Author

Ammara Saleem

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Open access Jul 2026

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

BACKGROUND Rheumatoid arthritis is a chronic autoimmune disorder that causes severe pain and inflammation that gradually destroys joints. OBJECTIVES Tetrahydropyrimidine-5-carboxylate (THP) has been investigated for its anti-inflammatory and anti-arthritic effects using both in vitro and in vivo approaches. METHODS In vitro anti-inflammatory activity of THP was assessed using protein denaturation and membrane stabilization assays at various concentrations. For in vivo anti-inflammatory activity, carrageenan-induced paw edema and xylene-induced ear edema models were performed in rats. For anti-arthritic potential, all rats except normal control group, were given an injection of Complete Freund's Adjuvant (CFA; 0.15 mL) into the left hind paw on day one. Treatment with THP at 25, 50 and 100 mg/kg was started orally from 8th day till 28th day. Methotrexate (1 mg/kg) was the standard treatment; the normal and disease groups received vehicle. The effects of treatment on body weight, paw edema, pain, blood chemistry, neurotransmitters and oxidative stress biomarkers were assessed. RESULTS THP exhibited significant In-vitro and in-vivo anti-inflammatory potential in dose dependent manner. THP (25-100mg/kg) treatment significantly decreased paw edema, arthritic index and pain, while restoring body weight, muscular strength, oxidative stress biomarkers and blood parameters in treated rats compared with the disease control. Treatment with THP notably modulated the mRNA expression of RANKL, OPG, MMP-13, COX-2, TNF-α, IL-6 and IL-4 compared with disease control, as evidenced by histology of the ankle joint of treated rats. THP-treated rats exhibited higher levels of serotonin and noradrenaline in sciatic nerve homogenates. CONCLUSION The results showed that THP had significant dose-dependent anti-inflammatory, anti-arthritic, antioxidant and analgesic effects, suggesting that it could be a safe therapy for inflammatory and arthritic diseases, as it showed an LD50 > 2000mg/kg.

Marwah Rehman, Ammara Saleem, Muhammad Furqan Akhtar · 0 citations
Jul 2026

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

BACKGROUND Rheumatoid arthritis is a systemic autoimmune disorders of joints. Its available therapies having serious adverse effects, high cost and poor patient compliance. OBJECTIVE The present study aimed to evaluate the anti-inflammatory and anti-arthritic potential of 3, 4-dimethoxybenzoic acid or Veratric acid (VA) by in-vitro and in-vivo assays. Additionally, acute toxicity of VA was performed. METHODOLOGY The anti-inflammatory activity was assessed by Xylene-induced ear edema, and Carrageenan-induced paw edema models in Wistar rats. The VA was given at doses of 20, 40, and 80 mg/kg, with Piroxicam (10mg/kg) as standard drug. For anti-arthritic action, 0.1 ml of Complete Freund's adjuvant was intradermally inoculated in left posterior paw on first day while treatment with VA at 20, 40, 80, and VA 80 mg/kg + methotrexate and methotrexate (1 mg/kg) as standard drug were given orally on the 8th day for 21 days. RESULTS Treatment with VA exhibited a substantial reinstatement of body weight, paw edema, arthritic scores, and oxidative stress in difference to disease control. All treatment groups exhibited notable down-regulation (p < .0001) of IL-6, TNF-α, IL-β, COX-2, and NF-κB and up-regulation of IL-10, 1-κβ, IL-4 in contrast to disease control. The combination group had exhibited noticeable anti-arthritic potential in comparison to individual treatment groups. In acute toxicity study, LD50 of VA was greater than 2000 mg/kg. CONCLUSION 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.

Ammara Saleem, Afnan Afnan, Muhammad Irfan et al. · 0 citations