Melatonin in Medicinal and Food Plants : Occurrence, Bioavailability, and Health Potential for Humans

Melatonin is a widespread molecule among living organisms involved in multiple biological, hormonal, and physiological processes at cellular, tissue, and organic levels. It is well-known for its ability to cross the blood-brain barrier, and renowned antioxidant effects, acting as a free radical scavenger, up-regulating antioxidant enzymes, reducing mitochondrial electron leakage, and interfering with proinflammatory signaling pathways. Detected in various medicinal and food plants, its concentration is widely variable. Plant generative organs (e.g., flowers, fruits), and especially seeds, have been proposed as having the highest melatonin concentrations, markedly higher than those found in vertebrate tissues. In addition, seeds are also rich in other substances (lipids, sugars, and proteins), constituting the energetic reserve for a potentially growing seedling and beneficial for the human diet. Thus, given that dietary melatonin is absorbed in the gastrointestinal tract and transported into the bloodstream, the ingestion of medicinal and plant foods by mammals as a source of melatonin may be conceived as a key step in serum melatonin modulation and, consequently, health promotion

Resveratrol increases rate of apoptosis caused by purine analogues in malignant lymphocytes of chronic lymphocytic leukemia

In this study, we attempted to assess the interactions of resveratrol, a natural compound present in various plant species, with the purine analogues fludarabine and cladribine in terms of their effects on DNA damage and apoptosis in chronic lymphocytic leukemia (CLL) cells. The experiments were performed ex vivo using short-term cell cultures of blood and bone marrow cells from newly diagnosed untreated patients. We analyzed the expression of active caspase-3 and the BCL-2/BAX ratio as markers of apoptosis and the expression of phosphorylated histone H2AX (γH2AX) and activated ATM kinase, which are reporters of DNA damage. The results of our study revealed that resveratrol induced apoptosis in CLL cells in a tumor-specific manner but did not affect non-leukemic cells, and apoptosis was associated with a decreased BCL2/BAX ratio. Here, we report for the first time that both resveratrol + fludarabine and resveratrol + cladribine caused a higher rate of apoptosis in comparison to the rate caused by a single drug. The percentage of apoptotic cells induced by resveratrol alone was higher in the group of patients with better prognostic markers than in those with worse prognostic markers. However, the rates of apoptosis caused by resveratrol combined with purine analogues were independent of ZAP-70 and CD38 expression and the clinical state of the disease; they were only dependent on the presence of high-risk cytogenetic abnormalities. We also observed an increase in γH2AX expression together with a rise in activated ATM in most of the analyzed samples. The obtained results indicate that resveratrol might warrant further study as a new therapeutic option for CLL patients. This naturally occurring substance may be used as a single agent, especially in older persons for whom there are some limitations for the use of aggressive treatment. On the other hand, a lower purine analogue dose could potentially be used in combination with resveratrol because of their combined effect. One of the mechanisms of action of resveratrol is the induction of DNA damage, which ultimately leads to apoptosis

Simvastatin and purine analogs have a synergic effect on apoptosis of chronic lymphocytic leukemia cells

Despite many therapeutic regimens introduced recently, chronic lymphocytic leukemia (CLL) is still an incurable disorder. Thus, there is an urgent need to discover novel, less toxic and more effective drugs for CLL patients. In this study, we attempted to assess simvastatin, widely used as a cholesterol-lowering drug, both as a single agent and in combination with purine analogs—fludarabine and cladribine—in terms of its effect on apoptosis and DNA damage of CLL cells. The experiments were done in ex vivo short-term cell cultures of blood and bone marrow cells from newly diagnosed untreated patients. We analyzed expression of active caspase-3 and the BCL-2/BAX ratio as markers of apoptosis and the expression of phosphorylated histone H2AX (named γH2AX) and activated ATM kinase (ataxia telangiectasia mutated kinase), reporters of DNA damage. Results of our study revealed that simvastatin induced apoptosis of CLL cells concurrently with lowering of BCL-2/BAX ratio, and its pro-apoptotic effect is tumor-specific, not affecting normal lymphocytes. We observed that combinations of simvastatin+fludarabine and simvastatin+cladribine had a synergic effect in inducing apoptosis. Interestingly, the rate of apoptosis caused by simvastatin alone and in combination was independent of markers of disease progression like ZAP-70 and CD38 expression or clinical stage according to Rai classification. We have also seen an increase in γH2AX expression in parallel with activation of ATM in most of the analyzed samples. The results suggest that simvastatin can be used in the treatment of CLL patients as a single agent as well as in combination with purine analogs, being equally effective both in high-risk and good-prognosis patients. One of the mechanisms of simvastatin action is inducing DNA damage that ultimately leads to apoptosis

Vitamin D in SARS-CoV-2 infection

Background. SARS-CoV-2 virus is one of the largest RNA viruses, included in the coronavirus group, showing tropism to airway epithelial cells. SARS-CoV-2 causes an acute respiratory infectious disease, Covid-19. According to WHO reports, mortality due to Covid-19 is higher in the elderly and in those burdened with comorbidities such as diabetes, obstructive pulmonary disease, coronary artery disease, cancer, hypertension, hepatitis B, obesity or chronic kidney disease. Objective. The aim of the study was to review the current literature on the influence and importance of vitamin D levels on the course of SARS-CoV-2 infection. Material and method. A systematic review of studies published from January 1, 2009 to June 31, 2021 has been performed. For this purpose, bibliographic databases such as PubMed and Scopus were searched. The following keywords and combinations were used: Covid-19, vitamin D, 25-hydroxy-vitamin D, vitamin D supplementation, SARS-CoV-2. Results. It has been shown that vitamin D plays an important role in the mechanisms of the innate immunity in the course of the acute respiratory infections. The overlapping factors of the severity of COVID-19 disease, vitamin D deficiency, and the prevalence of obesity, age scare, ethnicity, has led some researchers to hypothesize that vitamin D supplementation may be promising as a preventive or therapeutic measure for COVID-19. Conclusions. A very important factor that has an immunomodulatory character is vitamin D, the adequate supplementation of which can be a preventive or therapeutic measure in case of SARS-CoV-2 infection, especially in elderly people, with obesity and other chronic diseases

Effect of Camp Level on Thallus Growth and Gametangia Development in Macroalga Chara Vulgaris (Charales, Charophyta)

cAMP is a second messenger which plays a regulatory role in a wide variety of biological processes in organisms ranging from prokaryotes to higher eukaryotes, but knowledge of its role in macroalgae and vascular plants is limited. We modified cAMP levels in the macroalga Chara vulgaris thallus and studied the effects on thallus growth and gametangia development: db-cAMP (permeable analog of cAMP), adenylate cyclase (AC) activator, forskolin and theophylline (cAMP phosphodiesterase (PDE) inhibitor) were used to elevate cAMP levels, and the AC inhibitors 2'-dAdo and 2'-d3'-AMP were used to decrease them. The results suggest that in Chara vulgaris the cAMP pathway may regulate both vegetative thallus growth and gametangia development, and that these effects may depend on this second-messenger level. Elevated cAMP stimulated thallus growth and delayed gametangia development; decreased cAMP inhibited thallus growth and accelerated maturation of both antheridia and oogonia. These results suggest that the cAMP pathway participates in regulation of developmen-tal processes in Chara vulgaris and that thallus growth and gametangia development require different cAMP lev-els in cells