieved. The mean length of follow-up was 34.1 ± 7.1 months. The mean age was 40.4 ± 4.0 years and the mean BMI was 27.1 ± 1.6 kg/m2. No significant difference was evidenced in the visual analogue scale, Harris hip score, Hip Outcome Score—Sport subscale, and Non-Arthritic Hip Score. No difference was observed in the complication rate: reoperation (p = 0.6) and progression to THA (p = 0.4). Conclusions: Tobacco smoking does not appear to influence the outcomes of arthroscopic management for FAI. At approximately 34 months of follow-up, no difference was found in pain, PROMs, reoperation rate, and progression to THA. Full article
(This article belongs to the Section Orthopedics)
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22 pages, 5425 KB  
Article
Phytochemical, Cytoprotective Profiling, and Anti-Inflammatory Potential of Colchicum luteum in Rheumatoid Arthritis: An Experimental and Simulation Study
by Huda Abbasi, Maria Sharif, Peter John, Attya Bhatti, Muhammad Qasim Hayat and Qaisar Mansoor
Nutrients 2024, 16(23), 4020; https://doi.org/10.3390/nu16234020 - 24 Nov 2024
Cited by 1 | Viewed by 2063
Abstract
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first [...] Read more.
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by severe pain, inflammation, and joint deformity. Currently, it affects 1% of the population, with a projection to exceed 23 million cases by 2030. Despite significant advancements, non-steroidal anti-inflammatory drugs (NSAIDs), the first line of treatment, are associated with a range of adverse effects. Consequently, plant-based derivatives are being utilized as an effective alternative. This study evaluates the anti-inflammatory and safety profile of Colchicum luteum hydroethanolic extract (CLHE) in comparison to NSAIDs, with a focus on COX-2 and TNFα inhibition. Methods: CLHE potential was evaluated by phytochemical screening and in vitro bioactivity assays. Toxicity profile was conducted in Human Colon Epithelial Cells (HCEC) and Balb/c mice. Anti-inflammatory potential was explored in a collagen-induced arthritic (CIA) mice model. Bioactive compounds were identified computationally from GCMS data and subjected to docking and simulation studies against COX2 and TNFα. Results: CLHE demonstrated significant antioxidant (IC-50 = 6.78 µg/mL) and anti-inflammatory (IC-50 = 97.39 µg/mL) activity. It maintained 50% cell viability at 78.5 μg/µL in HCEC cells and exhibited no toxicity at a dose of 5000 mg/kg in mice. In the CIA model, CLHE significantly reduced paw swelling, arthritic scoring, C-reactive protein levels, and spleen indices, outperforming ibuprofen. Expression analysis confirmed the downregulation of COX-2, TNFα, and MMP-9. Histopathological analysis indicated the superior efficacy of CLHE compared to ibuprofen in reducing inflammation, synovial hyperplasia, and bone erosion. Computational studies identified compound-15 (CL15), (4-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-2-oxo pyrrolidine-3-carboxylic acid), a non-toxic compound with strong binding affinities to COX-2 (−12.9 KJ/mol), and TNF-α (−5.8 KJ/mol). Conclusions: The findings suggest the potential of Colchicum luteum as a safer, anti-inflammatory, and multi-targeted alternative to NSAIDs for RA treatment. Full article
(This article belongs to the Special Issue Effects of Plant Extracts on Human Health)
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23 pages, 10070 KB  
Article
Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats
by Biljana Bufan, Mirjana Marčetić, Jasmina Djuretić, Ivana Ćuruvija, Veljko Blagojević, Dragana D. Božić, Violeta Milutinović, Radmila Janković, Jelena Sopta, Jelena Kotur-Stevuljević and Nevena Arsenović-Ranin
Biology 2024, 13(10), 818; https://doi.org/10.3390/biology13100818 - 12 Oct 2024
Viewed by 1832
Abstract
The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the [...] Read more.
The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund’s adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect. Full article
(This article belongs to the Special Issue Animal Models of Arthritis)
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16 pages, 23556 KB  
Article
The Therapeutic Potential of Intra-Articular Injection of Synthetic Deer Antler Peptides in a Rat Model of Knee Osteoarthritis
by Yu-Chou Hung, Li-Jin Chen, Jen-Hung Wang, Tsung-Jung Ho, Guo-Fang Tseng and Hao-Ping Chen
Int. J. Mol. Sci. 2024, 25(11), 6041; https://doi.org/10.3390/ijms25116041 - 30 May 2024
Cited by 2 | Viewed by 3525
Abstract
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture’s pain relief and chondroprotective effect in a rat model of [...] Read more.
Synthetic deer antler peptides (TSKYR, TSK, and YR) stimulate the proliferation of human chondrocytes and osteoblasts and increase the chondrocyte content of collagen and glycosamino-glycan in vitro. This study investigated the peptide mixture’s pain relief and chondroprotective effect in a rat model of collagenase-induced osteoarthritis. Thirty-six adult male Sprague–Dawley rats were divided into three groups: control (saline), positive control (hyaluronic acid), and ex-perimental (peptides). Intra-articular collagenase injections were administered on days 1 and 4 to induce osteoarthritis in the left knees of the rats. Two injections of saline, hyaluronic acid, or the peptides were injected into the same knees of each corresponding group at the beginning of week one and two, respectively. Joint swelling, arthritic pain, and histopathological changes were evaluated. Injection of the peptides significantly reduced arthritic pain compared to the control group, as evidenced by the closer-to-normal weight-bearing and paw withdrawal threshold test results. Histological analyses showed reduced cartilage matrix loss and improved total cartilage degeneration score in the experimental versus the control group. Our findings suggest that intra-articular injection of synthetic deer antler peptides is a promising treatment for osteoarthritis. Full article
(This article belongs to the Special Issue Osteoarthritis Biomarkers, Diagnosis and Treatments)
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20 pages, 4313 KB  
Article
Onosma bracteatum Wall Aqueous–Ethanolic Extract Suppresses Complete Freund’s Adjuvant-Induced Arthritis in Rats via Regulation of TNF-α, IL-6, and C-Reactive Protein
by Farah Zafar, Ghazala Shaheen, Hafiz Muhammad Asif, Mohd Farhan, Ghazala Muteeb and Mohammad Aatif
Molecules 2024, 29(8), 1830; https://doi.org/10.3390/molecules29081830 - 17 Apr 2024
Cited by 4 | Viewed by 2299
Abstract
Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous–ethanolic extract of O. bracteatum leaves (AeOB) in a rat [...] Read more.
Onosma bracteatum Wall (O. bracteatum) has been used traditionally for the management of arthritis; however, its therapeutic potential warrants further investigation. This study aimed to evaluate the anti-arthritic effects of the aqueous–ethanolic extract of O. bracteatum leaves (AeOB) in a rat model of complete Freund’s adjuvant (CFA)-induced arthritis. Rats were treated with AeOB (250, 500, and 750 mg/kg), indomethacin (10 mg/kg), or a vehicle control from days 8 to 28 post-CFA injection. Arthritic score, paw diameter, and body weight were monitored at regular intervals. X-ray radiographs and histopathological analysis were performed to assess arthritic severity. Inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and C-reactive protein (CRP) were quantified by qPCR and icromatography. Phytochemical analysis of AeOB revealed alkaloids, flavonoids, phenols, tannins, Saponins, and glycosides. AeOB also exhibited antioxidant potential with an IC50 of 73.22 µg/mL in a DPPH assay. AeOB and diclofenac exhibited anti-inflammatory and anti-arthritic activities. Rats treated with AeOB at 750 mg/kg and indomethacin showed significantly reduced arthritic symptoms and joint inflammation versus the CFA control. The AeOB treatment downregulated TNF-α and IL-6 and decreased CRP levels compared with arthritic rats. Radiography and histopathology also showed improved prognosis. These findings demonstrate the anti-arthritic potential of AeOB leaves. Full article
(This article belongs to the Section Natural Products Chemistry)
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11 pages, 771 KB  
Article
Outcomes of Hip Arthroscopy in Patients with Systemic Inflammatory Diseases: A Matched Cohort 5-Year Follow-Up Study
by Nicole D. Rynecki, Dhruv S. Shankar, Allison M. Morgan, Shalen Kouk and Thomas Youm
Surgeries 2023, 4(4), 511-521; https://doi.org/10.3390/surgeries4040050 - 3 Oct 2023
Cited by 2 | Viewed by 1901
Abstract
The purpose of this study was to determine if there is a difference in hip survivorship rates and patient-reported outcomes (PROs) at a 5-year follow-up after arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) between patients with versus without systemic inflammatory diseases (SIDs). A [...] Read more.
The purpose of this study was to determine if there is a difference in hip survivorship rates and patient-reported outcomes (PROs) at a 5-year follow-up after arthroscopic treatment of femoroacetabular impingement syndrome (FAIS) between patients with versus without systemic inflammatory diseases (SIDs). A retrospective single-surgeon matched cohort study of FAIS patients who underwent hip arthroscopy and had a minimum of a 5-year follow-up was conducted. Subjects with SIDs were matched at a ratio of 2:3 of age and body mass index (BMI) with respect to controls without SIDs. Subjects completed the modified Harris Hip Score (mHHS) and Non-Arthritic Hip Score (NAHS) prior to surgery and at a 2-year and 5-year follow-up. Survival distributions for time to reoperation and to total hip arthroplasty (THA) were compared between groups using the log-rank test. Fifteen subjects with SIDs (mean age 41.5 years) were matched with twenty-five controls (41.8 years). There were no significant differences in reoperation rates (SIDs 27% vs. controls 20%, p = 0.71) or THA conversion rates (SIDs 7% vs. controls 12%, p = 1.00) at the 5-year follow-up, nor were there differences in survival distributions for reoperations (p = 0.72) or THAs (p = 0.55). There were no significant differences in postoperative mHHS (SIDs 79.3 vs. controls 88.5, p = 0.09) or NAHS (SIDs 82.7 vs. controls 89.3, p = 0.77) by the 5-year follow-up. At the 5-year follow-up, FAIS patients with comorbid SIDs experienced a significant clinical improvement from hip arthroscopy that is comparable to that of FAIS patients without SIDs. Full article
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20 pages, 5933 KB  
Article
Curcumin Co-Encapsulation Potentiates Anti-Arthritic Efficacy of Meloxicam Biodegradable Nanoparticles in Adjuvant-Induced Arthritis Animal Model
by Bilal Aslam, Asif Hussain, Muhammad Naeem Faisal, Zia-ud-Din Sindhu, Rifat Ullah Khan, Ibrahim A. Alhidary, Shabana Naz and Vincenzo Tufarelli
Biomedicines 2023, 11(10), 2662; https://doi.org/10.3390/biomedicines11102662 - 28 Sep 2023
Cited by 9 | Viewed by 3209
Abstract
This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation [...] Read more.
This study aimed to evaluate the anti-arthritic activity of curcumin and meloxicam co-loaded PLGA nanoparticles in adjuvant-induced arthritic rats. PLGA nanoparticles encapsulating curcumin (nCur) and meloxicam (nMlx) alone and in combination (nCur/Mlx) were used to characterize zeta size and potential, polydispersity index, encapsulation efficiency (%), compound–polymer interactions (FT-IR analysis), and surface morphology (SEM imaging). In vivo, Complete Freund’s adjuvant-induced arthritic rats were intraperitoneally (i.p.) administered with curcumin, meloxicam, curcumin plus meloxicam, nCur, nMlx, and nCur/Mlx for 28 consecutive days. Results showed that nCur, nMlx, and nCur/Mlx significantly (p ≤ 0.05) reduced paw swelling and arthritic score, restored body weight and the immune organ index (thymus and spleen), as well as attenuated serum inflammatory markers (RF, CRP, and PGE2) and oxidative stress parameters (MDA, SOD, and CAT) in adjuvant-induced arthritic rats compared to free compounds. In addition, mono- and dual-compound-loaded nanoparticles significantly (p ≤ 0.05) down-regulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), up-regulated anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ), and modulated OPG and RANKL expressions in paw tissue. The aforementioned results were further confirmed through radiological and histopathological examinations. Furthermore, the anti-arthritic effect of nCur/Mlx was notably (p ≤ 0.05) enhanced compared to nCur or nMlx alone. In conclusion, the co-nanoencapsulation of curcumin could potentiate the anti-arthritic activity of meloxicam and could provide a novel therapeutic approach for the formulation of nanocarrier pharmaceutical products for the management of arthritis. Full article
(This article belongs to the Special Issue Health-Related Applications of Natural Molecule Derived Structures)
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23 pages, 2600 KB  
Article
Crocus sativus L. Extract (Saffron) Effectively Reduces Arthritic and Inflammatory Parameters in Monotherapy and in Combination with Methotrexate in Adjuvant Arthritis
by Martin Chrastina, František Dráfi, Katarína Pružinská, Silvester Poništ, Kevine Silihe Kamga, Sasan Khademnematolahi, František Bilka, Peter Novák, Ľudmila Pašková and Katarína Bauerová
Nutrients 2023, 15(19), 4108; https://doi.org/10.3390/nu15194108 - 22 Sep 2023
Cited by 5 | Viewed by 4228
Abstract
Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron—SF) [...] Read more.
Rheumatoid arthritis (RA), an autoimmune disease, is characterized by inflammation that affects not only the liver but also other organs and the musculoskeletal system. The standard therapy for RA is methotrexate (MTX), which has safety limitations. The extract from Crocus sativus L. (saffron—SF) is also known for its anti-inflammatory effects. Therefore, we decided to investigate the potential benefit of SF in monotherapy via two doses (SF1—25 mg/kg of b.w.; SF2—50 mg/kg of b.w.) and in combination with MTX (0.3 mg/kg of b.w., twice a week) using adjuvant arthritis in rats. To evaluate these therapeutic settings, we used biometric, immunological, and biochemical parameters, as well as the relative gene expression of the mRNA in the liver. Our results showed a statistically significant increase in the experimental animals’ body weight and the arthritic score (AS) on day 14 for monotherapy with SF1 and SF2. The change of hind paw volume (CHPV) was significant only for SF2 monotherapy on the 14th day of the experiment. A combination of SF1 and SF2 with MTX significantly modulated all the biometric parameters during the experimental period. Additionally, AS and CHPV improved considerably compared to MTX monotherapy on day 21. Furthermore, all monotherapies and combination therapies were significant for the biochemical parameter γ-glutamyl transferase (GGT) in the joint. GGT activity in the spleen was less pronounced; only MTX in combination with SF1 significantly modified this parameter. The higher dose of SF monotherapy (SF2) was similarly significant with respect to immunological parameters, such as plasmatic IL-17A, IL-1β, and MMP-9 on day 21. The combination of both doses of SF with MTX significantly improved these immunological parameters, except for C-reactive protein (CRP), which was influenced only by the higher dose of SF2 in combination with MTX in plasma at the end of the experiment. A different effect was found for the relative expression of CD36 mRNA, where only SF1 significantly decreased gene expression in the liver. However, the relative gene mRNA expression of IL-1β in the liver was significantly reduced by the SF monotherapies and the combination of both SF doses with MTX. Our findings showed SF’s partial antiarthritic and anti-inflammatory potential in monotherapy, but the effect was stronger in combination with MTX. Full article
(This article belongs to the Special Issue The Role of Natural Compounds in Autoimmune Diseases)
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16 pages, 2242 KB  
Article
Anti-Arthritic and Immunomodulatory Potential of Methanolic, n-Hexane, and Ethyl Acetate Fractions of Bark of Acacia modesta on Complete Freund’s Adjuvant-Induced Arthritis in Rats
by Kiran Mashaal, Arham Shabbir, Mahtab Ahmad Khan, Huma Hameed, Muhammad Shahzad, Ali Irfan, Gamal A. Shazly, Aisha Mobashar, Tasleem Akhtar, Zaib Ali Shaheryar and Yousef A. Bin Jardan
Pharmaceutics 2023, 15(9), 2228; https://doi.org/10.3390/pharmaceutics15092228 - 29 Aug 2023
Cited by 11 | Viewed by 2503
Abstract
Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the [...] Read more.
Rheumatoid arthritis is an autoimmune disorder and topic of interest for researchers due to its increasing frequency and limited treatment. Acacia modesta Wall is known to treat rheumatic disorders in the traditional system of medicinal plants. Traditional medicines are still required for the treatment of this disease due to the large number of side-effects caused by commercial medicines. In the current study, the antiarthritic potential of methanolic extract (AM-metha), n-hexane (AM-hexa) fraction, and ethyl acetate (AM-etha) fraction of the bark of A. modesta against a complete Freund’s adjuvant rat model was evaluated. Evaluation using a digital plethysmometer, macroscopic evaluation, and histopathological evaluation were conducted to determine the paw volume and arthritic scoring. ELISA was performed to assess the PGE2 levels. RT-PCR was used to evaluate the expression levels of MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF. Biochemical and hematological analyses were also conducted. GC/MS was also carried out to analyze the presence of medicinal compounds. The data revealed a marked reduction in the paw volume, arthritic scoring, and histopathological parameters, indicating the anti-arthritic potential of the plant. Treatment with plant extracts and fractions markedly down-regulated MMP2, MMP3, MMP9, NF-κB, IL6, IL1β, TNFα, and VEGF levels. Similarly, PGE2 levels were also found to be ameliorated in the treatment groups, indicating the immunomodulatory property of plant bark. Plant treatment nearly normalized hematological parameters such as counts of WBCs, RBCs, and platelets, along with Hb content, thereby validating the anti-arthritic activity. GC/MS analysis disclosed the presence of strong anti-inflammatory compounds such as lupeol, oleic acid, and squalene. The study showed that A. modesta possesses anti-arthritic and immunomodulatory potential linked to significant down-regulation of pro-inflammatory and inflammatory biomarkers. Full article
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