The Effects of Fisetin and Curcumin on Oxidative Damage Caused by Transition Metals in Neurodegenerative Diseases.

Neurodegenerative diseases pose a significant health challenge for the elderly. The escalating presence of toxic metals and chemicals in the environment is a potential contributor to central nervous system dysfunction and the onset of neurodegenerative conditions. Transition metals play a crucial role in various pathophysiological mechanisms associated with prevalent neurodegenerative diseases such as Alzheimer's and Parkinson's. Given the ubiquitous exposure to metals from diverse sources in everyday life, the workplace, and the environment, most of the population faces regular contact with different forms of these metals. Disturbances in the levels and homeostasis of certain transition metals are closely linked to the manifestation of neurodegenerative disorders. Oxidative damage further exacerbates the progression of neurological consequences. Presently, there exists no curative therapy for individuals afflicted by neurodegenerative diseases, with treatment approaches primarily focusing on alleviating pathological symptoms. Within the realm of biologically active compounds derived from plants, flavonoids and curcuminoids stand out for their extensively documented antioxidant, antiplatelet, and neuroprotective properties. The utilization of these compounds holds the potential to formulate highly effective therapeutic strategies for managing neurodegenerative diseases. This review provides a comprehensive overview of the impact of abnormal metal levels, particularly copper, iron, and zinc, on the initiation and progression of neurodegenerative diseases. Additionally, it aims to elucidate the potential of fisetin and curcumin to inhibit or decelerate the neurodegenerative process.

Berberine: Pharmacological Features in Health, Disease and Aging.

BACKGROUND: Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. OBJECTIVE: This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. METHODS: Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. RESULTS: Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. CONCLUSION: Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

An Update on Glutathione's Biosynthesis, Metabolism, Functions, and Medicinal Purposes.

Glutathione (GSH) has been the focus of increased scientific interest in the last decades. It plays a crucial role in all major physiological processes by supplying antioxidant defenses through participating in cellular redox reactions in the human body and other living organisms. GSH also participates in detoxifying xenobiotics, protecting protein thiols from crosslinking and oxidation, regulating the cell cycle, storing cysteine, etc. The significant role of GSH in the most important physiological processes has been highlighted, such as maintaining the redox balance and reducing oxidative stress due to its ability to inactivate the reactive oxygen, nitrogen, and sulfur species. It can also enhance metabolic detoxification and regulate the function of the immune system. All of these characteristics make it a universal biomarker since its proper balance is essential for improving health and treating some age-related disorders. This review presents a current concept of the synthesis and metabolism of GSH; its main functions in a living organism, and as a precursor and cofactor; data on the use of GSH for medicinal purposes in the prevention and treatment of some diseases, as well as a nutritional strategy to maintain a normal pool of GSH in the body. The data were gathered by searching relevant information in multiple databases, such as PubMed, Scopus, ScienceDirect, and Google Scholar.

Caffeic Acid Phenethyl Ester: A Potential Therapeutic Cancer Agent?

BACKGROUND: Propolis and its major phenolic compound, caffeic acid phenethyl ester (CAPE), have garnered considerable scientific interest due to their anti-inflammatory properties and potential therapeutic applications. OBJECTIVES: This narrative review explores the potential utility of CAPE in cancer treatment. METHODS: We comprehensively reviewed relevant studies from scientific databases (PubMed and Web of Science) from 2000 to 2022. Our search focused on keywords such as cancer, natural drugs, caffeic acid phenethyl ester, CAPE, cancer cell lines, antitumor effects, and propolis. RESULTS: CAPE exhibits diverse biological benefits, including antimicrobial, antioxidant, antiviral, anti-inflammatory, cytotoxic, and potentially anti-carcinogenic properties. Numerous studies have demonstrated its wide-ranging antitumor effects on various cancer cell lines, including growth inhibition, apoptosis induction, tumor invasiveness prevention, malignancy suppression, and anti-angiogenic activity. CONCLUSION: Following comprehensive preclinical toxicity assessments, further evaluation of CAPE's efficacy and safety through clinical trials is highly recommended to elucidate its potential health benefits in diverse forms of human cancer.

The Role of Astaxanthin as a Nutraceutical in Health and Age-Related Conditions.

The current review provides an up-to-date analysis of scientific data on astaxanthin (ASX) sources and experimental studies on its health benefits as a potent antioxidant in the aging process. ASX is a liposoluble carotenoid nutrient and reddish-orange pigment, naturally synthesized by numerous microalgae, yeasts, and bacteria as secondary metabolites. Provides a reddish hue to redfish and shellfish flesh that feed on ASX-producing microorganisms. The microalga Haematococcus pluvialis is the most important source for its industrial bioproduction. Due to its strong antioxidant properties, numerous investigations reported that natural ASX is a more significant antioxidant agent than other antioxidants, such as vitamin C, vitamin E, and ß-carotene. Furthermore, several data show that ASX possesses important nutraceutical applications and health benefits, especially in healthy aging processes. However, further studies are needed for a deeper understanding of the potential mechanisms through which ASX could lead to its effective role in the healthy aging process, such as supporting brain health and skin homeostasis. This review highlights the current investigations on the effective role of ASX in oxidative stress, aging mechanisms, skin physiology, and central nervous system functioning, and shows the potential clinical implications related to its consumption.

Polyphenols in Metabolic Diseases.

Polyphenols (PPs) are a large group of phytochemicals containing phenolic rings with two or more hydroxyl groups. They possess powerful antioxidant properties, multiple therapeutic effects, and possible health benefits in vivo and in vitro, as well as reported clinical studies. Considering their free-radical scavenging and anti-inflammatory properties, these substances can be used to treat different kinds of conditions associated with metabolic disorders. Many symptoms of metabolic syndrome (MtS), including obesity, dyslipidemia, atherosclerosis, elevated blood sugar, accelerating aging, liver intoxication, hypertension, as well as cancer and neurodegenerative disorders, are substantially relieved by dietary PPs. The present study explores the bioprotective properties and associated underlying mechanisms of PPs. A detailed understanding of these natural compounds will open up new opportunities for producing unique natural PP-rich dietary and medicinal plans, ultimately affirming their health benefits.

Selenium: An Antioxidant with a Critical Role in Anti-Aging.

Aging is characterized by an imbalance between damage inflicted by reactive oxygen species (ROS) and the antioxidative defenses of the organism. As a significant nutritional factor, the trace element selenium (Se) may remodel gradual and spontaneous physiological changes caused by oxidative stress, potentially leading to disease prevention and healthy aging. Se is involved in improving antioxidant defense, immune functions, and metabolic homeostasis. An inadequate Se status may reduce human life expectancy by accelerating the aging process or increasing vulnerability to various disorders, including immunity dysfunction, and cancer risk. This review highlights the available studies on the effective role of Se in aging mechanisms and shows the potential clinical implications related to its consumption. The main sources of organic Se and the advantages of its nanoformulations were also discussed.

Effect of methylmercury on fetal neurobehavioral development: an overview of the possible mechanisms of toxicity and the neuroprotective effect of phytochemicals.

Methylmercury (MeHg) is a global environmental pollutant with neurotoxic effects. Exposure to MeHg via consumption of seafood and fish can severely impact fetal neurobehavioral development even when MeHg levels in maternal blood are as low as about 5 µg/L, which the mother tolerates well. Persistent motor dysfunctions and cognitive deficits may result from trans-placental exposure. The present review summarizes current knowledge on the mechanisms of MeHg toxicity during the period of nervous system development. Although cerebellar Purkinje cells are MeHg targets, the actions of MeHg on thiol components in the neuronal cytoskeleton as well as on mitochondrial enzymes and induction of disturbances of glutamate signaling can impair extra-cerebellar functions, also at levels well tolerated by adult individuals. Numerous herbal substances possess neuroprotective effects, predominantly represented by natural polyphenolic molecules that might be utilized to develop natural drugs to alleviate neurotoxicity symptoms caused by MeHg or other Hg compounds.

Flavonoids and stilbenoids as a promising arsenal for the management of chronic arsenic toxicity.

Rapid industrial and technological development has impacted ecosystem homeostasis strongly. Arsenic is one of the most detrimental environmental toxins and its management with chelating agents remains a matter of concern due to associated adverse effects. Thus, safer and more effective alternative therapy is required to manage arsenic toxicity. Based on existing evidence, native and indigenous plant-based active biomolecules appear as a promising strategy to mitigate arsenic-induced toxicity with an acceptable safety profile. In this regard, various phytochemicals (flavonoids and stilbenoids) are considered important classes of polyphenolic compounds with antioxidant and chelation effects, which may facilitate the removal of arsenic from the body more effectively and safely with regard to conventional approaches. This review presents an overview of conventional chelating agents and the potential role of flavonoids and stilbenoids in ameliorating arsenic toxicity. This report may provide a roadmap for identifying novel prophylactic/therapeutic strategies for managing arsenic toxicity.

Ellagic Acid: A Review on Its Natural Sources, Chemical Stability, and Therapeutic Potential.

Ellagic acid (EA) is a bioactive polyphenolic compound naturally occurring as secondary metabolite in many plant taxa. EA content is considerable in pomegranate (Punica granatum L.) and in wood and bark of some tree species. Structurally, EA is a dilactone of hexahydroxydiphenic acid (HHDP), a dimeric gallic acid derivative, produced mainly by hydrolysis of ellagitannins, a widely distributed group of secondary metabolites. EA is attracting attention due to its antioxidant, anti-inflammatory, antimutagenic, and antiproliferative properties. EA displayed pharmacological effects in various in vitro and in vivo model systems. Furthermore, EA has also been well documented for its antiallergic, antiatherosclerotic, cardioprotective, hepatoprotective, nephroprotective, and neuroprotective properties. This review reports on the health-promoting effects of EA, along with possible mechanisms of its action in maintaining the health status, by summarizing the literature related to the therapeutic potential of this polyphenolic in the treatment of several human diseases.

Arsenic intoxication: general aspects and chelating agents.

Arsenic (As) is widely used in the modern industry, especially in the production of pesticides, herbicides, wood preservatives, and semiconductors. The sources of As such as contaminated water, air, soil, but also food, can cause serious human diseases. The complex mechanism of As toxicity in the human body is associated with the generation of free radicals and the induction of oxidative damage in the cell. One effective strategy in reducing the toxic effects of As is the usage of chelating agents, which provide the formation of inert chelator-metal complexes with their further excretion from the body. This review discusses different aspects of the use of metal chelators, alone or in combination, in the treatment of As poisoning. Consideration is given to the therapeutic effect of thiol chelators such as meso-2,3-dimercaptosuccinic acid, sodium 2,3-dimercapto-1-propanesulfonate, 2,3-dimercaptopropanol, penicillamine, ethylenediaminetetraacetic acid, and other recent agents against As toxicity. The review also considers the possible role of flavonoids, trace elements, and herbal drugs as promising natural chelating and detoxifying agents.