小白菊内酯是一种倍半萜烯内酯类天然产物,分离自艾菊、观光木等药用植物,这些植物广泛应用于发热、驱虫和抗炎等。近年来的研究证实小白菊内酯具有多种重要的药理活性,如抗肿瘤、抗病毒、抗炎和抗动脉粥样硬化等,小白菊内酯传统上主要用来治疗偏头痛、发热和类风湿性关节炎等。
Parthenolide (PTL) has a dose-dependent growth inhibition effect on NSCLC cells Calu-1, H1792, A549, H1299, H157, and H460. Parthenolide can induce cleavage of apoptotic proteins such as CASP8, CASP9, CASP3 and PARP1 both in concentration- and time-dependent manner in tested lung cancer cells, indicating that apoptosis is trigged after Parthenolide exposure. In addition to induction of apoptosis, Parthenolide also induces G 0 /G 1 cell cycle arrest in a concentration-dependent manner in A549 cells and G 2 /M cell cycle arrest in H1792 cells.
Only Parthenolide, the HDAC inhibitor with anti-inflammatory features, displayed a potent anti-apoptotic effect in Phb1 KO hepatocytes. Indeed, TSA and Parthenolide-treated hepatocytes showed increased levels of FXR, and reduced levels of CYP7A1, HDAC4, TNFα, TRAIL and Bax suggesting a less toxic effect of bile acids as a results of specific HDAC inhibition, resulting in the attenuation of the Phb1 KO hepatocytes apoptotic response. Importantly, Parthenolide exerts a protective effect from the liver injury after BDL in Phb1 KO mice. Indeed, Parthenolide treatment results in a reduction of the mortality rate of this mice after BDL associated with a lower apoptotic response as revealed by a reduction of necrotic areas, Tunel-staining, as well as decreased ALT (8431±957 vs.4225±210 U/L) and AST (4805±300 vs.2242±438 U/L) activities compared to control Phb1 KO mice.