灵芝子实体高压超临界CO2提取物及其抗肝癌作用与Ras/Raf/MEK/ERK信号通路的关系。

PubMed ID
发表日期 2020年月

原始出处 药理学前沿
Frontiers in pharmacology
作者 Zhu  Liping  Wu  Min  Li  Peng  Zhou  Yanfei  Zhong  Jinyi  Zhang  Zhiqiang  Li  Ye  Yao  Weixi  Xu  Jianhua 

文献标题 灵芝子实体高压超临界CO2提取物及其抗肝癌作用与Ras/Raf/MEK/ERK信号通路的关系。
High-Pressure Supercritical CO2 Extracts of Ganoderma lucidum Fruiting Body and Their Anti-hepatoma Effect Associated With the Ras/Raf/MEK/ERK Signaling Pathway.

文献摘要

灵芝作为一种著名的药用菌,具有抗肿瘤、保肝等多种药理作用。与普通乙醇回流法相比,超临界CO2萃取法具有提取时间短、温度低、无溶剂残留等优点。然而,采用无夹带剂的高压超临界CO2从灵芝中提取抗肿瘤活性物质并研究其抗肝癌作用的研究尚未见报道。以65、85、105mpa高压超临界CO2萃取物G65、G85、G105和乙醇回流萃取物(GLE)为实验材料,研究其抗肝癌活性及其分子机制。紫外分光光度法和高效液相色谱法测定,G85的总三萜含量显著高于G65和GLE,但与G105无显著差异。GLE、G65和G85对两株肝癌细胞株(QGY7703和SK-Hep1)具有抑制细胞增殖、阻滞细胞周期于G2/M期、诱导细胞凋亡的作用,其中G85作用最强。结果表明,高压超临界CO2提取物对人肝癌细胞的体外杀伤作用与其总三萜含量一致。G85在体内具有明显的抗肝癌作用,毒性较低。进一步的机制研究表明,这些提取物的抗肿瘤作用与其抑制Ras/Raf/MEK/ERK信号通路有关。我们的研究结果表明,灵芝子实体的高压超临界CO2萃取可以获得一种富含三萜类化合物的抗肿瘤药物,对治疗人类肝癌具有潜在的临床意义。


As a noted medicinal mushroom, Ganoderma lucidum (G. lucidum) has been reported to have a number of pharmacological effects such as anti-tumor and liver protection. Compared with the common ethanol reflux method, supercritical CO2 extraction has obvious advantages in obtaining antitumor extracts from G. lucidum fruiting body such as short extraction time, low temperature and no solvent residue. However, Using high-pressure supercritical CO2 without entrainer to obtain the antitumor extracts from G. lucidum and studying their anti-hepatoma effect have not been reported. In this study, high-pressure supercritical CO2 extracts obtained under 65, 85, and 105 MPa pressure named as G65, G85, G105 respectively and ethanol reflux extract (GLE) were used to investigate their anti-hepatoma activity and the underlying molecular mechanism. The total triterpenoid content of G85 was significantly higher than that of G65 and GLE, but did not differ significantly from that of G105 by UV and high-performance liquid chromatography. GLE, G65, and G85 could inhibit cell proliferation, arrest cell cycle in G2/M phase, and induce apoptosis in two liver cancer cell lines (QGY7703 and SK-Hep1), of which G85 had the strongest effect. The results showed that the potency of their cytotoxicity of the high-pressure supercritical CO2 extracts on human hepatoma carcinoma cells in vitro was consistent with their total triterpenoid content. G85 exhibited significant anti-hepatoma effect with low toxicity In vivo. Further mechanistic investigation revealed that the anti-tumor effect of these extracts was associated with their inhibition of Ras/Raf/MEK/ERK signaling pathway. Our findings suggest that the high-pressure supercritical CO2 extraction of G. lucidum fruiting body can be used to obtain a triterpenoid-rich anti-tumor agent, which may have potential clinical significance for the treatment of human hepatoma.


获取全文 10.3389/fphar.2020.602702