| DOI: 10.29090/psa.2026.02.26.9351 | Pharm Sci Asia 2026; 53(2), 179-194 |
A Chou-Talalay synergy framework reveals dose-sparing analgesic, antipyretic and anti-inflammatory effects of Melastoma malabathricum leaf extract combined with nanocurcumin in miceThi Phuong Nhung Tran*, Hong Quan Bui, Huyen Trang Luu, Ngoc Thuan Nguyen, Thi Truc Ly Le, Hoa Hong Chau Truong
- Institute of Biotechnology - Food, Industrial University of Ho Chi Minh City, Ho Chi Minh City, 70000, Vietnam
Pain, inflammation, and fever share overlapping mediator networks, supporting dose-sparing, multi-target combinations. We evaluated a standardized Melastoma malabathricum leaf extract (ME) combined with nanocurcumin (NC) using Chou-Talalay quantitative synergy analysis and multi-model in vivo validation. ME and NC were quality-controlled by chromatographic fingerprinting and physicochemical characterization. In LPS-stimulated RAW 264.7 macrophages, single-agent and fixed-ratio combination dose-response relationships were modeled by median-effect analysis to compute combination index (CI) and dose-reduction index (DRI). For in vivo validation, Swiss albino mice were randomized into five groups per model: (i) vehicle control, (ii) model-matched positive control (tramadol, meloxicam, or paracetamol), (iii) ME alone (200 mg/kg), (iv) NC alone (50 mg/kg), and (v) ME+NC combination. Efficacy was assessed using hot-plate and formalin nociception, carrageenan-induced paw edema, and Brewer’s yeast-induced pyrexia, with reference drugs to confirm assay sensitivity. ME+NC showed consistent synergism across effect levels (Fa 0.50-0.90), with CI 0.62-0.79 at Fa 0.50-0.75 and 0.58 at Fa 0.90, corresponding to practical dose-sparing (DRI ? 2.2-2.6 for ME and 2.7-3.1 for NC). In vivo, the combination produced the greatest improvements across pain, inflammation, and fever models versus either monotherapy, alongside larger reductions in pro-inflammatory cytokines and COX-2/iNOS and favorable shifts in oxidative stress markers, and was well tolerated under the study conditions, without evidence of overt short-term toxicity. Overall, ME+NC is a quality-controlled, CI/DRI-defined synergistic combination with coherent multi-symptom efficacy, warranting pharmacokinetic–pharmacodynamic optimization and evaluation in longer-term disease settings.
Keyword:
Melastoma malabathricum; Nanocurcumin; Chou-Talalay; Synergy; Dose-sparing; Analgesic
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