# Anti‐Arthritic Potential of Pyrazoline Derivative Against Complete Freund's Adjuvant Induced Arthritis in Rats

**Authors:** Jian Li, Irfan Anjum, Halima Qadir, Faiza Naseer, Mehreen Arif, Muhammad Riaz, Rabia Gul, Madiha Kanwal, Bei Zhuang

PMC · DOI: 10.1111/jcmm.71030 · Journal of Cellular and Molecular Medicine · 2026-02-24

## TL;DR

This study tested a new pyrazoline compound in rats with arthritis and found it reduced inflammation and joint damage, suggesting potential as a treatment for rheumatoid arthritis.

## Contribution

The study demonstrates the anti-arthritic potential of a novel pyrazoline derivative in a rat model of arthritis.

## Key findings

- The compound reduced paw edema and arthritis scores in a dose-dependent manner.
- Levels of pro-inflammatory cytokines like TNF-α and NF-κB were significantly lowered.
- Histopathological analysis showed reduced joint inflammation and synovial hyperplasia.

## Abstract

This research explored the potential of a synthesised pyrazoline derivative 5‐ethoxy 5‐hydroxy 3‐methyls 4, 5‐dihydro 1Hpyrazol 1 yl (pyridine 4 yl) methanone [5‐E‐5‐H‐PD], against arthritis using a Complete Freund's Adjuvant (CFA)‐induced arthritis in a rat model. Sprague–Dawley rats were used to induce arthritis via subplantar injection of CFA (0.1 mL) into their right hind paw. Animals were divided into 6 groups (n = 4): normal, arthritis, standard drug (methotrexate 1 mg/kg intraperitoneally), and 3 treatment groups receiving 5‐E‐5‐H‐PD, 10, 20 and 40 mg/kg orally for 21 days. Clinical signs (paw volume and arthritis score), pro‐inflammatory cytokines, and histopathological alterations were evaluated. The 5‐E‐5‐H‐PD groups showed a reduction in paw edema in a dose‐dependent manner. On day 21, paw volume in the 40 mg/kg dose animals decreased significantly to 2.31 ± 0.12 mm compared to 4.82 ± 0.14 mm in the disease animals (p < 0.001). Arthritis scores reduced from 3.8 ± 0.2 (control) to 1.5 ± 0.3 in the high‐dose treatment group. Serum IL‐10, TNF‐α, and NF‐κB levels were significantly reduced to 66.75 ± 3.0 pg/mL, 34.50 ± 1.8 pg/mL and 9.50 ± 0.6 pg/mL respectively, compared to the arthritis induced rats 129.8 ± 2.0 pg/mL, 77.75 ± 1.5 pg/mL and 28.50 ± 1.3 pg/mL respectively, compared to the arthritis induced rats (112.3 ± 5.5, 96.8 ± 4.3, 123.1 ± 6.2 pg/mL, p < 0.001). Histopathology analysis confirmed reduced synovial hyperplasia and inflammatory infiltration in treated joints. The pyrazoline derivative, 5‐E‐5‐H‐PD, demonstrated significant anti‐arthritic effects in the CFA‐induced rat model by reducing inflammation, cytokine expression and joint destruction. These findings support further investigation into pyrazoline‐based compounds as promising therapeutic agents for RA.

## Linked entities

- **Chemicals:** methotrexate (PubChem CID 4112), IL-10 (PubChem CID 146070)
- **Diseases:** arthritis (MONDO:0005578), rheumatoid arthritis (MONDO:0008383)

## Full-text entities

- **Genes:** IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, Pdlim3 (PDZ and LIM domain 3) [NCBI Gene 114108] {aka Actn2lp, Alp}, Cat (catalase) [NCBI Gene 24248] {aka CS1, Cas1, Cat01, Catl, Cs-1}, Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, Il10 (interleukin 10) [NCBI Gene 25325] {aka IL10X, If2a}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}, Ptgs2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 29527] {aka COX-2, Cox2, PGHS-2, PHS II, Pghs2}, Got2 (glutamic-oxaloacetic transaminase 2) [NCBI Gene 25721] {aka ASPATA, mAAT}
- **Diseases:** Arthritic Paw Edema (MESH:D004487), cancer (MESH:D009369), weakness of bones and joints (MESH:D018908), mitochondrial damage (MESH:D028361), Arthritis pain (MESH:D010146), Inflammation (MESH:D007249), hypoxemia (MESH:D000860), cartilage degradation (MESH:D002357), Arthritic (MESH:D015535), immune-mediated (MESH:C567355), hypoxic (MESH:D002534), autoimmune disease (MESH:D001327), gastrointestinal ulceration (MESH:D014456), Rheumatic factor (MESH:D012216), joint damage (MESH:D007592), toxicity (MESH:D064420), RF (MESH:D001171), joint pain (MESH:D018771), bone erosion (MESH:D014077), bone destruction (MESH:D001847), synovitis (MESH:D013585), infection (MESH:D007239), cardiovascular complications (MESH:D002318), joint deformities (MESH:D016916), hematologic (MESH:D006402), RA (MESH:D001172), Arthritis (MESH:D001168), erythema (MESH:D004890), hyperplasia (MESH:D006965), joint destruction (MESH:D008105), hepatic or renal toxicity (MESH:D056486), anaemia (MESH:D000743), Deformity (MESH:D009140)
- **Chemicals:** hydrazine hydrate (MESH:C029424), nitrogen (MESH:D009584), EDTA (MESH:D004492), prostaglandin (MESH:D011453), oxygen (MESH:D010100), ibuprofen (MESH:D007052), paraffin (MESH:D010232), chalcones (MESH:D047188), metal (MESH:D008670), piroxicam (MESH:D010894), pyrazolidine-3,5-diones (MESH:C443742), diclofenac (MESH:D004008), methotrexate (MESH:D008727), water (MESH:D014867), PD (MESH:D010165), MDA (MESH:D008315), Pyrazoles (MESH:D011720), Haematoxylin (MESH:D006416), sulfinpyrazone (MESH:D013442), H &amp; E (MESH:D006371), antipyrine (MESH:D000983), 5-ethoxy 5-hydroxy 3-methyls 4, 5-dihydro 1Hpyrazol 1 yl (pyridine 4 yl) methanone (-), ROS (MESH:D017382), 6-Methoxyflavone (MESH:C000593132), diethyl ether (MESH:D004986), formaldehyde (MESH:D005557), hydrogen (MESH:D006859), alcohol (MESH:D000438), eosin (MESH:D004801), polypropylene (MESH:D011126), GSH (MESH:D005978)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Mycobacterium tuberculosis (species) [taxon 1773], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932970/full.md

## References

46 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932970/full.md

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Source: https://tomesphere.com/paper/PMC12932970