Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

Rocejanasaroj, A; Tencomnao, Tewin; Sangkitikomol, W

doi:10.4238/2014.january.10.12

Cited by 19 publications

(15 citation statements)

References 37 publications

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“… 44 Interestingly, PPARγ has also shown to regulate LRP1 and P-gp expressions. 45 , 46 In vivo and in vitro studies demonstrated treatment with the PPARγ activators cilostazol, a selective phosphodiesterase 3 inhibitor, and Thunbergia laurifolia , widely used as an antidote, to upregulate hepatic LRP1 protein expression in vivo 45 and P-gp activity in vitro, 46 respectively. Thus, enhanced LRP1 and P-gp efflux function by oleocanthal could also be mediated, at least in part, by activating PPARγ.…”

Section: Resultsmentioning

confidence: 99%

Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model

Qosa

Batarseh

Mohyeldin

et al. 2015

ACS Chem. Neurosci.

125

128

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Numerous clinical and preclinical studies have suggested several health promoting effects for the dietary consumption of extra-virgin olive oil (EVOO) that could protect and decrease the risk of developing Alzheimer’s disease (AD). Moreover, recent studies have linked this protective effect to oleocanthal, a phenolic secoiridoid component of EVOO. This protective effect of oleocanthal against AD has been related to its ability to prevent amyloid-β (Aβ) and tau aggregation in vitro, and enhance Aβ clearance from the brains of wild type mice in vivo; however, its effect in a mouse model of AD is not known. In the current study, we investigated the effect of oleocanthal on pathological hallmarks of AD in TgSwDI, an animal model of AD. Mice treatment for 4 weeks with oleocanthal significantly decreased amyloid load in the hippocampal parenchyma and microvessels. This reduction was associated with enhanced cerebral clearance of Aβ across the blood-brain barrier (BBB). Further mechanistic studies demonstrated oleocanthal to increase the expression of important amyloid clearance proteins at the BBB including P-glycoprotein and LRP1, and to activate the ApoE-dependent amyloid clearance pathway in the mice brains. The anti-inflammatory effect of oleocanthal in the brains of these mice was also obvious where it was able to reduce astrocytes activation and IL-1β levels. Finally, we could recapitulate the observed protective effect of oleocanthal in an in vitro human-based model, which could argue against species difference in response to oleocanthal. In conclusion, findings from in vivo and in vitro studies provide further support for the protective effect of oleocanthal against the progression of AD.

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Section: Resultsmentioning

confidence: 99%

Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model

Qosa

Batarseh

Mohyeldin

et al. 2015

ACS Chem. Neurosci.

125

128

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“…A previous report exhibited an increase of P-glycoprotein and a decrease in some cytochrome P450 isoenzymes such as CYP2E1 in HepG2 cells treated with T. laurifolia. 34 P-glycoprotein expressed in hepatocytes and the bloodbrain barrier 35 function as a biological barrier by extruding toxins and xenobiotics out of cells. In the brain, P-glycoprotein did not only increase the efflux but also inhibited the influx of the drug across the blood-brain barrier of nonhuman primates.…”

Section: Resultsmentioning

confidence: 99%

Thunbergia laurifolia Linn. Extract Protects Ethanol Addiction and Increases Dopamine Synthesis

2021

TJNPR

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Ethanol consumption is a widespread problem throughout the world. Ethanol mainly acts on dopaminergic system which is a major circuit in mediating the reward system of ethanol and other drugs leading to the change in behaviour. 1,2 Dopaminergic neurons in the ventral tegmental area (VTA) innervates several brain areas including the nucleus accumbens affected by acute and chronic ethanol exposure. Ethanol was shown to cause excitation of dopaminergic neurons in the VTA in vitro and in vivo. 3 The enhancement of the firing rate of the VTA dopaminergic neurons correlates with dopamine release and tyrosine hydroxylase of the VTA and nucleus accumbens. 4,5 On the other hand, chronic ethanol administration decreases the VTA dopaminergic neurons firing rate and activity. 6,7 The dopaminergic connection between the VTA and nucleus accumbens is associated with a critical role in addiction and anxiety-like behaviours. 8,9 Ethanol addicted rodents spent more time in the non-preference compartment of the conditioned place preference (CPP) behaviour model after chronic ethanol administration. 10,11 The changes of synaptic output induced by chronic ethanol administration

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“…It functions as a transporter via excretion of drugs, toxic agents, and xenobiotics from cells. Several natural compounds, dietary phytochemicals, and herbal medicines have the ability to modulate P-gp function and cause effects such as drug-drug, herb-drug, and herb-toxicant interactions [45]. In this study, P-gp expression in UACC732 cells treated with lipoproteins was assessed using flow cytometry.…”

Section: Discussionmentioning

confidence: 99%

Lipoproteins modulate growth and P-glycoprotein expression in drug-resistant HER2-overexpressed breast cancer cells

Siti

Seoparjoo

Shahrul

2019

Heliyon

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Background Drug resistance remains as a challenge in the treatment of HER2-overexpressed breast cancer. Emerging evidence from clinical studies show relation of oxidized low density lipoprotein (LDL) and very low density lipoprotein (VLDL) level with drug resistance. However, the underlying molecular mechanisms for this effect remain unclear. Therefore, the aim of this study was to determine the effects of oxidized-LDL and VLDL in drug-resistant HER2-overexpressed breast cancer cells. Methods An in vitro cell model for tamoxifen-resistant HER2 overexpressed UACC732 cells was created using the pulse method. Cells were exposed to oxidized LDL (oxLDL) and very low density lipoprotein (VLDL) separately. Effects on cell morphology was studied using phase contrast microscopic changes. Percentage of cell viability was measured using proliferation assay kit. Development of tamoxifen resistance was determined based on P-gp expression with flow cytometry. Further analysis includedcell death measurement with flow cytometry method. Results UACC732 cells exposed to VLDL exhibited fibroblast-like morphology. This was further supported by proliferation assay, where the percentage of cell viability achieved more than 100% with 100 μg/ml of VLDL exposure, indicating cell proliferation. Findings also showed that VLDL caused reduction in expression of Pgp in resistant cells compared to resistant cells alone (p = 0.02). Conclusion Results of this study suggest that VLDL may play a role in growth of drug-resistant HER2-overexpressing cells. Lower expression of P-gp in presence of VLDL need to be investigated further.

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Thunbergia laurifolia extract minimizes the adverse effects of toxicants by regulating P-glycoprotein activity, CYP450, and lipid metabolism gene expression in HepG2 cells

Cited by 19 publications

References 37 publications

Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model

Oleocanthal Enhances Amyloid-β Clearance from the Brains of TgSwDI Mice and in Vitro across a Human Blood-Brain Barrier Model

Thunbergia laurifolia Linn. Extract Protects Ethanol Addiction and Increases Dopamine Synthesis

Lipoproteins modulate growth and P-glycoprotein expression in drug-resistant HER2-overexpressed breast cancer cells

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