类黄酮对寿命、脂肪积累、抗逆性和基因调控的影响涉及mTOR、SKN-1和DAF-16。

Flavonoids' Effects on Longevity, Fat Accumulation, Stress Resistance and Gene Modulation Involve mTOR, SKN-1 and DAF-16.

作者信息

Guerrero-Rubio María Alejandra, Hernández-García Samanta, García-Carmona Francisco, Gandía-Herrero Fernando

机构信息

Unidad Docente de Biología, Departamento de Bioquímica y Biología Molecular A, Facultad de Veterinaria, Regional Campus of International Excellence "Campus Mare Nostrum'', Universidad de Murcia, 30100 Murcia, Spain.

出版信息

Antioxidants (Basel). 2021 Mar 12;10(3):438. doi: 10.3390/antiox10030438.

Flavonoids are potential nutraceutical compounds present in diary food. They are considered health-promoting compounds and promising drugs for different diseases, such as neurological and inflammatory diseases, diabetes and cancer. Therefore, toxicological and mechanistic studies should be done to assert the biological effects and identify the molecular targets of these compounds. In this work we describe the effects of six structurally-related flavonoids-baicalein, chrysin, scutellarein, 6-hydroxyflavone, 6,7-dihydroxyflavone and 7,8-dihydroxyflavone-on lifespan and stress resistance. The results showed that chrysin, 6-hydroxyflavone and baicalein prolonged lifespan by up to 8.5%, 11.8% and 18.6%, respectively. The lifespan extensions caused by these flavonoids are dependent on different signaling pathways. The results suggested that chrysin's effects are dependent on the insulin signaling pathway via DAF-16/FOXO. Baicalein and 6-hydroxyflavone's effects are dependent on the SKN-1/Nfr2 pathway. In addition, microarray analysis showed that baicalein downregulates important age-related genes, such as mTOR and PARP.

黄酮类化合物是乳制品中存在的潜在营养化合物。它们被认为是促进健康的化合物，也是治疗不同疾病（如神经疾病、炎症性疾病、糖尿病和癌症）的有前景的药物。因此，应该进行毒理学和作用机制研究，以确定这些化合物的生物学效应并识别其分子靶点。在这项工作中，我们描述了六种结构相关的黄酮类化合物——黄芩素、白杨素、野黄芩素、6-羟基黄酮、6,7-二羟基黄酮和7,8-二羟基黄酮——对寿命和抗逆性的影响。结果表明，白杨素、6-羟基黄酮和黄芩素分别使寿命延长了8.5%、11.8%和18.6%。这些黄酮类化合物引起的寿命延长依赖于不同的信号通路。结果表明，白杨素的作用通过DAF-16/FOXO依赖于胰岛素信号通路。黄芩素和6-羟基黄酮的作用依赖于SKN-1/Nfr2通路。此外，微阵列分析表明，黄芩素下调了重要的衰老相关基因，如mTOR和PARP。