Alpha-lipoic Acid: An Antioxidant with Anti-Aging Properties for Disease Therapy.

The anti-aging effects of alpha-lipoic acid (αLA), a natural antioxidant synthesized in human tissues, have attracted a growing interest in recent years. αLA is a short- -chain sulfur-containing fatty acid occurring in the mitochondria of all kinds of eukaryotic cells. Both the oxidized disulfide of αLA and its reduced form (dihydrolipoic acid, DHLA) exhibit prominent antioxidant function. The amount of αLA inside the human body gradually decreases with age resulting in various health disorders. Its lack can be compensated by supplying from external sources such as dietary supplements or medicinal dosage forms. The primary objectives of this study were the analysis of updated information on the latest two-decade research regarding the use of αLA from an anti-aging perspective. The information was collected from PubMed, Wiley Online Library, Scopus, ScienceDirect, SpringerLink, Google Scholar, and clinicaltrials.gov. Numerous in silico, in vitro, in vivo, and clinical studies revealed that αLA shows a protective role in biological systems by direct or indirect reactive oxygen/nitrogen species quenching. αLA demonstrated beneficial properties in the prevention and treatment of many age-related disorders such as neurodegeneration, metabolic disorders, different cancers, nephropathy, infertility, and skin senescence. Its preventive effects in case of Alzheimer's and Parkinson's diseases are of particular interest. Further mechanistic and clinical studies are highly recommended to evaluate the wide spectrum of αLA therapeutic potential that could optimize its dietary intake for prevention and alleviation disorders related to aging.

LC-MS/MS bioanalytical method for the quantitative analysis of nifedipine, bisoprolol, and captopril in human plasma: Application to pharmacokinetic studies.

In this study, the development and validation of an accurate and highly sensitive LC-MS/MS method were performed for the estimation of nifedipine, bisoprolol and captopril in real human plasma. Liquid-liquid extraction using tert-butyl methyl ether was efficiently applied for extraction of the analytes from plasma samples. The chromatographic separation was carried out using an isocratic elution mode on the X-terra MS C18 column (4.6 × 50 mm, 3.5 µm). The mobile phase consisted of methanol-0.1% formic acid (95:5, v/v) for determination of nifedipine and bisoprolol and acetonitrile-0.1% formic acid (70:30, v/v) for determination of captopril with a flow rate of 0.5 ml/min. Acceptable results regarding the different validation characteristics of the analytes were obtained in accordance with US Food and Drug Administration recommendations for bioanalytical methods. The developed approach was linear over concentration ranges of 0.5-130.0, 50.0-4,500.0 and 0.3-30.0 ng/ml for nifedipine, captopril and bisoprolol, respectively. The method revealed a sufficient lower limit of quantification in the range of 0.3-50.0 ng/ml, as well as high recovery percentages, indicating high bioanalytical applicability. The proposed method was efficiently applied to a pharmacokinetic evaluation of a fixed-dose combination of the analytes in healthy male volunteers.

Natural Ingredients to Improve Immunity.

The immune system protects the body from infectious agents such as bacteria, viruses, or fungi. Once encountered with pathogens or antigens, the innate and adaptive arms of the immune system trigger a strong immune response to eliminate them from the system and protect the body. Thus, well-balanced immunity is pivotal for maintaining human health, as an insufficient level of immune defense leads to infections and tumors. In contrast, the excessive functioning of the immune system causes the development of autoimmune diseases and allergies. Strong immunity requires adequate nutrition, dietary interventions, and sufficient intake of certain vitamins (vitamin C, vitamin D, and folic acid) and minerals (magnesium, zinc, and selenium). Therefore, nutritional and micronutrient deficiencies lead to compromised immunity. Several natural ingredients have shown potent immunomodulatory properties. The immune-enhancing properties of many plants and fungi are due to containing bioactive phytoconstituents such as polyphenols, terpenoids, ß-glucans, vitamins, etc. Probiotics and prebiotics can be used as innovative tools to reduce intestinal inflammation and downregulate hypersensitivity reactions. Plant sources of melatonin, a multifunctional molecule with proven anti-inflammatory and immunomodulatory properties, have been discovered relatively recently. The bioactive compounds augment the immune response by directly increasing the cytotoxic activity of natural killer cells, macrophages, and neutrophils. Many phytoconstituents prevent cell damage due to their powerful antimicrobial, antioxidant, and anti-inflammatory properties. The present review attempts to understand the molecular mechanisms underlying the immune-enhancing properties of some bioactive compounds from plants, fungi, animals, microorganisms, and other natural sources.

Metformin Attenuates Postinfarction Myocardial Fibrosis and Inflammation in Mice.

Diabetes is a major risk factor for the development of cardiovascular disease with a higher incidence of myocardial infarction. This study explores the role of metformin, a first-line antihyperglycemic agent, in postinfarction fibrotic and inflammatory remodeling in mice. Three-month-old C57BI/6J mice were submitted to 30 min cardiac ischemia followed by reperfusion for 14 days. Intraperitoneal treatment with metformin (5 mg/kg) was initiated 15 min after the onset of reperfusion and maintained for 14 days. Real-time PCR was used to determine the levels of COL3A1, αSMA, CD68, TNF-α and IL-6. Increased collagen deposition and infiltration of macrophages in heart tissues are associated with upregulation of the inflammation-associated genes in mice after 14 days of reperfusion. Metformin treatment markedly reduced postinfarction fibrotic remodeling and CD68-positive cell population in mice. Moreover, metformin resulted in reduced expression of COL3A1, αSMA and CD68 after 14 days of reperfusion. Taken together, these results open new perspectives for the use of metformin as a drug that counteracts adverse myocardial fibroticand inflammatory remodeling after MI.

Chaotropic salts impact in HPLC approaches for simultaneous analysis of hydrophilic and lipophilic drugs.

Simultaneous determination of drugs with different physicochemical properties necessitates thorough research and careful selection of high-performance liquid chromatography conditions. In the present study, various concepts of high-performance liquid chromatography method development for this aim have been discussed. Moreover, the work was motivated by the advantages of utilizing different chaotropic anions as a new promising approach to overcome the limitations of ion-pairing agents commonly used for this purpose. Based on log P values, atorvastatin (log P = 6.36) and lisinopril (log P = -1.22) were chosen as representative examples for lipophilic and hydrophilic drugs, respectively. Several simple, economic, fast, and reliable high-performance liquid chromatography methods were developed for their simultaneous analysis and are presented in a comparative manner, highlighting their advantages and limitations. Peak elution profile showed satisfying retentions and resolution about 3. Photo-diode array calculations were exploited for identifying the molecules by their ultra-violet spectra and peak purity, calculated and presented as rectangular-shaped ratio grams. The linearity check showed excellent results and satisfactory system suitability parameters of both peaks. This confirms the investigation results and conclusions for the influence of the chaotropic salts on N-containing molecules, by increasing their retentivities, and improving peak shapes, even on different quality columns without end-capping and base-deactivating of separation matrixes.

Health Technology Assessment Implementation in Ukraine: Current Status and Future Perspectives.

OBJECTIVES: The need for improving healthcare decision making by implementing health technology assessment (HTA) has been a top priority in Ukraine since 2016. This study sought to provide a tailor-made HTA implementation roadmap, drawing on insights from national stakeholders. METHODS: We conducted a survey using a questionnaire already applied in previous HTA research. We assessed the status of HTA when reforms were initiated in 2016 and examined perspectives on possible future developments among policy makers and representatives of pharmaceutical companies and patient organizations. RESULTS: Thirty-two respondents answered the survey. Forty-eight percent of respondents were not aware of HTA training in Ukraine, but 91 percent preferred having either a graduate or postgraduate training. Experts stated that funding for HTA research and for critical appraisal of HTA submissions was limited, but in the future, they would increase funding mainly from public sources. A public HTA agency with academic support was the most preferred organizational structure. Eighty-eight percent of respondents opted for full transparency, making the HTA agency's recommendations and the related appraisal reports publicly available. A great majority of participants preferred mandating the use of local data in certain categories and indicated the importance of evaluating the transferability of international evidence. Healthcare priority and cost-effectiveness were the most important criteria for decisions, applied with a soft explicit threshold. CONCLUSIONS: Ukraine is in the early phase of implementing HTA and our study provides a clear vision of national stakeholders about the future directions. In addition, learning from the experiences of other countries may help the implementation process.

Hepatoprotective Effect of Melatonin in Toxic Liver Injury in Rats.

Background and objectives: toxic liver injury results in nitrooxidative stress. Melatonin is a potent free radical scavenger, an inducible nitric oxide synthase (iNOS) inhibitor and an activator of antioxidant enzymes. The aim of this study was to investigate the hepatoprotective effect of exogenous melatonin on animals with acute toxic hepatitis. Material and methods: 36 healthy Sprague-Dawley male rats were split into three equal groups and given carbon tetrachloride (CCl4), 2 g/kg (CCl4 group) or the same dose of CCl4 and melatonin, 10 mg/kg (CCl4/melatonin group) or saline (control group). The effect of melatonin on prooxidant and antioxidant system indexes, NO and NOS levels in serum and liver, data of mitochondrial chain functions and cytolysis in liver were evaluated in all three groups. Results: melatonin significantly decreased activities of AST, ALT, ceruloplasmine and thiobarbituric acid reactive substance (TBARS) in serum. Catalase activity was lowered in serum but not in the liver. Hepatic TBARS, lipid hydroperoxides and glutathione concentrations were decreased, while superoxide dismutase, mitochondrial cytochrome oxidase and succinate dehydrogenase activities increased. Melatonin inhibited synthesis of stable NO metabolites in serum: NO2-by 37.9%; NO3-by 29.2%. There was no significant difference in content NO2-in the liver, but concentration of NO3-increased by 32.6%. Melatonin significantly reduced iNOS concentrations both in serum (59.7%) and liver (57.8%) but did not affect endothelial isoform enzyme activities neither in serum, nor in liver. The histopathological liver lesions observed in the CCl4/melatonin group were less severe than those seen in the CCl4 group. Conclusions: we demonstrated an ameliorating effect of melatonin on prooxidants and antioxidants, NO-NOS systems balance, mitochondrial function and histopathological lesions in the liver in rats with CCl4-induced hepatitis.

Metformin Protects the Heart Against Hypertrophic and Apoptotic Remodeling After Myocardial Infarction.

Cardiovascular complications are the most prevalent cause of morbidity and mortality in diabetic patients. Metformin is currently the first-line blood glucose-lowering agent with potential relevance to cardiovascular diseases. However, the underpinning mechanisms of action remain elusive. Here, we report that metformin represses cardiac apoptosis at least in part through inhibition of Forkhead box O1 (FoxO1) pathway. In a mouse model of ischemia-reperfusion (I/R), treatment with metformin attenuated cardiac and hypertrophic remodeling after 14 days of post-reperfusion. Additionally, cardiac expression of brain-like natriuretic peptide (BNP) was significantly reduced in metformin-treated mice after 14 days of cardiac I/R. In cultured H9C2 cells, metformin counteracted hypertrophic and apoptotic responses to metabolic or hypoxic stress. FoxO1 silencing by siRNA abolished anti-apoptotic effect of metformin under hypoxic stress in H9C2 cells. Taken together, these results suggest that metformin protects the heart against hypertrophic and apoptotic remodeling after myocardial infarction.