Microbiology and Biotechnology Letters (한국미생물·생명공학회지)

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Neuraminidase-inhibition Activity of Nodakenetin from Gongjin-dan Fermented by Lactic Acid Bacteria

유산균으로 발효한 침향공진단으로부터 분리한 Nodakenetin의 Neuraminidase 활성 억제 효능

  • Seo, Ji Hyun (Science Research Park, LG Household and Healthcare Ltd.) ;
  • Park, Dong Jun (Science Research Park, LG Household and Healthcare Ltd.) ;
  • Lee, So Young (Science Research Park, LG Household and Healthcare Ltd.) ;
  • Cho, Ho Song (Science Research Park, LG Household and Healthcare Ltd.) ;
  • Jin, Mu Hyun (Science Research Park, LG Household and Healthcare Ltd.)
  • Received : 2020.01.30
  • Accepted : 2020.03.11
  • Published : 2020.09.28
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Abstract

The purpose of this study was to identify the changes in the components of unfermented Gongjin-dan (GD) and fermented Gongjin-dan (FGD) and to confirm whether GD or FGD has an inhibitory effect on viral neuraminidase (NA) activity. A major component of FGD was isolated and identified as nodakenetin, which is the aglycone of nodakenin. After fermentation, the nodakenetin content in FGD was approximately 10-fold higher than that in GD. Then, we examined the viral NA-inhibitory activity of GD, FGD, nodakenin, and nodakenetin. At a concentration of 500 ㎍/ml, FGD inhibited viral NA activity by 92% compared to the DMSO-treated control, while GD barely inhibited viral NA activity. In addition, 250 ㎍/ml of nodakenetin inhibited viral NA activity by 68% compared to the control, while nodakenin inhibited viral NA activity by only 4% at the same concentration as nodakenetin. Collectively, these results suggest that FGD has a more remarkable viral NA-inhibitory activity than GD because the content of the anti-viral component nodakenetin was higher in FGD due to the hydrolysis of nodakenin by Lactobacillus plantarum KCTC 3104.

대표적인 한방 보약 처방인 원방공진단을 재해석한 침향공진단 (당귀, 녹용, 산수유, 및 침향의 혼합추출물)을 유산균으로 발효하고, 침향공진단 성분 중 발효를 통해 증가하는 성분을 분리, 정제하고 nodakenetin임을 동정하였다. 발효 전 침향공진단(침향공진단 농축액 1% 함유 MRS 배지, unfermented Gongjin-dan, GD) 및 발효후 침향공진단(침향공진단 발효액, fermented Gongjin-dan, FGD)에서의 nodakenetin 함량 분석 결과, 각각 6 ㎍/ml과 70 ㎍/ml으로 발효를 통해 nodakenetin이 약 10배 이상 증가하였다. 한편, 고서에 전해지는 공진단의 면역력 강화 효능에 근거하여, GD 및 FGD의 인플루엔자 바이러스 증식 억제 효능을 확인하고자 Neuraminidase (NA) 활성 평가법(NA activity assay)을 실시하였다. 실험 결과, GD는 NA 활성을 억제하지 못하였으나, FGD는 농도의존적으로 NA 활성을 억제하였으며 500 ㎍/ml에서 대조군 대비 약 92%의 억제율을 보였다. 또한, 발효를 통해 증가한 침향공진단의 성분인 nodakenetin과 그 배당체인 nodakenin에 대한 NA 활성 평가 결과, nodakenin은 NA 활성을 거의 억제하지 못하였으나, nodakenetin은 농도의존적으로 NA 활성을 억제하였으며 250 ㎍/ml에서 대조군 대비 약 68%의 억제율을 보였다. 이상의 결과들을 종합하여, 유산균 발효를 통해 침향공진단 내에 미량 존재하던 nodakenetin이 nodakenin의 가수분해로 인해 증가하였으며, NA 활성 억제 성분인 nodakenetin이 증가함으로 인해 FGD도 높은 NA 활성 억제 효능을 보였다고 판단할 수 있었다.

Keywords

References

  1. Wi YL. 1990. Seuideughyobang, pp. 271. Uiseongdang, Seoul.
  2. Heo J. 1993. Hangul Donguibogam. pp. 817. Minjoong-Seogak, Seoul.
  3. Kim HJ, Hwang SY, Mok JY, Hwang BS, Jeong SI, Jang SI. 2009. Gagam-Gongjindan extract attenuates immune responses to ovalbumin in Balb/c mice. Kor. J. Herbology 24: 127-135.
  4. Hwang DY. 2014. Daeyeog Jeungmaeg.Bangyaghabpyeon. pp. 163-164. Namsandang, Seoul.
  5. Lee KH, Choi DK. 2016. Study on classification system and use of song dynasty Agarwood Line. Chin. Hist. Res. 100: 171-203.
  6. You YH, Koh JH, Chung SO, Jun WJ, Kim KM. 2009. Effects of fermented Ssanghwatang on swimming capacity in mice. Food. Sci. Biotechnol. 18: 275-277.
  7. Kerry RG, Patra JK, Gouda S, Park YH, Shin HS, Das G. 2018. Benefaction of probiotics for human health: A review. J. Food Drug Anal. 26: 927-939. https://doi.org/10.1016/j.jfda.2018.01.002
  8. Suez J, Zmora N, Segal E, Elinav E. 2019. The pros, cons, and many unknowns of probiotics. Nat. Med. 25: 716-729. https://doi.org/10.1038/s41591-019-0439-x
  9. Knackstedt R, Knackstedt T, Gatherwright J. 2019. The role of topical probiotics in skin conditions: A systematic review of animal and human studies and implications for future therapies. Exp. Dermatol. 29: 15-21. https://doi.org/10.1111/exd.14032
  10. Siezen RJ, Tzeneva VA, Castioni A, Wels M, Phan H, Rademaker J, et al. 2010. Phenotypic and genomic diversity of Lactobacillus plantarum strains isolated from various environmental niches. Environ. Microbiol. 12: 758-773. https://doi.org/10.1111/j.1462-2920.2009.02119.x
  11. Herbel SR, Vahjen W, Wieler LH, Guenther S. 2013. Timely approaches to identify probiotic species of the genus Lactobacillus. Gut Pathog. 5: 27. https://doi.org/10.1186/1757-4749-5-27
  12. Sun Z, Harris H, McCann A, Guo C, Argimon S, Zhang W, et al. 2015. Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera. Nat. Commun. 6: 8322. https://doi.org/10.1038/ncomms9322
  13. Arasu MV, Kim DH, Kim PI, Jung MW, Ilavenil S, Jane M, et al. 2014. In vitro antifungal, probiotic and antioxidant properties of novel Lactobacillus plantarum K46 isolated from fermented sesame leaf. Ann. Microbiol. 64: 1333-1346. https://doi.org/10.1007/s13213-013-0777-8
  14. Murofushi Y, Villena J, Morie K, Kanmani P, Tohno M, Shimazu T, et al. 2015. The toll-like receptor family protein P105/MD1 complex is involved in the immunoregulatory effect of exopolysaccharides from Lactobacillus plantarum N14O. Mol. Immunol. 64: 63-75. https://doi.org/10.1016/j.molimm.2014.10.027
  15. Wang K, Li W, Rui X, Chen X, Jiang M, Dong M. 2014. Characterization of a novel exopolysaccharide with antitumor activity from Lactobacillus plantarum 70810. Int. J. Biol. Macromol. 63: 133-139. https://doi.org/10.1016/j.ijbiomac.2013.10.036
  16. Woo JY, Gu W, Kim KA, Jang SE, Han MJ, Kim DH. 2014. Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model. Anaerobe 27: 22-26. https://doi.org/10.1016/j.anaerobe.2014.03.003
  17. Jung YJ, Han DO, Choi BH, Park C, Lee HJ, Kim SH, et al. 2007. Effect of fermented herbal extracts, HP-1 on enzyme activities and gene expressions related to alcohol metabolism in ethanolloaded rats. Korean J. Oriental Physiol. Pathol. 21: 387-391.
  18. Zhang P, Yang XW. 2009. Biotransformation of nodakenin and simultaneous quantification of nodakenin and its aglycone in incubated system of human intestinal bacteria by HPLC method. J. Asian Nat. Prod. Res. 11: 371-379. https://doi.org/10.1080/10286020902767716
  19. Kwang JL, Song NY, Roh JH, Liang C, Ma JY. 2013. Analysis of bioconversed components in fermented Jaeumganghwa-tang by Lactobacillus. J. Appl. Biol. Chem. 56: 131-135. https://doi.org/10.3839/jabc.2013.021
  20. Yang MC, Jeong SW, Ma JY. 2011. Analysis of constituents in Sipjundaebo-tangs fermented by lactic acid bacteria. Korean J. Microbiol. Biotechnol. 39: 350-356.
  21. Kim DS, Roh JH, Cho CW, Ma JY. 2012. Analysis of nodakenetin from Samultangs fermented by lactose bacteria strains. Kor. J. Herbology 27: 35-39. https://doi.org/10.6116/kjh.2012.27.1.35
  22. Lee KW, Cho HK, Yoo HR, Seol IC, Kim YS. 2018. The effects of an extract of fermented Artemisiae Iwayomogii Herba, Curcumae longae, Crataegi fructus and Salviae miltiorrhizae radix on antiinflammation associated with dyslipidemia and anti-oxidation in RAW264.7 and HUVEC Cells. J. Int. Korean Med. 39: 480-494. https://doi.org/10.22246/jikm.2018.39.4.480
  23. Kang DH, Kim HS. 2011. Functionality analysis of korean medicine fermented by Lactobacillus strains. Korean J. Microbiol. Biotechnol. 39: 259-265.
  24. Lee JH, Jo DC, Kim CG, Moon SJ, Park TY, Ko YS. et al. 2013. A literature review of effectiveness on the Gongjin-dan (Gongchendan). J. Korean Med. Rehabi. 23: 69-78.
  25. Moscona A. 2005. Neuraminidase Inhibitors for Influenza. N. Engl. J. Med. 353: 1363-1373. https://doi.org/10.1056/NEJMra050740
  26. Liu AL, Wang HD, Lee MY, Wang YT, Du GH. 2008. Structure- activity relationship of flavonoids as influenza virus neuraminidase inhibitors and their in vitro anti-viral activities. Bioorg. Med. Chem. 16: 1741-1747.
  27. Kim EH, Lee JH, Song MS, Baek YH, Choi YK, Ma JY. 2012. Administration of novel oriental medicine, KIOM-C, protect against influenza virus. J. Biomed. Res. 13: 149-156. https://doi.org/10.12729/jbr.2012.13.2.149
  28. Lee SH, Shin DS, Kim JS, Oh KB, Kang SS. 2003. Antibacterial coumarins from Angelica gigas roots. Arch. Pharm. Res. 26: 449-452. https://doi.org/10.1007/BF02976860
  29. Seong GU, Beak ME, Lee YJ, Won JH. 2018. Quality evaluation of Angelica gigas Nakai with different drying methods and different root parts. Kor. J. Herbology 33: 85-91. https://doi.org/10.6116/kjh.2018.33.1.85
  30. Landete JM, Curiel JA, Rodriguez H, Rivas B, Munoz R. 2014. Aryl glycosidases from Lactobacillus plantarum increase antioxidant activity of phenolic compounds. J. Funct. Foods. 7: 322-329. https://doi.org/10.1016/j.jff.2014.01.028
  31. Kim DH, Kim DY, Kim YC, Jung JW, Lee S, Yoon BH, et al. 2007. Nodakenin, a coumarin compound, ameliorates scopolamineinduced memory disruption in mice. Life Sci. 80: 1944-1950. https://doi.org/10.1016/j.lfs.2007.02.023
  32. Gao Q, Jeon SJ, Jung HA, Lee HE, Park SJ, Lee YH, et al. 2015. Nodakenin enhances cognitive function and adult hippocampal neurogenesis in mice. Neurochem. Res. 40: 1438-1447. https://doi.org/10.1007/s11064-015-1612-3
  33. Xiong Y, Wang JS, Yu H, Zhang X, Miao C, Ma S. 2014. The effects of nodakenin on airway inflammation, hyper-responsiveness and remodeling in a murine model of allergic asthma. Immunopharmacol. Immunotoxicol. 36: 341-348. https://doi.org/10.3109/08923973.2014.947035
  34. Hideji T, Yun YS, Hiroshi M, Koich T, Lee SR. 1994. Cytotoxic coumarins from the roots of Angelica gigas Nakai. J. Oriental Bot. Res. 7: 13-15.