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<p>Hepatocellular carcinoma (HCC) is a rising worldwide health problem characterized by high mortality. The presence of early asymptomatic phases, the delay in diagnosis, and limited options for curative surgical interventions all enhanced its severity. Various contributing factors, including HBV, chronic alcohol consumption, exposure to aflatoxin, smoking, and others, lead to the development of HCC. ROS and ROS-driven inflammation play a critical role in hepatocarcinogenesis by activating tumor-promoting signaling pathways and changes the tumor microenvironment (TME) through inducing fibrogenic programming. Dynamic interactions among tumor cells, stromal components, and immune cells inside the TME create an immunosuppressive, pro-carcinogenic milieu conducive to tumor progression through immune evasion. In addition, ECM remodelling further enhances the tumor aggressiveness. Natural compounds, especially honey, have been investigated as potential complementary agent in preclinical and mechanistic studies. Honey is a complex natural matrix rich in flavonoids and polyphenols. It scavenges ROS, re-establishing redox homeostasis which eventually shut down ROS-mediated inflammatory pathways. Preclinical evidences demonstrate that honey influences tumor growth through repression of tumor-promoting routes, including PI3K/Akt/mTOR and Wnt/β-catenin signaling, and promotes the mitochondrial-mediated apoptosis. Experimental studies suggested that honey and its flavonoids offer a multidisciplinary approach for HCC management and chemosensitization in association with modern chemotherapeutic agents such as sorafenib, doxorubicin, cisplatin, 5-FU, and PD-1/PD-L1 blockade. This systematic review, covering studies from 2017 to 2025, brings the current molecular and immunological evidence which highlights their relevance for clinical translation. Upcoming studies need to prioritize the standardization of honey-based formulations, the optimization of delivery systems, and the implementation of rigorous clinical trials to evaluate safety, dosing parameters, and therapeutic efficacy.</p><p><b>Clinical trial number</b>: Not applicable.</p>

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Molecular and immunological insights into honey as a complementary approach in hepatocellular carcinoma: a systematic review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Sheetal Kundu,
  • Rajesh Kumar

摘要

Hepatocellular carcinoma (HCC) is a rising worldwide health problem characterized by high mortality. The presence of early asymptomatic phases, the delay in diagnosis, and limited options for curative surgical interventions all enhanced its severity. Various contributing factors, including HBV, chronic alcohol consumption, exposure to aflatoxin, smoking, and others, lead to the development of HCC. ROS and ROS-driven inflammation play a critical role in hepatocarcinogenesis by activating tumor-promoting signaling pathways and changes the tumor microenvironment (TME) through inducing fibrogenic programming. Dynamic interactions among tumor cells, stromal components, and immune cells inside the TME create an immunosuppressive, pro-carcinogenic milieu conducive to tumor progression through immune evasion. In addition, ECM remodelling further enhances the tumor aggressiveness. Natural compounds, especially honey, have been investigated as potential complementary agent in preclinical and mechanistic studies. Honey is a complex natural matrix rich in flavonoids and polyphenols. It scavenges ROS, re-establishing redox homeostasis which eventually shut down ROS-mediated inflammatory pathways. Preclinical evidences demonstrate that honey influences tumor growth through repression of tumor-promoting routes, including PI3K/Akt/mTOR and Wnt/β-catenin signaling, and promotes the mitochondrial-mediated apoptosis. Experimental studies suggested that honey and its flavonoids offer a multidisciplinary approach for HCC management and chemosensitization in association with modern chemotherapeutic agents such as sorafenib, doxorubicin, cisplatin, 5-FU, and PD-1/PD-L1 blockade. This systematic review, covering studies from 2017 to 2025, brings the current molecular and immunological evidence which highlights their relevance for clinical translation. Upcoming studies need to prioritize the standardization of honey-based formulations, the optimization of delivery systems, and the implementation of rigorous clinical trials to evaluate safety, dosing parameters, and therapeutic efficacy.

Clinical trial number: Not applicable.