Due to its health benefits, resveratrol (RE) is one of the most researched natural polyphenols. Resveratrol's health benefits were first highlighted in the early 1990s in the French paradox study, ...which opened extensive research activity into this compound. Ever since, several pharmacological activities including antioxidant, anti-aging, anti-inflammatory, anti-cancerous, anti-diabetic, cardioprotective, and neuroprotective properties, were attributed to RE. However, results from the available human clinical trials were controversial concerning the protective effects of RE against diseases and their sequelae. The reason for these conflicting findings is varied but differences in the characteristics of the enrolled patients, RE doses used, and duration of RE supplementation were proposed, at least in part, as possible causes. In particular, the optimal RE dosage capable of maximizing its health benefits without raising toxicity issues remains an area of extensive research. In this context, while there is a consistent body of literature on the protective effects of RE against diseases, there are relatively few reports investigating its possible toxicity. Indeed, toxicity and adverse effects were reported following consumption of RE; therefore, extensive future studies on the long-term effects, as well as the in vivo adverse effects, of RE supplementation in humans are needed. Furthermore, data on the interactions of RE when combined with other therapies are still lacking, as well as results related to its absorption and bioavailability in the human body. In this review, we collect and summarize the available literature about RE toxicity and side effects. In this process, we analyze in vitro and in vivo studies that have addressed this stilbenoid. These studies suggest that RE still has an unexplored side. Finally, we discuss the new delivery methods that are being employed to overcome the low bioavailability of RE.
Cancer is a leading cause of morbidity and mortality around the globe. Reactive oxygen species (ROS) play contradicting roles in cancer incidence and progression. Antioxidants have attracted ...attention as emerging therapeutic agents. Among these are flavonoids, which are natural polyphenols with established anticancer and antioxidant capacities. Increasing evidence shows that flavonoids can inhibit carcinogenesis via suppressing ROS levels. Surprisingly, flavonoids can also trigger excessive oxidative stress, but this can also induce death of malignant cells. In this review, we explore the inherent characteristics that contribute to the antioxidant capacity of flavonoids, and we dissect the scenarios in which they play the contrasting role as pro-oxidants. Furthermore, we elaborate on the pathways that link flavonoid-mediated modulation of ROS to the prevention and treatment of cancer. Special attention is given to the ROS-mediated anticancer functions that (-)-epigallocatechin gallate (EGCG), hesperetin, naringenin, quercetin, luteolin, and apigenin evoke in various cancers. We also delve into the structure-function relations that make flavonoids potent antioxidants. This review provides a detailed perspective that can be utilized in future experiments or trials that aim at utilizing flavonoids or verifying their efficacy for developing new pharmacologic agents. We support the argument that flavonoids are attractive candidates for cancer therapy.
Sestrin2 (SESN2), a highly conserved stress-inducible metabolic protein, is known to repress reactive oxygen species (ROS) and provide cytoprotection against various noxious stimuli including ...genotoxic and oxidative stress, endoplasmic reticulum (ER) stress, and hypoxia. Studies demonstrate that the upregulation of Sestrin2 under conditions of oxidative stress augments autophagy-directed degradation of Kelch-like ECH-associated protein 1 (Keap1), which targets and breaks down nuclear erythroid-related factor 2 (Nrf2), a key regulator of various antioxidant genes. Moreover, ER stress and hypoxia are shown to induce Sestrins, which ultimately reduce cellular ROS levels. Sestrin2 also plays a pivotal role in metabolic regulation through activation of the key energy sensor AMP-dependent protein kinase (AMPK) and inhibition of mammalian target of rapamycin complex 1 (mTORC1). Other downstream effects of Sestrins include autophagy activation, antiapoptotic effects in normal cells, and proapoptotic effects in cancer cells. As perturbations in the aforementioned pathways are well documented in multiple diseases, Sestrin2 might serve as a potential therapeutic target for various diseases. Thus, the aim of this review is to discuss the upstream regulators and the downstream effectors of Sestrins and to highlight the significance of Sestrin2 as a biomarker and a therapeutic target in diseases such as metabolic disorders, cardiovascular and neurodegenerative diseases, and cancer.
MicroRNAs in Cardiac Hypertrophy Wehbe, Nadine; Nasser, Suzanne Awani; Pintus, Gianfranco ...
International journal of molecular sciences,
09/2019, Letnik:
20, Številka:
19
Journal Article
Recenzirano
Odprti dostop
Like other organs, the heart undergoes normal adaptive remodeling, such as cardiac hypertrophy, with age. This remodeling, however, is intensified under stress and pathological conditions. Cardiac ...remodeling could be beneficial for a short period of time, to maintain a normal cardiac output in times of need; however, chronic cardiac hypertrophy may lead to heart failure and death. MicroRNAs (miRNAs) are known to have a role in the regulation of cardiac hypertrophy. This paper reviews recent advances in the field of miRNAs and cardiac hypertrophy, highlighting the latest findings for targeted genes and involved signaling pathways. By targeting pro-hypertrophic genes and signaling pathways, some of these miRNAs alleviate cardiac hypertrophy, while others enhance it. Therefore, miRNAs represent very promising potential pharmacotherapeutic targets for the management and treatment of cardiac hypertrophy.
Different pathways implicated in the effects of flavonoids on blood pressure regulation.
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•Increased flavonoid consumption imparts antihypertensive benefits.•Luteolin, Quercetin, ...Kaempferol, Epicatechin, and Daidzein increase eNOS activity.•Many flavonoids reduce oxidative stress and improve endothelial function.•Many flavonoids induce vasodilation by modulating K+ and Ca2+ ion channels.
Flavonoids are a diverse group of bioactive polyphenolic compounds abundant in dietary plants and herbs. Regular consumption of flavonoids exerts cardio-vasculoprotective effects and may reduce the onset or progression of many cardiovascular diseases, particularly hypertension. Observational studies suggest inverse associations among either of these three combinations: a) anthocyanin intake and risk of myocardial infarction (MI), b) flavanone intake and risk of ischemic stroke and c) flavonol intake and risk of type 2 diabetes mellitus. Human randomized controlled trials (RCTs) show that catechins and quercetin impart significant blood pressure lowering effects. Mechanistically, flavonoids mediate their antihypertensive effects through increasing nitric oxide (NO) bioavailability, reducing endothelial cell oxidative stress or modulating vascular ion channel activity. In this review, we focus on the six main subgroups of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones. We further discuss their antihypertensive effects, and their possible mechanisms of regulating blood pressure. We conclude by addressing the safety of these compounds as well as their potential use in hypertension management and treatment.
As the world faces the most serious and widespread pandemic in recent history, claiming nearly 1,945,610 lives and infecting over 90 million individuals up to January 13, 2021, controlling the spread ...of COVID-19 is still limited to efforts done by the general population implementing rules and restrictions passed by world governments and organizations. As we wait for the approved vaccines to become widely distributed, the best approach to fighting the spread of this disease is mostly preventative depending largely on individuals' compliance. This study aimed to determine the knowledge, attitude and practices (KAP) towards COVID-19 in Lebanon.
A descriptive analysis was performed to describe the outcome measures of knowledge, attitudes and practices towards COVID-19 on a convenience sample from the Lebanese population in relation to socio-demographic characteristics and level of concern towards COVID-19. One thousand eight hundred sixty-one participants filled in an online survey (response rate: 18.5%) distributed by social media to social networks of the research team members.
Participants were mainly young (49.4% between 18 and 24 years) and males (73.7%). Participants showed an overall appropriate knowledge of COVID-19 (67.1%) and positive attitude (around 90% were optimistic about treatment and vaccination) and had good preventive practices towards COVID-19 (around 75% washed hands and avoided public places). Knowledge and practices correlated positively with marriage, age, education, working in a healthcare field and with the level of concern about getting COVID-19.
This study found good overall levels of KAP among the studied Lebanese population. This can help in controlling the spread of COVID-19 if individuals were forced to adhere to social distancing and appropriate preventative practices.
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