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

Background 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. Methods 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. Results 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. Conclusion 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. Systematic review registration https://inplasy.com/ , identifier INPLASY INPLASY2025120006.