Anti-arthritic Activity Research Articles

Esculin-loaded nanoparticles ameliorate adjuvant-induced polyarthritis via subduing inflammatory and oxidative stress biomarkers in Wistar rats.

Rheumatoid arthritis is an autoimmune disorder affecting multiple joints and requires lifelong treatment. Present study was designed to formulate Esculin-loaded chitosan nanoparticles (ENPs) and evaluation of its anti-inflammatory and anti-arthritic action. The acute toxicity study of ENPs was also performed. ENPs were synthesized using the ion gelation method and their characterization was done. The formulated ENPs had a particlesize of 205.1nm, a polydispersity index of 0.574, zeta potential of 3.6 ± 0.1mV, and entrapment efficiency of 68%, SEM analysis showed round spherical and irregularity from the outer surface, XRD revealed amorphous nature. Drug release from the carrier by erosion method. For anti-arthritic potential, 0.1ml Complete Freund's Adjuvant was injected in the left hind paw of all Wistar rats except normal rats on day 1 and treatment with ENPS at 5, 10, 20, ESC and methotrexate (standard drug) was started at 8th day orally and continued for 21days. Treatment with methotrexate, ESC, and ENPsrevealed a significant reduction of paw edema and pain, restoration of body and immune organ weight, Treatment with ENPs 20mg/kg remarkably (p < 0.0001) restored serotonin and noradrenaline level, oxidation status, hematological and biochemical parameters with significant down-regulation (p < 0.0001) of IL-6, COX-2, TNF-alpha, NF-κβ whereas, up-regulation of IL-4 and IL-10 in comparison to disease control group as obvious from histological examination of sciatic nerve, liver, and ankle joint. The LD50 of ENPs was more than 2000mg/kg in the acute toxicity study. The ENPs exhibited anti-inflammatory and anti-arthritic activities especially ENPs at 20mg/kg.

Kundur (Boswellia Serrata): Medicinal Importance in Perspective of Unani Medicine and Pharmacological Studies

Kundur, the Indian olibanum tree, is a member of the Burseraceae family and grows best in the dry mountainous regions of the Middle East, Northern Africa, and India. This tree has small to huge branches. The tree's oleo-gum resin is removed and stored from the incision created in its trunk. Resin makes roughly 30–60% of oleo-gum resin, with organic solvent-soluble essential oils making up the remaining 5–10%. Gum-resin extracts from Boswellia serrata have long been used in traditional medicine to treat a variety of chronic inflammatory diseases. Four primary pentacyclic triterpenic acids found in the resinous component of Boswellia serrata are β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid. This oleo-gum resin is quite popular among traditional practitioners of traditional Chinese and Indian Systems of medicine because of its wide range of useful biological properties such as anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrheal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial, anti-fungal, anti-complementary, and analgesic activity etc.

Carvone-loaded chitosan nanoparticles alleviate joint destruction by downregulating the expression of pro, inflammatory cytokines and MMP-13 in adjuvant-induced rat model.

Rheumatoid arthritis is an autoimmune illness causing deformity, edema, and joint tenderness. Its long-term treatment burdens the healthcare system and leads to toxicity, and thus, finding safe, effective, and affordable therapies is essential. The current study aimed to exhibit the anti-arthritic activity of Carvone-loaded chitosan nanoparticles to treat Freund's complete adjuvant (FCA) arthritis in rats. Healthy albino rats (n = 35) were distributed into seven groups. The 1st group worked as normal control, while the 2nd was arthritic control. The 3rd group received methotrexate (10mg/kg/week). The 4th group received Carvone (60mg/kg/day), while the 5th (30mg/kg/day), 6th (45mg/kg/day), and 7th (60mg/kg/day) groups received Carvone-C-NPs, respectively. Nanoparticles, prepared by the ion gelation method, were characterized by zeta size, potential, scanning electron microscopy, and Fourier transform infrared microscopy. NPs have zeta size (78.82 ± 0.02nm) and potential (19.96 ± 0.02mV). A significant reduction was shown in paw swelling (5.52 ± 0.05mm), arthritic score (2.81 ± 0.23), and rheumatoid factor (14.56 ± 0.68IU/L) by Carvone-C-NPs. qRT-PCR results showed significant down-regulation of pro-inflammatory cytokines [TNF-α (0.25 ± 0.03), IL-1β (0.21 ± 0.06), IL-17a (0.16 ± 0.12), and IL-33 (0.15 ± 0.01)] and up-regulation of anti-inflammatory cytokines [IL-4 (0.85 ± 0.06) and IL-10 (0.66 ± 0.04)] in ankle joint of Carvone-C-NPs treated group. The radiographical and histopathological findings showed reduced pannus formation, joint swelling, and synovial hyperplasia in the Carvone-C-NPs treated group. Overall, it is concluded that Carvone-C-NPs have remarkable anti-arthritic activity and promising anti-inflammatory properties.

Phytochemical characterization and anti-arthritic potential of green-synthesized CuO nanoparticles derived from the Bistorta amplexicaulis root extract.

Rheumatoid arthritis is an autoimmune disease that mainly causes joint damage. The patient experiences loss of appetite, pain, fever, and fatigue. The present study was designed to phytochemically characterize and evaluate the anti-arthritic activity of green-synthesized copper oxide (CuO) nanoparticles (NPs) using the hydroalcoholic extract of Bistorta amplexicaulis roots in an adjuvant-induced arthritic rat model. For this purpose, crude powdered plant material was used for proximate analysis, and the plant extract was assessed for qualitative phytochemical analysis, mineral contents, and flavonoid and phenolic contents, as well as quantitative phytochemical analysis through reversed-phase high-performance liquid chromatography (RP-HPLC) and Fourier-transform infrared (FTIR) spectroscopy. The in vitro antioxidant activity of both extracts was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The biosynthesized CuO NPs from the Bistorta amplexicaulis extract showed anti-arthritic activity due to the presence of flavonoids and phenols, which showed a pain reliever effect by blocking the cyclo-oxygenase enzyme and has immune suppressant activity, thus securing the joint from destruction. The nanoparticles were characterized by zeta size, zeta potential, scanning electron microscopy (SEM), and FTIR spectroscopy. Forty-eight albino rats were divided randomly into six treatment groups. The zeta size and zeta potential of the nanoparticles were 186.8nm and -9.23mV, respectively. Joint stiffness, spleen weight, thymus weight, and paw thickness showed a significant decrease after treatment with NPs. The hematological parameters such as red blood cells (RBCs) and hemoglobin showed a significant increase, while platelets and white blood cells (WBCs) showed a significant decrease in NP-treated groups. C-reactive protein (CRP), rheumatoid factor (RF), liver and kidney function biomarkers, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels showed a significant decrease at both low and high doses of green-synthesized CuO nanoparticles from the Bistorta amplexicaulis root extract. The final data were analyzed by one way and two-way analysis of variance (ANOVA) and Tukey's multi-comparison test. So, from this study, it was concluded that both the plant root extract and green-synthesized CuO nanoparticles have anti-arthritic potential, but CuO NPs showed remarkable results.

Formulation and Evaluation of Anti-Arthritic Activity of Newly Prepared Rajata Bhasma

Formulation and Evaluation of Anti-Arthritic Activity of Newly Prepared Rajata Bhasma

Safety Assessment of Cat’s Whiskers Flavonoid in Development Toxicity of Zebrafish Embryos

Introduction: The pharmacological significance of 5-hydroxy-3,7,4'-trimethoxy flavone (5HTMF), a flavonoid isolated from Cleome gynandra L. (Capparidaceae), in mononuclear lymphocytes of patients with Rheumatoid Arthritis (RA) has been well-documented. In previous studies, the anti-inflammatory and anti-arthritis activity of CWF was reported. Method: However, there is a lack of information on the toxicity of 5HTMF. This study aimed to assess the embryonic toxicity of 5HTMF on zebrafish embryos, using dexamethasone as a standard for liver toxicity. At 12 hours post fertilization (hpf), no significant toxicity from 5HTMF was observed on allantoic membrane development. Results: By 24 hpf, 20% of embryos showed minor changes in tail development at a 100 μM concentration of 5HTMF, while dexamethasone (10 μM) disrupted the allantoic membrane in 61.11% of embryos. In the liver toxicity assay, 5HTMF did not show any significant toxicity. Conclusion: At 48 hpf, dexamethasone exhibited substantial toxicity at a concentration of 10 μM. In conclusion, the findings suggest that 5HTMF may be a safe and non-toxic dietary supplement for treating chronic inflammatory conditions such as RA.

Evaluation of the anti-arthritic properties of Litsea glutinosa (L.) C.B. Rob Bark: An integrated analysis utilizing in-silico, in-vitro, and in-vivo approaches, along with identification of major compounds

The current study explored the anti-arthritic properties of Litsea glutinosa bark extracts. The dried bark of L. glutinosa was defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The bioactive compounds present in the extract were analysed by GC-MS and LC-MS. The methanol extract of L. glutinosa (MELG) was evaluated at different concentrations (25–400 mg/ml) for its in-vitro anti-arthritic efficacy using membrane stabilization and protein denaturation techniques. In in-vivo evaluation paw diameter, arthritic score, arthritic index, body weight, organ weight, and haematological and biochemical parameters were measured to assess anti-arthritic potential. Subsequently, pro-inflammatory and inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), IL-1β, cyclooxygenase-2 (COX-2), IL-13, and IL-10 were determined. The Compounds identified by GC–MS and LC-MS were subjected to an in-silico molecular docking analysis utilizing AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer against COX-2, IL-1β, IL-6, and TNF-α. The in vitro anti-arthritic effect of MELG exhibited a dose-dependent reduction in membrane stabilization (67.9 % at 400 µg/ml) and protein denaturation assay (66.6 % at 400 µg/ml). MELG treated rats improved all arthritic parameters. Significant restoration of pro-inflammatory cytokines was observed in rats administered with MELG (200 & 400 mg/kg). In the MELG (400 mg/kg) treated group, there was a significant reduction in IL-10 (P˂0.001) and IL-13 (P˂0.05) levels and a substantial rise in IL-6 (P˂0.01), TNF-α (P̂˂0.001), and IL-1β (P˂0.01) levels. The presence of phytoconstituents was analyzed by GC–MS (Fourteen compounds) and LC-MS (Ten compounds). Boldine identified by LC-MS analysis, exhibited good docking scores against COX-2 (-8.7), IL-1β (-6.3 kcal/mol), IL-6 (-6.2 kcal/mol), and TNF-α (-6.7 kcal/mol).The presence of bioactive compound, boldine in MELG might be responsible for its anti-arthritic activity.

Pristimerin inhibits the progression of antibody-induced autoimmune arthritis

Objectives Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. Pro-inflammatory cytokines produced by various immune cells drive the chronic inflammatory processes that lead to joint damage. Many drugs are available for the treatment of RA, but a significant proportion of patients do not respond adequately to them and/or have severe adverse effects. Accordingly, there is an urgent need for new therapeutics for RA. Therefore, we tested pristimerin, a natural triterpenoid, for its anti-arthritic activity in experimental RA. Method Collagen antibody-induced arthritis (CAIA) was induced in DBA/1 mice. After the onset of arthritis, mice were injected daily intraperitoneally with pristimerin or vehicle for 9 days. The severity of clinical arthritis was graded and further validated by micro-computed tomography and histological examination of the hind paws. Defined mediators of arthritogenic processes were quantified by gene expression in the spleen and further validated by immunohistochemistry of paws. Results We observed that pristimerin can effectively control arthritis progression in CAIA mice. A preliminary exploration of the mechanisms showed that pristimerin targeted key pro-inflammatory cytokines and chemokines, along with specific mediators of angiogenesis, bone remodelling, and cellular signalling, including the Notch signalling pathway. Conclusions This is the first report on pristimerin for its use in the treatment of antibody-induced arthritis and for the targeting of Notch pathway in arthritis by this triterpenoid. As pristimerin can control the effector phase of arthritis, our results are promising for the translation of this experimental therapy to RA patients.

Phytochemical Profiling and Pharmacological Evaluation of Methanolic Leaf Extract of C. digyna for Cytotoxic, Anti-inflammatory, Antioxidant, Antiarthritic, and Analgesic Activities.

Caesalpinia digyna (Family: Fabaceae) is traditionally used in Ayurvedic medicine for various medicinal purposes, including as a treatment for wounds, leprosy, skin diseases, fever, diabetes, etc. Although the root and stem of this plant have a significant medicinal value, there was little research on the leaves of this plant. This study aimed to investigate the qualitative phytochemical profile and evaluate the invitro cytotoxic, anti-inflammatory, antioxidant, and antiarthritic activities, as well as the invivo anti-inflammatory and analgesic activities, of C. digyna leaf extract. The methanolic extract of C. digyna leaves was prepared using an ultrasonic-assisted extraction process. Invitro and invivo anti-inflammatory activities were evaluated using the hypotonicity-induced hemolysis and carrageenan-induced paw edema methods, respectively. Additionally, the extract was assessed for invitro DPPH (1, 1-diphenyl-2-picrylhydrazyl) free radical scavenging, antiarthritic (protein denaturation), and invivo analgesic (acetic acid-induced writhing and tail immersion) activities. Brine shrimp lethality bioassay (BSLB) showed moderate cytotoxic activity (LC50 = 2.25 μg/mL) compared with the standard vincristine sulfate (LC50 = 1.61 μg/mL). Invitro, anti-inflammatory activity exhibited 85.13% (IC50 value = 2.51 μg/mL) inhibition of Human Red Blood Cell (HRBC) membrane lysis at a concentration of 2000 μg/mL whereas invivo anti-inflammatory study exerted its maximum effect (p < 0.05) at 400 mg/kg bw dose. This extract also showed significant antioxidant (IC50 = 0.218 μg/mL), antiarthritic (83.61% inhibition) activity, and moderate analgesic effect (p < 0.05) in both methods. These research findings indicated that C. digyna leaves extract has potent antioxidant, analgesic, and anti-inflammatory effects which can be used as a supplementary medication for inflammatory pain-relieving factors. In future, finding the mechanism involved in these effects could have significant impact on clinical science.

Design, Synthesis and Evaluation of Benzimidazole Derivatives as IL-6 Inhibitors and Their Role in Rheumatoid Arthritis.

Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a major role in the development of Rheumatoid Arthritis (RA). In the present study, benzimidazole and benzene sulfonyl scaffold were identified as pharmacophore by analysis of literature reports and novel small molecule IL-6 inhibitors were designed. These were screened via docking with IL-6 (PDB: 1ALU), then and through Lipinski's rule of 5. Based on docking score, 10 best compounds (4a-4e and 7a-7e) were selected for synthesis and evaluated for IL-6 inhibitory activity invitro. Compounds 4b and 7b showed the maximum inhibition of IL-6 (87.55% and 82.75%, respectively). These compounds were further explored for anti-arthritic activity invivo using the Incomplete Freund's Adjuvant Model and by morphological and histopathological studies of the inflamed paw. Compound 4b was significantly more active than compound 7b and both were found to be slightly less active than methotrexate. These findings indicate that a benzimidazole nucleus linked to a benzene sulphonyl moiety may prove to be a useful template for the development of new chemical moieties against RA.

A Piper nigrum based zinc oxide nanoparticles for anti-arthritic and antioxidant activity

Background: Zinc oxide nanoparticles (ZnONPs) are among the most effective metallic oxide nanoparticles for biological applications. They have potential anti-inflammatory and anti-oxidant properties, desirable biocompatibility, lower toxicity, and minimal cost. Methodology: Using diverse plant extracts for an ecologically friendly production of metallic nanoparticles is a better choice than conventional chemical synthesis techniques. The present study is decisive on the ZnONPs synthesis from a Piper nigrum extract (Pn-ZnONPs). Morphological characteristics of ZnONPs have been studied using UV-spectroscopy, DLS, SEM, and TEM. Further, it is analyzed for its anti-inflammatory (proteinase, collagenase, lipooxygenase, and elastase) and anti-oxidant properties (DPPH˙, SOD, NO, H2O2, and OH). Results and discussion: Synthesis of nanoparticles has been confirmed via visible spectroscopy with maximum absorbance of 350nm, having particle size and zeta potential of 80 nm and +7.4 mV, respectively. SEM and TEM analysis confirmed the nanoparticle's shape to be spherical and arranged compactly. Further, biogenic nanoparticles show desired anti-inflammatory properties by inhibiting the activity of collagenase (68.72%), elastase (65.16%), lipooxygenase (58.098%), and denaturation of protein (65.36%). It also exhibits the capability to suppress Superoxide radicals (64.87%), DPPH (65.46%), Hydrogen Peroxide (64.89%), Hydroxyl radical (68.45%), and Nitric oxide radicals (71.343%), which are responsible for the pathogenesis of many inflammatory disorders. Conclusion: This suggests that P. nigrum Zinc nanoparticles may be a promising agent in treating various inflammatory disorders, such as cancer, Rheumatoid Arthritis, Psoriasis, and others.

Evaluation of the Activity of Olibanum Oil as an Immune Booster in Rats

The applications of herbal medicine have recently acquired growing interest in range of the prophylaxis and treatment of diseases. Olibanum has been used since ancient eras and several reports studied the pharmacological characteristics of boswellic acid, particularly their effect on the inflammatory response, analgesic properties, and anti-arthritic activity mostly in cell lines, but new approaches include animal models to assess these natural derivatives effects taking into consideration of being safer than synthetic preparations. The impact of olibanum oil on several parameters was studied in rats during this study. These included white blood cell (WBC) count, lactate dehydrogenase (LDH), and C reactive protein (CRP), as well as other pro-inflammatory cytokines like tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6), and the cytokine interleukin -10 (IL-10) that is anti-inflammatory. Total WBCs in addition to IL-10 levels significantly increased in the oil-treated group in comparison with the control one, while the rats treated with olibanum oil revealed a significant reduced level of LDH, CRP, IL-6 and TNF- α compared with the controls (p &lt; 0.05). These outcomes indicate that olibanum oil treatment are manifested by cytokine changes, it can improve the anti-inflammatory response and down-regulate the pro-inflammatory cytokines. So, the promising impact of olibanum oils as an immunomodulator could be used in alternative therapies.

UPLC/HR-ESI-MS/MS and GC/MS profiling of Eriobotrya japonica L. fruit in correlation to its antioxidant, anti-inflammatory, and anti-arthritic effects.

Eriobotrya japonica Lindl. (Loquat) fruit is a subtropical edible fruit originally from China. It grows well in Egypt, but it is not widely known. In the current study, the fruit was extracted with 80% ethanol to get the total ethanol extract (TEE). A part of which was fractionated by dichloromethane to yield polar and nonpolar fractions (PF and NPF). The antioxidant and anti-inflammatory activities of the TEE were in vitro evaluated. The complete Freund's adjuvant (CFA) arthritis model was used to explore the in vivo biological assessment of the anti-arthritic properties in vivo of the TEE, PF, and NPF of the fruit. Additionally, the inspected limbs detached from all animals were subjected to histological inspection. Moreover, GC/MS analysis of the unsaponifiable (USF) and saponifiable (SF) fractions of the NPF was performed. Furthermore, 64 metabolites from various chemical classes were identified using UHPLC/HR-MS/MS analysis of the TEE of the fruit in both positive and negative ionization modes. The positive ionization mode of loquat fruit allowed for the first time the detection of two kinds of lyso-glycerophospholipids (Lyso-GPLs): lyso-glycerophosphoethanolamines (Lyso-PtdEtn) and lyso-glycerophosphocholines (Lyso-PtdCho). The fruit extracts exhibited a notable in vivo anti-arthritic activity by decreasing paw thickness in the treated rats and adjusting the inflammatory mediators. The TEE showed the highest anti-arthritic activity, followed by the PF that showed an observed activity, while the NPF exhibited the lowest activity. Histopathological findings showed a marked improvement in the arthritic condition of the excised limbs. Thus, E. japonica fruit may be considered as a promising natural antioxidant and anti-arthritic agent.

Therapeutic potential of d-limonene in rheumatoid arthritis: Modulation of inflammatory, anti-inflammatory cytokines, and prostaglandin E2.

Rheumatoid arthritis (RA) is a persistent autoimmune disorder predominantly affecting the joint structures, eliciting inflammatory responses, and ultimately leading to degenerative changes without proper medical intervention. Ultimately, this can severely impair joint function and impact the patient's quality of life. Current treatment approaches include disease-modifying anti-rheumatic drugs, non-steroidal anti-inflammatory drug, corticosteroids, and biologic therapies for RA management. The current study contributes to the ongoing advancements in RA treatment. d-Limonene is a monocyclic monoterpene. It is present in essential oils of various aromatic plants, such as Lippia alba and Artemisia dracunculus, and in citrus fruits such as lemon and orange. It has reported anti-inflammatory and anti-nociceptive properties and was selected for the current study as a potential anti-arthritic candidate. It was administered at three dosages (25, 50, 100 mg/kg, b.w., p.o) in Complete Freund's adjuvant-induced arthritic rats over 28 days. The efficacy of the compound was compared to piroxicam, a widely used standard drug for treating RA. The anti-arthritic activity of the compound was assessed by measuring arthritic scoring and plethysmometry at both baseline and post-intervention stages. Additional confirmation of the investigation was sought by performing biochemical and hematological activities. Moreover, quantitative polymerase chain reaction was employed to determine the levels of messenger RNA expression for transcription factors such as tumor necrosis factor-α, interleukin (IL)-1β, nuclear factor-κB, matrix metalloproteinase-3, IL-6, and IL-4 in the blood. The levels of PGE2 were evaluated by enzyme-linked immunosorbent assay. The histopathological and radiographic studies were also carried out for further confirmation. The results of these findings supported our assertion regarding the anti-arthritic potential of the compound.

Promising Anti-Inflammatory Properties of Ursolic Acid Isolated from Atylosia goensis.

Indigenous plants are plant species that are native to a specific region and have evolved naturally and adapted to local environmental conditions over a long period. This study aimed to explore the anti-arthritic effects of Atylosia goensis, an indigenous plant species in the Western Ghats of India. An ethanolic extract of Atylosia goensis was obtained using the Soxhlet extraction method, which revealed a diverse array of phytochemicals through liquid chromatography-mass spectroscopy (LC-MS). Key compounds, including fatty acids, sterols, and potential health-beneficial compounds, were identified, and one prominent phytoconstituent, ursolic acid, was spectroscopically characterized using 1H NMR, 13C NMR, and mass spectrometry. The research also examined the anti-inflammatory activity and in-vitro and in-vivo anti-arthritic activity of ethanolic extract. The ethanol extract exhibited notable inhibition of Cox-2, indicating potential anti-inflammatory effects. The in vivo anti-arthritic activity of ursolic acid was evaluated at different doses (200 and 400 mg/kg) over a 24-day period. Ursolic acid significantly reduced joint edema, particularly at higher doses, thereby emphasizing its anti-inflammatory properties. Biomarker analysis revealed dose-dependent attenuation of disease-associated biomarker levels, supporting the potential therapeutic efficacy of ursolic acid in arthritis management. Moreover, the hepatoprotective potential of ursolic acid was evident in biochemical parameters, including SGPT, SGOT, and ALP levels. Both doses of ursolic acid effectively mitigated liver dysfunction induced in the disease control group, demonstrating its protective role in liver health. Histopathological assessments corroborated these findings, indicating a reduction in inflammatory areas following ursolic acid treatment, especially at higher doses. This experimental work provides valuable information on the therapeutic potential of Atylosia goensis and ursolic acid, emphasizing their roles in anti-inflammatory and hepatoprotective applications. This study contributes to the understanding of plant-derived compounds for potential pharmaceutical use in the management of inflammatory and arthritic conditions.

Anti-arthritic activity of Trayodashang guggulu, a classical Ayurvedic formulation against complete Freund’s adjuvant-induced rheumatoid arthritis in rats

BackgroundRheumatoid arthritis is a chronic autoimmune disease affecting millions of people across the world. Trayodashang guggulu (TG) is a classical Ayurvedic formulation used for the treating joint diseases since decades in the Indian system of traditional medicine. The aim of the study was to evaluate anti-arthritic activity of TG against complete Freund’s adjuvant-induced arthritis in Wistar rats.MethodsArthritis was induced by single injection of 0.1 ml complete Freund’s adjuvant into the intraplanter surface of left hind paw of Wistar rats. TG was administered orally at the doses of 100, 200, 400 and 800 mg/kg body weight for 14 days. In the preventive dose group, TG was administered at the dose of 100 mg/kg body weight, orally for 28 days. Paw swelling, joint circumference, serum rheumatoid factor, C-reactive protein, serum IL-1β, TNF-α and histopathological parameters were assessed for the evaluation of arthritis. Effects of TG were compared with standard allopathic drug ibuprofen.ResultsTG reversed complete Freund’s adjuvant-induced arthritis in rats when used for 14 and 28 days. Serum rheumatoid factor, C-reactive protein, IL-1β and TNF-α were decreased in rats treated with both standard drug ibuprofen and TG.ConclusionOral administration of TG reduced experimentally induced rheumatoid arthritis in rats by reversing elevated level of serum biochemical markers as well as reducing joint destruction similar to ibuprofen. Results obtained from the study paved the way in exploring more specific mechanisms of action of TG involving in vitro and in silico models.

Protective effect of Tecoma stans (L.) Juss.ex Kunth in CFA-induced arthritic rats

Ethnopharmacological relevanceTecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. Aim of the studyThe objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. Materials and methodThe ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1β, IL-6, and TNF-α receptors. ResultsThe ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities −10.4, −7.4, −7 and −6.2 kcal/mol against COX-2, IL-1β, TNF-α, and IL-6 respectively, confirmed through in silico study. ConclusionsThe observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.

Quality by design-based optimization of teriflunomide and quercetin combinational topical transferosomes for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an immune-mediated inflammatory disease. Combination therapy is anticipated to surpass monotherapy by targeting multiple pathways involved in RA progression. The present aim is to develop a combination of Teriflunomide (TFD) and Quercetin (QCN) loaded transferosomal gel to enhance permeability and achieve localized delivery to joint tissues. TFD or QCN transferosomes were optimized employing a 3-level, 3-factorial design Box-Behnken design (BBD). The transferosomes exhibited sustained in-vitro drug release. The topical combination gel underwent thorough evaluation of rheology, and also ex-vivo studies showed enhanced permeability through rat skin. The synergistic combination of TFD and QCN effectively suppressed NO, TNF-α and IL-6 levels in in-vitro RAW 264.7 cells. The cytotoxicity in HaCaT cell lines indicates non-toxicity of the gel, further confirmed by skin irritation study conducted in rats. The in-vivo anti-arthritic activity was evaluated in complete freund’s adjuvant induced rat paw edema model illustrates the effectiveness of the combination transferosomal gel compared to other treatment groups. In conclusion, the topical delivery of TFD and QCN combination transferosomal gel demonstrated anti-arthritic activity through localized delivery whichallows for dose reduction, thereby may reduce the systemic drug exposure and mitigate the side effects associated with oral administration of TFD.

Wutou decoction attenuates rheumatoid arthritis in rats through SIRT1-mediated deacetylation of the HMGB1/NF-κB pathway

Ethnopharmacological relevanceIn traditional Chinese medicine (TCM), Wutou Decoction (WTD) has long been used to alleviate arthritis. Emerging studies have reported that WTD could improve the symptoms of rheumatoid arthritis (RA). However, the mechanism by which WTD is involved in the treatment of RA remains elusive, posing a challenge to the worldwide acceptance of WTD as an efficient RA therapy. Aim of the studyThis study investigated the antiarthritic efficacy of WTD in a collagen-induced arthritis (CIA) rat model and explored silent information regulator 1 (SIRT1)-mediated deacetylation of the high mobility group box 1 (HMGB1)/NF-κB pathway. Materials and methodsA rat CIA model was used to evaluate the antiarthritic activity of WTD. Clinical arthritis score assessment, left ankle thickness assessment, micro-CT, histopathological staining, immunofluorescence staining, and ELISA were conducted to elucidate the anti-inflammatory effects of WTD. The M1 macrophage polarization state, cell viability, and invasion were also determined to assess the effects of WTD on macrophage proliferation and invasion in vitro. Additionally, in vivo and in vitro HMGB1 nuclear translocation and NF-κB activation were analysed. Finally, deacetylase activity was assessed by Western blot, NAD+/NADH analysis, and co-immunoprecipitaion. ResultsWTD significantly alleviated arthritis in CIA rats and inhibited pathological changes in joint lesions while concurrently suppressing TNF-α, IL-6, and IL-1β release. Mechanistically, WTD suppressed M1 infiltration in ankle tissues and their invasion in vitro. Furthermore, WTD downregulated HMGB1/p65 nuclear translocation and acetylation, which may be associated with SIRT1 upregulation. ConclusionsOverall, WTD potentially alleviates RA through SIRT1-mediated downregulation of HMGB1 and NF-κB acetylation.

Fumaric acid per se and in combination with methotrexate arrests inflammation via moderating inflammatory and oxidative stress biomarkers in arthritic rats

Objective: Fumaric acid is a dicarboxylic acid that belongs to the phenolic class enriched in fruits and vegetables that are traditionally used for the treatment of various ailments. The research was planned to find out the anti-inflammatory and anti-arthritic activities of fumaric acid using in-vitro and in-vivo assays. Moreover, safety study was also done. Materials and methods: The 0.1 ml complete Freund’s adjuvant was injected in left hind paw in all Wistar rats except normal rats at day 1 to induced arthritis. The treatment with fumaric acid at 10, 20, 40, and fumaric acid 40 mg/kg together with methotrexate (MTX) was administered to immunized rats at 8th day via oral gavage and continued till 28th day though, MTX was administered as standard control. Results: The fumaric acid notably (p < 0.0001) lessened the paw edema and arthritic scoring, reinstated body and immune organ weight, and oxidation status in treated rats. Fumaric acid notably restored altered C-reactive protein, rheumatoid factor, liver function tests, ESR, WBCs, RBCs and Hb levels in treated rats. The fumaric acid in combination noticeably (p < 0.01–0.0001) suppressed the expression of TNF- α, IL-6, IL-1β, NF-kβ, and COX-2, and over expressed IL-4, and IL-10 in contrast to other treated groups. Fumaric acid had presented a dose-dependent antioxidant, anti-inflammatory and anti-arthritic activities while notable activity exhibited by fumaric acid in combination with MTX. The fumaric acid exhibited non-significant clinical signs of toxicity and mortality in acute toxicity study. The LD50 was more than 2000 mg/kg. Conclusion: Fumaric acid in combination can be used as disease-modifying anti-rheumatic drug but it will need extensive pre-clinical and clinical studies.