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X. Yao, Xinbing Wang, Chengzhi Gu, H. Zeng, W. Chen, Hui Tang (2016)Chemical composition, N-nitrosamine inhibition and antioxidant and antimicrobial properties of essential oil from Coreopsis tinctoria flowering tops
Natural Product Research, 30
M. Asensi, I. Medina, Á. Ortega, J. Carretero, Maleeha Bano, E. Obrador, J. Estrela (2002)Inhibition of cancer growth by resveratrol is related to its low bioavailability.
Free radical biology & medicine, 33 3
Wujie Cai, Lijing Yu, Yu Zhang, Li Feng, Si-yuan Kong, Hong-sheng Tan, Hongxi Xu, Cheng Huang (2016)Extracts of Coreopsis tinctoria Nutt. Flower Exhibit Antidiabetic Effects via the Inhibition of α-Glucosidase Activity
Journal of Diabetes Research, 2016
Yin-jun Yang, Xin-guang Sun, Jin-jun Liu, L. Kang, Sibao Chen, B. Ma, B. Guo (2016)Quantitative and Qualitative Analysis of Flavonoids and Phenolic Acids in Snow Chrysanthemum (Coreopsis tinctoria Nutt.) by HPLC-DAD and UPLC-ESI-QTOF-MS
Shunjie Yu, Haoran Zhao, Wenjing Yang, R. Amat, Jun Peng, Yike Li, Kai Deng, Xinmin Mao, Y. Jiao (2019)The Alcohol Extract of Coreopsis tinctoria Nutt Ameliorates Diabetes and Diabetic Nephropathy in db/db Mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM Pathways
BioMed Research International, 2019
Jing Xie, Li Li, Yurui Shi, Rongda Chen, Guiming Liu, Mengxue Wang, Meizhu Zheng, Ning Zhang (2019)Simultaneous UPLC-MS/MS determination of six components in rat plasma after oral administration of Smilacis glabrae Roxb. extract.
Biomedical chromatography : BMC
Ha Mu-la (2012)Experimental Study on Antihypertension and in vivo Antioxidant Function of Coreopsis Extract
Chinese Journal of Experimental Traditional Medical Formulae
(2016)Quantitative and qualitative analysis of flavonoids and phenolic acids in snow chrysanthemum (Coreopsis tinctoria nutt
M. Saltos, Blanca Puente, I. Faraone, L. Milella, N. Tommasi, A. Braca (2015)Inhibitors of α-amylase and α-glucosidase from Andromachia igniaria Humb. & Bonpl.
Phytochemistry Letters, 14
C. Zălaru, C. Crisan, I. Călinescu, Z. Moldovan, Isabela Tarcomnicu, S. Lițescu, R. Tatia, L. Moldovan, D. Boda, M. Iovu (2014)Polyphenols in Coreopsis tinctoria Nutt. fruits and the plant extracts antioxidant capacity evaluation
Central European Journal of Chemistry, 12
J. Kil, Y. Son, Y. Cheong, Nam‐Ho Kim, H. Jeong, J. Kwon, Eoh-Jin Lee, T. Kwon, Hun-taeg Chung, H. Pae (2011)Okanin, a chalcone found in the genus Bidens, and 3-penten-2-one inhibit inducible nitric oxide synthase expression via heme oxygenase-1 induction in RAW264.7 macrophages activated with lipopolysaccharide
Journal of Clinical Biochemistry and Nutrition, 50
Jing Xie, Li Li, Yurui Shi, Rongda Chen, Guiming Liu, Mengxue Wang, Meizhu Zheng, Ning Zhang (2019)Simultaneous ultra‐performance liquid chromatography–tandem mass spectrometry determination of six components in rat plasma after oral administration of Smilacis glabrae Roxb. extract
Shumin Lan, Jing-ming Lin, Ni Zheng (2014)Evaluation of the Antioxidant Activity of Coreopsis Tinctoria Nuff. and Optimisation of Isolation by Response Surface Methodology
Acta Pharmaceutica, 64
Qiang Yang, Yu-hua Sun, Li Zhang, Lei Xu, Meng-ying Hu, L. Xiaoyan, Feng Shi, Zheng-yi Gu (2014)Antihypertensive Effects of Extract from Flower Buds of Coreopsis tinctoria on Spontaneously Hypertensive Rats
Chinese Herbal Medicines, 6
Ning Li, Dali Meng, Yingni Pan, Qingling Cui, Guo-xun Li, Ni Hui, Sun Yu, Degang Qing, Xiaoguang Jia, Yingni Pan, Yue Hou (2015)Anti-neuroinflammatory and NQO1 inducing activity of natural phytochemicals from Coreopsis tinctoria
Journal of Functional Foods, 17
N. Begmatov, Jun Li, K. Bobakulov, S. Numonov, H. Aisa (2018)The chemical components of Coreopsis tinctoria Nutt. and their antioxidant, antidiabetic and antibacterial activities
Natural Product Research, 34
T. Walle, Faye Hsieh, M. DeLegge, J. Oatis, U. Walle (2004)HIGH ABSORPTION BUT VERY LOW BIOAVAILABILITY OF ORAL RESVERATROL IN HUMANS
Drug Metabolism and Disposition, 32
Yuyan Liang, H. Niu, Limei Ma, D. Du, L. Wen, Q. Xia, Wen Huang (2017)Eriodictyol 7-O-β-D glucopyranoside from Coreopsis tinctoria Nutt. ameliorates lipid disorders via protecting mitochondrial function and suppressing lipogenesis
Molecular Medicine Reports, 16
Yong Deng, S. Lam, Jing Zhao, Shao-Ping Li (2017)Quantitative analysis of flavonoids and phenolic acid in Coreopsis tinctoria Nutt. by capillary zone electrophoresis
Teresa Dias, Bo Liu, P. Jones, P. Houghton, H. Mota-Filipe, A. Paulo (2012)Cytoprotective effect of Coreopsis tinctoria extracts and flavonoids on tBHP and cytokine-induced cell injury in pancreatic MIN6 cells.
Journal of ethnopharmacology, 139 2
Yu-hua Sun, Jun Zhao, Hongtao Jin, Yan-Po Cao, Tingyong Ming, Lan-lan Zhang, Mengqiao Hu, Hasimu Hamlati, S. Pang, Xue-Ping Ma (2013)Vasorelaxant effects of the extracts and some flavonoids from the buds of Coreopsis tinctoria
Pharmaceutical Biology, 51
B. Jiang, Qiuyue Lv, Wenting Wan, Liang Le, Lijia Xu, Ke-Ping Hu, P. Xiao (2018)Transcriptome analysis reveals the mechanism of the effect of flower tea Coreopsis tinctoria on hepatic insulin resistance.
Food & function, 9 11
L. Chen, D. Hu, S. Lam, L. Ge, D. Wu, J. Zhao, Z. Long, W. Yang, B. Fan, S. Li (2016)Comparison of antioxidant activities of different parts from snow chrysanthemum (Coreopsis tinctoria Nutt.) and identification of their natural antioxidants using high performance liquid chromatography coupled with diode array detection and mass spectrometry and 2,2'-azinobis(3-ethylbenzthiazoline-s
Journal of chromatography. A, 1428
Limin Guo, Wensheng Zhang, Shiming Li, Chi-Tang Ho (2015)Chemical and nutraceutical properties of Coreopsis tinctoria
Journal of Functional Foods, 13
S. Lam, Sio Lam, Jing Zhao, Shao-Ping Li (2016)Rapid Identification and Comparison of Compounds with Antioxidant Activity in Coreopsis tinctoria Herbal Tea by High-Performance Thin-Layer Chromatography Coupled with DPPH Bioautography and Densitometry.
Journal of food science, 81 9
J. Marier, P. Vachon, A. Gritsas, Jie Zhang, J. Moreau, M. Ducharme (2002)Metabolism and Disposition of Resveratrol in Rats: Extent of Absorption, Glucuronidation, and Enterohepatic Recirculation Evidenced by a Linked-Rat Model
Journal of Pharmacology and Experimental Therapeutics, 302
Zhiyuan Ma, Shirui Zheng, Haixia Han, J. Meng, Xi Yang, S. Zeng, Hui Zhou, Huidi Jiang (2016)The bioactive components of Coreopsis tinctoria (Asteraceae) capitula: Antioxidant activity in vitro and profile in rat plasma
Journal of Functional Foods, 20
(2018)e chemical components of Coreopsis tinctoria nutt. and their antioxidant, antidiabetic and antibacterial activities
Hindawi Journal of Analytical Methods in Chemistry Volume 2020, Article ID 4247128, 7 pages https://doi.org/10.1155/2020/4247128 Research Article Determination and Pharmacokinetics of Okanin in Rat Plasma by UltraHigh Performance Liquid Chromatography Coupled with Triple-Quadrupole Tandem Mass Spectrometry 1 1 1 1 1 1 Yurui Shi, Rongda Chen, Jing Xie, Li Li , Guiming Liu, Meizhu Zheng, and Ning Zhang e College of Chemistry, Changchun Normal University, Changchun 130032, China e College of Jiamusi, Heilongjiang University of Chinese Medicine, Harbin 150040, China Correspondence should be addressed to Li Li; email@example.com and Ning Zhang; firstname.lastname@example.org Received 6 February 2020; Revised 8 June 2020; Accepted 4 August 2020; Published 28 August 2020 Academic Editor: Jose Vicente Ros Lis Copyright © 2020 Yurui Shi et al. .is 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. Okanin is a major ﬂavonoid found in Coreopsis tinctoria Nutt., arousing huge interest recently for its considerable biological characteristics including antioxidant, antineurotoxic, and antidiabetic activities. An ultrahigh performance liquid chromatog- raphy triple-quadrupole tandem mass spectrometry (UPLC-MS) was successfully used to determine okanin in rat plasma after oral administration of okanin. Bavachalcone acted as an internal standard (IS). By gradient elution, IS and analyte were separated on a C column for 7 min at a ﬂow rate of 0.25 mL/min with acetonitrile-0.1% acetic acid mobile phase. .e stability, matrix eﬀect, extraction recovery, accuracy, precision, linearity, and selectivity of the method were ﬁrstly demonstrated. .e major phar- macokinetic parameters of okanin in rat plasma were then measured using the developed UPLC-MS method. An UPLC- quadrupole time-of-ﬂight mass spectrometry (UPLC-Q-TOF-MS) was ﬁnally established to obtain the speciﬁc and accurate mass of okanin in rat plasma after oral administration, and its proposed fragmentation was further elaborated. of inducible nitric oxide synthetase in macrophages acti- 1. Introduction vated by lipopolysaccharides via nuclear factor-erythroid 2- In China, Coreopsis tinctoria Nutt.’s (C. tinctoria) capitula is related factor 2-dependent heme oxygenase-1 expression consumed as herbal tea, and its extracts exhibit various . Furthermore, okanin could signiﬁcantly inhibit biological activities including antioxidant [1–4], antihy- α-glucosidase with IC values about 0.02 mM, suggesting pertensive [5, 6], antineuroinﬂammatory , antidiabetic that it is a potential drug for the treatment of diabetes . activities [8–11], hepatic insulin resistance , and anti- Besides, okanin showed signiﬁcant anti-neuroinﬂammatory hyperlipidemic eﬀects . Okanin refers to a major ﬂa- activity with the IC value at 15.54μM, suggesting that it vonoid found in C. tinctoria  having attracted can treat neurodegenerative diseases . considerable attention for its potential contribution to the Due to the signiﬁcant pharmacological eﬀects, eﬀective pharmacological activity of C. tinctoria. Okanin had the methods for the identiﬁcation of ﬂavonoids in C. tinctoria prominent eﬀect on DPPH scavenging acts with EC as become necessary. .e ﬂavonoids including okanin from C. 6.2μM, which was stronger than those of butylated tinctoria had been successfully analyzed by UPLC, HPLC- hydroxytoluene and ascorbic acid with EC as 45.8μM and MS, high-performance thin-layer chromatography, and 30.4μM, separately . Meanwhile, okanin showed a better capillary zone electrophoresis methods [1, 16, 18–21]. antioxidant activity than quercetin in cellular experiments HPLC-MS has been proved to be the most eﬃcient analytical with IC as 11.0μM . Kil et al. reported that okanin method for analyzing ﬂavonoids in C. tinctoria among these inhibited the production of nitric oxide and the expression methods [16, 19]. Meanwhile, it is very important to study 2 Journal of Analytical Methods in Chemistry TM the pharmacokinetic behavior of okanin or C. tinctoria in USA) combined with an ACQUITY UPLC C guard order to better understand their pharmacological action. column was used for the separation. .e column temper- Only one report emphasized the characterization of the ature was set at 35 C. .e binary mobile phase system was pharmacokinetics of okanin and isookanin, the two most composed by 0.1% acetic acid (A) and acetonitrile (B). .e prominent antioxidants, in rat plasma after oral adminis- gradient conditions of the mobile phase included: 0–2 min, tration of 100 mg/kg ethanol extract of C. tinctoria capitula; 95–20% (A); 2-3 min, 20–20% (A); 3–3.5 min, 20–95% (A); however, the pharmacokinetic parameters of two targets 3.5–7 min, 95–95% (A). .e ﬂow rate was kept at 0.25 mL/ only measured the time to reach C (T ) and the min for an overall 7-min run time. .e volume of sample max max maximum plasma concentration (C ) . Nevertheless, injection was 5μL. Mass spectrometer was further improved max the pharmacokinetic behaviors of okanin and isookanin as follows: capillary voltage, 3.50 kV (+); source temperature, ° ° were not clear according to limited pharmacokinetic pa- 120 C; and desolvation temperature 300 C. Nitrogen was rameters. In the meantime, several studies have shown that served as the desolvation and cone gas, and ﬂow rates were the pharmacokinetic parameters of the target components set at 600 and 50 L/h, respectively. Argon acted as the −3 were signiﬁcantly diﬀerent after herb extract or monomer collision gas at 2.89 ×10 mbar pressure. Multiple reaction administration, suggesting a potential pharmacokinetic in- monitoring (MRM) in the positive ion mode was selected in teraction among multiple components in herb extracts this study. .e dwell time was automatically set by MassLynx [22–25]. .erefore, simply monitoring the pharmacokinetic NT 4.1 software. All data obtained from the centroid mode parameters of target compounds in herb extracts does not were further processed by MassLynx NT 4.1 software. .e represent the pharmacokinetic behavior of monomer ad- improved MRM transitions and energy parameters in- ministration. For example, the half-life of resveratrol in cluding cone voltage and collision energy of okanin and IS animal or human body was only 8–14 minutes after oral are listed in Supplementary Table 1. administration of monomer [22–24], but a slower elimi- .e full-scan mass range was set at 50–1200 for obtaining nation half-life of resveratrol was up to 5.60 h after ad- accurate mass of okanin by UPLC-Q-TOF-MS analysis. .e ministration of Smilacis glabrae extract . To our mass spectrometer conditions were listed as follows: gas knowledge, no reports have quantitatively determined temperature 550 C, spray gas 50 psi, auxiliary gas 50 psi, okanin in rat plasma after oral monomer administration. curtain gas 35 psi, ion spray voltage 5500 V, declustering In this work, an eﬀective UPLC–MS/MS method cou- potential 90 V, and collision energy for MS was 35 V. pled with multichannel segmented selected reaction mon- itoring program was developed for measuring the levels of 2.3. Calibration Standards and Quality Control Samples. okanin in rat plasma after oral monomer administration. Bavachalcone served as an internal standard (IS). .e One mg/mL of okanin was prepared with methanol as standard stock solution. .en, the standard stock solution structures of the okanin and IS are shown in Figure 1. .e major pharmacokinetic parameters of okanin in rat plasma was diluted 10 times as working solution. In the meantime, one mg/mL of bavachalcone was prepared with methanol as were then measured using the developed UPLC-MS/MS method. .e speciﬁc and accurate masses of okanin in rat an IS solution. Calibration standards, low, intermediate, and high levels of quality control (QC) samples were prepared plasma were ﬁnally obtained using UPLC-Q-TOF-MS, and its proposed fragmentation was further elaborated. using spiking blank rat plasma with appropriate volumes of the working solutions. Six serial concentrations were 1.956, 10.95, 40.40, 200.20, 2. Experimental 800.24, and 1390 ng/mL for calibration standard solution. .e concentrations of the low, intermediate, and high levels 2.1.ChemicalsandReagents. Okanin and bavachalcone with of QC samples were 10.01, 500.10, and 1000.20 ng/mL for purities over 98% were provided by Shanghai Yuanye Bio- okanin. All samples were incubated at −20 C before Technology Co., Ltd. (Shanghai, China). Heparin sodium application. was provided by Aﬀandi (Shanghai, China). HPLC grade acetonitrile, acetic acid, and methanol were purchased from E. Merck (Darmstadt, Germany). .e SPE cartridges (C , 2.4.SampleCleanup. Two hundred microlitres of calibration 6 cc/500 mg) were provided by Wan Cheng Bo Da (Beijing, standards, QC samples, and plasma samples were added to a China). Triple deionized water was adopted during the study 1.5 mL Eppendorf tube containing 400μL blank plasma, and and then puriﬁed with a Millipore puriﬁcation system 50μL of IS solution (22.06 ng/mL) was added to respective (Bedford, MA, USA). tube. Before loading the sample, the SPE cartridges were washed with 3 mL of methanol and 5 mL of puriﬁed water 2.2. UPLC-MS/MS Conditions. An UPLC-MS/MS method TM separately. .e mixture in respective tube was vortexed for was carried out using an ACQUITY UPLC system 1.0 min and then loaded onto a SPE cartridges. .e SPE combined with a Waters Micromass Quattro Premier ® ® cartridges were separately eluted with 2 mL puriﬁed water XE triple-quadrupole tandem mass spectrometer analyzer and 4.5 mL of methanol. .e resulting eluate was dried with (Waters Corp., Milford, MA, USA) with an electrospray TM nitrogen. .e residue was redissolved in 50 μL methanol and ionization (ESI) interface. An ACQUITY BEH C col- centrifuged at 16,000 ×g for 15 min. Five microlitres of umn (100 × 2.1 mm, 1.7μm; Waters Corp., Milford, MA, Journal of Analytical Methods in Chemistry 3 O O OH HO OH OH HO OH OH OH (a) (b) Figure 1: Chemical structures of (a) okanin and (b) bavachalcone. aliquot was subsequently injected into the UPLC-MS for procedures. .e short-term stability was also assessed by investigation. analyzing the QC sample retained in the autosampler (4 C) for 36 h. .e QC sample was stored at −20 C for 30 days in order to evaluate long-term stability. .e freeze-thaw sta- 2.5. Method Validation bility of QC samples was evaluated by transferring them from −20 C to room temperature for three complete freeze- 2.5.1. Speciﬁcity and Linearity of Calibration Curves, LLOD, thaw cycles. .e stability was demonstrated if the percentage and LLOQ. In order to study the possible endogenous in- deviation was no more than 15% of the nominal terference on okanin and IS, the blank plasma from six rats, concentration. the corresponding blank plasma added with okanin and IS, and the plasma of rats after oral administration of okanin were analyzed by UPLC-MS/MS, respectively. .e retention 2.6. Pharmacokinetic Analysis. .e pharmacokinetics of times (R ) and MRM transitions were adopted for analyzing okanin was investigated using male Sprague Dawley (SD) okanin and IS. Meanwhile, the accurate mass of okanin and its rats (250± 20 g) from Animal Safety Evaluation Center of proposed fragmentation mechanism in rat plasma after oral Heilongjiang University of Chinese Medicine (China). .e administration were obtained using UPLC-Q-TOF-MS. rats were divided into control and treatment groups with six Calibration curve for okanin was plotted for the peak animals each. .e rats were maintained under a light/dark area ratio of okanin/IS versus plasma concentrations by a 1/ ° ° cycle of 12 h, in the temperature range of 22 C± 2 C to x -weighted liner least-square regression model. .e lower ambient temperature, and at a humidity of 50%± 5%. Before limit of detection (LLOD) was deﬁned as the lowest con- the experiment, all rats were fasted for 12 h, but allowed to centration with at least three signal-to-noise ratios. .e drink water freely. Each rat in the treatment and control lower limit of quantiﬁcation (LLOQ) was deﬁned as the group were treated with 1 mg/kg okanin and an equal lowest concentration on the standard curve that can be volume of distilled water in an oral manner, separately. quantitated with an accuracy of 80–120% and a precision Blood samples (approximately 0.4 mL) were collected into value not exceeding 20%. 1.5 mL heparinized polythene tubes from the suborbital venous plexus before administration and at 0, 0.083, 0.167, 0.33, 0.50, 0.75, 1.0, 2.0, 4.0, 8.0, 12.0, and 24 h after ad- 2.5.2.MatrixEﬀect,ExtractionRecovery,Accuracy,Precision, ministration. .en, the blood samples were immediately and Stability. Intraday and interday accuracy and precision centrifuged at 13,000 rpm for 10 min, and samples were were assessed from replicate analyses (n � 6) of low, middle, processed as described in Section 2.4. and high concentrations of QC samples in the same day and over three consecutive days, respectively. .e concentration of sample was calculated according to the standard curve 2.7. Data Analysis. According to observing plasma con- equation prepared on the same day. .e precision of the centration versus time curve, maximum plasma concen- method was calculated as the relative standard deviation tration (C ) and the time to reach C (T ) were max max max (RSD) and was less than 15%. Accuracy was expressed as the directly determined. .e elimination rate constant (Kel) was relative error (RE) and was within ±15%. .e recovery and then obtained via linear regression analysis on the log-linear matrix eﬀects were measured using low-, middle- and high- portion of the plasma concentration versus time curve. .e concentration QC samples with six replicates. .e recovery other major pharmacokinetic parameters of okanin in rat was assessed by comparing the peak areas of the spiked plasma including half life (t ), the mean residence time 1/2 samples to those of the untreated sample. .e matrix eﬀect from zero to the sampling time (MRT ) and to inﬁnity 0–t was determined by comparing the peak areas of spiked blank (MRT ), and area under the plasma concentration versus 0–∞ plasma (A) to the peak areas of the solution standards in time curve from zero to the sampling time (AUC ) and to 0–t methanol at equal concentrations (B). .e matrix factor inﬁnity (AUC ) were determined using WinNonlin 0–∞ (MF) was expressed as the ratio of (A/B × 100), and the MF Professional Version 5.2.1 (http://www.pharsight.com). .e values ranged from 80% to 120%. .e stabilities of okanin in results were expressed as arithmetic mean± standard de- plasma were evaluated by analyzing the three concentrations viation (mean± SD, n � 6). of QC samples at diﬀerent storage and processing 4 Journal of Analytical Methods in Chemistry 2.38 8.64e4 7.52e4 100 100 100 2.38 80 80 80 60 60 60 40 40 40 20 20 20 0 0 0 01234567 01234567 01234567 Time (min) Time (min) Time (min) A B C (a) 4.97e5 4.97e5 100 100 100 4.03 4.03 80 80 80 60 60 60 40 40 40 20 20 20 0 0 0 01234567 01234567 01234567 Time (min) Time (min) Time (min) AB C (b) Figure 2: Representative MRM chromatograms of okanin and bavachalcone (IS) in positive ion mode: (a) okanin and (b) bavachalcone (IS). (A) Blank plasma. (B) Blank plasma spiked with okanin and IS. (C) Plasma sample 1 h after oral administration of okanin (1 mg/kg) (mean± SD, n � 6). retention times of 2.83 and 4.03 were identiﬁed by com- 3. Results and Discussion paring retention time, precursors, and MRM transitions 3.1.OptimizationofUPLC-MS/MSConditions. As described with those of standards. Under the UPLC-MS/MS condi- in Section 2.2, in order to obtain symmetric peak shape, high tions, no noticeable interfering peaks were detected over- sensitivity, and a short run time for the separation, an ac- lapped with analyte elution times in blank rat plasma. curate and reliable UPLC method for analyzing okanin and Moreover, no interference appeared between IS and okanin, IS in rat plasma after administration had been successfully suggesting eﬃcient separation of okanin and IS. .e results established. showed that the developed method had signiﬁcant speciﬁcity Okanin and IS were separately injected into the mass and selectivity for the analysis of okanin in rat plasma. Okanin in rat plasma eluted at 2.38 min showed a spectrometer for the optimization of MS/MS conditions, and the positive ESI mode was taken for more robust and stable major molecular ion at m/z 289.0717 in the positive mode, intensity of signal for both okanin and IS than those of the suggesting the accurate mass to be 288.0717 (calculated for negative mode. .e MRM transitions and energy parameters C H O ) by the high-resolution Q-TOF analyses for 15 13 6 of okanin and IS in the positive ESI mode were further structural conﬁrmation. In UPLC-Q-TOF-MS/MS ex- optimized, and the results are shown in Supplementary periment, the ion at m/z 289.0717 yielded four fragment Table 1. .e MRM transitions were detected at m/z ions at m/z 271.0431, 163.0388, 153.0182, and 135.0439, respectively. As shown in Figure 3, the ion atm/z 163.0388 289.14⟶153.25 and m/z 325.14⟶ 269.19 for okanin and IS, respectively. .e results indicated that the MRM model was produced by losing A’s ring. .e predominant fragmentation ion at m/z 135.0439 and 153.0182 was used in this study can eﬀectively determine the target compounds in rat plasma. formed from the cleavage of position 3 in the three-carbon chain, and the charge is retained in ring A and ring B, respectively. Minor fragment m/z 271.0431 was produced directly from the parent ion of m/z 289.0717 due to the 3.2. Method Validation neutral loss of one molecule of water, indicating the ex- 3.2.1. Speciﬁcity, Calibration Curve, LLOD, and LLOQ. istence of orthophenol hydroxyl in the structure. .e Figure 2 presents typical MRM chromatograms in the proposed fragmentation mechanism was elaborated in positive ion mode of blank plasma, blank plasma stabbed Figure 3. with okanin and IS, and plasma sample 1 h after oral ad- Calibration curve was linear over the concentration ministration of okanin (1 mg/kg). Okanin and IS with ranges of 1.956–1390 ng/mL for okanin, and representative Relative abundance Relative abundance Relative abundance Relative abundance Relative abundance Relative abundance Journal of Analytical Methods in Chemistry 5 153.0182 [M + H-A-ring] O + [M + H-135] 163.0388 3 4 1 OH 135.0439 289.0717 OH HO OH 271.0431 OH [M + H-153] 0 50 100 150 200 250 300 (m/z) Figure 3: UPLC-MS Q-TOF spectra and the proposed fragmentation pathways of okanin. conditions. .e results suggested the good stability of okanin over diﬀerent storage conditions. 3.3. Application to Pharmacokinetic Study. Okanine in rat plasma was successfully determined by developed UPLC- MS/MS after oral administration of okanine monomer at a dose of 1 mg/kg. As shown in Figure 4, the mean plasma concentration versus time curves were plotted. After oral administration, plasma concentrations of okanin were de- termined for 24 h, and okanin was detected in plasma up to 8 h. 0 As listed in Supplementary Table 5, the major phar- macokinetic parameters were determined for control rats or 0 5 10 15 20 25 Time (h) rats that treated with 1 mg/kg of okanin. At aT of 0.167 h, max the rat plasma concentration of okanin reached the maxi- Figure 4: Plasma concentration vs. time proﬁles of okanin in rats mum concentration (C ) of 1296.12± 60.31 ng/mL max after oral administration of okanin (1 mg/kg) (mean± SD, n � 6). (mean± SD), revealing quick absorption of okanin into blood circulatory system. An existing report suggested T max regression equation was y � 19.979x + 337.59 and r � 0.9980 and C values for okanin of 0.333 h and 10.5μM after oral max (Supplementary Table 2). Good linearity was obtained. .e administration of 100 mg/kg ethanol extract of C. tinctoria LLOD and LLOQ were determined at 0.675 and 1.956 ng/ capitula . In contrast to the literature which reported mL, respectively, revealing that the presented method is T values, okanin was absorbed into blood more quickly max suﬃcient for the analysis of okanin in rat plasma. by orally administered monomer than the extract of C. tinctoria, indicating a possible pharmacokinetic interaction of multiple components in the extract of C. tinctoria. Our 3.2.2.Precision,Accuracy,ExtractionRecovery,MatrixEﬀect, conclusion was consistent with that of literatures [22–25]. andStability. As shown in Supplementary Table 3, the intra- To further study the pharmacokinetic behaviors of and interday precision of okanin were changed by less than okanin, more pharmacokinetic parameters including t , 1/2 5.94%, and the intra- and interday accuracy were between K , AUC , AUC MRT , and MRT values were el 0–t 0–∞, 0–t 0–∞ 2.23% to 5.97% and 1.86% to 7.40%, separately. .e results determined here. .e concentrations of okanin in rat plasma revealed that the developed method was suitable for de- were decreased quickly, and the shortest elimination half life termining okanin in rat plasma. (t ) at 0.89± 0.09 h was observed for okanin. .e K values 1/2 el In order to evaluate the reproducibility of the method, were 0.75± 0.08 for okanin. .e AUC and AUC 0–t 0–∞ the extraction recovery and matrix eﬀect experiments were values of okanin were 1728.78± 146.64 and carried out, and the results are listed in Supplementary 1826.51± 149.59 ng·h/mL, respectively. MRT and 0–t Table 4. .e mean extraction recoveries of okanin were MRT values for okanin were 1.14± 0.06 h and 0–∞ greater than 101.06%, indicating that the optimized prep- 1.36± 0.10 h, separately. aration was feasible and reproducible. .e values of the matrix factors of three levels QC samples ranged from 4. Conclusions 97.44% to 102.46%, indicating that no coeluting endogenous substances from plasma signiﬁcantly aﬀected the ionization An eﬀective UPLC–MS/MS method was developed for of the okanin. As listed in Supplementary Table 4, the analyzing okanin in rat plasma after oral administration stability of okanin was measured under diverse potential okanin monomer for the ﬁrst time. Compared with the Concentration (ng/ml) Intensity 6 Journal of Analytical Methods in Chemistry  T. Ming, Y. H. Sun, M. Y. Hu et al., “Experimental study on literature report, more pharmacokinetic parameters of anti-hypertension and in vivo antioxidant function of core- okanin including T , C , t , K , AUC , AUC max max 1/2 el 0–t 0–∞, opsis extract,” Chinese Journal of Experimental Traditional MRT , and MRT values were obtained in this study. 0–t 0–∞ Medical Formulae, vol. 18, pp. 249–252, 2012. Meanwhile, target okanin had shorter T by monomer max  Y.-H. Sun, J. Zhao, H.-T. Jin et al., “Vasorelaxant eﬀects of the administration than that of herb extract administration, extracts and some ﬂavonoids from the buds of Coreopsis suggesting a potential pharmacokinetic interaction among tinctoria,” Pharmaceutical Biology, vol. 51, no. 9, multiple components in herb extract. .e pharmacokinetic pp. 1158–1164, 2013. behaviors for okanin provide the basis for further studies to  N. Li, D. Meng, Y. Pan et al., “Anti-neuroinﬂammatory and elucidate the mechanisms of action and facilitate clinical NQO1 inducing activity of natural phytochemicals from application. Coreopsis tinctoria,” Journal of Functional Foods, vol. 17, pp. 837–846, 2015.  N. Begmatov, J. Li, K. Bobakulov et al., “.e chemical Data Availability components ofCoreopsistinctoria nutt. and their antioxidant, antidiabetic and antibacterial activities,” Natural Product .e data used to support the ﬁndings of this study are in- Research, vol. 34, no. 12, pp. 1–5, 2018. cluded within the article.  W. Cai, L. Yu, Y. Zhang et al., “Extracts of Coreopsis tinctoria nutt ﬂower exhibit antidiabetic eﬀects via the inhibition of Conflicts of Interest α-glucosidase activity,” Journal of Diabetes Research, vol. 2016, no. 23, pp. 1–9, 2016. .e authors declare that they have no conﬂicts of interest  T. Dias, B. Liu, P. Jones, P. J. Houghton, H. Mota-Filipe, and with respect to this study. A. Paulo, “Cytoprotective eﬀect of Coreopsis tinctoria extracts and ﬂavonoids on tBHP and cytokine-induced cell injury in Acknowledgments pancreatic MIN6 cells,” Journal of Ethnopharmacology, vol. 139, no. 2, pp. 485–492, 2012. .is study was supported by the National Natural Science  S. Yu, H. Zhao, W. Yang et al., “.e alcohol extract of Co- Foundation of China (no. 81373899), the Natural Science reopsis tinctoria nutt ameliorates diabetes and diabetic ne- Foundation of Jilin Province of China (nos. 20180101153JC phropathy in db/db mice through miR-192/miR-200b and PTEN/AKT and ZEB2/ECM pathways,” BioMed Research and JJKH20181168KJ), and the Academic Innovation International, vol. 2019, Article ID 5280514, 12 pages, 2019. Foundation of Changchun Normal University of China (nos.  B. Jiang, Q. Lv, W. Wan et al., “Transcriptome analysis reveals Cscxy2018001 and Cscxy2017025). the mechanism of the eﬀect of ﬂower tea Coreopsis tinctoria on hepatic insulin resistance,” Food & Function, vol. 9, no. 11, Supplementary Materials pp. 5607–5620, 2018.  Y. Liang, H. Niu, L. Ma et al., “Eriodictyol 7-O-β-D gluco- Table 1: precursor/product ion pairs and parameters for pyranoside from Coreopsis tinctoria nutt ameliorates lipid MRM of okanin used in this study. Table 2: regression disorders via protecting mitochondrial function and sup- equations, linearity, LLOD, and LLOQ. Table 3: intraday and pressing lipogenesis,” Molecular Medicine Reports, vol. 16, interday precision and accuracy (n = 6). Table 4: extraction no. 2, pp. 1298–1306, 2017. recovery, matrix eﬀect, and stability results at low, middle,  Q. Yang, Y.-H. Sun, L. Zhang et al., “Antihypertensive eﬀects and high concentration levels (mean± SD, n = 6). Table 5: of extract from ﬂower buds of Coreopsis tinctoria on spon- the main pharmacokinetic parameters after oral adminis- taneously hypertensive rats,”ChineseHerbalMedicines, vol. 6, tration of okanin with 1 mg/kg (mean± SD; n = 6). (Sup- no. 2, pp. 103–109, 2014.  Z. Ma, S. Zheng, H. Han et al., “.e bioactive components of plementary Materials) Coreopsis tinctoria (asteraceae) capitula: antioxidant activity in vitro and proﬁle in rat plasma,”JournalofFunctionalFoods, References vol. 20, pp. 575–586, 2016.  J.-S. Kil, Y. Son, Y.-K. Cheong et al., “Okanin, a chalcone  L. Guo, W. Zhang, S. Li, and C.-T. Ho, “Chemical and found in the genus bidens, and 3-penten-2-one inhibit in- nutraceutical properties of Coreopsis tinctoria,” Journal of ducible nitric oxide synthase expression via heme oxygenase-1 Functional Foods, vol. 13, pp. 11–20, 2015. induction in RAW264.7 macrophages activated with lipo-  S. Lan, J. Lin, and N. Zheng, “Evaluation of the antioxidant polysaccharide,” Journal of Clinical Biochemistry and Nutri- activity of Coreopsis tinctoria nuﬀ. and optimisation of iso- tion, vol. 50, no. 1, pp. 53–58, 2011. lation by response surface methodology,” Acta Pharmaceu-  M. B. V. Saltos, B. F. N. Puente, I. Faraone, L. Milella, tica, vol. 64, no. 3, pp. 369–378, 2014. N. D. Tommasi, and A. Braca, “Inhibitors of α-amylase and  X. Yao, X. Wang, C. Gu, H. Zeng, W. Chen, and H. Tang, α-glucosidase from Andromachia igniaria humb & bonpl,” “Chemical composition, N-nitrosamine inhibition and anti- Phytochemistry Letters, vol. 14, pp. 45–50, 2015. oxidant and antimicrobial properties of essential oil from  L. X. Chen, D. J. Hu, S. C. Lam et al., “Comparison of an- Coreopsis tinctoria ﬂowering tops,” Natural Product Research, tioxidant activities of diﬀerent parts from snow chrysanthe- vol. 30, no. 10, pp. 1170–1173, 2016. mum (Coreopsis tinctoria nutt.) and identiﬁcation of their  C. Zalaru, ˘ C. C. Cri¸an, s I. Calinescu ˘ et al., “Polyphenols in Coreopsis tinctoria nutt. fruits and the plant extracts anti- natural antioxidants using high performance liquid chro- matography coupled with diode array detection and mass oxidant capacity evaluation,” Central European Journal of Chemistry, vol. 12, no. 8, pp. 858–867, 2014. spectrometry and 2,2′-azinobis (3-ethylbenzthiazoline- Journal of Analytical Methods in Chemistry 7 sulfonic acid) diammonium salt-based assay,” Journal of Chromatography A, vol. 1428, pp. 134–142, 2016.  Y. Yang, X. Sun, J. Liu et al., “Quantitative and qualitative analysis of ﬂavonoids and phenolic acids in snow chrysan- themum (Coreopsis tinctoria nutt.) by HPLC-DAD and UPLC-ESI-QTOF-MS,” Molecules, vol. 21, no. 10, p. 1307,  S.-C. Lam, S.-F. Lam, J. Zhao, and S.-P. Li, “Rapid identiﬁ- cation and comparison of compounds with antioxidant ac- tivity in Coreopsis tinctoria herbal tea by high-performance thin-layer chromatography coupled with DPPH bio- autography and densitometry,” Journal of Food Science, vol. 81, no. 9, pp. C2218–C2223, 2016.  Y. Deng, S.-C. Lam, J. Zhao, and S.-P. Li, “Quantitative analysis of ﬂavonoids and phenolic acid in Coreopsis tinctoria nutt. by capillary zone electrophoresis,” Electrophoresis, vol. 38, no. 20, pp. 2654–2661, 2017.  M. Asensi, I. Medina, A. Ortega et al., “Inhibition of cancer growth by resveratrol is related to its low bioavailability,”Free Radical Biology and Medicine, vol. 33, no. 3, pp. 387–398,  J.-F. Marier, P. Vachon, A. Gritsas, J. Zhang, J.-P. Moreau, and M. P. Ducharme, “Metabolism and disposition of resveratrol in rats: extent of absorption, glucuronidation, and enter- ohepatic recirculation evidenced by a linked-rat model,” Journal of Pharmacology and Experimental erapeutics, vol. 302, no. 1, pp. 369–373, 2002.  T. Walle, F. Hsieh, M. H. DeLegge, J. E. Oatis, and U. K. Walle, “High absorption but very low bioavailability of oral resveratrol in humans,” Drug Metabolism and Disposition, vol. 32, no. 12, pp. 1377–1382, 2004.  J. Xie, L. Li, Y. R. Shi et al., “Simultaneous UPLC-MS/MS determination of six components in rat plasma after oral administration of smilacis glabrae roxb extract,” Biomedical Chromatography, vol. 33, no. 12, pp. 1–10, 2019.
Journal of Analytical Methods in Chemistry – Hindawi Publishing Corporation
Published: Aug 28, 2020
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