Abstract
Background: Schisandra chinensis has been widely used. It has many pharmacological activities. Lignans, including schizandrol A, schizandrin A, schisandrin B, schisanhenol, gomisin E, gomisin H, gomisin J, gomisin N, etc., are the major active ingredients of Schisandra chinensis.
Objective: In the present study, the liquid chromatography-tandem mass spectrometric (LCMS/ MS) method was developed for the simultaneous quantification of Schisandra lignans in normal rats.
Methods: Nifedipine was used as an internal standard, and chromatographic separation was achieved on Agela Venusil C18 Plus (4.6*100 mm, 3μm). Aqueous solution containing 0.1% (v/v) formic acid was used as the mobile phase A, and methanol solution containing 0.1% (v/v) formic acid was used as the mobile phase B for gradient elution. The flow rate was 0.8 mL/min. Multiple reaction monitoring (MRM) mode with positive electrospray ionization was used to detect the analytes.
Results: The calibration curves provided reliable responses at concentrations of 0.5-200 ng/ml for schizandrin A, schisandrin B, schisanhenol, gomisin E, gomisin H, gomisin N, concentrations of 10-200 ng/ml for schizandrol A, and concentrations of 5-200 ng/ml for gomisin J. The inter- and intra-day coefficients of variations (CVs) for the precision ranged from 6.70% (3.44%) to 11.66% (10.38%). The inter- and intra-day accuracies of eight lignans ranged from 95.70% (93.89%) to 104.59% (106.13%). No significant variation of any of the lignans occurred in the stability tests.
Conclusion: The established method can be successfully applied to the pharmacokinetic study of the Schisandra lignan extract in normal rats.
Graphical Abstract
[1]
Sheng, Y.H.; Wang, R.; Wang, Y.K.; Li, M.M.; Liu, F.X.; Huang, X.; Chen, C.B. Evaluation of multicomponent changes of Schisandra chinensis fruits with different drying process by UPLC-QQQ-MS-based targeted metabolomics analysis. J. Chem., 2022, (15), 1-10.
[http://dx.doi.org/10.1155/2022/2616122]
[http://dx.doi.org/10.1155/2022/2616122]
[2]
Kim, M.J.; Park, K.H.; Yang, H.J.; Jang, D.J.; Lee, H.Y.; Park, Y.M.; Kim, B.S.; Shin, D.Y. Ameliorative effects of Schizandra chinensis extracts and their soybean powder blends to diabetes mellitus. J. Food Nutr. Res., 2022, 1(1), 8-18.
[http://dx.doi.org/10.12691/jfnr-10-1-2]
[http://dx.doi.org/10.12691/jfnr-10-1-2]
[3]
Li, H.; Chen, C.; Feng, Y.b.; Lin, H.; Andrey, T.; Wang, C.M.; Li, H.; Chen, J.G.; Sun, J.H. Comparative study of the components and anti-fatigue effect of Schisandra chinensis polysaccharides from China and Russia. Nat. Prod. Commun., 2022, 17(2), 1-10.
[http://dx.doi.org/10.1177/1934578X221076]
[http://dx.doi.org/10.1177/1934578X221076]
[4]
Shi, X.; Han, B.; Zhang, B.; Chu, Z.; Zhang, X.; Lu, Q.; Han, J. Schisandra chinensis polysaccharides prevent cardiac hypertrophy by dissociating thioredoxin-interacting protein/thioredoxin-1 complex and inhibiting oxidative stress. Biomed. Pharmacother., 2021, 139, 111688.
[http://dx.doi.org/10.1016/j.biopha.2021.111688] [PMID: 34243612]
[http://dx.doi.org/10.1016/j.biopha.2021.111688] [PMID: 34243612]
[5]
Zhang, F.; Zhai, J.; Weng, N.; Gao, J.; Yin, J.; Chen, W. A comprehensive review of the main lignan components of Schisandra chinensis (North Wu Wei Zi) and schisandra sphenanthera (South Wu Wei Zi) and the lignan-induced drug-drug interactions based on the inhibition of cytochrome P450 and P-glycoprotein activities. Front. Pharmacol., 2022, 13, 816036.
[http://dx.doi.org/10.3389/fphar.2022.816036] [PMID: 35359848]
[http://dx.doi.org/10.3389/fphar.2022.816036] [PMID: 35359848]
[6]
Panossian, A.; Wikman, G. Pharmacology of Schisandra chinensis bail.: An overview of Russian research and uses in medicine. J. Ethnopharmacol., 2008, 118(2), 183-212.
[http://dx.doi.org/10.1016/j.jep.2008.04.020] [PMID: 18515024]
[http://dx.doi.org/10.1016/j.jep.2008.04.020] [PMID: 18515024]
[7]
Li, Z.; He, X.; Liu, F.; Wang, J.; Feng, J. A review of polysaccharides from Schisandra chinensis and Schisandra sphenanthera: Properties, functions and applications. Carbohydr. Polym., 2018, 184, 178-190.
[http://dx.doi.org/10.1016/j.carbpol.2017.12.058] [PMID: 29352909]
[http://dx.doi.org/10.1016/j.carbpol.2017.12.058] [PMID: 29352909]
[8]
Harsha, C.; Banik, K.; Bordoloi, D.; Kunnumakkara, A.B. Antiulcer properties of fruits and vegetables: A mechanism based perspective. Food Chem. Toxicol., 2017, 108(Pt A), 104-119.
[http://dx.doi.org/10.1016/j.fct.2017.07.023] [PMID: 28711545]
[http://dx.doi.org/10.1016/j.fct.2017.07.023] [PMID: 28711545]
[9]
Mocan, A. Crișan, G.; Vlase, L.; Crișan, O.; Vodnar, D.; Raita, O.; Gheldiu, A.M.; Toiu, A.; Oprean, R.; Tilea, I. Comparative studies on polyphenolic composition, antioxidant and antimicrobial activities of Schisandra chinensis leaves and fruits. Molecules, 2014, 19(9), 15162-15179.
[http://dx.doi.org/10.3390/molecules190915162] [PMID: 25247685]
[http://dx.doi.org/10.3390/molecules190915162] [PMID: 25247685]
[10]
Nowak, A. Zakłos-Szyda, M.; Błasiak, J.; Nowak, A.; Zhang, Z.; Zhang, B. Potential of Schisandra chinensis (Turcz.) Baill. in human health and nutrition: A review of current knowledge and Schisandra sphenanthera: properties, functions and applications. Nutrients, 2019, 11(2), 333-352.
[http://dx.doi.org/10.3390/nu11020333] [PMID: 30720717]
[http://dx.doi.org/10.3390/nu11020333] [PMID: 30720717]
[11]
Zhou, Y.; Men, L.; Sun, Y.; Wei, M.; Fan, X. Pharmacodynamic effects and molecular mechanisms of lignans from Schisandra chinensis Turcz. (Baill.), a current review. Eur. J. Pharmacol., 2021, 892, 173796.
[http://dx.doi.org/10.1016/j.ejphar.2020.173796] [PMID: 33345853]
[http://dx.doi.org/10.1016/j.ejphar.2020.173796] [PMID: 33345853]
[12]
Opletal, L.; Sovová, H.; Bártlová, M.; Opletal, L.; Sovová, H.; Bártlová, M. Dibenzo[a,c]cyclooctadiene lignans of the genus Schisandra: importance, isolation and determination. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2004, 812(1-2), 357-371.
[http://dx.doi.org/10.1016/S1570-0232(04)00646-4] [PMID: 15556508]
[http://dx.doi.org/10.1016/S1570-0232(04)00646-4] [PMID: 15556508]
[13]
Qiu, F.; Liu, H.; Duan, H.; Chen, P.; Lu, S.J.; Yang, G.Z.; Lei, X.X. Isolation, structural elucidation of three new triterpenoids from the stems and leaves of Schisandra chinensis (Turcz) Baill. Molecules, 2018, 23(7), 1624-1630.
[http://dx.doi.org/10.3390/molecules23071624] [PMID: 29973497]
[http://dx.doi.org/10.3390/molecules23071624] [PMID: 29973497]
[14]
Li, J.H.; Li, W.; Luo, S.; Ma, C.H.; Liu, S.X. Alternate ultrasound/microwave digestion for deep eutectic hydro-distillation extraction of essential oil and polysaccharide from Schisandra chinensis (Turcz.) Baill. Molecules, 2019, 24(7), 1288-1310.
[http://dx.doi.org/10.3390/molecules24071288] [PMID: 30987021]
[http://dx.doi.org/10.3390/molecules24071288] [PMID: 30987021]
[15]
Chen, S.Y.; Shi, J.J.; Zou, L.S.; Liu, X.H.; Tang, R.M.; Ma, J.M.; Yan, Y.; Zhao, H. Effects of different processing methods on lignans and organic acids in Schisandrae Chinensis fructus. Chung Kuo Yao Hsueh Tsa Chih, 2018, 53(23), 1984-1991.
[http://dx.doi.org/10.11669/cpj.2018.23.003]
[http://dx.doi.org/10.11669/cpj.2018.23.003]
[16]
Xu, M.; Yan, T.; Gong, G.; Wu, B.; He, B.; Du, Y.; Xiao, F.; Jia, Y. Purification, structural characterization, and cognitive improvement activity of a polysaccharides from Schisandra chinensis. Int. J. Biol. Macromol., 2020, 163, 497-507.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.275] [PMID: 32629059]
[http://dx.doi.org/10.1016/j.ijbiomac.2020.06.275] [PMID: 32629059]
[17]
Wei, M.; Liu, Y.; Pi, Z.; Li, S.; Hu, M.; He, Y.; Yue, K.; Liu, T.; Liu, Z.; Song, F.; Liu, Z. Systematically characterize the anti-Alzheimer’s disease mechanism of lignans from S. chinensis basedon in-vivo ingredient analysis and target-network pharmacology strategy by UHPLC-Q-TOF-MS. Molecules, 2019, 24(7), 1203.
[http://dx.doi.org/10.3390/molecules24071203] [PMID: 30934777]
[http://dx.doi.org/10.3390/molecules24071203] [PMID: 30934777]
[18]
Yang, B.; Liu, B.; Liu, Y.; Han, H.; Kuang, H. Cognitive enhancement of volatile oil from the stems of Schisandra chinensis Baill. in Alzheimer’s disease rats. Can. J. Physiol. Pharmacol., 2018, 96(6), 550-555.
[http://dx.doi.org/10.1139/cjpp-2016-0194] [PMID: 29714500]
[http://dx.doi.org/10.1139/cjpp-2016-0194] [PMID: 29714500]
[19]
Chen, S.Y.; Shi, J.J.; Zou, L.S.; Liu, X.; Tang, R.M.; Ma, J.M.; Wang, C.C.; Tan, M.X.; Chen, J.L. Quality evaluation of wild and cultivated fructus based on simultaneous determination of multiple bioactive constituents combined with multivariate statistical analysis. Molecules, 2019, 24(7), 1335-1349.
[http://dx.doi.org/10.3390/molecules24071335] [PMID: 30987393]
[http://dx.doi.org/10.3390/molecules24071335] [PMID: 30987393]
[20]
Chen, X.; Tang, R.; Liu, T.; Dai, W.; Liu, Q.; Gong, G.; Song, S.; Hu, M.; Huang, L.; Wang, Z. Physicochemical properties, antioxidant activity and immunological effects in vitro of polysaccharides from Schisandra sphenanthera and Schisandra chinensis. Int. J. Biol. Macromol., 2019, 131, 744-751.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.03.129] [PMID: 30904534]
[http://dx.doi.org/10.1016/j.ijbiomac.2019.03.129] [PMID: 30904534]
[21]
Wu, Z.; Liang, D.; Xu, M.; Liu, Y.; Xie, H. A comparative pharmacokinetic study of Schisandrol B after oral administration of Schisandrol B monomer and Schisandra chinensis extract. Curr. Pharm. Anal., 2021, 17(2), 273-284.
[http://dx.doi.org/10.2174/1573412916666191114122101]
[http://dx.doi.org/10.2174/1573412916666191114122101]
[22]
Gong, J.E.; Kim, J.E.; Lee, S.J.; Choi, Y.J.; Jin, Y.J.; Choi, Y.W.; Choi, S.I.; Hwang, D.Y. Anti-cancer effects of α-cubebenoate derived from Schisandra chinensis in CT26 colon cancer cells. Molecules, 2022, 27(3), 737-748.
[http://dx.doi.org/10.3390/molecules27030737] [PMID: 35164001]
[http://dx.doi.org/10.3390/molecules27030737] [PMID: 35164001]
[23]
Szopa, A.; Ekiert, R.; Ekiert, H. Current knowledge of Schisandra chinensis (Turcz.) Baill. (Chinese magnolia vine) as a medicinal plant species: A review on the bioactive components, pharmacological properties, analytical and biotechnological studies. Phytochem. Rev., 2017, 16(2), 195-218.
[http://dx.doi.org/10.1007/s11101-016-9470-4] [PMID: 28424569]
[http://dx.doi.org/10.1007/s11101-016-9470-4] [PMID: 28424569]
[24]
Wu, X.; Zhou, Y.; Yin, F.; Dai, G.; Li, L.; Xu, B.; Ji, D.; Sun, Y.; Mao, C.; Lu, T. Comparative pharmacokinetics and tissue distribution of schisandrin, deoxyschisandrin and schisandrin B in rats after combining acupuncture and herb medicine (schisandra chinensis). Biomed. Chromatogr., 2014, 28(8), 1075-1083.
[http://dx.doi.org/10.1002/bmc.3122] [PMID: 24474333]
[http://dx.doi.org/10.1002/bmc.3122] [PMID: 24474333]
[25]
Yüksel, B. Öncü, T.; Şen, N. Assessing caffeine levels in soft beverages available in Istanbul, Turkey: An LC-MS/MS application in food toxicology. Toxicol. Anal. Clin., 2023, 35(1), 33-43.
[http://dx.doi.org/10.1016/j.toxac.2022.08.004]
[http://dx.doi.org/10.1016/j.toxac.2022.08.004]
[26]
Yüksel, B. Şen, N. Development and validation of a GC-FID method for determination of cocaine in illicit drug samples. Marmara Pharm. J., 2018, 22(4), 511-518.
[http://dx.doi.org/10.12991/jrp.2018.92]
[http://dx.doi.org/10.12991/jrp.2018.92]
[27]
Zhang, K.; Wang, M.; Yao, Y.; Huang, T.; Liu, F.; Zhu, C.; Lin, C. Pharmacokinetic study of seven bioactive components of Xiaoyan Lidan Formula in cholestatic and control rats using UPLC-MS/MS. Biomed. Pharmacother., 2021, 139, 111523.
[http://dx.doi.org/10.1016/j.biopha.2021.111523] [PMID: 33831838]
[http://dx.doi.org/10.1016/j.biopha.2021.111523] [PMID: 33831838]
[28]
Liu, K.; Song, Y.; Liu, Y.; Peng, M.; Li, H.; Li, X.; Feng, B.; Xu, P.; Su, D. An integrated strategy using UPLC-QTOF-MSE and UPLC-QTOF-MRM (enhanced target) for pharmacokinetics study of wine processed Schisandra chinensis fructus in rats. J. Pharm. Biomed. Anal., 2017, 139, 165-178.
[http://dx.doi.org/10.1016/j.jpba.2017.02.043] [PMID: 28284081]
[http://dx.doi.org/10.1016/j.jpba.2017.02.043] [PMID: 28284081]
[29]
Liu, B.; Gou, X.; Bai, X.; Hou, X.; Li, D.; Zhong, G.; Jin, J.; Huang, M. Simultaneous determination of seven taxoids in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Taxus yunnanensis extracts. J. Pharm. Biomed. Anal., 2015, 107, 346-354.
[http://dx.doi.org/10.1016/j.jpba.2015.01.001] [PMID: 25645339]
[http://dx.doi.org/10.1016/j.jpba.2015.01.001] [PMID: 25645339]
[30]
Sun, S.; Wang, R.; Fan, J.; Zhang, G.; Zhang, H. Effects of danshen tablets on pharmacokinetics of atorvastatin calcium in rats and its potential mechanism. Pharm. Biol., 2018, 56(1), 104-108.
[http://dx.doi.org/10.1080/13880209.2018.1424209] [PMID: 29322864]
[http://dx.doi.org/10.1080/13880209.2018.1424209] [PMID: 29322864]
[31]
Yang, K.; Qiu, J.; Huang, Z.; Yu, Z.; Wang, W.; Hu, H.; You, Y. A comprehensive review of ethnopharmacology, phytochemistry, pharmacology, and pharmacokinetics of Schisandra chinensis (Turcz.) Baill. and Schisandra sphenanthera Rehd. et Wils. J. Ethnopharmacol., 2022, 284, 114759.
[http://dx.doi.org/10.1016/j.jep.2021.114759] [PMID: 34678416]
[http://dx.doi.org/10.1016/j.jep.2021.114759] [PMID: 34678416]
[32]
Liu, X.; Cong, L.; Wang, C.; Li, H.; Zhang, C.; Guan, X.; Liu, P.; Xie, Y.; Chen, J.; Sun, J. Pharmacokinetics and distribution of schisandrol A and its major metabolites in rats. Xenobiotica, 2019, 49(3), 322-331.
[http://dx.doi.org/10.1080/00498254.2017.1418543] [PMID: 29251086]
[http://dx.doi.org/10.1080/00498254.2017.1418543] [PMID: 29251086]
[33]
Xu, M.; Wang, G.; Xie, H.; Huang, Q.; Wang, W.; Jia, Y. Pharmacokinetic comparisons of schizandrin after oral administration of schizandrin monomer, Fructus Schisandrae aqueous extract and Sheng-Mai-San to rats. J. Ethnopharmacol., 2008, 115(3), 483-488.
[http://dx.doi.org/10.1016/j.jep.2007.10.016] [PMID: 18060709]
[http://dx.doi.org/10.1016/j.jep.2007.10.016] [PMID: 18060709]
[34]
Ding, Z.; Xiao, J.; Zhang, Y.; Jiang, Y.; Chen, W.; Hu, J.; Guo, Y.; Zhang, B. Pharmacokinetics and liver uptake of three Schisandra lignans in rats after oral administration of liposome encapsulating β-cyclodextrin inclusion compound of Schisandra extract. J. Liposome Res., 2019, 29(2), 121-132.
[http://dx.doi.org/10.1080/08982104.2018.1430830] [PMID: 30821573]
[http://dx.doi.org/10.1080/08982104.2018.1430830] [PMID: 30821573]
[35]
Zhan, S.; Guo, W.; Shao, Q.; Fan, X.; Li, Z.; Cheng, Y. A pharmacokinetic and pharmacodynamic study of drug-drug interaction between ginsenoside Rg1, ginsenoside Rb1 and schizandrin after intravenous administration to rats. J. Ethnopharmacol., 2014, 152(2), 333-339.
[http://dx.doi.org/10.1016/j.jep.2014.01.014] [PMID: 24462784]
[http://dx.doi.org/10.1016/j.jep.2014.01.014] [PMID: 24462784]
[36]
Wei, B.; Li, Q.; Fan, R.; Su, D.; Ou, X.; Chen, K.; Chen, X.; Jia, Y.; Bi, K. UFLC-MS/MS method for simultaneous determination of six lignans of Schisandra chinensis (Turcz.) baill. in normal and insomniac rats brain microdialysates and homogenate samples: Towards an in-depth study for its sedative-hypnotic activity. J. Mass Spectrom., 2013, 48(4), 448-458.
[http://dx.doi.org/10.1002/jms.3176] [PMID: 23584938]
[http://dx.doi.org/10.1002/jms.3176] [PMID: 23584938]
