Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways
Abstract
:1. Introduction
2. B[a]P-Induced Oxidative Liver Damage
2.1. Oxidative Damage Induced by B[a]P in the Liver
2.2. Metabolism and Excretion of B[a]P and Their Hepatic Consequences
3. Hepatoprotective Potential of Flavonoids against B[a]P-Induced Liver Damage
3.1. Classification of Flavonoids
3.2. Antioxidant Effects of Flavonoids and B[a]P in the Liver
Flavonoid | ROS | MDA | Antioxidant Enzyme | NRF2 Regulator | Refs. | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
NRF2 | HO1 | NQO | SOD | CAT | GSH | GPX | ||||||
Anthocyanidin | Pelargonidin | ↓ | ↓ | ↑ | ↑ | ↑ | [77] | |||||
Cyanidin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | [78] | |||
↓ | ↑ | ↑ | JNK↓ | [79] | ||||||||
Delphinidin | ↓ | ↑ | ↑ | ↑ | Keap1↓ | [80] | ||||||
↓ | ↑ | PI3K/Akt↑ | [81] | |||||||||
↑ | ↑ | [82] | ||||||||||
Chalcone | Phloretin | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | AMPK↑ Keap1↓ | [83] | |||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | AMPK↑ | [84] | |||||
↓ | ↑ | ↑ | ↑ | ERK↑ | [85] | |||||||
Xanthohumol | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | AKT↑ AMPK↑ | [86] | ||||
↓ | ↓ | ↑ | ↑ | ↑ | [87] | |||||||
Flavonols | Quercetin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | Keap1↓ | [88] | ||
↓ | ↓ | ↑ | NF-kB↓ | [89] | ||||||||
↓ | ↓ | ↑ | ↑ | ↑ | NF-kB↓ | [90] | ||||||
Kaempferol | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | [91] | |||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [92] | |||||
↓ | ↓ | ↑ | ↑ | ↑ | AMPK↑ | [93] | ||||||
↓ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | AKT↑ | [94] | ||||
↓ | ↑ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [95] | |||||
Rutin | ↓ | ↑ | ↑ | [96] | ||||||||
↓ | ↑ | ↑ | ↑ | [97] | ||||||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | [98] | |||||
Myricetin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [99] | |||
↓ | ↓ | ↑ | ↑ | [100] | ||||||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | AMPK↑ | [101] | |||||
Isorhamnetin | ↓ | ↑ | [102] | |||||||||
Flavanone | Naringenin | ↓ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [103] | ||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | SIRT1↑ | [104] | |||||
↓ | ↑ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [105] | |||||
Hesperidin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | Keap1↓ | [106] | ||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [107] | ||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [108] | |||||
↓ | ↑ | ↑ | MAPK↑ | [109] | ||||||||
Eriodictyol | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | [110] | ||||
Flavanonols | Taxifolin | ↓ | ↓ | ↑ | ↑ | NF-kB↓ | [111] | |||||
Flavones | Apigenin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [112] | |
↓ | ↓ | ↑ | ↑ | NF-kB↓ | [113] | |||||||
Wogonin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [114] | ||||
Luteolin | ↓ | ↑ | ↑ | ↑ | ↑ | NF-kB↓ | [115] | |||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | KEAP↓ | [116] | ||
↓ | ↑ | [117] | ||||||||||
Tangeretin | ↓ | ↑ | ↑ | ↑ | ↑ | MAPK↑ | [118] | |||||
Chrysin | ↓ | ↓ | ↑ | ↑ | ↑ | ↑ | [119] | |||||
Isoflavonoids | Genistein | ↓ | ↑ | ↑ | [120] | |||||||
Daidzein | ↓ | ↑ | [121] | |||||||||
↓ | ↓ | ↑ | ↑ | ↑ | ↑ | [122] |
3.3. Regulation of B[a]P Metabolism by Flavonoids in the Liver
Flavonoid | Phase I Enzyme | Phase II Enzyme | Phase III Enzyme | B[a]P | Refs. | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
AhR | CYP1A1 | CYP1B1 | Other CYPs | NRF2 | PXR | GST | UGT | Metabolism | Detoxification | ||||
Anthocyanidin | Pelargonidin | ↑ | ↑ | CYP1A2↑ | [132] | ||||||||
Chalcone | Phloretin | CYP1A2↓ CYP3A4↓ | ↑ | ↑ | [133] | ||||||||
↑ | [134] | ||||||||||||
Flavonols | Quercetin | ↑ | [135] | ||||||||||
↑ | CYP2↑ CYP3↑ | [136] | |||||||||||
↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ABCC1↑ | ↑ | ↑ | [51] | ||||
Kaempferol | ↓ | ↓ | CYP1A2↓ | [137] | |||||||||
CYP2E1↓ | [138] | ||||||||||||
↓ | ↓ | ↓ | ↓ | ↓ | ↓ | [126] | |||||||
Rutin | ↑ | ↑ | [139] | ||||||||||
↑ | CYP1A2↑ | [140] | |||||||||||
CYP2E1↑ | ↑ | [141] | |||||||||||
Myricetin | CYP2C8↓ | [142] | |||||||||||
↓ | ↑ | ↓ | ↑ | [108] | |||||||||
Isorhamnetin | ↑ | ↑ | ↑ | ↑ | ↑ | ↑ | ABCC1↑ | ↑ | ↑ | [51] | |||
Flavanone | Eriodictyol | CYP2E1↓ CYP3A11↓ | ↑ | ↑ | [143] | ||||||||
Sakuranetin | CYP1A2↓ CYP2C9↓ | ↑ | ↓ | [144] | |||||||||
Flavanonols | Taxifolin | CYP2E1↓ CYP1A2↓ CYP3A4↓ | ↑ | [145] | |||||||||
Flavones | Apigenin | CYP4F2↓ | [146] | ||||||||||
↓ | ↓ | ↓ | Total contents↓ | ↑ | ↓ | ↑ | [127] | ||||||
Wogonin | ↓ | ↓ | [129] | ||||||||||
↓ | CYP2E1↓ | n.s. | ↓ | n.s. | [128] | ||||||||
Luteolin | CYP1A2↓ CYP3A4↓ | ↓ | [147] | ||||||||||
ABCA1↑ | [148] | ||||||||||||
↓ | ↓ | ↓ | ↓ | ↓ | ↓ | [126] | |||||||
Tangeretin | ↓ | ↓ | CYPs↓ | ↑ | [149] | ||||||||
Chrysin | ↑ | [150] | |||||||||||
CYP2E1↑ | ↑ | [151] | |||||||||||
↑ | n.s. | ↑ | ↑ | ↑ | [130] | ||||||||
Isoflavonoids | Genistein | ↑ | ↑ | [152] | |||||||||
↓ | ↓ | [153] | |||||||||||
↑ | ↑ | [154] | |||||||||||
↑ | [155] | ||||||||||||
Daidzein | ↑ | ↑ | [154] | ||||||||||
↑ | ↑ | [156] |
3.4. B[a]P-Induced Liver Disease and Flavonoid
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Kim, M.; Jee, S.-C.; Sung, J.-S. Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways. Antioxidants 2024, 13, 180. https://doi.org/10.3390/antiox13020180
Kim M, Jee S-C, Sung J-S. Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways. Antioxidants. 2024; 13(2):180. https://doi.org/10.3390/antiox13020180
Chicago/Turabian StyleKim, Min, Seung-Cheol Jee, and Jung-Suk Sung. 2024. "Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways" Antioxidants 13, no. 2: 180. https://doi.org/10.3390/antiox13020180
APA StyleKim, M., Jee, S.-C., & Sung, J.-S. (2024). Hepatoprotective Effects of Flavonoids against Benzo[a]Pyrene-Induced Oxidative Liver Damage along Its Metabolic Pathways. Antioxidants, 13(2), 180. https://doi.org/10.3390/antiox13020180