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XING Yuanyue, REN Siqi, LIU Qiwei, YANG Jinni, DONG Haijuan, SONG Rui, ZHANG Zunjian. Intestinal absorption mechanism of saikosaponin d in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2022, 53(4): 473-480. DOI: 10.11665/j.issn.1000-5048.20220410
Citation: XING Yuanyue, REN Siqi, LIU Qiwei, YANG Jinni, DONG Haijuan, SONG Rui, ZHANG Zunjian. Intestinal absorption mechanism of saikosaponin d in vitro and in vivo[J]. Journal of China Pharmaceutical University, 2022, 53(4): 473-480. DOI: 10.11665/j.issn.1000-5048.20220410
shu

Intestinal absorption mechanism of saikosaponin d in vitro and in vivo

  • 1.

    Key Laboratory of Drug Quality Control & Pharmacovigilance, China Pharmaceutical University, Ministry of Education, Nanjing 210009

  • 2.

    The Public Laboratory Platform of China Pharmaceutical University, Nanjing 210009, China

Funds: This study was supported by the Natural Science Foundation of Jiangsu Province (No. BK20161456), Jiangsu Provincial Drug Administration Scientific Research Program (No.202016) and the Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance (No.DQCP20/21PQ06)
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  • Received Date: April 10, 2022
  • Revised Date: June 07, 2022
    Graphical Abstract
    • Abstract
  • In order to reveal the intestinal absorption mechanism of saikosaponin d (SSd) in vitro and in vivo, the current research investigated the effects of different experimental conditions (time, concentration, temperature, pH, intestinal segments), transporter inhibitors, paracellular pathway enhancer, metabolic enzyme inhibitors on the intestinal absorption of SSd, in Caco-2 monolayers and a single pass perfusion model in rats.The results showed that the apparent permeability coefficient (Papp) and effective permeability coefficient (Peff) of SSd were 4.75 × 10-7 - 6.38 × 10-7 cm/s and 0.19 × 10-4- 0.27 × 10-4 cm/s, respectively, indicating that it was a low permeability compound, and that the transmembrane transport of SSd was concentration-dependent (0.5-5 μmol/L) and time-dependent (0-180 min).Ileum was the main absorption site for SSd. Experimental results based on Caco-2 monolayers showed that the P-gp inhibitor and paracellular permeability enhancer significantly increased the absorption of SSd (P < 0.05), which was consistent with the results obtained in rats. Inhibitors of OATPs and OCTs showed different results in vitro and in vivo, which may be related to the lower expression of them in jejunum.In summary, the intestinal absorption of SSd occurs through a carrier-mediated and energy-dependent transport, as well as passive diffusion, and P-glycoprotein plays an important role in the active transport of SSd.
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    • References (32)
  • [1]
    . Biomed Pharmacother，2020，131：110679.
    [2]
    Yuan BC，Yang R，Ma YS，et al. A systematic review of the active saikosaponins and extracts isolated from Radix Bupleuri and their applications［J］. Pharm Biol，2017，55（1）：620-635.
    [3]
    Boto REF，Almeida P，Queiroz JA. Thiacarbocyanine as ligand in dye-affinity chromatography for protein purification［J］. Biomed Chromatogr，2008，22（3）：278-288.
    [4]
    Yan ZX，Chen Y，Li TX，et al. Identification of metabolites of Si-Ni-San，a traditional Chinese medicine formula，in rat plasma and urine using liquid chromatography/diode array detection/triple-quadrupole spectrometry［J］. J Chromatogr B Analyt Technol Biomed Life Sci，2012，885/886：73-82.
    [5]
    Xu L，Song R，Tian JX，et al. Analysis of saikosaponins in rat plasma by anionic adducts-based liquid chromatography tandem mass spectrometry method［J］. Biomed Chromatogr，2012，26（7）：808-815.
    [6]
    Hu SCS，Lai YC，Lin CL，et al. Inclusion complex of saikosaponin-d with hydroxypropyl-β-cyclodextrin：improved physicochemical properties and anti-skin cancer activity［J］. Phytomedicine，2019，57：174-182.
    [7]
    Li Y，Gao XX，Wang H，et al. Study on intestinal absorption of Chaigui granules in vitro based on UPLC-Q/exactive orbitrap-MS/MS［J］. J Shanxi Med Univ （山西医科大学学报），2020，51（2）：165-170.
    [8]
    Du T，Zeng M，Chen L，et al. Chemical and absorption signatures of Xiao Chaihu Tang［J］. Rapid Commun Mass Spectrom，2018，23：1107-1125.
    [9]
    Chen Y，Wang JY，Yuan L，et al. Interaction of the main components from the traditional Chinese drug pair Chaihu-Shaoyao based on rat intestinal absorption［J］. Molecules，2011，16（11）：9600-9610.
    [10]
    Ren SQ，Liu JJ，Xue YW，et al. Comparative permeability of three saikosaponins and corresponding saikogenins in Caco-2 model by a validated UHPLC-MS/MS method［J］. J Pharm Anal，2021，11（4）：435-443.
    [11]
    Keiser M，Kaltheuner L，Wildberg C，et al. The organic anion-transporting peptide 2B1 is localized in the basolateral membrane of the human jejunum and caco-2 monolayers［J］. J Pharm Sci，2017，106（9）：2657-2663.
    [12]
    Xu F，Zhu L，Qian CQ，et al. Impairment of intestinal monocarboxylate transporter 6 function and expression in diabetic rats induced by combination of high-fat diet and low dose of streptozocin：involvement of butyrate-peroxisome proliferator-activated receptor-γ activation［J］. Drug Metab Dispos，2019，47（6）：556-566.
    [13]
    Engel K，Wang J. Interaction of organic cations with a newly identified plasma membrane monoamine transporter［J］. Mol Pharmacol，2005，68（5）：1397-1407.
    [14]
    Wang C，Zhou YM，Gong XH，et al. In vitro and in situ study on characterization and mechanism of the intestinal absorption of 2，3，5，4'-tetrahydroxy-stilbene-2-O-β-D-glucoside［J］. BMC Pharmacol Toxicol，2020，21（1）：7.
    [15]
    Yang H，Zhai BT，Fan Y，et al. Intestinal absorption mechanisms of araloside A in situ single-pass intestinal perfusion and in vitro Caco-2 cell model［J］. Biomed Pharmacother，2018，106：1563-1569.
    [16]
    Citi S. Protein kinase inhibitors prevent junction dissociation induced by low extracellular calcium in MDCK epithelial cells［J］. J Cell Biol，1992，117（1）：169-178.
    [17]
    Zhang WZ，Liu H，Liu CF. Biopharmaceutics classification and intestinal absorption of chikusetsusaponin IVa［J］. Biopharm Drug Dispos，2019，40（8）：276-281.
    [18]
    Shinohara Y，Yoshikawa K，Terada H. Effect of the weakly acidic uncoupler 2，4-dinitrophenol and dimethyl sulfoxide on the coordination of Mg2+ with ATP. Possible mechanism of activation of the isolated F1-ATPase by 2，4-dinitrophenol［J］. Biophys Chem，1990，36（3）：201-208.
    [19]
    Fois CAM，Le TYL，Schindeler A，et al. Models of the gut for analyzing the impact of food and drugs［J］. Adv Healthc Mater，2019，8（21）：e1900968.
    [20]
    Adachi Y，Suzuki H，Sugiyama Y. Quantitative evaluation of the function of small intestinal P-glycoprotein：comparative studies between in situ and in vitro［J］. Pharm Res，2003，20（8）：1163-1169.
    [21]
    Yee SY. In vitro permeability across caco-2 cells （colonic） can predict in vivo （small intestinal） absorption in man—fact or myth［J］. Pharm Res，1997，14：763-766.
    [22]
    Antonescu IE，Rasmussen KF，Neuhoff S，et al. The permeation of acamprosate is predominantly caused by paracellular diffusion across caco-2 cell monolayers：a paracellular modeling approach［J］. Mol Pharm，2019，16（11）：4636-4650.
    [23]
    Tang C，Fu QC，Chen X，et al. The biotransformation of Bupleuri Radix by human gut microbiota［J］. Xenobiotica，2020，50（9）：1011-1022.
    [24]
    Roth M，Obaidat A，OATPs Hagenbuch B.，OATs and OCTs：the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies［J］. Br J Pharmacol，2012，165（5）：1260-1287.
    [25]
    Karlgren M，Vildhede A，Norinder U，et al. Classification of inhibitors of hepatic organic anion transporting polypeptides （OATPs）：influence of protein expression on drug-drug interactions［J］. J Med Chem，2012，55（10）：4740-4763.
    [26]
    Sch?fer AM，Meyer Zu Schwabedissen HE，Bien-M?ller S，et al. OATP1A2 and OATP2B1 are interacting with dopamine-receptor agonists and antagonists［J］. Mol Pharm，2020，17（6）：1987-1995.
    [27]
    Volpe DA. Drug-permeability and transporter assays in Caco-2 and MDCK cell lines［J］. Future Med Chem，2011，3（16）：2063-2077.
    [28]
    Sun HJ，Wang JF，Lv J. Effects of glycyrrhizin on the pharmacokinetics of paeoniflorin in rats and its potential mechanism［J］. Pharm Biol，2019，57（1）：550-554.
    [29]
    Ranaldi G，Seneci P，Guba W，et al. Transport of the antibacterial agent oxazolidin-2-one and derivatives across intestinal （Caco-2） and renal （MDCK） epithelial cell lines［J］. Antimicrob Agents Chemother，1996，40（3）：652-658.
    [30]
    Zakeri-Milani P，Barzegar-Jalali M，Azimi M，et al. Biopharmaceutical classification of drugs using intrinsic dissolution rate （IDR） and rat intestinal permeability［J］. Eur J Pharm Biopharm，2009，73（1）：102-106.
    [31]
    MacLean C，Moenning U，Reichel A，et al. Regional absorption of fexofenadine in rat intestine［J］. Eur J Pharm Sci，2010，41（5）：670-674.
    [32]
    Jin S，Lee S，Jeon JH，et al. Enhanced intestinal permeability and plasma concentration of metformin in rats by the repeated administration of red ginseng extract［J］. Pharmaceutics，2019，11（4）：189.
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