Adapalene induces adipose browning through the RARß-p38 MAPK-ATF2 pathway.

Adipose browning has recently been reported to be a novel therapeutic strategy for obesity. Because the retinoic acid receptor (RAR) is a potential target involved in browning, adapalene (AD), an anti-acne agent with RAR agonism, was examined in detail for its effects on adipose browning and the underlying mechanisms in vitro and in vivo. AD upregulated the expression of adipose browning-related markers in a concentration-dependent manner, promoted mitochondrial biogenesis, increased oxygen consumption rates, and lowered lipid droplet sizes in differentiated 3T3/L1 white adipocytes. Among the three retinoic acid receptors (RARα, RARß, and RARγ), knockdown of the gene encoding RARß mitigated AD-induced adipose browning. Similarly, LE135 (a selective RARß antagonist) attenuated AD action, suggesting that AD promotes adipose browning through RARß. Sequential phosphorylation of p38 mitogen-activated protein kinase (MAPK) and activating transcription factor 2 (ATF2) was critical for AD-induced adipose browning, based on the observations that either SB203580 (a p38 MAPK inhibitor) or ATF2 siRNA reduced the effects of AD. In vivo browning effects of AD were confirmed in C57BL/6J mice and high-fat diet-induced obese (DIO) mice after oral administration of AD either acutely or chronically. This study identifies new actions of AD as an adipose browning agent and demonstrates that RARß activation followed by increased phosphorylation of p38 MAPK and ATF2 appears to be a key mechanism of AD action.

Icosapent ethyl: safely reducing cardiovascular risk in adults with elevated triglycerides.

INTRODUCTION: In patients at high cardiovascular risk, the rate of events remains elevated despite traditional, evidence-based lipid-lowering therapy. Residual hypertriglyceridemia is an important contributor to this risk. However, prior medications with triglyceride-lowering effects have not reduced adverse clinical outcomes in the statin era. AREAS COVERED: The present review summarizes evidence and recommendations related to triglyceride-lowering therapy in the primary and secondary preventive settings. We provide an overview of findings from recent meta-analyses, important observational studies, and a detailed description of landmark trials, including the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT). We further review recommendations from current guidelines. EXPERT OPINION: Icosapent ethyl is a stable, highly purified ethyl ester of eicosapentaenoic acid that safely and effectively reduces cardiovascular events in the contemporary setting. It is prescribed at a dose of 2 grams twice daily and is indicated in patients at high cardiovascular risk who have fasting or non-fasting triglyceride levels ≥150 mg/dl despite maximally tolerated statin treatment, or in individuals with triglyceride levels ≥500 mg/dl. Conversely, omega-3 fatty acid preparations containing a combination of eicosapentaenoic acid and docosahexaenoic acid are not indicated for reduction of cardiovascular risk and should be actively deprescribed.

A structurally optimized FXR agonist, MET409, reduced liver fat content over 12 weeks in patients with non-alcoholic steatohepatitis.

BACKGROUND & AIMS: The benefits of farnesoid X receptor (FXR) agonists in patients with non-alcoholic steatohepatitis (NASH) have been validated, although improvements in efficacy and/or tolerability remain elusive. Herein, we aimed to assess the performance of a structurally optimized FXR agonist in patients with NASH. METHODS: In this 12-week, randomized, placebo-controlled study, we evaluated MET409 - a non-bile acid agonist with a unique chemical scaffold - in patients with NASH. Patients were randomized to receive either 80 mg (n = 20) or 50 mg (n = 19) of MET409, or placebo (n = 19). RESULTS: At Week 12, MET409 lowered liver fat content (LFC), with mean relative reductions of 55% (80 mg) and 38% (50 mg) vs. 6% in placebo (p <0.001). MET409 achieved ≥30% relative LFC reduction in 93% (80 mg) and 75% (50 mg) of patients vs. 11% in placebo (p <0.001) and normalized LFC (≤5%) in 29% (80 mg) and 31% (50 mg) of patients vs. 0% in placebo (p <0.05). An increase in alanine aminotransferase (ALT) was observed with MET409, confounding Week 12 changes from baseline (-25% for 80 mg, 28% for 50 mg). Nonetheless, MET409 achieved ≥30% relative ALT reduction in 50% (80 mg) and 31% (50 mg) of patients vs. 17% in placebo. MET409 was associated with on-target high-density lipoprotein cholesterol decreases (mean changes of -23.4% for 80 mg and -20.3% for 50 mg vs. 2.6% in placebo) and low-density lipoprotein cholesterol (LDL-C) increases (mean changes of 23.7% for 80 mg and 6.8% for 50 mg vs. -1.5% in placebo). Pruritus (mild-moderate) occurred in 16% (50 mg) and 40% (80 mg) of MET409-treated patients. CONCLUSION: MET409 lowered LFC over 12 weeks in patients with NASH and delivered a differentiated pruritus and LDL-C profile at 50 mg, providing the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced through structural optimization. LAY SUMMARY: Activation of the farnesoid X receptor (FXR) is a clinically validated approach for treating non-alcoholic steatohepatitis (NASH), although side effects such as itching or increases in low-density lipoprotein cholesterol are frequently dose-limiting. MET409, an FXR agonist with a unique chemical structure, led to significant liver fat reduction and delivered a favorable side effect profile after 12 weeks of treatment in patients with NASH. These results provide the first clinical evidence that the risk-benefit profile of FXR agonists can be enhanced.

Volixibat in adults with non-alcoholic steatohepatitis: 24-week interim analysis from a randomized, phase II study.

BACKGROUND & AIMS: Volixibat is an inhibitor of the apical sodium-dependent bile acid transporter (ASBT) that has been hypothesized to improve non-alcoholic steatohepatitis (NASH) by blocking bile acid reuptake and stimulating hepatic bile acid production. We studied the safety, tolerability and efficacy of volixibat in patients with NASH. METHODS: In this double-blind, phase II dose-finding study, adults with ≥5% steatosis and NASH without cirrhosis (N = 197) were randomized to receive volixibat (5, 10 or 20 mg) or placebo once daily for 48 weeks. The endpoints of a predefined interim analysis (n = 80), at week 24, were: ≥5% reduction in MRI-proton density fat fraction and ≥20% reduction in serum alanine aminotransferase levels. The primary endpoint was a ≥2-point reduction in non-alcoholic fatty liver disease activity score without worsening fibrosis at week 48. RESULTS: Volixibat did not meet either interim endpoint; the study was terminated owing to lack of efficacy. In participants receiving any volixibat dose, mean serum 7-alpha-hydroxy-4-cholesten-3-one (C4; a biomarker of bile acid synthesis) increased from baseline to week 24 (+38.5 ng/ml [SD 53.18]), with concomitant decreases in serum total cholesterol (-14.5 mg/dl [SD 28.32]) and low-density lipoprotein cholesterol (-16.1 mg/dl [SD 25.31]). These changes were generally dose-dependent. On histological analysis, a greater proportion of participants receiving placebo (38.5%, n = 5/13) than volixibat (30.0%, n = 9/30) met the primary endpoint. Treatment-emergent adverse events (TEAEs) were mainly mild or moderate. No serious TEAEs were related to volixibat. Diarrhoea was the most common TEAE overall and the most common TEAE leading to discontinuation. CONCLUSIONS: Increased serum C4 and decreased serum cholesterol levels provide evidence of target engagement. However, inhibition of ASBT by volixibat did not elicit a liver-related therapeutic benefit in adults with NASH. LAY SUMMARY: A medicine called volixibat has previously been shown to reduce cholesterol levels in the blood. This study investigated whether volixibat could reduce the amount of fat in the liver and reduce liver injury in adults with an advanced form of non-alcoholic fatty liver disease. Volixibat did not reduce the amount of fat in the liver, nor did it have any other beneficial effect on liver injury. Participants in the study generally tolerated the side effects of volixibat and, as in previous studies, the main side effect was diarrhoea. These results show that volixibat is not an effective treatment for people with fatty liver disease. CLINICAL TRIAL IDENTIFIER: NCT02787304.

Impact of omega-3 fatty acid oral therapy on healing of chronic venous leg ulcers in older adults: Study protocol for a randomized controlled single-center trial.

BACKGROUND: This trial addresses the global problem of chronic venous leg ulcers (CVLUs), wounds that cause significant infirmity for an estimated 9.7 million people annually, mainly older adults with comorbidities. Advanced therapies are needed because standard topical therapies are often ineffective or yield only short-term wound healing. Thus, we are testing a new oral therapy containing the bioactive elements of fish oil, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for targeting and reducing the high numbers of activated polymorphonuclear leukocytes (PMN) in wound microenvironments that keep CVLUs "trapped" in a chronic inflammatory state. METHODS: This double-blind RCT will include 248 eligible adults ≥ 55 years of age with CVLUs receiving standard care at a large Midwest outpatient wound clinic. Participants are randomized to two groups: 12 weeks of daily oral therapy with EPA + DHA (1.87 g/day of EPA + 1.0 g/day of DHA) or daily oral therapy with placebo. At 0, 4, 8, and 12 weeks, across the two groups, we are pursuing three specific aims: Aim 1. Compare levels of EPA + DHA-derived lipid mediators, and inflammatory cytokines in blood and wound fluid; Subaim 1a. Compare inflammatory cytokine gene expression by PMNs in blood; Aim 2. Compare PMN activation in blood and wound fluid, and PMN-derived protease levels in wound fluid; Aim 3. Compare reduction in wound area, controlling for factors known to impact healing, and determine relationships with lipid mediators, cytokines, and PMN activation. Subaim 3a. Compare frequency of CVLU recurrence and levels of study variables in blood between the randomly assigned two subgroups (continuing EPA + DHA therapy versus placebo therapy beyond week 12) within the EPA + DHA group with healed CVLUs after 3 months of therapy. Subaim 3b. Compare symptoms of pain at all time points and quality of life at first and last time points across the two groups and two subgroups. DISCUSSION: This trial will provide new evidence about the effectiveness of EPA + DHA oral therapy to target and reduce excessive PMN activation systemically and locally in patients with CVLUs. If effective, this therapy may facilitate healing and thus be a new adjunct treatment for CVLUs in the aging population. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03576989; Registered on 13 June 2018.

Association of Non-LDL Indices with Recurrent Stroke Risk while on Lipid-Modifying Therapy.

AIMS: Low-density lipoprotein (LDL)-lowering statin therapy is an established secondary stroke prevention strategy. However, the differential impact of key non-LDL levels on recurrent stroke risk, while on lipid-modifying therapy (LT), remains unclear. METHODS: We analyzed the dataset of a multicenter trial involving 3640 recent (＜4 months) noncardioembolic stroke patients followed for 2 years. Participants were categorized into four groups of presumed improving lipid profile: level 0, no LT prescribed; level I, LT use with low high-density lipoprotein cholesterol (HDL-C) (＜40 mg/dL for men; ＜50 mg/dL for women); level II, LT use with high HDL-C (≥ 40 mg/dL and ≥ 50 mg/dL, respectively); and level III, level II with low triglycerides (＜150 mg/dL). Independent associations of LT category with stroke, major vascular events (MVEs; stroke/coronary heart disease/vascular death), and all-cause death were assessed. RESULTS: LTs were mostly statins (＞95%). The unadjusted recurrent stroke rate declined with LT category level (9.2% for level 0; 8.4% for level I; 7.5% for level II; and 5.7% for level III). Compared with level 0, the adjusted hazard ratio of stroke for level I was 0.78 (95% confidence interval (CI), 0.59-1.03), level II 0.80 (0.54-1.18), and level III 0.63 (0.43-0.91). Multivariable analyses of MVEs and all-cause death followed a similar pattern of declining risk with higher LT category level. CONCLUSIONS: Compared with the nonuse of LT, there may be a hierarchy of residual vascular risk after stroke by non-LDL type and target, while on LT. Particularly, stroke patients with low HDL-C levels on LT may benefit from additional therapeutic strategies to improve their outcomes.

Datos de vida real en el uso de IPCSK9 / Real life data on the use of inhibitors of proprotein convertase subtilisin/kexine type 9

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Slowing down lipolysis significantly enhances the oral absorption of intact solid lipid nanoparticles.

Only a limited amount of orally administered lipid nanoparticles are absorbed as intact particles due to lipolysis by lipases in the gastrointestinal tract. It is hypothesized that by counteracting lipolysis, more particles will survive gastrointestinal digestion and be absorbed as intact particles. In this study, incorporation of a lipase inhibitor orlistat (OLST), as well as polyethylene glycol (PEG) coating, is employed to slow down the lipolysis using solid lipid nanoparticles (SLNs) as model particles. To explore the in vivo behaviors of the particles, near-infrared fluorescent probes with absolute aggregation-caused quenching (ACQ) properties are used to label and track the unmodified, PEG-coated and OLST-loaded SLNs. The in vitro lipolysis study indicates very fast first-order degradation of unmodified SLNs and significantly decreased degradation of OLST-SLNs. Live imaging reveals the same trend of slowed-down lipolysis in vivo which correlates well with the in vitro lipolysis. The scanning of ex vivo gastrointestinal segments confirms the considerably prolonged residence time of OLST-SLNs, mirroring the significantly decreased lipolysis rate. The observation of fluorescence in the blood, though very weak, and in the liver speaks of the oral absorption of intact SLNs. The substantially higher hepatic levels of OLST-SLNs than unmodified SLNs should be attributed to the significantly enhanced survival rate because both particles exhibit similar cellular recognition as well as similar physicochemical properties except for the survival rate. Similarly, slowing down lipolysis also contributes to the significantly enhanced cumulative lymphatic transport of OLST-SLNs (7.56% vs. 1.27% for the unmodified SLNs). The PEG coating slows down the lipolysis rate as well but not to the degree as done by OLST. As a result, the gastrointestinal residence time of PEG-SLNs has been moderately prolonged and the hepatic levels moderately increased. The weakened cellular recognition of PEG-SLNs implies that the enhanced oral absorption is solely ascribed to the slowed-down lipolysis and enhanced mucus penetration. In conclusion, the oral absorption of intact SLNs can be significantly enhanced by slowing down lipolysis, especially by OLST, showing potential as carriers for the oral delivery of labile biomacromolecules.

Pharmacologic and Pharmacodynamic Equivalence of 2 Formulations of Orlistat.

We sought to establish the bioequivalence of 2 weight-loss aids: orlistat 27-mg chewable tablet and orlistat 60-mg capsule, measured pharmacodynamically as percentage fecal fat excretion. Two open-label, single-center, randomized, 3-period, 3-treatment crossover studies were conducted in adults with body mass index 25-33 kg/m2 . For each 9-day treatment period, subjects received orlistat 27-mg chewable tablet, 60-mg capsule, or 120-mg capsules (2 60-mg capsules) 3 times daily; a 2-day washout separated treatments. Primary bioequivalence analyses were based on 2 1-sided tests of the 90% CI of the ratio of geometric means using log-transformed data (study 1) and by the dose-scale method to calculate bias-corrected and accelerated 90% CI of relative bioavailability (f) using nontransformed data (study 2). Bioequivalence was established if 90% CIs fell within 0.80-1.25. In total, 48 and 144 subjects were randomized in study 1 and study 2, respectively. Bioequivalence between the formulations was established in both studies: study 1 ratio of geometric means of percentage fecal fat excretion was 0.96 (2 1-sided tests, 90% CI 0.87-1.06); study 2-point estimate of f was 1.09 (bias-corrected and accelerated 90% CI 0.98-1.22). Tolerability of the 27-mg tablet was consistent with the 60-mg capsule; mild gastrointestinal effects were most common.

A randomised, double-blind, placebo-controlled phase 1 study of the safety, tolerability and pharmacodynamics of volixibat in overweight and obese but otherwise healthy adults: implications for treatment of non-alcoholic steatohepatitis.

BACKGROUND: Accumulation of toxic free cholesterol in hepatocytes may cause hepatic inflammation and fibrosis. Volixibat inhibits bile acid reuptake via the apical sodium bile acid transporter located on the luminal surface of the ileum. The resulting increase in bile acid synthesis from cholesterol could be beneficial in patients with non-alcoholic steatohepatitis. This adaptive dose-finding study investigated the safety, tolerability, pharmacodynamics, and pharmacokinetics of volixibat. METHODS: Overweight and obese adults were randomised 3:1 to double-blind volixibat or placebo, respectively, for 12 days. Volixibat was initiated at a once-daily dose of 20 mg, 40 mg or 80 mg. Based on the assessment of predefined safety events, volixibat dosing was either escalated or reduced. Other dose regimens (titrations and twice-daily dosing) were also evaluated. Assessments included safety, tolerability, stool hardness, faecal bile acid (FBA) excretion, and serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and lipids. RESULTS: All 84 randomised participants (volixibat, 63; placebo, 21) completed the study, with no serious adverse events at doses of up to 80 mg per day (maximum assessed dose). The median number of daily bowel evacuations increased from 1 (range 0-4) to 2 (0-8) during volixibat treatment, and stool was looser with volixibat than placebo. Volixibat was minimally absorbed; serum levels were rarely quantifiable at any dose or sampling time point, thereby precluding pharmacokinetic analyses. Mean daily FBA excretion was 930.61 µmol (standard deviation [SD] 468.965) with volixibat and 224.75 µmol (195.403) with placebo; effects were maximal at volixibat doses ≥20 mg/day. Mean serum C4 concentrations at day 12 were 98.767 ng/mL (standard deviation, 61.5841) with volixibat and 16.497 ng/mL (12.9150) with placebo. Total and low-density lipoprotein cholesterol levels decreased in the volixibat group, with median changes of - 0.70 mmol/L (range - 2.8 to 0.4) and - 0.6990 mmol/L (- 3.341 to 0.570), respectively. CONCLUSIONS: This study indicates that maximal inhibition of bile acid reabsorption, as assessed by FBA excretion, occurs at volixibat doses of ≥20 mg/day in obese and overweight adults, without appreciable change in gastrointestinal tolerability. These findings guided dose selection for an ongoing phase 2 study in patients with non-alcoholic steatohepatitis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02287779 (registration first received 6 November 2014).

Prevalencia de dislipidemias en la región capital: resultados preliminares del estudio EVESCAM / Prevalence of dyslipidemias in the capital region: preliminary results of the EVESCAM study

Las dislipidemias son un factor de riesgo para enfermedades cardiovasculares. Se desconoce la prevalencia actual de dislipidemias en la región Capital de Venezuela. Objetivo: Determinar la prevalencia de dislipidemias en adultos de la región capital evaluados en el estudio EVESCAM. Métodos: Estudio poblacional, observacional, transversal de muestreo aleatorio poliestratificado por conglomerados. Se evaluaron 7 comunidades de la Región Capital desde julio de 2015 hasta enero de 2016: El Retiro; Miranda Casco Central y Bello Campo; Los Teques: La Cima; Guatire: Centro y Castillejo y rural: Guatire: La Candelaria. Participaron 416 sujetos desde los 20 años de edad. Los puntos de corte para definir las dislipidemias fueron hipoalfalipoproteinemia: colesterol HDL < 40 mg/dL; hipertrigliceridemia: triglicéridos (TG) ≥ 150 mg/dL; hipercolesterolemia: colesterol total ≥ 200 mg/dL; colesterol LDL elevado: colesterol LDL ≥ de 130 mg/dL; dislipidemia aterogénica: TG ≥ 150 mg/dL más colesterol HDL bajo (mujeres: < 40 mg/dl y hombres: < 50 mg/dl). Las frecuencias se expresaron en porcentajes y se aplicó el estadístico Chi cuadrado, un valor de p < 0,05 fue considerado como estadísticamente significativo. Resultados: La dislipidemia con mayor prevalencia fue la hipoalfalipoproteinemia (67.1%) seguida de la LDLc elevada (20%), hipercolesterolemia (17,1%), hipertrigliceridemia (12,0%) y por último dislipidemia aterogenica (9,4%). La hipoalfalipoproteinemia, fue mayor en hombres que en mujeres (81,6% y 60,8%; respectivamente, p < 0,001) presentándose con mayor prevalencia en el grupo etario de 20 a 40 años al contrario del resto de las dislipidemias. Conclusión: La hipoalfalipoproteinemia persiste como la dislipidemia más prevalente de la región(AU)

Dyslipidemias are a risk factor for cardiovascular diseases. The current prevalence of dyslipidemias in the Capital Region of Venezuela is unknown. Objective: To determine the prevalence of dyslipidemias in adults from the capital region of Venezuela evaluated in the EVESCAM study. Methods: apopulation based, observational, cross-sectional, and cluster sampling study was desing. Seven communities from the Capital Region were evaluated from July 2015 to January 2016: El Retiro; Miranda- Chacao: Casco Central y Bello Campo; Los Teques: La Cima; Guatire: Centro y Castillejo y Rural: Guatire: Candelaria. 416 subjects were included. Dyslipidemias was define as hypoalphalipoproteinemia: HDL cholesterol <40 mg/ dL; hypertriglyceridemia: triglycerides ≥ 150 mg/dL; hypercholesterolemia: total cholesterol ≥ 200 mg/dL; High LDL cholesterol: ≥ 130 mg/dL; therogenic dyslipidemia: triglycerides ≥ 150 mg / dL and low HDL cholesterol (women: <40 mg / dl and men: <50 mg / dl). The frequencies were expressed as percentages and Chi-square test was applied to assess differences. The level of statistical significance accepted was a p-value < 0.05. Results: The most prevalent dyslipidemia was hypoalphalipoproteinemia (67.1%) followed by elevated LDLc (20%), hypercholesterolemia (17.1%), hypertriglyceridemia (12.0%), and atherogenic dyslipidemia (9.4%). Hypoalphalipoproteinemia was higher in men than women (81.6% and 60.8%, respectively, p <0.001), with a higher prevalence at the age group of 20 to 40 years, unlike the rest of dyslipidemias. Conclusion: The hypoalphalipoproteinemia persists as the most prevalent dyslipidemia in the region(AU)

[Blood fatty acids in the development and correction of metabolic syndrome]. / Zhirnye kisloty krovi v formirovanii i korrektsii metabolicheskogo sindroma.

AIM: to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA). SUBJECTS AND METHODS: Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA. RESULTS: Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells. CONCLUSION: The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.

Selection of the Optimal Herbal Compositions of Red Clover and Pomegranate According to Their Protective Effect against Climacteric Symptoms in Ovariectomized Mice.

This study aimed to ascertain the optimal range of red clover dry extracts (RC) and dried pomegranate concentrate powder (PCP) to induce anti-climacteric effects. Thus, the dose ranges showing protective effect of mixed formulae consisting of RC and PCP were examined in ovariectomized mice. At 28 days after bilateral ovariectomy (OVX), mixed herbal compositions (RC:PCP = 1:1, 1:2, 1:4, 1:8, 2:1, 4:1, and 8:1) were administered orally, at 120 mg/kg once daily for 84 days. We evaluated that RC and PCP mixture attenuate OVX-caused obesity, hyperlipidemia, hepatic steatosis, and osteoporosis. Compared to OVX-induced control mice, body weight and abdominal fat weight in OVX-induced mice were significantly decreased, concomitantly with increase of uterus weight by RC:PCP mixture. Additionally, significant increases in serum estradiol levels were observed in all RC:PCP-treated mice. RC:PCP mixture also showed protective effect against OVX-induced hyperlipidemia, hepatic steatosis. Total body and femur mean bone mineral density (BMD), osteocalcin, bALP contents were effectively increased by RC:PCP mixture. Taken together, RC:PCP mixture (2:1, 1:1, and 4:1) has remarkable protective effects against the changes induced by OVX. In particular, RC:PCP mixture (2:1) shows the strongest effect and may be considered as a potential protective agent against climacteric symptoms.

Antilipogenic and anti-inflammatory activities of Codonopsis lanceolata in mice hepatic tissues after chronic ethanol feeding.

This study evaluated the antilipogenic and anti-inflammatory effects of Codonopsis lanceolata (C. lanceolata) root extract in mice with alcohol-induced fatty liver and elucidated its underlying molecular mechanisms. Ethanol was introduced into the liquid diet by mixing it with distilled water at 5% (wt/v), providing 36% of the energy, for nine weeks. Among the three different fractions prepared from the C. lanceolata root, the C. lanceolata methanol extract (CME) exhibited the most remarkable attenuation of alcohol-induced fatty liver with respect to various parameters such as hepatic free fatty acid concentration, body weight loss, and hepatic accumulations of triglyceride and cholesterol. The hepatic gene and protein expression levels were analysed via RT-PCR and Western blotting, respectively. CME feeding significantly restored the ethanol-induced downregulation of the adiponectin receptor (adipoR) 1 and of adipoR2, along with their downstream molecules. Furthermore, the study data showed that CME feeding dramatically reversed ethanol-induced hepatic upregulation of toll-like receptor- (TLR-) mediated signaling cascade molecules. These results indicate that the beneficial effects of CME against alcoholic fatty livers of mice appear to be with adenosine- and adiponectin-mediated regulation of hepatic steatosis and TLR-mediated modulation of hepatic proinflammatory responses.

The role of red yeast rice for the physician.

Red yeast rice is an ancient Chinese dietary staple and medication used by millions of patients as an alternative therapy for hypercholesterolemia. In recent years, the use of red yeast rice has grown exponentially due to increased public interest in complementary and alternative medications and the publication of several randomized, controlled trials demonstrating its efficacy and safety in different populations. The most promising role for red yeast rice is as an alternative lipid-lowering therapy for patients who refuse to take statins because of philosophical reasons or patients who are unable to tolerate statin therapy due to statin-associated myalgias. However, there is limited government oversight of red yeast rice products, wide variability of active ingredients in available formulations, and the potential of toxic byproducts. Therefore, until red yeast rice products are regulated and standardized, physicians and patients should be cautious in recommending this promising alternative therapy for hyperlipidemia.