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.
Kanwal Asif, Ambreen Malik Uttra, Arham Shabbir et al.· Biomolecules & biomedicine· 0 citations
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.
INTRODUCTION/OBJECTIVE
Digera muricata (DM) contains phenolic compounds and quercetin and β-caryophyllene, which exhibit anticancer, anti-inflammatory, and antioxidant activities. The present study was conducted with the objective of examining the hepatoprotective role of DM ethanolic extract in a hepatotoxic model of Sprague-Dawley rats.
METHODS
Sprague-Dawley (SD) male rats were divided into the following groups: Normal Control (NC); hepatotoxic disease control (DC); hepatotoxic group treated with a low dose (LD) of DM (LDDM-INH+RIF); hepatotoxic group treated with a high dose (HD) of DM (HDDMINH+RIF), and reference control (RC) standard drug silymarin for 21 days. The hepatoprotective action was explored by measuring various liver function enzymes and lipid profiles. Oxidative stress parameters were investigated by their concentrations in the plasma and liver tissue of all study groups.
RESULTS
Spectroscopic analysis revealed that the total phenolic and flavonoid contents of DM extract were 69.48 mg Gallic Acid Equivalents per gram (GAE/g) and 49.59 mg Catechin Equivalents per gram (CE/g), respectively. Gallic acid (6.89 mg/g) and rutin (24.78 mg/g) were identified as the predominant phenolic compounds. The extract exhibited 2,2-Diphenyl-1- picrylhydrazyl (DPPH) radical scavenging activity with an IC50 of 179 µg/mL compared to 20.65 µg/mL for BHT.
DISCUSSION
Treatment with DM significantly (p < 0.05) decreased serum cholesterol, total protein, and triglyceride levels in LDDM-INH+RIF and HDDM-INH+RIF groups relative to hepatotoxic control. Similarly, plasma liver function enzymes were reduced in a dose-dependent manner. Antioxidant analysis indicated a significant (p < 0.05) elevation of superoxide dismutase (SOD) and glutathione (GSH), accompanied by a significant decline in malondialdehyde (MDA) levels in both plasma and liver tissues compared with the disease control group.
CONCLUSION
DM exhibited significant hepatoprotective effects in isoniazid- and rifampicininduced hepatotoxic rats, primarily through its antioxidant activity. The extract enhanced hepatic and plasma antioxidant enzymes (SOD, GSH) while reducing lipid peroxidation (MDA). It also normalized liver function markers, cholesterol, and triglyceride levels, consistent with histopathological improvements. These protective effects are attributed to the phenolic and flavonoid constituents of the extract.
Bushra Shaukat, Md. Mujahid, M. Rahman et al.· Recent advances in inflammat...· 0 citations