Watermelon seeds in modulating oxidative stress and inflammatory pathways in rheumatoid arthritis: In Silico and In Vivo Insights

Objective This study targeted watermelon (Citrullus lanatus) seed powder (WSP) to evaluate its nutritional composition, antioxidant activity, and in silico as well as in vivo anti-arthritic potential in male Sprague Dawley rats. Methodology : The nutritional contents of WSP were analyzed, followed by the TPC contents and antioxidant activity via DPPH and ABTS assays. Moreover, FTIR spectroscopy was carried out to identify functional compounds. Later, in silico study via molecular docking was performed to assess quercetin, ferulic acid, and β-sitosterol interaction with superoxide dismutase (PDB: 1P7G) for anti-oxidative prediction, which was further confirmed by conducting in vivo study. Results The results revealed promising levels of crude fat (39.62%) and protein (23.84%), with efficient amount of potassium, calcium, and phosphorous. The aqueous ethanolic extract showed the maximum antioxidant activity, as DPPH = 73.50% and ABTS = 80.31 µM Fe ²⁺ /100g) due to higher TPC (766.7 mgGAE/100g) and TFC (71.47 mgQE/100g) contents. Moreover, molecular docking showed the higher binding affinity (-8.2 kcal/mol) of quercetin than others. In vivo study showed that the reduced CAT & TAC, and increased MDA levels were improved by the 400 mg/kg/day WSP to 58.73 ± 2.87 U/mL, 1.19 ± 0.01 mmol Trolox equivalents/L, and 6.02 ± 0.28 nmol/mL, respectively. Furthermore, inflammatory markers were also improved in G4 (TNF-α = 9.03 ± 0.70 pg/mL, CRP = 0.86 ± 0.03 mg/L, and IL-6 = 5.91 ± 0.13 pg/mL). Additionally, the histopathology showed the more efficient potential of WSP (400 mg/kg BW) in rats. Conclusion WSP demonstrated dose-responsive antioxidant restoration and reduction of systemic inflammation, supporting its low-cost functional and nutraceutical potential.