Korean Journal of Plant Resources (한국자원식물학회지)

The Plant Resources Society of Korea (한국자원식물학회)
권호 표지
DOI QR코드

DOI QR Code

Bioavailability and Anti-inflammatory Effect of Fermented Red Ginseng in BALB/c Mouse

BALB/c 마우스에서 발효 홍삼 Ginsenoside의 생체이용율과 항염효과

  • Lee, Eun Kyu (Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University) ;
  • Bae, Chu Hyun (Central Institute, hy Co., Ltd.) ;
  • Kim, Yu Jin (Central Institute, hy Co., Ltd.) ;
  • Park, Soo-Dong (Central Institute, hy Co., Ltd.) ;
  • Shim, Jae-Jung (Central Institute, hy Co., Ltd.) ;
  • Yu, Youngbob (Department of Herbal Pharmaceutical Development and Emergency Medical Rescue, Nambu University) ;
  • Lee, Jung-Lyoul (Central Institute, hy Co., Ltd.)
  • 이은규 (한양대학교 약학과) ;
  • 배주현 ((주)에치와이 중앙연구소) ;
  • 김유진 ((주)에치와이 중앙연구소) ;
  • 박수동 ((주)에치와이 중앙연구소) ;
  • 심재중 ((주)에치와이 중앙연구소) ;
  • 유영법 (남부대학교 한방제약개발학과.응급구조학과) ;
  • 이정열 ((주)에치와이 중앙연구소)
  • Received : 2021.07.23
  • Accepted : 2021.08.10
  • Published : 2021.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

The fermented red ginseng by microorganism is known to increase pharmacological activity in vivo. To evaluate the bioavailablity of red ginseng fermented by probiotics, we conducted the pharmacokinetic study of ginsenoside Rb1, Rd and total ginsenosides (TG, ginsenosides Rb1 + Rd + Rg1 + F2 + Rg3 + compound K) in BALB/C mice. The AUC value of ginsenoside Rb1 in mice serum administered with 600mg/kg drugs showed 21.93 ± 14.68 ng·h/mL (RGw, water extract), 275.211 ± 110.04 ng·h/mL (RGe, 50% ethanol extract) and 404.91 ± 162.57 ng·h/mL (fRGe, fermented red ginseng extract). Analysis of ginsenoside Rd also showed a higher ACU value in fRGe than in RGw or RGe. And the AUC value of total ginsenosides in mice serum treated with 600 mg/kg were observed 42.12 ± 23.44 ng·h/mL (RGw), 321.44 ± 133.5 ng·h/mL (RGe) and 537.33 ± 229.01 ng·h/mL (fRGe), respectively. Cmax value of ginsenoside Rb1 in mice administered with 600mg/kg were observed 3.67 ± 3.34 ng/mL (RGw), 23.27 ± 8.81 ng/mL (RGe) and 25.52 ± 7.29 ng/mL (fRGe). These results can be considered that the fermented red ginseng has more bioavailability than that of unfermented red ginseng. In quantitative analysis of the inflammation-related cytokines IL-1β and TNF, no significant difference was found between the fermented red ginseng (fRGe) and the red ginseng (RGe).

본 연구에서는 발효홍삼과 발효하지 않은 홍삼을 BALB/c mouse에 경구투여한 후 혈청을 채취하여 주요 진세노사이드 생체이용율을 LC-MS/MS이용하여 분석하였다. 또한 이들의 항염효과를 IL-1𝛽, TNF 정량분석을 통해 비교하였다. 홍삼을 발효하였을 때, Rd를 포함한 전체적인 총 진세노사이드 함량이 증가하는 것을 확인하였으며, 마우스에게 투여하였을 총 진세노사이드 TG 의 혈액 검출량 AUC 또한 발효홍삼을 섭취하였을 때 높은 것을 확인하였다. Cmax값 또한 동일하게 발효홍삼을 섭취하였을 때 증가하는 것을 확인하였다. 염증지표를 확인 하였을때 유도군과 비교하여 IL-1𝛽, TNF의 감소효과는 확인하였으나 그룹간의 유의적 차이는 발생하지 않았다. 이상의 연구결과로 probiotics가 발효홍삼의 ginsenoside 생체이용율을 향상시키는 중요한 요인임을 확인하였고, 이는 probiotics를 이용한 천연물 발효제제의 적용 확장과 그 산업적 활용성 증대에 기여할 수 있을 것으로 사료된다.

Keywords

References

  1. Ahn, N.G. 2015. Changes in chemical composition during red ginseng manufacturing process. Department of Food Engineering, MS Thesis, Kongju National Univ., Korea (in Korean).
  2. Akao, T., Kida. H, Kanaoka. M, Hattori. M and Kobashi. K. 1998. Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng. J. Pharm. Pharmacol. 50:1155-1160. https://doi.org/10.1111/j.2042-7158.1998.tb03327.x
  3. Cho, J.Y. 2009. Immuno-regulatory efficacy or red ginseng derived ingredients. Food Preservation and Processing Industry. pp. 6-12 (in Korean).
  4. Choi, J.H., W.J. Kim, J.W. Yang, H.S. Sung and S.K. Hong. 1981. Variation of ginseng extract by heat treatment. J. Korean Agricultural Chemical Society 24(1):50-58 (in Korean).
  5. Choi, J.W., M.J. Oh, S.K. Ha, Y. Park and H.Y. Park. 2016. Characterization and optimization for beverage manufacture using Korea red ginseng extract. Korean Journal of Food Preservation and Processing Industry 23(3):319-325. https://doi.org/10.11002/kjfp.2016.23.3.319
  6. Choi, S.Y., J.S. Park, C.H. Shon, C.Y. Lee, J.M. Ryu, D.J. Son, B.Y. Hwang, H.S. Yoo, Y.C. Cho, J. Lee, J.W. Kim and Y.S. Roh. 2019. Fermented Korean red ginseng extract enriched in Rd and Rg3 protects against non-alcoholic fatty liver disease through regulation of mTORC1. Nutrients 11:2963. https://doi.org/10.3390/nu11122963
  7. Hasegawa, H., K.S. Lee, T. Nagaoka, Y. Tezuka, M. Uchiyama, S. Kakota and S. Ikuo. 2000. Pharmacokinetics of ginsenoside deglycosylated by intestinal bacteria and its transformation to biologically active fatty acid esters. Biol. Pharm. Bull. 23(3)298-304. https://doi.org/10.1248/bpb.23.298
  8. Her, Y., Y.C. Lee, J.H. Oh, Y.E. Choi, C.W. Lee, J.S. Kim, H.M. Kim and J.W. Yang. 2012. An application of β-glycosidase to transformation of ginsenosides for the effective production of specific ginsenosides with biological efficacy. Biotechnol. Bioprocess Eng. 17:538-546. https://doi.org/10.1007/s12257-011-0678-2
  9. Kim, H.I., J.K. Kim, J.Y. Kim, M.J. Han and D.H. Kim. 2018. Fermented red ginseng and ginsenoside Rd alleviate ovalbumin-induced allergic rhinitis in mice by suppressing IgE, interleukin-4, and interleukin-5 expression. J. Ginseng Res. 43(4):635-644. https://doi.org/10.1016/j.jgr.2019.02.006
  10. Kim, J.H., Y.S. Kim, M.Y. Kim and J.Y. Cho. 2017. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J. Ginseng Res. 41: 435-443. https://doi.org/10.1016/j.jgr.2016.08.004
  11. Kim, J.K., J.Y. Kim, S.E. Jang, M.S. Choi, H.M. Jang, H.H. Yoo and D.H. Kim. 2018. Fermented red ginseng alleviates cyclophosphamide-induced immunosuppression and 2,4,6-trinitrobenzenesulfonic acid-induced colitis in mice by regulation macrophage activation and T cell differentiation. Am. J. Chin. Med. 48(8):1879-1897.
  12. Kim, J.K., M.S. Choi, W.H. Jeung, J. Ra, H.H. Yoo and D.H. Kim. 2019. Effects of gut microbiota on the pharmacokinetics of protopanaxadiol ginsenosides Rd, Rg3, F2, and compound K in healthy volunteers treated orally with red ginseng. J. Ginseng Res. 44(4):611-618. https://doi.org/10.1016/j.jgr.2019.05.012
  13. Kim, K.A., H.H. Yoo, G. Wang, D.H. Yu, M.J. Jin, H.L. Choi, K.Y. G.D. Laetitia and D.H. Kim. 2015. A prebiotic fiber increases the formation and subsequent absorption of compound K following oral administration of ginseng in rats. J. Ginseng Res. 39:183-187. https://doi.org/10.1016/j.jgr.2014.11.002
  14. Kim, S.C., C.E. Hwang, B.O.L. Kim, K.H. Lee, J.H. Lee, K.M. Cho and O.S. Joo. 2021. Comparison of ginsenoside (Rg1, Rb1) content and radical-scavenging activities of wild-simulated ginseng extract with respect to the solvent. Korea J. Food Preserv. 28(2):261-269. https://doi.org/10.11002/kjfp.2021.28.2.261
  15. Ko, S.K., C.R. Lee, Y.E. Choi, B.Ok. Im, J.H. Sung and K.R. Yoon. 2003. Analysis of ginsenosides of white and red ginseng concentrates. Korean J. Food Sci. Technol. 35(3):536-539.
  16. Lee, G.S., K.Y. Nam and J.E. Choi. 2013. Ginsenoside composition and quality characteristics of red ginseng extracts prepared with different extracting methods. Korean J. Medicinal Crop. Sci. 21(4):276-281 https://doi.org/10.7783/KJMCS.2013.21.4.276
  17. Lee, S.J., Y. Kim and M.G. Kim. 2015. Changes in the ginsenoside content during the fermentation process using microbial strains. J Ginseng Res. 39(4):392-397. https://doi.org/10.1016/j.jgr.2015.05.005
  18. Li, X., J.S. Han, Y.J. Park, S.J. Kang, J.S. Kim, K.Y. Nam, K.T. Lee and J.E. Choi. 2009. Extracting conditions for promoting ginsenoside contents and taste of red ginseng water extract. J. Crop Sci. 54:287-293.
  19. Nam, K.Y and D.C. Yang. 2009. The main ingreadients and efficacy of Koryeo red ginseng. Korean J. Plant Resources 16(1):33-39 (in Korean).
  20. Park, H. 2019. The role of gut microbiota in ginsenoside meta-bolism and biotransformatino of ginsenoside by lactic acid bacteria. 2019. Curr. Top. Lact. Acid Bact. Probiotics 5(1):1-12. https://doi.org/10.35732/ctlabp.2019.5.1.1
  21. Saba, E., D. Jeong, M. Irfan, Y.Y. Lee, S.J. Park, C.K. Park and M.H. Rhee. 2018. Anti-inflammatory activity of Rg3-enriched Korean red ginseng extract in murine model of sepsis. Evid. Based Complement. Alternat. Med. 2018:6874692.
  22. Shim, J.S., G.G. Park and Y.S. Park. 2014. Bioconversion of puffed red ginseng extract using β-glucosidase-producing lactic acid bacteria. Food Eng. Prog. 18(4):332-340. https://doi.org/10.13050/foodengprog.2014.18.4.332
  23. Trinh, H.T. 2011. Intestinal microflora enhance the anti-pruritic activities of several glycosides from herbal medicines. Department of Pharmacy, Ph.D. Thesis, Kyeonghee Univ., Korea.
  24. U.S. Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER) (U.S.FDA). 2005. Guidance for industry estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. USA. pp. 1-27.
  25. Wakabayashi, C., H. Hasegawa, J. Murata, and I. Saiki. 1997. In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration. Oncol. Res. 9:411-417.
  26. Zhang, X., S. Chen, F. Duan, A.L. Shaojing, L.W. Zhong, W. Sheng, J. Che, J. Xu and S. Xiao. 2020. Prebiotics enhance the biotransformation and bioavailability of ginsenosides in rats by modulating gut microbiota. J. Ginseng Res. 45(2): 334-343.