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Current Drug Metabolism

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

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Research Article

A Comprehensive Study on the Chemical Constituents and Pharmacokinetics of Erzhi Formula and Jiawei Erzhi Formula Based on Targeted and Untargeted LC-MS Analysis

Author(s): Tongtong Zhu, Wanning Chen, Chunyue Han, Zhijie Gao, Erwei Liu, Xiumei Gao, Zhifei Fu* and Lifeng Han*

Volume 23, Issue 14, 2022

Published on: 07 February, 2023

Page: [1130 - 1142] Pages: 13

DOI: 10.2174/1389200224666230130093412

Price: $65

Abstract

Background: Erzhi formula (EZF) is a traditional Chinese medicine prescription, which has been widely used in the treatment of osteoporosis and premature ovarian failure.

Objective: To enhance curative effects, the other two herbal medicines, including Spatholobi Caulis (SC) and Achyranthes bidentata Blume (ABB), were added into the original EZF formula to obtain two new Jiawei-EZF (JW-EZF) preparations. To clarify the effect of the compatibility of herbs for original formulas, the chemical constituents and bioactive compounds in vivo were detected.

Methods: An efficient and sensitive targeted and untargeted UHPLC/ESI-Q-Orbitrap MS method, together with mass defect filter and precursor ion list, was established firstly for the profiling of different EZF formulas. Furthermore, eleven absorbed compounds (apigenin, luteoloside, luteolin, oleuropein, wedelolactone, acteoside, specnuezhenide, 11-methyloleoside, ecliptasaponin A, formononetin, and β-ecdysone) were simultaneously quantified in rat plasma.

Results: A total of 124, 162, and 177 compounds were identified or tentatively identified in EZF, JW-3-EZF (EZF+SC) and JW-4-EZF (EZF+SC+ABB), respectively. 110 compounds were found to be common constituents in the three formulas. Moreover, 66 prototypes were unambiguously identified in the rats' plasma after oral administration of the three formulas using the same strategy. 11 out of the 66 absorbed components were simultaneously quantitated in the pharmacokinetic (PK) study. Compared to the original EZF, the plasma AUC(0-24h) and AUC(0-∞) of apigenin, 11-methyloleoside, luteolin, luteoloside, wedelolactone, and acteoside were found to be significantly increased after oral administration of JW-3-EZF, and plasma AUC(0-24h) and AUC(0-∞) of apigenin, wedelolactone, and acteoside, were also found to be significantly increased after JW-4-EZF administration.

Conclusion: The combined qualitative and quantitative methods were used to provide a potential approach to the characterization and quality control of the Traditional Chinese Medicine (TCM) and its preparations.

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[1]
Qin, X.; Niu, Z.; Han, X.; Yang, Y.; Wei, Q.; Gao, X.; An, R.; Han, L.; Yang, W.; Chai, L.; Liu, E.; Gao, X.; Mao, H. Anti-perimenopausal osteoporosis effects of Erzhi formula via regulation of bone resorption through osteoclast differentiation: A network pharmacology-integrated experimental study. J. Ethnopharmacol., 2021, 270(3), 113815.
[http://dx.doi.org/10.1016/j.jep.2021.113815] [PMID: 33444724]
[2]
Jiang, J.; Yin, J.; Liu, X.; Wang, H.; Lu, G. Erzhi formula extracts reverse renal injury in diabetic nephropathy rats by protecting the renal podocytes. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-13.
[http://dx.doi.org/10.1155/2018/1741924] [PMID: 30210570]
[3]
Zhao, H.M.; Zhang, X.Y.; Lu, X.Y.; Yu, S.R.; Wang, X.; Zou, Y.; Zuo, Z.Y.; Liu, D.Y.; Zhou, B.G. Erzhi pill protected experimental liver injury against apoptosis via the PI3k/Akt/Raptor/Rictor pathway. Front. Pharmacol., 2018, 9, 283-294.
[http://dx.doi.org/10.3389/fphar.2018.00283] [PMID: 29636693]
[4]
Li, X.; Lu, X.; Fan, D.; Li, L.; Lu, C.; Tan, Y.; Xia, Y.; Zhao, H.; Fan, M.; Xiao, C. Synergistic effects of erzhi pill combined with methotrexate on osteoblasts mediated via the Wnt1/LRP5/β-catenin signaling pathway in collagen-induced arthritis rats. Front. Pharmacol., 2020, 11, 228.
[http://dx.doi.org/10.3389/fphar.2020.00228] [PMID: 32218732]
[5]
Liang, W.; Li, X.; Li, G.; Hu, L.; Ding, S.; Kang, J.; Shen, J.; Li, C.; Asakawa, T. Sirt1/Foxo Axis plays a crucial role in the mechanisms of therapeutic effects of Erzhi pill in ovariectomized rats. Evid. Based Complement. Alternat. Med., 2018, 2018, 1-12.
[http://dx.doi.org/10.1155/2018/9210490] [PMID: 30224934]
[6]
Wu, X.F.; Duan, L.X.; Gao, X.L.; Guo, M.L.; Wang, D.M. Study on preventive and therapeutic effects of Erzhi Pills on mice with Parkinson’s disease induced by MPTP. Zhongguo Zhongyao Zazhi, 2019, 44(19), 4219-4224.
[http://dx.doi.org/10.19540/j.cnki.cjcmm.20190603.405] [PMID: 31872702]
[7]
Chinese Pharmacopoeia Commission. The Pharmacopoeia of the People’s Republic of China; Chemical Industry Press: Beijing, 2015, Vol. 1, .
[8]
Mei, Y.; Wei, L.; Tan, M.; Wang, C.; Zou, L.; Chen, J.; Cai, Z.; Yin, S.; Zhang, F.; Shan, C.; Liu, X. Qualitative and quantitative analysis of the major constituents in Spatholobi Caulis by UFLC-Triple TOF-MS/MS and UFLC-QTRAP-MS/MS. J. Pharm. Biomed. Anal., 2021, 194, 113803.
[http://dx.doi.org/10.1016/j.jpba.2020.113803] [PMID: 33317912]
[9]
Liu, X.Y.; Zhang, L.; Yang, X.W.; Zhang, Y.B.; Xu, W.; Zhang, P.; Zhao, W.; Peng, K.F.; Gong, Y.; Liu, N.F. Simultaneous detection and quantification of 57 compounds in Spatholobi caulis applying ultra fast liquid chromatography with tandem mass spectrometry. J. Sep. Sci., 2020, 43(23), 4247-4262.
[http://dx.doi.org/10.1002/jssc.202000496] [PMID: 32975894]
[10]
Mei, Y.; Wei, L.; Chai, C.; Zou, L.; Liu, X.; Chen, J.; Tan, M.; Wang, C.; Cai, Z.; Zhang, F.; Yin, S. A method to study the distribution patterns for metabolites in xylem and phloem of Spatholobi caulis. Molecules, 2019, 25(1), 167.
[http://dx.doi.org/10.3390/molecules25010167] [PMID: 31906156]
[11]
Cheng, Q.; Tong, F.; Shen, Y.; He, C.; Wang, C.; Ding, F. Achyranthes bidentata polypeptide k improves long-term neurological outcomes through reducing downstream microvascular thrombosis in experimental ischemic stroke. Brain Res., 2019, 1706, 166-176.
[http://dx.doi.org/10.1016/j.brainres.2018.11.010] [PMID: 30414726]
[12]
Shen, H.-M.; Pan, R.-L.; Hu, W.-Q.; Pan, J.; Huang, L.; Luan, C.-C. Achyranthes bidentata polypeptides prevent apoptosis by inhibiting the glutamate current in cultured hippocampal neurons. Neural Regen. Res., 2020, 15(6), 1086-1093.
[http://dx.doi.org/10.4103/1673-5374.270317] [PMID: 31823889]
[13]
Li, M.; Wang, X.; Han, L.; Jia, L.; Liu, E.; Li, Z.; Yu, H.; Wang, Y.; Gao, X.; Yang, W. Integration of multicomponent characterization, untargeted metabolomics and mass spectrometry imaging to unveil the holistic chemical transformations and key markers associated with wine steaming of Ligustri lucidi fructus. J. Chromatogr. A, 2020, 1624, 461228.
[http://dx.doi.org/10.1016/j.chroma.2020.461228] [PMID: 32540070]
[14]
Wang, Y.; Feng, K.; Li, M.; Han, L.; Wang, W.; Si, D.; Chen, X.; Yang, W.; Gao, X.; Liu, E. Identification of prototypes from Ligustri Lucidi Fructus in rat plasma based on a data‐dependent acquisition and multicomponent pharmacokinetic study. Biomed. Chromatogr., 2020, 34(7), e4833.
[http://dx.doi.org/10.1002/bmc.4833] [PMID: 32198769]
[15]
Li, M.; Si, D.; Fu, Z.; Sang, M.; Zhang, Z.; Liu, E.; Yang, W.; Gao, X.; Han, L. Enhanced identification of the in vivo metabolites of Ecliptae Herba in rat plasma by integrating untargeted data-dependent MS2 and predictive multiple reaction monitoring-information dependent acquisition-enhanced product ion scan. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2019, 1109, 99-111.
[http://dx.doi.org/10.1016/j.jchromb.2019.02.001] [PMID: 30743142]
[16]
Du, G.; Fu, L.; Jia, J.; Pang, X.; Yu, H.; Zhang, Y.; Fan, G.; Gao, X.; Han, L. Validated UPLC-MS/MS method for quantification of seven compounds in rat plasma and tissues: Application to pharmacokinetic and tissue distribution studies in rats after oral administration of extract of Eclipta prostrata L. Biomed. Chromatogr., 2018, 32(6), e4191.
[http://dx.doi.org/10.1002/bmc.4191] [PMID: 29349861]
[17]
Wang, Y.; Feng, R.; Wang, R.; Yang, F.; Li, P.; Wan, J.B. Enhanced MS/MS coverage for metabolite identification in LC-MS-based untargeted metabolomics by target-directed data dependent acquisition with time-staggered precursor ion list. Anal. Chim. Acta, 2017, 992, 67-75.
[http://dx.doi.org/10.1016/j.aca.2017.08.044] [PMID: 29054151]
[18]
Pan, H.; Yang, W.; Yao, C.; Shen, Y.; Zhang, Y.; Shi, X.; Yao, S.; Wu, W.; Guo, D. Mass defect filtering-oriented classification and precursor ions list-triggered high-resolution mass spectrometry analysis for the discovery of indole alkaloids from Uncaria sinensis. J. Chromatogr. A, 2017, 1516, 102-113.
[http://dx.doi.org/10.1016/j.chroma.2017.08.035] [PMID: 28838651]
[19]
Fu, L.; Ding, H.; Han, L.; Jia, L.; Yang, W.; Zhang, C.; Hu, Y.; Zuo, T.; Gao, X.; Guo, D. Simultaneously targeted and untargeted multicomponent characterization of Erzhi Pill by offline two-dimensional liquid chromatography/quadrupole-Orbitrap mass spectrometry. J. Chromatogr. A, 2019, 1584, 87-96.
[http://dx.doi.org/10.1016/j.chroma.2018.11.024] [PMID: 30473109]
[20]
Guo, J.; Zhang, L.; Shang, Y.; Yang, X.; Li, J.; He, J.; Gao, X.; Chang, Y. A strategy for intelligent chemical profiling-guided precise quantitation of multi-components in traditional Chinese medicine formulae-QiangHuoShengShi decoction. J. Chromatogr. A, 2021, 1649, 462178.
[http://dx.doi.org/10.1016/j.chroma.2021.462178] [PMID: 34038783]
[21]
Li, Z.; Wei, W.; Li, H.; Wu, S.; Huang, Y.; Yao, C.; Zhang, J.; Li, J.; Bi, Q.; Guo, D. A systematic strategy integrating solid-phase extraction, full scan range splitting, mass defect filter and precursor ion list for comprehensive metabolite profiling of Danqi Tongmai tablet in rats. J. Pharm. Biomed. Anal., 2021, 198, 113989.
[http://dx.doi.org/10.1016/j.jpba.2021.113989] [PMID: 33684829]
[22]
Guo, N.; Yu, Y.; Ablajan, K.; Li, L.; Fan, B.; Peng, J.; Yan, H.; Ma, F.; Nie, Y. Seasonal variations in metabolite profiling of the fruits of Ligustrum lucidum Ait. Rapid Commun. Mass Spectrom., 2011, 25(12), 1701-1714.
[http://dx.doi.org/10.1002/rcm.5036] [PMID: 21598330]
[23]
Deng, Y.; Ma, Y.; Liu, H.; Zhang, Y.; Wei, Z.; Liu, G.; Tang, X.; Jia, X. Structure determination, bitterness evaluation and hepatic gluconeogenesis inhibitory activity of triterpenoids from the Momordica charantia fruit. Food Chem., 2022, 372, 131224.
[http://dx.doi.org/10.1016/j.foodchem.2021.131224] [PMID: 34624787]
[24]
Yang, W.Z.; Ye, M.; Qiao, X.; Wang, Q.; Bo, T.; Guo, D.A. Collision-induced dissociation of 40 flavonoid aglycones and differentiation of the common flavonoid subtypes using electrospray ionization ion-trap tandem mass spectrometry and quadrupole time-of-flight mass spectrometry. Eur. J. Mass Spectrom. (Chichester, Eng.), 2012, 18(6), 493-503.
[http://dx.doi.org/10.1255/ejms.1206] [PMID: 23654194]
[25]
Tian, X.Y.; Li, M.X.; Lin, T.; Qiu, Y.; Zhu, Y.T.; Li, X.L.; Tao, W.D.; Wang, P.; Ren, X.X.; Chen, L.P. A review on the structure and pharmacological activity of phenylethanoid glycosides. Eur. J. Med. Chem., 2021, 209, 112563.
[http://dx.doi.org/10.1016/j.ejmech.2020.112563] [PMID: 33038797]
[26]
Wang, Z.; Qu, Y.; Wang, L.; Zhang, X.; Xiao, H. Ultra-high performance liquid chromatography with linear ion trap-Orbitrap hybrid mass spectrometry combined with a systematic strategy based on fragment ions for the rapid separation and characterization of components in Stellera chamaejasme extracts. J. Sep. Sci., 2016, 39(7), 1379-1388.
[http://dx.doi.org/10.1002/jssc.201500981] [PMID: 26861765]
[27]
Shuai, L.; Liu, H.; Liao, L.; Lai, T.; Lai, Z.; Du, X.; Duan, Z.; Wu, Z.; Luo, T. Widely targeted metabolic analysis revealed the changed pigmentation and bioactive compounds in the ripening Berchemia floribunda (Wall.) Brongn. fruit. Food Sci. Nutr., 2021, 9(3), 1375-1387.
[http://dx.doi.org/10.1002/fsn3.2093] [PMID: 33747452]
[28]
Wei, W.; Li, S.; Cheng, L.; Hao, E.; Hou, X.; Zhou, H.; Deng, J.; Yao, X. Comprehensive characterization of the chemical constituents in Yiganmingmu oral liquid and the absorbed prototypes in cynomolgus monkey plasma after oral administration by UPLC-Q-TOF-MS based on the self built components database. Chin. Med., 2021, 16(1), 35.
[http://dx.doi.org/10.1186/s13020-021-00443-0] [PMID: 33910600]
[29]
Zuo, L.; Liu, L.; Yang, Y.; Yang, J.; Chen, M.; Zhang, H.; Kang, J.; Zhang, X.; Wang, J.; Sun, Z. An entire process optimization strategy for comprehensive in vivo metabolite profiling of prucalopride in rats based on ultra-performance liquid chromatography with q-exactive hybrid quadrupole–orbitrap high-resolution mass spectrometry. Front. Pharmacol., 2021, 12, 610226.
[http://dx.doi.org/10.3389/fphar.2021.610226] [PMID: 34025397]
[30]
Wang, T.; Xiao, J.; Hou, H.; Li, P.; Yuan, Z.; Xu, H.; Liu, R.; Li, Q.; Bi, K. Development of an ultra-fast liquid chromatography–tandem mass spectrometry method for simultaneous determination of seven flavonoids in rat plasma: Application to a comparative pharmacokinetic investigation of Ginkgo biloba extract and single pure ginkgo flavonoids after oral administration. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2017, 1060, 173-181.
[http://dx.doi.org/10.1016/j.jchromb.2017.05.021] [PMID: 28622621]
[31]
He, J.; Feng, Y.; Ouyang, H.; Yu, B.; Chang, Y.; Pan, G.; Dong, G.; Wang, T.; Gao, X. A sensitive LC–MS/MS method for simultaneous determination of six flavonoids in rat plasma: Application to a pharmacokinetic study of total flavonoids from mulberry leaves. J. Pharm. Biomed. Anal., 2013, 84, 189-195.
[http://dx.doi.org/10.1016/j.jpba.2013.06.019] [PMID: 23850933]
[32]
Qing, W.; Wang, Y.; Li, H.; Ma, F.; Zhu, J.; Liu, X. Preparation and characterization of copolymer micelles for the solubilization and in vitro release of luteolin and luteoloside. AAPS PharmSciTech, 2017, 18(6), 2095-2101.
[http://dx.doi.org/10.1208/s12249-016-0692-y] [PMID: 28004344]
[33]
Feng, S.X.; Li, X.H.; Wang, M.M.; Hao, R.; Li, M.M.; Zhang, L.; Wang, Z. A sensitive HPLC–MS method for simultaneous determination of thirteen components in rat plasma and its application to pharmacokinetic study of Tanreqing injection. J. Pharm. Biomed. Anal., 2018, 148, 205-213.
[http://dx.doi.org/10.1016/j.jpba.2017.10.006] [PMID: 29040937]
[34]
Zhang, D.; Sun, L.; Li, H.; Cui, Y.; Liu, S.; Wu, P.; Zhao, D.; Zhao, P.; Zhang, X. Pharmacokinetic comparison of nine bioactive components in rat plasma following oral administration of raw and wine processed Ligustri Lucidi Fructus by ultra‐high‐performance liquid chromatography coupled with triple quadrupole mass spectrometry. J. Sep. Sci., 2020, 43(21), 3995-4005.
[http://dx.doi.org/10.1002/jssc.202000625] [PMID: 32864882]
[35]
Ding, Y.; Ju, Z.; Ma, C. A validated LC-MS/MS method for the determination of specnuezhenide and salidroside in rat plasma and its application to a pharmacokinetic study. Biomed. Chromatogr., 2018, 32(12), e4353.
[http://dx.doi.org/10.1002/bmc.4353] [PMID: 30062793]
[36]
Cheruvu, H.S.; Yadav, N.K.; Valicherla, G.R.; Arya, R.K.; Hussain, Z.; Sharma, C.; Arya, K.R.; Singh, R.K.; Datta, D.; Gayen, J.R. LCMS/MS method for the simultaneous quantification of luteolin, wedelolactone and apigenin in mice plasma using hansen solubility parameters for liquid-liquid extraction: Application to pharmacokinetics of Eclipta alba chloroform fraction. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2018, 1081-1082, 76-86.
[http://dx.doi.org/10.1016/j.jchromb.2018.01.035] [PMID: 29518720]
[37]
Li, L.; Huang, X.; Peng, J.; Zheng, M.; Zhong, D.; Zhang, C.; Chen, X. Wedelolactone metabolism in rats through regioselective glucuronidation catalyzed by uridine diphosphate-glucuronosyltransferases 1As (UGT1As). Phytomedicine, 2016, 23(4), 340-349.
[http://dx.doi.org/10.1016/j.phymed.2016.01.007] [PMID: 27002404]
[38]
Tao, Y.; Du, Y.; Li, W.; Cai, B. Development and validation of an UHPLC–MS/MS approach for simultaneous quantification of five bioactive saponins in rat plasma: Application to a comparative pharmacokinetic study of aqueous extracts of raw and salt-processed Achyranthes bidentata. J. Pharm. Biomed. Anal., 2018, 151, 164-169.
[http://dx.doi.org/10.1016/j.jpba.2017.12.024] [PMID: 29331795]

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