Jun Zhang, Dandan Wang, Liwei Zou, Min Xiao, Yufeng Zhang, Ziwei Li, Ling Yang, Guangbo Ge, Zhong Zuo. Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines[J]. Journal of Pharmaceutical Analysis, 2020, 10(3): 253-262.
Citation: Jun Zhang, Dandan Wang, Liwei Zou, Min Xiao, Yufeng Zhang, Ziwei Li, Ling Yang, Guangbo Ge, Zhong Zuo. Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines[J]. Journal of Pharmaceutical Analysis, 2020, 10(3): 253-262.

Rapid bioluminescence assay for monitoring rat CES1 activity and its alteration by traditional Chinese medicines

  • Publish Date: Jun. 15, 2020
  • In traditional Chinese medicine herbs (TCM), including Radix Salviae Miltiorrhizae (Danshen), Radix Puerariae Lobatae (Gegen), Radix Angelicae Sinensis (Danggui), and Rhizoma Chuanxiong (Chuanxiong) are widely used for the prevention and treatment of cardiovascular diseases and also often co-administered with Western drugs as a part of integrative medicine practice. Carboxylesterase 1 (CES1) plays a pivotal role in the metabolisms of pro-drugs. Since (S)-2-(2-(6-dimethylamino)-benzothiazole)-4,5-dihydro-thiazole-4-carboxylate (NLMe) has recently been identified by us as a selective CES1 bioluminescent sensor, we developed a rapid method using this substrate for the direct measurement of CES1 activity in rats. This bioluminescence assay was applied to determine CES1 activity in rat tissues after a two-week oral administration of each of the four herbs noted above. The results demonstrated the presence of CES1 enzyme in rat blood and all tested tissues with much higher enzyme activity in the blood, liver, kidney and heart than that in the small intestine, spleen, lung, pancreas, brain and stomach. In addition, the four herbs showed tissue-specific effects on rat CES1 expression. Based on the CES1 biodistribution and its changes after treatment in rats, the possibility that Danshen, Gegen and Danggui might alter CES1 ac-tivities in human blood and kidney should be considered. In summary, a selective and sensitive biolu-minescence assay was developed to rapidly evaluate CES1 activity and the effects of orally administered TCMs in rats.
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