Harnessing Clerodendrum serratum and its Nanoformulations: A tri-modal evaluation for improved anti-inflammatory, analgesic, and antioxidant activities

Aim of the study The aim of this study was to evaluate the anti-inflammatory, analgesic and antioxidant activities of Clerodendrum serratum extract (CSE), its silver nanoparticles (AgNPs), and PEGylated nanoparticles (PEG-AgNPs) using in vivo , and in silico approaches. Material and methods Acute and chronic inflammation were induced using carrageenan and FCA in wistar rats, respectively. Animals were treated with Clerodendrum serratum extract (CSE), AgNPs, or PEG-AgNPs, and evaluated for paw edema, inflammatory scores, body weight, hematological, biochemical, and histopathological parameters. Analgesic, antioxidant, cytokine (TNF-α, IL-6), and molecular docking analyses were performed to assess anti-inflammatory efficacy and mechanistic insights. Result and Discussion Analgesic evaluation using hot-plate and tail-flick assays demonstrated that at the highest doses, CSE at 400 mg/kg produced analgesic effects of 71% and 67%, AgNPs at 0.4 mg/kg achieved 83% and 86%, and PEG-AgNPs at 0.4 mg/kg exhibited the strongest activity with 86% and 85%, respectively, comparable to the standard drug diclofenac at 10 mg/kg, exhibiting 92% and 89% activity supporting their potent anti-nociceptive activity. Flow cytometry analysis revealed that both CSE and AgNP treatments dose-dependently reduced intracellular ROS levels, with PEG-AgNPs at 0.4 mg/kg exhibiting the most potent antioxidant effect, showing 35% of ROS population. In vivo analysis of pro-inflammatory cytokines from serum of CSE, AgNPs, and PEG-AgNPs treated group demonstrated dose-dependently reduction of IL-6 and TNF-α. CSE at 400 mg/kg, AgNPs at 0.4 mg/kg, and PEG-AgNPs at 0.4 mg/kg exhibited the most significant inhibitory effects, with PEG-AgNPs demonstrating superior efficacy by reducing IL-6 to 64 pg/mL and TNF-α to 72 pg/mL. In silico analysis revealed strong binding interactions of CSE phytoconstituents with COX-1, COX-2, and 5-LOX, with the best docking score of -10.36, supporting their anti-inflammatory potential. The predicted ADME-toxicity analysis indicated high absorption, favorable pharmacokinetics, limited CNS penetration, and no hepatotoxicity or mutagenicity despite selective CYP inhibition. Conclusion PEGylated silver nanoparticles of Clerodendrum serratum extract demonstrated superior anti-inflammatory, analgesic, and antioxidant activities compared to CSE and AgNPs, and the integration of in vivo , and in silico findings provides robust evidence suggesting PEG-AgNPs as a promising nanotherapeutic strategy for managing inflammation and related disorders.