(A1–A3) Chemical structures of RUT, EOD, and DHED. (B) qPCR analysis of mRNA expression for AHR target genes in mouse primary hepatocytes after treatment with the tested compounds RUT, EOD, and DHED at 5 ?M. Significance was determined by one-way analysis of variance test (*P < 0.05; **P < 0.01; ***P < 0.001 vs. vehicle group). (C–H) Luciferase assays for AHR activation in HepG2 (C–E) and Hepa-1c1c7 cells (F–H). The values are presented as the mean ± S.E.M. *P < 0.05; **P < 0.01; ***P < 0.001, compared with that of AHR-luciferase + dimethylsulfoxide, by one-way analysis of variance test.
AHR activation could trigger hepatotoxicity (Fader and you can Zacharewski, 2017), hepatic steatosis (Kawano mais aussi al., 2010), general metabolic dysfunction (Zhang mais aussi al., 2015), and you can bile acidic disruption (Gao et al., 2016). “Shennong’s Antique out-of Materia Medica,” more old natural treatments book when you look at the Asia, keeps recorded Elizabeth. rutaecarpa since producing light poisoning inside the humans (Yang, 1998). Has just, specific knowledge shown that Elizabeth. rutaecarpa government results in liver poisoning (Qi et al., 2011; Cohen mais aussi al., 2012), while anyone else discover zero high hepatotoxicity (Yang, 2008). Also, as the biggest constituents, Rut, EOD, and you can DHED was in fact and advertised to possess prospective hepatotoxicity (Zhang et al., 2011; Lin ainsi que al., 2015). Hence, whether E. rutaecarpa reasons hepatotoxicity may vary predicated on fresh requirements and you may stays debatable.
Metabolomics has been utilized to analyze alterations in endogenous metabolites after government away from conventional Chinese medication (Zhang et al., 2010a; Wang mais aussi al., 2017). Even if you to definitely study indicated that E. rutaecarpa altered endogenous metabolites (Zhang mais aussi al., 2010b), the fresh procedure of these changes as well as their part when you look at the effectiveness and toxicity will always be unexplored.