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Int. J. Mol. Sci. 2018, 19(1), 305; https://doi.org/10.3390/ijms19010305

Compatibility with Panax notoginseng and Rehmannia glutinosa Alleviates the Hepatotoxicity and Nephrotoxicity of Tripterygium wilfordii via Modulating the Pharmacokinetics of Triptolide

1
Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China
2
Department of Pharmacology, School of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Rd., Nanjing 210023, China
3
Jiangsu Key Laboratory for High Technology Research of Traditional Chinese Medicine Formulae, 138 Xianlin Rd., Nanjing University of Chinese Medicine, Nanjing 210023, China
*
Author to whom correspondence should be addressed.
Received: 7 December 2017 / Revised: 6 January 2018 / Accepted: 11 January 2018 / Published: 19 January 2018
(This article belongs to the Special Issue Traditional Medicine – Unraveling Its Molecular Mechanism)
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Abstract

Tripterygium wilfordii (TW) and the representative active component triptolide show positive therapeutic effect on the autoimmune disorders and simultaneously ineluctable hepatotoxicity and nephrotoxicity. Combinational application of Panax notoginseng (PN) and Rehmannia glutinosa (RG) weakens the toxicity of TW according the clinical application of traditional Chinese medicine. This article was aimed at the mechanism of decreasing toxicity of TW by the combinational application of PN and RG. Biochemical and pathohistological analysis were utilized to assess the toxicity on liver and kidney in rats administrated with TW, TW-PN, TW-RG and TW-PN-RG for 3 and 7 days. Meanwhile, the pharmacokinetics profiling of triptolide and wilforlide A was determined based on the plasma concentration analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). TW-induced alkaline phosphatase (ALP), the marker for liver injury, was enhanced from 22.83 ± 1.29 to 40.73 ± 1.42 King’s unit/100 mL (p < 0.01) at day 7. TW-PN-RG decreased the serum ALP of TW-treated rats at 30.15 ± 1.27 King’s unit/100 mL (p < 0.01). For nephrotoxicity, TW pronouncedly elevated serum creatinine (SCr) in rats from 20.33 ± 1.77 to 49.82 ± 2.35 μmol/L (p < 0.01). However, rats treated with TW-PN-RG showed lower SCr at 30.48 ± 1.98 μmol/L (p < 0.01). Moreover, TW-PN-RG significantly decreased the TW-induced elevation of total bilirubin (T-BIL), alanine amino transferase (ALT), aspartate amino transferase (AST), blood urea nitrogen (Bun), and reversed the TW-resulted pathohistological characteristics of liver and kidney. The delayed time to reach Cmax (Tmax) and reduced maximum concentration (Cmax) and area under plasma concentration-time curve (AUC) of triptolide and wilforlide A were explored in rats with combinational formulas. Synergism of PN and RG obviously prolonged the half-life (t1/2) and apparent volume of distribution (Vd), but exerted no action on the clearance rate. The compatibility of TW, PN and RG influences intracorporal process of both triptolide and wilforlide A on the steps of absorption and tissue distribution contributing to less toxicity of TW on liver and kidney. View Full-Text
Keywords: Tripterygium wilfordii; triptolide; hepatotoxicity; nephrotoxicity; pharmacokinetics Tripterygium wilfordii; triptolide; hepatotoxicity; nephrotoxicity; pharmacokinetics
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, Q.; Li, Y.; Liu, M.; Duan, J.; Zhou, X.; Zhu, H. Compatibility with Panax notoginseng and Rehmannia glutinosa Alleviates the Hepatotoxicity and Nephrotoxicity of Tripterygium wilfordii via Modulating the Pharmacokinetics of Triptolide. Int. J. Mol. Sci. 2018, 19, 305.

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