Department of Health and Exercise Science, Colorado State University, Fort Collins, CO 80523, USA.
Free Radic Biol Med. 2013 Mar;56:102-11. doi: 10.1016/j.freeradbiomed.2012.11.016. Epub 2012 Nov 30.
Increased production of reactive oxygen species has been implicated in the pathogenesis of cardiovascular disease (CVD), and enhanced endogenous antioxidants have been proposed as a mechanism for regulating redox balance. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcriptional regulator of phase II antioxidant enzymes, and activation of Nrf2 has been suggested to be an important step in attenuating oxidative stress associated with CVD. A well-defined combination of five widely studied medicinal plants derived from botanical sources (Bacopa monniera, Silybum marianum (milk thistle), Withania somnifera (Ashwagandha), Camellia sinensis (green tea), and Curcuma longa (turmeric)) has been shown to activate Nrf2 and induce phase II enzymes through the antioxidant response element. The purpose of these experiments was to determine if treatment of cardiomyocytes with this phytochemical composition, marketed as Protandim, activates Nrf2, induces phase II detoxification enzymes, and protects cardiomyocytes from oxidant-induced apoptosis in a Nrf2-dependent manner. In cultured HL-1 cardiomyocytes, phytochemical treatment was associated with nuclear accumulation of Nrf2, significant induction of phase II enzymes, and concomitant protection against hydrogen peroxide-induced apoptosis. The protection against oxidant stress was abolished when Nrf2 was silenced by shRNA, suggesting that our phytochemical treatment worked through the Nrf2 pathway. Interestingly, phytochemical treatment was found to be a more robust activator of Nrf2 than oxidant treatment, supporting the use of the phytochemicals as a potential treatment to increase antioxidant defenses and protect heart cells against an oxidative challenge.
活性氧的产生增加与心血管疾病（CVD）的发病机制有关，增强内源性抗氧化剂已被提出作为调节氧化还原平衡的机制。核因子（红细胞衍生 2）样 2（Nrf2）是 II 期抗氧化酶的转录调节剂，Nrf2 的激活被认为是减轻与 CVD 相关的氧化应激的重要步骤。从植物来源（Bacopa monniera、Silybum marianum（乳蓟）、Withania somnifera（Ashwagandha）、Camellia sinensis（绿茶）和 Curcuma longa（姜黄））中广泛研究的五种药用植物的明确组合已被证明可通过抗氧化反应元件激活 Nrf2 并诱导 II 期酶。这些实验的目的是确定用这种植物化学组合物（称为 Protandim）治疗心肌细胞是否可以激活 Nrf2、诱导 II 期解毒酶，并以 Nrf2 依赖的方式保护心肌细胞免受氧化剂诱导的细胞凋亡。在培养的 HL-1 心肌细胞中，植物化学处理与 Nrf2 的核积累、II 期酶的显著诱导以及与过氧化氢诱导的细胞凋亡的伴随保护有关。当 Nrf2 被 shRNA 沉默时，对氧化剂应激的保护作用被消除，这表明我们的植物化学处理是通过 Nrf2 途径起作用的。有趣的是，与氧化剂处理相比，植物化学处理被发现是更有效的 Nrf2 激活剂，支持使用植物化学物质作为增加抗氧化防御并保护心脏细胞免受氧化应激挑战的潜在治疗方法。
