Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2016 Sep 7;21(9):1191.
doi: 10.3390/molecules21091191.

Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula

Yueting Li  1   2 , Yuan Lu  3 , Jianchun Hu  4   5 , Zipeng Gong  6 , Wu Yang  3   7 , Aimin Wang  8 , Jiang Zheng  9 , Ting Liu  10 , Tingting Chen  11   12 , Jie Hu  13   14 , Ling Mi  15   16 , Yongjun Li  17 , Yanyu Lan  18 , Yonglin Wang  19
Affiliations
Comparative Study

Pharmacokinetic Comparison of Scutellarin and Paeoniflorin in Sham-Operated and Middle Cerebral Artery Occlusion Ischemia and Reperfusion Injury Rats after Intravenous Administration of Xin-Shao Formula

Yueting Li et al. Molecules. .

Abstract

Xin-Shao formula is a folk remedy widely used in China to prevent and cure stroke. Cerebral ischemic reperfusion (I/R) injury often takes place during the treatment of stroke. Information about the pharmacokinetic behavior of the remedy under cerebral I/R injury conditions is lacking. The present study aimed to compare the pharmacokinetic properties of scutellarin and paeoniflorin, two major bioactive components of Xin-Shao formula, under physiological state in cerebral I/R injury rats. Neurobehavioral dysfunction was evaluated and cerebral infarcted volume was measured in middle cerebral artery occlusion I/R injury (MCAO) rats. Plasma samples were collected at various time points after a single dose (intravenous, i.v.) of Xin-Shao formula. The levels of plasma scutellarin and paeoniflorin at the designed time points were determined by a UPLC-MS/MS method, and drug concentration versus time plots were constructed to estimate pharmacokinetic parameters. Increase in terminal elimination half-life (t1/2z) and mean residence time (MRT(0-t)) of scutellarin as well as elevation in area under the plasma drug concentration-time curve from 0 h to the terminal time point (AUC(0-t)) and maximum plasma drug concentration (Cmax) of paeoniflorin, along with decreased clearance of paeoniflorin and scutellarin as well as reduced apparent volume of distribution (Vz) of paeoniflorin, were observed in MCAO rats, compared with those in sham-operated animals. The elimination of scutellarin and paeoniflorin were reduced in cerebral I/R injury reduced rats.

Keywords: MCAO; UPLC-MS/MS; Xin-Shao formula; paeoniflorin; pharmacokinetics; scutellarin.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The structures of scutellarin (A); paeoniflorin (B); and puerarin (C, IS).
Figure 2
Figure 2
Neurobehavioral disability and infarct regions caused by middle cerebral artery occlusion I/R injury (MCAO), evaluated by neurobehavioral scores and 2,3,5-triphenyltetrazolium chloride (TTC) staining. (A) Neurobehavioral scores; (B) TTC staining of brain; and (C) infarct volume (%). Rats exposed to 1 h ischemia followed by 24 h reperfusion to establish MCAO model. Neurobehavioral disability of rats was assessed (n = 12), and brain tissues were collected for TTC staining (n = 6). Data are mean ± standard deviation (SD), ##: p < 0.01 for MCAO vs. sham-operated group.
Figure 3
Figure 3
Typical selected ion recording (SIR) chromatograms obtained from analyses of blank plasma (A); blank plasma spiked with the scutellarin, paeoniflorin, and IS (B); and plasma samples from normal rats 15 min following the intravenous administration of Xin-Shao formula extracts (C).
Figure 4
Figure 4
The mean plasma concentration vs. time profile of the two components following the intravenous administration of Xin-Shao formula extracts in sham-operated and MCAO rats. (A): scutellarin and (B): paeoniflorin. Each value represents mean ± SD (n = 6).
See this image and copyright information in PMC

References

    1. Donnan G.A., Fisher M., Macleod M., Davis S.M. Stroke. Lancet. 2008;371:1612–1623. doi: 10.1016/S0140-6736(08)60694-7. - DOI - PubMed
    1. Zeng M.F., Pan L.M., Zhu H.X., Zhang Q.C., Guo L.W. Comparative pharmacokinetics of baicalin in plasma after oral administration of Huang-Lian-Jie-Du-Tang or pure baicalin in MCAO and sham-operated rats. Fitoterapia. 2010;81:490–496. doi: 10.1016/j.fitote.2010.01.004. - DOI - PubMed
    1. Fujimura M.K., Tominaga T.J., Chan P.H. Neuroprotective effect on antioxidant in ischemic brain injury: Involvement of neuronal apoptosis. Neurocrit. Care. 2005;2:59–66. doi: 10.1385/NCC:2:1:059. - DOI - PubMed
    1. Chen C., Venketasubramanian N., Gan R.N., Lambert C., Picard D., Chan B.P., Chan E., Bousser M.G., Xuemin S. Danqi Piantang Jiaonang (DJ), a traditional Chinese medicine, in poststroke recovery. Stroke. 2009;3:859–863. doi: 10.1161/STROKEAHA.108.531616. - DOI - PubMed
    1. Wang Y.L., Huang Y., Zheng L., Wang A.M., Long Y.J., He X., Lan Y.Y. Study on the compound compatibility of Xinshao freeze-dried powder injection. Chin. J. Exp. Tradit. Med. Form. 2007;13:38–40.

Publication types

MeSH terms

LinkOut - more resources