curcumin and fisetin

Cellular senescence is a hallmark of aging, it is a permanent state of cell cycle arrest induced by cellular stresses. During the aging process, senescent cells (SCs) increasingly accumulate in tissues, causing a loss of tissue-repair capacity because of cell cycle arrest in progenitor cells and produce proinflammatory and matrix-degrading molecules which are known as the senescence-associated secretory phenotype (SASP), and thereby contribute to the development of various age-related diseases. Genetic evidence has demonstrated that clearance of SCs can delay aging and extend healthspan. Senolytics, small molecules that can selectively kill SCs, have been developed to treat various age-related diseases. In recent years, emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog. Some of the compounds have been validated in animal models and have great potential to be pushed to clinical applications. In this review, we will discuss cellular senescence and its potential as a target for treating age-related diseases, and summarize the known natural compounds as senolytic agents and their applications.

Topics: Aging; Animals; Cell Cycle Checkpoints; Cellular Senescence; Curcumin; Cytotoxins; Dioxolanes; Flavonoids; Flavonols; Humans; Quercetin

Lung cancer is a prominent cause of cancer-associated mortality worldwide. The main reason for high mortality due to lung cancer is attributable to the fact that the diagnosis is generally made when it has spread beyond a curable stage and cannot be treated surgically or with radiation therapy. Therefore, new approaches like dietary modifications could be extremely useful in reducing lung cancer incidences. Several fruits and vegetables offer a variety of bioactive compounds to afford protection against several diseases, including lung cancer. A number of research studies involving dietary agents provide strong evidence for their role in the prevention and treatment of lung cancer, and have identified their molecular mechanisms of action and potential targets. In this review article, we summarize data from in-vitro and in-vivo studies and where available, in clinical trials, on the effects of some of the most promising dietary agents against lung cancer.

Topics: Adenocarcinoma; Administration, Oral; Animals; Anticarcinogenic Agents; Antineoplastic Agents, Phytogenic; Catechin; Curcumin; Flavonoids; Flavonols; Humans; Indoles; Isothiocyanates; Lung Neoplasms; Plant Extracts; Polyphenols

Accumulating data clearly indicate that induction of apoptosis is an important event for chemoprevention of cancer by naturally occurring dietary agents. In mammalian cells, apoptosis has been divided into two major pathways: the extrinsic pathway, activated by pro-apoptotic receptor signals at the cellular surface; and the intrinsic pathway, which involves the disruption of mitochondrial membrane integrity. This process is strictly controlled in response to integrity of pro-death signaling and plays critical roles in development, maintenance of homeostasis, and host defense in multicellular organisms. For chemoprevention studies, prostate cancer (PCa) represents an ideal disease due to its long latency, its high incidence, tumor marker availability, and identifiable preneoplastic lesions and risk groups. In this article, we highlight the studies of various apoptosis-inducing dietary compounds for prevention of PCa in vitro in cell culture, in preclinical studies in animals, and in human clinical trials.

Topics: Adenocarcinoma; Aged; Animals; Apoptosis; Carotenoids; Catechin; Clinical Trials as Topic; Curcumin; Drug Screening Assays, Antitumor; Flavonoids; Flavonols; Genistein; Humans; Lycopene; Lythraceae; Male; Mice; Mice, Nude; Mice, Transgenic; Middle Aged; Neoplasm Proteins; Pentacyclic Triterpenes; Phytotherapy; Plant Extracts; Prostatic Neoplasms; Resveratrol; Stilbenes; Tumor Cells, Cultured

Topics: Cell Cycle Checkpoints; Curcumin; Cyclin-Dependent Kinase Inhibitor p21; Flavonoids; Flavonols; Heterochromatin; Neoplasms; Quercetin

Some of the challenges of yeast encapsulation protocols are low phytochemical internalization rates and limited intracellular compartments of yeasts. This study uses an ultrasound-assisted batch encapsulation (UABE) protocol to optimize the encapsulation of curcumin and fisetin by recovering nonencapsulated biomaterial and further incorporating it into nonloaded yeasts in three encapsulation stages (1ES, 2ES and 3ES). The effect of selected acoustic energies (166·7 and 333·3 W l

Topics: Antioxidants; Curcumin; Flavonols; Saccharomyces cerevisiae

Alzheimer's disease (AD) is the most common form of dementia with the numbers expected to increase dramatically as our society ages. There are no treatments to cure, prevent, or slow down the progression of the disease. Age is the single greatest risk factor for AD. However, to date, AD drug discovery efforts have generally not taken this fact into consideration. Multiple changes associated with brain aging, including neuroinflammation and oxidative stress, are important contributors to disease development and progression. Thus, due to the multifactorial nature of AD, the one target strategy to fight the disease needs to be replaced by a more general approach using pleiotropic compounds to deal with the complexity of the disease. In this perspectives piece, our alternative approach to AD drug development based on the biology of aging is described. Starting with plants or plant-derived natural products, we have used a battery of cell-based screening assays that reflect multiple, age-associated toxicity pathways to identify compounds that can target the aspects of aging that contribute to AD pathology. We have found that this combination of assays provides a replicable, cost- and time-effective screening approach that has to date yielded one compound in clinical trials for AD (NCT03838185) and several others that show significant promise.

Topics: Aging; Alzheimer Disease; Antioxidants; Curcumin; Eriodictyon; Ethnopharmacology; Flavonols; Humans; Indole Alkaloids; Neuroprotective Agents; Plant Preparations

Cell osmoporation is a simple and straightforward procedure of creating food-grade biocapsules. This study proposes a new protocol of sequential cell osmoporation stages and evaluates its impact on the efficiency of curcumin and fisetin internalization into Saccharomyces cerevisiae cells. To the best of our knowledge, this is the first report in the literature regarding the subject. To assess how multiple osmoporation stages influence the encapsulation efficiency (% EE), encapsulated amount of curcumin (IC) and fisetin (IF) into S. cerevisiae cells and cell viability, the residual supernatant was used for the subsequent encapsulation stages and viability was assessed by the CFU method. Quantification was carried through direct extraction, using an ultrasonic bath and UV-Vis spectrophotometry. Experimental data demonstrated that the addition of a second osmoporation stage increases both the EE (% EE) and the amount of encapsulated curcumin and fisetin (IC and IF). As a result, the EE was considerably improved and the obtained microcapsules contained a higher amount of the targeted bioactive compounds in its internal structure. However, adding a third osmoporation stage proved to less beneficial to the process efficiency due to its lower yield and the significant negative impact to cell viability.. For the first time in the literature, a protocol of serial osmoporation stages to enhance the encapsulation efficiency of hydrophobic low molecular weight molecules (curcumin and fisetin) into Saccharomyces cerevisiae cells was determined. By increasing overall efficiency, this protocol empowers the encapsulation process and creates a rational way to reduce waste for future industrial osmoporation applications.

Topics: Biological Transport; Capsules; Cell Survival; Curcumin; Flavonoids; Flavonols; Hydrophobic and Hydrophilic Interactions; Osmosis; Saccharomyces cerevisiae

Encapsulation into yeast microcarriers provides an appealing alternative to biomimetic systems by employing natural, pre-formed vehicles for the stabilization and delivery of bioactives compounds. However, current (diffusion-limited) methods of encapsulation using yeast require long time scales and heating which lead to poor encapsulation efficiencies and yields. This study evaluates the usage of vacuum infusion to encapsulate two model bioactives, curcumin and fisetin, into yeast and yeast cell wall particles and the physical parameters, e.g. vacuum level, concentration of carrier solvent, log p value of bioactive, etc., which facilitate the process of vacuum infusion. Encapsulation efficiencies were determined using UV-vis spectrophotometry. Localization of bioactives within yeast microcarriers was determined using confocal and multiphoton (two-photon) microscopy. 99% vacuum, or 1.0kPa, and 35% ethanol (v/v) provide the optimal conditions for the encapsulation of both curcumin and fisetin; compared to the diffusion-limited method, vacuum infusion is able to encapsulate 3× more curcumin and 2× more fisetin into yeast microcarrier and requires 288-fold less time. Enhanced encapsulation efficiencies and yield as well as rapid encapsulation process technology presented in this study can transform the use of cell based carriers for encapsulation and delivery of bioactives.

Topics: Cell Wall; Curcumin; Flavonoids; Flavonols; Hydrophobic and Hydrophilic Interactions; Saccharomyces cerevisiae; Vacuum

Although the cause of dopaminergic cell death in Parkinson's disease (PD) remains unknown, oxidative stress has been strongly implicated. Because of their ability to combat oxidative stress, diet derived phenolic compounds continue to be considered as potential agents for long-term use in PD. This study was aimed at investigating whether the natural phenolic compounds curcumin, naringenin, quercetin, fisetin can be neuroprotective in the 6-OHDA model of PD. Unilateral infusion of 6-OHDA into the medial forebrain bundle produced a significant loss of tyrosine hydroxylase (TH)-positive cells in the substantia nigra (SN) as well as a decreased of dopamine (DA) content in the striata in the vehicle-treated animals. Rats pretreated with curcumin or naringenin showed a clear protection of the number of TH-positive cells in the SN and DA levels in the striata. However, neither pretreatment with quercetin nor fisetin had any effects on TH-positive cells or DA levels. The ability of curcumin and naringenin to exhibit neuroprotection in the 6-OHDA model of PD may be related to their antioxidant capabilities and their capability to penetrate into the brain.

Topics: 3,4-Dihydroxyphenylacetic Acid; Animals; Antioxidants; Curcumin; Disease Models, Animal; Dopamine; Flavanones; Flavonoids; Flavonols; Homovanillic Acid; Male; Neurons; Neuroprotective Agents; Oxidopamine; Parkinson Disease; Phenols; Quercetin; Rats; Rats, Sprague-Dawley; Tyrosine 3-Monooxygenase