生物抗氧剂α-硫辛酸和二氢硫辛酸的药理与临床应用

α-硫辛酸(1ipoic acid)是1951年由Reed首次从猪肝中分离出来的矢然产物,它作为辅酶参与三梭酸循环中的α-酮酸的氧化脱羧反应.最初α-硫锌酸被列入维生素类,但随后的研究发现,人和动物均能合成.50多年来,对它的认识一直停留在其能量代谢方面的作用;而今,大量的研究各种转向α-硫辛酸及其还原态二氢硫锌酸的抗氧化作用以及其在多种疾病中的预防和治疗作用.     

人参皂苷用于肝脏疾病的研究进展

人参皂苷是五加科人参属人参的主要有效成分,目前发现其单体多达150余种,且不同人参皂苷单体的药理作用也各有差异。人参皂苷主要有抗肿瘤、抗老年痴呆等作用。近年来的研究表明,人参皂苷在肝脏疾病如肝癌、肝纤维化、肝损伤和肝炎等,以及肝移植与肝脏切除中已经显现出一定的治疗作用。人参皂苷在肝脏疾病中的作用机制较为复杂,主要是通过抗氧化、抗炎等作用来保护肝细胞和调节肝功能。本文在查阅国内外文献的基础上,综述了人参皂苷在肝脏疾病治疗中的研究进展,同时就其作用机制进行了阐述,以期为该成分在肝脏疾病中的进一步研究提供参考。     

天然产物通过GSH在防治肝病中的作用及机制研究

谷胱甘肽（GSH）是哺乳动物体内最丰富的非蛋白硫醇,具有强大的抗氧化、解毒、调节细胞凋亡和免疫等功能。在多种肝脏疾病中,GSH的稳态会因合成和运输受损或者过度消耗而破坏。GSH稳态受损不仅会产生可氧化蛋白质、DNA和脂质的ROS,而且会影响参与代谢、增殖等多种信号传导途径,从而导致各种肝病的发生。黄酮类等天然产物具有良好的防治肝病的作用。本综述介绍了GSH在肝脏疾病中的作用以及药物干预机制,为肝脏疾病的防治提供新的思路。     

生物抗氧剂α-硫辛酸和二氢硫辛酸的药理与临床应用

α-硫辛酸（lipoicacid）是1951年由Reed首次从猪肝中分离出来的天然产物，它作为辅酶参与三波酸循环中α-酮酸的氧化脱按反应。最初。硫辛酸被列入维生素类，但随后的研究发现，人和动物均能自行合成肝。40年来，对它的认识一直停留在其能量代谢方面的作用；而今，大量的研究工作转向a一硫辛酸及其还原态二氢硫辛酸的抗氧化作用以及其在多种疾病中的预防和治疗作用【‘一引。la．硫辛酸和H氢硫辛酸的抗氧性能众所周知，在人体代谢过程中，氧自由基（也称活性氧，ROS）占很大比重。自由基在人体内经常不断地产生和清除，这种动态平衡一旦…     

α-硫辛酸与核因子-КB信号通路

α-硫辛酸是一个在少数细胞内合成的二硫化合物,它的天然功能是作为丙酮酸脱氢酶和α-酮戊二酸脱氢酶复合体中的辅酶。药理剂量下,α-硫辛酸是一个多功能的抗氧化剂,具有一般抗氧化剂所不能及的抗氧化性．它可以对与氧化应激有关的多种疾病如心脏病、糖尿病、高血压、局部缺血一再灌注、退行性病变等具有预防和治疗作用.     

Nrf2/ARE信号通路与肝脏疾病的研究进展

对近几年关于Nrf2在各种肝脏疾病中作用的文献进行分析、归纳、总结,发现Nrf2/ARE信号通路的激活在防治病毒性肝炎、酒精性和非酒精性肝炎、胆汁淤积型肝损伤、肝纤维化、肝癌等肝脏疾病中起着重要作用。Nrf2/ARE通路在肝脏病理生理学过程中发挥重要作用,可能为防治肝脏疾病提供新的治疗靶点。     

姜黄素应用于肝脏疾病的研究进展

肝脏是机体内具有葡萄糖和脂类代谢、血浆蛋白合成、红细胞的处理、激素的产生和解毒［1］等多种功能的重要器官,在维持机体稳态的过程中起着重要作用。肝脏疾病会严重影响人体健康,甚至威胁人类生命。原发性肝癌、肝炎、肝硬化和脂肪肝是最常见的肝脏疾病类型。许多医学研究已经证明了核因子κB（ NF-κB）作用的信号通路和氧化应激在肝脏疾病发病机制中的重要性［2］,亦有研究证明了饮食中的抗氧化剂如槲皮素、原花青素、维生素 E和姜黄素等对肝脏疾病的改善作用［3］。     

脂质组学在肝脏疾病中的研究进展

肝脏疾病是一类常见病、多发病,严重威胁人类的生命健康,肝脏疾病的研究已成为当今器质性疾病领域研究的热点与难点,近年来,学者们通过研究发现肝脏疾病与机体的脂质化合物代谢密切相关。脂质组学是代谢组学的重要分支,能通过分析机体的脂质变化水平来评价肝脏疾病、寻找表征肝脏疾病的生物标志物、研究肝脏疾病发生的可能机制,在肝脏疾病的研究中发挥着巨大的作用。该文在对脂质组学研究方法进行综述的同时,还以不同类型的肝脏疾病为出发点,重点对近年来脂质组学在肝脏疾病中的应用进行了归纳与分析,以期为肝脏疾病的深入研究和肝脏疾病的临床治疗提供参考。     

α-硫辛酸的临床应用概况

α-硫辛酸是已知天然抗氧化剂中效果最强的一种,具有多种生物学活性,对糖尿病、局部缺血再灌注损伤和冠心病等疾病有预防和治疗作用。近年来国内学者进行了大量实验研究和临床观察,表明其在防治糖尿病、保护缺血再灌注损伤以及其他疾病方面均有一定的疗效。本文综合近几年国内学者对硫辛酸临床用途的临床研究和动物实验进展,为临床应用提供参考。     

人体内的强效抗氧化剂硫辛酸

硫辛酸是一种超强的抗氧化剂.因同时具有脂溶性和水溶性,极易进入到人体细胞内.对保护肝脏、预防老年痴呆、提高血液中胰岛素的作用、预防糖尿病性白内障都有着不可替代的作用.同时并能够大大提高其它抗氧化剂的抗氧化功能.     

Preparations of alpha-lipoic acid: the dynamics of their content in the blood and their effect on hemostasis in lesions of the human liver

The changes in blood coagulating activity before and after treatment with alpha-lipoic acid drugs as compared with blood lipoic acid content were studied in 130 patients with chronic diffuse diseases of the liver of the virus and alcohol etiology. A moderate correlation between the increase in blood alpha-lipoic acid concentration in patients with the liver diseases during the replacement therapy with alpha-lipoic acid drugs and a number of parameters of thrombelastogram was established. It was shown that relief of coenzyme deficit against the background of treatment with lipoic acid is associated with relief of hypocoagulative syndrome and an elevation of the blood ATP level. It is suggested that the ability of the coenzyme to stimulate the bioenergetic protection of hemostasis processes plays the important role in the mechanism of action of alpha-lipoic acid drugs.     

Pharmacokinetics of preparations of lipoic acid and their effect on ATP synthesis, processes of microsomal and cytosol oxidation in hepatocytes in liver damage in man

The features of the pharmacokinetics of preparations of alpha-lipoic acid (lipoic acid, thioctacide) as compared with their pharmacodynamic effects were studied in 125 patients with chronic diffuse diseases of the liver of viral and alcohol etiology. After a single administration of the preparations, the authors found an elevation of the maximal blood concentrations and an increase of alpha-lipoic acid elimination half-life in patients with liver cirrhosis as compared with chronic hepatitis patients. During the replacement therapy and elimination of alpha-lipoic acid deficiency by using the preparations containing lipoic acid, there is commonly an increase ATP content, an elevation of functioning mass of hepatocytes and activation of liver detoxifying function according to the data of the tests of galactose cytosol oxidation, microsomal oxidation of antipyrine and conjugation of bilirubin.     

Protective effect of lipoic acid against methotrexate-induced oxidative stress in liver mitochondria

Methotrexate (MTX) is a folic acid antagonist widely used as a cytotoxic chemotherapeutic agent for leukemia and other malignancies. The purpose of this study was to investigate the damage caused by MTX on liver mitochondria and its protection by using antioxidant properties of lipoic acid. MTX substantially affects mitochondrial function by reducing glutathione levels leading to disturbances in antioxidant enzyme defense system. Lipoic acid occurs naturally in mitochondria as a coenzyme. In various studies lipoic acid has been convincingly shown to exhibit an antioxidant role when supplemented exogenously. We studied the effect of lipoic acid pre-treatment on the toxicity of MTX in mouse liver mitochondria focusing specifically on the oxidative stress. MTX caused a significant rise in the mitochondrial lipid peroxidation (LPO), protein carbonyl (PC) content and superoxide radical generation. It also affected the mitochondrial thiol profile. Pre-treatment of mice with lipoic acid (35 mg/kg) markedly lowered mitochondrial LPO, PC content and superoxide radical generation. It also restored decreased enzymatic and non-enzymatic antioxidants of mitochondria. It is suggested that lipoic acid has a potential role in suppressing MTX-induced mitochondrial toxicity, and it affords protection either by reversing the decline of antioxidants or by the directly scavenging the free radicals.     

Lipoic acid supplementation and endothelial function

Endothelial dysfunction is caused by all the recognized cardiovascular risk factors and has been implicated in the complex processes leading to the initiation and progression of atherosclerosis. Short-term treatment with lipoic acid is shown in the current issue of the British Journal of Pharmacology to improve endothelial function of aortic rings of old rats. The age-related decrease in phosphorylation of nitric oxide synthase and Akt was improved by lipoic acid supplementation. The improved phosphorylation status may have been due to reduced activity of the phosphatase PPA2, associated with decreased levels of endothelial ceramide induced by lipoic acid. Neutral sphingomyelinase activity was also reduced by lipoic acid, which was due, at least in part, to increased glutathione levels in endothelial cells. The favourable antioxidant, anti-inflammatory, metabolic and endothelial effects of lipoic acid shown in rodents, in this and other recently published studies, warrant further assessment of its potential role for prevention and treatment of cardiovascular diseases.     

Alpha-lipoic acid protects against hepatic ischemia-reperfusion injury in rats

BACKGROUND AND AIM: To evaluate the protective effect of alpha-lipoic acid in reducing oxidative damage after severe hepatic ischemia/reperfusion (IR) injury. METHODS: Wistar albino rats were subjected to 45 min of hepatic ischemia, followed by 60 min reperfusion period. Lipoic acid (100 mg/kg i.p.) was administered 15 min prior to ischemia and immediately before reperfusion period. At the end of the reperfusion period aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity, and cytokine, TNF-alpha and IL-1beta levels were determined in serum samples. Malondialdehyde (MDA), and glutathione (GSH) levels and myeloperoxidase (MPO) activity were determined in the liver tissue samples while formation of reactive oxygen species was monitored by using chemiluminescence (CL) technique with luminol and lucigenin probes. Tissues were also analyzed histologically. Results: Serum ALT, AST, and LDH activities and TNF-alpha and IL-1beta levels were elevated in the I/R group, while this increase was significantly lower in the group of animals treated concomitantly with lipoic acid. Hepatic GSH levels, significantly depressed by I/R, were elevated back to control levels in lipoic acid-treated I/R group. Furthermore, increases in tissue luminol and lucigenin CL, MDA levels and MPO activity due to I/R injury were reduced back to control levels with lipoic acid treatment. CONCLUSION: Since lipoic acid administration alleviated the I/R-induced liver injury and improved the hepatic structure and function, it seems likely that lipoic acid with its antioxidant and oxidant-scavenging properties may be of potential therapeutic value in protecting the liver against oxidative injury due to ischemia-reperfusion.     

Effects of lipoic acid and dihydrolipoic acid on total erythrocytic thiols under conditions of restricted glucose in vitro

The effects of lipoic acid and dihydrolipoic acid were explored on total thiol maintenance in diabetic and non-diabetic human erythrocytes in vitro over 22 hr in a 37 degrees C incubation system with no added glucose. Over 18-22.5 hr after treatment in both non-diabetic and diabetic cells, lipoic acid (1 mM) was associated with greater loss of cellular thiols than dihydrolipoic acid (1 mM), compared to respective control values. At 0.1 mM, in non-diabetic cells, although lipoic acid-treated cells' thiol levels were significantly lower than control, there was no significant difference between dihydrolipoic acid-treated cells and control cells regarding thiol levels. In addition, at 0.1 mM, dihydrolipoic acid-treated diabetic cells showed a reduction in thiol levels compared to control. At 0.01 mM, lipoic acid-treated cells had significantly lower measured thiol levels compared with diabetic cells exposed to dihydrolipoic acid, whereas in non-diabetic cells, dihydrolipoic acid-treated erythrocytic thiol levels were significantly greater than those treated with lipoic acid, although there were no other significant differences between the groups. At 22.5 hr, control values of methaemoglobin rose to 6.4 +/- 1.1% in diabetic cells and 3.6 +/- 2.1% in non-diabetic cells. Lipoic acid (1 mM) showed greater methaemoglobin formation in diabetic rather than non-diabetic cells (13.6 +/- 1.5% versus 11.6 +/- 1.5%), whereas dihydrolipoic acid-treated diabetic and non-diabetic cells were less potent in methaemoglobin generation (8.5 +/- 2.4% and 8.4 +/- 1.4%, respectively). These studies suggest that in certain circumstances such as hypoglycaemia, lipoic acid administration may actually be detrimental to cellular oxidant protection status.     

Curcumin,Silybin Phytosome® and α‐R‐Lipoic Acid Mitigate Chronic Hepatitis in Rat by Inhibiting Oxidative Stress and Inflammatory Cytokines Production

Chronic hepatitis is recognized as a worldwide health problem that gradually progresses towards cirrhosis and hepatocellular carcinoma. Despite the large number of experiments using animal models for allergic hepatitis, it is still difficult to produce a picture of chronic hepatitis. Therefore, this study was conducted to introduce an animal model approximating to the mechanism of chronicity in human hepatitis. The study also aimed to examine the hepatoprotective effects of curcumin, silybin phytosome^® and α‐R‐lipoic acid against thioacetamide (TAA)‐induced chronic hepatitis in rat model. TAA was administered intraperitoneally at a dose of 200 mg/kg three times weekly for 4 weeks. At the end of this period, a group of rats was killed to assess the development of chronic hepatitis in comparison with their respective control group. TAA administration was then discontinued, and the remaining animals were subsequently allocated into four groups. Group 1 was left untreated, whereas groups 2–4 were allowed to receive daily oral doses of curcumin, silybin phytosome^® or α‐R‐lipoic acid, respectively, for 7 weeks. Increases in hepatic levels of malondialdehyde associated with TAA administration were inhibited in groups receiving supplements. Furthermore, glutathione depletion, collagen deposition, macrophage activation and nuclear factor κappa‐B expression as well as tumour necrosis factor‐α and interleukin‐6 levels were significantly decreased in response to supplements administration. Serological analysis of liver function and liver histopathological examination reinforced the results. The above evidence collectively indicates that the antioxidant and anti‐inflammatory activities of curcumin, silybin phytosome^® and α‐R‐lipoic acid may confer therapeutic efficacy against chronic hepatitis.     

Protective role of DL-alpha-lipoic acid against mercury-induced neural lipid peroxidation.

Experimental neurotoxicity in rat models was induced by an intramuscular injection of mercuric chloride. dl-alpha-lipoic acid was administered as an antidote in three protocols of experimental design. Two protocols of short-term exposure of mercury was designed, one with prophylactic therapy and the other with curative therapy of lipoic acid. The third protocol was with prophylactic therapy of lipoic acid on long-term exposure of mercury. Enhanced lipid peroxidation, depleted non-enzymic and perturbed enzymic antioxidant status were observed in cerebral cortex, cerebellum and sciatic nerves of the toxic groups. The ameliorating effect of lipoic acid and its therapeutic efficacy during various modes of therapy, on the antioxidant status was established in the nervous tissues.     

18α-和18β-甘草酸治疗肝病的疗效比较

18α-甘草酸是18β-甘草酸的差向异构体,二者对急、慢性免疫性肝损伤和多种化学性急、慢性肝损伤动物模型均有显著的肝脏保肝作用,临床上治疗各种类型的肝病(包括重症、急、慢性病毒性肝炎和化学性肝病以及肝纤维化)均有效。综述了18α-甘草酸与18β-甘草酸在治疗病毒性肝炎、肝纤维化以及其他肝病的作用,并作了临床疗效比较,发现18α-甘草酸(甘草酸二铵)优于国产的18β-甘草酸(甘草酸单铵),但弱于日本产的18β-甘草酸(甘草酸苷)。     

Lipoic acid attenuates Aroclor 1260‐induced hepatotoxicity in adult rats

The present study was aimed to investigate the mechanistic aspect of Aroclor 1260‐induced hepatotoxicity and its protection by lipoic acid. The adult male Albino rats were divided into six groups. Group I served as control. Group II received lipoic acid (35 mg/kg/day). Aroclor 1260 was given to rats by oral gavage at doses 20, 40, or 60 mg/kg/day (Groups III, IV, and V, respectively). Group VI was pretreated with lipoic acid (35 mg/kg/day) 24 h before Aroclor 1260 (40 mg/kg/day). Treatment in all groups was continued for further 15 consecutive days. Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities and total bilirubin, total cholesterol, and triglycerides were significantly increased while total protein, total albumin, and high‐density lipoprotein were significantly decreased. Hydrogen peroxide production and lipid peroxidation were significantly increased while superoxide dismutase and catalase activities and reduced glutathione (GSH) content was significantly decreased in liver. Caspase‐3 & ‐9 activities were significantly increased in liver. Lipoic acid pretreatment significantly reverted all these abnormalities toward their normal levels. In conclusion, Aroclor 1260 induced liver dysfunction, at least in part, by induction of oxidative stress. Apoptotic effect of hepatic cells is involved in Aroclor 1260‐induced liver injury. Lipoic acid could protect rats against Aroclor 1260‐induced hepatotoxicity. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 913–922, 2016.