# Ficus pandurata as a Functional Phytotherapeutic: Inhibiting JAK2/STAT3 Signaling and Activating Mitochondrial Apoptosis in Hepatocellular Carcinoma

## TL;DR

Ficus pandurata extract shows promise as a natural treatment for liver cancer by triggering cell death and reducing inflammation.

## Contribution

The study identifies Ficus pandurata as a dual-action phytotherapeutic targeting both apoptosis and inflammation in liver cancer.

## Key findings

- FPHPE inhibited growth of multiple liver cancer cell lines and suppressed tumor growth in mice.
- FPHPE activated mitochondrial apoptosis and reduced JAK2/STAT3 signaling and inflammatory markers.
- The extract showed no systemic toxicity in the xenograft mouse model.

## Abstract

Chronic inflammation plays a key role in the development of hepatocellular carcinoma (HCC), one of the most prevalent and lethal forms of liver cancer. This study aimed to evaluate the anti‐HCC potential of the petroleum ether extract of Ficus pandurata Hance (FPHPE), a traditional hepatoprotective herb, focusing on its pro‐apoptotic and anti‐inflammatory actions via the JAK2/STAT3 signaling pathway. In vitro experiments demonstrated significant growth inhibition of HepG2, SMMC7721, and Hep3B cells following FPHPE treatment. GC–MS profiling identified 26 phytoconstituents, including friedelane, seseline, bergaptan, and tocopherols, many with known bioactivity. In a xenograft mouse model, FPHPE markedly suppressed tumor growth without causing systemic toxicity. Mechanistic analyses demonstrated that FPHPE activated mitochondria‐mediated apoptosis, as confirmed by Annexin V/PI flow cytometry, Western blot quantification from three biological replicates, TEM imaging showing disrupted cristae, and JC‐1 staining revealing mitochondrial membrane depolarization. Concurrently, FPHPE downregulated phosphorylated and total JAK2/STAT3, inhibited STAT3 nuclear translocation, and suppressed key downstream effectors (iNOS, COX2, c‐Myc, Vimentin, and Slug). ELISA further confirmed a reduction of pro‐inflammatory cytokines TNF‐α and IL‐1β in tumor tissues. Together, these findings establish FPHPE as a dual‐action phytotherapeutic candidate that interrupts both survival and inflammatory pathways, positioning
F. pandurata
as a promising source for nutraceuticals or complementary therapies against inflammation‐driven liver cancer.

Triterpenoid‐ and coumarin‐rich Ficus pandurata Hance petroleum ether extract (FPHPE) significantly inhibited HepG2, SMMC7721, and Hep3B proliferation and suppressed tumor burden in xenograft mice without systemic toxicity. Comprehensive validation confirmed mitochondria‐mediated apoptosis through Annexin V/PI flow cytometry, Western blot, TEM visualization of cristae disruption, and JC‐1 detection of membrane depolarization. Mechanistically, FPHPE inhibited JAK2/STAT3 signaling, prevented STAT3 nuclear translocation, and downregulated oncogenic and inflammatory mediators (c‐Myc, iNOS, COX2, Vimentin, Slug, TNF‐α, IL‐1β), supporting its potential as a functional nutraceutical.