Maier I. Synergistic antitumor effects of quercetin and triptolide in hepatocellular carcinoma via modulation of PI3K/AKT/mTOR and Nrf2 signaling pathways. World J Gastroenterol 2026; 32(33): 118638 [DOI: 10.3748/wjg.118638]
Corresponding Author of This Article
Irene Maier, PhD, Researcher, Department of Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria. irene.maier@meduniwien.ac.at
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Pathology
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review-article
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Maier I. Synergistic antitumor effects of quercetin and triptolide in hepatocellular carcinoma via modulation of PI3K/AKT/mTOR and Nrf2 signaling pathways. World J Gastroenterol 2026; 32(33): 118638 [DOI: 10.3748/wjg.118638]
World J Gastroenterol. Sep 7, 2026; 32(33): 118638 Published online Sep 7, 2026. doi: 10.3748/wjg.118638
Synergistic antitumor effects of quercetin and triptolide in hepatocellular carcinoma via modulation of PI3K/AKT/mTOR and Nrf2 signaling pathways
Irene Maier
Irene Maier, Department of Internal Medicine I, Medical University of Vienna, Vienna A-1090, Austria
Author contributions: Maier I conceived and designed the study, conducted the literature review, prepared the figures, and drafted and revised the manuscript.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
Corresponding author: Irene Maier, PhD, Researcher, Department of Internal Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, Vienna A-1090, Austria. irene.maier@meduniwien.ac.at
Received: January 7, 2026 Revised: March 28, 2026 Accepted: May 9, 2026 Published online: September 7, 2026 Processing time: 214 Days and 8.2 Hours
Abstract
Phytochemicals derived from traditional Chinese medicine have demonstrated therapeutic potential in liver cancer. Among these, quercetin has been reported to modulate immunosuppressive mechanisms and attenuate liver injury and carcinogenesis. This review focuses on the synergistic effects of triptolide (TP) and quercetin, particularly their co-inhibitory actions on cell proliferation and the mammalian target of rapamycin signaling pathway in preclinical studies. Quercetin administration (80 mg/kg) reduced serum alanine aminotransferase and aspartate aminotransferase levels, as well as biomarkers for oxidative stress. It also mitigated TP-induced inhibition of the protein kinase B/mammalian target of rapamycin pathway and reversed excessive ferroptosis, as evidenced by decreased Fe2+ accumulation and lipid peroxidation (malondialdehyde). In contrast, hepatic glutathione and superoxide dismutase levels were elevated, along with enhanced nuclear expression of nuclear factor erythroid 2-related factor 2. Moreover, mRNA expression of heme oxygenase-1, nicotinamide adenine dinucleotide (phosphate) hydrogen dehydrogenase (quinone) 1, and glutamate-cysteine ligase catalytic subunit was upregulated. Collectively, these findings suggest that quercetin attenuates TP-induced immunological liver injury via activation of the nuclear factor erythroid 2-related factor 2/antioxidant response element signaling pathway. Compared with monotherapy, the combination of TP and quercetin shows enhanced antitumor effects by inhibiting cell proliferation, inducing apoptosis through transcriptional regulation, and suppressing migration and invasion.
Core Tip: The combination of quercetin and triptolide demonstrates enhanced antitumor effects by reducing tumor growth and oxidative stress while modulating the protein kinase B/mammalian target of rapamycin signaling pathway. Plant-derived bioactive compounds and herbal formulations have shown promise in hepatocellular carcinoma therapy, particularly in combination regimens that exert anticancer and anti-inflammatory effects through modulation of the tumor microenvironment. Quercetin may also inhibit triptolide-induced liver injury and carcinogenesis by regulating the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway, which is associated with cell proliferation.
