An Approach to Characterizing the Complicated Sequential Metabolism of Salidroside in Rats

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2016 Jun 2

PMID 27248984

Citations 7

Authors

Zhiqiang Luo

Xiaoyun Ma

Yang Liu

Lina Lu

Ruirui Yang

Guohua Yu

Mohan Sun

Shaokun Xin

Simin Tian

Xinjing Chen

Haiyu Zhao

Affiliations

Soon will be listed here.

Abstract

Metabolic study of bioactive compounds that undergo a dynamic and sequential process of metabolism is still a great challenge. Salidroside, one of the most active ingredients of Rhodiola crenulata, can be metabolized in different sites before being absorbed into the systemic blood stream. This study proposed an approach for describing the sequential biotransformation process of salidroside based on comparative analysis. In vitro incubation, in situ closed-loop and in vivo blood sampling were used to determine the relative contribution of each site to the total metabolism of salidroside. The results showed that salidroside was stable in digestive juice, and it was metabolized primarily by the liver and the intestinal flora and to a lesser extent by the gut wall. The sequential metabolism method described in this study could be a general approach to characterizing the metabolic routes in the digestive system for natural products.

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References

Diaz Lanza A, Abad Martinez M, Fernandez Matellano L, Recuero Carretero C, Villaescusa Castillo L, Silvan Sen A . Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity. Planta Med. 2001; 67(3):219-23. DOI: 10.1055/s-2001-12004. View

Kelly G . Rhodiola rosea: a possible plant adaptogen. Altern Med Rev. 2001; 6(3):293-302. View

Nan J, Jiang Y, Park E, Ko G, Kim Y, Sohn D . Protective effect of Rhodiola sachalinensis extract on carbon tetrachloride-induced liver injury in rats. J Ethnopharmacol. 2003; 84(2-3):143-8. DOI: 10.1016/s0378-8741(02)00293-3. View

Zhang L, Yu H, Sun Y, Lin X, Chen B, Tan C . Protective effects of salidroside on hydrogen peroxide-induced apoptosis in SH-SY5Y human neuroblastoma cells. Eur J Pharmacol. 2007; 564(1-3):18-25. DOI: 10.1016/j.ejphar.2007.01.089. View

Zhang Y, Wu W, Han F, Chen Y . LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine. Biomed Chromatogr. 2008; 22(12):1360-7. DOI: 10.1002/bmc.1066. View

Skopinska-Rozewska E, Malinowski M, Wasiutynski A, Sommer E, Furmanowa M, Mazurkiewicz M . The influence of Rhodiola quadrifida 50% hydro-alcoholic extract and salidroside on tumor-induced angiogenesis in mice. Pol J Vet Sci. 2008; 11(2):97-104. View

Wang H, Ding Y, Zhou J, Sun X, Wang S . The in vitro and in vivo antiviral effects of salidroside from Rhodiola rosea L. against coxsackievirus B3. Phytomedicine. 2008; 16(2-3):146-55. DOI: 10.1016/j.phymed.2008.07.013. View

Zhang J, Liu A, Hou R, Zhang J, Jia X, Jiang W . Salidroside protects cardiomyocyte against hypoxia-induced death: a HIF-1alpha-activated and VEGF-mediated pathway. Eur J Pharmacol. 2009; 607(1-3):6-14. DOI: 10.1016/j.ejphar.2009.01.046. View

Yu S, Shen Y, Liu J, Ding F . Involvement of ERK1/2 pathway in neuroprotection by salidroside against hydrogen peroxide-induced apoptotic cell death. J Mol Neurosci. 2009; 40(3):321-31. DOI: 10.1007/s12031-009-9292-6. View

10.

Hu X, Lin S, Yu D, Qiu S, Zhang X, Mei R . A preliminary study: the anti-proliferation effect of salidroside on different human cancer cell lines. Cell Biol Toxicol. 2010; 26(6):499-507. DOI: 10.1007/s10565-010-9159-1. View

11.

Zhu Y, Shi Y, Wu D, Ji Y, Wang X, Chen H . Salidroside protects against hydrogen peroxide-induced injury in cardiac H9c2 cells via PI3K-Akt dependent pathway. DNA Cell Biol. 2011; 30(10):809-19. DOI: 10.1089/dna.2010.1183. View

12.

Koncic M, Tomczyk M . New insights into dietary supplements used in sport: active substances, pharmacological and side effects. Curr Drug Targets. 2013; 14(9):1079-92. DOI: 10.2174/1389450111314090016. View

13.

Luo Z, Liu Y, Zhao B, Tang M, Dong H, Zhang L . Ex vivo and in situ approaches used to study intestinal absorption. J Pharmacol Toxicol Methods. 2013; 68(2):208-216. DOI: 10.1016/j.vascn.2013.06.001. View

14.

Fang D, Chen Y, Xu B, Ren K, He Z, He L . Development of lipid-shell and polymer core nanoparticles with water-soluble salidroside for anti-cancer therapy. Int J Mol Sci. 2014; 15(3):3373-88. PMC: 3975343. DOI: 10.3390/ijms15033373. View

15.

Wang J, Li J, Lu A, Zhang K, Li B . Anticancer effect of salidroside on A549 lung cancer cells through inhibition of oxidative stress and phospho-p38 expression. Oncol Lett. 2014; 7(4):1159-1164. PMC: 3961258. DOI: 10.3892/ol.2014.1863. View

16.

Guo N, Zhu M, Han X, Sui D, Wang Y, Yang Q . The metabolism of salidroside to its aglycone p-tyrosol in rats following the administration of salidroside. PLoS One. 2014; 9(8):e103648. PMC: 4125138. DOI: 10.1371/journal.pone.0103648. View

17.

Liu S, Yu X, Hu B, Zou Y, Li J, Bo L . Salidroside rescued mice from experimental sepsis through anti-inflammatory and anti-apoptosis effects. J Surg Res. 2015; 195(1):277-83. DOI: 10.1016/j.jss.2015.01.021. View

18.

Zhang L, Zhao H, Liu Y, Dong H, Lv B, Fang M . Metabolic routes along digestive system of licorice: multicomponent sequential metabolism method in rat. Biomed Chromatogr. 2015; 30(6):902-12. DOI: 10.1002/bmc.3626. View

19.

Ren W, Xin S, Han L, Zuo R, Li Y, Gong M . Comparative metabolism of four limonoids in human liver microsomes using ultra-high-performance liquid chromatography coupled with high-resolution LTQ-Orbitrap mass spectrometry. Rapid Commun Mass Spectrom. 2015; 29(21):2045-56. DOI: 10.1002/rcm.7365. View

20.

Hu Z, Wang Z, Liu Y, Wu Y, Han X, Zheng J . Metabolite Profile of Salidroside in Rats by Ultraperformance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry and High-Performance Liquid Chromatography Coupled with Quadrupole-Linear Ion Trap Mass Spectrometry. J Agric Food Chem. 2015; 63(41):8999-9005. DOI: 10.1021/acs.jafc.5b04510. View