Orientin

1 Arum sp. 2 Aspalathus sp. 3 Cannabis sp. 4 Capsicum sp. 5 Carlina sp. 6 Chamaecytisus sp. 7 Daphne sp. 8 Fagopyrum sp. 9 Gypsophila sp. 10 Helenium sp. 11 Hypericum sp. 12 Lemna sp. 13 Linum sp. 14 Lythrum sp. 15 Ocimum sp. 16 Origanum sp. 17 Passiflora sp. 18 Sigesbeckia sp. 19 Tamarindus sp. 20 Tanacetum sp. 21 Viola sp. 22 Vitex sp. 23 Wikstroemia sp.

Vascular barrier protective effects of orientin and isoorientin in LPS-induced inflammation in vitro and in vivo.[Pubmed:24792192]

Vascul Pharmacol. 2014 Jul;62(1):3-14.

Endothelial cell protein C receptor (EPCR) can be shed from the cell surface, and this process is mediated by tumor necrosis factor-alpha converting enzyme (TACE), and high levels of soluble EPCR are involved in vascular inflammation. Orientin, one of the C-glycosyl flavonoids, has been known to have anxiolytic and antioxidative activities. However, the effect of Orientin on lipopolysaccharide (LPS)-induced inflammatory response has not been studied. Here we investigated the barrier protective effects of Orientin against pro-inflammatory responses induced by LPS and the associated signaling pathways. We found that Orientin inhibited LPS-induced barrier disruption, expression of cell adhesion molecules (CAMs), and adhesion/transendothelial migration of monocytes to human endothelial cells. Orientin induced potent inhibition of phorbol-12-myristate 13-acetate (PMA) and LPS-induced EPCR shedding. Orientin also suppressed LPS-induced hyperpermeability and leukocyte migration in vivo. Furthermore, Orientin suppressed the production of tumor necrosis factor-alpha (TNF-alpha) or Interleukin (IL)-6 and the activation of nuclear factor-kappaB (NF-kappaB) or extracellular regulated kinases (ERK) 1/2 by LPS. Moreover, treatment with Orientin resulted in reduced LPS-induced lethal endotoxemia. These results suggest that Orientin protects vascular barrier integrity by inhibiting hyperpermeability, expression of CAMs, and adhesion and migration of leukocytes, thereby endorsing its usefulness as a therapy for vascular inflammatory diseases.

Orientin alleviates cognitive deficits and oxidative stress in Abeta1-42-induced mouse model of Alzheimer's disease.[Pubmed:25497709]

Life Sci. 2015 Jan 15;121:104-9.

AIMS: beta-Amyloid (Abeta)-mediated neurotoxicity plays a critical role in the pathogenesis of Alzheimer's disease (AD), possibly including Abeta-induced mitochondrial dysfunction and oxidative stress. Previous studies have demonstrated that Orientin (Ori) possesses antioxidation capabilities in vitro. Therefore, current study is to demonstrate that Ori can activate Nrf2/HO-1 signaling and alleviate apoptosis induced by Abeta1-42, and ameliorate cognitive deficits in AD mice. MAIN METHODS: AD models were made by injecting Abeta1-42 into the bilateral hippocampus of mice. The mice were randomly assigned to three groups: the normal mice and Abeta1-42-induced AD mice with saline, and Abeta1-42-induced AD mice with Ori (5mg/kg), and were injected intraperitoneally once a day for 15 days. After the Morris Water Maze (MWM) test, mice were sacrificed and brains were harvested for biochemical analysis. KEY FINDINGS: Results indicated that Ori could ameliorate cognitive deficits in AD mice. Levels of oxidative stress, indicated by production of reactive oxygen species (ROS), 3-nitrotyrosine (3-NT), 4-hydroxy-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG), were significantly decreased after Ori treatment. In addition, the current study showed that Ori could attenuate mitochondrial dysfunction induced by Abeta1-42, and subsequently inhibited the mitochondrial apoptotic pathway. Ori induced the nuclear translocation of Nrf2, which enhanced the expression of HO-1 and activation of the redox signaling pathway. SIGNIFICANCE: Ori might alleviate cognitive deficits and oxidative stress in AD mice, which might be a potential therapeutic drug for AD.

Vitexin, orientin and other flavonoids from Spirodela polyrhiza inhibit adipogenesis in 3T3-L1 cells.[Pubmed:20878708]

Phytother Res. 2010 Oct;24(10):1543-8.

To investigate the adipogenesis inhibitory effect on lipid accumulation, 3T3-L1 cells were treated with fractions and isolated flavonoids of Spirodela polyrhiza. An ethanol extract of S. polyrhiza was fractionated into three fractions. The butanol soluble fraction (SPB) exhibited potent antiadipogenesis activity and decreased C/EBPalpha and PPARgamma protein expression level in 3T3-L1 cells without significant cytotoxicity. The flavonoids were isolated from SPB and their chemical structures were identified as chrysoeriol (1), apigenin (2), luteolin (3), vitexin (4), cosmosin (5), Orientin (6) and luteolin-7-O-beta-d-glucoside (7) by spectroscopic analysis. Studies on the adipogenesis and intracellular triglyceride accumulation inhibitory effect showed that compounds 4 and 6 had the highest activity and decreased C/EBPalpha and PPARgamma protein expression level in 3T3-L1 cells. These results suggest that the flavonoids isolated from SPB, especially compounds 4 and 6, contribute to the inhibitory activity of S. polyrhiza in 3T3-L1 cells.

Neuroprotective effects of orientin on hydrogen peroxideinduced apoptosis in SHSY5Y cells.[Pubmed:24366367]

Mol Med Rep. 2014 Mar;9(3):947-54.

Neurodegenerative diseases remain a global issue which affects the ageing population. Efforts towards determining their aetiologies to understand their pathogenic mechanisms are underway in order to identify a pathway through which therapeutic measures can be applied. One such pathogenic mechanism, oxidative stress (OS), is widely considered to be involved in neurodegenerative disease. Antioxidants, most notably flavonoids, have promising potential for therapeutic use as shown in in vitro and in vivo studies. In view of the importance of flavonoids for combating OS, this study investigated the neuroprotective effects of Orientin, which has been reported to be capable of crossing the bloodbrain barrier. The maximum nontoxic dose (MNTD) of Orientin against SHSY5Y neuroblastoma cells was determined using a 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide (MTT) assay. The effects of the MNTD and the half MNTD ((1/2)MNTD) of Orientin on cell cycle progression and intracellular reactive oxygen species (ROS) levels, as well as the activity of caspases 3/7, 8 and 9 after exposure to 150 microM of hydrogen peroxide (H2O2) were also determined using flow cytometry, a 2',7'dichlorodihydrofluoresceindiacetate (DCFHDA) assay and caspase assay kits, respectively. The results revealed that Orientin at Orientin at the MNTD, the percentage of apoptotic cells was significantly reduced compared with that in cells treated with 150 microM H2O2 alone. The results also showed that, although Orientin at the MNTD and (1/2)MNTD did not reduce intracellular ROS levels, it significantly inhibited the activity of caspases 3/7. Caspase 9 was significantly inactivated with Orientin at the MNTD. Findings from this study suggest that the neuroprotection conferred by Orientin was the result of the intracellular mediation of caspase activity.

Orientin improves depression-like behavior and BDNF in chronic stressed mice.[Pubmed:25788013]

Mol Nutr Food Res. 2015 Jun;59(6):1130-42.

SCOPE: Oxidative stress is involved in chronic stress-induced depression and the disruption of neurotransmission and neuroplasticity. Recently, Orientin, a phenolic compound abundant in some fruits, millet, and herbs, has been shown to have antioxidant properties. This study investigated the potential antidepressant effects of Orientin against chronic stress and its underlying mechanisms. METHODS AND RESULTS: The chronic unpredictable mild stress (CUMS) model was used to investigate the effects of Orientin on behavior and biochemical alterations in mice. After 2 weeks of the CUMS protocol, the mice were treated with Orientin (20 mg/kg and 40 mg/kg, oral gavage) for 3 weeks. Administration of Orientin significantly alleviated the CUMS-induced depression-like behavior, including sucrose preference reduction, locomotor activity decline, and hypomotility. Orientin treatment attenuated the oxidative stress markers and increased the concentrations of serotonin and norepinephrine in the hippocampus and prefrontal cortex of CUMS mice. Orientin treatment also increased the brain-derived neurotrophic factor and synapse-associated proteins (synaptophysin and postsynaptic density protein 95) of CUMS mice. CONCLUSION: Orientin exerts antidepressant-like effects on CUMS mice, specifically by improving central oxidative stress, neurotransmission, and neuroplasticity. Therefore, supplementation with Orientin-enriched food or fruit could be beneficial as a preventive strategy for chronic stress-induced depression.

Radiation protection by the ocimum flavonoids orientin and vicenin: mechanisms of action.[Pubmed:11023610]

Radiat Res. 2000 Oct;154(4):455-60.

In previous studies, flavonoids, Orientin and vicenin, that were isolated from the leaf extract of Ocimum sanctum, were found to protect mice against radiation injury. Several flavonoids are known to be good antioxidants. Therefore, the effect of Orientin and vicenin on radiation-induced lipid peroxidation in vivo and their antioxidant activity in vitro were studied. Adult mice were injected intraperitoneally with 50 microgram/kg of Orientin or vicenin and exposed whole-body to 3 Gy of gamma radiation. Lipid peroxidation was measured in the liver 15 min to 8 h postirradiation. The antioxidant activity of Orientin/vicenin (10-500 microM) was studied by measuring inhibition of hydroxyl radicals generated by the Fenton reaction (Fe(3+)-EDTA-ascorbic acid-H(2)O(2)) in vitro. The compounds were also tested for possible pro-oxidant and iron chelation activities at the above concentrations in the in vitro system. Orientin and vicenin provided almost equal protection against radiation-induced lipid peroxidation in mouse liver. Both compounds showed a significantly greater free radical-inhibiting activity in vitro than DMSO. Neither Orientin nor vicenin showed any pro-oxidant activity at the concentrations tested. Both compounds inhibited free radical formation in the absence of EDTA. Free radical scavenging appears to be a likely mechanism of radiation protection by these flavonoids.

Orientin-induced cardioprotection against reperfusion is associated with attenuation of mitochondrial permeability transition.[Pubmed:21283956]

Planta Med. 2011 Jul;77(10):984-91.

In this study, we provide new evidence that Orientin from bamboo leaves (Phyllostachys nigra) protect H9c2 cardiomyocytes against ischemia/reperfusion (I/R) injury through the mitochondrial apoptotic pathway. A previous work has identified that Orientin could protect myocardium against ischemia/reperfusion injury. Mitochondria are both critical determinants of cardioprotection and crucial targets of cardioprotective signaling. Their role during reperfusion is conspicuously critical because the conditions promote apoptosis through the mitochondrial pathway and necrosis though irreversible damage to mitochondria, which is in association with mitochondrial permeability transition (MPT). After myocardial ischemia, opening of the mPTP is a critical determinant of cell death. The relationship of Orientin and mPTP in mediating reperfusion-induced cardiomyocytes injury is still elusive. Here, our results indicate that the protective effect of Orientin in H9c2 cells subjected to I/R injury is associated with depression of the mPTP opening, resultant mitochondrial dysfunction, and apoptosis. Further investigation of cellular mechanisms revealed that these effects were associated with inhibition of reactive oxygen species (ROS) generation, repolarization of mitochondrial membrane potential (Deltapsi(m)), suppression of mitochondrial cytochrome C release, enhancement of the Bcl-2 level, and inhibition of Bax and Smac/DIABLO levels. Furthermore, these beneficial effects of Orientin were blocked by the phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin, and Orientin could enhance Akt phosphorylation. In summary, we demonstrate that Orientin protects H9c2 cardiomytocytes against I/R-induced apoptosis by modulating the mPTP opening, and this role of Orientin may involve the PI3K/Akt signaling pathway.

Orientin is a naturally occurring bioactive flavonoid that possesses diverse biological properties, including anti-inflammation, anti-oxidative, anti-tumor, and cardio protection. Orientin is a promising neuroprotective agent suitable for therapy for neuropathic pain.

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