1,721,032 research outputs found
Possible Effects of Dietary Anthocyanins on Diabetes and Insulin Resistance
No full textDiabetes is reaching epidemic proportions worldwide. Many dietary compounds have been found to exert health beneficial effects against different pathologies including diabetes. Most bioactive compounds have been identified in fruits and vegetables and their mechanisms of action explored both in vitro and in vivo. In particular, great interest has been given to polyphenols and especially to a specific subset of molecules, i.e. anthocyanins. Several lines of evidence suggest that anthocyanins have positive effects on human health by inducing a number of biological activities. This review will give an overview on the influence of dietary anthocyanins on preventing and managing type 2 diabetes In particular, in vitro and in vivo studies will be presented.The article also reviews the potential clinical impact of the antidiabetic activity of anthocyanins and outlines the major challenges of using anthocyanins for diabetes treatment
Perspectives in Designing Multifunctional Molecules in Antipsychotic Drug Discovery
No full textPreclinical Research A novel and promising approach to overcome the limits of single-target therapy is represented by the multitarget approach. This strategy aims to simultaneously modulate several targets involved in the pathophysiology of a multifactorial disease, with the potential to enhance therapeutic effectiveness and improve drug safety. Although there has been a marked growth in the design of multitarget drugs (MTDs) in the last years in the context of anti-Alzheimer and anti-cancer drug discovery, a parallel expansion was not observed in antipsychotic drugs, even that for psychiatric disorders there is a cogent medical need for new treatments. The discovery of new MTDs is a challenging task and we will describe the main strategies that have been developed over the years for the design of multifunctional molecules in antipsychotic drug discovery. In particular, we will focus on the few available MTDs based on the design of selective serotonin re-uptake inhibitors, used as antidepressants and in the treatment of schizophrenia
Effect of the Marine Polyketide Plocabulin on Tumor Progression
Full text linkMarine sponges represent one of the richest sources of natural marine compounds with anticancer potential. Plocabulin (PM060184), a polyketide originally isolated from the sponge Lithoplocamia lithistoides, elicits its main anticancer properties binding tubulin, which still represents one of the most important targets for anticancer drugs. Plocabulin showed potent antitumor activity, in both in vitro and in vivo models of different types of cancers, mediated not only by its antitubulin activity, but also by its ability to block endothelial cell migration and invasion. The objective of this review is to offer a description of plocabulin’s mechanisms of action, with special emphasis on the antiangiogenic signals and the latest progress on its development as an anticancer agent
Natural compounds to overcome cancer chemoresistance: Toxicological and clinical issues
No full textDefects in initiating or executing cell death programs are responsible for cancer chemoresistance. The growing understanding of apoptotic programs suggests that compounds simultaneously inhibiting multiple signaling pathways might provide a better therapeutic outcome than that of individual inhibitors
Overview of the Anticancer Potential of the "King of Spices" Piper nigrum and Its Main Constituent Piperine
Full text linkThe main limits of current anticancer therapy are relapses, chemoresistance, and toxic effects resulting from its poor selectivity towards cancer cells that severely impair a patient's quality of life. Therefore, the discovery of new anticancer drugs remains an urgent challenge. Natural products represent an excellent opportunity due to their ability to target heterogenous populations of cancer cells and regulate several key pathways involved in cancer development, and their favorable toxicological profile. Piper nigrum is one of the most popular spices in the world, with growing fame as a source of bioactive molecules with pharmacological properties. The present review aims to provide a comprehensive overview of the anticancer potential of Piper nigrum and its major active constituents-not limited to the well-known piperine-whose undeniable anticancer properties have been reported for different cancer cell lines and animal models. Moreover, the chemosensitizing effects of Piper nigrum in association with traditional anticancer drugs are depicted and its toxicological profile is outlined. Despite the promising results, human studies are missing, which are crucial for supporting the efficacy and safety of Piper nigrum and its single components in cancer patients
Nrf2: a potential therapeutic target for naturally occurring anticancer drugs?
Full text linkNuclear factor (erythroid-derived-2)-like 2 is one of the most efficient cytoprotective rheostats against exogenous or endogenous oxidative insults. At present, the modulation of the Nrf2 pathway represents an interesting and highly explored strategy in the oncological area. Area covered: In this review, we present and discuss the different modulation of the Nrf2 pathway by some natural compounds with a well demonstrated anticancer activity, and critically analyze the challenges associated with the development of an Nrf2-based anticancer strategy. Expert opinion: Many natural compounds with a well-defined anticancer activity are able to modulate this pathway. Both Nrf2 inducers and inhibitors can be useful as anticancer strategy. However, since Nrf2 modulates many networks potentially involved in the detoxification process of anticancer drugs, its activation in cancer cells could lead to chemoresistance. The switch between a beneficial or detrimental role of Nrf2 in cancer cells essentially depends on the tight control of its activity, the specific conditions of tumor microenvironment, and cell type. In line with the paucity of clear data related to the mechanisms underpinning the role of Nrf2 in cancer development and chemoresistance, discovery and development of Nrf2-based strategies is one of the most critical and challenging assignments for fighting cancers
Marine Sponge Natural Products with Anticancer Potential: An Updated Review
Full text linkDespite the huge investment into research and the significant effort and advances made in the search for new anticancer drugs in recent decades, cancer cure and treatment continue to be a formidable challenge. Many sources, including plants, animals, and minerals, have been explored in the oncological field because of the possibility of identifying novel molecular therapeutics. Marine sponges are a prolific source of secondary metabolites, a number of which showed intriguing tumor chemopreventive and chemotherapeutic properties. Recently, Food and Drug Administration-approved drugs derived from marine sponges have been shown to reduce metastatic breast cancer, malignant lymphoma, and Hodgkin’s disease. The chemopreventive and potential anticancer activity of marine sponge-derived compounds could be explained by multiple cellular and molecular mechanisms, including DNA protection, cell-cycle modulation, apoptosis, and anti-inflammatory activities as well as their ability to chemosensitize cancer cells to traditional antiblastic chemotherapy. The present article aims to depict the multiple mechanisms involved in the chemopreventive and therapeutic effects of marine sponges and critically explore the limitations and challenges associated with the development of marine sponge-based anticancer strategy
Janus Kinase Inhibitors and Coronavirus Disease (COVID)-19: Rationale, Clinical Evidence and Safety Issues
Full text link: We are witnessing a paradigm shift in drug development and clinical practice to fight the novel coronavirus disease (COVID-19), and a number of clinical trials have been or are being testing various pharmacological approaches to counteract viral load and its complications such as cytokine storm. However, data on the effectiveness of antiviral and immune therapies are still inconclusive and inconsistent. As compared to other candidate drugs to treat COVID-19, Janus Kinase (JAK) inhibitors, including baricitinib and ruxolitinib, possess key pharmacological features for a potentially successful repurposing: convenient oral administration, favorable pharmacokinetic profile, multifunctional pharmacodynamics by exerting dual anti-inflammatory and anti-viral effects. Baricitinib, originally approved for rheumatoid arthritis, received Emergency Use Authorization in November 2020 by the Food and Drug Administration in combination with remdesivir for the treatment of COVID-19 in hospitalized patients ≥ 2 years old who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation. By July 2021, the European Medicines Agency is also expected to issue the opinion on whether or not to extend its use in hospitalised patients from 10 years of age who require supplemental oxygen. Ruxolitinib, approved for myelofibrosis, was prescribed in patients with COVID-19 within an open-label Emergency Expanded Access Plan. This review will address key milestones in the discovery and use of JAK inhibitors in COVID-19, from artificial intelligence to current clinical evidence, including real world experience, and critically appraise emerging safety issues, namely infections, thrombosis, and liver injury. An outlook to ongoing studies (clinicaltrials.gov) and unpublished pharmacovigilance data is also offered
The Alcoholic Bark Extract of Terminalia Arjuna Exhibits Cytotoxic and Cytostatic Activity on Jurkat Leukemia Cells
No full textBackground: Natural products are characterized by complex chemical composition and
are capable of concurrently modulate several signalling pathways. Considering the biological complexity
of carcinogenesis, natural products represent key components of the therapeutic armamentarium
for oncological diseases. The bark of Terminalia arjuna is used in traditional Ayurvedic
medicine for its astringent, expectorant, cardiotonic, styptic, and antidysenteric properties. Alongside
its traditional uses, Terminalia arjuna exhibits different biological activities including antimutagenic
and anticarcinogenic.
Objective: This study was designed to evaluate the toxic effects of an alcoholic extract obtained
from the bark of T. arjuna on a human T-lymphoblastic cell line (Jurkat). We explored the phytochemical
composition and investigated the cytotoxic, cytostatic, genotoxic, and anti-genotoxic effects.
Methods: The phytochemical composition was analyzed using spectrophotometric methods; all the
biological endpoints were assessed through flow cytometry.
Results: The phytochemical screening showed that polyphenols represent about 64% of the extract.
Moreover, the extract was cytotoxic on Jurkat cells by inducing both apoptosis and necrosis and
blocked the cell cycle in the G2/M phase. Additionally, it was found that the extract lacks any genotoxic
effect, but was not effective in protecting Jurkat cells from the DNA damage induced by H2O2
and etoposide.
Conclusion: The results of our study show the toxic effects of Terminalia arjuna on Jurkat cells
and confirm the pivotal role played by natural compounds in the oncological field. Further studies
should be performed to better understand its clinical potential and deepen its toxicological profile
Review Article Potential Effects of Pomegranate Polyphenols in Cancer Prevention and Therapy
Full text linkCopyright © 2015 Eleonora Turrini et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Cancer is the second leading cause of death and is becoming the leading one in old age. Vegetable and fruit consumption is inversely associated with cancer incidence and mortality. Currently, interest in a number of fruits high in polyphenols has been raised due to their reported chemopreventive and/or chemotherapeutic potential. Pomegranate has been shown to exert anticancer activity, which is generally attributed to its high content of polyphenols. This review provides a comprehensive analysis of known targets and mechanisms along with a critical evaluation of pomegranate polyphenols as future anticancer agents. Pomegranate evokes antiproliferative, anti-invasive, and antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins, upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate blocks the activation of inflammatory pathways including, but not limited to, the NF
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