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A study on the PK and BA profiles in the mouse body for leonurine O/O microemulsion with determination by the LC-MS/MS method

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Abstract

Leonurine (LE) has been found to have therapeutic efficacy in cerebral thrombosis, but its poor solubility in water leads to very low bioavailability. In this article, a leonurine O/O microemulsion (LE-ME) was prepared and investigated for its in vivo pharmacokinetic behavior and bioavailability in the mouse body using an aqueous suspension of leonurine (LE-SWW) for the control group. A simple, sensitive and specific method, HPLC-MS/MS, was developed for detection of the LE content in mouse plasma using n-benzoyl-l-arginine ethyl ester as an internal standard. The results demonstrated that the C max of LE-ME was 2.46-fold higher than that of the suspension following oral administration. The absolute bioavailability was 10.95 %, while that of the suspension was only 1.78 %. The T 1/2β and MRT of LE-ME were 3.04- and 4.19-fold those of the suspension, respectively. In addition, following intramuscular administration of LE-ME, the absolute bioavailability was 37.45 %. The results indicated that LE-ME is a promising drug-delivery system to enhance the absorption and bioavailability of LE.

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References

  • Chao Z (2002) Pharmacokinetics of leonurine in rats. Chin Pharm J. 37:39–41

    Google Scholar 

  • Chen GM (1991) Motherwort research survey. J Shenyang C Pharm. 8:296–298

    Google Scholar 

  • Chen CX, Kwan CY (2001) Endothelium-independent vasorelaxation by leonurine, a plant alkaloid purified from Chinese motherwort. Life Sci 68:953–960

    Article  CAS  PubMed  Google Scholar 

  • Guan YJ, Ma AL (2012) Analysis of the pharmacological effects of motherwort. Seek Med. 10:791

    Google Scholar 

  • Hussain N, Jaitley V, Florence AT (2001) Recent advances in the understanding of uptake of microparticulates across the gastrointestinal lymphatics. Adv Drug Rev. 50:107–142

    Article  CAS  Google Scholar 

  • Kawakami K, Yoshikawa T, Hayashi T et al (2002) Microemulsion formulation for enhanced absorption of poorly soluble drugs: II. In vivo study. J Controll Release. 81:75–82

    Article  CAS  Google Scholar 

  • Li X, Yuan PL, Zhao YQ et al (2011) Effects of leonurine hydrochloride on medically induced incomplete abortion in early pregnancy rats. Eur J Obstet Gynecol Reprod Biol. 159:375–380

    Article  CAS  PubMed  Google Scholar 

  • Li BH, Wu JD, Li XL (2013a) Simultaneous determination and pharmacokinetic study of stachydrine and leonurine in rat plasma after oral administration of herba leonuri extract by LC-MS/MS. J Pharm Biomed Anal 76:192–199

    Article  CAS  PubMed  Google Scholar 

  • Li X, Yuan FL, Zhao YQ et al (2013b) Effect of leonurine hydrochloride on endothelin and the endothelin receptor-mediated signal pathway in medically-induced incomplete abortion in rats. Eur J Obstet Gynecol Reprod Biol. 169:299–303

    Article  CAS  PubMed  Google Scholar 

  • Liu XH, Xin H, Hou AJ et al (2009) Protective effects of Leonurine in neonatal rat hypoxic cardiomyocytes and rat infarcted heart. Clin Exp Pharm Phys. 36:696–703

    Article  CAS  Google Scholar 

  • Liu XH, Pan LL, Chen PF et al (2010a) Leonurine improves ischemia-induced myocardial injury though antioxidative activity. Phytomedicine 17:753–759

    Article  CAS  PubMed  Google Scholar 

  • Liu XH, Pan LL, Gong QH et al (2010b) Leonurine (SCM-198) improves cardiac recovery in rat during chronic infarction. Eur J Pharm. 649:236–241

    Article  CAS  Google Scholar 

  • Liu XH, Pan LL, Zhu YZ (2012a) Active chemical compounds of traditional Chinese medicine herba leonuri: implications for cardiovascular diseases. Clin Exp Pharm Phys. 39:274–282

    Article  CAS  Google Scholar 

  • Liu HC, Zhang XJ, Du YY et al (2012b) Leonurine protects brain injury by increased activities of UCP4, SOD, CAT and Bcl-2, decreased levels of MDA and Bax, and ameliorated ultrastructure of mitrochondria in experimental stroke. Brain Res 1474:73–81

    Article  CAS  PubMed  Google Scholar 

  • Liu XH, Pan LL, Yang HB et al (2012c) Leonurine attenuates lipopolysaccharide-induced inflammatory responses in human endothelial cells: involvement of reactive oxygen species and NF-κB pathways. Eur J Pharmacol. 680:108–114

    Article  CAS  PubMed  Google Scholar 

  • Liu CH, Guo W, Maerz S et al (2013a) 3,5-Dimethoxy-4-(3-(2-carbonyl-ethyldisulfanyl) -propionyl)-benzoic acid 4-guanidino-butyl ester: a novel twin drug that prevents primary cardiac myocytes from hypoxia-induced apoptosis. Eur J Pharm. 700:118–126

    Article  CAS  Google Scholar 

  • Liu XH, Pan LL, Deng HY et al (2013b) Leonurine (SCM-198) attenuates myocardial fibrotic response via inhibition of NADPH oxidase 4. Free Radical Biol Med 54:93–104

    Article  CAS  Google Scholar 

  • Loh KP, Qi J, Tan BKH et al (2010) Leonurine protects middle cerebral artery occluded rats though antioxidant effect and regulation of mitochondrial function. Stroke 41:2661–2668

    Article  CAS  PubMed  Google Scholar 

  • Lu CH, Wu HF, Zhou A et al (2008) Preparation of puerarin nanoparticles and its pharmacokinetics in mice. Chin Hosp Pharm J. 28:1977–1980

    CAS  Google Scholar 

  • Ma L, Fan YN, Wu HF et al (2013) Tissue distribution and targeting evaluation of TMP after oral administration of TMP-loaded microemulsion to mice. Drug Dev Ind Pharm 39:1951–1958

    Article  CAS  PubMed  Google Scholar 

  • Pan EY, Wu HF, Lu CH et al (2010) O/O type of puerarin nanoemulsion the absorption of transport mechanism in rats and particle correlation study. China J Chin Mater Med. 35:2674–2678

    CAS  Google Scholar 

  • Qi J (2010) Eonurine protective effect on cerebral ischemia in rats and its mechanism. Fudan university, Shanghai

    Google Scholar 

  • Shi XR, Hong ZY, Liu HR et al (2011) Neuroprotective effect of SCM 198 on 6-hydroxydopamine-induced behavioral deficit in rats and cytotoxicity in neuronal SH-SY5Y cell. Neurochem Inter. 58:851–860

    Article  CAS  Google Scholar 

  • Wan ML, Liu ZR, Gui SY et al (2011) Preparation of oral tetramethylpyrazine oil/oil microemulsion and its pharmacokinetics in rats. J Anhui TCM C. 30:60–64

    CAS  Google Scholar 

  • Wang L, Wu HF, Lu CH et al (2009) The pathway of absorption and conveying of puerarin microemulsion-in-oil. Acta Pharm Sin. 44:798–802

    CAS  Google Scholar 

  • Wu HF, Lu CH, Zhou A et al (2009) Enhanced oral bioavailability of puerarin using microemulsion vehicle. Drug Dev Ind Pharm. 35:138–144

    Article  CAS  PubMed  Google Scholar 

  • Wu HF, Zhou A, Lu CH et al (2011) Examination of lymphatic transport of puerarin in unconscious lymph duct-cannulated rats after administration in microemulsion drug delivery systems. Eur J Pharm Sci 42:348–353

    Article  CAS  PubMed  Google Scholar 

  • Wu HF, Zhou A, Lu CH et al (2012) Absorption and distribution of puerarin nanoemulsion with different particle size. Chin Pharm J. 47:44–49

    CAS  Google Scholar 

  • Xu QL, Zhou P, Li JM et al (2012) Inhibitory effect of syringoylagmatine on platelet aggregation in rabbit. Anhui Medical Pharm J. 16:1762–1764

    Google Scholar 

  • Yang PF, Cai XL, Zhou K et al (2014) A novel oil-body nanoemulsion formulation of ginkgolide B: pharmacokinetics study and in vivo pharmacodynamics evaluations. J Pharm Sci 103:1075–1084

    Article  CAS  PubMed  Google Scholar 

  • Yuan M, Zhao YH, Li JM (2011) Synthesis and anti-platelet aggregation activity cloves acid derivatives. Chin J New Drugs. 20:1801–1804

    CAS  Google Scholar 

  • Zhu Q, Cai WM, Sha XY et al (2012) Quantification of leonurine, a novel potential cardiovascular agent, in rat plasma by liquid chromatography-tandem mass spectrometry and its application to pharmacokinetic study in rats. Biomed Chromatogr 26:518–523

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmaceutics, Anhui University of Chinese Medicine, 103 Mei Shan Road, Hefei, Anhui, China

    Yanan Sun, Xiang Zhang, Yuan Yuan, Qi Ding & Chuanhua Lu

  2. Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, Hefei, 20038, Anhui, China

    Tao Lu

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  1. Yanan Sun
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  2. Xiang Zhang
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  3. Tao Lu
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  4. Yuan Yuan
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  5. Qi Ding
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  6. Chuanhua Lu
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Correspondence to Chuanhua Lu.

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Sun, Y., Zhang, X., Lu, T. et al. A study on the PK and BA profiles in the mouse body for leonurine O/O microemulsion with determination by the LC-MS/MS method. Eur J Drug Metab Pharmacokinet 41, 423–432 (2016). https://doi.org/10.1007/s13318-015-0268-3

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  • DOI: https://doi.org/10.1007/s13318-015-0268-3

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