The crucial involvement of gamma-Mangostin and CYP1B1 in the mechanism underlying the toxicity caused by cigarette smoke extract: In silico and in vitro insights
》》Journal：Toxicology.
》》相关产品： Gamma-Mangostin (SJ-MN0904)
》》产品引用描述：
》》Abstract：
Cigarette smoke extracts (CSE) contain harmful substances that significantly contribute to respiratory conditions. Previous studies have primarily focused on the presence of carcinogens in CSE. However, it should be noted that other compounds may also synergistically contribute to a greater impact. This study proposes an innovative collaboration between natural products in CSE and carcinogens to enhance CSE-induced acute toxicity. Bioinformatics analysis coupled with experimental validation have elucidated the pivotal role of CYP1B1 in CSE-induced acute toxicity. Inhibitors targeting CYP1B1 have demonstrated preferential cytotoxicity towards cells exhibiting elevated levels of CYP1B1 expression. Afterwards, we conducted a virtual screening of the CSE composition database to identify a potential inhibitor for CYP1B1. After analyzing docking scores and complex interaction modes, γ-mangostin emerged as a highly promising CYP1B1 inhibitor. Molecular docking and dynamics were used to elucidate the complex structure formed between γ-mangostin and CYP1B1. Further investigations suggest that γ-mangostin can synergistically interact with carcinogens in CSE, causing cellular harm and contributing significantly to acute toxicity induced by CSE. Furthermore, γ-mangostin showed increased affinity towards CYP1B1 variants L432V and N453S, suggesting that organisms with these genetic variations may be more susceptible to cell damage caused by CSE. These new perspectives enhance our understanding of the mechanism behind acute toxicity associated with CSE and offer new possibilities for improving preventive measures and treatment strategies.
》》部分实验数据展示：
Figure 6. The synergistic effect of γ-mangostin enhances the acute toxicity of CSE. (A) Variation in cell viability of A549 cells after exposure to γ-mangostin with different concentrations for 24 h. (B) The difference in cytotoxicity of CSE on the cell viability of A549 cell lines when γ-mangostin and CSE were co-administered. (C) The difference in cytotoxicity of CSE on the cell viability of A549 cell lines when TMS (1 µm) and CSE were co-administered. (D) The protein expression changes of CYP1B1 and γ-H2AX when γ-mangostin and CSE (10 %) were co-administered.
