Bioactive molecules from terrestrial and seafood resources in hypertension treatment: focus on molecular mechanisms and targeted therapies.

Hypertension (HTN), a complex cardiovascular disease (CVD), significantly impacts global health, prompting a growing interest in complementary and alternative therapeutic approaches. This review article seeks to provide an up-to-date and thorough summary of modern therapeutic techniques for treating HTN, with an emphasis on the molecular mechanisms of action found in substances found in plants, herbs, and seafood. Bioactive molecules have been a significant source of novel therapeutics and are crucial in developing and testing new HTN remedies. Recent advances in science have made it possible to understand the complex molecular mechanisms underlying blood pressure (BP)-regulating effects of these natural substances better. Polyphenols, flavonoids, alkaloids, and peptides are examples of bioactive compounds that have demonstrated promise in influencing several pathways involved in regulating vascular tone, reducing oxidative stress (OS), reducing inflammation, and improving endothelial function. The article explains the vasodilatory, diuretic, and renin-angiotensin-aldosterone system (RAAS) modifying properties of vital plants such as garlic and olive leaf. Phytochemicals from plants are the primary in traditional drug development as models for novel antihypertensive drugs, providing diverse strategies to combat HTN due to their biological actions. The review also discusses the functions of calcium channel blockers originating from natural sources, angiotensin-converting enzyme (ACE) inhibitors, and nitric oxide (NO) donors. Including seafood components in this study demonstrates the increased interest in using bioactive chemicals originating from marine sources to treat HTN. Omega-3 fatty acids, peptides, and minerals obtained from seafood sources have anti-inflammatory, vasodilatory, and antioxidant properties that improve vascular health and control BP. Overall, we discussed the multiple functions of bioactive molecules and seafood components in the treatment of HTN.

Ameliorative Effect of Acetyl L-carnitine in Alzheimer's Disease via Downregulating of Homocysteine Levels in Hyperhomocysteinemia Induced Cognitive Deficit in Mouse Model.

AIMS: The study was aimed at exploring the role of Acetyl L-Carnitine supplementation attenuating dementia and degradation of cognitive abilities in Hyperhomocysteinemia induced AD manifestations in the mouse model. BACKGROUND: Alzheimer's disease (AD) is a neurological disorder that is marked by dementia, and degradation of cognitive abilities. There is great popularity gained by natural supplements as the treatment for AD, due to the higher toxicities of synthetic drugs. Hyperhomocysteinemia causes excitotoxicity to the cortical neurons, which brought us to the point that amino acids possibly have a role in causing cholinergic deformities, which are an important etiological parameter in AD. Acetyl L-Carnitine a methyl donor with the presence of three chemically reactive methyl groups linked to a nitrogen atom was found to possess neuroprotective activity against experimental models of AD. OBJECTIVE: The objective of the present investigation was to investigate and evaluate the pharmacological effect of Acetyl L-Carnitine against hyperhomocysteinemia induced Alzheimer's disease (AD) in the mouse model. MATERIALS AND METHODS: The animals were divided into normal control (vehicle-treated), HHcy (dl-Homocysteine thiolactone treated) negative control, test group i.e., low dose (50mg/kg, p.o) of acetyl L-carnitine (L-ALC), high dose (100mg/kg,p.o) of acetyl L-carnitine (H-ALC), L-ALC+ SOV (Sodium orthovanadate) and H-ALC+SOV. HHcy was induced by administration of dl-Homocysteine thiolactone (dl-HCT; 1 g/kg, p.o.) on day-1 to day-15 of experimental schedule to all animals except normal control. The changes in the behaviour pattern of the animals due to neuroinflammation, and cholinergic dysfunction were examined in rotarod, novel objective recognition, passive avoidance, elevated plus maze, and morris water maze analysis. Biochemical investigation includes the estimation of total homocysteine (tHcy), Creatinine Kinase (CK), Acetylcholinesterase (AChE), thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and IL-6 and TNF-α. RESULTS: Supplementation of ALC in mouse considerably lowered the HHcy-induced AD manifestations in the experimental animals. It was found that ALC and SOV successfully diminished the behaviour abnormalities and lessened the Hcy-induced alteration in systemic Hcy levels, CK activity, and cholinergic dysfunction with improved bioenergetics in the Prefrontal cortex of the mice. CONCLUSION: ALC was found to improve the HHcy-induced cognitive disabilities which was found to be associated with the decreased systemic levels of Hcy, CK, and cholinergic abnormalities. It also combats the oxidative stress-induced neuroinflammation with diminished pro-inflammatory markers in the pre frontal cortex. The outcomes collectively indicate ALC's potential to be used as a supplementation in the pharmacotherapy of AD.

Drug Repurposing Approach for Developing Novel Therapy Against Mupirocin-Resistant Staphylococcus aureus.

Multidrug resistance (MDR) is a major health issue for the treatment of infectious diseases throughout the world. Staphylococcus aureus (S. aureus) is a Gram-positive bacteria, responsible for various local and systemic infections in humans. The continuous and abrupt use of antibiotics against bacteria such as S. aureus results in the development of resistant strains. Presently, mupirocin (MUP) is the drug of choice against S. aureus and MDR (methicillin-resistant). However, S. aureus has acquired resistance against MUP as well due to isoleucyl-tRNA synthetase (IleS) mutation at sites 588 and 631. Thus, the aim of the present study was to discover novel bioactives against MUP-resistant S. aureus using in silico drug repurposing approaches. In silico drug repurposing techniques were used to obtain suitable bioactive lead molecules such as buclizine, tasosartan, emetine, medrysone, and so on. These lead molecules might be able to resolve this issue. These leads were obtained through molecular docking simulation based virtual screening, which could be promising for the treatment of MUP-resistant S. aureus. The findings of the present work need to be validated further through in vitro and in vivo studies for their clinical application.

A novel approach in the management of hyperhomocysteinemia.

Hyperhomocysteinemia (Hhcy) is a biochemical alteration with plasma levels of homocysteine higher than 15 µmol/L, associated with atherosclerosis, and with vascular thrombosis by disrupting endothelial cells. Homocysteine is a sulfur-containing amino acid derived from methionine which is an essential amino acid. Excess homocysteine produced in the body is expelled out by liver and kidney from the systemic circulation. Hhcy is caused by the excess deficiencies of the vitamins like pyridoxine (B6), folic acid (B9), or cyanocobalamin (B12). High protein consumers are usually at risk for hyperhomocysteinemia because of low plasma B12 levels. It is approximated that mild Hhcy occurs in 5-7% of the general population and 40% in patients with vascular disease. Patients with heart failure, impaired renal function, and diabetes should be screened since the prevalence of Hhcy in these patients appears to be quite high. In this article, we hypothesise that citicoline is a novel drug for the management of Hhcy. Furthermore, the side effects of citicoline are also minimal and self-limiting. If this strategy is validated, citicoline will be the cost-effective way to be administered for Hhcy. Many evidences are available which suggest that ignoring homocysteine levels in patients with the vascular disease would be unwise. Thus, there is an urgent need for health care providers to develop effective preventions and interventions program (folic acid, Vitamin B6 and Vitamin B12 supplementation as well as lifestyle change) to reduce this disorder.

Role of atrial natriuretic peptide in ischemic preconditioning-induced cardioprotection in the diabetic rat heart.

BACKGROUND: It has been noted that nitric oxide (NO) is involved in the ischemic preconditioning (IPC)-mediated cardioprotection. Diabetes is a downregulator of atrial natriuretic peptide (ANP), resulting in low expression of endothelial nitric oxide synthase (eNOS) by which NO level get reduced. The purpose of the present study was to investigate the role of ANP in attenuated cardioprotective effect of IPC in the diabetic rat heart. METHODS: The heart was isolated from the diabetic rat and mounted on Langendorff's apparatus, subjected to 30-min ischemia and 120-min reperfusion. IPC was mediated by four cycles of 5-min ischemia and 5-min reperfusion. The infarct size was estimated using triphenyltetrazolium chloride stain, and coronary effluent was analyzed for lactate dehydrogenase and creatinine kinase-MB release to assess the degree of myocardial injury. The cardiac release of NO was estimated indirectly by measuring the release of nitrite in coronary effluent. RESULTS: IPC-mediated cardioprotection was significantly attenuated in the diabetic rat as compared with the normal rat. Perfusion of ANP (0.1 µM/L) in the diabetic rat heart significantly restored the attenuated cardioprotective effect of IPC and also increased the release of NO. However, this observed cardioprotection was significantly attenuated by perfusion of N-nitro L-arginine methyl ester, an eNOS inhibitor (100 µM/L) noted in terms of increase in myocardial infarct size, release of lactate dehydrogenase and creatinine kinase-MB, and also decreases in release of NO. CONCLUSIONS: Thus, it is suggested that ANP restores the attenuated cardioprotective effect in the diabetic heart which may be due to increase in the expression of eNOS and subsequent increase in the activity of NO.