Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.
Alpha-lipoic acid as a dietary supplement: molecular mechanisms and therapeutic potential.
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DOI：
10.1016/j.bbagen.2009.07.026
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发表时间：
2009-10
影响因子：
3
通讯作者：
Hagen, Tory M.
中科院分区：
文献类型：
--
作者：
Shay, Kate Petersen;Moreau, Regis F.;Smith, Eric J.;Smith, Anthony R.;Hagen, Tory M.
α-硫辛酸（LA）已成为多种维生素配方，抗衰老补充剂，甚至宠物食品中的常见成分。它被明确定义为预防糖尿病性多发性神经病的疗法，并清除自由基，螯合金属，恢复细胞内谷胱甘肽水平，否则会随年龄下降。LA的生物化学特性与其生物学效应有何关系？在此，我们回顾了使用细胞和动物模型发现的LA的分子机制，以及LA对人类受试者的影响。虽然LA长期以来被吹捧为抗氧化剂，但它也显示出改善葡萄糖和抗坏血酸处理，增加eNOS活性，通过转录因子Nrf 2激活II期解毒，并通过抑制NF-κ-B降低MMP-9和VCAM-1的表达。LA及其还原形式二氢硫辛酸可以利用其化学性质作为氧化还原对，通过形成混合二硫化物来改变蛋白质构象。有益的效果是实现低微摩尔水平的LA，这表明它的一些治疗潜力超出了抗氧化剂的严格定义。目前的试验正在研究LA的这些有益特性是否使其不仅适用于糖尿病，而且适用于预防血管疾病，高血压和炎症。
Alpha-lipoic acid (LA) has become a common ingredient in multivitamin formulas, anti-aging supplements, and even pet food. It is well-defined as a therapy for preventing diabetic polyneuropathies, and scavenges free radicals, chelates metals, and restores intracellular glutathione levels which otherwise decline with age. How do the biochemical properties of LA relate to its biological effects? Herein, we review the molecular mechanisms of LA discovered using cell and animal models, and the effects of LA on human subjects. Though LA has long been touted as an antioxidant, it has also been shown to improve glucose and ascorbate handling, increase eNOS activity, activate Phase II detoxification via the transcription factor Nrf2, and lower expression of MMP-9 and VCAM-1 through repression of NF-kappa-B. LA and its reduced form, dihydrolipoic acid, may use their chemical properties as a redox couple to alter protein conformations by forming mixed disulfides. Beneficial effects are achieved with low micromolar levels of LA, suggesting that some of its therapeutic potential extends beyond the strict definition of an antioxidant. Current trials are investigating whether these beneficial properties of LA make it an appropriate treatment not just for diabetes, but also for the prevention of vascular disease, hypertension, and inflammation.
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DOI：
10.1073/pnas.0804336105
发表时间：
2008-07-22
影响因子：
11.1
作者：
Boivin, Benoit;Zhangt, Sheng;Tonks, Nicholas K.
通讯作者：
Tonks, Nicholas K.
影响因子：
2.9
作者：
Akiba, S;Matsugo, S;Konishi, T
通讯作者：
Konishi, T
影响因子：
9.3
作者：
Anuradha, B;Varalakshmi, P
通讯作者：
Varalakshmi, P
影响因子：
3.4
作者：
Bernkop-Schnürch, A;Reich-Rohrwig, E;Kratzel, M
通讯作者：
Kratzel, M
影响因子：
5.8
作者：
Biewenga, GP;Dorstijn, MA;Bast, A
通讯作者：
Bast, A