A Narrative Review of the Pharmacology of Ginsenoside Compound K

Overview

Journal Ann Transl Med

Publisher AME Publishing Company

Date 2022 Mar 14

PMID 35280413

Authors

Tao Liu

Lu Zhu

Li Wang

Affiliations

Soon will be listed here.

Abstract

Background And Objective: The ginsenoside compound K [20-o-beta-dglucopyranosyl-20 (S)-protopanaxadiol; CK] is the main deglycosylated metabolite of ginsenoside. As a rare ginsenoside converted from the active substance of ginseng by intestinal bacteria, CK has higher biological activity than other ginsenosides. It has demonstrated diverse and intriguing biological activities, including anti-carcinogenic, anti-diabetic, anti-inflammation, anti-allergy, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects. The purpose of this review was to elucidate the rich pharmacological activities and related mechanisms of ginsenoside CK and , as well as the potential therapeutic value of CK as a drug in a variety of systemically related diseases.

Methods: The PubMed database was searched for articles published in English from February 2008 to December 2021 using related keywords such as "Ginsenoside compound K", "compound K", and "CK". About 140 research papers and reports written in English were identified. These papers mainly concentrated on the pharmacological activities of CK in cancer prevention, immune regulation, diabetic improvement, central nervous system (CNS) protection, cardiovascular protection, skin improvement, and hepatoprotection.

Key Content And Findings: This paper describes the synthesis, pharmacokinetics, and adverse reactions of CK, as well as great detailed summarized of the relevant pharmacological activities. Such diverse intriguing biological properties of CK have been found.

Conclusions: On account of CK's numerous pharmacological activities and anti-carcinogenic, anti-inflammation, antiallergic, anti-diabetic, anti-angiogenesis, anti-aging, neuroprotective, and hepatoprotective effects, strong evidence is available for CK as a preventive or therapeutic agent for various diseases. However, further studies are needed to evaluate the safety and effectiveness of CK as a drug and its application in the medical field.

Citing Articles

Anti-Inflammatory Effects of Fermented and Aged Mountain-Cultivated Ginseng Sprouts via Suppression of MAPK-NF-κB Pathway in Lipopolysaccharide-Stimulated RAW264.7 Macrophages.

Cao D, Woo M, Kim E, Ahn B, Prayoga A, Kang S Food Sci Nutr. 2024; 12(11):9566-9576.

PMID: 39619973 PMC: 11606880. DOI: 10.1002/fsn3.4518.

The role of Chinese herbal medicine in the regulation of oxidative stress in treating hypertension: from therapeutics to mechanisms.

Jin Z, Lan Y, Li J, Wang P, Xiong X Chin Med. 2024; 19(1):150.

PMID: 39468572 PMC: 11520704. DOI: 10.1186/s13020-024-01022-9.

Application of microorganisms in Panax ginseng: cultivation of plants, and biotransformation and bioactivity of key component ginsenosides.

Ji H, Guo L, Yu D, Du X Arch Microbiol. 2024; 206(11):433.

PMID: 39412649 DOI: 10.1007/s00203-024-04144-8.

Ginsenoside compound K induces ferroptosis via the FOXO pathway in liver cancer cells.

Chen J, Wang Z, Fu J, Cai Y, Cheng H, Cui X BMC Complement Med Ther. 2024; 24(1):174.

PMID: 38664638 PMC: 11044296. DOI: 10.1186/s12906-024-04471-9.

Endophytic fungi of Panax sokpayensis produce bioactive ginsenoside Compound K in flask fermentation.

Rai S, Singh L, Shaanker R, Jeyaram K, Parija T, Sahoo D Sci Rep. 2024; 14(1):9318.

PMID: 38654024 PMC: 11039684. DOI: 10.1038/s41598-024-56441-3.

References

Zhang Z, Du G, Wang C, Wen X, Calway T, Li Z . Compound K, a Ginsenoside Metabolite, Inhibits Colon Cancer Growth via Multiple Pathways Including p53-p21 Interactions. Int J Mol Sci. 2013; 14(2):2980-95. PMC: 3588026. DOI: 10.3390/ijms14022980. View

Xie T, Li Z, Li B, Sun R, Zhang P, Lv J . Characterization of ginsenoside compound K metabolites in rat urine and feces by ultra-performance liquid chromatography with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Biomed Chromatogr. 2019; 33(11):e4643. DOI: 10.1002/bmc.4643. View

Wang R, Zhang M, Hu S, Liu K, Tai Y, Tao J . Ginsenoside metabolite compound-K regulates macrophage function through inhibition of β-arrestin2. Biomed Pharmacother. 2019; 115:108909. DOI: 10.1016/j.biopha.2019.108909. View

Wang C, Zhang Z, Wan J, Zhang C, Anderson S, He X . Protopanaxadiol, an active ginseng metabolite, significantly enhances the effects of fluorouracil on colon cancer. Nutrients. 2015; 7(2):799-814. PMC: 4344561. DOI: 10.3390/nu7020799. View

Joh E, Lee I, Jung I, Kim D . Ginsenoside Rb1 and its metabolite compound K inhibit IRAK-1 activation--the key step of inflammation. Biochem Pharmacol. 2011; 82(3):278-86. DOI: 10.1016/j.bcp.2011.05.003. View

Wu L, Jin Y, Yin C, Bai L . Co-transformation of Panax major ginsenosides Rb₁ and Rg₁ to minor ginsenosides C-K and F₁ by Cladosporium cladosporioides. J Ind Microbiol Biotechnol. 2012; 39(4):521-7. DOI: 10.1007/s10295-011-1058-9. View

Kwak C, Son Y, Gu M, Kim G, Lee I, Kye Y . A Bacterial Metabolite, Compound K, Induces Programmed Necrosis in MCF-7 Cells via GSK3β. J Microbiol Biotechnol. 2015; 25(7):1170-6. DOI: 10.4014/jmb.1505.05057. View

Bae M, Cho J, Choi I, Park H, Lee M, Kim D . Compound K, a metabolite of ginsenosides, facilitates spontaneous GABA release onto CA3 pyramidal neurons. J Neurochem. 2010; 114(4):1085-96. DOI: 10.1111/j.1471-4159.2010.06833.x. View

Hasegawa H, Sung J, MATSUMIYA S, Uchiyama M . Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med. 1996; 62(5):453-7. DOI: 10.1055/s-2006-957938. View

10.

Kang K, Kim Y, Kim S, Chae S, Koh Y, Kim H . G1 phase arrest of the cell cycle by a ginseng metabolite, compound K, in U937 human monocytic leukamia cells. Arch Pharm Res. 2005; 28(6):685-90. DOI: 10.1007/BF02969359. View

11.

Yang Y, Liu X, Li S, Chen Y, Zhao Y, Wei Y . Genome-scale CRISPR screening for potential targets of ginsenoside compound K. Cell Death Dis. 2020; 11(1):39. PMC: 6971025. DOI: 10.1038/s41419-020-2234-5. View

12.

Fan H, Wang Y, Zhang X, Chen J, Zhou Q, Yu Z . Ginsenoside compound K ameliorates imiquimod-induced psoriasis-like dermatitis through inhibiting REG3A/RegIIIγ expression in keratinocytes. Biochem Biophys Res Commun. 2019; 515(4):665-671. DOI: 10.1016/j.bbrc.2019.06.007. View

13.

Liu Y, Perumalsamy H, Kang C, Kim S, Hwang J, Koh S . Intracellular synthesis of gold nanoparticles by for delivery of peptide CopA3 and ginsenoside and anti-inflammatory effect on lipopolysaccharide-activated macrophages. Artif Cells Nanomed Biotechnol. 2020; 48(1):777-788. DOI: 10.1080/21691401.2020.1748639. View

14.

Park E, Lee K, Jung S, Lee D, Won K, Yun Y . Compound K, an intestinal metabolite of ginsenosides, inhibits PDGF-BB-induced VSMC proliferation and migration through G1 arrest and attenuates neointimal hyperplasia after arterial injury. Atherosclerosis. 2013; 228(1):53-60. DOI: 10.1016/j.atherosclerosis.2013.02.002. View

15.

Hou J, Xue J, Zhao X, Wang Z, Li W, Li X . Octyl ester of ginsenoside compound K as novel anti-hepatoma compound: Synthesis and evaluation on murine H22 cells in vitro and in vivo. Chem Biol Drug Des. 2017; 91(4):951-956. DOI: 10.1111/cbdd.13153. View

16.

Chen W, Wang J, Luo Y, Wang T, Li X, Li A . Ginsenoside Rb1 and compound K improve insulin signaling and inhibit ER stress-associated NLRP3 inflammasome activation in adipose tissue. J Ginseng Res. 2016; 40(4):351-358. PMC: 5052408. DOI: 10.1016/j.jgr.2015.11.002. View

17.

Lee S, Kwon M, Jang J, Sohng J, Jung H . The ginsenoside metabolite compound K inhibits growth, migration and stemness of glioblastoma cells. Int J Oncol. 2017; 51(2):414-424. PMC: 5505016. DOI: 10.3892/ijo.2017.4054. View

18.

Kang K, Piao M, Kim K, Zheng J, Yao C, Cha J . Compound K, a metabolite of ginseng saponin, inhibits colorectal cancer cell growth and induces apoptosis through inhibition of histone deacetylase activity. Int J Oncol. 2013; 43(6):1907-14. DOI: 10.3892/ijo.2013.2129. View

19.

Wang Y, Zhu H, Li H, Li Y, Zhao B, Jin Y . Ginsenoside compound K inhibits nuclear factor-kappa B by targeting Annexin A2. J Ginseng Res. 2019; 43(3):452-459. PMC: 6606818. DOI: 10.1016/j.jgr.2018.04.002. View

20.

Lee C, Bae I, Han J, Choi G, Hwang K, Kim D . Compound K inhibits MMP-1 expression through suppression of c-Src-dependent ERK activation in TNF-α-stimulated dermal fibroblast. Exp Dermatol. 2014; 23(11):819-24. DOI: 10.1111/exd.12536. View