Synergistic anti-inflammatory effects of the aqueous extract from Desmodium heterophyllum and photobiomodulation in a carrageenan-induced paw edema model

Inflammation is a complex biological response that, when uncontrolled, contributes to the development and worsening of several pathological conditions. Identifying safe and effective anti-inflammatory strategies remains an important therapeutic challenge. In this context, medicinal plants and photobiomodulation therapy (PBM) have emerged as promising approaches due to their immunomodulatory potential. This study aimed to investigate the anti-inflammatory properties of the aqueous extract from Desmodium heterophyllum (AEDh), alone and in combination with PBM, using a carrageenan-induced paw edema model. AEDh was obtained, chemically characterized through high-resolution mass spectrometry, and evaluated for cytotoxicity and nitric oxide (NO) production in J774A.1 and RAW 264.7 macrophages. In vivo anti-inflammatory activity was assessed in BALB/c mice subjected to carrageenan-induced paw edema and treated with AEDh (50–250 mg/kg), PBM (780 nm, 70 mW, 35 J/cm²), or their combination. Paw thickness was measured for up to 4 h post-induction, and cytokine levels (IL-1β, IL-6, TNF, IFN-γ) were quantified by enzyme-linked immunosorbent assay (ELISA). AEDh showed no cytotoxicity at the concentrations tested and significantly reduced NO production in vitro. In vivo, both AEDh and PBM reduced paw edema, with the combined treatment—especially AEDh at 250 mg/kg—producing a more pronounced effect, comparable to dexamethasone. The combination also markedly reduced pro-inflammatory cytokines, particularly IL-1β and IL-6, supporting a synergistic action. AEDh demonstrated relevant anti-inflammatory and immunomodulatory activity, which was further enhanced when combined with PBM. These findings highlight the therapeutic potential of integrating herbal medicine and photobiomodulation as a safe and effective strategy for managing inflammatory conditions. Keywords: Desmodium heterophyllum; Photobiomodulation; Cytokines; Synergistic effect; Low-level laser therapy.