Kamebakaurin

Kamebakaurin, a compound of kaurane diterpenes was isolated from traditional Chinese medicinal plant Isodon excia. It is a potent inhibitor of NF-kappaB activation by directly targeting DNA-binding activity of p50^[6].

Treated with different concentrations of kamebakaurin (0-30μM;24 h), The activity of HCT116 cells did not decrease significantly, but Kamebakaurin inhibits HIF-1α protein expression in cells ^[1]. Kamebakaurin (0.1, 1.0, 5 μM) significantly inhibited the LPS-induced production of nitric oxide (NO) in a concentration-dependent fashion in activated microglial cells^[2]. Kamebakaurin (0-500ng/ml;4h)dose-dependently attenuated iNOS gene expression in LPS-activated dendritic cells (DCs). Kamebakaurin significantly inhibited the gene expression and protein production of the inflammatory cytokines TNF-α, IL-12, and IL-1β^[4].

Kamebakaurin (50 mg/kg;40 days;p.o.) produced significant growth inhibition of HCT116 cells in tumor xenograft model^[1]. Kamebakaurin dose-dependently suppressed the inflammation in an adjuvant arthritis model. Oral administration of 20 mg/kg kamebakaurin resulted in the 75% decrease of paw volume^[3]. Pretreatment with Kamebakaurin reduced the magnitude of Acetaminophen (N-acetyl-p-aminophenol, APAP)-induced increases in plasma levels of hepatic injury markers, lipid peroxidation, and inflammatory response^[5].

References:
[1]. Wang KS, Ma J, et,al. Kamebakaurin inhibits the expression of hypoxia-inducible factor-1α and its target genes to confer antitumor activity. Oncol Rep. 2016 Apr;35(4):2045-52. doi: 10.3892/or.2016.4576. Epub 2016 Jan 19. PMID: 26781327.
[2]. Kim BW, Koppula S, et,al.Anti-neuroinflammatory activity of Kamebakaurin from Isodon japonicus via inhibition of c-Jun NH?-terminal kinase and p38 mitogen-activated protein kinase pathway in activated microglial cells. J Pharmacol Sci. 2011;116(3):296-308. doi: 10.1254/jphs.10324fp. Epub 2011 Jun 25. PMID: 21705843.
[3]. Lee JH, Choi JK, et,al. Anti-inflammatory effect of kamebakaurin in in vivo animal models. Planta Med. 2004 Jun;70(6):526-30. doi: 10.1055/s-2004-827152. PMID: 15241890.
[4]. Kim JY, Kim HS, et,al. Inhibition of TAK1 by kamebakaurin in dendritic cells. Int Immunopharmacol. 2013 Jan;15(1):138-43. doi: 10.1016/j.intimp.2012.11.004. Epub 2012 Nov 15. PMID: 23159603.
[5]. Yoshioka H, Aoyagi Y, et,al. Suppressive effect of kamebakaurin on acetaminophen-induced hepatotoxicity by inhibiting lipid peroxidation and inflammatory response in mice. Pharmacol Rep. 2017 Oct;69(5):903-907. doi: 10.1016/j.pharep.2017.04.004. Epub 2017 Apr 12. PMID: 28624597.
[6]. Lee JH, et,al.Kaurane diterpene, kamebakaurin, inhibits NF-kappa B by directly targeting the DNA-binding activity of p50 and blocks the expression of antiapoptotic NF-kappa B target genes. J Biol Chem. 2002 May 24;277(21):18411-20. doi: 10.1074/jbc.M201368200. Epub 2002 Mar 4. PMID: 11877450.

Kamebakaurin 是一种从传统中药植物 Isodon excia 中分离出来的贝壳杉烷二萜类化合物。它是一种有效的 NF-kappaB 激活抑制剂，可直接靶向 p50^[6] 的 DNA 结合活性。

Kamebakaurin处理不同浓度(0-30μM;24 h)后，HCT116细胞的活性没有明显下降，但Kamebakaurin抑制细胞内HIF-1α蛋白的表达^[1]。 Kamebakaurin (0.1, 1.0, 5 μM) 在活化的小胶质细胞中以浓度依赖性方式显着抑制 LPS 诱导的一氧化氮 (NO) 的产生^[2]。 Kamebakaurin (0-500ng/ml;4h)剂量依赖性地减弱 LPS 激活的树突细胞 (DC) 中的 iNOS 基因表达。 Kamebakaurin显着抑制炎性细胞因子TNF-α、IL-12和IL-1β的基因表达和蛋白生成^[4]。

Kamebakaurin（50 mg/kg；40 天；口服）在肿瘤异种移植模型中对 HCT116 细胞产生显着的生长抑制作用^[1]。 Kamebakaurin 以剂量依赖性方式抑制辅助性关节炎模型中的炎症。口服 20 mg/kg 的龟贝卡林可使足爪体积减少 75%^[3]。使用 Kamebakaurin 预处理可降低对乙酰氨基酚（N-乙酰基-对氨基苯酚，APAP）诱导的肝损伤标志物、脂质过氧化和炎症反应血浆水平升高的程度^[5]。