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

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.