Vitamin E isoforms α-tocotrienol and γ-tocopherol prevent cerebral infarction in mice

Mishima, Kenichi; Tanaka, Takamitsu; Pu, Fengling; Egashira, Nobuaki; Iwasaki, Katsunori; Hidaka, Ryoji; Matsunaga, Kazuhisa; Takata, Jiro; Karube, Yoshiharu; Fujiwara, Michihiro

doi:10.1016/s0304-3940(02)01293-4

Cited by 91 publications

(66 citation statements)

References 20 publications

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“…In studies on vitamin E and its isomers (forms of tocopherols), it was found that these vitamins may reduce the severity of amyloid fibril formation by reducing oxidative metabolites. Studies by Mishima et al [46] also showed that the antioxidant power of α-tocotrienol is greater than that of α-tocopherol. The difference is in the greater number of double bonds that the former compound has (3 double bonds in the lipophilic tail).…”

Section: Discussionmentioning

confidence: 95%

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Ghahghaei

Bathaie

Kheirkhah

et al. 2013

Cellular and Molecular Biology Letters

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Abstract:Aβ is the main constituent of the amyloid plaque found in the brains of patients with Alzheimer's disease. There are two common isoforms of Aβ: the more common form, Aβ 40 , and the less common but more amyloidogenic form, Aβ 42 . Crocin is a carotenoid from the stigma of the saffron flower and it has many medicinal properties, including antioxidant effects. In this study, we examined the potential of crocin as a drug candidate against Aβ 42 amyloid formation. The thioflavin T-binding assay and electron microscopy were used to examine the effects of crocin on the extension and disruption of Aβ 42 amyloids. To further investigate the relationship between crocin and Aβ 42 structure, we analyzed peptide conformation using the ANS-binding assay and circular dichroism (CD) spectroscopy. An increase in the thioflavin T fluorescence intensity upon incubation revealed amyloid formation in Aβ 42 . It was found that crocin has the ability to prevent amyloid formation by decreasing the fluorescence intensity. Electron microscopy data also indicated that crocin decreased the amyloid fibril content of Aβ. The ANS-binding assay showed that crocin decreased the hydrophobic area in incubated Aβ 42 . CD spectroscopy results also showed that the peptide undergoes a structural change to α-helical and β-turn. Our study shows that the anti-amyloidogenic effect of crocin may be exerted not only by the inhibition of Aβ amyloid formation but also by the Unauthenticated Download Date | 5/12/18 7:38 AM CELLULAR & MOLECULAR BIOLOGY LETTERS 329 disruption of amyloid aggregates. Therefore, crocin could be essential in the search for therapies inhibiting aggregation or disrupting aggregation.

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Section: Discussionmentioning

confidence: 95%

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Ghahghaei

Bathaie

Kheirkhah

et al. 2013

Cellular and Molecular Biology Letters

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“…15 In addition, administration of VE reportedly ameliorates cerebral infarction in rats. 16 Considering that administration of VE analog SMTP-7 to tMCAo mice showed weak peroxynitrite reactions ( Figure 2), it is believed that anti-inflammatory effects of SMTP-7 in the mice are at least in part caused by its direct antioxidative actions.…”

Section: Discussionmentioning

confidence: 99%

Distinct Effects of Tissue-Type Plasminogen Activator and SMTP-7 on Cerebrovascular Inflammation Following Thrombolytic Reperfusion

Miyazaki

Kimura

Ohata

et al. 2011

Stroke

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Background and Purpose-Thrombolysis therapy using tissue-type plasminogen activator (t-PA) is occasionally accompanied by harmful outcomes, including intracerebral hemorrhage. We have reported that Stachybotrys microspora triprenyl phenol-7 (SMTP-7), a candidate thrombolytic drug, has excellent therapeutic effect on cerebral infarction in embolic stroke model in mice; however, little is known regarding whether this agent influences cerebrovascular inflammation following thrombolytic reperfusion. The current study aimed to compare the effects of recombinant t-PA (rt-PA) and SMTP-7 on cerebrovascular inflammation. Methods-The impact of rt-PA-and SMTP-7-induced thrombolytic reperfusion on leukocyte dynamics was investigated in a photochemically induced thrombotic middle cerebral artery occlusion (tMCAo) model in mice. Results-Both rt-PA and SMTP-7 administration in tMCAo mice (each 10 mg/kg) resulted in thrombolytic reperfusion.The SMTP-7-administered mice showed relatively mild rolling and attachment of leukocytes to the vascular wall in the middle cerebral vein, with weak peroxynitrite reactions and proinflammatory gene expression (IL-1␤, TNF-␣, ICAM-1, and VCAM-1); thus, a small infarct volume compared with rt-PA-administered mice. In vitro study suggested that rt-PA at 20 g/mL, but not SMTP-7 at a similar concentration, promotes cytokine-induced reactive oxygen species generation in cultured endothelial cells; moreover, SMTP-7 suppressed cytokine-induced VCAM-1 induction in the cells and leukocyte/ endothelial cell adhesions. Conclusions-Relatively mild cerebrovascular inflammation and cerebral infarction in the SMTP-7 mice, compared with in rt-PA mice, is thought to be caused at least in part by direct antioxidative actions of SMTP-7 in ECs. (Stroke. 2011; 42:1097-1104.)

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“…α-Tocotrienol provided the most potent neuroprotection among all vitamin E analogs. Reported effects of tocotrienol independent of antioxidant property (Sen et al, 2000(Sen et al, ) 2002 Rat; Oral tocotrienol crosses the blood-brain barrier to reach brain tissue; more so for fetal brain while pregnant mother is supplemented with tocotrienol (Roy et al, ) 2003 Mouse; At nM concentrations α-tocotrienol, in contrast with α-tocopherol, protects against glutamate-induced neuronal death by suppressing inducible 12-lipoxygenase activation (Khanna et al, 2003(Khanna et al, ) 2003 Mouse; Injected α-tocotrienol decreased the size of the cerebral infarcts 1 day after stroke; γ-tocotrienol and delta-tocotrienol did not protect (Mishima et al, 2003(Mishima et al, ) 2003 Human; Tocotrienols induced IKBKAP expression: a possible therapy for familial dysautonomia (Anderson et al, 2003(Anderson et al, ) 2004 Rat; α-Tocotrienol provided the most potent neuroprotection among vitamin E analogs on cultured striatal neurons (Osakada et al, 2004) Hypocholesterolemic 1986 Chicken; Three double bonds in the isoprenoid chain essential for the inhibition of cholesterogenesis; tocopherols do not share this property (Qureshi et al, 1986(Qureshi et al, ) 1991 Human; Lowered serum cholesterol in hypercholesterolemics (Qureshi et al, 1991b); lowered both serum total cholesterol (TC) and low-density-lipoprotein cholesterol (Tan et al, 1991) Pigs; Reduced plasma cholesterol, apolipoprotein B, thromboxane B2, and platelet factor 4 in pigs with inherited hyperlipidemias (Qureshi et al, 1991a(Qureshi et al, ) 1992 In vitro; Post-transcriptional suppression of HMG-CoA reductase by a process distinct from other known inhibitors of cholesterol biosynthesis (Pearce et al, 1992(Pearce et al, ) 1993 Regulate cholesterol production in mammalian cells by post-transcriptional suppression of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Parker et al, 1993(Parker et al, ) 1994 HepG2; The farnesyl side chain and the methyl/hydroxy substitution pattern of gammatocotrienol responsible for HMG CoA reductase suppression (Pearce et al, 1994(Pearce et al, ) 1995 isoprenoid-mediated suppression of mevalonate synthesis depletes tumor tissues of two intermediate products, farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are incorporated post-translationally into growth control-associated proteins Human; Lowered plasma cholesterol level in hypercholesterolemic subjects …”

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confidence: 99%

Tocotrienols: Vitamin E beyond tocopherols

2006

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In nature, eight substances have been found to have vitamin E activity: α-, β-, γ-and δ-tocopherol; and α-, β-, γ-and δ-tocotrienol. Yet, of all papers on vitamin E listed in PubMed less than 1% relate to tocotrienols. The abundance of α-tocopherol in the human body and the comparable efficiency of all vitamin E molecules as antioxidants, led biologists to neglect the non-tocopherol vitamin E molecules as topics for basic and clinical research. Recent developments warrant a serious reconsideration of this conventional wisdom. Tocotrienols possess powerful neuroprotective, anticancer and cholesterol lowering properties that are often not exhibited by tocopherols. Current developments in vitamin E research clearly indicate that members of the vitamin E family are not redundant with respect to their biological functions. α-Tocotrienol, γ-tocopherol, and δ-tocotrienol have emerged as vitamin E molecules with functions in health and disease that are clearly distinct from that of α-tocopherol. At nanomolar concentration, α-tocotrienol, not α-tocopherol, prevents neurodegeneration. On a concentration basis, this finding represents the most potent of all biological functions exhibited by any natural vitamin E molecule. An expanding body of evidence support that members of the vitamin E family are functionally unique. In recognition of this fact, title claims in manuscripts should be limited to the specific form of vitamin E studied. For example, evidence for toxicity of a specific form of tocopherol in excess may not be used to conclude that high-dosage "vitamin E" supplementation may increase all-cause mortality. Such conclusion incorrectly implies that tocotrienols are toxic as well under conditions where tocotrienols were not even considered. The current state of knowledge warrants strategic investment into the lesser known forms of vitamin E. This will enable prudent selection of the appropriate vitamin E molecule for studies addressing a specific need.

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Vitamin E isoforms α-tocotrienol and γ-tocopherol prevent cerebral infarction in mice

Cited by 91 publications

References 20 publications

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

The protective effect of crocin on the amyloid fibril formation of aβ42 peptide in vitro

Distinct Effects of Tissue-Type Plasminogen Activator and SMTP-7 on Cerebrovascular Inflammation Following Thrombolytic Reperfusion

Tocotrienols: Vitamin E beyond tocopherols

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