eng Innovesen Journals Decipher Ayurveda 3107-8214 2025-06-07 01 01 55 63 20 research-article Anurag Sharma 1 Ravi Gautam 2 Amber Mishra 3 Neelanchal Trivedi 4 Invertis Institute of Pharmacy, Invertis University, Bareilly Invertis Institute of Pharmacy, Invertis University, Bareilly Invertis Institute of Pharmacy, Invertis University, Bareilly Invertis Institute of Pharmacy, Invertis University, Bareilly Crinum asiaticum (Amaryllidaceae) and Linum usitatissimum (Linaceae) possess complementary anti - inflammatory chemistries Amaryllidaceae alkaloids (e.g., lycorine) and phenolic/flavonoid pools yet standardized synergy a cross cellular and in vivo models remains underexplored. S tandardize leaf extracts, quantify fixed ratio interactions, and evaluate mechanistic and translational correlates in macrophage and acute edema models. CAE ( Crinum asiaticum ethanolic leaf extract) (95% ethanolic extract) was standardized to lycorine (HPLC) and phenolics; LUE ( Linum usitatissimum hydroalcoholic leaf extract) (70% ethanolic extract) to phenolics/flavonoids, guided by recent profiling literature. Antiinflammatory activity was assessed in LP stimulated RAW 264.7 cells (NO by Griess; TNFα/PGE2 by EL=SA; MTT), with cytokine/signaling exploration (=L6, MCP1; iNOS/COX2; NF κB p65) and Chou Talalay combination indices (CI) at 50%/75% effect for CAE:LUE ratios (1:1, 2:3, 3:2). In vivo efficacy was examined in carrageenan paw edema (vehicle, diclofenac 10 mg/kg, CAE 120 mg/kg, LUE 180 mg/kg, & combinations totaling 300 mg/kg), with AUC, tissue biomarkers (MPO, MDA, nitrite, H2O2, GSH, catalase), and blinded histology; a CAE:LUE 2:3 hydrogel (1% w /w) was evaluated for localized edema and ex vivo release (Higuchi kinetics). Standardization yielded CAE lycorine 2.78% w/w and LUE phenolics/flavonoids 24.9/10.1 mg/g; viability was ≥90% to 60 μg/mL. Single agent =C50 (μg/mL): CAE NO 22.7, TNFα 31.4, PGE2 >120; LUE NO 36.1, TNFα 49.6, PGE2 76.8. The 2:3 ratio enhanced potency (=C5 0: NO 11.3; TNFα 18.2; PGE2 54.7) with C= indicating synergy strengthening at higher effects (NO 0.64→0.51; TNFα 0.71→0.59). =n vivo, 2:3 inhibited edema 61.9% at 4 h (diclofenac 66.7%), reduced AUC 36.4%, improved biomarkers, and lowered histology scor es; the hydrogel achieved 41.5% inhibition and 52.3% release at 8 h. A CAE:LUE 2:3 combination exhibits synergistic, multi - pathway anti - inflammatory efficacy with oral and topical promise. https://innovesenjournals.in/r/imrs/public/article.php?id=20 Crinum asiaticum Linum usitatissimum Lycorine Phenolics Synergistic effects RAW 264.7 Carrageenan Oxidative stress Hydrogel