Xanthohumol prevents atherosclerosis by reducing arterial cholesterol content via CETP and apolipoprotein E in CETP-transgenic mice.

BACKGROUND: Xanthohumol is expected to be a potent anti-atherosclerotic agent due to its inhibition of cholesteryl ester transfer protein (CETP). In this study, we hypothesized that xanthohumol prevents atherosclerosis in vivo and used CETP-transgenic mice (CETP-Tg mice) to evaluate xanthohumol as a functional agent. METHODOLOGY/PRINCIPAL FINDINGS: Two strains of mice, CETP-Tg and C57BL/6N (wild-type), were fed a high cholesterol diet with or without 0.05% (w/w) xanthohumol ad libitum for 18 weeks. In CETP-Tg mice, xanthohumol significantly decreased accumulated cholesterol in the aortic arch and increased HDL cholesterol (HDL-C) when compared to the control group (without xanthohumol). Xanthohumol had no significant effect in wild-type mice. CETP activity was significantly decreased after xanthohumol addition in CETP-Tg mice compared with the control group and it inversely correlated with HDL-C (%) (P<0.05). Furthermore, apolipoprotein E (apoE) was enriched in serum and the HDL-fraction in CETP-Tg mice after xanthohumol addition, suggesting that xanthohumol ameliorates reverse cholesterol transport via apoE-rich HDL resulting from CETP inhibition. CONCLUSIONS: Our results suggest xanthohumol prevents cholesterol accumulation in atherogenic regions by HDL-C metabolism via CETP inhibition leading to apoE enhancement

Establishment of an Efficient Fermentation System of Gamma-Aminobutyric Acid by a Lactic Acid Bacterium, <i>Enterococcus avium</i> G-15, Isolated from Carrot Leaves

In the present study, we successfully isolated a carrot leaf-derived lactic acid bacterium that produces gamma-aminobutyric acid (GABA) from monosodium L-glutamate (L-MSG) at a hyper conversion rate. The GABA-producing bacterium, identified as Enterococcus (E.) avium G-15, produced 115.7±6.4 g/l GABA at a conversion rate of 86.0±5.0% from the added L-MSG under the optimum culture condition by a continuous L-MSG feeding method using a jar-fermentor, suggesting that the bacterium displays a great potential ability for the commercial-level fermentation production of GABA. Using the reverse transcription polymerase chain reaction (RT-PCR) method, we analyzed the expression of genes for the GABA transporter and glutamate decarboxylase, designated gadT and gadG, respectively, which were cloned from the E. avium G-15 chromosome. Both genes were expressed even without the added L-MSG, but their expression was enhanced by the addition of L-MSG.This work was supported by Hiroshima Biocluster (a Cooperative Link of Unique Science and Technology for Economy Revitalization), Japan (M.S.)

Expression analyses in mice liver and ab. aorta.

<p>(A) SR-B1 and (B) LCAT protein expression in liver. Data was standardized for β-actin expression. (N = 15; CETP-Tg mice control, N = 18; CETP-Tg mice xanthohumol, N = 11; CETP-Tg mice Chow, N = 6; wild-type mice control, N = 8; wild-type mice xanthohumol) (C, D) Transcript analyses of liver (upper) and ab. aorta (lower) in CETP-Tg mice (C) and wild-type mice (D). (N = 12; CETP-Tg mice control, N = 13; CETP-Tg mice xanthohumol, N = 9 to 10; CETP-Tg mice Chow, N = 5; wild-type mice control, N = 7 to 8; wild-type mice xanthohumol) All data were standardized for GAPDH expression. Expression levels of control group (without xanthohumol) were set at 1.0. Means±SEM. *<i>P</i><0.05, **<i>P</i><0.01.</p

Effect of xanthohumol on serum cholesterol and CETP activity.

<p>Serum HDL-C concentration in the control group (closed circle), xanthohumol group (opened circle) and Chow group (closed triangle) of CETP-Tg mice (A), and in the control group (closed square) and xanthohumol group (opened square) of wild-type mice (B) over time. (C) Serum CETP activity after 18 weeks of treatment. (D) Correlation of serum CETP activity and HDL-C/T-Cho (%) in CETP-Tg mice fed HCD after 18 weeks. CE content of serum (E) and HDL-fraction (F) after 18 weeks. (N = 15; CETP-Tg mice control, N = 16; CETP-Tg mice xanthohumol, N = 10; CETP-Tg mice Chow, N = 3; wild-type mice control, N = 8; wild-type mice xanthohumol) Means±SEM. *<i>P</i><0.05, **<i>P</i><0.01.</p

Changes in cholesterol accumulation over 18 weeks.

<p>Data are presented as cholesterol amount in the aortic arch (A) and liver (B). (N = 15; CETP-Tg mice control, N = 18; CETP-Tg mice xanthohumol, N = 12; CETP-Tg mice Chow, N = 10; wild-type mice control, N = 7; wild-type mice xanthohumol) Means±SEM. *<i>P</i><0.05, **<i>P</i><0.01.</p

Xanthohumol increased apoE protein expression in CETP-Tg mice after 18 weeks.

<p>(A) Serum (upper) and HDL-fraction (lower), and (B) liver tissue. Data are represented as relative expression: the CETP-Tg mice control group was set at 1.0. (N = 8; CETP-Tg mice control, N = 8; CETP-Tg mice xanthohumol, N = 3; CETP-Tg mice Chow, N = 6; wild-type mice control, N = 7; wild-type mice xanthohumol) Means±SEM. *<i>P</i><0.05, **<i>P</i><0.01.</p

CKD, Brain Atrophy, and White Matter Lesion Volume: The Japan Prospective Studies Collaboration for Aging and DementiaPlain-Language summary

Rationale &amp; Objective: Chronic kidney disease, defined by albuminuria and/or reduced estimated glomerular filtration rate (eGFR), has been reported to be associated with brain atrophy and/or higher white matter lesion volume (WMLV), but there are few large-scale population-based studies assessing this issue. This study aimed to examine the associations between the urinary albumin-creatinine ratio (UACR) and eGFR levels and brain atrophy and WMLV in a large-scale community-dwelling older population of Japanese. Study Design: Population-based cross-sectional study. Setting &amp; Participants: A total of 8,630 dementia-free community-dwelling Japanese aged greater than or equal to 65 years underwent brain magnetic resonance imaging scanning and screening examination of health status in 2016-2018. Exposures: UACR and eGFR levels. Outcomes: The total brain volume (TBV)-to-intracranial volume (ICV) ratio (TBV/ICV), the regional brain volume-to-TBV ratio, and the WMLV-to-ICV ratio (WMLV/ICV). Analytical Approach: The associations of UACR and eGFR levels with the TBV/ICV, the regional brain volume-to-TBV ratio, and the WMLV/ICV were assessed by using an analysis of covariance. Results: Higher UACR levels were significantly associated with lower TBV/ICV and higher geometric mean values of the WMLV/ICV (P for trend = 0.009 and <0.001, respectively). Lower eGFR levels were significantly associated with lower TBV/ICV, but not clearly associated with WMLV/ICV. In addition, higher UACR levels, but not lower eGFR, were significantly associated with lower temporal cortex volume-to-TBV ratio and lower hippocampal volume-to-TBV ratio. Limitations: Cross-sectional study, misclassification of UACR or eGFR levels, generalizability to other ethnicities and younger populations, and residual confounding factors. Conclusions: The present study demonstrated that higher UACR was associated with brain atrophy, especially in the temporal cortex and hippocampus, and with increased WMLV. These findings suggest that chronic kidney disease is involved in the progression of morphologic brain changes associated with cognitive impairment