Pharmacokinetics of the Yougui pill in experimental autoimmune encephalomyelitis model rats and its pharmacological activity in vitro
Authors Liu H, Qiu F, Yang X, Zhao H, Bian B, Wang L
Received 1 February 2019
Accepted for publication 17 May 2019
Published 16 July 2019 Volume 2019:13 Pages 2357—2370
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Cristiana Tanase
Haolong Liu,1,2,* Feng Qiu,1,* Xinwei Yang,1 Haiyu Zhao,3 Baolin Bian,3 Lei Wang1
1School of Traditional Chinese Medicine, Beijing Key Lab of TCM Collateral Disease Theory Research, Capital Medical University, Beijing 100069, China; 2Beijing Institute For Drug Control, Beijing Key Laboratory of Analysis and Evaluation on Chinese Medicine, Beijing 100035, China; 3Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China
*These authors contributed equally to this work
Purpose: To determine the pharmacokinetic properties and pharmacological activity of the Yougui pill (YGP), which is a well-known Chinese medicine formula.
Methods: An ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry via electrospray ionization interface (UPLC-ESI-MS/MS) method was developed and validated for the simultaneous determination of several components in rat plasma. The method was then successfully applied to the pharmacokinetics of six bioactive components in experimental autoimmune encephalomyelitis (EAE) model rats after oral administration of YGP. The expression of cAMP response element binding protein (CREB) and growth-associated protein-43 (GAP-43) in SH-SY5Y cells treated with these six components, YGP extract, and YGP-containing serum were investigated to determine the pharmacodyamic material basis of YGP. Six bioactive components were detected in rat plasma, including songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside, which were rapidly absorbed after administration in EAE model rats.
Results: The main pharmacokinetic parameters of six bioactive components were determined, and the constituents increased CREB and GAP-43 expressions in serum-deprived SH-SY5Y cells. The YGP-containing serum, six bioactive components, and YGP extract significantly increased the expression of both CREB and GAP-43 (P<0.01), and there was no difference between the three groups.
Conclusion: The songorine, benzoylhypaconitine, benzoylmesaconitine, neoline, karacoline and sweroside were confirmed as the major bioactive components in YGP. The acquired data will be helpful for understanding the pharmacological and effective constituents of YGP.
Keywords: Yougui pill, experimental autoimmune encephalomyelitis, pharmacokinetics, pharmacology
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