Ginsenoside CK, a secondary ginsenoside biotransformed from major ginsenosides, is more bioavailable and soluble than its parent ginsenosides and holds great significance[1]. Naturally absent, Ginsenoside CK can be generated from other protopanaxadiol (PPD)-type ginsenosides by the intestinal microflora of humans or rats[2]. As a bacterial metabolite of Ginsenoside-Rb1, Ginsenoside CK exhibits anti-inflammatory effects mainly by reducing inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and proinflammatory cytokines[3]. Ginsenoside CK potently inhibited the production of nitric oxide and prostaglandin E2 in LPS-induced RAW 264.7 cells, with IC50 values of 0.012 and 0.004mM, respectively[4].
In vitro, treatment of HepG2 cells with Ginsenoside CK (8, 4, and 2µM) for 24h resulted in dose-dependent inhibition of hepatic glucose production, accompanied by a decrease in Phosphoenolpyruvate carboxykinase (PEPCK) protein level and an increase in adenosine-5’ monophosphate kinase (AMPK) phosphorylation[5]. Ginsenoside CK (0.01-10µM) was applied to H₂O₂-stimulated MC3T3-E1 cells with or without H₂O₂ for 48h, and the result was found that Ginsenoside CK formed hydrogen bonds with IkBα kinase, increased alkaline phosphatase activity, type I collagen expressions, while decreasing reactive oxygen species and nitric oxide production as well as IL-1β expression[6].
In vivo, DBA/1 mice with collagen-induced arthritis (CIA) were treated with Ginsenoside CK (28, 56, or 112mg/kg/d, ig) or the positive control methotrexate (2mg/kg, ig, every 3d) for 34d, and Ginsenoside CK treatment significantly ameliorated the pathologic manifestations of CIA mice, remarkably inhibited T lymphocyte proliferation, and marginally inhibited the proliferation of B lymphocytes[7]. OLETF rats treated with a high-fat diet (HFD) were administered orally Ginsenoside CK (25 and 10mg/kg) for 12 weeks, which resulted in decreased plasma glucose levels and improved liver cell morphology[8].
References:
[1] Sharma A, Lee HJ. Ginsenoside Compound K: Insights into Recent Studies on Pharmacokinetics and Health-Promoting Activities. Biomolecules. 2020;10(7):1028.
[2] Yang XD, Yang YY, Ouyang DS, Yang GP. A review of biotransformation and pharmacology of ginsenoside compound K. Fitoterapia. 2015;100:208-220.
[3] Kim JH, Yi YS, Kim MY, Cho JY. Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases. J Ginseng Res. 2017;41(4):435-443.
[4] Park EK, Shin YW, Lee HU, et al. Inhibitory effect of ginsenoside Rb1 and compound K on NO and prostaglandin E2 biosyntheses of RAW264.7 cells induced by lipopolysaccharide. Biol Pharm Bull. 2005;28(4):652-656.
[5] Wei S, Li W, Yu Y, et al. Ginsenoside Compound K suppresses the hepatic gluconeogenesis via activating adenosine-5'monophosphate kinase: A study in vitro and in vivo. Life Sci. 2015;139:8-15.
[6] Kang S, Siddiqi MH, Yoon SJ, et al. Therapeutic potential of compound K as an IKK inhibitor with implications for osteoarthritis prevention: an in silico and in vitro study. In Vitro Cell Dev Biol Anim. 2016;52(9):895-905.
[7] Liu KK, Wang QT, Yang SM, Chen JY, Wu HX, Wei W. Ginsenoside compound K suppresses the abnormal activation of T lymphocytes in mice with collagen-induced arthritis. Acta Pharmacol Sin. 2014;35(5):599-612.
[8] Hwang YC, Oh DH, Choi MC, et al. Compound K attenuates glucose intolerance and hepatic steatosis through AMPK-dependent pathways in type 2 diabetic OLETF rats. Korean J Intern Med. 2018;33(2):347-355.