Research progress on large-scale preparation and biological activity of ginsenoside CK

  • CAO Jingyi ,
  • CAO Yuan ,
  • ZHANG Jiaru ,
  • ZHOU Yangjialan ,
  • GUO Zhenni ,
  • SHAO Juanjuan
Expand
  • (College of Science and Technology, Agricultural University of Hebei, Cangzhou 061000, China)

Received date: 2024-05-14

  Revised date: 2024-06-24

  Online published: 2025-03-28

Abstract

Ginseng is a valuable Chinese herbal medicine, and rare ginsenosides are the most effective functional components in ginseng.The preparation of rare ginsenosides by biotransformation has become a research hotspot.Ginsenoside compound K (ginsenoside CK) has the capacity to be anti-tumor, anti-inflammatory, anti-aging skin, anti-diabetes, anti-depression, and anti-osteoporosis agents, while maintains other beneficial biological properties.In this paper, the methods suitable for large-scale preparation of ginsenoside CK and its biological activity were systematically reviewed to provide reference for the massive production of ginsenoside CK and further exploration of its pharmacological mechanism.

Cite this article

CAO Jingyi , CAO Yuan , ZHANG Jiaru , ZHOU Yangjialan , GUO Zhenni , SHAO Juanjuan . Research progress on large-scale preparation and biological activity of ginsenoside CK[J]. Food and Fermentation Industries, 2025 , 51(5) : 371 -379 . DOI: 10.13995/j.cnki.11-1802/ts.039872

References

[1] KEUM Y S, PARK K K, LEE J M, et al.Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng[J].Cancer Letters, 2000, 150(1):41-48.
[2] 李忆红, 梁雨璐, 解嘉琪, 等.中药皂苷类化合物生物转化研究进展[J].中草药, 2024, 55(3):989-1003.
LI Y H, LIANG Y L, XIE J Q, et al.Research progress on biotransformation of saponins from traditional Chinese medicine[J].Chinese Traditional and Herbal Drugs, 2024, 55(3):989-1003.
[3] 张薇. 人参根际土壤真菌与内生真菌的多样性及人参皂苷生物催化活性菌株的筛选[D].大连:辽宁师范大学, 2011.
ZHANG W.Diversity of rhizosphere soil fungi and endophytic fungi of ginseng and screening of biocatalytic strains of ginsenosides[D].Dalian:Liaoning Normal University, 2011.
[4] 袁松竹, 王斌, 周旋, 等.稀有人参皂苷生物转化的研究进展[J].食品工业科技, 2023, 44(12):480-489.
YUAN S Z, WANG B, ZHOU X, et al.Research progress on the biotransformation of rare ginsenosides[J].Science and Technology of Food Industry, 2023, 44(12):480-489.
[5] 赵升铭, 周旋, 袁松竹, 等.达玛烷型人参皂苷羧酸衍生物结构与抗肿瘤机制研究进展[J/OL].中成药, 2024 (2024-02-27.http://kns.cnki.net/kcms/detail/31.1368.R.20240227.0948.004.html.
ZHAO S M, ZHOU X, YUAN S Z, et al.Research progress on Structure and anti-tumor mechanism of dammarane ginsenoside carboxylic acid derivatives[J/OL].Proprietary Chinese medicine:1-9 2024 (2024-02-27).http://kns.cnki.net/kcms/detail/31.1368.R.20240227.0948.004.html
[6] MURUGESAN M, MATHIYALAGAN R, BOOPATHI V, et al.Production of minor ginsenoside CK from major ginsenosides by biotransformation and its advances in targeted delivery to tumor tissues using nanoformulations[J].Nanomaterials, 2022, 12(19):3427.
[7] 赵会芬. 人参皂苷CK辅助治疗原发性肝癌的临床观察[J].医学综述, 2013, 19(15):2837-2840.
ZHAO H F.Clinical observation of adjuvant therapy of ginsenoside CK on primary hepatocellular carcinoma[J].Medical Recapitulate, 2013, 19(15):2837-2840.
[8] OH J M, KIM E, CHUN S.Ginsenoside compound K induces ros-mediated apoptosis and autophagic inhibition in human neuroblastoma cells in vitro and in vivo[J].International Journal of Molecular Sciences, 2019, 20(17):4279.
[9] YANG W H, ZHOU J L, GU Q Y, et al.Combinatorial enzymatic catalysis for bioproduction of ginsenoside compound K[J].Journal of Agricultural and Food Chemistry, 2023,71(7):3385-3397.
[10] CHI H, KIM D H, JI G E.Transformation of ginsenosides Rb2 and rc from Panax ginseng by food microorganisms[J].Biological and Pharmaceutical Bulletin, 2005, 28(11):2102-2105.
[11] ZHAO X S, WANG J, LI J, et al.Highly selective biotransformation of ginsenoside Rb1 to Rd by the phytopathogenic fungus Cladosporium fulvum (syn.Fulvia fulva)[J].Journal of Industrial Microbiology & Biotechnology, 2009, 36(5):721-726.
[12] 许凌巧, 王安琪, 何正有, 等.提高人参茎叶皂苷中稀有人参皂苷含量的工艺[J].食品工业, 2020, 41(2):50-53.
XU L Q, WANG A Q, HE Z Y, et al.The technology of increasing the content of rare ginsenosides in ginseng stem and leaf saponins[J].The Food Industry, 2020, 41(2):50-53.
[13] 杨宁, 杨世林, 赵余庆.稀有人参皂苷糖苷化合成方法的研究进展[J].现代药物与临床, 2014, 29(5):574-582.
YANG N, YANG S L, ZHAO Y Q.Research progress on glycosylation methods of rare ginsenosides[J].Drugs & Clinic, 2014, 29(5):574-582.
[14] 杨金玲, 高丽丽, 朱平.人参皂苷生物合成研究进展[J].药学学报, 2013, 48(2):170-178.
YANG J L, GAO L L, ZHU P.Advances in the biosynthesis research of ginsenosides[J].Acta Pharmaceutica Sinica, 2013, 48(2):170-178.
[15] HAN Y, SUN B, JIANG B, et al.Microbial transformation of ginsenosides Rb1, Rb3 and Rc by Fusarium sacchari[J].Journal of Applied Microbiology, 2010, 109(3):792-798.
[16] NICHOLSON J K, HOLMES E, WILSON I D.Gut microorganisms, mammalian metabolism and personalized health care[J].Nature Reviews.Microbiology, 2005, 3(5):431-438.
[17] MIWA M K, HORIMOTO T, KIYOHARA M, et al.Cooperation of β-galactosidase and β-N-acetylhexosaminidase from bifidobacteria in assimilation of human milk oligosaccharides with type 2 structure[J].Glycobiology, 2010, 20(11):1402-1409.
[18] 柯仲成, 杨楠, 侯雪峰, 等.大鼠肠道菌群对芍药苷体外代谢转化的研究[J].中国中药杂志, 2016, 41(20):3839-3845.
KE Z C, YANG N, HOU X F, et al.Metabolism of paeoniflorin by rat intestinal flora in vitro[J].China Journal of Chinese Materia Medica, 2016, 41(20):3839-3845.
[19] BAU E A, CHOO M K, PARK E K, et al.Metabolism of ginsenoside R(c) by human intestinal bacteria and its related antiallergic activity[J].Biological & Pharmaceutical Bulletin, 2002, 25(6):743-747.
[20] JEON J H, LEE J, PARK J H, et al.Effect of lactic acid bacteria on the pharmacokinetics and metabolism of ginsenosides in mice[J].Pharmaceutics, 2021, 13(9):1496.
[21] JIA L E, ZHAO Y Q, LIANG X J.Current evaluation of the millennium phytomedicine- ginseng (II):Collected chemical entities, modern pharmacology, and clinical applications emanated from traditional Chinese medicine[J].Current Medicinal Chemistry, 2009, 16(22):2924-2942.
[22] CHU L L, HANH N T Y, QUYEN M L, et al.Compound K production:Achievements and perspectives[J].Life, 2023, 13(7):1565.
[23] 马宗敏, 段绪红, 秦梦, 等.微生物发酵技术在中药苷类生物转化中的应用进展[J].世界科学技术-中医药现代化, 2017, 19(5):858-864.
MA Z M, DUAN X H, QIN M, et al.Microbial transformation of glycosides in Chinese herbal medicine[J].Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology, 2017, 19(5):858-864.
[24] JIANG Y Y, LI W N, FAN D D.Biotransformation of ginsenoside Rb1 to ginsenoside CK by strain XD101:A safe bioconversion strategy[J].Applied Biochemistry and Biotechnology, 2021, 193(7):2110-2127.
[25] LIU C Y, ZHOU R X, SUN C K, et al.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].Journal of Ginseng Research, 2015, 39(3):221-229.
[26] 高娟, 周安东, 原野, 等.黑曲霉降解人参皂苷Rb1制备稀有皂苷Compound K[J].生物技术进展, 2016, 6(2):98-104.
GAO J, ZHOU A D, YUAN Y, et al.Enzymatic degradation of ginsenoside Rb1 for preparation of compound K by Aspergillus niger sp.J7[J].Current Biotechnology, 2016, 6(2):98-104.
[27] 周伟. 稀有人参皂苷compound K的制备和活性研究[D].上海:复旦大学, 2008.
ZHOU W.Study on preparation and activity of rare ginsenoside compound K[D].Shanghai:Fudan University, 2008.
[28] 崔宇, 姜彬慧, 韩颖, 等.微生物对人参果总皂苷中人参皂苷化合物K的转化作用[J].中草药, 2007, 38(2):189-193.
CUI Y, JIANG B H, HAN Y, et al.Microbial transformation on ginsenoside compound K from total saponins in fruit of Panax ginseng[J].Chinese Traditional and Herbal Drugs, 2007, 38(2):189-193.
[29] JI Q, GAO Y G, ZHAO Y, et al.Determination of ginsenosides by Bacillus polymyxa conversion and evaluation on pharmacological activities of the conversion products[J].Process Biochemistry, 2015, 50(6):1016-1022.
[30] 武伦鹏, 白龙律, 韩春峰, 等.微生物转化人参主要皂苷 Rb1 为 CK 的研究[J].人参研究, 2016(2):7-11.
WU L P, BAI L L, HAN C F, et al.Study on microbial transformation of ginseng saponin Rb1 into CK[J].Ginseng Research, 2016(2):7-11.
[31] LI F, WU Z X, SUI X.Biotransformation of ginsenoside Rb1 with wild Cordyceps sinensis and Ascomycota sp.and its antihyperlipidemic effects on the diet-induced cholesterol of zebrafish[J].Journal of Food Biochemistry, 2020, 44(6):e13192.
[32] KIM M J, UPADHYAYA J, YOON M S, et al.Highly regioselective biotransformation of ginsenoside Rb2 into compound Y and compound K by β-glycosidase purified from Armillaria mellea mycelia[J].Journal of Ginseng Research, 2018, 42(4):504-511.
[33] 郭从亮, 杨晓艳, 陈子明, 等.一株植物内生菌Coniochaeta sp.对三七总皂苷中人参皂苷Rb1的特异性转化含量测定[J].中药材, 2016, 39(5):1075-1078.
GUO C L, YANG X Y, CHEN Z M, et al.The content determination of biotransformation of Rb1 in the total saponins of Panax notoginseng by a plant endophyte Coniochaeta sp[J].Journal of Chinese Medicinal Materials, 2016, 39(5):1075-1078.
[34] 文孟良, 李铭刚, 刚 杜, 等.一种链霉菌发酵三七皂苷制备稀有人参皂苷Compound K的工艺.药物生物技术, 2009, 16(1):18-18.
WEN M L, LI M G, GANG Du, et al.Process for preparing rare ginsenoside Compound K by fermentation of notoginseng saponins by Streptomyces.Pharmaceutical Biotechnology, 2009, 16(1):18-18.
[35] FU Y, YIN Z H, WU L P, et al.Biotransformation of ginsenoside Rb1 to ginsenoside C-K by endophytic fungus Arthrinium sp.GE 17-18 isolated from Panax ginseng[J].Letters in Applied Microbiology, 2016, 63(3):196-201.
[36] LIU Z, LI J X, WANG C Z, et al.Microbial conversion of protopanaxadiol-type ginsenosides by the edible and medicinal mushroom Schizophyllum commune:A green biotransformation strategy[J].ACS Omega, 2019, 4(8):13114-13123.
[37] XU Y Q, TANG Y Q, LIU T, et al.Optimization of rare ginsenosides and antioxidant activity quality of ginseng jiaosu based on probiotic strains and fermentation technology[J].Journal of Food Quality, 2023, 2023:5686929.
[38] KIM B G, CHOI S Y, KIM M R, et al.Changes of ginsenosides in Korean red ginseng (Panax ginseng) fermented by Lactobacillus plantarum M1[J].Process Biochemistry, 2010, 45(8):1319-1324.
[39] QUAN L H, KIM Y J, LI G H, et al.Microbial transformation of ginsenoside Rb1 to compound K by Lactobacillus paralimentarius[J].World Journal of Microbiology & Biotechnology, 2013, 29(6):1001-1007.
[40] CHOI H J, KIM E A, KIM D H, et al.The bioconversion of red ginseng ethanol extract into compound K by Saccharomyces cerevisiae HJ-014[J].Mycobiology, 2014, 42(3):256-261.
[41] CHENG L Q, KIM M K, LEE J W, et al.Conversion of major ginsenoside Rb1 to ginsenoside F2 by Caulobacter leidyia[J].Biotechnology Letters, 2006, 28(14):1121-1127.
[42] PARK S J, YOUN S Y, JI G E, et al.Whole cell biotransformation of major ginsenosides using Leuconostocs and Lactobacilli[J].Food Science and Biotechnology, 2012, 21(3):839-844.
[43] ZHENG Y, ZHENG Z Z, MING Y L, et al.Compound K producing from the enzymatic conversion of gypenoside by naringinase[J].Food and Chemical Toxicology, 2019, 130:253-261.
[44] KIM S Y, LEE H N, HONG S J, et al.Enhanced biotransformation of the minor ginsenosides in red ginseng extract by Penicillium decumbens β-glucosidase[J].Enzyme and Microbial Technology, 2022, 153:109941.
[45] GUO C L, CUI X M, YANG X Y, et al.Advances in studies on biotransformation of ginsensides[J].Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica, 2014, 39(20):3899-3904.
[46] LI W N, ZHANG X W, XUE Z Y, et al.Ginsenoside CK production by commercial snailase immobilized onto carboxylated chitosan-coated magnetic nanoparticles[J].Biochemical Engineering Journal, 2021, 174:108119.
[47] CAO S S, YANG F, TIAN F, et al.Immobilized β-glucosidase on Cu(PTA) for the green production of rare ginsenosides CK[J].Process Biochemistry, 2023, 133:169-178.
[48] CAO S S, LI R Z, TIAN F, et al.Construction of a hollow MOF with high sedimentation performance and co-immobilization of multiple-enzymes for preparing rare ginsenoside CK[J].Reaction Chemistry & Engineering, 2023, 8(11):2804-2817.
[49] 于兆慧, 刘其媛, 崔莉, 等.微球固定化蜗牛酶转化人参皂苷Rb1制备人参稀有皂苷Compound K研究[J].中草药, 2014, 45(21):3092-3097.
YU Z H, LIU Q Y, CUI L, et al.Transformation of rare ginsenoside Compound K from ginsenoside Rb1 catalyzed by snailase immobilization onto microspheres[J].Chinese Traditional and Herbal Drugs, 2014, 45(21):3092-3097.
[50] TIAN D D, WU Z S, LIU X C, et al.Synthesis of l-aspartic acid-based bimetallic hybrid nanoflowers to immobilize snailase for the production of rare ginsenoside compound K[J].Journal of Materials Chemistry B, 2023, 11(11):2397-2408.
[51] WANG P, TANG C C, LIU Y N, et al.Biotransformation of high concentrations of ginsenoside substrate into compound K by β-glycosidase from Sulfolobus solfataricus[J].Genes, 2023, 14(4):897.
[52] JIN X, YANG Q, CAI N.Preparation of ginsenoside compound-K mixed micelles with improved retention and antitumor efficacy[J].International Journal of Nanomedicine, 2018, 13:3827-3838.
[53] BORGO C, RUZZENE M.Role of protein kinase CK2 in antitumor drug resistance[J].Journal of Experimental & Clinical Cancer Research, 2019, 38(1):287.
[54] OLIVEIRA M M S, D’AULERIO R, YONG T, et al.Increased cross-presentation by dendritic cells and enhanced anti-tumour therapy using the Arp2/3 inhibitor CK666[J].British Journal of Cancer, 2023, 128(6):982-991.
[55] 范励雯. 人参皂苷CK通过EGFR/AKT/G6PC3轴抑制肺腺癌糖酵解提高培美曲塞疗效及机制研究[D].长春:吉林大学, 2023.
FAN L W.Ginsenoside CK inhibits glycolysis of lung adenocarcinoma through EGFR/AKT/G6PC3 axis to improve the therapeutic effect of pemetrexed and its mechanism[D].Changchun:Jilin University, 2023.
[56] 殷琪. 人参皂苷CK对人宫颈癌Hela细胞的抑制作用及机理研究[D].合肥:合肥工业大学, 2022.
YIN Q.Inhibitory effect and mechanism of ginsenoside CK on human cervical cancer Hela cells[D].Hefei:Hefei University of Technology, 2022.
[57] 张波. 人参皂苷CK对三阴性乳腺癌谷氨酰胺代谢的影响及作用机制[D].西安:西北大学, 2022.
ZHANG B.Effect of ginsenoside CK on glutamine metabolism in triple negative breast cancer and its mechanism[D].Xi’an:Northwest University, 2022.
[58] 李铭莹, 林霖, 王岩, 等.人参皂苷抗肿瘤机制及其纳米药物递送系统的研究进展[J].中草药, 2024, 55(2):688-696.
LI M Y, LIN L, WANG Y, et al.Research progress on antitumor mechanism and nano-drug delivery system for ginsenosides[J].Chinese Traditional and Herbal Drugs, 2024, 55(2):688-696.
[59] ZHANG J M, WANG Y J, JIANG Y Y, et al.Enhanced cytotoxic and apoptotic potential in hepatic carcinoma cells of chitosan nanoparticles loaded with ginsenoside compound K[J].Carbohydrate Polymers, 2018, 198:537-545.
[60] FAN H Y, WANG Y, ZHANG X L, et al.Ginsenoside compound K ameliorates imiquimod-induced psoriasis-like dermatitis through inhibiting REG3A/RegIIIγ expression in keratinocytes[J].Biochemical and Biophysical Research Communications, 2019, 515(4):665-671.
[61] KIM S, WANG R B, DHANDAPANI S, et al.Novel modified probiotic gold nanoparticles loaded with ginsenoside CK exerts an anti-inflammation effect via NF-κB/MAPK signaling pathways[J].Arabian Journal of Chemistry, 2024, 17(4):105650.
[62] PANICH U, SITTITHUMCHAREE G, RATHVIBOON N, et al.Ultraviolet radiation-induced skin aging:The role of DNA damage and oxidative stress in epidermal stem cell damage mediated skin aging[J].Stem Cells International, 2016, 2016:7370642.
[63] FENG M Y, ZHENG X, WAN J, et al.Research progress on the potential delaying skin aging effect and mechanism of tea for oral and external use[J].Food & Function, 2021, 12(7):2814-2828.
[64] KIM E H, KIM W.An insight into ginsenoside metabolite compound K as a potential tool for skin disorder[J].Evidence-Based Complementary and Alternative Medicine, 2018, 2018:8075870.
[65] JIN Y, WANG D D, IM W T, et al.Ketonization of ginsenoside C-K by novel recombinant 3-β-hydroxysteroid dehydrogenases and effect on human fibroblast cells[J].Molecules, 2023, 28(9):3792.
[66] LI W L, LI H Y, ZHENG L J, et al.Ginsenoside CK improves skeletal muscle insulin resistance by activating DRP1/PINK1-mediated mitophagy[J].Food & Function, 2023, 14(2):1024-1036.
[67] CHEN Q, REN D W, LIU L K, et al.Ginsenoside compound K ameliorates development of diabetic kidney disease through inhibiting TLR4 activation induced by microbially produced imidazole propionate[J].International Journal of Molecular Sciences, 2022, 23(21):12863.
[68] CHO W J, OH H, ABD EL-ATY A M, et al.Therapeutic potential of ginsenoside compound K in managing tenocyte apoptosis and extracellular matrix damage in diabetic tendinopathy[J].Tissue and Cell, 2024, 86:102275.
[69] SONG W, LI G, TANG Y, et al.Ginsenoside compound K inhibits oxidative stress and NLRP3 inflammasome activity in mice exposed to chronic unpredictable mild stress[J].Biotechnology & Biotechnological Equipment, 2019, 33(1):1372-1379.
[70] SHIN Y J, LEE D Y, KIM J Y, et al.Effect of fermented red ginseng on gut microbiota dysbiosis- or immobilization stress-induced anxiety, depression, and colitis in mice[J].Journal of Ginseng Research, 2023, 47(2):255-264.
[71] WEITZMANN M N, OFOTOKUN I.Physiological and pathophysiological bone turnover-role of the immune system[J].Nature Reviews.Endocrinology, 2016, 12(9):518-532.
[72] DING L L, GAO Z, WU S L, et al.Ginsenoside compound-K attenuates OVX-induced osteoporosis via the suppression of RANKL-induced osteoclastogenesis and oxidative stress[J].Natural Products and Bioprospecting, 2023, 13(1):49.
[73] ZHANG S, SHEN S H, MA P, et al.Biochemical targets and molecular mechanism of ginsenoside compound K in treating osteoporosis based on network pharmacology[J].International Journal of Molecular Sciences, 2022, 23(22):13921.
Outlines

/

〈 〉