Search Results (146)

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

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

The genus Acmella has received growing attention for its pharmacological properties, including its potential applications in musculoskeletal disorders (MSDs). Plants in this genus, such as Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella oleracea contain various bioactive compounds which have demonstrated anti-inflammatory, analgesic, and anti-arthritic properties. This systematic review evaluates the clinical and preclinical evidence supporting the use of plants from Acmella genus for the treatment of MSD, such as arthritis, osteoporosis, muscle injuries, joint inflammation, and other related pathologies. The methodology used in this study involved a systematic literature review, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, along with synthesis analysis and quality appraisal. The articles were retrieved from Scopus, Google Scholar, and PubMed databases. Eleven articles were further analyzed to determine the therapeutic potential of Acmella genus plants for musculoskeletal disorders. The plants included were Spilanthes acmella, Blainvillea acmella, Acmella uliginosa, and Acmella olerecia. The musculoskeletal disorders investigated were osteoporosis, osteoarthritis, and myopathies. The extracts from these plants were shown to decrease inflammation, enhance joint health, relieve pain, and stimulate osteogenic activity. These effects may be attributed to several active compounds found in these plants. The available evidence suggests that Spilanthes acmella and Blainvillea acmella have the potential to treat osteoporosis. Acmella oleracea and Acmella uliginosa have the potential to be used for the treatment of osteoarthritis, while Spilanthes acmella is used to treat myopathies. Further research is needed to establish the efficacy, optimal dosing, and safety of these plants. Full article

Seed oils from Borago officinalis (borage), Opuntia ficus-indica (prickly pear), and Calophyllum inophyllum (calophyllum or tamanu) are rich in bioactive fatty acids and have been traditionally used in cosmetic and industrial sectors. This study explored their fatty acid composition and investigated their in vitro antioxidant, anti-arthritic, neuroprotective, and antibiofilm activities. Fatty acid profiles were determined via gas chromatography. Antioxidant activity was assessed using DPPH and ABTS radical scavenging assays. Anti-arthritic potential was measured via bovine serum albumin denaturation. Neuroprotective properties were evaluated through acetylcholinesterase, butirylcholinesterase, and tyrosinase inhibition. Antibiofilm activity against five pathogenic strains was analyzed using crystal violet and MTT assays. Correlation analysis was used to associate fatty acid composition with bioactivity. Prickly pear oil exhibited the highest PUFA content (65.1%), mainly linoleic acid. Calophyllum oil was richer in saturated and monounsaturated fatty acids. All oils showed significant radical scavenging ability, with calophyllum oil showing the lowest DPPH IC₅₀ and borage oil, the highest ABTS activity. Borage and prickly pear oils demonstrated strong anti-arthritic potential. Calophyllum oil showed the most potent AChE inhibition. All oils showed tyrosinase inhibition; however, calophyllum did not show BChE inhibitory activity. Antibiofilm activity was species- and dose-dependent, with Staphylococcus aureus, Escherichia coli, and Acinetobacter baumannii being most affected. Thus, the tested oils exhibited multiple biological activities, influenced by their fatty acid composition. The in vitro antioxidant, anti-arthritic, neuroprotective, and antimicrobial properties support their potential use as functional food ingredients or nutraceuticals, especially for aging-related health concerns. Further in vivo and clinical studies are needed to confirm their efficacy. Full article

Colorectal cancer remains a significant global health concern. In this study, we investigated the anticancer potential of Circaea mollis Siebold & Zucc. (CS&Z), a traditional medicinal plant known for its anti-inflammatory, anti-arthritic, and antioxidant properties, in the treatment of colorectal cancer. We found that CS&Z induces apoptosis and G1/S phase cell cycle arrest in colorectal cancer cells, primarily through the suppression of the proto-oncogene c-Myc. Specifically, the depletion of RPL5, a ribosomal protein associated with c-Myc regulation, reversed the suppression of c-Myc by CS&Z. Additionally, when co-administered with the standard chemotherapeutic agents doxorubicin and 5-fluorouracil, CS&Z demonstrated synergistic effects, thereby further emphasizing its potential efficacy as a therapeutic option for the treatment of colorectal cancer. Moreover, the constituents of CS&Z, detected through liquid chromatography–mass spectrometry analysis, reportedly exhibit anticancer activities. Taken together, our findings suggest that CS&Z holds promise as a natural product capable of modulating oncogenic signaling in colorectal cancer and may serve as a complementary agent in future therapeutic strategies. Full article

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the inflammation of synovial fluid. The incidence of cardiovascular diseases (CVDs) is increasing in RA patients. This research is the first report to investigate the anti-arthritic effect of avocado peel nutraceutical (APN) and its potential in mitigating the cardiovascular risk associated with RA. The antioxidant activity and phytochemical composition of APN were assessed. The potential interaction of APN’s active compounds with protein tyrosine phosphatase non-receptor type 22 (PTPN22) was studied using molecular docking. The impact of APN on the plasma lipid profile, oxidative and inflammatory markers, and the indices of coronary risk and atherogenicity as CVD markers were evaluated. The gene expression of COX-2, IL-6, IL-1β, IL-10, and TNF-α in liver and spleen tissues were measured. The rat gut microbiota profile was investigated using 16S rRNA amplicon sequencing. APN exhibited high antioxidant activity, low atherogenicity and thrombogenicity indices, and a high ratio of hypocholesterolemic to hypercholesterolemic fatty acids indicating its cardioprotective potential. The administration of APN led to a reduction in oxidative stress markers, inflammatory markers, dyslipidemia, and CVD markers. APN administration downregulated the expression of COX-2, IL-6, IL-1β, and TNF-α genes, while the IL-10 gene was significantly upregulated in the liver and spleen. Treatment with APN was favorable in restoring eubiosis in the gut by modulating RA-associated bacterial taxa linked to impaired immune function and cardiometabolic diseases. In molecular docking, β-amyrin and ellagic acid showed the highest binding affinity for PTPN22. APN may represent a promising approach to ameliorating the cardiovascular risk of RA. The present results will be offering a foundation for future in-depth research in nutraceuticals from agriculture by-products. Additionally, they will be supporting the public health policies aimed at preventing and controlling rheumatoid arthritis. Full article

Biancaea decapetala (Roth) O. Deg. (Fabaceae), traditionally used by the Hmong people to treat rheumatoid arthritis (RA), has not been extensively studied for the correlation between its anti-inflammatory activity and its active components. Protosappanoside D (PTD), a new component, has been isolated for the first time from the extract of Biancaea decapetala. This study focused on the anti-arthritic and anti-inflammatory effects of Biancaea decapetala extracts (BDE) and PTD, along with their pharmacokinetic–pharmacodynamic (PK-PD) analysis. In the adjuvant-induced arthritis (AA) rat model, HE staining and cytokine assays showed that BDE alleviated joint damage and reduced inflammatory cytokines, similar to the positive control. In the LPS-induced inflammatory cell model, both BDE and PTD demonstrated anti-inflammatory effects by inhibiting the secretion of inflammatory factors. A PK-PD analysis of BDE in AA rats and inflammatory cells, as well as an analysis of PTD as a monomer, was conducted. The results indicated that PTD had different regulatory effects on cytokines like TNF-α, with a certain lag and sustained effects. These findings suggest the potential of BDE and PTD as treatments for rheumatoid arthritis, though further in vivo studies and clinical trials are needed. Full article

In recent decades, applications related to sensing have grown increasingly, transforming and expanding their fields into innovative research. Lately, researchers have demonstrated that immobilizing metal nanoparticles on glass-based platforms may render innovative perspectives for sensing applications. As a result, the focus of this study was to develop glass-based platforms functionalized with silver nanoparticles, intending them to be utilized in sensing applications. The purpose of using glass-based platforms is due to their availability and eco-friendly features, which will make them suitable for such applications. The study uses a glass-based platform functionalized/modified with organosilanes (such as mercaptoalkyl trialkoxysilane), which can have a high affinity for Ag NPs. By decorating the glass surface with Ag NPs, it becomes active for the adsorption of the mercapto derivatives and further usage in sensing applications (specific drugs with an antitumoral, anti-hypertensive, antiarthritic role, neurotransmitters, etc.) but also for specific classes of pollutants for environmental applications. Therefore, the desired purpose of this study was to develop glass-based platforms decorated with Ag NPs and their further use in the selective adsorption of thioderivatives (cysteine was selected as a model component) even from a mixture of amino acids (cysteine, alanine, and threonine). Full article

Most eukaryotic and prokaryotic cells have the potential to secrete a group of structures/membrane-bound organelles, collectively referred to as extracellular vesicles (EVs), which offer several advantages to producer/receiver cells. This review provides an overview of EVs from plant sources with emphasis on their health-promoting potential and possible use as therapeutic agents. This review highlights the essential biological effects of plant-derived extracellular vesicles, including immune modulation, anticancer activities, protection against chemical toxicity and pathogens, as well as anti-aging, anti-melanogenesis, and anti-arthritic effects, along with ongoing clinical studies. Evidence revealed that plant-derived EVs’ contents exert their beneficial properties through regulating important signaling pathways by transferring miRNAs and other components. Taken all together, the data proposed that plant-derived EVs can be utilized as nutritional compounds and therapeutic agents, such as drug carriers. However, this emerging research area requires further in vitro/in vivo studies and clinical trials to determine the exact underlying mechanisms of EVs’ positive health effects in treating various diseases. Full article

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 12a–h and pyrazole–indole conjugates 14a–d were prepared from our previous works via the direct reaction of 5-amino-pyrazoles 10a–d with N-alkyl isatin 11a,b, and 1H-indole-3-carbaldehyde (13), respectively, using the previously reported procedure. The potential biological activities of 12a–h and 14a–d 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 12a–h and 14a–d 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 Ų thus possess good intestinal absorption. Conclusions: The two series of pyrazole–isatin conjugates 12a–h and pyrazole–indole conjugates 14a–d 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

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

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

Background/Objectives: Numerous diseases such as diabetes, Alzheimer’s disease, and cancer have spread in the whole world, especially in the Arab world. Also, various applications of Schiff-base functionalized nanoparticles and copper oxide nanoparticles (CuO-NPs) such as therapeutic applications have been discovered. Thus, the current research highlights (i) the synthesis of copper oxide nanoparticles (CuO-NPs) produced with a Schiff base (SB) serving as a capping agent during their synthesis and (ii) assessment of the in vitro biological activities of Schiff base-synthesized copper oxide nanoparticles (SB-CuO-NPs) and a Schiff base (SB). Methods: SB-CuO-NPs were characterized using ultraviolet-visible (UV-Vis) spectroscopy, zeta potential, DLS analysis, and transmission electron microscope (TEM). It also focuses on assessing the in vitro biological applications and activities, including antioxidant, scavenging, anti-diabetic, anti-Alzheimer, anti-arthritic, anti-inflammatory, cytotoxic activities, and enzymes inhibitory potential, of Schiff base-synthesized copper oxide nanoparticles (SB-CuO-NPs) and a Schiff base (SB) using methods described in the literature. Results: The results of the biological activities of the SB-CuO-NPs were compared with those of the SB. The SB-CuO-NPs demonstrated superior in vitro biological activities when compared to the SB from which they were produced. Conclusions: The results of this investigation concluded that the CuO-NPs, synthesized with the SB serving as an alternative capping agent, exhibited enhanced biological efficacy relative to the original SB. In the future, the biological efficiency of SB-CuO-NPs against diabetes, Alzheimer’s, and cancer diseases will be assessed in experimental animals (in vivo). Full article

Oncostatin M (OSM) plays a crucial role in diverse inflammatory reactions. Although the food bioactive compound naringenin (NAR) exerts various useful effects, including antitussive, anti-inflammatory, hepatoprotective, renoprotective, antiarthritic, antitumor, antioxidant, neuroprotective, antidepressant, antinociceptive, antiatherosclerotic, and antidiabetic effects, the modulatory mechanism of NAR on OSM expression in neutrophils has not been specifically reported. In the current work, we studied whether NAR modulates OSM release in neutrophil-like differentiated (d)HL-60 cells. To assess the modulatory effect of NAR, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence assay were employed. While exposure to granulocyte-macrophage colony-stimulating factor (GM-CSF) induced elevated OSM release and mRNA expression, the elevated OSM release and mRNA expression were diminished by the addition of NAR in dHL-60 cells. While the phosphorylation of phosphatidylinositol 3-kinase, protein kinase B (Akt), and nuclear factor (NF)-κB was upregulated by exposure to GM-CSF, the upregulated phosphorylation was inhibited by the addition of NAR in dHL-60 cells. Consequently, the results indicate that the food bioactive compound NAR may have a positive effect on health (in health promotion and improvement) or may play a role in the prevention of inflammatory diseases. Full article

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized primarily by the synovial infiltration of inflammatory cells. Macrophage infiltration in the joint synovium is one of the early hallmarks of RA disease activity. Cortex periplocae, which has been widely employed in traditional Chinese medicine (TCM) to alleviate RA, harbors a bioactive compound known as Periploca sepium periplosides (PePs). In this study, collagen antibody-induced arthritis (CAIA) was established in mice through the administration of collagen antibodies and lipopolysaccharide (LPS), followed by treatment with PePs. The therapeutic effects of PePs were evaluated by measuring paw thickness, clinical arthritis scores, and histological changes in joint tissues. Flow cytometry and qRT-PCR were used to assess macrophage polarization in vivo and in vitro. The findings indicate that PePs effectively attenuated CAIA by suppressing the polarization of RAW264.7 cells towards the M1 phenotype while promoting their polarization towards the M2 phenotype. These results provide valuable insights into the scientific significance of PePs as a potential therapeutic agent for RA. Full article