Abstract
Background and Objective
Taohong Siwu Decoction (TSD) is a classic traditional Chinese medicine (TCM) compound with pharmacological effects such as vasodilation and hypolipidemia. Paeoniflorin (PF) is one of the active ingredients of TSD. The aim of this study was to evaluate the pharmacokinetics of PF in herbal extracts and their purified forms in rats.
Method
A sensitive and rapid high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS-MS) method for the determination of PF in rat plasma was developed. Rats were divided into three groups, and given PF solution, water extract of white peony root (WPR), or TSD by gavage. At different predetermined timepoints after gavage, blood was collected from the orbital vein. The pharmacokinetic parameters of PF in the plasma of rats in the three groups was determined.
Results
The pharmacokinetic studies showed that the time to reach maximum concentration (Tmax) of PF in the purified forms group was relatively high, while the half-lives (T½) of PF in the TSD and WPR groups were longer. Among the three groups, PF in the purified forms group had the maximum area under the concentration–time curve (AUC0-t = 732.997 µg/L·h) and the largest maximum concentration (Cmax = 313.460 µg/L), which showed a significant difference compared with the TSD group (P < 0.05). Compared with the purified group, the clearance (CLz/F = 86.004 L/h/kg) and the apparent volume of distribution (Vz/F = 254.787 L/kg) of PF in the TSD group increased significantly (P < 0.05).
Conclusions
A highly specific, sensitive, and rapid HPLC–MS-MS method was developed and applied for the determination of PF in rat plasma. It was found that TSD and WPR can prolong the action time of paeoniflorin in the body.
Similar content being viewed by others
References
Chang R, Liu J, Luo Y, Huang T, Li Q, Wen J, et al. Isoflavones’ effects on pharmacokinetic profiles of main iridoids from Gardeniae Fructus in rats. J Pharm Anal. 2020;10(6):571–80.
Liu L, Duan JA, Su SL, Liu P, Tang YP, Qian DW. Siwu series decoctions for treating primary dysmenorrea of gynecology blood stasis syndrome–research progress of Taohong Siwu decoction. Zhongguo Zhong Yao Za Zhi. 2015;40(5):814–21.
Wang S, Liu Q, Jiang H, Cheng Y, Yan Y, Zhang J, Pei J. Active components and mechanism of Taohong Siwu Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking technology. Zhongguo Zhong Yao Za Zhi. 2020;45(22):5373–82 (Chinese).
Chen G, Xie Y, Liu Y, Jin S, Chen Z, Zhang P, et al. Taohong Siwu decoction for femoral head necrosis: a protocol for systematic review. Medicine (Baltimore). 2020;99(13): e19368.
Zhang X, Li P, Hua Y, Ji P, Yao W, Ma Q, et al. Urinary metabolomics study the mechanism of Taohong Siwu Decoction intervention in acute blood stasis model rats based on liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2018;1074–1075:51–60.
Wang M, Liu Z, Hu S, Duan X, Zhang Y, Peng C, et al. Taohong siwu decoction ameliorates ischemic stroke injury via suppressing pyroptosis. Front Pharmacol. 2020;11: 590453.
Tan Z, Jiang X, Zhou W, Deng B, Cai M, Deng S, et al. Taohong siwu decoction attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via TGFBR1 signaling pathway. J Ethnopharmacol. 2021;270: 113838.
Chen FF, Wang MM, Xia WW, Peng DY, Han L. Tao-Hong-Si-Wu Decoction promotes angiogenesis after cerebral ischaemia in rats via platelet microparticles. Chin J Nat Med. 2020;18(8):620–7.
Fuping Z, Wuping L, Linhua W, Chengxi P, Fuqiang Z, Yi Z, et al. Tao-Hong-Si-Wu decoction reduces ischemia reperfusion rat myoblast cells calcium overloading and inflammation through the Wnt/IP3R/CAMKII pathway. J Cell Biochem. 2019;120(8):13095–106.
Yuan G, Han A, Wu J, Lu Y, Zhang D, Sun Y, et al. Bao Yuan decoction and Tao Hong Si Wu decoction improve lung structural remodeling in a rat model of myocardial infarction: Possible involvement of suppression of inflammation and fibrosis and regulation of the TGF-beta1/Smad3 and NF-kappaB pathways. Biosci Trends. 2018;12(5):491–501.
Jin L, Zhang LM, Xie KQ, Ye Y, Feng L. Paeoniflorin suppresses the expression of intercellular adhesion molecule-1 (ICAM-1) in endotoxin-treated human monocytic cells. Br J Pharmacol. 2011;164(2):694–703.
Yang YL, Liu CF, Huang JY, et al. Analysis on quality value transfer of substance benchmarks of Taohong Siwu Decoction. Zhongguo Zhong Yao Za Zhi. 2021;46(4):801–9.
Zhang L, Wei W. Anti-inflammatory and immunoregulatory effects of paeoniflorin and total glucosides of paeony. Pharmacol Ther. 2020;207: 107452.
Hu MZ, Wang AR, Zhao ZY, Chen XY, Li YB, Liu B. Antidepressant-like effects of paeoniflorin on post-stroke depression in a rat model. Neurol Res. 2019;41:446–55.
Ma X, Zhang W, Jiang Y, Wen J, Wei S, Zhao Y. Paeoniflorin, a natural product with multiple targets in liver diseases-a mini review. Front Pharmacol. 2020;11:531.
Xiang Y, Zhang Q, Wei S, Huang C, Li Z, Gao Y. Paeoniflorin: a monoterpene glycoside from plants of Paeoniaceae family with diverse anticancer activities. J Pharm Pharmacol. 2020;72(4):483–95.
Seo EJ, Fischer N, Efferth T. Phytochemicals as inhibitors of NF-kappaB for treatment of Alzheimer’s disease. Pharmacol Res. 2018;129:262–73.
Xi S, Shi M, Jiang X, Minuk GY, Cheng Y, Peng Y, et al. The effects of Tao-Hong-Si-Wu on hepatic necroinflammatory activity and fibrosis in a murine model of chronic liver disease. J Ethnopharmacol. 2016;180:28–36.
Gan P, Zhong M, Huang X, et al. Pharmacokinetic comparisons of albiflorin and paeoniflorin after oral administration of Shaoyao-Gancao-Tang and single herb Paeony decoction to rats. Planta Med. 2012;78(3):237–43.
Shao CL, Cui GH, Guo HD. Effects and mechanisms of Taohong Siwu Decoction on the prevention and treatment of myocardial injury. Front Pharmacol. 2022;13: 816347.
Ma Q, Li PL, Hua YL, et al. Effects of Tao-Hong-Si-Wu decoction on acute blood stasis in rats based on a LC-Q/TOF-MS metabolomics and network approach. Biomed Chromatogr. 2018;32(4): e4144.
Wang X, Lu J, Li G, et al. Established UPLC-MS/MS procedure for multicomponent quantitative analysis of rat plasma: pharmacokinetics of Taohong Siwu Decoction in normal and acute blood stasis models. J Ethnopharmacol. 2023;305: 116094.
Zhang L, Yan R, Su R, et al. Bioavailability enhancement of osthole after oral administration of Bushen Yizhi prescription extract to rats followed by Cnidium monnieri (L.) Cusson fruits extract in comparison to pure osthole at different doses. J Ethnopharmacol. 2014;152(2):266–71.
Mu Y, Zhang J, Zhang S, et al. Traditional Chinese medicines Wu Wei Zi (Schisandra chinensis Baill) and Gan Cao (Glycyrrhiza uralensis Fisch) activate pregnane X receptor and increase warfarin clearance in rats. J Pharmacol Exp Ther. 2006;316(3):1369–77.
Wei C, Wang H, Sun X, et al. Pharmacological profiles and therapeutic applications of pachymic acid (review). Exp Ther Med. 2022;24(3):547.
Luo N, Li Z, Qian D, et al. Simultaneous determination of bioactive components of Radix Angelicae Sinensis-Radix Paeoniae Alba herb couple in rat plasma and tissues by UPLC-MS/MS and its application to pharmacokinetics and tissue distribution. J Chromatogr B Analyt Technol Biomed Life Sci. 2014;963:29–39.
Hattori M, Shu YZ, Shimizu M, et al. Metabolism of paeoniflorin and related compounds by human intestinal bacteria. Chem Pharm Bull (Tokyo). 1985;33(9):3838–46.
Zhou YX, Gong XH, Zhang H, et al. A review on the pharmacokinetics of paeoniflorin and its anti-inflammatory and immunomodulatory effects. Biomed Pharmacother. 2020;130: 110505.
Metsugi Y, Miyaji Y, Ogawara K, et al. Appearance of double peaks in plasma concentration–time profile after oral administration depends on gastric emptying profile and weight function. Pharm Res. 2008;25(4):886–95.
Yuan J, Wei F, Luo X, et al. Multi-component comparative pharmacokinetics in rats after oral administration of Fructus aurantii extract, Naringin, Neohesperidin, and Naringin-Neohesperidin. Front Pharmacol. 2020;11:933.
Zhang P, Ma H, Lin X, et al. Simultaneous quantification and rat pharmacokinetics of formononetin-7-O-β-d-glucoside and its metabolite formononetin by high-performance liquid chromatography-tandem mass spectrometry. J Sep Sci. 2020;43(15):2996–3005.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Funding
This work was supported by the National Natural Science Foundation of China (nos. 82074505, 82004430, 81973919), The Natural Science Foundation of Guangdong Province (no. 2023A1515011835), special projects in key fields of ordinary colleges and universities in Guangdong Province (no. 2022ZDZX2078), and general scientific research project of Guangdong Provincial Bureau of Traditional Chinese Medicine (no. 20231246).
Conflict of Interest
All authors declare that they have no conflict of interest.
Ethical Approval
The experimental design was approved by Guangzhou University of Chinese Medicine Committee on Animal Care and Use and the study was performed in accordance with the Internal Charter on the Humane Care and Use of Laboratory Animal.
Consent to Participate
Not applicable.
Availability of Data and Materials
Data for this study are available on request.
Consent for Publication
Not applicable.
Code Availability
Not applicable.
Authors’ Contributions
WL, YL, QW, SZ, WZ, and LY conceived the idea and designed the study. XL, MW, and QS participated in the experimental study and statistical analysis. WC and YX wrote the manuscript. All authors read and approved the final manuscript.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Chen, Wc., Liang, Xy., Xie, Ly. et al. Comparative Study on the Pharmacokinetics of Paeoniflorin, White Peony Root Water Extract, and Taohong Siwu Decoction After Oral Administration in Rats. Eur J Drug Metab Pharmacokinet 48, 301–310 (2023). https://doi.org/10.1007/s13318-023-00825-9
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13318-023-00825-9