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<p>Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with inflammation, oxidative stress, and progressive joint damage. Although kaempferol exhibits strong anti-inflammatory and antioxidant activities, its therapeutic application is limited by poor solubility and bioavailability. This study aimed to develop kaempferol-loaded solid lipid nanoparticles (K-SLNs) and evaluate their anti-arthritic potential in Freund’s Complete Adjuvant (FCA)-induced arthritic rats. The optimized K-SLNs showed a mean particle size of 95.08&#xa0;nm and a zeta potential of − 26.9&#xa0;mV, indicating good colloidal stability. SEM revealed uniform, slightly angular, elongated and sub-spherical geometry, while FTIR confirmed successful encapsulation of kaempferol. K-SLNs exhibited concentration-dependent antioxidant activity with a total phenolic content of 99.0 ± 1.25 and enhanced DPPH scavenging (84.20 ± 0.46%) activity compared to pure kaempferol (58.00 ± 0.60%). In vitro anti-inflammatory assays showed strong membrane stabilization (85.23 ± 1.12%), BSA inhibition (83.70 ± 0.56%), and egg albumin inhibition (86.17 ± 0.65%). In vivo, the K-SLNs (300&#xa0;mg/kg) significantly reduced paw swelling (4.85 ± 0.01&#xa0;mm) and arthritic score (0.90 ± 0.12) by day 35, comparable to methotrexate, and lowered serum RF to 41.06 ± 2.02&#xa0;IU/mL and ESR to 5.07 ± 0.08&#xa0;mm/h. Oxidative stress and organ injury were markedly attenuated, with restoration of SOD (9.20 ± 0.08 U/mL) and reduction of MDA (3.05 ± 0.04&#xa0;nmol/mL). qRT-PCR showed downregulation of IL-1β, TNF-α, COX-2, MMP-13, IL-17A, and IL-33 with upregulation of IL-4 and IL-10. Histopathology confirmed near-normal joint and organ architecture. Overall, K-SLNs demonstrated superior anti-arthritic efficacy compared to free kaempferol by effectively modulating inflammatory cytokines, oxidative stress markers, and cartilage-degrading enzymes, highlighting their potential as an advanced nanotherapeutic strategy for rheumatoid arthritis. These findings indicate that K-SLNs significantly enhance kaempferol’s efficacy while showing outcomes comparable to methotrexate, suggesting potential for reduced treatment-associated toxicity.</p>

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Kaempferol-loaded solid lipid nanoparticles attenuate cartilage degradation and inflammation by modulating the expression of pro and inflammatory cytokines, MMP-13 and oxidative stress markers in adjuvant induced arthritic rats

  • 期刊论文

  • 发表日期：

    2026年5月25日

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  • Anam Niamat,
  • Aftab Ahmad,
  • Nayla Munawar,
  • Muhammad Shahid,
  • Bushra Akhtar

摘要

Rheumatoid arthritis (RA) is a chronic autoimmune disease associated with inflammation, oxidative stress, and progressive joint damage. Although kaempferol exhibits strong anti-inflammatory and antioxidant activities, its therapeutic application is limited by poor solubility and bioavailability. This study aimed to develop kaempferol-loaded solid lipid nanoparticles (K-SLNs) and evaluate their anti-arthritic potential in Freund’s Complete Adjuvant (FCA)-induced arthritic rats. The optimized K-SLNs showed a mean particle size of 95.08 nm and a zeta potential of − 26.9 mV, indicating good colloidal stability. SEM revealed uniform, slightly angular, elongated and sub-spherical geometry, while FTIR confirmed successful encapsulation of kaempferol. K-SLNs exhibited concentration-dependent antioxidant activity with a total phenolic content of 99.0 ± 1.25 and enhanced DPPH scavenging (84.20 ± 0.46%) activity compared to pure kaempferol (58.00 ± 0.60%). In vitro anti-inflammatory assays showed strong membrane stabilization (85.23 ± 1.12%), BSA inhibition (83.70 ± 0.56%), and egg albumin inhibition (86.17 ± 0.65%). In vivo, the K-SLNs (300 mg/kg) significantly reduced paw swelling (4.85 ± 0.01 mm) and arthritic score (0.90 ± 0.12) by day 35, comparable to methotrexate, and lowered serum RF to 41.06 ± 2.02 IU/mL and ESR to 5.07 ± 0.08 mm/h. Oxidative stress and organ injury were markedly attenuated, with restoration of SOD (9.20 ± 0.08 U/mL) and reduction of MDA (3.05 ± 0.04 nmol/mL). qRT-PCR showed downregulation of IL-1β, TNF-α, COX-2, MMP-13, IL-17A, and IL-33 with upregulation of IL-4 and IL-10. Histopathology confirmed near-normal joint and organ architecture. Overall, K-SLNs demonstrated superior anti-arthritic efficacy compared to free kaempferol by effectively modulating inflammatory cytokines, oxidative stress markers, and cartilage-degrading enzymes, highlighting their potential as an advanced nanotherapeutic strategy for rheumatoid arthritis. These findings indicate that K-SLNs significantly enhance kaempferol’s efficacy while showing outcomes comparable to methotrexate, suggesting potential for reduced treatment-associated toxicity.