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Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

ABSTRACT: We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control group showed gradual increases up to 21% in systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with values at week 0. However, policosanol consumption had a dose-dependent reduction effect on SBP and also reduced DBP up to 17% in a dose-dependent manner. Heart rate (HR) bpm increased by six percent in the SHR control, whereas the 20 mg, 100 mg, and 200 mg of policosanol groups showed a reduction of 36%, 28%, and 34% respectively. Although serum total cholesterol (TC) level of SHR was not affected by policosanol consumption (70?80 mg/dL), serum triglyceride (TG) level significantly decreased in the SHR + 200 mg of PCO group. Serum high-density lipoprotein cholesterol (HDL-C) level was also significantly elevated by policosanol consumption. The % HDL-C/TC ratio was elevated in the policosanol group up to 67?70%, whereas the SHR control group showed a ratio of 58%. Serum cholesteryl ester transfer protein (CETP) activity was reduced by policosanol in a dose-dependent manner. Although the serum glutamate oxaloacetate transaminase (GOT)/ glutamate pyruvate transaminase (GPT) were similar across all groups, policosanol consumption caused reduction of reactive oxygen species (ROS) levels in hepatic tissue. The SHR control group showed a 2.1-fold higher serum C-reactive protein (CRP) level than the WKY group, whereas the CRP level decreased in the SHR + 200 mg of PCO group (up to 45%) than SHR control group. Aldosterone level was reduced in the policosanol group (up to 34%) in a dose-dependent manner compared to the control. In conclusion, eight weeks of policosanol consumption in SHR resulted in remarkable reduction of blood pressure, serum aldosterone, and serum TG levels along with the elevation of HDL-C and improvement of hepatic inflammation.

SUBMITTER: Cho KH

PROVIDER: S-EPMC6102548 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

Cho Kyung-Hyun KH Yadav Dhananjay D Kim Suk-Jeong SJ Kim Jae-Ryong JR

Molecules (Basel, Switzerland) 20180503 5

We investigated the antihypertensive effect of policosanol on spontaneously hypertensive rats (SHR). For this, we analyzed blood pressure, blood lipid, and lipoprotein properties in male SHR after consumption of Cuban policosanol (PCO). The experimental groups were as follows: normotensive Wistar Kyoto (WKY) control, SHR group fed normal diet (ND), SHR group fed 20 mg of PCO, SHR group fed 100 mg of PCO, and SHR group fed 200 mg of PCO per kg of body weight. After eight weeks, the SHR control gr ...[more]

PMID: 29751583

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Project description:BackgroundPatients with metabolic syndrome, who are characterized by co-existence of insulin resistance, hypertension, hyperlipidemia, and obesity, are also prone to develop non-alcoholic fatty liver disease (NAFLD). Although the prevalence and severity of NAFLD is significantly greater in men than women, the mechanisms by which gender modulates the pathogenesis of hepatic steatosis are poorly defined. The obese spontaneously hypertensive (SHROB) rats represent an attractive model of metabolic syndrome without overt type 2 diabetes. Although pathological manifestation caused by the absence of a functional leptin receptor has been extensively studied in SHROB rats, it is unknown whether these animals elicited sex-specific differences in the development of hepatic steatosis.MethodsWe compared hepatic pathology in male and female SHROB rats. Additionally, we examined key biochemical and molecular parameters of signaling pathways linked with hyperinsulinemia and hyperlipidemia. Finally, using methods of quantitative polymerase chain reaction (qPCR) and western blot analysis, we quantified expression of 45 genes related to lipid biosynthesis and metabolism in the livers of male and female SHROB rats.ResultsWe show that all SHROB rats developed hepatic steatosis that was accompanied by enhanced expression of SREBP1, SREBP2, ACC1, and FASN proteins. The livers of male rats also elicited higher induction of Pparg, Ppara, Slc2a4, Atox1, Skp1, Angptl3, and Pnpla3 mRNAs. In contrast, the livers of female SHROB rats elicited constitutively higher levels of phosphorylated JNK and AMPK and enhanced expression of Cd36.ConclusionBased on these data, we conclude that the severity of hepatic steatosis in male and female SHROB rats was mainly driven by increased de novo lipogenesis. Moreover, male and female SHROB rats also elicited differential severity of hepatic steatosis that was coupled with sex-specific differences in fatty acid transport and esterification.

Project description:Many policosanols from different sources, such as sugar cane and rice bran, have been marketed worldwide to improve blood lipid profiles. But so far, no comparative study has commenced elucidating the effect of different policosanols to improve the blood lipid profile and other beneficial effects. This study compared the efficacy of four different policosanols, including one sugar cane wax alcohol from Cuba (Raydel®) and three policosanols from China (Xi'an Natural sugar cane, Xi'an Realin sugar cane, and Shaanxi rice bran), to treat dyslipidemia in hyperlipidemic zebrafish. After 12 weeks of consumption of each policosanol (final 0.1% in diet, wt/wt) and a high-cholesterol diet (HCD, final 4%, wt/wt), the Raydel policosanol group and the Xi'an Natural policosanol group showed the highest survivability, of approximately 81%. In contrast, the Xi'an Realin policosanol and the Shaanxi policosanol groups showed 57% and 67% survivability, respectively. Among the five HCD groups, the Raydel policosanol group showed the lowest serum total cholesterol (TC, p < 0.001 versus HCD control) and triglyceride (p < 0.001 versus HCD control), with the highest percentage of high-density lipoproteins-cholesterol in TC. The Raydel policosanol group also showed the lowest serum aspartate aminotransferase and alanine aminotransferase levels, with the least infiltration of inflammatory cells and interleukin-6 production in hepatocytes with a marked reduction in reactive oxygen species (ROS) production and fatty liver changes. In the ovary, the Raydel policosanol group also showed the highest content of mature vitellogenic oocytes with the lowest production of reactive oxygen species and cellular apoptosis in ovarian cells. In the testes, the Raydel policosanol group also showed the healthiest morphology for spermatogenesis, with the lowest interstitial area and reactive oxygen species production in testicular cells. Conclusively, among the tested policosanols, Cuba (Raydel®) policosanol exhibited a comparatively better effect in maintaining zebrafish body weight, survivability, blood lipid profile, hepatic function biomarkers, fatty liver changes, ROS generation, inflammation, and restoration of the cell morphology in ovaries and testes affected by the HCD consumption.

Project description:We investigated the tissue regeneration and lipid-lowering effects of policosanol (PCO) by employing a hyperlipidemic zebrafish model. A reconstituted high-density lipoprotein containing policosanol (PCO-rHDL) facilitated greater cell growth and replication with less apoptosis and reactive oxygen species (ROS) production in BV-2 microglial cell lines. From in vivo study, injection of rHDL containing apolipoprotein A-I (ApoA-I) caused 76?±?4% (p?=?0.01) greater tissue regeneration activity than the phosphate-buffered saline (PBS) control, whereas PCO-rHDL caused 94?±?7% (p?=?0.002) increased regeneration. PCO in ethanol (EtOH) showed lower cholesteryl ester transfer protein (CETP) inhibitory ability than did anacetrapib, whereas PCO-rHDL showed higher inhibitory ability than anacetrapib, suggesting a synergistic effect between PCO and rHDL. Following 9 weeks of PCO consumption, the PCO group (0.003% PCO in Tetrabit) showed the highest survivability (80%), whereas normal diet (ND) and high-cholesterol diet (HCD) control groups showed 67% and 70% survival rates, respectively. Supplementation with a HCD resulted in two-fold elevation of CETP activity along with 3- and 2.5-fold increases in serum total cholesterol (TC) and triglycerides (TGs) levels, respectively. Consumption of PCO for 9 weeks resulted in 40?±?5% (p?=?0.01 vs. HCD) and 33?±?4% (p?=?0.02 vs. HCD) reduction of TC and TGs levels, respectively. Serum high-density lipoprotein cholesterol (HDL-C) level increased up to 37?±?2?mg/dL (p?=?0.004), whereas the percentage of HDL-C/TC increased up to 20?±?2% from 5?±?1% compared to the HCD control. The serum glucose level was reduced to 47?±?2% (p?=?0.002) compared to the HCD control. Fatty liver change and hepatic inflammation levels were remarkably increased upon HCD consumption and were two-fold higher than that under ND. However, the PCO group showed 58?±?5% (p?=?0.001) and 50?±?3% (p?=?0.006) reduction of inflammation enzyme levels and lipid content in hepatic tissue under HCD. In conclusion, PCO supplementation showed lipid-lowering and HDL-C-elevating effects with ameliorating fatty liver change. These in vivo anti-atherosclerotic and anti-diabetic effects of PCO are well associated with in vitro anti-apoptotic activities.

Project description:ᅟ: The present study comprised 17,096 Chinese hypertensive dyslipidemia patients who received lipid-lowering treatment for > 3 months in order to investigate blood pressure (BP) as well as low-density lipoprotein cholesterol (LDL-C) goal attainment rates in Chinese hypertensive dyslipidemia patients on antidyslipidemia drugs. The factors that interfered with BP, or BP and LDL-C goal attainment rates and antihypertensive treatment patterns, were analyzed. In total, 89.9% of the 17,096 hypertensive dyslipidemia patients received antihypertensive medications mainly consisting of a calcium channel blocker (CCB) (48.7%), an angiotensin receptor antagonist (ARB) (25.4%) and an angiotensin-converting enzyme inhibitor (ACEI) (15.1%). In cardiology departments, usage rates of β-blockers (19.2%) were unusually high compared to other departments (4.0-8.3%), whereas thiazide diuretics were prescribed at the lowest rate (0.3% vs 1.2-3.6%). The overall goal attainment rates for combined BP and LDL-C as well as BP or LDL-C targets were 22.9, 31.9 and 60.1%, respectively. The lowest BP, LDL-C and BP combined with LDL-C goal attainment rates were achieved in endocrine departments (19.9, 48.9 and 12.4%, respectively). Combination therapies showed no benefit particularly for BP goal achievement. A multivariate logistic regression analysis showed that age < 65 years, alcohol consumption, diabetes, coronary heart disease (CHD), cerebrovascular disease (CVD), chronic kidney disease (CKD), body mass index (BMI) ≥ 28 kg/m2 and not achieving total cholesterol goals were independent predictors for achieving BP, LDL-C or combined BP and LDL-C goals. In summary, the BP and LDL-C goal achievement rates in Chinese dyslipidemia outpatients with hypertension were low, especially in endocrine departments. Combination therapies were not associated with improvement of the goal achievement rates. TRIAL REGISTRATION: Clinical trial registration number NCT01732952.

Dataset Information

Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

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Blood Pressure Lowering Effect of Cuban Policosanol is Accompanied by Improvement of Hepatic Inflammation, Lipoprotein Profile, and HDL Quality in Spontaneously Hypertensive Rats.

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