Login Register Cart 0
Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

The Metabolic Pathways and Products of Ten Aconitum Alkaloids in Sanwujiao Pills from Eight Organs of Mice by UHPLC-Q-TOF-MS/MS

Author(s): Wen-Han Pei, Yu-Feng Huang, Ying Xie, Yuan Qu, Fan He* and Hua Zhou*

Volume 24, Issue 4, 2023

Published on: 12 June, 2023

Page: [290 - 302] Pages: 13

DOI: 10.2174/1389200224666230505122353

Price: $65

Abstract

Background: Sanwujiao pill (SWJP) is a Chinese herbal preparation widely used in China. It is an essential medicine for treating rheumatism and blood stasis. However, its safety in clinical use has always been the focus of patients because it contains toxic herbs of Aconitum carmichaelii Debx. and A. vilmorinianum Kom.

Objective: To further reveal the pharmaceutical and toxic effect substances and the action mechanism of SWJPs, the metabolites and their pathways of ten Aconitum alkaloids (AAs) in the preparation at different time points after oral administration in eight organs of mice were investigated.

Method: The biosamples were investigated by a four-step strategy of UPLC-Q-TOF-MS /MS technology.

Results: Aconitine (AC), mesaconitine (MA), and hypaconitine (HA) were not detected in any organs. The highest concentrations of the other seven AAs occurred at 0.5 h. Yunaconitine (YAC) was not detected in the brain; all seven AAs had the lowest concentration in the brain, and the metabolism was slow in the stomach. Twelve predicted metabolites were identified, the kidney and stomach were their primary distribution locations, and the most metabolites were found at 0.5h. The main metabolic pathways of the ten AAs were demethylation, deethylation, deoxygenation, hydroxylation, and deacetylation.

Conclusion: This is the first report about the metabolism of ten AAs in SWJPs in mice. Significantly, the metabolic pathways and products of four hidden toxic AAs were analyzed in vivo for the first time. The results were of great significance for the safety and effectiveness of SWJPs in clinical application.

« Previous Next »
Graphical Abstract

[1]
Ministry of Health. PRC. Formulation of Traditional Chinese Medicine. Pharmaceutical Standard of Ministry of Health of the People’s Republic of China, 1992, 20, Z20-Z11.
[2]
Xiao, S.Y.; Luo, C.Q.; Lv, D.; Wang, C.X.; Cui, X.M. Preparation of Sanwujiao extract-hydrogel and its therapeutic effect on rheumatoid arthritis. Chin. Tradit. Herbal Drugs, 2022, 53(13), 3929-3939.
[3]
Wen, J.; Liu, X.L.; Zhu, L.M.; Xiao, J.J.; Li, Q.D. Study on antiinflammatory analgesic anti-immune pharmaco-logical actions of Sanwu con-centrated decoction. Zhongchengyao, 2002, (06), 37-39.
[4]
Wen, J.; Cai, W. F.; Qin, J. Experimental study on the effect of Sanwu Jiao on hemorheology of acute "blood stasis" syndrome in rats. Yunnan J. Trad. Chin. Med. Materia Medica, 2002, (02), 32-33.
[http://dx.doi.org/10.16254/j.cnki.53-1120/r.2002.02.036]
[5]
Yu, Z.C.; Yang, Y.; Lu, Y.H. Experimental study on the effects of San-wu Jiao on hemodynamics and electr-ocardiogram. Yunnan J. Tradit. Chin. Med. Materia Medica, 2001, (04), 39-40.
[http://dx.doi.org/10.16254/j.cnki.53-1120/r.2001.04.044]
[6]
Huang, Y.F.; He, F.; Cui, H.; Zhang, Y.Y.; Yang, H.Y.; Liang, Z.S.; Dai, W.; Cheng, C.S.; Xie, Y.; Liu, L.; Liu, Z.Q.; Zhou, H. Systematic investigation on the distribution of four hidden toxic Aconitum alkaloids in commonly used Aconitum herbs and their acute toxicity. J. Pharm. Biomed. Anal., 2022, 208, 114471.
[http://dx.doi.org/10.1016/j.jpba.2021.114471] [PMID: 34814080]
[7]
Deng, J.; Han, J.; Chen, J.; Zhang, Y.; Huang, Q.; Wang, Y.; Qi, X.; Liu, Z.; Leung, E.L.H.; Wang, D.; Feng, Q.; Lu, L. Comparison of analgesic activities of aconitine in different mice pain models. PLoS One, 2021, 16(4), e0249276.
[http://dx.doi.org/10.1371/journal.pone.0249276] [PMID: 33793632]
[8]
Li, S.; Li, R.; Zeng, Y.; Meng, X.L.; Wen, C.B.; Zheng, S.C. Chemical components and pharmacological action of Aconiti Radix. Zhongguo Zhongyao Zazhi, 2019, 44(12), 2433-2443.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20190221.004] [PMID: 31359708]
[9]
Li, L.; Zhang, L.; Liao, T.; Zhang, C.; Chen, K.; Huang, Q. Advances on pharmacology and toxicology of aconitine. Fundam. Clin. Pharmacol., 2022, 36(4), 601-611.
[http://dx.doi.org/10.1111/fcp.12761] [PMID: 35060168]
[10]
Mi, L.; Li, Y.C.; Sun, M.R.; Zhang, P.L.; Li, Y.; Yang, H. A systematic review of pharmacological activities, toxicological mechanisms and pharmacokinetic studies on Aconitum alkaloids. Chin. J. Nat. Med., 2021, 19(7), 505-520.
[http://dx.doi.org/10.1016/S1875-5364(21)60050-X] [PMID: 34247774]
[11]
Zhou, W.; Liu, H.; Qiu, L.Z.; Yue, L.X.; Zhang, G.J.; Deng, H.F.; Ni, Y.H.; Gao, Y. Cardiac efficacy and toxicity of aconitine: A new frontier for the ancient poison. Med. Res. Rev., 2021, 41(3), 1798-1811.
[http://dx.doi.org/10.1002/med.21777] [PMID: 33512023]
[12]
Chan, Y.T.; Wang, N.; Feng, Y. The toxicology and detoxification of Aconitum: Traditional and modern views. Chin. Med., 2021, 16(1), 61.
[http://dx.doi.org/10.1186/s13020-021-00472-9] [PMID: 34315520]
[13]
Nyirimigabo, E.; Xu, Y.; Li, Y.; Wang, Y.; Agyemang, K.; Zhang, Y. A review on phytochemistry, pharmacology and toxicology studies of Aconitum. J. Pharm. Pharmacol., 2014, 67(1), 1-19.
[http://dx.doi.org/10.1111/jphp.12310] [PMID: 25244533]
[14]
Luo, C.Q.; Xiao, S.Y.; Lv, D.; Qu, Y.; Cui, X.M.; Duan, L.H. Study on HPLC fingerprintand multiindicator quantitative analysis of Sanwujiaowan. J. Yunnan Uni. Nat. Sci. Educ., 2022, 44(1), 150-159.
[http://dx.doi.org/10.7540/j.ynu.20210394]
[15]
Li, ZH; Li, YF; Mei, Q.; Zhu, Z.H. Detection of aconitine in sanwujiao by HPLC. Chin. J. Ethnomed. Ethnopharm., 2008, (9), 18-19.
[16]
He, J.X.; Xie, C.Z.; Cui, Z.; Cheng, J.; Xv, Q.; Zhu, Z.H. Determination of 2,4,3′,5′-tetrahydroxystilbene in Sanwujiao by HPLC. Huaxi Yaoxue Zazhi, 2008, 23(06), 722-723.
[http://dx.doi.org/10.13375/j.cnki.wcjps.2008.06.009]
[17]
Zhang, Y.; Zong, X.; Wu, J.L.; Liu, Y.; Liu, Z.; Zhou, H.; Liu, L.; Li, N. Pharmacokinetics and tissue distribution of eighteen major alkaloids of Aconitum carmichaelii in rats by UHPLC-QQQ-MS. J. Pharm. Biomed. Anal., 2020, 185, 113226.
[http://dx.doi.org/10.1016/j.jpba.2020.113226] [PMID: 32163851]
[18]
Zhang, M.; Peng, C.; Li, X. In vivo and in vitro metabolites from the main diester and monoester diterpenoid alkaloids in a traditional chinese herb, the aconitum species. Evid. Based Complement. Alternat. Med., 2015, 2015, 1-23.
[http://dx.doi.org/10.1155/2015/252434] [PMID: 25705235]
[19]
Zhang, H.; Wu, Q.; Li, W.; Sun, S.; Zhang, W.; Zhu, Z.; Zhang, G.; Chai, Y. Absorption and metabolism of three monoester-diterpenoid alkaloids in Aconitum carmichaeli after oral administration to rats by HPLC–MS. J. Ethnopharmacol., 2014, 154(3), 645-652.
[http://dx.doi.org/10.1016/j.jep.2014.04.039] [PMID: 24793215]
[20]
Liang, J.; Xu, F.; Zhang, Y.Z.; Huang, S.; Zang, X.Y.; Zhao, X.; Zhang, L.; Shang, M.Y.; Yang, D.H.; Wang, X.; Cai, S.Q. The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC–DAD–ESI-IT-TOF-MSn technique: A novel strategy for the systematic screening and identification of absorbed constituents and metabolites from traditional Chinese medicines. J. Pharm. Biomed. Anal., 2013, 83, 108-121.
[http://dx.doi.org/10.1016/j.jpba.2013.04.029] [PMID: 23727363]
[21]
Liu, S. Study on the Chemical Constituents of Fuzi and Aconitum Stapfianum; Nanchang University, 2021.
[22]
Tao, C.G. Study on the absorption, distribution and elimination of aconitum alkaloids; Chengdu University of Traditional Chinese medicine, 2008.
[23]
Zhou, J. Pharmacokinetics and cardiac distribution of hypaconitine in rats; Beijing University of Traditional Chinese medicine, 2010.
[24]
Sui, Z.G. Study on mebabolism of diester-diterpene aconitum alkaloids in vivo; Jilin University, 2009.
[25]
Chen, X.G.; Lai, Y.Q.; Cai, Z.W. Simultaneous analysis of aconitine and its metabolites by liquid chromatography-electrospray lon trap mass spectrometry. J. Chin. Mass Spectromet. Soc., 2012, 33(02), 65-73.
[26]
Bi, Y.F.; Liu, S.; Zhang, R.X.; Song, F.R.; Liu, Z.Q. Metabolites and metabolic pathways of mesaconitine in rat liver microsomal investigated by using UPLC-MS/MS method in vitro. Yao Xue Xue Bao, 2013, 48(12), 1823-1828.
[PMID: 24689241]
[27]
Xin, Y.; Zhang, Y.; Zhang, Z.; Zhang, W.G.; Lv, J. Analysis on metabolites of hypaconitine in Rats’ Urine by LC-MSn. Zhongguo Shiyan Fangjixue Zazhi, 2015, 21(04), 94-97.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy