Distribution, Biotransformation, Pharmacological Effects, Metabolic Mechanism and Safety Evaluation of Platycodin D: A Comprehensive Review

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Abstract

Platycodonis Radix (Jiegeng), the dried root of Platycodon grandiflorum, is a traditional herb used as both medicine and food. Its clinical application for the treatment of cough, phlegm, sore throat, pulmonary and respiratory diseases has been thousands of years in China. Platycodin D is the main active ingredient in Platycodonis Radix, which belongs to the family of pentacyclic triterpenoid saponins because it contains an oleanolane type aglycone linked with double sugar chains. Modern pharmacology has demonstrated that Platycodin D displays various biological activities, such as analgesics, expectoration and cough suppression, promoting weight loss, anti-tumor and immune regulation, suggesting that Platycodin D has the potential to be a drug candidate and an interesting target as a natural product for clinical research. In this review, the distribution and biotransformation, pharmacological effects, metabolic mechanism and safety evaluation of Platycodin D are summarized to lay the foundation for further studies.

Keywords: Platycodin D, distribution, biotransformation, pharmacological effects, metabolic mechanism, safety evaluation.

Graphical Abstract

[1]
Zhang, L.L.; Huang, M.Y.; Yang, Y.; Huang, M.Q.; Shi, J.J.; Zou, L.; Lu, J.J. Bioactive platycodins from Platycodonis Radix: Phytochemistry, pharmacological activities, toxicology and pharmacokinetics. Food Chem., 2020, 327127029
[http://dx.doi.org/10.1016/j.foodchem.2020.127029] [PMID: 32450486]
[2]
Ji, M.Y.; Bo, A.; Yang, M.; Xu, J.F.; Jiang, L.L.; Zhou, B.C.; Li, M.H. The Pharmacological effects and health benefits of Platycodon grandiflorus-a medicine food homology species. Foods, 2020, 9(2)E142
[http://dx.doi.org/10.3390/foods9020142] [PMID: 32023858]
[3]
Zhang, L.; Wang, Y.; Yang, D.; Zhang, C.; Zhang, N.; Li, M.; Liu, Y. Platycodon grandiflorus - an ethnopharmacological, phytochemical and pharmacological review. J. Ethnopharmacol., 2015, 164, 147-161.
[http://dx.doi.org/10.1016/j.jep.2015.01.052] [PMID: 25666431]
[4]
Li, L.; Wu, Y.Z.; Wang, J.B.; Yan, H.M.; Lu, J.; Wan, Y.; Zhang, B.L.; Zhang, J.H.; Yang, J.; Wang, X.Y.; Zhang, M.; Li, Y.; Miao, L.; Zhang, H. Potential treatment of COVID-19 with traditional Chinese medicine: What herbs can help win the battle with SARS-CoV-2? Engineering (Beijing) 2021.
[http://dx.doi.org/10.1016/j.eng.2021.08.020]
[5]
Li, X.Y.; Chen, L.; Ma, Y.Y.; Deng, W. Comparison of the content of total saponins and platycodin D in Platycodon grandiflorum from Sichuan of different cultivated years. Chinese pharmacy, 2018, 29(09), 1249-1252.
[6]
Wang, X.J.; He, N.W.; Deng, H.S. Determination of content of platycodin D in Platycodon grandiflorum from different areas by HPLC. Jiangxi Nongye Daxue Xuebao, 2014, 26(08), 57-60.
[7]
Zuo, J.; Yin, B.K.; Hu, X.Y. Research progress in the chemical constituents and modern pharmacology of Platycodon. Liaoning Zhongyiyao Daxue Xuebao, 2019, 21(01), 113-116.
[8]
Xie, X.X.; Zhang, C.; Zeng, J.X.; Mao, Z. Advances in the study of chemical constituents and pharmacological activities of Platycodon Grandiflorum Thunb. Chinese Medicine Bulletin, 2018, 17(05), 66-72.
[9]
Ku, S. Finding and producing probiotic glycosylases for the biocatalysis of ginsenosides: A mini review. Molecules, 2016, 21(5)E645
[http://dx.doi.org/10.3390/molecules21050645] [PMID: 27196878]
[10]
Ku, S.; You, H.J.; Park, M.S.; Ji, G.E. Effects of ascorbic acid on α-l-arabinofuranosidase and α-l-arabinopyranosidase activities from Bifidobacterium longum RD47 and its application to whole cell bioconversion of ginsenoside. J. Korean Soc. Appl. Biol. Chem., 2015, 58(6), 857-865.
[http://dx.doi.org/10.1007/s13765-015-0113-z] [PMID: 26612991]
[11]
Ahn, H.J.; You, H.J.; Park, M.S.; Johnston, T.V.; Ku, S.; Ji, G.E. Biocatalysis of platycoside E and platycodin D3 using fungal extracellular beta-glucosidase responsible for rapid platycodin D production. Int. J. Mol. Sci., 2018, 19(9), 2671.
[http://dx.doi.org/10.3390/ijms19092671] [PMID: 30205574]
[12]
Ha, I.J.; Ha, Y.W.; Kang, M.; Lee, J.; Park, D.; Kim, Y.S. Enzymatic transformation of platycosides and one-step separation of platycodin D by high-speed countercurrent chromatography. J. Sep. Sci., 2010, 33(13), 1916-1922.
[http://dx.doi.org/10.1002/jssc.200900842] [PMID: 20533341]
[13]
Kang, S.H.; Kim, T.H.; Shin, K.C.; Ko, Y.J.; Oh, D.K. Biotransformation of food-derived saponins, platycosides, into deglucosylated saponins including deglucosylated platycodin D and their anti-inflammatory activities. J. Agric. Food Chem., 2019, 67(5), 1470-1477.
[http://dx.doi.org/10.1021/acs.jafc.8b06399] [PMID: 30652865]
[14]
Kil, T.G.; Kang, S.H.; Kim, T.H.; Shin, K.C.; Oh, D.K. Enzymatic biotransformation of balloon flower root saponins into bioactive platycodin d by deglucosylation with caldicellulosiruptor bescii β-glucosidase. Int. J. Mol. Sci., 2019, 20(16)E3854
[http://dx.doi.org/10.3390/ijms20163854] [PMID: 31394870]
[15]
Shin, K.C.; Kim, D.W.; Woo, H.S.; Oh, D.K.; Kim, Y.S. Conversion of glycosylated platycoside e to deapiose-xylosylated platycodin D by cytolase PCL5. Int. J. Mol. Sci., 2020, 21(4)E1207
[http://dx.doi.org/10.3390/ijms21041207] [PMID: 32054089]
[16]
Yu, M.K.; Chai, Q.Y.; Liang, C.H. An analyze of the traditional Chinese medicine prevention and treatment interventions for COVID-19. J. Tradit. Chin. Med., 2020, 61(05), 383-387.
[17]
Kim, T.Y.; Jeon, S.; Jang, Y.; Gotina, L.; Won, J.; Ju, Y.H.; Kim, S.; Jang, M.W.; Won, W.; Park, M.G.; Pae, A.N.; Han, S.; Kim, S.; Lee, C.J.; Platycodin, D. Platycodin D, a natural component of Platycodon grandiflorum, prevents both lysosome- and TMPRSS2-driven SARS-CoV-2 infection by hindering membrane fusion. Exp. Mol. Med., 2021, 53(5), 956-972.
[http://dx.doi.org/10.1038/s12276-021-00624-9] [PMID: 34035463]
[18]
Wu, C.; Liu, Y.; Yang, Y.; Zhang, P.; Zhong, W.; Wang, Y.; Wang, Q.; Xu, Y.; Li, M.; Li, X.; Zheng, M.; Chen, L.; Li, H. Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods. Acta Pharm. Sin. B, 2020, 10(5), 766-788.
[http://dx.doi.org/10.1016/j.apsb.2020.02.008] [PMID: 32292689]
[19]
Bailly, C.; Vergoten, G. Glycyrrhizin: An alternative drug for the treatment of COVID-19 infection and the associated respiratory syndrome? Pharmacol. Ther., 2020, 214107618
[http://dx.doi.org/10.1016/j.pharmthera.2020.107618] [PMID: 32592716]
[20]
Wang, Y.; Chen, Y.J.; Xiang, C.; Jiang, G.W.; Xu, Y.D.; Yin, L.M.; Zhou, D.D.; Liu, Y.Y.; Yang, Y.Q. Discovery of potential asthma targets based on the clinical efficacy of traditional Chinese medicine formulas. J. Ethnopharmacol., 2020, 252112635
[http://dx.doi.org/10.1016/j.jep.2020.112635] [PMID: 32004629]
[21]
Lai, K.; Shen, H.; Zhou, X.; Qiu, Z.; Cai, S.; Huang, K.; Wang, Q.; Wang, C.; Lin, J.; Hao, C.; Kong, L.; Zhang, S.; Chen, Y.; Luo, W.; Jiang, M.; Xie, J.; Zhong, N. Clinical practice guidelines for diagnosis and management of cough-Chinese thoracic society (CTS) asthma consortium. J. Thorac. Dis., 2018, 10(11), 6314-6351.
[http://dx.doi.org/10.21037/jtd.2018.09.153] [PMID: 30622806]
[22]
Bousquet, J.; Czarlewski, W.; Zuberbier, T.; Mullol, J.; Blain, H.; Cristol, J.P.; De La Torre, R.; Pizarro Lozano, N.; Le Moing, V.; Bedbrook, A.; Agache, I.; Akdis, C.A.; Canonica, G.W.; Cruz, A.A.; Fiocchi, A.; Fonseca, J.A.; Fonseca, S.; Gemicioğlu, B.; Haahtela, T.; Iaccarino, G.; Ivancevich, J.C.; Jutel, M.; Klimek, L.; Kraxner, H.; Kuna, P.; Larenas-Linnemann, D.E.; Martineau, A.; Melén, E.; Okamoto, Y.; Papadopoulos, N.G.; Pfaar, O.; Regateiro, F.S.; Reynes, J.; Rolland, Y.; Rouadi, P.W.; Samolinski, B.; Sheikh, A.; Toppila-Salmi, S.; Valiulis, A.; Choi, H.J.; Kim, H.J.; Anto, J.M. Potential interplay between Nrf2, TRPA1, and TRPV1 in nutrients for the control of COVID-19. Int. Arch. Allergy Immunol., 2021, 182(4), 324-338.
[http://dx.doi.org/10.1159/000514204] [PMID: 33567446]
[23]
Bu, F.J. Construction of TRPA1 receptor electrochemical biosensor and its application in screening of pungent substances in Platycodon Grandiflorum; Tianjin University of Commerce, 2021, p. 7.
[24]
Xie, Y.; Sun, H.X.; Li, D.; Platycodin, D. Platycodin d improves the immunogenicity of newcastle disease virus-based recombinant Avian influenza vaccine in mice. Chem. Biodivers., 2010, 7(3), 677-689.
[http://dx.doi.org/10.1002/cbdv.200900183] [PMID: 20232336]
[25]
Zhou, Y.; Zhou, M.; Mao, S. Adjuvant effects of platycodin D on immune responses to infectious bronchitis vaccine in chickens. J. Poult. Sci., 2020, 57(2), 160-167.
[http://dx.doi.org/10.2141/jpsa.0180089] [PMID: 32461731]
[26]
Chung, J.W.; Noh, E.J.; Zhao, H.L.; Sim, J.S.; Ha, Y.W.; Shin, E.M.; Lee, E.B.; Cheong, C.S.; Kim, Y.S. Anti-inflammatory activity of prosapogenin methyl ester of platycodin D via nuclear factor-kappaB pathway inhibition. Biol. Pharm. Bull., 2008, 31(11), 2114-2120.
[http://dx.doi.org/10.1248/bpb.31.2114] [PMID: 18981583]
[27]
Fu, Y.; Xin, Z.; Liu, B.; Wang, J.; Wang, J.; Zhang, X.; Wang, Y.; Li, F.; Platycodin, D. Platycodin D inhibits inflammatory response in LPS-stimulated primary rat microglia cells through activating LXRα-ABCA1 signaling pathway. Front. Immunol., 2018, 8, 1929.
[http://dx.doi.org/10.3389/fimmu.2017.01929] [PMID: 29375565]
[28]
Wang, B.; Gao, Y.; Zheng, G.; Ren, X.; Sun, B.; Zhu, K.; Luo, H.; Wang, Z.; Xu, M. Platycodin D inhibits interleukin-13-induced the expression of inflammatory cytokines and mucus in nasal epithelial cells. Biomed. Pharmacother., 2016, 84, 1108-1112.
[http://dx.doi.org/10.1016/j.biopha.2016.10.052] [PMID: 27780139]
[29]
Wu, J.; Yang, G.; Zhu, W.; Wen, W.; Zhang, F.; Yuan, J.; An, L. Anti-atherosclerotic activity of platycodin D derived from roots of Platycodon grandiflorum in human endothelial cells. Biol. Pharm. Bull., 2012, 35(8), 1216-1221.
[http://dx.doi.org/10.1248/bpb.b-y110129] [PMID: 22863916]
[30]
Luo, Q.; Wei, G.; Wu, X.; Tang, K.; Xu, M.; Wu, Y.; Liu, Y.; Li, X.; Sun, Z.; Ju, W.; Qi, K.; Chen, C.; Yan, Z.; Cheng, H.; Zhu, F.; Li, Z.; Zeng, L.; Xu, K.; Qiao, J. Platycodin D inhibits platelet function and thrombus formation through inducing internalization of platelet glycoprotein receptors. J. Transl. Med., 2018, 16(1), 311.
[http://dx.doi.org/10.1186/s12967-018-1688-z] [PMID: 30442147]
[31]
Wu, J.T.; Yang, G.W.; Qi, C.H.; Zhou, L.; Hu, J.G.; Wang, M.S. Anti-inflammatory activity of platycodin d on alcohol-induced fatty liver rats via TLR4-MYD88-NF-κB signal path. Afr. J. Tradit. Complement. Altern. Med., 2016, 13(4), 176-183.
[http://dx.doi.org/10.21010/ajtcam.v13i4.23] [PMID: 28852734]
[32]
Liu, Y.M.; Cong, S.; Cheng, Z.; Hu, Y.X.; Lei, Y.; Zhu, L.L.; Zhao, X.K.; Mu, M.; Zhang, B.F.; Fan, L.D.; Yu, L.; Cheng, M.L. Platycodin D alleviates liver fibrosis and activation of hepatic stellate cells by regulating JNK/c-JUN signal pathway. Eur. J. Pharmacol., 2020, 876172946
[http://dx.doi.org/10.1016/j.ejphar.2020.172946] [PMID: 31996320]
[33]
Meng, Y.L.; Wang, W.M.; Lv, D.D.; An, Q.X.; Lu, W.H.; Wang, X.; Tang, G. The effect of Platycodin D on the expression of cytoadherence proteins P1 and P30 in Mycoplasma pneumoniae models. Environ. Toxicol. Pharmacol., 2017, 49, 188-193.
[http://dx.doi.org/10.1016/j.etap.2017.01.001] [PMID: 28073091]
[34]
Meng, Y.; Yang, Y.; Lu, W.; Wang, Y.; Qian, F.; Wang, X.; Zhang, Z.; Wang, W. The inhibition of platycodin D on Mycoplasma pneumoniae proliferation and its effect on promoting cell growth after anti-Mycoplasma pneumoniae treatment. Front. Cell. Infect. Microbiol., 2015, 4, 192.
[http://dx.doi.org/10.3389/fcimb.2014.00192] [PMID: 25629010]
[35]
Tao, W.; Su, Q.; Wang, H.; Guo, S.; Chen, Y.; Duan, J.; Wang, S. Platycodin D attenuates acute lung injury by suppressing apoptosis and inflammation in vivo and in vitro. Int. Immunopharmacol., 2015, 27(1), 138-147.
[http://dx.doi.org/10.1016/j.intimp.2015.05.005] [PMID: 25981110]
[36]
Khan, M.; Maryam, A.; Zhang, H.; Mehmood, T.; Ma, T. Killing cancer with platycodin D through multiple mechanisms. J. Cell. Mol. Med., 2016, 20(3), 389-402.
[http://dx.doi.org/10.1111/jcmm.12749] [PMID: 26648178]
[37]
Bailly, C.; Vergoten, G. Proposed mechanisms for the extracellular release of PD-L1 by the anticancer saponin platycodin D. Int. Immunopharmacol., 2020, 85106675
[http://dx.doi.org/10.1016/j.intimp.2020.106675] [PMID: 32531711]
[38]
Qin, H.; Du, X.; Zhang, Y.; Wang, R. Platycodin D, a triterpenoid saponin from Platycodon grandiflorum, induces G2/M arrest and apoptosis in human hepatoma HepG2 cells by modulating the PI3K/Akt pathway. Tumour Biol., 2014, 35(2), 1267-1274.
[http://dx.doi.org/10.1007/s13277-013-1169-1] [PMID: 24048756]
[39]
Lu, J.J.; Lu, D.Z.; Chen, Y.F.; Dong, Y.T.; Zhang, J.R.; Li, T.; Tang, Z.H.; Yang, Z. Proteomic analysis of hepatocellular carcinoma HepG2 cells treated with platycodin D. Chin. J. Nat. Med., 2015, 13(9), 673-679.
[http://dx.doi.org/10.1016/S1875-5364(15)30065-0] [PMID: 26412427]
[40]
Li, T.; Tang, Z.H.; Xu, W.S.; Wu, G.S.; Wang, Y.F.; Chang, L.L.; Zhu, H.; Chen, X.P.; Wang, Y.T.; Chen, Y.; Lu, J.J. Platycodin D triggers autophagy through activation of extracellular signal-regulated kinase in hepatocellular carcinoma HepG2 cells. Eur. J. Pharmacol., 2015, 749, 81-88.
[http://dx.doi.org/10.1016/j.ejphar.2015.01.003] [PMID: 25592318]
[41]
Li, T.; Xu, X.H.; Tang, Z.H.; Wang, Y.F.; Leung, C.H.; Ma, D.L.; Chen, X.P.; Wang, Y.T.; Chen, Y.; Lu, J.J. Platycodin D induces apoptosis and triggers ERK- and JNK-mediated autophagy in human hepatocellular carcinoma BEL-7402 cells. Acta Pharmacol. Sin., 2015, 36(12), 1503-1513.
[http://dx.doi.org/10.1038/aps.2015.99] [PMID: 26592509]
[42]
Li, W.; Tian, Y.H.; Liu, Y.; Wang, Z.; Tang, S.; Zhang, J.; Wang, Y.P. Platycodin D exerts in H22 tumor-bearing mice via improving immune function and inducing apoptosis. J. Toxicol. Sci., 2016, 41(3), 417-428.
[http://dx.doi.org/10.2131/jts.41.417] [PMID: 27193733]
[43]
Kong, Y.; Lu, Z.L.; Wang, J.J.; Zhou, R.; Guo, J.; Liu, J.; Sun, H.L.; Wang, H.; Song, W.; Yang, J.; Xu, H.X. Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene. Oncol. Rep., 2016, 36(3), 1447-1456.
[http://dx.doi.org/10.3892/or.2016.4935] [PMID: 27432230]
[44]
Chun, J.; Kim, Y.S. Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways. Chem. Biol. Interact., 2013, 205(3), 212-221.
[http://dx.doi.org/10.1016/j.cbi.2013.07.002] [PMID: 23867902]
[45]
Lu, Z.; Song, W.; Zhang, Y.; Wu, C.; Zhu, M.; Wang, H.; Li, N.; Zhou, Y.; Xu, H. Combined anti-cancer effects of platycodin d and sorafenib on androgen-independent and PTEN-deficient prostate cancer. Front. Oncol., 2021, 11648985
[http://dx.doi.org/10.3389/fonc.2021.648985] [PMID: 34026624]
[46]
Lee, E.J.; Kang, M.; Kim, Y.S. Platycodin D inhibits lipogenesis through AMPKα-PPARγ2 in 3T3-L1 cells and modulates fat accumulation in obese mice. Planta Med., 2012, 78(14), 1536-1542.
[http://dx.doi.org/10.1055/s-0032-1315147] [PMID: 22872592]
[47]
Kim, H.L.; Park, J.; Jung, Y.; Ahn, K.S.; Um, J.Y. Platycodin D, a novel activator of AMP-activated protein kinase, attenuates obesity in db/db mice via regulation of adipogenesis and thermogenesis. Phytomedicine, 2019, 52, 254-263.
[http://dx.doi.org/10.1016/j.phymed.2018.09.227] [PMID: 30599906]
[48]
Lee, H.; Bae, S.; Kim, Y.S.; Yoon, Y. WNT/β-catenin pathway mediates the anti-adipogenic effect of platycodin D, a natural compound found in Platycodon grandiflorum. Life Sci., 2011, 89(11-12), 388-394.
[http://dx.doi.org/10.1016/j.lfs.2011.07.006] [PMID: 21798269]
[49]
Hwang, Y.P.; Choi, J.H.; Kim, H.G.; Khanal, T. Gye,Song, G.Y.; Nam, M.S.; Lee, H.S.; Chung, Y.C.; Lee, Y.C.; Jeong, H.G. Saponins, especially platycodin D, from Platycodon grandiflflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells. Toxicol. Appl. Pharmacol., 2013, 267, 174-183.
[http://dx.doi.org/10.1016/j.taap.2013.01.001] [PMID: 23319015]
[50]
Han, Y.; Jin, S.W.; Lee, G.H.; Choi, J.H.; Lee, H.S.; Chung, Y.C.; Jeong, H.G.; Lee, K.Y. Stimulatory effects of platycodin D on osteoblast differentiation. J. Cell. Biochem., 2019, 120(8), 13085-13094.
[http://dx.doi.org/10.1002/jcb.28580] [PMID: 30887567]
[51]
Lee, S.K.; Park, K.K.; Kim, H.J.; Kim, K.R.; Kang, E.J.; Kim, Y.L.; Yoon, H.; Kim, Y.S.; Chung, W.Y.; Platycodin, D. Platycodin D blocks breast cancer-induced bone destruction by inhibiting osteoclastogenesis and the growth of breast cancer cells. Cell. Physiol. Biochem., 2015, 36(5), 1809-1820.
[http://dx.doi.org/10.1159/000430152] [PMID: 26184636]
[52]
Shi, C.; Li, Q.; Zhang, X.; Platycodin, D. Platycodin D protects human fibroblast cells from premature senescence induced by H2O2 through improving mitochondrial biogenesis. Pharmacology, 2020, 105(9-10), 598-608.
[http://dx.doi.org/10.1159/000505593] [PMID: 32008007]
[53]
Jung, E.; Hwang, W.; Kim, S.; Kim, Y.S.; Kim, Y.S.; Lee, J.; Park, D. Depigmenting action of platycodin D depends on the cAMP/Rho-dependent signalling pathway. Exp. Dermatol., 2011, 20(12), 986-991.
[http://dx.doi.org/10.1111/j.1600-0625.2011.01379.x] [PMID: 21995379]
[54]
Ceña-Diez, R.; Martin-Moreno, A.; de la Mata, F.J.; Gómez-Ramirez, R.; Muñoz, E.; Ardoy, M.; Muñoz-Fernández, M.Á. G1-S4 or G2-S16 carbosilane dendrimer in combination with Platycodin D as a promising vaginal microbicide candidate with contraceptive activity. Int. J. Nanomedicine, 2019, 14, 2371-2381.
[http://dx.doi.org/10.2147/IJN.S188495] [PMID: 31040662]
[55]
Kim, Y.P.; Lee, E.B.; Kim, S.Y.; Li, D.; Ban, H.S.; Lim, S.S.; Shin, K.H.; Ohuchi, K. Inhibition of prostaglandin E2 production by platycodin D isolated from the root of Platycodon grandiflorum. Planta Med., 2001, 67(4), 362-364.
[http://dx.doi.org/10.1055/s-2001-14317] [PMID: 11458457]
[56]
Pei, L.; Bao, Y.; Ma, L.; Wang, Q.; Ye, Y.; Han, X.; Liu, S.; Chen, X. A sensitive method for determination of platycodin d in rat plasma using liquid chromatography/tandem mass spectrometry and its application to a pharmacokinetic study. Planta Med., 2012, 78(3), 244-251.
[http://dx.doi.org/10.1055/s-0031-1280372] [PMID: 22095263]
[57]
Song, P.; Zhang, Y.; Ma, G.; Zhang, Y.; Zhou, A.; Xie, J. Gastrointestinal absorption and metabolic dynamics of Jujuboside A, a saponin derived from the seed of Ziziphus jujuba. J. Agric. Food Chem., 2017, 65(38), 8331-8339.
[http://dx.doi.org/10.1021/acs.jafc.7b02748] [PMID: 28868886]
[58]
Wang, J.; Shan, J.J.; Di, L.Q.; Wang, S.C.; Cai, B.C. Research progress in oral absorption and metabolism of pentacyclic triterpenoid saponins. Chin. Herb. Med., 2012, 43(01), 196-200.
[59]
Wang, J. Study on the Pharmacokinetics of Platycodin D; Nanjing University of Traditional Chinese Medicine, 2012.
[60]
Zhang, W.; Qian, S.H.; Qian, D.W.; Li, S.L. Screening of intestinal bacterial metabolites of Platycodin D using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry. Am. J. Chin. Med., 2016, 44(4), 817-833.
[http://dx.doi.org/10.1142/S0192415X16500452] [PMID: 27222071]
[61]
Lin, T.T.; Liu, Y.; Lai, C.J.S.; Yang, T.T.; Xie, J.B.; Zhang, Y.Q. The effect of ultrasound assisted extraction on structural composition, antioxidant activity and immunoregulation of polysaccharides from Ziziphus jujuba Mill var. spinosa seeds. Ind. Crops Prod., 2018, 125, 150-159.
[http://dx.doi.org/10.1016/j.indcrop.2018.08.078]
[62]
Shan, J.; Zou, J.; Xie, T.; Kang, A.; Zhou, W.; Deng, H.; Mao, Y.; Di, L.; Wang, S. Pharmacokinetics, intestinal absorption and microbial metabolism of single platycodin D in comparison to Platycodi radix extract. Pharmacogn. Mag., 2015, 11(44), 750-755.
[http://dx.doi.org/10.4103/0973-1296.165576] [PMID: 26600720]
[63]
Kwon, M.; Ji, H.K.; Goo, S.H.; Nam, S.J.; Kang, Y.J.; Lee, E.; Liu, K.H.; Choi, M.K.; Song, I.S. Involvement of intestinal efflux and metabolic instability in the pharmacokinetics of platycodin D in rats. Drug Metab. Pharmacokinet., 2017, 32(5), 248-254.
[http://dx.doi.org/10.1016/j.dmpk.2017.05.005] [PMID: 28743418]
[64]
Zhan, Q.; Zhang, F.; Gao, S.H.; Cai, F.; Jiang, B.; Sun, L.N.; Chen, W.S. An HPLC-MS/MS method for the quantitative determination of platycodin D in rat plasma and its application to the pharmacokinetics of Platycodi Radix extract. Chin. J. Nat. Med., 2014, 12(2), 154-160.
[http://dx.doi.org/10.1016/S1875-5364(14)60026-1] [PMID: 24636069]
[65]
Kim, T.H.; Lee, B.E.; Kim, E.J.; Choi, Y.S.; Lee, K.S.; Kim, H.R.; Kim, H.G. Determination of platycodin D and platycodin D3 in rat plasma using liquid chromatography-tandem mass spectrometry. Scientif. World J., 2014, 2014231293
[http://dx.doi.org/10.1155/2014/231293] [PMID: 24592150]
[66]
Huang, M.Y.; Jiang, X.M.; Xu, Y.L.; Yuan, L.W.; Chen, Y.C.; Cui, G.; Huang, R.Y.; Liu, B.; Wang, Y.; Chen, X.; Lu, J.J. Platycodin D triggers the extracellular release of programed death Ligand-1 in lung cancer cells. Food Chem. Toxicol., 2019, 131110537
[http://dx.doi.org/10.1016/j.fct.2019.05.045] [PMID: 31150782]
[67]
Lee, W.H.; Gam, C.O.; Ku, S.K.; Choi, S.H. Single oral dose toxicity test of platycodin d, a saponin from Platycodin radix in mice. Toxicol. Res., 2011, 27(4), 217-224.
[http://dx.doi.org/10.5487/TR.2011.27.4.217] [PMID: 24278575]