Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

Ohara, Kazuaki; Wakabayashi, Hideyuki; Taniguchi, Yoshimasa; Shindo, Kazutoshi; Yajima, Hiroaki; Yoshida, Aruto

doi:10.1016/j.bbrc.2013.10.168

Cited by 24 publications

(12 citation statements)

References 30 publications

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“…Macrophages are considered as major inflammatory cells during the formation of AS (27,28). Macrophages can develop into foam cells, and the lipid nucleus is formed after necrosis of foam cells, which is a major component of atherosclerotic plaques (29).…”

Section: Discussionmentioning

confidence: 99%

Tacrolimus reduces atherosclerotic plaque formation in ApoE-/- mice by inhibiting NLRP3 inflammatory corpuscles

Xiao¹,

Shang²,

Sun³

2019

Exp Ther Med

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Effect of tacrolimus on atherosclerotic plaques and its influence on Nod-like receptor protein 3 (NLRP3) inflammatory pathway were studied by establishing the mouse model of atherosclerosis. The mice were divided into 3 groups: C57BL/6 mouse group (WT group), ApoE-/mouse group (ApoE-/group) and ApoE-/mouse + tacrolimus intervention group (ApoE-/-+ Tac group). The area of atherosclerotic plaques and the pathological morphologic changes were observed. The NLRP3, interleukin-1β (IL-1β), IL-18, NLRP3 inflammatory corpuscles, pro-inflammatory factors IL-1β and IL-18 in the aorta were analyzed. The area of atherosclerotic plaques in ApoE-/mice was increased significantly, and it was significantly reduced after tacrolimus intervention. After tacrolimus intervention, the arterial intima became obviously thinner and no obvious cholesterol crystals were observed. The macrophage infiltration in atherosclerotic plaques was significantly increased, and the content of smooth muscle cells was also increased. The levels of serum IL-1β, IL-18 and NLRP3 in ApoE-/mice were significantly increased, and they remarkably declined after tacrolimus intervention. ROS content in atherosclerotic plaques was increased in ApoE-/mice, and it remarkably declined after tacrolimus intervention. The protein content of NLRP3, ASC, Casp-1, IL-1β and IL-18 in the aorta in ApoE-/mice was remarkably increased, and they were inhibited to some extent after tacrolimus intervention. In conclusion, it is speculated that tacrolimus may reduce the formation of AS through inhibiting ROS in macrophages and activation of NLRP3 inflammatory corpuscles and reducing the release of IL-1β and IL-18.

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Section: Discussionmentioning

confidence: 99%

Tacrolimus reduces atherosclerotic plaque formation in ApoE-/- mice by inhibiting NLRP3 inflammatory corpuscles

Xiao¹,

Shang²,

Sun³

2019

Exp Ther Med

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“…Extraction of Q3G from the leaves was performed according to the method stipulated by Ohara et al . 35 with modifications. Briefly, the dried leaves (100 g) were extracted with 2 L of 50% aqueous ethanol at room temperature for 12 h. The extract was filtered, and then concentrated under reduced pressure.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

Yang

Xiao

et al. 2016

Sci Rep

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Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L−1 or 24625.1 ± 1563.8 mg·h·L−1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L−1 or 1394.6 ± 868.1 mg·h·L−1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

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“…It has been reported that LDLR expression is also regulated by protein ubiquitination via the ubiquitin ligase MYLIP/IDOL 38, which is induced by LXR 39. As reported above, quercetin increases the expression of and activates LXRα 32, 33.…”

Section: Resultsmentioning

confidence: 72%

The molecular mechanism of the cholesterol‐lowering effect of dill and kale: The influence of the food matrix components

et al. 2016

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Foods are complex matrices containing many different compounds, all of which contribute to the overall effect of the food itself, although they have different mechanisms of action. While evaluating the effect of bioactive compounds, it is important to consider that the use of a single compound can hide the effects of the other molecules that can act synergistically or antagonistically in the same food. The aim of the present study was to evaluate the influence of food matrix components by comparing two edible plants (dill and kale) with cholesterol‐lowering potential and similar contents of their most representative bioactive, quercetin. The molecular effects of the extracts were evaluated in HepG2 cells by measuring the expression of sterol‐regulatory element‐binding proteins (SREBPs), 3‐hydroxy‐3‐methylglutaryl‐CoA reductase (HMGCR) and low density lipoprotein receptor (LDLR) at the mRNA and protein level. The results reported here show that both extracts reduced the cellular cholesterol level with a similar trend and magnitude. It is conceivable that the slightly different results are due to the diverse composition of minor bioactive compounds, indicating that only by considering food as a whole is it possible to understand the complex relationship between food, nutrition, and health in a foodomics vision.

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Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

Cited by 24 publications

References 30 publications

Tacrolimus reduces atherosclerotic plaque formation in ApoE-/- mice by inhibiting NLRP3 inflammatory corpuscles

Tacrolimus reduces atherosclerotic plaque formation in ApoE-/- mice by inhibiting NLRP3 inflammatory corpuscles

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

The molecular mechanism of the cholesterol‐lowering effect of dill and kale: The influence of the food matrix components

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