Skip to main content
Log in

Biotransformation of ginsenoside Rb1 and Rd to four rare ginsenosides and evaluation of their anti-melanogenic effects

  • Note
  • Published:
Journal of Natural Medicines Aims and scope Submit manuscript

Abstract

Improving physiological activity of primary ginsenosides through biotransformation is of great significance for food applications. In this study, gynostapenoside XVII, gynostapenoside LXXV, ginsenoside F2, and ginsenoside CK were obtained by enzymolysis of an accessible extract composed of ginsenoside Rb1 and Rd. Their effects on melanin content and tyrosinase activity were compared in vitro, and molecular docking simulation was employed to elucidate the interaction between tyrosinase and individual saponin. The results indicated that four rare ginsenosides decreased tyrosinase activity, melanin content and microphthalmia-associated transcription factor (MITF) expression level, more greatly than their primary ginsenosides, and they were more readily to bind with ASP10 and GLY68 at active site of tyrosinase to inhibit tyrosinase activity as well. These findings suggested that the rare ginsenosides obtained by enzymolysis had excellent anti-melanogenic effect, which could expand the application of ginsenosides in the field of functional foods and health supplements.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

References

  1. Patel S, Rauf A (2017) Adaptogenic herb ginseng (Panax) as medical food: Status quo and future prospects. Biomed Pharmacother 85:120–127. https://doi.org/10.1016/j.biopha.2016.11.112

    Article  CAS  PubMed  Google Scholar 

  2. Wu ZY, Raven PH (1996) Flora of China. Panax ginseng

  3. Li X, Liu J, Zuo TT, Hu Y, Li Z, Wang HD, Xu XY, Yang WZ, Guo DA (2022) Advances and challenges in ginseng research from 2011 to 2020: the phytochemistry, quality control, metabolism, and biosynthesis. Nat Prod Rep 39(4):875–909. https://doi.org/10.1039/d1np00071c

    Article  CAS  PubMed  Google Scholar 

  4. Cheng Y, Shen LH, Zhang JT (2005) Anti-amnestic and anti-aging effects of ginsenoside Rg1 and Rb1 and its mechanism of action. Acta Pharmacol Sin 26(2):143–149. https://doi.org/10.1111/j.1745-7254.2005.00034.x

    Article  CAS  PubMed  Google Scholar 

  5. Feng J, Yu Y, Song L, Zhang R, Cao Y, Du X, Tao F, Gao H, Xue P (2022) Comparison of the anti-inflammatory effects of different polar ginsenosides on rheumatoid arthritis. Ind Crop Prod 181:114845. https://doi.org/10.1016/j.indcrop.2022.114845

    Article  CAS  Google Scholar 

  6. Kim J, Phung HM, Lee S, Kim KT, Son TK, Kang KS, Lee S (2022) Anti-skin-aging effects of tissue-cultured mountain-grown ginseng and quantitative HPLC/ELSD analysis of major ginsenosides. J Nat Med 76(4):811–820. https://doi.org/10.1007/s11418-022-01633-2

    Article  CAS  PubMed  Google Scholar 

  7. Lee W, Park SH, Lee S, Chung BC, Song MO, Song KI, Ham J, Kim SN, Kang KS (2012) Increase in antioxidant effect of ginsenoside Re-alanine mixture by Maillard reaction. Food Chem 135(4):2430–2435. https://doi.org/10.1016/j.foodchem.2012.06.108

    Article  CAS  PubMed  Google Scholar 

  8. Yamabe N, Kim YJ, Lee S, Cho EJ, Park SH, Ham J, Kim HY, Kang KS (2013) Increase in antioxidant and anticancer effects of ginsenoside Re-lysine mixture by Maillard reaction. Food Chem 138(2–3):876–883. https://doi.org/10.1016/j.foodchem.2012.12.004

    Article  CAS  PubMed  Google Scholar 

  9. Meng H, Liu XK, Li JR, Bao TY, Yi F (2022) Bibliometric analysis of the effects of ginseng on skin. J Cosmet Dermatol 21(1):99–107. https://doi.org/10.1111/jocd.14450

    Article  PubMed  Google Scholar 

  10. Jin Y, Kim JH, Hong HD, Kwon J, Lee EJ, Jang M, Lee SY, Han AR, Nam TG, Hong SK, Huh TL, Kang NJ, Lim TG (2018) Ginsenosides Rg5 and Rk1, the skin-whitening agents in black ginseng. J Funct Foods 45:67–74. https://doi.org/10.1016/j.jff.2018.03.036

    Article  CAS  Google Scholar 

  11. Lee CS, Nam G, Bae IH, Park J (2019) Whitening efficacy of ginsenoside F1 through inhibition of melanin transfer in cocultured human melanocytes-keratinocytes and three-dimensional human skin equivalent. J Ginseng Res 43(2):300–304. https://doi.org/10.1016/j.jgr.2017.12.005

    Article  PubMed  Google Scholar 

  12. Lee Y, Kim KT, Kim SS, Hur J, Ha SK, Cho CW, Choi SY (2014) Inhibitory effects of ginseng seed on melanin. Pharmacogn Mag 10(38):272–275. https://doi.org/10.4103/0973

    Article  Google Scholar 

  13. Shin KC, Oh DK (2023) Biotransformation of platycosides, saponins from balloon flower root, into bioactive deglycosylated platycosides. Antioxidants (Basel) 12(2):327. https://doi.org/10.3390/antiox12020327

    Article  CAS  PubMed  Google Scholar 

  14. Lu Y, Luo Q, Jia X, Tam JP, Yang H, Shen Y, Li X (2023) Multidisciplinary strategies to enhance therapeutic effects of flavonoids from Epimedii Folium: Integration of herbal medicine, enzyme engineering, and nanotechnology. J Pharmaceut Anal 13(3):239–254. https://doi.org/10.1016/j.jpha.2022.12.001

    Article  Google Scholar 

  15. Sur B, Lee B (2022) Ginsenoside Rg3 modulates spatial memory and fear memory extinction by the HPA axis and BDNF-TrkB pathway in a rat post-traumatic stress disorder. J Nat Med 76(4):821–831. https://doi.org/10.1007/s11418-022-01636-z

    Article  CAS  PubMed  Google Scholar 

  16. Pan C, Yan Y, Zhao D (2022) The fate and intermediary metabolism of soyasapogenol in the rat. Molecules 28(1):284. https://doi.org/10.3390/molecules28010284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Xu QF, Fang XL, Chen DF (2003) Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J Ethnopharmacol 84(2–3):187–192. https://doi.org/10.1016/s0378-8741(02)00317-3

    Article  CAS  PubMed  Google Scholar 

  18. Fu Y (2019) Biotransformation of ginsenoside Rb1 to Gyp-XVII and minor ginsenoside Rg3 by endophytic bacterium Flavobacterium sp. GE 32 isolated from Panax ginseng. Lett Appl Microbiol 68(2):134–141. https://doi.org/10.1111/lam.13090

    Article  CAS  PubMed  Google Scholar 

  19. Shen YP, Wang HY, Lu Y, Xu LL, Yin HW, Tam JP, Yang H, Jia XB (2018) Construction of a novel catalysis system for clean and efficient preparation of Baohuoside I from Icariin based on biphase enzymatic hydrolysis. J Clean Prod 170:727–734. https://doi.org/10.1016/j.jclepro.2017.09.192

    Article  CAS  Google Scholar 

  20. Yang H, Yin HW, Shen YP, Xia GH, Zhang B, Wu XY, Cai BC, Tam JP (2016) A more ecological and efficient approach for producing diosgenin from Dioscorea zingiberensis tubers via pressurized biphase acid hydrolysis. J Clean Prod 131:10–19. https://doi.org/10.1016/j.jclepro.2016.05.030

    Article  CAS  Google Scholar 

  21. Tsuge A, Hisaka S, Hayashi H, Nose M (2020) Effect of hot water extract of a glycyrrhizin-deficient strain of Glycyrrhiza uralensis on contact hypersensitivity in mice. J Nat Med 74(2):415–420. https://doi.org/10.1007/s11418-019-01386-5

    Article  CAS  PubMed  Google Scholar 

  22. Yu H, Chen Y, Cheng Z, Li H, Bian H, Yang X, Lv J, Liu W, Su L, Sun P (2023) Anti-inflammatory oleanane-type triterpenoids produced by Nonomuraea sp. MYH522 through microbial transformation. J Agric Food Chem 71(8):3777–3789. https://doi.org/10.1021/acs.jafc.2c09062

    Article  CAS  PubMed  Google Scholar 

  23. Shen YP, Wang M, Chen YF, Xu LL, Lu Y, Zhou YY, Tam JP, Han F, Yang H, Jia XB (2019) Convenient preparation of sagittatoside B, a rare bioactive secondary flavonol glycoside, by recyclable and integrated biphase enzymatic hydrolysis. Enzyme Microb Technol 121:51–58. https://doi.org/10.1016/j.enzmictec.2018.12.002

    Article  CAS  PubMed  Google Scholar 

  24. Ferro S, Certo G, Luca LD, Germano MP, Rapisarda A, Gitto R (2016) Searching for indole derivatives as potential mushroom tyrosinase inhibitors. J Enzyme Inhib Med Chem 31(3):398–403. https://doi.org/10.3109/14756366.2015.1029470

    Article  CAS  PubMed  Google Scholar 

  25. Kim JH, Baek EJ, Lee EJ, Yeom MH, Park JS, Lee KW, Kang NJ (2015) Ginsenoside F1 attenuates hyperpigmentation in B16F10 melanoma cells by inducing dendrite retraction and activating Rho signalling. Exp Dermatol 24(2):150–152. https://doi.org/10.1111/exd.12586

    Article  CAS  PubMed  Google Scholar 

  26. An DS, Cui CH, Lee HG, Wang L, Kim SC, Lee ST, Jin F, Yu H, Chin YW, Lee HK, Im WT, Kim SG (2010) Identification and characterization of a novel Terrabacter ginsenosidimutans sp. nov. beta-glucosidase that transforms ginsenoside Rb1 into the rare gypenosides XVII and LXXV. AEM 76(17):5827–5836. https://doi.org/10.1128/AEM.00106-10

    Article  CAS  Google Scholar 

  27. Christensen LP (2009) Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res 55:1–99. https://doi.org/10.1016/S1043-4526(08)00401-4

    Article  CAS  PubMed  Google Scholar 

  28. Hsu BY, Lu TJ, Chen CH, Wang SJ, Hwang LS (2013) Biotransformation of ginsenoside Rd in the ginseng extraction residue by fermentation with lingzhi (Ganoderma lucidum). Food Chem 141(4):4186–4193. https://doi.org/10.1016/j.foodchem.2013.06.134

    Article  CAS  PubMed  Google Scholar 

  29. Kim JK, Cui CH, Liu Q, Yoon MH, Kim SC, Im WT (2013) Mass production of the ginsenoside Rg3(S) through the combinative use of two glycoside hydrolases. Food Chem 141(2):1369–1377. https://doi.org/10.1016/j.foodchem.2013.04.012

    Article  CAS  PubMed  Google Scholar 

  30. Cheng LQ, Na JR, Kim MK, Bang MH, Yang DC (2007) Microbial conversion of ginsenoside Rb-1 to minor ginsenoside F-2 and gypenoside XVII by Intrasporangium sp. GS603 isolated from soil. J Microbiol Biotechn 17(12):1937–1943

    CAS  Google Scholar 

  31. Liu CY, Zhou RX, Sun CK, Jin YH, Yu HS, Zhang TY, Xu LQ, Jin FX (2015) Preparation of minor ginsenosides C-Mc, C-Y, F2, and C-K from American ginseng PPD-ginsenoside using special ginsenosidase type-I from Aspergillus niger g.848. J Ginseng Res 39(3):221–229. https://doi.org/10.1016/j.jgr.2014.12.003

    Article  PubMed  Google Scholar 

  32. Zolghadri S, Bahrami A, Hassan Khan MT, Munoz-Munoz J, Garcia-Molina F, Garcia-Canovas F, Saboury AA (2019) A comprehensive review on tyrosinase inhibitors. J Enzyme Inhib Med Chem 34(1):279–309. https://doi.org/10.1080/14756366.2018.1545767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Goenka S, Johnson F, Simon SR (2021) Novel chemically modified curcumin (CMC) derivatives inhibit tyrosinase activity and melanin synthesis in B16F10 mouse melanoma cells. Biomolecules 11(5):674. https://doi.org/10.3390/biom11050674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim K (2015) Effect of ginseng and ginsenosides on melanogenesis and their mechanism of action. J Ginseng Res 39(1):1–6. https://doi.org/10.1016/j.jgr.2014.10.006

    Article  PubMed  Google Scholar 

  35. Lin Z, Xie R, Zhong C, Huang J, Shi P, Yao H (2022) Recent progress (2015–2020) in the investigation of the pharmacological effects and mechanisms of ginsenoside Rb1, a main active ingredient in Panax ginseng Meyer. J Ginseng Res 46(1):39–53. https://doi.org/10.1016/j.jgr.2021.07.008

    Article  PubMed  Google Scholar 

  36. Wu GS, Robertson DH, Brooks CL, Vieth M (2003) Detailed analysis of grid-based molecular docking: a case study of CDOCKER - A CHARMm-based MD docking algorithm. J Comput Chem 24(13):1549–1562. https://doi.org/10.1002/jcc.10306

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge the financial supports of the Nation Natural Science Foundation of China (81873196 and 81303313) and the Science and Technology Project of Changzhou City (CJ20220161).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Huan Yang, Yuping Shen or Anne S. Meyer.

Ethics declarations

Conflict of interest

The authors declare that there is no conflict of interest.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 11009 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhang, L., Wang, L., Chen, Y. et al. Biotransformation of ginsenoside Rb1 and Rd to four rare ginsenosides and evaluation of their anti-melanogenic effects. J Nat Med 77, 939–952 (2023). https://doi.org/10.1007/s11418-023-01719-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11418-023-01719-5

Keywords

Navigation