PDF(Pubmed)
Abstract：
Cimicifuga racemosa extracts (CREs) have gained well-established use for the treatment of menopausal symptoms such as hot flushes and excessive sweating, and weight gain. While the clinical effects of CREs have been well documented, the mechanisms underlying these effects are largely unknown. More recently, the metabolic effects of the CRE Ze 450 were demonstrated in cultured cells in vitro and in mouse models of obesity in vivo. At the molecular level, metabolic regulation, enhanced insulin sensitivity, and increased glucose uptake were linked to the activation of AMP-activated protein kinase (AMPK). Therefore, we tested the effects of Ze 450 on AMPK phosphorylation and thus activation in cells from different tissues, i.e., murine C2C12 myoblast cells, human HEPG2 liver cells, mouse HT22 neuronal cells, and in murine 3T3L1 adipocytes. Using a FRET-based HTRF-assay, we found that Ze 450 induced AMPK phosphorylation and the activation of this key enzyme of metabolic regulation in cells from various different tissues including C2C12 (muscle), HEPG2 (liver), HT22 (hippocampal), and 3T3-L1 (adipocyte) cells. In C2C12 muscle cells, enhanced AMPK activation was accompanied by reduced mitochondrial respiration and enhanced glucose uptake. Further, Ze 450 enhanced the resilience of the cells against oxidative death induced by ferroptosis inducers erastin or RSL3. Our findings suggest a general effect of Cimicifuga racemosa on AMPK activation in different tissues and across species. This may have a significant impact on expanded therapeutic applications of Ze 450, since AMPK activation and the related metabolic effects have been previously associated with anti-aging effects and the prevention of the metabolic syndrome.
摘要：
cimicifugaraceemosa提取物（CREs）已获得公认的用于治疗更年期症状，例如潮热和出汗过多，和体重增加。虽然CREs的临床效果已经得到了很好的证明，这些影响的潜在机制在很大程度上是未知的。最近,在体外培养细胞和体内肥胖小鼠模型中证明了CREZe450的代谢作用。在分子水平上,代谢调节，增强胰岛素敏感性，葡萄糖摄取的增加与AMP激活的蛋白激酶（AMPK）的激活有关。因此,我们测试了Ze450对AMPK磷酸化的影响，从而在来自不同组织的细胞中激活，即，鼠C2C12成肌细胞，人HEPG2肝细胞，小鼠HT22神经元细胞，和鼠3T3L1脂肪细胞。使用基于FRET的HTRF测定，我们发现，Ze450诱导AMPK磷酸化和激活的这种关键酶的代谢调节在细胞从各种不同的组织，包括C2C12（肌肉），HEPG2（肝脏），HT22（海马），和3T3-L1(脂肪细胞)细胞。在C2C12肌肉细胞中，AMPK激活增强伴随着线粒体呼吸减少和葡萄糖摄取增强.Further,Ze450增强了细胞抵抗铁凋亡诱导剂erastin或RSL3诱导的氧化死亡的弹性。我们的发现表明，消旋升麻对不同组织和跨物种的AMPK活化具有一般作用。这可能对Ze450的扩展治疗应用具有显著影响,因为AMPK激活和相关的代谢作用先前已经与抗衰老作用和代谢综合征的预防相关联。
