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Overview of the chemical, natural occurrence and antioxidant activity of terpenes

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Abstract

Terpenes are one of the most abundant groups of natural products that occur mostly in plants, being identified more than 30,000 different compounds. Chemically, terpene group is one of the most diverse in structure, sharing isoprene units as a common structural motif. The number of isoprene units that defined each terpene compound classifies them into several groups including hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterpenes, triterpenes, tetraterpenes and politerpenes. Terpenes, as a natural product group, have sparked a great interest in research because of their relevant and broad spectrum of health-promoting effects such as anti-inflammatory, antimicrobial, antitumor and antioxidant, among others. Nowadays, new findings in pharmacological area are in constant growing. Since oxidative stress has been involved in the pathophysiological development of approximately one hundred of different diseases including cancer, autoimmune diseases, heart attack and neurodegenerative diseases, there have been numerous attempts to cope with this redox imbalance. Exogenous compounds with antioxidant capacity provide a protective effect against free radical overproduction and its consequence cellular damage, being this one the most promising therapeutic strategy. Over the last recent years, there is an increasing interest in the search of antioxidant compounds among terpenes, existing emerging number of reports focused on this issue. This chapter will cover the chemistry, the natural occurrence and the most recent findings in antioxidant activity of terpenes.

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The antioxidant effects of alpha-terpinene (alpha-TH) and gamma-terpinene (gamma-TH) on the oxidation of methyl linoleate (LH), DNA, and erythrocytes induced by 2,2'-azobis(2-amidinopropane hydrochloride) (AAPH) were investigated. The results from erythrocytes and DNA were treated by means of chemical kinetic equations. It was found that either alpha- or gamma-TH was able to scavenge approximately 0.4 radicals when they protected DNA. alpha-TH can trap approximately 0.7 radicals when protecting erythrocytes and can trap approximately 0.5 radicals when protecting LH. gamma-TH can trap approximately 1.2 radicals when protecting erythrocytes and LH. Therefore, the antioxidant effectiveness of gamma-TH was higher than alpha-TH. gamma-TH contained a nonconjugated diene, and the diene in alpha-TH was conjugated. The obtained results implied that the nonconjugated diene benefited for antioxidant capacity more than a conjugated diene. Moreover, the reactions of alpha- and gamma-TH with 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) cation radical (ABTS(+) (*)) and 2,2'-diphenyl-1-picrylhydrazyl (DPPH) implicated that alpha- and gamma-TH were able to scavenge radicals directly. However, alpha- and gamma-TH promoted AAPH-induced hemolysis with a high concentration employed.
Article
The present study evaluated the antidiabetic and antioxidant effects of oleanolic acid (OA) from Ligustrum lucidum Ait (LLA) in alloxan-induced diabetic rats. OA in the alloxan-induced diabetic rats showed significant hypoglycemic activity by lowering blood glucose (at doses of 60 and 100 mg/kg for 40 days). The levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-c) in the OA-treated diabetic rats were lower, and the high-density lipoprotein cholesterol (HDL-c) level was higher than in the control diabetic rats. A significant reduction in the serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels of diabetic rats following OA treatment was also observed. Furthermore, OA treatment decreased the malondialdehyde (MDA) level, but increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activities of the liver and kidney in diabetic rats. These results indicate that OA could protect the liver function avoiding alloxan-induced damage; OA had hypoglycemic, hypolipidemic and antioxidant efficacy in the diabetic rats. The antioxidant ability of OA might be one of the mechanisms of its hypoglycemic and hypolipidemic effects.
Article
Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycemia. It is often associated with complications, such as cataracts. Cataract, characterized by cloudiness or opacity of the eye lens, is the leading cause of blindness worldwide. The present study investigated the effect of lutein, alone or combined with insulin on the progression of eye lens opacities in streptozotocin-diabetic rats for a period of 12 weeks. Tissue markers of oxidative stress were also determined at the end of the experiment. Herein we demonstrate that lutein treatment prevents the development and progression of cataracts (0 eyes with mature cataract, and ten out of 16 eyes with clear lenses in the lutein-treated diabetic animals group, vs. seven and three eyes in the non-treated diabetic group, respectively). Lipid peroxidation is significantly increased in diabetic lens (up to three-fold); lutein and insulin, alone or in combination, are able to prevent this alteration. Only insulin and lutein together could prevent the diabetes-induced decrease of glutathione content. The combined treatment with lutein and insulin is useful in preventing the development of cataracts in streptozotocin-induced diabetic rats, supporting its utility in diabetes management, especially when a tight metabolic control is difficult to achieve.
Article
Incorporation of 13C-labelled acetate into the hopanoids of the purple non-sulfur bacteria Rhodopseudomonas palustris and Rhodopseudomonas acidophila and the facultative methylotroph Methylobacterium organophilum showed that the bacteriohopane skeleton is built from an unique carbon/carbon linkage between the triterpenic hopane moiety and the C-5 carbon of a d-ribose derivative arising from the non-oxidative pentose phosphate pathway. Furthermore a probable compartmentation of the acetate metabolism could be observed in these bacteria. Whereas exogenous acetate was directly incorporated into the glucose derivatives and poly-(3-hydroxybutyrate), the isoprenic units were apparently solely synthesized from two acetate units arising from the glyoxylate cycle and a third one issued either from the glyoxylate cycle or from the Entner-Doudoroff pathway of glucose catabolism. Although an unknown biosynthetic pathway different from that usually proposed for isoprenoid biosynthesis can not be excluded, the former hypothesis explained all labelling patterns observed on the triterpenic skeleton.
Article
A diterpenoid, totarol (1), from Podocarpus nagi was evaluated as an antioxidant. This diterpenoid inhibited autoxidation of linoleic acid. Mitochondrial and microsomal lipid peroxidation induced by Fe(III)-ADP/NADH or Fe(III)-ADP/NADPH were also inhibited. Nagilactone E (2), a norditerpene lactone isolated from the same source, had no antioxidative activity. Furthermore, totarol protected red cells against oxidative hemolysis. This diterpene was shown to be effective in protecting biological systems against oxidative stresses.
Article
beta-Carotene and other carotenoids are thought to exert disease preventive actions by scavenging reactive free radicals, but the mechanisms of these reactions are poorly understood. We detected products formed by reaction of beta-carotene with alkoxyl, and alkylperoxyl free radicals generated by thermolysis of azobis(2,4-dimethylvaleronitrile) (AMVN) in benzene. Analyses by atmospheric pressure chemical ionization mass spectrometry identified two previously unknown classes of beta-carotene oxidation products. Substitution products contain one AMVN-derived radical adduct group and result from hydrogen transfer from the carotenoid polyene followed by radical recombination. Addition products contain two AMVN-derived adduct groups and result instead from sequential radical additions to the polyene. These product structures provide the first mechanistic explanation for the radical scavenging reactions of carotenoids.
Article
Diterpenoids, totarol (1), totaradiol (2), 19-hydroxytotarol (3), totaral (4), 4 beta-carboxy-19-nortotarol (5), sugiol (6), isolated from Podocarpus nagi, were evaluated as antioxidants. Microsomal lipid peroxidation induced by Fe(III)-ADP/NADPH and mitochondrial lipid peroxidation induced by Fe(III)-ADP/ NADH were inhibited by these terpenoids. They inhibited linoleic acid autoxidation but not generation of superoxide anion. Totarol (1) protected mitochondrial respiratory enzyme activities against NADPH induced oxidative injury. Totarane diterpenes from P. nagi were shown to be effective to protect biological systems and function against various oxidative stresses.
Article
Real time detection following laser flash photolysis of transient carotenoid radical cations and tocopheroxyl radicals formed in chloroform and bleaching of the carotenoids has allowed interaction between carotenoids and tocopherols to be studied. It is found that alpha-, beta-, and gamma-tocopherol reduce all the carotenoid radical cations investigated whereas the delta-tocopheroxyl radical can be reduced by lycopene and beta-carotene. Astaxanthin, canthaxanthin, and beta-apo-8'-carotenal radical cations are scavenged rapidly by all four tocopherol homologues whereas the other carotenoid radical cations react much more slowly with the tocopherols. The results allow the antioxidant hierarchy to be established: alpha-tocopherol > lycopene approximately beta-tocopherol approximately gamma-tocopherol > beta-carotene > zeaxanthin approximately delta-tocopherol > lutein > echinenone > canthaxanthin approximately beta-apo-8'-carotenal > astaxanthin.
Article
The antioxidant efficacy of alpha-carotene and comparison with beta-carotene in multilamellar liposomes prepared from egg yolk phosphatidyl choline (EYPC) exposed to the lipid soluble 2,2'-azobis (2,4-dimethyl valeronitrile) (AMVN) was investigated. Lipid peroxidation was measured as thiobarbituric acid reacting substances (TBARS) at 532 nm or as hydroperoxide formation at 234 nm after separation of phosphatidyl choline hydroperoxide (PCOOH) by high-pressure liquid chromatography (HPLC). Lutein and zeaxanthin, the hydroxyl derivatives of alpha- and beta-carotenes, and the chain breaking antioxidant alpha-tocopherol were also included in the study. AMVN being a lipid soluble, non polar azo initiator penetrates into the hydrophobic interior of the phospholipid bilayer, forming peroxyl radicals which peroxidate the phospholipid leading to PCOOH accumulation. All the carotenoids tested at 1 mol% relative to EYPC significantly suppressed the formation of PCOOH compared to control samples. In this system, alpha-carotene retarded PCOOH formation better than beta-carotene. Similarly, lutein was a better antioxidant than is zeaxanthin. But lutein and zeaxanthin were more effective antioxidants than alpha- and beta-carotenes, respectively. After 1 h of incubation of the carotenoid with AMVN, alpha-, beta-carotene, lutein and zeaxanthin limited PCOOH formation by 77%, 68%, 85% and 82%, respectively, while alpha-tocopherol elicited 90% reduction. AMVN incubated with EYPC for 2 h induced the formation of TBARS compared to control (P < 0.001). alpha-Carotene significantly suppressed the TBARS formation by 78% whilst beta-carotene, lutein, zeaxanthin and alpha-tocopherol elicited 60%, 91% and 80% reductions, respectively. Increasing the concentration of the carotenoid > 1 mol% to EYPC did not significantly increase protection of the membrane against free radical attack. Our findings suggest that alpha-carotene is a better antioxidant than is beta-carotene in phosphatidyl choline vesicles. It may, therefore, be useful in limiting free radical mediated peroxidative damage against membrane phospholipids in vivo.
Article
The effect of eugenol on the antioxidant status of the rat intestine after short and long term (15 days and 90 days respectively) oral administration of 1000 mg/kg.b.wt (a dosage which has been reported to be highly hepatoprotective) was studied. The level of lipid peroxidation products (TBARS) and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), superoxide dismutase (SOD) and catalase (CAT) were found to be near normal on eugenol treatment. The level of glutathione (GSH) did not show any change on 15 days of eugenol treatment, but it was increased significantly on 90 day eugenol treatment. The activity of glutathione-S-transferases (GSTs) was increased significantly in both 15 day eugenol treated and 90-day eugenol treated groups. The results suggest that eugenol is nontoxic, protective and induces glutathione-S-transferases (GSTs) and thereby it may facilitate the removal of toxic substances from the intestine.
Article
Andrographis paniculata (AP) treatment prevents BHC induced increase in the activities of enzymes y-Glutamyl transpeptidase, glutathione-S-transferase and lipid peroxidation. The activities of antioxidant enzymes like superoxide dismutase, catalase, glutathione peroxidase and the levels of glutathione were decreased following BHC effect. Administration of AP showed protective effects in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase as well the level of glutathione. The activity of lipid peroxidase was also decreased. The result indicate antioxidant and hepatoprotective action of A. paniculata.
Article
Emission rates of monoterpenes released by apple (Malus domestica Borkh) and cherry (Prunus avium L.) were estimated at different phenological stages. These measurements employed a dynamic flow-through Teflon chamber, sample collection onto cartridges filled with graphitized carbon and thermal desorption gas chromatography-mass spectrometry (GC-MS) for identification and quantification of the emitted volatiles. At full bloom the release of monoterpene hydrocarbons from cherry flowers was 1213 ng g(-1) dry weight (DW) h(-1), exceeding by approximately three-fold the emission rate of apple flowers (366 ng g(-1) DW h(-1)). Observed seasonal variations in biogenic volatile organic compound (VOC) emissions ranged over several order of magnitudes. At fruit-set and ripening stages, in fact, the hydrocarbon emission dramatically decreased reaching the lowest values at harvest time when leaves were fully mature (3-9 ng g(-1) DW h(-1)). Wide diversity in the composition of compounds from the species studied was also recorded. At blooming, linalool contributed significantly to the monoterpene emission from apple (94% of the emitted carbon) while alpha-pinene and camphene represented on average more than 60% of the total emitted volatiles from cherry flowers. Among the monoterpenes identified in flowers, alpha-pinene, camphene and limonene were also found in the foliage emission of both species. Fruit trees are relevant monoterpene emitters only at blooming and thus for a short period of the vegetative cycle. When leaves are fully developed, the carbon loss due to monoterpene emissions related to the photosynthetically carbon gain is negligible.
Article
Two new antioxidative diterpenoids, plectranthol A (3)[19-O-(3,4-dihydroxybenzoyl)-11,12-dihydroxy-20(10-->5)-abeo-abieta-1(10),6,8,11,13-tetraene] and plectranthol B (4)[12-O-(3-methyl-2-butenoyl)-19-O-(3,4-dihydroxybenzoyl)-11-hydroxyabieta-8,11,13-trienel along with two known diterpenoids, parvifloron E (1) and F (2) were isolated from the leaves of Plectranthus nummularius Briq. Antioxidative activities of the compounds were measured by the alpha,alpha-diphenyl-beta-picrylhydrazyl (DPPH) method.
Article
To investigate the inhibition capacities of carnosol, rosmanol, and epirosmanol, which are phenolic diterpenes from Rosmarinus officinalis, to oxidized low-density lipoprotein (LDL) formation in human blood and detect their scavenging activities to lipid free radical and superoxide anion in vitro. The antioxidant activities which were expressed with the inhibilities to lipid free radicals in the membrane lipid of cell and oxidized LDL formation were evaluated by TBARS assay and ESR method. The inhibition on the Cu2+-mediated oxidization of apo B formation in LDL was investigated by fluorescence spectroscopy. Carnosol, rosmanol, and epirosmanol had an inhibitory activity to lipid peroxidation and oxidized apo B formation in human bloods LDL. The IC50 were 7-10 micromol/L. The antioxidant mechanism was related to the scavenging activities to lipid free radical. carnosol, rosmanol, and epirosmanol showed the activity in inhibiting LDL oxidation.
Article
Lycopene, a nutritional antioxidant, was evaluated for its anticataract potential to further establish its role in cataract prevention. The ability of lycopene to modulate the biochemical parameters was investigated by in vitro studies. Enucleated rat lenses were maintained in organ culture containing Dulbecco's Modified Eagles Medium alone or in addition with 100 microM selenite and served as the normal and control groups, respectively. For the test group, the control medium was supplemented with 10 microM lycopene. The lenses were incubated for 24 h at 37 degrees C. At the end of the incubation period, the lenses were examined for morphologic variation, and biochemical parameters such as reduced glutathione, the lipid peroxidation product malondialdehyde, and the antioxidant enzymes glutathione peroxidase, glutathione S-transferase, superoxide dismutase, and catalase were estimated. In vivo selenite cataract was induced in 9-d-old rats by subcutaneous injection of sodium selenite (25 micromoles/kg of body weight). The rats in the test group were injected with lycopene (200 microg/kg body weight, intraperitoneally) 4 h before the selenite challenge. The incidence of cataract was observed when the rats first opened their eyes. Galactose cataract was induced in rats by feeding 30% galactose in the diet. Rats in the test group were fed orally with 200 microg/kg of lycopene daily, and rats in the control group received only vehicle. Cataract stages were graded at regular intervals. A fall (25%) in the glutathione level and a rise (32%) in the malondialdehyde content were observed in control as opposed to normal lenses. Lycopene supplementation in the medium significantly (P < 0.001) restored glutathione and malondialdehyde levels. A significant decrease in the activity of antioxidant enzymes also was observed in the control lenses. A significant restoration in the activities of superoxide dismutase (P < 0.05) and catalase and glutathione S-transferase (P < 0.01), with no effect on glutathione peroxidase, was observed in the lycopene-supplemented group. Lycopene also reduced the incidence of selenite cataract. Only 9% of the eyes in the test group developed dense nuclear opacity as opposed to 83% in the control group. A significant delay in the onset and progression of galactose cataract was observed with oral feeding of lycopene. Only 35% of the eyes developed mature cataract as opposed to 100% in the control group. Lycopene protects against experimental cataract development by virtue of its antioxidant properties, and it may be useful for prophylaxis or therapy against cataracts.
Article
As an attempt to search for bioactive natural constituents exerting antinociceptive and antiinflammatory activities, we examined the potency of the extract of Rubus coreanus fruits by the activity-guided fractionation. The EtOAc- and BuOH fraction and those alkaline hydrolysates showed significant antinociceptive effects as assessed by writhing-, hot plate- and tail flicks tests in mice and rats as well as antiinflammatory effect in rats with carrageenan-induced edema. BuOH extract was subjected to column chromatography to obtain a large amount of niga-ichigoside F(1) (1,23-hydroxytormentic acid 28-O-glc), which was again hydrolyzed in NaOH solution to yield an aglycone 23-hydroxytormentic acid (1a). The aglycone, 23-hydroxytormentic acid, was much more potent in both antinociceptive and antiinflammatory tests than the glycoside, niga-ichigoside F(1). The antiinflammatory effects of these compounds were further supported by the reduction of carrageenan-induced lipid peroxidation and hydroxyl radical in serum. These results suggested that 23-hydroxytormentic acid might be an active moiety of niga-ichigoside F(1) present in R. coreanus.
Article
We previously identified a novel endogenous substance, serofendic acid, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured cortical neurons against the cytotoxicity of glutamate and nitric oxide. Here, we reported the protective effect of serofendic acid on reactive oxygen species-induced oxidative stress using primary rat striatal cultures. In addition, we compared the neuroprotective effect and the radical-scavenging activity of serofendic acid with those of dimethyl sulfoxide (DMSO), because serofendic acid possesses a DMSO structure. Paraquat caused neuronal death, which was inhibited by a cell-permeable superoxide dismutase (SOD) mimetic, Mn(III)tetrakis(4-benzoic acid)porphyrin chloride (Mn-TBAP); a cell-permeable SOD/catalase mimetic, EUK-134 [manganese 3-methoxy N,N'-bis(salicylidene)ethylenediamine chloride]; and a ferrous ion chelator, 2,2'-dipyridyl, in rat striatal cultures. Serofendic acid (10-100 microM) suppressed the neurotoxicity of paraquat, whereas DMSO (10-100 microM) did not. By contrast, higher concentrations (30-300 mM) of DMSO ameliorated the paraquat-induced cell death. Furthermore, H(2)O(2) induced neurotoxicity, which was prevented by EUK-134 and 2,2'-dipyridyl. Serofendic acid (10-100 microM) also protected striatal neurons against the H(2)O(2)-induced toxicity. Higher concentrations (30-300 mM) of DMSO ameliorated H(2)O(2)-induced neuronal death, whereas lower concentrations (10-100 microM) did not. Electron spin resonance spectrometry with a spin-trapping technique revealed that serofendic acid and DMSO had approximately the same ability to inhibit the formation of the hydroxyl radical (.OH). These results suggest that the.OH-scavenging activity of serofendic acid is attributable to its DMSO structure and that the remaining components such as the atisane structure play an important role in eliciting neuroprotection at a concentration range of 10 to 100 microM.
Article
Antioxidants from several nutrients, e.g. vitamin E, beta-carotene, or flavonoids, inhibit the oxidative modification of low-density lipoproteins. This protective effect could possibly retard atherogenesis and in consequence avoid coronary heart diseases. Some studies have shown a positive effect of those antioxidants on cardiovascular disease. Another class of naturally occurring antioxidants are terpenoids, which are found in essential oils. The essential oil of Pinus mugo and the contained monoterpene terpinolene effectively prevent low-density lipoprotein (LDL)-oxidation. In order to test the mechanism by which terpinolene protects LDL from oxidation, LDL from human blood plasma enriched in terpinolene was isolated. In this preparation not only the lipid part of LDL is protected against copper-induced oxidation--as proven by following the formation of conjugated dienes, but also the oxidation of the protein part is inhibited, since loss of tryptophan fluorescence is strongly delayed. This inhibition is due to a retarded oxidation of intrinsic carotenoids of LDL, and not, as in the case of some flavonoids, attributable to a protection of intrinsic alpha-tocopherol. These results are in agreement with our previous results, which showed the same effects for a monoterpene from lemon oil, i.e. gamma-terpinene.
Article
Epidemiological studies have shown that there is a positive correlation between the incidence of coronary heart disease (CHD) and the blood cholesterol level. To study the effect of plant derived triterpene, lupeol and its ester lupeol linoleate, on blood lipid status and oxidant stress in heart and hemolysate, male albino Wistar rats were fed high cholesterol diet (normal rat chow supplemented with 4% cholesterol and 1% cholic acid; HCD) for 30 days. A significant increase (p<0.05) in plasma total cholesterol (4.22 fold) and triglycerides (1.7 fold) was observed in HCD fed rats, along with elevated LDL (3.56 fold) and VLDL (1.99 fold) cholesterol and decreased HDL cholesterol (34.14%). Treatment with lupeol and its derivative normalized the lipid profile. The significant increase (p<0.05) in lipid peroxidation (LPO) was paralleled by significantly diminished (p<0.05) activities of antioxidant enzymes (SOD, CAT and GPx) and decreased (p<0.05) concentration of antioxidant molecules (GSH, Vit C and Vit E) in cardiac tissue and hemolysate of HCD fed rats. The oxidative tissue injury in hypercholesterolemic rats was substantiated by the increase in cardiac marker, serum CPK and the drop in its activity in the heart tissue. Lupeol and lupeol linoleate treatment decreased the LPO levels and increased enzymatic and nonenzymatic antioxidants. CPK activity in the treated group was comparable with that of the control. These observations highlight the beneficial effects of the triterpene, lupeol and its linoleate ester derivative, in ameliorating the lipidemic-oxidative abnormalities in the early stage of hypercholesterolemic atherosclerosis.
Article
The effect of oleanolic acid (OA) pretreatment on myocardial ischemia-reperfusion (I-R) injury was investigated using an ex vivo rat heart model. Pretreatment with OA at daily doses (0.6 and 1.2 mmol/kg) for 3 days significantly protected against I-R injury in isolated rat hearts, as evidenced by the decrease in the extent of lactate dehydrogenase (LDH) leakage and improvement in contractile force recovery. The cardioprotection was associated with a slight increase in mitochondrial reduced glutathione (GSH) level and a significant increase in mitochondrial α-tocopherol (α-TOC) level, when compared with the unpretreated I-R group. To further investigate the mechanism of myocardial protection, pretreatment with a single dose of OA (1.2 mmol/kg) produced a time-dependent protection against myocardial I-R injury as assessed by LDH leakage, with the maximum extent of protection occurring at 48 hour post-dosing. The maximum cardioprotection was associated with parallel increases in mitochondrial GSH and α-TOC levels in ischemic-reperfused hearts, with the stimulation of the α-TOC level being optimal. Furthermore, buthionine sulfoximine/phorone (BSO/PHO) treatment, while abolishing the enhancing effect of OA on mitochondrial GSH, did not completely abrogate the cardioprotection against I-R injury. The remnant cardioprotection was associated with an increase in mitochondrial α-TOC level, when compared with the unpretreated I-R group with BSO/PHO. The results suggest that the cardioprotection afforded by OA pretreatment against I-R injury may at least in part be attributed to the enhancement of mitochondrial antioxidant mechanism mediated by GSH and α-TOC, particularly under I-R conditions. Abbreviations BSO:buthionine sulfoximine GSH:reduced glutathione I-R:ischemia-reperfusion α-LA:α-lipoic acid LDH:lactate dehydrogenase OA:oleanolic acid PHO:phorone α-TOC:α-tocopherol