Cardiovascular and Hematological Agents in Medicinal Chemistry最新文献

Statin drugs have long been used as a key component of lipid-lowering therapy, which is necessary for the prevention and treatment of atherosclerosis and cardiovascular diseases. Many studies focus on finding and refining new effects of statin drugs. In addition to the main lipidlowering effect (blocking cholesterol synthesis), statin drugs have a number of pleiotropic effects, including negative effects. The main beneficial effects of statin drugs on the components of the cardiovascular system are: anti-ischemic, antithrombotic, anti-apoptotic, antioxidant, endothelioprotective, anti-inflammatory properties, and a number of other beneficial effects. Due to these effects, statin drugs are considered one of the main therapeutic agents for the management of patients with cardiovascular pathologies. To date, many review manuscripts have been published on the myotoxicity, hepatotoxicity, nephrotoxicity, neurotoxicity and diabetogenic effects of statins. However, there are no review manuscripts considering the negative effect of statin drugs on myocardial contractile cells (cardiomyocytes). The purpose of this review is to discuss the negative effects of statin drugs on cardiomyocytes. Special attention is paid to the cardiotoxic action of statin drugs on cardiomyocytes and the mechanisms of increased serum levels of cardiac troponins. In the process of preparing this review, a detailed analysis of laboratory and experimental data devoted to the study of the negative effects of statin drugs on cardiomyocytes was carried out. The literature search was carried out with the keywords: statin drugs, negative effects, mechanisms, cardiac troponins, oxidative stress, apoptosis. Thus, statin drugs can have a number of negative effects on cardiomyocytes, in particular, increased oxidative stress, endoplasmic reticulum stress, damage to mitochondria and intercalated discs, and inhibition of glucose transport into cardiomyocytes. Additional studies are needed to confirm and clarify the mechanisms and clinical consequences of the negative effects of statin drugs on cardiomyocytes.

Aims: The study investigated the effect of L-tartaric acid on diminazene-indiuced vasorelaxation.

Background: Diminazene is known to induce vasorelaxation through the stimulation of angiotensin- converting enzyme (ACE-2).

Objective: This work was designed to study the effect of L-tartaric acid on diminazene-induced vasorelaxation using an ex vivo approach.

Materials and methods: In the current investigation, the inhibitory effect of L-tartaric acid on diminazene-induced relaxation.

Results: The results confirmed that L-tartaric acid was able to inhibit in a dose-dependent manner diminazene-induced vasorelaxation.

Conclusion: This investigation provides important experimental evidence of the efficacy of Ltartaric acid in inhibiting diminazene-induced vasorelaxation.

Background: The lack of a substantial breakthrough in the treatment of diabetes, a global issue, has led to an ongoing quest for herbs that contain bioactive elements with hypoglycemic properties.

Objective: To investigate the potential protective effect of Nigella sativa seeds ethanol extract and its active ingredient, thymoquinone, on streptozotocin-induced diabetic rats.

Methods: To induce diabetes, the male Wistar rats were administered an intraperitoneal injection of STZ at a dosage of 90 mg/kg body weight in 0.9 percent normal saline after being fasted for 16 hours and made diabetic Group 1; 7 rats non-diabetic control (saline-treated), Group 2; 7 untreated diabetic rats, Group 3; 7 diabetic rats treated orally with N. sativa extract at a dose of 100 mg/kg body weight, Group 4; 7 diabetic rats treated orally with thymoquinone at a dose of 10 mg/kg body weight and Group 5; 7 diabetic rats treated orally with Metformin at a dose of 5 mg/kg body weight. After the treatment of 28 days, all groups were examined for body weight and biochemical alterations.

Results: The results showed a significant decrease in blood glucose, urea, creatinine, uric acid, total protein, total cholesterol, low-density lipoprotein, and very low-density lipoprotein, while high-density lipoprotein was increased. Hepatic enzymes, alanine transaminase, aspartate aminotransferase, and alkaline phosphate were also normalized and significantly increased body weight.

Conclusion: These preliminary findings demonstrate that the ethanol extract of N. sativa seeds and its active ingredient, thymoquinone have a protective effect against streptozotocin-induced diabetic rats. The present study opens new vistas for the use of N. sativa and its bioactive compound, thymoquinone, regarding its clinical application as a new nontoxic antidiabetic agent for managing diabetes mellitus.

Aged garlic extract (AGE) is an odorless derivative of garlic prepared by extracting garlic cloves in an aqueous solution for twenty months. During the process of aging, reactive organosulfur compounds such as allicin present in garlic are converted to their stable isoforms such as S- Allyl cysteine. The unstable organo sulfurs in garlic (Allium sativum L.) have been reported to cause problems in the gastrointestinal (GI) tract with an extremely pungent odor to attain its therapeutic potential. But these pharmacologically safer sulfur compounds of AGE have been studied and reported to have exceptional therapeutic potential in human health and various diseases. SAllyl cysteine (SAC), Diallyl disulfide (DADS), Diallyl trisulfide (DATS), S-allyl-mercaptocysteine (SAMC), are the most studied organosulfur compounds in in-vitro as well as in-vivo research. Biomedical research suggests that these phytoconstituents exhibit antioxidant, cardioprotective, cancer preventive, neuroprotective, immunomodulatory, antilipidemic, antidiabetic, hepatoprotective, and antiobesity effects. The therapeutic potential of aged garlic extract has been found to be extensively beneficial in these conditions, and provide a vast future in biomedical chemistry, herbdrug synergy and drug designing. The purpose of this review is to provide a mechanistic understanding of various organosulfur compounds of AGE in human health and disease based on data provided in the literature.

Aims: The goal of this work was to evaluate the antihypertensive activity of Prunus armeniaca.

Background: Prunus armeniaca is known for its beneficial medicinal properties.

Objective: This study aimed to evaluate the effect of the aqueous extract of Prunus armeniaca L. (P. armeniaca) leaves (PAAE) on arterial blood pressure in normotensive and hypertensive rats.

Materials and methods: In the in vivo examination, N-omega-Nitro-L-arginine methyl ester hydrochloride( L-NAME)-induced hypertensive and normotensive rats received PAAE (160 and 100 mg/kg) orally for the acute experiment spanning 6 hours and for seven days for the subchronic treatment; their blood pressure parameters were also evaluated. In the in vitro experiment, isolated intact thoracic aortic rings were precontracted with KCl (80 mM) and epinephrine (EP) (10 μM), and vascular dilatation was assessed.

Results: PAAE lowered blood pressure parameters in L-NAME-induced hypertensive without affecting normotensive rats following oral administration, suggesting that PAAE possesses an antihypertensive effect. In addition, PAAE (0.25-1 mg/mL) revealed a vasorelaxant effect in thoracic aortic rings precontracted by EP (10 μM), and this effect was especially reduced in the presence of glibenclamide or nifedipine. However, PAAE (0.25-1 mg/mL) had only a minimal vasorelaxant effect on thoracic aortic rings precontracted by KCl (80 mM).

Conclusion: The results demonstrate that the P. armeniaca aqueous extract possesses potent antihypertensive and vasorelaxant activity, and its vasorelaxant activity seems to be mediated through the opening of ATP-sensitive K+ channels and inhibition of L-type calcium channels.

Background: Diabetic cardiomyopathy has emerged as a major cause of cardiac fibrosis, hypertrophy, diastolic dysfunction, and heart failure due to uncontrolled glucose metabolism in patients with diabetes mellitus. However, there is still no consensus on the optimal treatment to prevent or treat the cardiac burden associated with diabetes, which urges the development of dual antidiabetic and cardioprotective cardiac therapy based on natural products. This study investigates the cardiotoxic profile of glucose and the efficacy of AGE against glucose-induced cardiotoxicity in H9c2 cardiomyocytes.

Methods: The cellular metabolic activity of H9c2 cardiomyocytes under increasing glucose concentration and the therapeutic efficacy of AGE were investigated using the MTT cell cytotoxicity assay. The in vitro model was established in six groups known as 1. control, 2. cells treated with 25 μM glucose, 3. 100 μM glucose, 4. 25 μM glucose +35 μM AGE, 5. 100 μM glucose + 35 μM AGE, and 6. 35 μM AGE. Morphological and nuclear analyses were performed using Giemsa, HE, DAPI, and PI, respectively, whereas cell death was simultaneously assessed using the trypan blue assay. The antioxidant potential of AGE was evaluated by DCFH-DA assay, NO, and H202 scavenging assay. The activities of the antioxidant enzymes catalase and superoxide dismutase were also investigated. The antiglycative potential of AGE was examined by antiglycation assays, amylase zymography, and SDS PAGE. These results were then validated by in silico molecular docking and qRTPCR.

Results: Hyperglycemia significantly reduced cellular metabolic activity of H9c2 cardiomyocytes, and AGE was found to preserve cell viability approximately 2-fold by attenuating oxidative, fibrosis, and apoptotic signaling molecules. In silico and qRTPCR studies confirmed that organosulfur compounds target TNF-α, MAPK, TGF-β, MMP-7, and caspase-9 signaling molecules to ameliorate glucose-induced cardiotoxicity.

Conclusion: AGE was found to be an antidiabetic and cardioprotective natural product with exceptional therapeutic potential for use as a novel herb-drug therapy in the treatment of diabetic cardiomyopathy in future therapies.