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Immunology and Microbiology
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Abstract
Background: Numerous studies have established a strong association between hepatocellular carcinoma (HCC) and various co-morbidity factors, including smoking. Tobacco smoke is a significant source of benzo[a]pyrene, a highly carcinogenic compound known to cause liver damage. Cucurbitacin, a triterpene with diverse biological activities, exhibits antioxidant, antiinflammatory, and anticancer effects. However, its hepatoprotective properties have not been thoroughly investigated. In this study, we aimed to evaluate the hepatoprotective effects of cucurbitacin D, a novel analog of cucurbitacin, against liver injury induced by benzo[a]pyrene in human HepG2 cells.
Method: To investigate the hepatoprotective effect of cucurbitacin D against benzo[a]pyreneinduced liver damage, proliferation, clonogenicity, migration, invasion, Western blotting, and qPCR analyses were performed. The DCFDA assay was performed to determine the level of intracellular reactive oxygen species (ROS) in liver cells.
Results: Functional assays showed that cucurbitacin D exhibited cytoprotective effects against dose-dependent growth inhibition by benzo[a]pyrene in human HepG2 cells. This protective effect was likely associated with antioxidant potential of cucurbitacin D, as evidenced by the attenuation of ROS observed by fluorimeter and fluorescence microscopy. Western blotting analysis demonstrated Cucurbitacin D targets Nrf-2 signaling pathway and associated effector proteins including HO-1 and LC3A in protecting liver cells against benzo[a]pyrene induce oxidative damage. Further studies are underway to understand the underlying molecular mechanism of action.
Conclusion: The results of this study highlight the hepatoprotective properties of cucurbitacin D against liver injury induced by benzo[a]pyrene. These findings suggest that cucurbitacin D has potential as a valuable component in nutritional supplements aimed at promoting liver health and mitigating damage from toxic exposures.
Recommended Citation
Malik, Shabnam; Sikander, Mohammed; Rodriguiez, Anyssa; Zubieta, Daniel; Esparaza, Debanhi; Halaweish, Fathi T.; Khan, Sheema; Yallapu, Murali M.; Jaggi, Meena; and Chauhan, Subhash C., "Exploring Cucurbitacin D's Protective Mechanism Against Benzo[a]pyrene-Induced Liver Injury Through Nrf2 Activation" (2025). Research Symposium. 144.
https://scholarworks.utrgv.edu/somrs/2025/posters/144
Exploring Cucurbitacin D's Protective Mechanism Against Benzo[a]pyrene-Induced Liver Injury Through Nrf2 Activation
Background: Numerous studies have established a strong association between hepatocellular carcinoma (HCC) and various co-morbidity factors, including smoking. Tobacco smoke is a significant source of benzo[a]pyrene, a highly carcinogenic compound known to cause liver damage. Cucurbitacin, a triterpene with diverse biological activities, exhibits antioxidant, antiinflammatory, and anticancer effects. However, its hepatoprotective properties have not been thoroughly investigated. In this study, we aimed to evaluate the hepatoprotective effects of cucurbitacin D, a novel analog of cucurbitacin, against liver injury induced by benzo[a]pyrene in human HepG2 cells.
Method: To investigate the hepatoprotective effect of cucurbitacin D against benzo[a]pyreneinduced liver damage, proliferation, clonogenicity, migration, invasion, Western blotting, and qPCR analyses were performed. The DCFDA assay was performed to determine the level of intracellular reactive oxygen species (ROS) in liver cells.
Results: Functional assays showed that cucurbitacin D exhibited cytoprotective effects against dose-dependent growth inhibition by benzo[a]pyrene in human HepG2 cells. This protective effect was likely associated with antioxidant potential of cucurbitacin D, as evidenced by the attenuation of ROS observed by fluorimeter and fluorescence microscopy. Western blotting analysis demonstrated Cucurbitacin D targets Nrf-2 signaling pathway and associated effector proteins including HO-1 and LC3A in protecting liver cells against benzo[a]pyrene induce oxidative damage. Further studies are underway to understand the underlying molecular mechanism of action.
Conclusion: The results of this study highlight the hepatoprotective properties of cucurbitacin D against liver injury induced by benzo[a]pyrene. These findings suggest that cucurbitacin D has potential as a valuable component in nutritional supplements aimed at promoting liver health and mitigating damage from toxic exposures.
