# Intranasal natural products for influenza treatment: a systematic review and meta-analysis of preclinical studies

**Authors:** Kaiqi Zhang, Yao Lu, Jingwen Yang, Changqi Shi, Ning Zhao, Xiaojuan He, Cheng Lu, Li Li

PMC · DOI: 10.3389/fimmu.2026.1758831 · Frontiers in Immunology · 2026-03-10

## TL;DR

This study reviews preclinical evidence showing that intranasal natural products can improve survival and reduce viral load in influenza models.

## Contribution

The study provides the first systematic review and meta-analysis of intranasal natural products for influenza treatment in preclinical models.

## Key findings

- Intranasal natural products significantly increased survival rates in influenza models.
- They reduced viral titer and lung index in infected mice.
- Regulatory effects on body weight and inflammatory cytokines were observed.

## Abstract

Influenza imposes a heavy global public health burden, with current therapies limited by drug resistance and side effects. Natural products have antiviral potential, and intranasal delivery targets the respiratory tract. However, preclinical evidence lacks systematic evaluation, necessitating this review.

This study is a systematic review and meta-analysis conducted per the PRISMA guidelines. Studies meeting the inclusion criteria were retrieved and screened from the PubMed, Embase, Web of Science, China National Knowledge Internet, VIP Information Chinese Periodical Service Platform, China Biology Medicine Disc, and Wanfang Data Knowledge Service Platform databases. A meta-analysis was performed using R Studio software. The mean difference (MD) and relative risk (RR) were calculated using fixed effects or random effects models. Sources of heterogeneity, sensitivity, and publication bias were also explored.

A total of 23 studies were included. The results of the meta-analysis revealed that compared with the control treatment, intranasal natural products significantly increased the survival rate (RR = 3.47, 95% confidence interval [CI]: 2.44 to 4.93, p < 0.001) and reduced the viral titer (MD = −1.30, 95% CI: −2.27–−0.32, p=0.0092 < 0.01) and lung index (MD =−0.10, 95% CI: −0.19–−0.02, p = 0.015 < 0.05). In addition, intranasal natural products exerted regulatory effects on the body weight and inflammatory cytokines of influenza-infected mice.

The results show that intranasal natural products significantly increase survival and reduce the lung viral load in influenza models, with preliminary exploration of the underlying mechanisms and therapeutic potential. Owing to methodological limitations and heterogeneity, high-quality preclinical studies and standardized animal experiments are needed.

https://inplasy.com/, identifier INPLASY INPLASY2025120006.

## Linked entities

- **Diseases:** influenza (MONDO:0005812)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** infected (MESH:D007239), inflammatory (MESH:D007249), Influenza (MESH:D007251)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13008708/full.md

## References

64 references — full list in the complete paper: https://tomesphere.com/paper/PMC13008708/full.md

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Source: https://tomesphere.com/paper/PMC13008708