# Therapeutic Effects of Alkaloids on Influenza: A Systematic Review and Meta-Analysis of Preclinical Studies

## TL;DR

This study reviews preclinical evidence showing that alkaloids may help treat influenza by reducing viral load and inflammation, but more research is needed before clinical use.

## Contribution

The study provides a systematic review and meta-analysis of alkaloids' therapeutic effects on influenza in preclinical models.

## Key findings

- Alkaloids significantly correlate with reduced viral titers and improved survival rates in influenza models.
- Alkaloids do not effectively reduce TNF-α and IL-6 levels in influenza.
- Alkaloids may work by inhibiting key immune signaling pathways like TLR4/7/NF-κB and NLRP3.

## Abstract

Experimental evidence suggests that alkaloids have anti-influenza and anti-inflammatory effects. However, the risk of translating existing evidence into clinical practice is relatively high. We conducted a systematic review and meta-analysis of animal studies to evaluate the therapeutic effects of alkaloids in treating influenza, providing valuable references for future studies. Seven electronic databases were searched until October 2024 for relevant studies. The Review Manager 5.2 software was utilized to perform the meta-analysis. Our study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42024607535. Alkaloids are significantly correlated with viral titers, pulmonary inflammation scores, survival rates, lung indices, and body weight. However, alkaloid therapy is not effective in reducing the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). In addition, the therapeutic effects of alkaloids may be related to the inhibition of the Toll-like receptor 4 or 7/Nuclear factor (NF)-κB signaling pathway, NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome pathway, and the Antiviral innate immune response receptor RIG-I (RIG-I) pathway. Alkaloids are potential candidates for the prevention and treatment of influenza. However, extensive preclinical studies and clinical studies are needed to confirm the anti-influenza and anti-inflammatory properties of alkaloids.