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.
Ginsenoside CK，一种由主要人参皂苷化合物转化而来的次级人参皂苷，比其母体人参皂苷具有更高的生物利用度和溶解性，具有极其重要的意义[1]。Ginsenoside CK在自然界中不存在，但可以通过人类或大鼠的肠道微生物群从其他原人参二醇（PPD）型人参皂苷中生成[2]。作为Ginsenoside-Rb1的细菌代谢产物，Ginsenoside CK主要通过减少诱导型一氧化氮合酶（iNOS）、环氧合酶（COX）-2和促炎细胞因子来发挥抗炎作用[3]。Ginsenoside CK在LPS诱导的RAW 264.7细胞中强有力地抑制了一氧化氮和前列腺素E2的产生，其IC₅₀值分别为0.012mM和0.004mM[4]。
在体外，用Ginsenoside CK（8、4和2µM）处理HepG2细胞24小时，结果显示其以剂量依赖性方式抑制肝脏葡萄糖生成，同时伴随着磷酸烯醇式丙酮酸羧激酶（PEPCK）蛋白水平的降低和腺苷-5’-单磷酸激酶（AMPK）磷酸化的增加[5]。将Ginsenoside CK（0.01-10µM）应用于H₂O₂刺激的MC3T3-E1细胞，处理时间为48小时，结果显示Ginsenoside CK与IκBα激酶形成氢键，增加了碱性磷酸酶活性和I型胶原蛋白表达，同时降低了活性氧和一氧化氮的产生以及IL-1β的表达[6]。
在体内实验中，患有胶原诱导性关节炎（CIA）的DBA/1小鼠接受了Ginsenoside CK（28、56或112mg/kg/d，灌胃）或阳性对照药物甲氨蝶呤（2mg/kg，灌胃，每3天一次）治疗，持续34天。结果显示，Ginsenoside CK治疗显著改善了CIA小鼠的病理表现，显著抑制了T淋巴细胞的增殖，并轻度抑制了B淋巴细胞的增殖[7]。采用高脂饮食（HFD）处理的OLETF大鼠口服Ginsenoside CK（25和10mg/kg）12周，结果导致血浆葡萄糖水平降低和肝细胞形态改善[8]。