Pharmacokinetic Interaction of Astragaloside IV with Atractylenolide I and Prim-O-Glucosylcimifugin in Male Sprague Dawley Rats

Abstract

Astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin are main medicinal components of the traditional Chinese medicine prescription Yu-ping-feng which is composed of three herbs: Astragalus membranaceus, Atractylodes macrocephala, and Saposhnikovia divaricata. This study is aimed to assess the influence of atractylenolide I and prim-O-glucosylcimifugin on the pharmacokinetic profile of astragaloside IV so as to investigate the pharmacokinetic mechanisms of the Yu-ping-feng prescription. Fifteen Sprague Dawley rats were randomized to three groups; astragaloside IV, astragaloside IV plus atractylenolide I, and a combination of astragaloside IV, atractylenolide I, and prim-O-glucosylcimifugin were respectively administered to rats of these three groups via intragastric gavage. Serum samples were collected at different times after drug administration, and serum concentrations of astragaloside IV and atractylenolide I were simultaneously detected using HPLC-electrospray ionization-MS. Compared with administration of astragaloside IV alone, concentrations of astragaloside IV in the serum were significantly increased when it was given in combination with atractylenolide I or atractylenolide I+prim-O-glucosylcimifugin, with higher values for C_max (p = 0.019 and p = 0.033 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively) and AUC (p = 0.0052 and p = 0.0047 compared with astragaloside IV + atractylenolide I and astragaloside IV + atractylenolide I + prim-O-glucosylcimifugin groups, respectively). Improvement in mean oral C_max and mean systemic serum exposure because of the pharmacokinetic interaction between astragaloside IV and atractylenolide I might explain the rationale for the use of multiple herbs in Yu-ping-feng and of combinations of A.membranaceus and A. macrocephala.

Key words

pharmacokinetic interaction - astragaloside IV - atractylenolide I - Astragalus membranaceus - Atractylodes macrocephala - Yu-ping-feng - Leguminosae - Compositae - Umbelliferae

• References

• 1 Song J, Lu T, Xie L, Liu XD. [A serum pharmacological study on antioxidation effects of Huanglian Jiedu Tang]. Chin J Exp Tradit Med Form 2010; 16: 118-122 (In Chinese)
• 2 Zeng ZP, Jiang JG. Analysis of the adverse reactions induced by natural product-derived drugs. Br J Pharmacol 2010; 159: 1374-1391
• 3 Makino T, Sasaki SY, Ito Y, Kano Y. Pharmacological properties of traditional medicine: effects of Gyokuheifusan on murine antigen-specific antibody production. Biol Pharm Bull 2005; 28: 110-113
• 4 Makino T. [Pharmacological properties of Gyokuheifusan, a traditional Kampo medicinal formula]. Yakugaku Zasshi 2005; 125: 349-354 (In Japanese)
• 5 Chen XT, Li J, Cheng WM, Zhang L, Ge JF. Immunomodulating effects of fractioned polysaccharides isolated from Yu-Ping-Feng-powder in cyclophosphamide-treated mice. Am J Chin Med 2006; 34: 631-641
• 6 Gong CZ, Ma XB, Jin ZF, Wang C. Yu-ping-feng [M]. Beijing: Medicinal Technology Publishing Company of China; 2009: 5-30
• 7 Song J, Li J, Zheng SR, Jin Y, Huang Y. Anti-inflammatory and immunoregulatory effects of Yupingfeng powder on chronic bronchitis rats. Chin J Integr Med 2013; 19: 353-359
• 8 Lu T, Song J, Huang F, Deng YX, Xie L, Wang GJ, Liu XD. Comparative pharmacokinetics of baicalin after ig administration of pure baicalin, Radix Scutellariae extract and Huang-Lian-Jie-Du-Tang to rat. J Ethnopharmacol 2007; 110: 412-418
• 9 Lan K, He JL, Tian Y, Tan F, Jiang XH, Wang L, Ye LM. Intra-herb pharmacokinetics interaction between quercetin and isorhamentin1. Acta Pharmacol Sin 2008; 29: 1376-1382
• 10 Yeung WS. Qualitative research approach in traditional Chinese medicine. J Altern Complement Med 2009; 15: 5-7
• 11 Di B, Feng NP, Liu WY. Pharmacokinetic comparisons of Shuang–Huang–Lian with the different combinations of its constitutional herbs. J Ethnopharmacol 2006; 107: 401-405
• 12 State Food and Drug Administration. The Chinese pharmacopoeia, Volume 1. Beijing: China Medical Science Press; 2000: 249
• 13 Li ZP, Cao Q. Effects of astragaloside IV on myocardial calcium transport and cardiac function in ischemic rats. Acta Pharmacol Sin 2002; 23: 898-904
• 14 Zhang WJ, Hufnagl P, Binder BR, Wojta J. Antiinflammatory activity of astragaloside IV is mediated by inhibition of NF-kappaB activation and adhesion molecule expression. Thromb Haemost 2003; 90: 904-914
• 15 Wang YP, Li XY, Song CQ, Hu ZB. Effect of astragaloside IV on T, B lymphocyte proliferation and peritoneal macrophage function in mice. Acta Pharmacol Sin 2002; 23: 263-266
• 16 Hong F, Xiao WL, Ragupathi G, Lau CBS, Leung PC, Yeung KS, George C, Cassileth B, Kennelly E, Livingston PO. The known immunologically active components of Astragalus account for only a small proportion of the immunological adjuvant activity when combined with conjugate vaccines. Planta Med 2011; 77: 817-824
• 17 Zhang WD, Chen H, Zhang C, Liu RH, Li HL, Chen HZ. Astragaloside IV from Astragalus membranaceus shows cardioprotection during myocardial ischemia in vivo and in vitro . Planta Med 2006; 72: 4-8
• 18 Yung LY, Lam WS, Ho MKC, Hu YQ, Ip FCF, Pang H, Chin AC, Harley CB, Ip NY, Wong YH. Astragaloside IV and cycloastragenol stimulate the phosphorylation of extracellular signal-regulated protein kinase in multiple cell types. Planta Med 2012; 78: 115-121
• 19 Wang CH, Duan HJ, He LC. Inhibitory effect of atractylenolide I on angiogenesis in chronic inflammation in vivo and in vitro . Eur J Pharmacol 2009; 612: 143-152
• 20 Dai JN, Chen XH, Cheng WM, Liu X, Fan X, Shen ZD, Bi KS. A sensitive liquid chromatography–mass spectrometry method for simultaneous determination of two active chromones from Saposhnikovia root in rat plasma and urine. J Chromatogr B 2008; 868: 13-19
• 21 Jiang H, Shi J, Li Y. Screening for compounds with aromatase inhibiting activities from Atractylodes macrocephala Koidz. Molecules 2011; 16: 3146-3151
• 22 Gu YC, Wang GJ, Fawcett JP. Determination of astragaloside IV in rat plasma by liquid chromatography electrospray ionization mass spectrometry. J Chromatogr B 2004; 8: 285-288
• 23 Zheng SR, Li J, Song J. Simultaneous determination of three principal components in Yupingfeng decoction by HPLC-MS. Acta Univ Med Anhui 2011; 6: 191-196
• 24 Zhang WD, Zhang C, Liu RH, Li HL, Zhang JT, Mao C, Chen CL. Quantitative determination of astragaloside IV, a natural product with cardioprotective activity, in plasma, urine and other biological samples by HPLC coupled with tandem mass spectrometry. J Chromatogr B 2005; 822: 170-177
• 25 Huang HP, Liu CX, Li YL, Gao GL. Study on absorption kinetics of astragaloside IV in rats intestines. China J Chin Mater Med 2008; 33: 1609-1611
• 26 Li YJ, Zhang YS, Wang ZM, Zhu JJ, Tian Y, Chen B. Quantitative analysis of atractylenolide I in rat plasma by LC–MS/MS method and its application to pharmacokinetic study. J Pharm Biomed Anal 2012; 58: 172-176
• 27 Li W, Wen HM, Cui XB, Li X, Hong M. Active components of Atractylodes macrocephala on invigorating the spleen and stomach. J Nanjing Tradit Chin Med Univ 2006; 22: 366-367
• 28 State Food and Drug Administration. Appendix XIX B: Guidance for bioanalytical method validation. The Chinese pharmacopoeia, Volume 2. Beijing: China Medical Science Press; 2010: 195-196