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Colorectal cancer (CRC) is a common and highly metastatic cancer affecting people worldwide. Drug resistance and unwanted side effects are some of the limitations of current treatments for CRC. Naringenin (NAR) is a naturally occurring compound found in abundance in various citrus fruits such as oranges, grapefruits, and tomatoes. It possesses a diverse range of pharmacological and biological properties that are beneficial for human health. Numerous studies have highlighted its antioxidant, anticancer, and anti‐inflammatory activities, making it a subject of interest in scientific research. This review provides a comprehensive overview of the effects of NAR on CRC. The study's findings indicated that NAR: (1) interacts with estrogen receptors, (2) regulates the expression of genes related to the p53 signaling pathway, (3) promotes apoptosis by increasing the expression of proapoptotic genes (Bax, caspase9, and p53) and downregulation of the antiapoptotic gene Bcl2, (4) inhibits the activity of enzymes involved in cell survival and proliferation, (5) decreases cyclin D1 levels, (6) reduces the expression of cyclin‐dependent kinases (Cdk4, Cdk6, and Cdk7) and antiapoptotic genes (Bcl2, x‐IAP, and c‐IAP‐2) in CRC cells. In vitro CDK2 binding assay was also performed, showing that the NAR derivatives had better inhibitory activities on CDK2 than NAR. Based on the findings of this study, NAR is a potential therapeutic agent for CRC. Additional pharmacology and pharmacokinetics studies are required to fully elucidate the mechanisms of action of NAR and establish the most suitable dose for subsequent clinical investigations. Significance statement: The review discusses the molecular and biochemical processes related to naringenin (NAR's) effects on colorectal cancer (CRC), emphasizing its diverse pharmacological and biological properties. NAR interacts with estrogen receptors, regulates gene expression related to the p53 signaling pathway, promotes apoptosis, inhibits enzymes involved in cell survival and proliferation, decreases cyclin D1 levels, and reduces the expression of cyclin‐dependent kinases and antiapoptotic genes in CRC cells. In vitro studies demonstrate that NAR derivatives have better inhibitory activities on CDK2 than NAR, suggesting their potential as therapeutic agents for CRC. [ABSTRACT FROM AUTHOR]

Background: Despite several hundred clinical trials of drugs that initially showed promise, there has been limited clinical improvement in Alzheimer's disease (AD). This may be attributed to the existence of at least 25 abnormal cellular pathways that underlie the disease. It is improbable for a single drug to address all or most of these pathways, thus even drugs that show promise when administered alone are unlikely to produce significant results. According to previous studies, eight drugs, namely, dantrolene, erythropoietin, lithium, memantine, minocycline, piracetam, riluzole, and silymarin, have been found to target multiple pathways that are involved in the development of AD. Among these drugs, riluzole is currently indicated for the treatment of medical conditions in both adult patients and children and has gained increased attention from scientists due to its potential in the excitotoxic hypothesis of neurodegenerative diseases. Objective: The aim of this study was to investigate the effects of drugs on AD based on cellular and molecular mechanisms. Methods: The literature search for this study utilized the Scopus, ScienceDirect, PubMed, and Google Scholar databases to identify relevant articles. Results: Riluzole exerts its effects in AD through diverse pathways including the inhibition of voltage‐dependent sodium and calcium channels, blocking AMPA and NMDA receptors and inhibiting the release of glutamic acid release and stimulation of EAAT1‐EAAT2. Conclusion: In this review article, we aimed to review the neuroprotective properties of riluzole, a glutamate modulator, in AD, which could benefit patients with the disease. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra, leading to various motor and non‐motor symptoms. Several cellular and molecular mechanisms such as alpha‐synuclein (α‐syn) accumulation, mitochondrial dysfunction, oxidative stress and neuroinflammation are involved in the pathogenesis of this disease. MicroRNAs (miRNAs) play important roles in post‐transcriptional gene regulation. They are typically about 21–25 nucleotides in length and are involved in the regulation of gene expression by binding to the messenger RNA (mRNA) molecules. miRNAs like miR‐221 play important roles in various biological processes, including development, cell proliferation, differentiation and apoptosis. miR‐221 promotes neuronal survival against oxidative stress and neurite outgrowth and neuronal differentiation. Additionally, the role of miR‐221 in PD has been investigated in several studies. According to the results of these studies, (1) miR‐221 protects PC12 cells against oxidative stress induced by 6‐hydroxydopamine; (2) miR‐221 prevents Bax/caspase‐3 signalling activation by stopping Bim; (3) miR‐221 has moderate predictive power for PD; (4) miR‐221 directly targets PTEN, and PTEN over‐expression eliminates the protective action of miR‐221 on p‐AKT expression in PC12 cells; and (5) miRNA‐221 controls cell viability and apoptosis by manipulating the Akt signalling pathway in PD. This review study suggested that miR‐221 has the potential to be used as a clinical biomarker for PD diagnosis and stage assignment. [ABSTRACT FROM AUTHOR]

Background: Tamoxifen (TAM) is often recommended as a first‐line treatment for estrogen receptor‐positive breast cancer (BC). However, TAM resistance continues to be a medical challenge for BC with hormone receptor positivity. The function of macro‐autophagy and autophagy has recently been identified to be altered in BC, which suggests a potential mechanism for TAM resistance. Autophagy is a cellular stress‐induced response to preserve cellular homeostasis. Also, therapy‐induced autophagy, which is typically cytoprotective and activated in tumor cells, could sometimes be non‐protective, cytostatic, or cytotoxic depending on how it is regulated. Objective: This review explored the literature on the connections between hormonal therapies and autophagy. We investigated how autophagy could develop drug resistance in BC cells. Methods: Scopus, Science Direct, PubMed, and Google Scholar were used to search articles for this study. Results: The results demonstrated that protein kinases such as pAMPK, BAX, and p‐p70S6K could be a sign of autophagy in developing TAM resistance. According to the study's findings, autophagy plays an important role in BC patients' TAM resistance. Conclusion: Therefore, by overcoming endocrine resistance in estrogen receptor‐positive breast tumors, autophagy inhibition may improve the therapeutic efficacy of TAM. [ABSTRACT FROM AUTHOR]

Background: Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus. Objective: In this review, we have focused on Que's medicinal prospects as a neuroprotective drug. Methods: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. Results: The findings of this research demonstrate that (1) Que protected the blood‐brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1‐4, antioxidant activity, and Nrf2 levels in the brain. Conclusion: We discuss recent research on Que‐mediated Nrf2 expression in the management of several NLDs in this paper. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is frequently linked to metabolic disorders and is prevalent in obese and diabetic patients. The pathophysiology of NAFLD involves multiple factors, including insulin resistance (IR), oxidative stress (OS), inflammation, and genetic predisposition. Recently, there has been an emphasis on the use of herbal remedies with many people around the world resorting to phytonutrients or nutraceuticals for treatment of numerous health challenges in various national healthcare settings. Pomegranate (Punica granatum) parts, such as juice, peel, seed and flower, have high polyphenol content and is well known for its antioxidant capabilities. Pomegranate polyphenols, such as hydrolyzable tannins, anthocyanins, and flavonoids, have high antioxidant capabilities that can help lower the OS and inflammation associated with NAFLD. The study aimed to investigate whether pomegranate parts could attenuate OS, inflammation, and other risk factors associated with NAFLD, and ultimately prevent the development of the disease. The findings of this study revealed that: 1. pomegranate juice contains hypoglycemic qualities that can assist manage blood sugar levels, which is vital for avoiding and treating NAFLD. 2. Polyphenols from pomegranate flowers increase paraoxonase 1 (PON1) mRNA and protein levels in the liver, which can help protect liver enzymes and prevent NAFLD. 3. Punicalagin (PU) is one of the major ellagitannins found in pomegranate, and PU‐enriched pomegranate extract (PE) has been shown to inhibit HFD‐induced hyperlipidemia and hepatic lipid deposition in rats. 4. Pomegranate fruit consumption, which is high in antioxidants, can decrease the activity of AST and ALT (markers of liver damage), lower TNF‐α (a marker of inflammation), and improve overall antioxidant capacity in NAFLD patients. Overall, the polyphenols in pomegranate extracts have antioxidant, anti‐inflammatory, hypoglycemic, and protective effects on liver enzymes, which can help prevent and manage NAFLD effects on liver enzymes, which can help prevent and manage NAFLD. [ABSTRACT FROM AUTHOR]

ABSTRACT This study investigated the effects of different doses of vitamin E on oxidative stress, cognitive function, and gene expression in aged mice. A total of 32 male mice, aged 12 months, were divided into a control group and three treatment groups. These groups received varying daily doses of vitamin E for a period of 28 days. The results showed significant improvements in cognitive function, specifically in working memory and spatial learning, in the groups that received vitamin E (100, 200, or 400 mg/kg) compared to the control group. The markers of oxidative stress and antioxidant enzyme activities also demonstrated improvements, with higher doses of vitamin E showing greater effects. The analysis of gene expression revealed increased expression of SIRT1, Nrf2, and Calstabin2, particularly at higher doses of vitamin E. These findings suggest that vitamin E supplementation may help counteract age‐related cellular changes. The study concludes that vitamin E supplementation can reduce oxidative stress, enhance cognitive function, and affect genetic markers of aging in mice, which may have therapeutic benefits in addressing age‐related cognitive decline and oxidative damage. Further research is necessary to investigate the clinical implications of these findings in humans. [ABSTRACT FROM AUTHOR]