Novel Therapeutical Approaches to Managing Atherosclerotic Risk

Atherosclerosis is a multifactorial vascular disease that leads to inflammation and stiffening of the arteries and decreases their elasticity due to the accumulation of calcium, small dense Low Density Lipoproteins (sdLDL), inflammatory cells, and fibrotic material. A review of studies pertaining to cardiometabolic risk factors, lipids alterations, hypolipidemic agents, nutraceuticals, hypoglycaemic drugs, atherosclerosis, endothelial dysfunction, and inflammation was performed. There are several therapeutic strategies including Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) inhibitors, inclisiran, bempedoic acid, Glucagon-Like Peptide-1 Receptor agonists (GLP-1 RAs), and nutraceuticals that promise improvement in the atheromatous plaque from a molecular point of view, because have actions on the exposure of the LDL-Receptor (LDL-R), on endothelial dysfunction, activation of macrophages, on lipid oxidation, formations on foam cells, and deposition extracellular lipids. Atheroma plaque reduction both as a result of LDL-Cholesterol (LDL-C) intensive lowering and reducing inflammation and other residual risk factors is an integral part of the management of atherosclerotic disease, and the use of valid therapeutic alternatives appear to be appealing avenues to solving the problem.

Role of Vegetables to Prevent Heart Diseases

Heart diseases due to hyperlipidemia (primary or secondary) can lead to cause chest pain, heart attacks, strokes, cardiac arrhythmias, cardiac failure. Because of these risks, treatment is often recommended for people with hyperlipidemia, because it is well known factor to increase incidence of heart diseases. This may lead to development of atherosclerotic plaques which is major etiological factor for establishing coronary artery disease (CAD). Hypolipidemic drugs used in allopathy include Statins, Fibric acids, Niacin, and Resins but all have their low compliance due to frequent side effects. Medicinal herbs like Onion and Ginger are hypolipidemic agents commonly used as flavoring agents and making foods spicy and tasty. We have compared hypolipidemic potential between these two medicinal herbs. The study was conducted at Ghurki Trust teaching hospital, Lahore from January to June 2018. Eighty secondary hyperlipidemic patients were enrolled after getting written consent which was approved by Ethics committee of the hospital. They were divided in two equal groups comprising 40 patients in each group. Group-I was treated by Ginger 10 grams daily in three divided doses for 2 months. Group-II was advised to take Onion 200 grams daily in divided amount with each meal i.e.; breakfast, lunch, and dinner for two months. After two months therapy it was observed by statistical analysis that 10 grams ginger reduced TC (total cholesterol) of 38 hyperlipidemia patients 12.4 gm/dl and LDL-C (low density lipoprotein cholesterol) 27.3 mg/dl. In group-II, onion reduced TC in 35 patients 17.9 mg/dl and LDL-C 14.8 mg/dl. Changes in tested parameters are significant bio statistically with p-values <0.01 to <0.001. We concluded from this research work that Onion and Ginger reduces risk of CAD by decreasing plasma total cholesterol and LDL cholesterol

Amino acid ester-coupled caffeoylquinic acid derivatives as potential hypolipidemic agents: synthesis and biological evaluation

Amino acid ester-coupled caffeoylquinic acid derivatives as potential hypolipidemic agents.

HERBAL COMMUNITY: Another consideration about Pharmacognosy

The metabolic disorders are main and increasing public-health and clinical challenge worldwide because of urbanization, excessive energy intake, increasing obesity, and sedentary life styles. According to International Diabetes Federation (IFD) diabetes is one of the major metabolic disorders and a dangerous risk factor for heart problems. Twenty five percent of the world’s adults have metabolic disorders. Recently in year 2013 the American Heart Association also reported that adults have abnormal serum lipid profile. Allopathic drugs used as hypolipidemic agents have number of unwanted effects. Herbal therapy for Hyperlipidemia is getting attention due to their less frequent side effects. In this study we have compared hypolipidemic effects of Fenofibrate 40 mg with Nigella sativa. Seventy five hyperlipidemic patients from National Hospital Lahore were enrolled for study. Consent was taken from all enrolled participants and were divided in three equal numbers ie; twenty five in each group. Group 1 was on Nigella sativa, group 2 was on Gemfibrozil and third group was on placebo therapy. They were advised to take drugs for two months. After completion of study pretreatment and post treatment values of LDL cholesterol were analyzed statistically. In 25 patients who were on Nigella sativa, their LDL cholesterol decreased from 191.14±3.45 to 159.40±2.98 mg/dl. 31.7 mg/dl LDL reduction was observed when compared with placebo group. In 25 patients who were on Fenofibrate 40 mg, their LDL cholesterol decreased from 197.77±3.91 mg/dl to 159.62±2.20 mg/dl. LDL reduction in this group was 38.2 mg/dl. These changes are highly significant with p-values of <0.001. We concluded from this study that hypolipidemic characteristic of Nigella sativa is comparable and therapeutically as effective as traditionally used hypolipidemic medication Fenofibrate.

Sea Buckthorn and Grape Extract Might Be Helpful and Sustainable Phyto-Resources as Associated Hypolipidemic Agents—Preliminary Study

Phytotherapy can enhance the beneficial health outcomes in the prevention of obesity and is able to improve the function of the metabolic organs, like the liver and kidneys. Since sea buckthorn (SBT) and grape extracts are known as abundant sources of polyphenol, we assumed that the extracts of these two plants might have a hypolipidemic effect and an improved metabolic function in obese rats treated with atorvastatin. One hundred and twelve white Wistar rats were divided equally into seven groups (G.I–VII) and orally treated as follows: G.I, atorvastatin 20 mg × kg·bw−1; G.II, atorvastatin 20 mg × kg·bw−1 + SBT 100 mg × kg·bw−1; G.III, atorvastatin 20 mg × kg·bw−1 + grape extract 100 mg × kg·bw−1; G.IV, grape extract 100 mg × kg·bw−1; G.V, SBT 100 mg × kg·bw−1; G.VI, high-fat diet (HFD); group VII was considered the control group. After two and six months of administration, the rats were sacrificed, and blood samples were taken for biochemical analyses. The statistical results (analysis of variance (ANOVA)) showed that a combination of SBT and grape extracts with atorvastatin significantly reduced (p ˂ 0.001) the lipid parameters. After six months, the liver and kidneys improved their functioning, showing a statistically significant change (p ˂ 0.001) in the grape and sea buckthorn groups compared to the other groups. In addition, grape extract and SBT combined with atorvastatin proved to be potent hypolipidemic agents, so associations with phytodietary supplements can be considered as a valuable means of combating hypolipidemia and decreasing risk factors.

Metoprolol-induced hyperkalemia – A case report

Hyperkalemia is a condition that increased serum potassium levels, which can lead to life-threatening cardiac conditions. A 59-year-old female patient admitted to an emergency medicine ward with complaints of gradually progressive retrosternal chest pain. She was a known case of diabetes mellitus (DM), hypertension, and ischemic heart disease with a positive family history of DM and hypertension. She has treated with tablet metoprolol 12.5 mg twice daily from 20 days. On examination, the patient was restless due to unstable angina BP in the range of 110/70–180/90 mm of Hg, PR range 84–86 bpm, and SPO2 – 98%. Laboratory investigation revealed that the HbA1c was 7.19, and mean blood glucose of the past 90 days was in average control. Ultrasonography shows the Grade I renal parenchymal disease. The serum blood sugar level was elevated. Serum troponin I was 0.91 ng/ml. Ultrasonography abdomen was normal. Electro cardiogram: Sinus tachycardia suspected left inferior hemiblock, poor R-wave progression, inverted T- wave, and slide ST segments elevation and 2D-echocardiogram: IHD and RWMA at rest (basal inferior moderate left ventricle dysfunction). On hospital admission, the patient was treated with antiplatelet agents, anticoagulant, insulin, anti-ischemic agents, hypolipidemic agents, and potassium binder resins and diuretics. Patients with diabetes and kidney dysfunction have a higher risk of hyperkalemia in concomitants therapy with beta-blockers, so the health care workers should be aware of life-threatening events due to hyperkalemia secondary to beta-blockers. This case-report adds the evidence on the electrolyte related adverse drug reactions due to the beta-blockers.

Synthesis and In Vitro Evaluation of Caffeoylquinic Acid Derivatives as Potential Hypolipidemic Agents

A series of novel caffeoylquinic acid derivatives of chlorogenic acid have been designed and synthesized. Biological evaluation indicated that several synthesized derivatives exhibited moderate to good lipid-lowering effects on oleic acid-elicited lipid accumulation in HepG2 liver cells. Particularly, derivatives 3d, 3g, 4c and 4d exhibited more potential lipid-lowering effect than the positive control simvastatin and chlorogenic acid. Further studies on the mechanism of 3d, 3g, 4c and 4d revealed that the lipid-lowering effects were related to their regulation of TG levels and merit further investigation.

Effects of сramizol on expression of the ApoA1 gene in rats with experimental hyperlipidemia

An imidazole derivative cramizol, has lipid-lowering and anti-atherogenic effects. Cramizol reduces blood levels of cholesterol and triglycerides, and also reduces the atherogenic index in animals with acute hyperlipidemia induced by Triton WR-1339. Cramizol and the lipid-lowering drug fenofibrate exhibited similar effectiveness as hypolipidemic agents. Cramizol also restores the expression of the Apoa1 gene in rats with experimentally induced hyperlipidemia to normal values. This may be a basis of its hypolipidemic and anti-atherogenic action.

Investigation of the sustained-release mechanism of hydroxypropyl methyl cellulose skeleton type Acipimox tablets

In this study, we investigate the production of hypolipidemic agents in the form of Acipimox sustained-release tablets, using a wet pelleting process. The purpose of this research is to reduce the total intake time for patients and to lower the initial dose in such that the adverse reactions could be reduced. This study adopts the single-factor method and orthogonal experiments by using hydroxypropyl methyl cellulose (HPMC K15M) as the main sustained-release prescription composition. The final prescription is Acipimox 20%, HPMC K15M 26.67%, sodium carboxymethyl cellulose 30%, polyethylene glycol (PEG 6000) 1%, ethyl cellulose 16.6%, lactose 4.67% and magnesium stearate 1%. The dissolution of tablets reached 85.88% in 8 h. The difference in the weight, hardness and friability of the tables met the requirements in the Chinese Pharmacopoeia; to test the stability, a temperature and illumination accelerated test method was used, the results indicate that the Acipimox sustained-release tablets should be sealed and stored in a dark, cool area. A preliminary study on the tablets’ releasing mechanism showed that their release curve fitted the Higuchi model (the formula is Mt/M∞ = 31.137 t1/2–3.605 (R2 = 0.9903)). The Acipimox tablets’ release principle is dominated by the diffusion mechanism.