Juglans regia has been used to treat inflammatory and arthritic disorders in traditional medicine. The present study aimed to investigate the antiarthritic and anti-inflammatory potential of ethanolic leaves extract of J. regia. Arthritis was induced in rodents with Freunds complete adjuvant. J. regia treatment was started on 8^th day of arthritis induction and sustained for 20 days. Acute inflammatory models were developed using carrageenan, histamine, serotonin, and dextran. Qualitative and GC-MS analyses were also performed. Arthritis was determined using an arthritis scoring index and histopathological examination of ankle joints. RT-PCR was performed to determine the expression of pro-inflammatory markers (TNF-α, NF-κB, IL-6, IL-1β, and COX-2) and anti-inflammatory IL-4. PGE2 levels were evaluated using an ELISA. Blood and biochemical parameters were also determined. Paw edema was measured using a digital plethysmometer. Treatment with extracts inhibited arthritic development and attenuated paw edema along with all histopathological parameters. The expression levels of pro-inflammatory cytokines and COX-2 were downregulated, while IL-4 was upregulated. PGE2 levels were also reduced in extract-treated groups. Blood and biochemical parameters were nearly normalized in the treatment groups. Both extracts significantly inhibited carrageenan, histamine, serotonin, and dextran-induced paw edema. Qualitative phytochemical screening and GC-MS analysis confirmed that extracts possessed potential medicinal compounds. In conclusion, ethanol and n-hexane extracts of J. regia leaves have immunomodulatory and anti-inflammatory effects that ameliorate experimentally induced arthritis and edema. The inhibition of autacoids may also be one of the mechanisms inducing the immunomodulatory effect.

This study investigates the anti-inflammatory and immunomodulatory effects of a Benzimidazole derivative 2-((1H-benzo[d]imiadazol-2-yl) thio)-1-3, 5-diphenyl-1h-pyrazol-1-yl)ethanone (BZ), in both chronic and acute inflammation models. For induction of arthritis, Freund’s Complete Adjuvant was used. After inducing arthritis in rats, three different doses of benzimidazole derivative (25,50 and 100 mg/kg) were given. The treatment started on the 7th day and continued for 3 weeks. Piroxicam was used as the standard drug. On the last day of treatment, the rats were sacrificed. Paw edema and arthritis were determined using digital water plethysmometry and arthritic score index. Various hematological parameters, including red blood cells (RBC), white blood cells (WBC) and hemoglobin (Hb), along with biochemical markers such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea and creatinine were also evaluated. The mRNA levels of IL-6 and TNF-α were determined using a quantitative polymerase chain reaction (qPCR). Prostaglandin E2 (PGE2) levels were measured via ELISA. Carrageenan induced paw edema was employed for determining anti-inflammatory activity. Treatment with different doses of Benzimidazole derivative decreased paw edema and decreased arthritic progression. All histopathological parameters were concluded to be decreased after the given treatment. The analysis of qPCR showed decreased levels of Tumour necrosis factor (TNF-α) and Interleukin-6 (IL-6). Enzyme-linked immunosorbent assay (ELISA) demonstrated a decreased level of PGE2 in all groups that were treated with the benzimidazole derivative. Results obtained from all groups treated with the benzimidazole derivative were significantly comparable to those of piroxicam. Treatment groups restored RBC and Hb levels. The Benzimidazole derivative exhibited significant anti-inflammatory and immunomodulatory effects by reducing paw edema, arthritic progression, and inflammatory markers (TNF-α, IL-6, and PGE2), demonstrating potential as a therapeutic agent for inflammatory conditions.

Apigenin is a phytochemical obtained from Chamomilla recutita. Its role in interstitial cystitis is not yet known. The present study is aimed at understanding the uroprotective and spasmolytic effects of apigenin in cyclophosphamide-induced interstitial cystitis. The uroprotective role of apigenin was analyzed by qRT-PCR, macroscopic analysis, Evans blue dye leakage, histological evaluation, and molecular docking. The spasmolytic response was measured by adding cumulative concentrations of apigenin to isolated bladder tissue pre-contracted with KCl (80 mM) and carbachol (10⁻⁹–10⁻⁴) on non-incubated and pre-incubated tissues with atropine, 4DAMP, methoctramine, glibenclamide, barium chloride, nifedipine, indomethacin, and propranolol. Apigenin inhibited pro-inflammatory cytokines (IL-6, TNF-α and TGF 1-β) and oxidant enzymes (iNOS) while increasing antioxidant enzymes (SOD, CAT, and GSH) in CYP-treated groups compared to the control. Apigenin restored normal tissue of the bladder by decreasing pain, edema, and hemorrhage. Molecular docking further confirmed the antioxidant and anti-inflammatory properties of apigenin. Apigenin produced relaxation against carbachol-mediated contractions, probably via blockade of M₃ receptors, K_ATP channels, L-type calcium channels, and prostaglandin inhibition. While the blockade of M₂ receptors, K_IR channels, and β-adrenergic receptors did not contribute to an apigenin-induced spasmolytic effect, apigenin presented as a possible spasmolytic and uroprotective agent with anti-inflammatory, antioxidant effects by attenuating TGF-β/iNOS-related tissue damage and bladder muscle overactivity. Thus, it is a potential agent likely to be used in treatment of interstitial cystitis.