Alpha pyrrolidinovalerophenone (α-PVP) administration impairs spatial learning and memory in rats through brain mitochondrial dysfunction.

Novel psychoactive substances (NPS) consumption has increased in recent years, thus NPS-induced cognitive decline is a current source of concern. Alpha-pyrrolidinovalerophenone (α-PVP), as a member of NPS, is consumed throughout regions like Washington, D.C., Eastern Europe, and Central Asia. Mitochondrial dysfunction plays an essential role in NPS-induced cognitive impairment. Meanwhile, no investigations have been conducted regarding the α-PVP impact on spatial learning/memory and associated mechanisms. Consequently, our study investigated the α-PVP effect on spatial learning/memory and brain mitochondrial function. Wistar rats received different α-PVP doses (5, 10, and 20 mg/kg) intraperitoneally for 10 sequential days; 24 h after the last dose, spatial learning/memory was evaluated by the Morris Water Maze (MWM). Furthermore, brain mitochondrial protein yield and mitochondrial function variables (Mitochondrial swelling, succinate dehydrogenase (SDH) activity, lipid peroxidation, Mitochondrial Membrane Potential (MMP), Reactive oxygen species (ROS) level, brain ADP/ATP proportion, cytochrome c release, Mitochondrial Outer Membrane (MOM) damage) were examined. α-PVP higher dose (20 mg/kg) significantly impaired spatial learning/memory, mitochondrial protein yield, and brain mitochondrial function (caused reduced SDH activity, increased mitochondrial swelling, elevated ROS generation, increased lipid peroxidation, collapsed MMP, increased cytochrome c release, elevated brain ADP/ATP proportion, and MOM damage). Moreover, the lower dose of α-PVP (5 mg/kg) did not alter spatial learning/memory and brain mitochondrial function. These findings provide the first evidence regarding impaired spatial learning/memory following repeated administration of α-PVP and the possible role of brain mitochondrial dysfunction in these cognitive impairments.

Longevity and anti-aging effects of curcumin supplementation.

Aging is a gradual and irreversible process that is accompanied by an overall decline in cellular function and a significant increase in the risk of age-associated disorders. Generally, delaying aging is a more effective method than treating diseases associated with aging. Currently, researchers are focused on natural compounds and their therapeutic and health benefits. Curcumin is the main active substance that is present in turmeric, a spice that is made up of the roots and rhizomes of the Curcuma longa plant. Curcumin demonstrated a positive impact on slowing down the aging process by postponing age-related changes. This compound may have anti-aging properties by changing levels of proteins involved in the aging process, such as sirtuins and AMPK, and inhibiting pro-aging proteins, such as NF-κB and mTOR. In clinical research, this herbal compound has been extensively examined in terms of safety, efficacy, and pharmacokinetics. There are numerous effects of curcumin on mechanisms related to aging and human diseases, so we discuss many of them in detail in this review.

Citrus flavonoids and adhesion molecules: Potential role in the management of atherosclerosis.

Atherosclerosis as a chronic inflammatory disorder is accompanied with oxidative stress which causes a high morbidity and mortality. Adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), P-selectin, and E-selectin, are amongst the most important contributors in atherosclerosis. In such cases, dietary interventions with functional foods containing natural antioxidant and anti-inflammatory constituents are of a great interest. Citrus fruits are rich sources of flavonoids as natural pigments with potent antioxidant and anti-inflammatory activities. This study aims to review current evidence regarding the role of citrus flavonoids in the management of atherosclerosis with a focus on their effect on adhesion molecules. Electronic databases including PubMed, Scopus, and Web of Science were searched with the names of adhesion molecules and flavonoids from inception until January 2023. The included articles highly support the beneficial effects of citrus flavonoids in preclinical models of atherosclerosis. Quercetin, naringin and naringenin, hesperidin and hesperetin, nobiletin, rutin, luteolin, apigenin, and kaempferol are the most common flavonoids in citrus fruits which could modulate adhesion molecules including ICAM-1, VCAM-1, E-selectin, and P-selectin. Additionally, markers of chronic inflammation such as interleukins, tumor necrosis factor-α, nuclear factor-κB, and nitric oxide signaling, as well as oxidative stress markers like superoxide dismutase and glutathione were all normalized upon administration of citrus flavonoids. Conclusively, this review confirms the modulatory role of flavonoids on adhesion molecules in atherosclerosis based on the preclinical evaluations. Thus, citrus fruits can be further studied in atherosclerotic patients regarding their activity in reducing adhesion molecules.

A review on garlic as a supplement for Alzheimer's disease: a mechanistic insight in its direct and indirect effects.

Alzheimer's disease (AD) is one of the most complicated neurodegenerative diseases causing dementia in human beings. Aside from that incidence of AD is increasing also its treatment is very complicated. There are several known hypotheses regarding the pathology of Alzheimer's disease, including the Amyloid beta hypothesis, Tau hypothesis, inflammation hypothesis, and cholinergic hypothesis, which are investigated in different researches to completely elucidate the pathology of AD. Aside from these some new mechanisms such as immune, endocrine, and vagus pathways, as well as bacteria metabolite secretions are being explained as other causes that are somehow related to AD pathogenesis. There is still no definite treatment for Alzheimer's disease that can completely cure and eradicate AD. Garlic (Allium sativum) is a traditional herb used as a spice in different cultures and due to the organosulfur compounds like allicin it possesses highly anti-oxidant properties and the benefits of garlic in cardiovascular diseases like hypertension and atherosclerosis is examined and reviewed, although its beneficiary effects in neurodegenerative diseases such as AD is not completely understood. In this review, we discuss the effects of garlic based on its components such as allicin, S-allyl cysteine on Alzheimer's disease and the mechanisms that garlic components can be beneficiary for AD patients, including its effects amyloid beta, oxidative stress, tau protein, gene expression, and cholinesterase enzymes. Based on the literature review we have done, garlic has revealed beneficiary effects on Alzheimer's disease, especially in animal studies; however, more studies should be done on human populations to find the exact mechanism of garlic effects on AD patients.

The Neurotoxic Mechanisms of Graphene Family Nanomaterials at the Cellular Level: A Solution-based Approach Review.

The graphene family nanomaterials (GFNs) have been recognized to have potential applications in biomedicine, especially in the rag nostic, drug delivery and neuroimaging. Multiple studies have examined the neurotoxicity of GFNs to assay their toxic effects on organisms and ecosystems. In this article, we reviewed the different neurotoxicity effects of GFNs at intracellular levels, including nucleus-related effects and cytosolic mechanisms, as well as extracellular levels, including effects on enzyme activity, oxidative stress, behavior, neurotransmitters, and central nervous system (CNS). Furthermore, for the sake of the solution, we discussed the reducing ways of graphene toxicity. A schematic description is shown in Fig. (1).

Epigenetic effects of graphene oxide and its derivatives: A mini-review.

Graphene oxide (GO), an engineered nanomaterial, has a two-dimensional structure with carbon atoms arranged in a hexagonal array. While it has been widely used in many industries, such as biomedicine, electronics, and biosensors, there are still concerns over its safety. Recently, many studies have focused on the potential toxicity of GO. Epigenetic toxicity is an important aspect of a material's toxicological profile, since changes in gene expression have been associated with carcinogenicity and disease progression. In this review, we focus on the epigenetic alterations caused by GO, including DNA methylation, histone modification, and altered expression of non-coding RNAs. GO can affect DNA methyltransferase activity and disrupt the methylation of cytosine bases in DNA strands, leading to alteration of genome expression. Modulation of histones by GO, targeting histone deacetylase and demethylase, as well as dysregulation of miRNA and lncRNA expression have been reported. Further studies are required to determine the mechanisms of GO-induced epigenetic alterations.