Tumor necrosis factor is a cytokine and member of the TNF superfamily, which consists of various transmembrane proteins with a homologous TNF domain. It is the first cytokine to be described as an adipokine as secreted by adipose tissue.
Flavonoids are a class of polyphenolic secondary metabolites found in plants, and thus commonly consumed in the diets of humans.
Alcoholic liver disease (ALD), also called alcohol-related liver disease (ARLD), is a term that encompasses the liver manifestations of alcohol overconsumption, including fatty liver, alcoholic hepatitis, and chronic hepatitis with liver fibrosis or cirrhosis.
Fatty liver disease (FLD), also known as hepatic steatosis and steatotic liver disease (SLD), is a condition where excess fat builds up in the liver. Often there are no or few symptoms. Occasionally there may be tiredness or pain in the upper right side of the abdomen. Complications may include cirrhosis, liver cancer, and esophageal varices.
Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids.
Silibinin (INN), also known as silybin (both from Silybum, the generic name of the plant from which it is extracted), is the major active constituent of silymarin, a standardized extract of the milk thistle, containing a mixture of flavonolignans consisting of silibinin, isosilibinin, silychristin, silidianin, and others. Silibinin itself is a mixture of two diastereomers, silybin A and silybin B, in approximately equimolar ratio. Silibinin is used in pure forms as a medication, and more frequently as an active ingredient in milk thistle–derived herbal supplements.
Quercetin is a plant flavonol from the flavonoid group of polyphenols. It is found in many fruits, vegetables, leaves, seeds, and grains; capers, red onions, and kale are common foods containing appreciable amounts of it. It has a bitter flavor and is used as an ingredient in dietary supplements, beverages, and foods.
Paneth cells are cells in the small intestine epithelium, alongside goblet cells, enterocytes, and enteroendocrine cells. Some can also be found in the cecum and appendix. They are located below the intestinal stem cells in the intestinal glands and the large eosinophilic refractile granules that occupy most of their cytoplasm.
Myricetin is a member of the flavonoid class of polyphenolic compounds, with antioxidant properties. Common dietary sources include vegetables, fruits, nuts, berries, tea, and red wine.
Ursolic acid, is a pentacyclic triterpenoid identified in the epicuticular waxes of apples as early as 1920 and widely found in the peels of fruits, as well as in herbs and spices like rosemary and thyme.
Hovenia dulcis, the Japanese raisin tree or oriental raisin tree, is a hardy tree found in Asia, from Eastern China and Korea to the Himalayas, growing preferably in a sunny position on moist sandy or loamy soils. The tree known for its health benefits when consumed in tea, introduced as an ornamental tree to several countries, also bears edible fruit. It is considered to be one of the most pervasive invaders in Brazilian subtropical forests.
Nuclear factor erythroid 2-related factor 2 (NRF2), also known as nuclear factor erythroid-derived 2-like 2, is a transcription factor that in humans is encoded by the NFE2L2 gene. NRF2 is a basic leucine zipper (bZIP) protein that may regulate the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation, according to preliminary research. In vitro, NRF2 binds to antioxidant response elements (AREs) in the promoter regions of genes encoding cytoprotective proteins. NRF2 induces the expression of heme oxygenase 1 in vitro leading to an increase in phase II enzymes. NRF2 also inhibits the NLRP3 inflammasome.
Hydroxycarboxylic acid receptor 2 (HCA2), also known as GPR109A and niacin receptor 1 (NIACR1), is a protein which in humans is encoded (its formation is directed) by the HCAR2 gene and in rodents by the Hcar2 gene. The human HCAR2 gene is located on the long (i.e., "q") arm of chromosome 12 at position 24.31 (notated as 12q24.31). Like the two other hydroxycarboxylic acid receptors, HCA1 and HCA3, HCA2 is a G protein-coupled receptor (GPCR) located on the surface membrane of cells. HCA2 binds and thereby is activated by D-β-hydroxybutyric acid (hereafter termed β-hydroxybutyric acid), butyric acid, and niacin (also known as nicotinic acid). β-Hydroxybutyric and butyric acids are regarded as the endogenous agents that activate HCA2. Under normal conditions, niacin's blood levels are too low to do so: it is given as a drug in high doses in order to reach levels that activate HCA2.
Chronic systemic inflammation (SI) is the result of release of pro-inflammatory cytokines from immune-related cells and the chronic activation of the innate immune system. It can contribute to the development or progression of certain conditions such as cardiovascular disease, cancer, diabetes mellitus, chronic kidney disease, non-alcoholic fatty liver disease, autoimmune and neurodegenerative disorders, and coronary heart disease.
Fisetin (7,3′,4′-flavon-3-ol) is a plant flavonol from the flavonoid group of polyphenols. It can be found in many plants, where it serves as a yellow/ochre colouring agent. It is also found in many fruits and vegetables, such as strawberries, apples, persimmons, onions and cucumbers. Its chemical formula was first described by Austrian chemist Josef Herzig in 1891.
Chrysophanol, also known as chrysophanic acid, is a fungal isolate and a natural anthraquinone. It is a C-3 methyl substituted chrysazin of the trihydroxyanthraquinone family.
Tropoflavin, also known as 7,8-dihydroxyflavone, is a naturally occurring flavone found in Godmania aesculifolia, Tridax procumbens, and primula tree leaves. It has been found to act as a potent and selective small-molecule agonist of the tropomyosin receptor kinase B (TrkB), the main signaling receptor of the neurotrophin brain-derived neurotrophic factor (BDNF). Tropoflavin is both orally bioavailable and able to penetrate the blood–brain barrier. A prodrug of tropoflavin with greatly improved potency and pharmacokinetics, R13, is under development for the treatment of Alzheimer's disease.
Geniposide, the glycoside form of genipin, is a bioactive iridoid glycoside that is found in a wide variety of medicinal herbs, such as Gardenia jasminoides (fruits) . Geniposide shows several pharmacological effects including neuroprotective, antidiabetic, hepatoprotective, anti-inflammatory, analgesic, antidepressant-like, cardioprotective, antioxidant, immune-regulatory, antithrombotic and antitumoral activity. These pharmacology benefits arise through the modulating action of geniposide on several proteins and genes that are associated with inflammatory and oxidative stress processes.
R13 is a small-molecule flavonoid and orally active, potent, and selective agonist of the tropomyosin receptor kinase B (TrkB) – the main signaling receptor for the neurotrophin brain-derived neurotrophic factor (BDNF) – which is under development for the potential treatment of Alzheimer's disease. It is a structural modification and prodrug of tropoflavin (7,8-DHF) with improved potency and pharmacokinetics, namely oral bioavailability and duration. The compound is a replacement for the earlier tropoflavin prodrug R7 and has similar properties to it. It was developed because while R7 displayed a good drug profile in animal studies, it showed almost no conversion into tropoflavin in human liver microsomes. In contrast to R7, R13 is readily hydrolyzed into tropoflavin in human liver microsomes.
4'-Hydroxyflavanone is a naturally occurring monohydroxybenzoic acid and a member of the 4'-hydroxyflavanones family. It is white to pale orange in color and generally soluble in organic solvents such as chloroform and ethanol, but insoluble with water. 4'-Hydroxyflavanone is a naturally occurring product with cosmetic and potential clinical applications that is found in plants such as carnations.
