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

**Authors:** Tássio Malber Oliveira, Diego Mendes Xavier, Gracimério José Guarneire, Nerilson Marques Lima, Roberta Maria Abrão, Luiz Gustavo Vilela Filho, Brendha Sena Costa, Sandra Bertelli Ribeiro Castro, Caio César de Souza Alves, Alessandra de Paula Carli, Murilo Xavier Oliveira

PMC · DOI: 10.1007/s10103-026-04822-7 · 2026-02-21

## TL;DR

This study shows that combining a plant extract with light therapy can reduce inflammation more effectively than either treatment alone, offering a promising new approach for treating inflammatory conditions.

## Contribution

First study to demonstrate the synergistic anti-inflammatory effects of Desmodium heterophyllum extract combined with photobiomodulation.

## Key findings

- The combination of Desmodium heterophyllum extract and photobiomodulation significantly reduced paw edema and pro-inflammatory cytokines comparable to dexamethasone.
- The extract showed no cytotoxicity to macrophage cell lines and reduced nitric oxide production in vitro.
- The synergistic treatment supports the development of safe integrative strategies for managing inflammation.

## Abstract

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.

First study to demonstrate the synergistic anti-inflammatory effects of Desmodium heterophyllum extract combined with photobiomodulation;Significant reduction in edema and pro-inflammatory cytokines comparable to dexamethasone;Extract exhibited excellent biocompatibility, with no cytotoxicity to macrophage cell lines;Findings support the development of safe and effective integrative therapeutic strategies for inflammatory conditions.

First study to demonstrate the synergistic anti-inflammatory effects of Desmodium heterophyllum extract combined with photobiomodulation;

Significant reduction in edema and pro-inflammatory cytokines comparable to dexamethasone;

Extract exhibited excellent biocompatibility, with no cytotoxicity to macrophage cell lines;

Findings support the development of safe and effective integrative therapeutic strategies for inflammatory conditions.

## Linked entities

- **Chemicals:** dexamethasone (PubChem CID 5743), nitric oxide (PubChem CID 145068)

## Full-text entities

- **Genes:** Pla2g1b (phospholipase A2, group IB, pancreas) [NCBI Gene 18778] {aka Pla2a, sPLA2IB}, Hsp90aa1 (heat shock protein 90, alpha (cytosolic), class A member 1) [NCBI Gene 15519] {aka 86kDa, 89kDa, Hsp86-1, Hsp89, Hsp90, Hspca}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}, COX1 (cytochrome c oxidase subunit I) [NCBI Gene 17708] {aka CoxI}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Hspa4 (heat shock protein family A (Hsp70) member 4) [NCBI Gene 15525] {aka 70kDa, APG-2, Hsp110, Hsp70RY, mKIAA4025}, Ifng (interferon gamma) [NCBI Gene 15978] {aka IFN-g, If2f, Ifg}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 17709], Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}
- **Diseases:** gastritis (MESH:D005756), inflammatory cytokines (MESH:D000080424), type 2 diabetes (MESH:D003924), Cytotoxicity (MESH:D064420), ulcers (MESH:D014456), cardiovascular complications (MESH:D002318), arthritis (MESH:D001168), rheumatoid arthritis (MESH:D001172), metabolic disorders (MESH:D008659), acute (MESH:D000208), dermatitis (MESH:D003872), edema (MESH:D004487), kidney failure (MESH:D051437), cancer (MESH:D009369), neurodegenerative disorders (MESH:D019636), Inflammation (MESH:D007249)
- **Chemicals:** flavonoid (MESH:D005419), DMSO (MESH:D004121), sulfuric acid (MESH:C033158), reactive oxygen species (MESH:D017382), Tween 20 (MESH:D011136), luteolin (MESH:D047311), LPS (MESH:D008070), thromboxanes (MESH:D013931), polyphenol (MESH:D059808), adenosine triphosphate (MESH:D000255), CO2 (MESH:D002245), L-glutamine (MESH:D005973), TFA (MESH:D014269), dexamethasone (MESH:D003907), phenyl-methyl-sulfonyl fluoride (MESH:D010664), H3PO4 (MESH:C030242), amino acids (MESH:D000596), MTT (MESH:C070243), sulfanilamide (MESH:D000077145), penicillin (MESH:D010406), D. heterophyllum extract (-), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MESH:C022616), NO (MESH:D009569), liquiritigenin (MESH:C083152), alkaloids (MESH:D000470), Griess reagent (MESH:C095000), benzethonium chloride (MESH:D001558), water (MESH:D014867), Acetonitrile (MESH:C032159), streptomycin (MESH:D013307), sodium nitrite (MESH:D012977), tetramethylbenzidine (MESH:C021758), ethylene diaminetetraacetic acid (MESH:D004492), prostaglandins (MESH:D011453), xylazine (MESH:D014991), quercetin (MESH:D011794), nitrogen (MESH:D009584), hexose (MESH:D006601), Carrageenan (MESH:D002351), NaCl (MESH:D012965)
- **Species:** Grona heterophylla (species) [taxon 1784723], Linochilus heterophyllus (species) [taxon 587511], Mangifera indica (mango, species) [taxon 29780], Mus musculus (house mouse, species) [taxon 10090], Eugenia uniflora (Brazil-cherry, species) [taxon 119951]
- **Cell lines:** BALB/c — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0184), J774A.1 — Mus musculus (Mouse), Mouse reticulum cell sarcoma, Cancer cell line (CVCL_0358), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), c — Mus musculus (Mouse), Hepatocellular carcinoma of the mouse, Cancer cell line (CVCL_9103)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12924869/full.md

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Source: https://tomesphere.com/paper/PMC12924869