Increase In High-density Lipoprotein Cholesterol Research Articles

Fat-1 expression alleviates atherosclerosis in transgenic rabbits.

Atherosclerosis is the main cause of cardiovascular diseases. The Fat‐1 gene can express the n‐3 fatty acid desaturase, which converts n‐6 polyunsaturated fatty acids (PUFA) to n‐3 PUFAs. The role of n‐3 PUFAs in atherosclerosis is widely debated. This study explored the effect of n‐3 PUFAs on atherosclerosis in rabbits. In this study, atherosclerosis was induced in Fat‐1 transgenic rabbits and their littermate (WT) rabbits by feeding a high‐cholesterol diet containing 0.3% cholesterol and 3% soybean oil for 16 weeks. Plasma lipid, fatty acid and pathological analyses of atherosclerotic lesions were conducted. Fatty acid composition in the liver and muscle showed that n‐3 PUFAs increased and n‐6 PUFAs decreased in the Fat‐1 group. Plasma high‐density lipoprotein cholesterol (HDL‐C) levels were significantly increased in the Fat‐1 group, and the atherosclerotic lesion area of the aortic arch in Fat‐1 transgenic rabbits was significantly reduced. Histological analysis showed that smooth muscle cells (SMCs) in atherosclerotic lesions decreased significantly. In conclusion, n‐3 PUFAs improve atherosclerosis in Fat‐1 transgenic rabbits, and this process may depend on the increase in plasma HDL‐C and the decrease in the amount of SMCs in atherosclerotic plaques.

The Effects and Safety of Chinese Herbal Medicine on Blood Lipid Profiles in Placebo-Controlled Weight-Loss Trials: A Systematic Review and Meta-Analysis

This study was conducted to assess the effects and safety of Chinese herbal medicine (CHM) on blood lipids among adults with overweight or obesity. Fourteen bibliographic databases were comprehensively searched, from their respective inceptions up to April 2021, for randomised placebo-controlled weight-loss trials using CHM formulation on total cholesterol, triglycerides, LDL cholesterol, and HDL cholesterol over ≥4 weeks. Data collection, risk of bias assessment, and statistical analyses were guided by the Cochrane Handbook (v6.1). Continuous outcomes were expressed as the mean difference with 95% confidence intervals, and categorical outcomes were expressed as a risk ratio with 95% confidence intervals. All analyses were two-tailed with a statistical significance of p < 0.05. Fifteen eligible studies with 1,533 participants were included in this meta-analysis. Findings from meta-analyses indicated that CHM interventions, compared to placebo, reduced triglyceride (MD −0.21 mmol/L, 95% CI −0.41 to −0.02, I2 = 81%) and increased HDL cholesterol (MD 0.16 mmol/L, 95% CI 0.04 to 0.27, I2 = 94%) over a median of 12 weeks. The reduction in total cholesterol and LDL cholesterol were not statistically significant. Furthermore, the tendency of reduced triglycerides was identified among overweight participants with high baseline triglycerides. Attrition rates and frequency of adverse events were indifferent between the two groups. CHM may provide lipid-modulating benefits on triglycerides and HDL cholesterol among participants with overweight/obesity, with the tendency for significant triglyceride reduction observed among overweight participants with high baseline triglycerides. However, rigorously conducted randomised controlled trials with larger sample sizes are required to validate these findings.

Recombinant Hirudin Protects the Vasculature and Myocardium in Atherosclerotic Rats by Inhibiting the p38 MAPK/NF-kB Signaling Pathway

Recombinant hirudin (r-hirudin) has a good anticoagulant effect and has a certain inhibitory effect on atherosclerosis (AS), however, its intrinsic mechanism of inhibiting AS is still unclear. In this study, we investigated the mechanism underlying the vascular and myocardial protective effects of r-hirudin in AS rats through animal experiments. A rat AS model was established by high-fat diet feeding combined with common carotid artery balloon injury. The model rats were given low, medium, or high doses of r-hirudin (0.05, 0.1, or 0.2 mg/kg/ day), simvastatin tablets (1 mg/kg/day) and p38 mitogen-activated protein kinase (MAPK) pathway inhibitors (SB203580, 100 mg/kg/day) by gavage for 8 weeks. The results showed that in AS rats, r-hirudin significantly alleviated pathological changes in the common carotid artery and myocardial tissue; decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels; increased highdensity lipoprotein-cholesterol (HDL-C) levels; decreased serum oxidized low-density lipoprotein (ox-LDL), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and endothelin (ET)-1 levels; increased nitric oxide (NO) levels; and decreased p38 MAPK, nuclear factor-kappa B (NF-κB), caspase-9, caspase-3 mRNA and protein expression. This study showed that r-hirudin may protect blood vessels and the myocardium in AS rats by adjusting blood lipid levels and inhibiting the p38 MAPK/NF-κB signaling pathway to exert anti-inflammatory and anti-apoptotic effects and protect the vascular endothelium.

A Review On The Potential Of Spirulina And Its Application In Nutraceuticals And Pharmaceuticals

Microalgae and lactic acid bacteria have become an innovative and promising resource of nutritional supplements as they are commercially cultivated to produce valuable compounds, including protein, pigments, lipids, essential amino acids, monounsaturated and polyunsaturated fatty acids, carotenoids, steroids and vitamins. The pharmacological actions, such as nutraceutical improvements, lowering LDL cholesterol levels, anti-inflammation, antioxidation, antitumor, immunological enhancement, and hepatorenal protection from Spirulina spp and Lactic acid Bacillus have been reported recently. Based on the therapeutic potential of spriulina fermentation based lactic acid bacteria, different application studies such as, determining the effect of Spirulina fermentation with Lactic acid bacteria (FSL) on enhancing the Nutraceutical properties of Spirulina species, investigating the effect of Spirulina fermentation with Lactic acid bacteria (FSL) on lowering the LDL cholesterol and increasing HDL cholesterol, and evaluating the cytotoxic effect and influence of FSL on human cancer cell line was reviewed in the current article.

Effects of Long-Acting Somatostatin Analogues on Lipid Metabolism in Patients with Newly Diagnosed Acromegaly: A Retrospective Study of 120 Cases.

The short-term effects of long-acting somatostatin analogues (SSAs) on lipid profiles in patients with acromegaly are not well studied. We retrospectively analyzed the effects of SSAs on lipid profiles and associated cardiovascular risk factors in a cohort of 120 newly diagnosed acromegaly patients. In this study, 69 females and 51 males were included. These patients were treated with either octreotide LAR (OCT) or lanreotide SR (LAN) for 3 months. After SSAs treatment, both GH and IGF-1 significantly decreased (p<0.001). Triglyceride (TG), total to high-density lipoprotein cholesterol (HDL-C) ratio, and lipoprotein (a) [Lp(a)] levels were significantly decreased, while HDL-C levels were increased (p<0.05). The reduction of mean serum GH (GHm) was positively associated with the decrease of TG (r=0.305, p=0.001) and Lp(a) (r=0.257, p=0.005), as well as the increase of HDL-C (r=-0.355, p<0.001). The changes of lipid profiles were observed only in OCT group, but not in LAN group. In addition, systolic blood pressure (SBP) had significantly declined after SSAs treatment, with an average reduction of 4.4 mmHg (126.7±1.28 vs. 122.3±1.44 mmHg, p=0.003), while no change was observed regarding diastolic blood pressure (DBP) (p>0.05). Fasting insulin, fasting C-peptide, and HOMA-IR were significantly decreased after SSAs treatment. In conclusion, our current study revealed that short-term SSAs treatment improves lipid profiles and other cardiovascular risk factors in patients with acromegaly.

Effects of n-6 PUFA-rich soybean oil, MUFA-rich olive oil and camellia seed oil on weight and cardiometabolic profiles among Chinese women: a 3-month double-blind randomized controlled-feeding trial.

Previous studies have suggested that replacing saturated fat with unsaturated fat is beneficial for cardiometabolic health. However, research that directly compares the effects of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs) is rare. The present 3-month, three-arm, randomized, controlled-feeding trial aimed to investigate the effects of n-6 PUFA- and MUFA-rich cooking oils on body weight and cardiometabolic profiles among middle-aged and elderly Chinese women at high cardiovascular risk. Ninety participants were recruited and randomly assigned to groups fed diets using n-6 PUFA-rich soybean oil (SO, n = 30), MUFA-rich olive oil (OO, n = 30), and MUFA-rich camellia seed oil (CSO, n = 30) as cooking oils considering traditional Chinese eating habits for 3 months. Participants were required to eat only the foods provided for lunch and dinner, and avoid intake of edible oils in breakfast. Body weight and cardiovascular profiles were measured at the baseline, middle, and end of the intervention, and group differences in changes of outcomes during intervention were examined by a linear mixed model. We found no significant difference in the changes of body weight among the SO group (mean change, 0.31 kg; 95% CI, -0.88 to 0.27), the OO group (mean change, -0.13 kg; 95% CI, -0.62 to 0.36), and the CSO group (mean change, -0.72 kg; 95% CI, -1.38 to -0.07). For secondary outcomes, the OO group showed a slight increase in HDL cholesterol (P = 0.03), while the CSO group showed greater reduction in aspartate aminotransferase (AST) (P = 0.02) when compared with the SO group. These results suggested that MUFA-rich OO and CSO exerted more favorable effects on cardiometabolic profiles among middle-aged and elderly Chinese women at high cardiovascular risk than the n-6 PUFA-rich SO.

Evaluation of the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia in the secondary health care in the Brazilian Unified Health System (SUS)

Cardiovascular diseases (CVD) are one of the main causes of mortality in the world. Dyslipidemia treatment can reduce the number of deaths caused by CVD, by decreasing the lipid profile. Evaluate the pharmacotherapeutic follow-up effectiveness in patients with dyslipidemia, regarding clinical and laboratory aspects. A quasi-experimental trial was performed in 12 months. The studied population was included patients with dyslipidemia who received a pharmacotherapeutic follow-up, which was evaluated according to the Pharmacotherapy Workup developed by the Brazilian Ministry of Health. Clinical and laboratory evaluations were performed at the baseline, after a 6 and 12-months period. The statistical analyzes were performed with the normality test of Lilliefors, Cramer Von Misses, and Anderson Darling, later the t-paired test. This study demonstrated that after 6-months of intervention, statistically significant results were verified in the reduction of LDL-cholesterol, total cholesterol, increase in HDL-cholesterol, and reduction in the blood pressure. It was observed that for high-risk patients, the achievement of targets in the lipid profile and HbA1C occurred only after 12-months, because, this population needs more aggressive targets and expressive interventions. Pharmacotherapeutic follow-up in patients with dyslipidemia reduced lipid blood levels and promoted positive clinical and laboratory outcomes.

A COMPARATIVE STUDY OF LIPID PROFILE IN CHRONIC ALCOHOLICS AND NON ALCOHOLICS IN TERTIARY HOSPITAL

BACKGROUND: Alcoholism is a signicant threat to public health in developed and developing countries. Over the last 30-40 years, alcohol consumption has increased in quantity and frequency. Alcohol use predisposes subjects to changes in lipid prole associated with coronary risk. AIM: 1] To study lipid prole in chronic alcoholics by measuring serum total cholesterol triglycerides, HDL, LDLand VLDL. 2]To compare lipid prole changes in chronic alcoholics and non-alcoholics MATERIALS AND METHODS: A Hospital-based cross-sectional study was conducted with patients attending the General Medicine department in Santhiram medical college and general hospital, of which 30 alcoholic and 30 non-alcoholic were taken into the present study. RESULTS: There was a signicant rise in TC, TGL, HDL, LDL and VLDL of chronic alcoholics compared with non-alcoholics with p-value 0.001, &lt;0.001, 0.004, 0.290, &lt;0.001, respectively. Lipid prole was compared among moderate and heavy drinkers and found increased levels of TC, TGL, LDL&amp; VLDL with p-value &lt;0.001, 0.001, 0.002 &amp; 0.001 respectively in heavy drinkers. There is a decrease in HDLcholesterol among heavy drinkers compared with moderate drinkers, p-value 0.011, which is signicant. But remains elevated compared to non-alcoholics. CONCLUSION: This study shows that alcohol intake increases lipid parameters. Moderate alcohol intake increases HDL cholesterol, whereas heavy alcohol consumption increases TC, TGL, LDL&amp; VLDLand decreases HDL.

Effect of yoga on cardiac autonomic tone and lipid profile in perimenopausal women

Introduction: Cardiovascular diseases and cholesterol levels are increased postmenopausal/perimenopausal women. Cardiac autonomic tone as assessed with heart rate variability (HRV) is also altered in postmenopausal women. Yoga practice improves vasomotor symptoms in postmenopausal women. Whether yoga can improve HRV and cholesterol levels in perimenopausal women is not clear. Methods: Sixty perimenopausal women, not on any medication, were randomized into two groups; yoga (n=30, age 44±2.64 years) and control (n=30, age 46±5.09 years). The yoga group practiced meditation, pranayama, and few simple asanas for 40 min/day, 6 days/week for four weeks along with their daily routine activities. The control group practiced no additional exercises except their daily routine activities. Short-term HRV, lipid profile, and other biochemical parameters were assessed at the beginning and after four weeks and compared. Results: Both groups were comparable in terms of their age body mass index (BMI), blood pressure (BP), heart rate (HR), and respiratory rate at 0 week. The yoga group showed a decrease in BMI, HR, systolic BP, total cholesterol [167.81±32.69 vs 144.46±26.98 mg/dl, p=0.013], LDL-cholesterol [118.19±28.25 vs 94.33±23.55 mg/dl, 0.002]; and an increase in HDL-cholesterol (49.62±6.34 vs 56.37±8.19 mg/dl, p=0.004), markers of cardiac parasympathetic tone [SDNN {33.3(24.35-40.1) vs 43.2(34.4-50.1) ms, p=0.041}, rMSSD {25.2(21.95-33.05) vs 30.6(25.1-38.0) ms, p=0.034}, and high frequency power] after four weeks of yoga practice. Conclusion: Parasympathetic tone and HDL-cholesterol increased, whereas total and LDL-cholesterol, BMI, HR, and systolic BP decreased in perimenopausal women after four weeks of yoga practice. It is suggested that yoga can be a cardio-protective alternative therapeutic measure in perimenopausal women.

Diabetic Cardiovascular Autonomic Neuropathy: Effects of Simvastatin and Omega-3 Polyunsaturated Fatty Acids on Insulin Resistance and Lipid Profile Parameters

Introduction. Currently, there is no unified treatment algorithm of cardiac autonomic neuropathy (CAN) in patients with type 2 diabetes mellitus (T2DM). The aim of the study was to investigate the effects of simvastatin (SIM) and -3 polyunsaturated fatty acids (-3 PUFAs) on blood lipid profile and insulin resistance (IR) in patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Materials and methods. The study involved 72 patients with T2DM and definite CAN. Patients were divided into four groups: 1st - received standard hypoglycemic therapy - control (n = 15); 2nd (n = 22) – in addition simvastatin (SIM) 20.0 mg/q.d.; 3rd (n = 18) - in addition 1 capsule/q.d. of the ω-3 PUFAs; 4th (n = 17) - in addition SIM 10.0 mg/q.d and 1 capsule/q.d of the ω-3 PUFAs for three months. The concentration of glucose, glycated hemoglobin A1c, immunoreactive insulin (IRI), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG) in the blood were determined. Homeostasis model assessment IR (HOMA-IR), atherogenic coefficient (AC), TG/LDL-C, TG/TC, TG/LDL-C and TG and glucose index (TyG) were calculated. Results. Prescription of SIM was accompanied by a statistically significant decrease in TC, LDL-C, TG concentrations. In parallel, SIM induced a decrease of AC, TG/HDL-C, increase in HDL-C, and does not affect the IRI, HOMA-IR, TG/LDL-C, TG/TC, TC/LDL-C/HDL-C, TyG. The use of ω-3 PUFAs has contributed to a significant reduction in TG, AC, TG/LDL-C, TG/TC, TG/HDL-C, TyG index, increase in HDL-C, and was not accompanied by changes in IRI content, HOMA-IR, TC, LDL-C, and TC/LDL-C/HDL-C. The combined prescription of SIM and -3 PUFAs was accompanied by more pronounced, statistically significant changes in the blood lipid spectrum, as well as a decrease in the IRI and HOMA-IR. Conclusions. Obtained results justify the appropriateness of combined simvastatin and -3 polyunsaturated fatty acids prescription to patients with type 2 diabetes mellitus and definite cardiac autonomic neuropathy. Keywords: diabetes mellitus, cardiac autonomic neuropathy, treatment.

Decrease of LDL Cholesterol through Increase of HDL Cholesterol by Administering Garcinia mangostana L. Peel Extract in White Mice

Highlight:Ethanol extract of Garcinia mangostana L. peel reduce malondialdehyde.Garcinia mangostana L. peel extract can increase non-radical products which impact in decreasing LDL cholesterol and increasing HDL cholesterol. Abstract:Atherosclerosis contributes to coronary heart disease which may lead to fatality. High cholesterol consumption, stress, and smoking can increase LDL cholesterol in the blood. Consumption of unsaturated fats, high fiber foods, exercise, quitting smoking, losing weight, and giving hypolipidemic drugs, especially herbs, can increase HDL cholesterol and decrease LDL cholesterol. Garcinia mangostana L. peel extract can decrease LDL cholesterol by increasing reverse HDL cholesterol transport to the liver. The study used post test control group design. This study was experimental laboratory research with population of hypercholesterolemic male white mice aged 3-4 weeks with 100-200 grams weight. The HDL and LDL cholesterol data were collected through an enzymatic method by spectrophotometer. This study used analysis of variance (Anova) with significance level of α &lt;0.05. The experiment divided the subjects into positive and negative control groups with dosage variations of 50, 150, 250, and 350 mg/kgBW. Examination of hypercholesterolemia in white mice was conducted on the 8th day. The examination of HDL and LDL cholesterol given peel extract of Garcinia mangostana L. was conducted on the 22nd day. The analysis showed that giving Garcinia mangostana L. peel extract for various dosages could significantly decrease LDL cholesterol and increase HDL cholesterol (p &lt;0.05). Peel extract of Garcinia mangostana L. that contained mangosteen could increase non-radical products that could prevent the transfer of ester cholesterol from HDL to VLDL which impact in increasing HDL cholesterol and decreasing LDL cholesterol.

A Significant Increase of Estimated Glomerular Filtration Rate After Switching From Fenofibrate to Pemafibrate in Type 2 Diabetic Patients.

BackgroundDyslipidemia is one of the major risk factors for cardiovascular disease (CVD), along with hypertension, diabetes, smoking and obesity. Approximately 70% of CVD risk remains even after treatment of elevated low-density lipoprotein-cholesterol (LDL-C) by statins. High triglyceride (TG) and low high-density lipoprotein-cholesterol (HDL-C) level are potential therapeutic targets to prevent CVD. Fibrates were associated with a greater reduction in TG, and a greater increase in HDL-C. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). Fibrates improve atherogenic dyslipidemia by mediating PPARα. Pemafibrate is a novel member of the selective PPARα modulator (SPPARMα) family that was designed to have a higher PPARα agonistic activity and selectivity than previous fibrates. Here, we aimed to study the influences of the switching from fenofibrate to pemafibrate on metabolic parameters in type 2 diabetic patients.MethodsWe retrospectively picked up type 2 diabetic patients who had undergone the switching from fenofibrate to pemafibrate, and compared metabolic parameters before the switching with the data at 3, 6 and 12 months after the switching.ResultsWe found 15 patients with type 2 diabetes. Serum alanine aminotransferase significantly decreased at 6 months after the switching as compared with baseline. The estimated glomerular filtration rate (eGFR) significantly increased at 3, 6 and 12 months after the switching from fenofibrate to pemafibrate as compared with baseline. Serum uric acid (UA) levels significantly increased at 3 and 6 months after the switching as compared with baseline. We did not observe changes in other metabolic parameters after the switching.ConclusionWe observed a significant increase of eGFR and serum UA after the switching from fenofibrate to pemafibrate in type 2 diabetic patients. Recent evidences suggest that the improvement of eGFR is beneficially associated with the development of CVD in type 2 diabetic patients. Considering the impact on eGFR, pemafibrate may effectively reduce CVD as compared with fenofibrate.

A Significant Increase of Estimated Glomerular Filtration Rate After Switching From Fenofibrate to Pemafibrate in Type 2 Diabetic Patients

Background: Dyslipidemia is one of the major risk factors for cardiovascular disease (CVD), along with hypertension, diabetes, smoking and obesity. Approximately 70% of CVD risk remains even after treatment of elevated low-density lipoprotein-cholesterol (LDL-C) by statins. High triglyceride (TG) and low high-density lipoprotein-cholesterol (HDL-C) level are potential therapeutic targets to prevent CVD. Fibrates were associated with a greater reduction in TG, and a greater increase in HDL-C. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). Fibrates improve atherogenic dyslipidemia by mediating PPARalpha. Pemafibrate is a novel member of the selective PPARalpha modulator (SPPARMalpha) family that was designed to have a higher PPARalpha agonistic activity and selectivity than previous fibrates. Here, we aimed to study the influences of the switching from fenofibrate to pemafibrate on metabolic parameters in type 2 diabetic patients. Methods: We retrospectively picked up type 2 diabetic patients who had undergone the switching from fenofibrate to pemafibrate, and compared metabolic parameters before the switching with the data at 3, 6 and 12 months after the switching. Results: We found 15 patients with type 2 diabetes. Serum alanine aminotransferase significantly decreased at 6 months after the switching as compared with baseline. The estimated glomerular filtration rate (eGFR) significantly increased at 3, 6 and 12 months after the switching from fenofibrate to pemafibrate as compared with baseline. Serum uric acid (UA) levels significantly increased at 3 and 6 months after the switching as compared with baseline. We did not observe changes in other metabolic parameters after the switching. Conclusion: We observed a significant increase of eGFR and serum UA after the switching from fenofibrate to pemafibrate in type 2 diabetic patients. Recent evidences suggest that the improvement of eGFR is beneficially associated with the development of CVD in type 2 diabetic patients. Considering the impact on eGFR, pemafibrate may effectively reduce CVD as compared with fenofibrate. Cardiol Res. 2021;000(000):000-000 doi: https://doi.org/10.14740/cr1333

Evaluation of Antidiabetic Activity of Sargassum tenerrimum in Streptozotocin-Induced Diabetic Mice

Diabetes mellitus has become the most predominant disease in most of the developing and developed countries. Diabetes could occur at any stage of life for which a change in sedentary life style is the possible solution. Despite the introduction of several medications, to curtail the side effects associated with diabetes mellitus, there is no medication or treatment for complete cure. Existing medications and treatments are targeted to mitigate the intensity of the disease which abruptly could result in organ failure. Rather than the available types of treatments, natural medication is reported to produce commendable results. Extracts of many medicinal plants and seaweeds have been documented to possess anti-diabetic properties. A brown alga, S. tenerrimum, found on the west coast of India, is chosen in this study to analyse the anti-diabetic property of its methanolic extract. This extract was used to treat streptozotocin-induced diabetic mice. An experimental design was framed based on acute toxicity studies to determine the change in blood glucose level, body weight, lipid profile, liver enzymes (SGPT and SGOT) and the renal function markers (urea and creatinine). After 15 days of treatment, an increase in body weight and HDL cholesterol was observed while the total cholesterol, VLDL, LDL, serum triglyceride, SGOT, SGPT, creatinine and urea decreased with 250 mg/Kg.bw of S. tenerrimum methanolic extract in Streptozotocin-induced diabetic mice group. This difference is significant (p&lt;0.05) when compared with a healthy non-diabetic mice group and a treated diabetic mice group. This proves that the methanolic extract of S. tenerrimum possess anti-diabetic property. Further research could explore the active compounds that can be used in the formulation of herbal medicine for diabetes mellitus.

Comparison of biochemical and safety parameters of regular kratom (Mitragyna speciosa Korth.) users at two different time periods

ABSTRACT Introduction Kratom is a medicinal plant native to Southeast Asia. This present study was primarily undertaken to investigate changes in the vital signs, hematological, and biochemical parameters of regular kratom users. Method Five male regular kratom users were recruited for this longitudinal study. Subjects volunteered to undergo two sessions of blood tests and vital signs assessments after a 3-month interval (baseline: T1; after 3 months: T2). Result There were no significant alterations found in the hematological and biochemical of kratom users, except for a decrease in white cell count after a 3-month interval. In general, the kidney, liver function tests, thyroid, and glucose parameters were not significantly affected. Calcium, total protein, and globulin levels were significantly increased at T2 compared to T1, but all these parameters were within the normal reference range. There were alterations in the lipid profile, where total cholesterol and LDL cholesterol parameters were elevated at both T1 and T2, while significant increase in HDL cholesterol, and decrease in triglycerides levels were observed at T2 compared to T1. Conclusion Our results indicated that continuous consumption of kratom decoction at a daily mitragynine dose of 76.3–114.8 mg did not appear to alter the safety hematological and biochemical parameters of kratom users.

Cholesteryl ester transfer protein inhibitors: from high-density lipoprotein cholesterol to low-density lipoprotein cholesterol lowering agents?

Cholesteryl ester transfer protein (CETP) is a liver-synthesized glycoprotein whose main functions are facilitating transfer of both cholesteryl esters from high-density lipoprotein (HDL) particles to apolipoprotein B (apoB)-containing particles as well as transfer of triglycerides from apoB-containing particles to HDL particles. Novel crystallographic data have shown that CETP exchanges lipids in the circulation by a dual molecular mechanism. Recently, it has been suggested that the atherosclerotic cardiovascular disease (ASCVD) benefit from CETP inhibition is the consequence of the achieved low-density lipoprotein cholesterol (LDL-C) and apoB reduction, rather than through the HDL cholesterol (HDL-C) increase. The use of CETP inhibitors is supported by genetic evidence from Mendelian randomization studies, showing that LDL-C lowering by CETP gene variants achieves equal ASCVD risk reduction as LDL-C lowering through gene proxies for statins, ezetimibe, and proprotein convertase subtilisin-kexin Type 9 inhibitors. Although first-generation CETP inhibitors (torcetrapib, dalcetrapib) were mainly raising HDL-C or had off-target effects, next generation CETP inhibitors (anacetrapib, evacetrapib) were also effective in reducing LDL-C and apoB and have been proven safe. Anacetrapib was the first CETP inhibitor to be proven effective in reducing ASCVD risk. In addition, CETP inhibitors have been shown to lower the risk of new-onset diabetes, improve glucose tolerance, and insulin sensitivity. The newest-generation CETP inhibitor obicetrapib, specifically designed to lower LDL-C and apoB, has achieved significant reductions of LDL-C up to 45%. Obicetrapib, about to enter phase III development, could become the first CETP inhibitor as add-on therapy for patients not reaching their guideline LDL-C targets.

Ephedra alata extracts exerts anti-obesity, anti-hyperglycemia, anti-antipyretic and analgesic effects

PurposeThis study paper aims to evaluate the Phytochemical Composition, anti-obesity, anti-antipyretic and analgesic effect of Ephedra alata (Ea) extracts.Design/methodology/approachObesity was induced in male Wistar rats through a high-fat/fructose diet (HF/FD). Control rats received a standard diet.FindingsResults of this study showed that the Ea methanol extract (MEEa) exhibited a prominent selective inhibitory effect against lipase activity (IC50 = 1.29 mg/ml) as compared to water and ethyl acetate extracts (with IC50 = 1.63 and 1.89, respectively). Also, MEEa exert antipyretic and analgesic activities. In high-fat-high-fructose diet rats, the administration of MEEa inhibited lipase activity in the intestine, pancreas and serum by 53%, 40% and 53%, respectively. It was found to significantly decrease body weight by 20% (p = 0.09) and delay the absorption of triglycerides (TG), total cholesterol (TC), LDL-cholesterol (LDL-C) and increase HDL-cholesterol (HDL-C). In addition, MEEa efficiently decreased a-amylase activity in the intestine, pancreas and serum by 43%, 26% and 46%, respectively, and blood glucose level by 35% (p = 0.06).Originality/valueTo the best of the authors’ knowledge, this study demonstrates for the first time that MEEa are efficient in preventing obesity and hyperglycemia, pain and fever.

Abstract 11998: The microRNA-378 and Estrogen-Related Receptor Gamma Axis Regulates Metabolic Inflammation and Lipoprotein Metabolism: A Potential Therapeutic Target for Atherosclerosis

MicroRNAs (miRNAs) are non-coding small RNAs that interact with their targeted mRNAs, resulting in decay or translational repression of the targeted mRNAs. The estrogen-related receptor (ERR)γ is an orphan nuclear hormone receptor. MiRNAs and ERRγ play pivotal roles in the pathophysiological conditions of metabolic diseases. The objective of this study is to determine the impact of miR-378a and its targeted gene ERRγ in metabolic inflammation and HDL metabolism, and explore the therapeutic potential of antigomic miRNA in atherosclerosis. Bioinformatics analysis of hepatic miRNA sequencing profile from mice fed a lipogenic diet (high-fructose) revealed that miR-378a was upregulated and served as a hub in a regulatory network that collaboratively targets multiple metabolic signal molecules in energy metabolism, mitochondrial fatty acid β-oxidation (FAO), and lipoprotein metabolism. Specifically, the upregulated miR-378a induced by fructose suppressed expression of ERRγ and genes involved in FAO (e.g., PPARα, CPT1α and ACOX1). In contrast, genetic depletion of miR-378a (miR-378aKO) significantly enhanced ERRγ expression, ameliorated mitochondrial oxidative stress and metabolic inflammation. Furthermore, miR-378aKO markedly stimulated expression of genes involved in HDL metabolism, including LXRα, ABCA1 and aopA4, leading to the increase of HDL-cholesterol and decrease of LDL-cholesterol in blood circulation. An in vivo VLDL secretion assay further revealed that miR-378aKO inhibited biogenesis and secretion of VLDL from the KO mouse liver, suggesting an improvement of atherogenic status in the absence of miR-378a. More importantly, treated the fructose-fed mice with nanoparticles carrying antagomir against miR-378a successfully reduced hepatic miR-378a expression, which was associated with significant restoration of ERRγ signaling and the associated mitochondrial FAO and HDL metabolism, indicated by the increased gene expression of PPARα, CPT1α and ACOX-1 as well as LXRα and apoA4, in the treated mice. Conclusion: These data indicate that manipulating miR-378a level can restore ERRγ signaling, improve FAO and lipoprotein metabolism. This novel finding may lend support to the therapeutic strategy of atherosclerosis.

The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels.

Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.

Genetic Variation in the Mitochondrial Glycerol-3-Phosphate Acyltransferase Is Associated With Liver Injury.

Most of the genetic basis of chronic liver disease remains undiscovered. To identify genetic loci that modulate the risk of liver injury, we performed genome-wide association studies on circulating levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin across 312,671 White British participants in the UK Biobank. We focused on variants associated with elevations in all four liver biochemistries at genome-wide significance (P<5×10-8 ) and that replicated using Mass General Brigham Biobank in 19,323 European ancestry individuals. We identified a genetic locus in mitochondrial glycerol-3-phosphate acyltransferase (GPAM rs10787429) associated with increased levels of ALT (P=1.4×10-30 ), AST (P=3.6×10-10 ), ALP (P=9.5×10-30 ), and total bilirubin (P=2.9×10-12 ). This common genetic variant was also associated with an allele dose-dependent risk of alcohol-associated liver disease (odd ratio [OR]=1.34, P=2.6×10-5 ) and fatty liver disease (OR=1.18, P=5.8×10-4 ) by International Classification of Diseases, 10th Revision codes. We identified significant interactions between GPAM rs10787429 and elevated body mass index in association with ALT and AST (P=7.1×10-9 and 3.95×10-8 , respectively), as well as between GPAM rs10787429 and weekly alcohol consumption in association with ALT, AST, and alcohol-associated liver disease (P=4.0×10-2 , 1.6×10-2 , and 1.3×10-2 , respectively). Unlike previously described genetic variants that are associated with an increased risk of liver injury but confer a protective effect on circulating lipids, GPAM rs10787429 was associated with an increase in total cholesterol (P=2.0×10-17 ), LDL cholesterol (P=2.0×10-10 ), and HDL cholesterol (P=6.6×10-37 ). Single-cell RNA-sequencing data demonstrated hepatocyte-predominant expression of GPAM in cells that co-express genes related to VLDL production (P=9.4×10-103 ). Genetic variation in GPAM is associated with susceptibility to liver injury. GPAM may represent a therapeutic target in chronic liver disease.