A Comparative Study on the Metabolism of Epimedium koreanum Nakai-Prenylated Flavonoids in Rats by an Intestinal Enzyme (Lactase Phlorizin Hydrolase) and Intestinal Flora
The aim of this study was to compare the significance of the intestinal hydrolysis of prenylated flavonoids in Herba Epimedii by an intestinal enzyme and flora. Flavonoids were incubated at 37 °C with rat intestinal enzyme and intestinal flora. HPLC-UV was used to calculate the metabolic rates of the parent drug in the incubation and LC/MS/MS was used to determine the chemical structures of metabolites generated by different flavonoid glycosides. Rates of flavonoid metabolism by rat intestinal enzyme were quicker than those of intestinal flora. The sequence of intestinal flora metabolic rates was icariin > epimedin B > epimedin A > epimedin C > baohuoside I, whereas the order of intestinal enzyme metabolic rates was icariin > epimedin A > epimedin C > epimedin B > baohuoside I. Meanwhile, the LC/MS/MS graphs showed that icariin produced three products, epimedin A/B/C had four and baohuoside I yielded one product in incubations of both intestinal enzyme and flora, which were more than the results of HPLC-UV due to the fact LC/MS/MS has lower detectability and higher sensitivity. Moreover, the outcomes indicated that the rate of metabolization of flavonoids by intestinal enzyme were faster than those of intestinal flora, which was consistent with the HPLC-UV results. In conclusion, the metabolic pathways of the same components by intestinal flora and enzyme were the same. What’s more, an intestinal enzyme such as lactase phlorizin hydrolase exhibited a more significant metabolic role in prenylated flavonoids of Herba Epimedi compared with intestinal flora.
References
[1]
Cui, L.; Zhang, Z.H.; Tan, X.B.; Wei, Y.J.; Jin, X.; Jia, X.B. Enhancement of Epimedium fired with suet oil based on in vivo formation of self-assembled flavonoid compound nanomicelles. Molecules 2012, 17, 12984–12996, doi:10.3390/molecules171112984.
[2]
Han, H.; Shan, Q.; Zhou, F.J.; Zhang, X.X.; Hou, W.B. Research progress in metabolites of active constitutes from Epimedii Herbal. Drugs Clin. 2013, 28, 78–81.
[3]
Zeng, S.H.; Gong, X.; Guo, J.; Fei, Z.J.; Xu, Y.Q.; Roe, B.A.; Wang, Y. Development of a EST dataset and characterization of EST-SSRs in traditional Chinese medicinal plant, Epimedum sagiitatum (Sieb. Et Zucc.) Maxim. BMC Genomics 2010, 11, 94, doi:10.1186/1471-2164-11-94.
[4]
Chen, Y.; Zhao, Y.H.; Jia, X.B.; Ding, A.W. Simultaneous determination of five main flavonoids in herb Epimedii from different species by RP-HPLC-UV. Chin. Pharm. 2008, 19, 431–432.
[5]
Guo, Q.; Wu, X.Y.; Ning, Q.; Lv, X. Analysis and quality evaluation of five falvonoids in folium and rhizome of Epimedii Folium. Chin. Tradit. Herb. Drugs 2011, 42, 2028–2035.
[6]
Xu, Y.; Li, Z.; Yuan, L.; Zhang, X.; Lu, D.; Huang, H.; Wang, Y. Variation of epimedins A–C and icariin in ten representative populations of Epimedium brevicornu Maxim., and implications for utilization. Chem. Biodivers. 2013, 10, 711–721, doi:10.1002/cbdv.201100424.
[7]
Chen, Y.; Wang, J.Y.; Jia, X.B.; Tan, X.B.; Hu, M. Rloe of intestinal hydrolase in the absorption of prenylated flavonoids present in Yinyanghuo. Molecules 2011, 16, 1336–1348, doi:10.3390/molecules16021336.
[8]
Zhang, G.; Qi, L.; Hung, W.Y.; Shi, Y.Y.; Leung, P.C.; Yeung, H.Y.; Leung, K.S. Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption. Bone 2006, 38, 818–825, doi:10.1016/j.bone.2005.11.019.
[9]
Chang, Q.; Wang, G.N.; Li, Y.; Zhang, L.; You, C.; Zheng, Y. Oral absorption and excretion of icaritin, an aglycone and also active metabolite of prenylflavonoids from the Chinese medicine Herba Epimedii in rats. Phytomed 2012, 19, 1024–1028, doi:10.1016/j.phymed.2012.05.017.
[10]
Yao, Z.H.; Liu, M.Y.; Dai, Y.; Zhang, Y.; Qin, Z.F.; Tu, F.J.; Yao, X.S. Metabolism of Epimedium-derived flavonoid glycosides in intestinal flora of rabbits and its inhibition by gluconolactone. Chin. J. Nat. Med. 2011, 9, 461–465.
[11]
Liu, T.H.; Wang, Y.; Wang, B.X.; Wu, L.J. Studies on the metabolism of icariin by intestinal bacteria part I: The transformation of icariin by intestinal flora. Chin. Tradit. Herb. Drugs 2000, 31, 834–836.
[12]
Hong, X.; Wang, X.C.; Yong, E.L.; Gong, Y.H. Determination of breviflavone A and B in Epimedium herbs with liquid chromatography-tandem mass spectrometry. J. Pharm. Biomed. Anal. 2009, 49, 853–857, doi:10.1016/j.jpba.2008.12.036.
[13]
Gao, M.T.; Ma, F.F.; Wu, S.H.; Luo, T.S.; Zhang, C.G. Research advanced in pharmacological effects of icarrin. Med. Plant 2013, 4, 79–82.
[14]
Jin, Y.; Wu, C.S.; Zhang, J.L.; Li, Y.F. A new strategy for the discovery of epimedium metabolites using high-performance liquid chromatography with high resolution mass spectrometry. Anal. Chim. Acta 2013, 768, 111–117, doi:10.1016/j.aca.2013.01.012.
[15]
Ming, L.G.; Chen, K.M.; Xian, C.J. Functions and action mechanisms of flavonoids genistein and icariin in regulating bone remodeling. J. Cell. Physiol. 2013, 228, 513–521, doi:10.1002/jcp.24158.
[16]
Kuokkanen, M.; Enattah, N.S.; Oksanen, A.; Savilahti, E.; Orpana, A.; J？rvel？, I. Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia. Gut 2003, 52, 647–652, doi:10.1136/gut.52.5.647.
[17]
Wilkinson, A.P.; Gee, J.M.; Dupont, M.S.; Needs, P.W.; Mellon, F.A.; Williamson, G.; Johnson, I.T. Hydrolysis by lac-tase phlorizin hydrolase is the first step in the uptake of daidzein glucosides by rat small intestine in vitro. Xenobiotica 2003, 33, 255–264.
[18]
Nandakumar, N.; Balasubramanian, M.P. Hesperidin a citrus bioflavonoid modulates hepatic biotransformation enzymes and enhances intrinsic antioxidants in experimental breast cancer rats challenged with 7, 12-dimethylbenz (a) anthracene. J. Exp. Ther. Oncol. 2012, 9, 321–335.
[19]
Peter, C.H. Absorption, bioavailability, and metabolism of flavonoids. Pharm. Biol. 2004, 42, 74–83.
[20]
Akao, T.; Che, Q.M.; Kyoichi, K.; Hattori, M.; Namba, T. A purgative action of barbaloin is induced by Eubacterium sp. Strain BAR, a human intestinal anaerobic, capable of transforming barbaloin to aloe emodin anthrone. Biol. Pharm. Bull. 1996, 19, 136–138, doi:10.1248/bpb.19.136.
[21]
Sesink, A.L.; Arts, I.C.; Faassen-Peters, M.; Hollman, P.C. Intestinal uptake of quercetin-3-glucoside in rats involves hydrolysis by lactase phlorizin hydrolase. J. Nutr. 2003, 133, 773–776.
