Kim Jeong-Seok, Jeong Seon-Hwa, Han Sin-Hee, Yi Ho-Keun
Department of Physical Education, College of Education, Chonbuk National University, Jeonju, South Korea.
Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, Jeonju, South Korea.
Clin Exp Pharmacol Physiol. 2018 Jun;45(6):547-555. doi: 10.1111/1440-1681.12914. Epub 2018 Feb 13.
Gomisin A from the fruit of Schisandra chinensis has many pharmacological properties, including hepato-protective, anti-diabetic, and anti-oxidative stress. However, the potential benefit of gomisin A is still not well understood, especially in aging progression. Therefore, the aim of this study was to clarify whether the promotion of mitochondrial biogenesis and autophagy of gomisin A affects anti-aging progression, and its mechanism. Intermediate (PD32) human diploid fibroblast (HDF) cells were brought to stress-induced premature senescence (SIPS) using hydrogen peroxide. Gomisin A inhibited reactive oxygen species production even in the SIPS-HDF cells. Gomisin A was also able to attenuate the activity of senescence-associated β-galactosidase and the production of pro-inflammatory molecules in the SIPS as well as aged HDF cells. The antioxidant activity of gomisin A was determined by recovering the Cu/Zn, Mn-SOD, and HO-1 expression in the SIPS-HDF cells. In mechanistic aspect, gomisin A inhibited the mitogen-activated protein kinase pathway and the translocation of nuclear factor kappa B to the nucleus. In addition, gomisin A promoted the autophagy and mitochondrial biogenesis factors through the translocation of nuclear factor erythroid 2-related factor-2, and inhibited aging progression in the SIPS-HDF cells. In summary, the enhanced properties of mitochondrial biogenesis and autophagy of gomisin A has a benefit to control age-related molecules against SIPS-induced chronic oxidative stress, and gomisin A may be a potential therapeutic compound for the enhancement of intracellular homeostasis to aging progression.
五味子果实中的五味子甲素具有多种药理特性，包括肝脏保护、抗糖尿病和抗氧化应激。然而，五味子甲素的潜在益处仍未得到充分了解，尤其是在衰老进程方面。因此，本研究的目的是阐明五味子甲素促进线粒体生物发生和自噬是否会影响抗衰老进程及其机制。使用过氧化氢使中期（PD32）人二倍体成纤维细胞（HDF）进入应激诱导的早衰（SIPS）状态。五味子甲素即使在SIPS-HDF细胞中也能抑制活性氧的产生。五味子甲素还能够减弱SIPS以及衰老HDF细胞中衰老相关β-半乳糖苷酶的活性和促炎分子的产生。通过恢复SIPS-HDF细胞中铜/锌超氧化物歧化酶、锰超氧化物歧化酶和血红素加氧酶-1的表达来确定五味子甲素的抗氧化活性。在机制方面，五味子甲素抑制丝裂原活化蛋白激酶途径以及核因子κB向细胞核的转位。此外，五味子甲素通过核因子红系2相关因子-2的转位促进自噬和线粒体生物发生因子，并抑制SIPS-HDF细胞中的衰老进程。总之，五味子甲素增强的线粒体生物发生和自噬特性有利于控制与年龄相关的分子，抵抗SIPS诱导的慢性氧化应激，并且五味子甲素可能是一种潜在的治疗化合物，可以增强细胞内稳态以延缓衰老进程。
