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Wogonin alleviates BaP-induced DNA damage and oxidative stress in human airway epithelial cells by dual inhibiting CYP1A1 activity and expression.
Ni, Zhenhua; Ma, Honghong; Li, Xiaodong; Zou, Liwei; Liu, Zongjun; Wang, Xiongbiao; Ma, Hong; Yang, Ling.
Afiliación
  • Ni Z; Center for Systems Pharmacokinetics, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Ma H; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Li X; Center for Systems Pharmacokinetics, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Zou L; Center for Systems Pharmacokinetics, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Liu Z; Center for Systems Pharmacokinetics, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Wang X; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Ma H; Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Yang L; Shanghai Institute of Acupuncture and Meridian, Shanghai, China.
Environ Toxicol ; 38(11): 2717-2729, 2023 Nov.
Article en En | MEDLINE | ID: mdl-37515497
Benzo[a]pyrene (BaP) is a common air pollutant that has been reported to cause oxidative stress and carcinogenesis. Wogonin, a flavonoid compound extracted from the roots of Scutellaria baicalensis, has been found to possess a variety of pharmacological activities, including anti-inflammatory and anti-cancer effects. The purpose of this study was to examine the ability of wogonin to alleviate the cytotoxicity induced by BaP in human airway epithelial cells and explore the corresponding mechanism. Our study found that wogonin treatment inhibited DNA damage and reactive oxygen species overproduction induced by BaP in human airway epithelial cells. In vitro enzyme assays showed that wogonin significantly inhibited the enzymatic activity of CYP1A1. In addition, wogonin decreased the basal level of CYP1A1 and inhibited the CYP1A1 overexpression induced by BaP, whereas overexpression of CYP1A1 partially reversed the effect of wogonin on BaP-induced DNA damage. Meanwhile, a CYP1A1 inhibitor and CYP1A1 knockdown also showed these same effects. Further studies showed that wogonin regulates CYP1A1 expression by inhibiting CDK7 and CDK9 activity. The use of CDK7 or CDK9 inhibitors decreased BaP-induced cytotoxicity and CYP1A1 expression. Finally, we found that the methoxy group of wogonin was crucial for its inhibitory activity. In conclusion, our data indicated that wogonin could effectively relieve BaP induced cytotoxicity, and its mechanism was related to the dual inhibition of CYP1A1 activity and expression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Environ Toxicol Asunto de la revista: SAUDE AMBIENTAL / TOXICOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos