Dhanwantaram kashayam,an Ayurvedic polyherbal formulation,reduces oxidative radicals and reverts lipids profile towards normal in diabetic rats

BackgroundHyperglycemia and hyper oxidative stress are indicators of diabetes mellitus which is also accompanied with decreased levels of antioxidant enzymes. While oxidative stress is important in increasing insulin secretion and controlling blood sugar level at the same time excess oxidative stress leads to the destruction of beta cells of pancreas resulting in to low insulin production and hyperglycemia. A balance between the levels of oxidative radicals and insulin production is needed, but is not defined yet. Hyperglycemia also leads to hyperlipidemia which can contribute to various health conditions like cardiovascular diseases.ObjectivesThis study was designed to study the oxidative stress and lipid levels in diabetic rats. This also was designed to elucidate the effect of Dhanwantaram Kashayam, an Ayurvedic polyphenolic derived from plants on lipid metabolism and oxidative radical scavenging in diabetic rats.MethodsRats were made diabetic by injecting streptozotocin. Different enzymes involved in oxidative radical scavenging and lipid profiles including triglycerides, total cholesterol, free fatty acids and phospholipids were estimated using standard methods reported elsewhere.ResultsLevel of antioxidant enzymes were lower in diabetic rats compared to normal controls. Administration of Dhanwantaram Kashayam restored the enzyme activity as well as reduced levels of different lipids in diabetic rats.ConclusionsAdministration of Dhanwantaram Kashayam increased the activity levels of antioxidant enzymes and reduced the levels of total cholesterol, phospholipids and triglycerides. The results of this study point to the possibility of developing Dhanwantaram Kashayam as a dietary supplement which can alleviate the complications associated with diabetes or prevent them altogether.     

Low-level environmental lead and cadmium exposures and dyslipidemia in adults: Findings from the NHANES 2005–2016

BackgroundPrevious experimental and occupational health studies have shown the toxic effects of relatively high-level cadmium and lead on lipid metabolism. However, limited studies investigated the relationships between serum lipid levels and exposure to low-level lead and cadmium in adults.ObjectiveTo investigate the associations between lead and cadmium levels in blood and dyslipidemia in adults.MethodsA retrospective cross-sectional study of 7,457 adults aged 20–79 years who were recruited in the National Health and Nutrition Examination Survey (NHANES, 2005–2016) was conducted. Multivariate linear and logistic regressions were used to examine the associations of blood lead and cadmium levels with serum lipid profiles and risk of dyslipidemia, respectively.ResultsThe weighted geometric means [95% confidence intervals (CIs)] of lead and cadmium in blood were 1.23 (1.21, 1.25) μg/dL and 0.36 (0.35, 0.37) μg/L, respectively. Blood lead was significantly associated with serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and apolipoprotein B (Apo B) levels after adjusting for covariates. Compared with the adults in the lowest blood lead quartile (≤0.76 μg/dL), those in the highest lead quartile (>1.90 μg/dL) had higher risks of elevated TC (OR = 1.88, 95% CI: 1.59–2.22), non-HDL-C (OR = 1.59, 95% CI: 1.33–1.91), LDL-C (OR = 1.68, 95% CI: 1.41–1.99) and Apo B (OR = 2.00, 95% CI: 1.46–2.73). However, the single effect of cadmium exposure and the joint effect of lead and cadmium exposures on dyslipidemia were not observed.ConclusionBlood lead well below the current recommended level was positively associated with the risk of dyslipidemia in adults, while the low-level cadmium exposure currently observed in adults did not show any significant associations with lipid levels.     

血脂异常及动脉粥样硬化中医研究进展

“血脂异常”及“动脉粥样硬化”是现代医学病名,古代医书中虽无此病名记载,但却不乏与之相关的论述.现代中医根据其临床表现将其归属于“眩晕”、“胸痹”、“中风”、“痰浊”、“血瘀”、“脉痹”、“血痹”、“脱疽”等病症范畴.现代中医学者对血脂异常、动脉粥样硬化的中医病名认识、病因病机探讨及二者之间的联系进行了大量的理论和实验研究,对血脂异常和动脉粥样硬化有了新的认识.动脉粥样硬化是引起心脑血管疾病的首要原因,也是其发病的病理基础,而血脂异常又是动脉粥样硬化发病的主要因素之一.故对血脂异常和动脉粥样硬化发病机制及防治策略的研究,不仅是西医研究的热点,同时也是中医中药研究重点,值得我们一生探索.     

Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets

Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4.     

Identification of a novel boronic acid as a potent,selective, and orally active hormone sensitive lipase inhibitor

Hormone sensitive lipase (HSL) is an attractive therapeutic target of dyslipidemia. We designed and synthesized several compounds as reversible HSL inhibitors with a focus on hydrophobic interactions, which was thought to be effective upon the HSL inhibitory activity. In these efforts, we identified boronated compound 12 showing a potent HSL inhibitory activity with an IC₅₀ value of 7 nM and a high selectivity against cholinesterases. Furthermore, compound 12 is the first boron containing HSL inhibitor that has shown an antilipolytic effect in rats after oral administration at 3 mg/kg.     

G protein-coupled receptor 12 deficiency results in dyslipidemia and obesity in mice

Obesity has been proposed to be a result of an imbalance in the physiological system that controls and maintains the body energy homeostasis. Several G-protein coupled receptors (GPCRs) are involved in the regulation of energy homeostasis. To investigate the importance of GPCR12, mice deficient of this receptor (GPCR12 KO) were studied regarding metabolism. Expression of GPCR12 was found primarily in the limbic and sensory systems, indicating its possible involvement in motivation, emotion together with various autonomic functions, and sensory information processing. GPCR12 KO mice were found to have higher body weight, body fat mass, lower respiratory exchange ratio (RER), hepatic steatosis, and were dyslipidemic. Neither food intake nor energy in faeces was affected in the GPCR12 KO mice. However, lower energy expenditure was found in the GPCR12 KO mice, which may explain the obesity. In conclusion, GPCR12 is considered important for the energy balance since GPCR12 KO mice develop obesity and have lower energy expenditure. This may be important for future drugs that target this receptor.     

鼠李糖乳杆菌grx10降血脂效果初探

目的采用随机、双盲、安慰剂对照研究,观察鼠李糖乳杆菌grx10对血脂异常者血脂水平的改善作用。方法筛选符合纳入排除标准的血脂指标检测异常者,随机分为对照组、低剂量组、高剂量组。对照组给予安慰剂10g/d,低剂量组给予grx10粉剂4g/d(3.2×10~(10) CFU/d)以及安慰剂6g/d,高剂量组给予grx10粉剂10g/d(8.0×10~(10) CFU/d)。试验周期为2周洗脱期+6周干预期。观察记录受试者干预前后血脂水平等。结果 44人完成试验,其中高剂量组17人,低剂量组14人,安慰剂组13人。益生菌高剂量干预组血清TC、TG、LDL-C水平与干预前相比显著下降(P0.05);三组间比较血脂改变差值差异无统计学意义。结论 grx10达到一定剂量时可降低人体血清TC、TG、LDL-C水平,后续本研究将继续扩大样本量,进一步明确grx10的降脂效果。     

Structure-guided design and synthesis of isoflavone analogs of GW4064 with potent lipid accumulation inhibitory activities

Our group has previously reported a series of isoflavone derivatives with antidyslipidemic activity. With this background, a series of isoflavone analogs of GW4064 were designed, synthesized and evaluated the lipid-lowering activity of analogs. As a result, most of compounds significantly reduced the lipid accumulation in 3T3-L1 adipocytes and four of them (10a, 11, 15c and 15d) showed stronger inhibitory than GW4064. The most potent compound 15d exhibited promising agonistic activity for FXR in a cell-based luciferase reporter assay. Meanwhile, 15d up-regulated FXR, SHP and BSEP gene expression and down-regulated the mRNA expression of lipogenesis gene SREBP-1c. Besides, an improved safety profile of 15d was also observed in a HepG2 cytotoxicity assay compared with GW4064. The obtained biological results were further confirmed by a molecular docking study showing that 15d fitted well in the binding pocket of FXR and interacted with some key residues simultaneously.     

Co-administration of APD668, a G protein-coupled receptor 119 agonist and linagliptin,a DPPIV inhibitor,prevents progression of steatohepatitis in mice fed on a high trans-fat diet

Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, hepatocyte injury with or without fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present study, we investigated the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor on the progression of steatohepatitis in mice fed on a high trans-fat diet. In this study, monotherapy with either APD668 or linagliptin caused a reduction in the levels of ALT, AST, glucose, cholesterol and epididymal fat mass but the effect was more pronounced upon treatment with combination of both drugs.On the other hand, combined treatment of APD668 with linagliptin demonstrated a non-significant additive effect in reduction of hepatic triglyceride (?78%) and cholesterol (?56%) compared to monotherapy groups. Moreover, co-administration of APD668 and linagliptin resulted in enhanced levels of active GLP-1 with additional benefit of significant synergistic decrease in body weight gain (?19%) in mice. We speculated that the enhanced effect observed with the combination treatment could be due to either 1) direct activation of GPR119 receptors present in liver and intestine or 2) enhanced active GLP-1 levels or 3) decreased degradation of GLP-1 in-vivo through DPPIV inhibition. Therefore, these findings clearly suggest that GPR119 receptor agonists in combination with DPPIV inhibitors may represent a promising therapeutic strategy for the treatment of non-alcoholic steatohepatitis.     

Combined efficacy of Vigna radiata (L.) R. Wilczek and Amorphophallus paeoniifolius (Dennst.) Nicolson on serum lipids in albino rats

Coronary Artery Disease (CAD) is a major killer disease throughout the world. Dyslipidemia is a major contributor to the risk of CAD. Several dietary articles traditionally used in India and other South Asian countries reduced dyslipidemia. The present study was undertaken to evaluate the combined effect of Mung bean (Vigna radiata) and Elephant foot yam (Amorphophallus paeoniifolius) on serum lipids and atherogenic indices in albino rats and to compare it with a standard drug Cholestyramine. Thirty healthy albino rats of both sexes (150–200 g) were randomized to 5 groups of 6 animals each. The grouping were done based on the following criteria: Group I: Normal Control Group, Group II: (Standard Group): Cholestyramine resin 5 mg/kg bw, Group III: (Half Dose Group): Drug powder at 540 mg/kg bw, Group IV: (Effective Dose Group): Drug powder at 1080 mg/kg bw, and Group V: (Double Dose Group): Drug powder at 2160 mg/kg bw. Lipid profile was estimated at the beginning and after 30 days of treatment. The Effective and Double doses of the drug reduced Total cholesterol along with levels of Triglycerides, Low density lipoprotein and Very low density lipoprotein levels significantly (p < 0.01) along with a significant (p < 0.01) increase in high density lipoproteins (HDL) in rats. There was also significant (p < 0.01) improvement in atherogenic indices like Castelli Risk Index I, Non HDL C/HDL, Castelli risk Index II, TG/HDL, Atherogenic coefficient and Atherogenic Index of Plasma. The combination of powdered sprouted mung bean and yam powder have excellent lipid lowering potential.