# Evaluation of Andrographis paniculata in a mouse model of influenza A viral infection using oral administration and a translationally relevant dose

**Authors:** Kashif Shamim, Grace C. Burnett, Jin Zhang, Nessma H. Ahmed, Shabana I. Khan, Amar G. Chittiboyina, Ikhlas A. Khan, Gailen D. Marshall, John T. Bates, Nirmal D. Pugh

PMC · DOI: 10.3389/fphar.2026.1749384 · Frontiers in Pharmacology · 2026-02-05

## TL;DR

This study evaluates the effects of Andrographis paniculata extract on influenza in mice using a clinically relevant dose and oral administration.

## Contribution

The study uses a translationally relevant mouse model and oral administration to assess the antiviral effects of a standardized Andrographis extract.

## Key findings

- Oral administration of the extract reduced lung viral load in mice by five-fold by day 3 post-infection.
- The extract inhibited NF-κB and iNOS while activating Nrf2, suggesting anti-inflammatory and antioxidant effects.

## Abstract

Ethnobotanically, Andrographis paniculata aerial parts have been used to alleviate the symptoms of viral infections, colds, and sore throats. Although the utility of Andrographis for these indications has had widespread acceptance, multiple knowledge gaps, regarding mechanisms and specific clinical applications, exist for this botanical. Prior rodent studies have limited applicability to inform future clinical applications due to routes of administration used, nonclinical high doses tested, and exclusive evaluation of chemically purified compounds.

Experiments used a commercial extract of A. paniculata manufactured from aerial parts that was standardized to contain ≥10% andrographolides. In vitro evaluation measured NF-κB in THP-1 monocytes, iNOS in RAW 264.7 macrophages and Nrf2 in HepG2 cells. In vivo research used a non-lethal influenza A mouse model with two groups (A. paniculata treatment and vehicle control). Following infection, mice were gavaged daily for 8 days–treatment group received 250 mg extract/kg body weight (dose equivalent to the human label-recommended daily intake).

The extract inhibited NF-κB and iNOS while activating Nrf2. Although andrographolide contributed to these effects, the findings indicate the presence of additional active constituents that have not yet been characterized. In the mouse model, oral administration of the extract produced a roughly five-fold reduction in lung viral load by day 3 post-infection (p < 0.021) compared with control animals.

Based on the clinically relevant design of our mouse model, the results lay the groundwork for future preclinical research to determine optimal treatment schedule/dosage and immune mechanisms, thereby informing the design for future resilience efficacy clinical trials.

## Linked entities

- **Genes:** NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790], NOS2 (nitric oxide synthase 2) [NCBI Gene 4843], GABPA (GA binding protein transcription factor subunit alpha) [NCBI Gene 2551]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** 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}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}, Nos2 (nitric oxide synthase 2, inducible) [NCBI Gene 18126] {aka MAC-NOS, NOS-II, Nos-2, Nos2a, i-NOS, iNOS}
- **Diseases:** irritation (MESH:D001523), influenza (MESH:D007251), loss (MESH:D016388), inflammation (MESH:D007249), fever (MESH:D005334), paralysis (MESH:D010243), weight loss (MESH:D015431), infected (MESH:D007239), influenza A viral infection (MESH:D014777), sore throat (MESH:D010612), cytokine storm (MESH:D000080424)
- **Chemicals:** Andrographolide (MESH:C030419), 14-deoxy-11,12-didehydroandrographolide (MESH:C495626), Immulina (MESH:C459207), ethanol (MESH:D000431), nitric oxide (MESH:D009569), water (MESH:D014867), 14-deoxyandrographolide (MESH:C114791), Curcumin (MESH:D003474), A. paniculata (-), Parthenolide (MESH:C002669), neoandrographolide (MESH:C082497), DMSO (MESH:D004121), LPS (MESH:D008070), sucrose (MESH:D013395)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Escherichia coli (E. coli, species) [taxon 562], Homo sapiens (human, species) [taxon 9606], Staphylococcus aureus (species) [taxon 1280], Arthrospira (genus) [taxon 35823], Influenza A virus (no rank) [taxon 11320], Andrographis paniculata (species) [taxon 175694]
- **Cell lines:** HepG2 — Homo sapiens (Human), Hepatoblastoma, Cancer cell line (CVCL_0027), RAW 264.7 — Mus musculus (Mouse), Mouse leukemia, Cancer cell line (CVCL_0493), THP-1 — Homo sapiens (Human), Childhood acute monocytic leukemia, Cancer cell line (CVCL_0006)

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12916569/full.md

## References

27 references — full list in the complete paper: https://tomesphere.com/paper/PMC12916569/full.md

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Source: https://tomesphere.com/paper/PMC12916569