# Nanoparticle delivery of combined plant extracts enhances immune response in immunocompromised rats

**Authors:** Selvia S. Milad, Hisham A. Elshoky, Sara E. Ali, Marwa S. Khattab, Mahmoud Z. Attia, Afaf M. Azouz

PMC · DOI: 10.1038/s41598-025-21329-3 · 2025-11-07

## TL;DR

This study shows that combining plant extracts with nanoparticles can boost immunity in rats with weakened immune systems.

## Contribution

The novel finding is that nanoparticle delivery of combined plant extracts significantly enhances immunomodulatory effects at lower doses.

## Key findings

- Nanoparticle formulations of herbal extracts improved immune markers like white blood cells and cytokines in immunosuppressed rats.
- C.CS-based nanoparticles showed better therapeutic performance at a reduced dosage of 100 mg/kg.
- All treatments increased Ki-67 expression, indicating improved cell growth and immune health.

## Abstract

Recently, the world has been dealing with diseases that spread easily and weaken the body’s natural defenses. Boosting natural immunity can help prevent these diseases. This study sought to assess the immunomodulatory effects of extracts from Illicium verum, Saussurea costus, and Glycyrrhiza glabra, both individually and in conjunction with chitosan and carboxy chitosan nanoparticles (CS NPs and C.CS NPs), in immunosuppressed male rats. The primary objective was to assess whether the combined plant extracts exhibit superior immunomodulatory effects compared to single treatments. The herbal extracts were tested chemically. The nanoparticles and loaded herbal extracts were studied for size, charge, and chemical structure, and their safety was tested on two cell types. The study used 104 adult male rats, divided into 13 groups: a control group, an immunosuppressed group, three groups treated with herbal extracts, two nano groups, and six groups treated with loaded herbal extracts. Immunosuppression was caused by injecting 20 mg of dexamethasone weekly. Herbal extracts, CS NPs, C.CS NPs, and the loaded herbal extracts were given orally every day after day for 28 days. The study checked immune health, tissue structure, and cell growth marker Ki-67. All treatments improved immune health by increasing white blood cells, complement 3 and 4, interferon-gamma, and tumor necrosis factor levels, and raised Ki-67 expression. Incorporation of chitosan and methyl carboxy chitosan (C.Cs) nanoparticles amplified the immunostimulatory effect at a reduced dosage of 100 mg/kg, with the C.Cs-based formulation exhibiting enhanced therapeutic performance. The results highlight the promise of nanoparticle-formulated herbal extracts, especially C.CS-loaded variants, as potent immunomodulatory agents with enhanced therapeutic efficacy.

## Linked entities

- **Proteins:** Mki67 (antigen identified by monoclonal antibody Ki 67)
- **Chemicals:** dexamethasone (PubChem CID 5743), chitosan (PubChem CID 129662530), carboxy chitosan (PubChem CID 129852377)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** tumor necrosis factor [NCBI Gene 103694380], Ifng (interferon gamma) [NCBI Gene 25712] {aka IFNG2, If2f}
- **Chemicals:** dexamethasone (MESH:D003907), C.Cs (-), CS (MESH:D002586), chitosan (MESH:D048271)
- **Species:** Glycyrrhiza glabra (species) [taxon 49827], Dolomiaea costus (kuth, species) [taxon 324593], Rattus norvegicus (brown rat, species) [taxon 10116], Illicium verum (Chinese star-anise, species) [taxon 124778]

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12594806/full.md

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Source: https://tomesphere.com/paper/PMC12594806