Tetrahydropyrimidine-5-carboxylate attenuates experimentally induced inflammation through regulation of inflammatory and oxidative stress biomarkers in Wistar rats.

Protective Effects of Geraniol in Rheumatoid Arthritis Through Attenuation of Inflammation and Oxidative Stress.

INTRODUCTION/OBJECTIVE Rheumatoid arthritis is a chronic inflammatory disease of the joints. Geraniol, an acyclic monoterpene alcohol, is present in essential oils of various plants and is known to possess anti-inflammatory, immunomodulatory, and antioxidant properties. The study aimed to evaluate the effects of geraniol on the development of arthritis in a Freund's complete adjuvant (FCA)-induced rat model using a pretreatment (pre-induction) design. METHODS Thirty-six Sprague-Dawley rats (100-200 g) of either sex were randomly allocated to six experimental groups using a lottery method: normal control group, arthritic disease control group (FCA 0.15 ml, intradermal), geraniol-treated groups (50, 100, and 200 mg/kg, oral gavage), and standard control group (piroxicam-beta-cyclodextrin 10 mg/kg). Development of arthritis, paw thickness, and paw edema were determined periodically. Hematoxylin and eosin (H&E) staining was performed to examine the histopathological alterations in ankle joints. On day 21, blood samples were collected for hematological evaluations; mRNA expression levels and antioxidant activities of biomarkers were determined using qRT-PCR and spectrophotometric analysis, respectively. RESULTS Geraniol pretreatment was associated with reduced arthritic scores, paw edema, and joint thickness compared with the disease control group. Pretreatment with geraniol attenuated alterations in hematological parameters, reduced MDA levels, and improved antioxidant activity by increasing GSH, SOD, and CAT levels. Additionally, it downregulated the expression levels of IL-6, IL-1β, TNF-α, and hypoxia-inducible factor-1α (HIF-1α) compared with the disease control group. DISCUSSION Administration of geraniol resulted in the reduction of inflammatory parameters, hematological parameters, and prooxidant markers, and downregulated IL-6, IL-1β, TNF-α, and hypoxia- inducible factor-1α (HIF-1α) associated with rheumatoid arthritis, while increasing antioxidant markers. CONCLUSION Geraniol pretreatment was associated with reduced severity of arthritis, lower inflammatory cytokine mRNA expression, and improved oxidative stress markers in an FCA-induced rat model. These findings reflect effects on disease development in a pretreatment (pre-induction) experimental model and do not represent therapeutic efficacy in established rheumatoid arthritis. Further studies using post-induction treatment designs are required to evaluate potential therapeutic relevance.

Preclinical evaluation of 3,4-dimethoxybenzoic acid alone and in combination for adjuvant-induced arthritis in Wistar rats.

It can be inferenced from data that VA can be safely used to treat arthritis especially in combination with MTX but it should be further evaluated in combination for long term use.

Anti-Inflammatory Effects of Chrysin (5,7-Dihydroxyflavone) in Freund's Complete Adjuvant-Induced Arthritis in Rats

Background: Inflammation is a key pathological process underlying arthritis and contributes to progressive damage to the joints, cartilage, and surrounding tissues. Persistent inflammatory responses are associated with infiltration of inflamma-tory cells, pannus formation, cartilage degradation, and bone erosion, ultimately leading to impaired joint function. Chrysin (5,7-dihydroxyflavone) is a naturally occurring flavonoid found in various plants, honey, and propolis. It possesses several pharmacological properties, particularly anti-inflammatory and antioxidant activities, which may help attenuate inflamma-tory tissue damage. Therefore, the present study was designed to evaluate the anti-inflammatory effects of chrysin in an experimentally induced arthritic rat model using histopathological assessment of joint tissues.Methodology: This study determined the healing effect of Chrysin in a FCA-induced arthritic rat model. Chrysin was inject-ed intraperitoneally on the 8th post-administration day of FCA, and treatment continued for the next three consecutive weeks. GraphPad Prism was used to analyse the results, considering p-values ≤ 0.05 statistically significant. Results: Anti-inflammatory effect of Chrysin upon bones and cartilage was determined by Ankle joint histopathology. Upon histopathology, Chrysin reduced the severity of arthritis in the joint, infiltration of inflammatory cells, subcutaneous in-flammation, cartilage erosion, bone erosion and pannus formation. Piroxicam was used as a reference drug to compare the anti-arthritic effect of Chrysin.Conclusion: Results showed that Chrysin possesses anti-arthritic effects and may be a potential drug for the treatment of arthritis. 

Sabinene attenuates inflammation and oxidative stress in CFA-induced arthritis: In vivo and in silico evidence implicating TLR4/NLRP3/NF-κB signaling.

Rheumatoid arthritis (RA) is a chronic immune-mediated disease in which persistent inflammation and oxidative stress contribute to progressive joint damage. This study evaluated the prophylactic effects of sabinene in complete Freund's adjuvant (CFA)-induced arthritis and explored potential molecular associations using integrated in vivo and computational approaches. Rats were allocated to vehicle control, arthritic control, piroxicam, or sabinene groups (15, 30, or 60 mg/kg; n = 6/group); sabinene was administered orally beginning 30 minutes before CFA injection and continued for 28 days. Paw swelling, hematological and biochemical parameters, inflammatory and oxidative-stress markers, and gene expression were assessed, followed by network pharmacology, enrichment analysis, and molecular docking. Sabinene dose-dependently attenuated CFA-induced paw swelling and body-weight loss and improved hematological, hepatic, renal, and inflammatory parameters. Treatment also enhanced antioxidant defenses and reduced lipid peroxidation, prostaglandin E₂, 5-lipoxygenase, and anti-cyclic citrullinated peptide antibody levels. Sabinene reduced messenger RNA expression of nuclear factor kappa B (NF-κB), toll-like receptor 4 (TLR4), NOD-like receptor family pyrin domain-containing 3 (NLRP3), caspase-1, gasdermin D, and other pro-inflammatory genes while increasing interleukin-4 and interleukin-10 expression. Network pharmacology identified 133 overlapping sabinene-RA targets, and molecular docking predicted interactions with tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), signal transducer and activator of transcription 3 (STAT3), and interferon gamma (IFN-γ). These findings support a prophylactic protective effect of sabinene against CFA-induced arthritis associated with reduced inflammation, improved antioxidant status, and modulation of inflammasome-related gene expression. Further protein-level, functional, and post-induction studies are required to confirm the proposed mechanisms and therapeutic relevance.

L-Arginine Ameliorates Cyclophosphamide-Induced Toxicity Via Targeting Inflammatory Pathways and Oxidative Stress Mitigation

Cyclophosphamide (CP)-induced toxicity was widely recognized previously. Therefore, L-Arginine, a compound with potent anti-inflammatory and antioxidant properties, was evaluated for its ability to ameliorate CP-related toxic changes in male albino rats. Twenty-eight mature male albino rats were divided into four groups (7 rats/each) and treated orally as follows: Group I functioned as the untreated control group, Group II received CP at a dose of 50 mg/kg body weight (B.Wt.), and Group III was treated with L-Arginine (L-Arg) (200 mg/kg B.Wt.), whereas Group IV was co-administered CP and L-Arg at the same previously stated doses. The treatment protocols were administered orally three times weekly for eight weeks. Among the hematological findings, leukopenia and thrombocytopenia were the most prominent alterations in the CP-treated group associated with increments in red blood cells (RBCs) count and hemoglobin (Hb) level. Moreover, the CP-exposed group exhibited significant elevations in serum hepatic enzyme activities, urea, creatinine, and cystatin-C concentrations with a significant decrement in serum testosterone level. Additionally, it showed marked elevations in serum levels of some inflammatory and oxidative markers such as inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), nuclear factor-kappa B (NF-κB), and malondialdehyde (MDA) with marked decrease in catalase (CAT) activity and reduced glutathione (GSH) level. These biochemical alterations correlated histopathologically with multiple hepatic, renal, and testicular lesions, which were represented by inflammatory cell infiltration, vascular congestion, varying degrees of degeneration, and interstitial edema. L-Arg administration partially alleviated CP-induced hemato-biochemical disturbances and restored the histo-architecture of the affected organs. Overall, these results verified the multi-organ toxicity of CP and highlighted the mitigation effect of L-Arg against CP-induced hematological, biochemical, and histopathological alterations.

Tetrandrine nanocrystals for rheumatoid arthritis: enhanced therapeutic efficacy associated with reduced JAK1 and STAT3 expression.