Names | |
---|---|
IUPAC name 3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid | |
Systematic IUPAC name (2R,4aS,6aS,12bR,14aS,14bR)-10-Hydroxy-2,4a,6a,9,12b,14a-hexamethyl-11-oxo-1,2,3,4,4a,5,6,6a,11,12b,13,14,14a,14b-tetradecahydropicene-2-carboxylic acid | |
Other names Tripterine | |
Identifiers | |
3D model (JSmol) | |
ChemSpider | |
ECHA InfoCard | 100.164.266 |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
| |
| |
Properties | |
C29H38O4 | |
Molar mass | 450.619 g·mol−1 |
Appearance | Crystalline solid |
Melting point | 213 °C (415 °F; 486 K) [1] |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). |
Celastrol (tripterine) is a chemical compound isolated from the root extracts of Tripterygium wilfordii (Thunder god vine) and Tripterygium regelii (Regel's threewingnut). Celastrol is a pentacyclic nortriterpen quinone and belongs to the family of quinone methides. In mice, celastrol is an NR4A1 agonist that alleviates inflammation and induces autophagy. [2] Also in mice, celastrol increase expression of IL1R1, which is the receptor for the cytokine interleukin-1 (IL-1). IL1R1 knock-out mice exposed to celastrol exhibit no leptin-sensitizing or anti-obesity effect. [3]
In in vitro and in vivo animal experiments, celastrol exhibits antibacterial, [4] antioxidant, [5] anti-inflammatory, [6] [7] anticancer, [8] [9] [10] [11] [12] and insecticidal [13] activities. It has been shown to have obesity-controlling effects in mice by inhibiting negative regulators of leptin. [14] [15] [16] Celastrol has also shown to possess (by inhibition of NF-κB in the hypothalamus [17] ) anti-diabetic effects on diabetic nephropathy and improve whole-body insulin resistance. [18]
Celastrol inhibits IKK-NF-κB signaling via multiple molecular targets: direct inhibition of IKKα and β kinases, inactivation of CDC37 and p23, which are HSP90 chaperone proteins, inhibition of proteasome function and activation of HSF1, which triggers the heat shock response. The available evidence indicates that celastrol bonds covalently to the thiol groups of cysteine residues in its molecular targets. [19]
Celastrol also has demonstrated in vitro inhibitory effects against the carbapenemase of CRE Klebsiella pneumoniae , in combination with thymol, a monoterpene. [20]
Leptin is a protein hormone predominantly made by adipocytes and its primary role is likely to regulate long-term energy balance.
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are endogenous and a normal part of the body's control and others are obtained exogenously through pharmaceutical drugs or diet.
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a family of transcription factor protein complexes that controls transcription of DNA, cytokine production and cell survival. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, heavy metals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.
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.
Honokiol is a lignan isolated from the bark, seed cones, and leaves of trees belonging to the genus Magnolia. It has been identified as one of the chemical compounds in some traditional eastern herbal medicines along with magnolol, 4-O-methylhonokiol, and obovatol.
Toll-like receptor 4 is a protein that in humans is encoded by the TLR4 gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an intracellular signaling pathway NF-κB and inflammatory cytokine production which is responsible for activating the innate immune system.
Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the RELA gene.
Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKK-α) also known as IKK1 or conserved helix-loop-helix ubiquitous kinase (CHUK) is a protein kinase that in humans is encoded by the CHUK gene. IKK-α is part of the IκB kinase complex that plays an important role in regulating the NF-κB transcription factor. However, IKK-α has many additional cellular targets, and is thought to function independently of the NF-κB pathway to regulate epidermal differentiation.
NEDD8 is a protein that in humans is encoded by the NEDD8 gene. This ubiquitin-like (UBL) protein becomes covalently conjugated to a limited number of cellular proteins, in a process called NEDDylation similar to ubiquitination. Human NEDD8 shares 60% amino acid sequence identity to ubiquitin. The primary known substrates of NEDD8 modification are the cullin subunits of cullin-based E3 ubiquitin ligases, which are active only when NEDDylated. Their NEDDylation is critical for the recruitment of E2 to the ligase complex, thus facilitating ubiquitin conjugation. NEDD8 modification has therefore been implicated in cell cycle progression and cytoskeletal regulation.
B-cell lymphoma 3-encoded protein is a protein that in humans is encoded by the BCL3 gene.
Leptin receptor, also known as LEP-R or OB-R, is a type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295. Its location is the cell membrane, and it has extracellular, trans-membrane and intracellular sections.
TNFAIP3-interacting protein 2 is a protein that in humans is encoded by the TNIP2 gene. TNIP2 contains multiple amino acid sites that are phosphorylated and ubiquitinated.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 is a protein that in humans is encoded by the MALT1 gene. It's the human paracaspase.
Oleanolic acid or oleanic acid is a naturally occurring pentacyclic triterpenoid related to betulinic acid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins.
Cornus officinalis, the Japanese cornel or Japanese cornelian cherry, is a species of flowering plant in the dogwood family Cornaceae. Despite its name, it is native to China and Korea as well as Japan. It is not to be confused with C. mas, which is also known as the Cornelian cherry. It is not closely related to the true cherries of the genus Prunus.
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.
A quinone methide is a type of conjugated organic compound that contain a cyclohexadiene with a carbonyl and an exocyclic methylidene or extended alkene unit. It is analogous to a quinone, but having one of the double bonded oxygens replaced with a carbon. The carbonyl and methylidene are usually oriented either ortho or para to each other. There are some examples of transient synthetic meta quinone methides.
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
Xanthatin, or (3aR,7S,8aS)-7-methyl-3-methylidene-6-[(E)-3-oxobut-1-enyl]-4,7,8,8a-tetrahydro-3aH-cyclohepta[b]furan-2-one (C15H18O3) is a major bioactive compound found in the leaves of the Xanthium strumarium (Asteracae) plant. It is classified as a natural sesquiterpene lactone. Xanthatin is believed to have anti-inflammatory, anti-tumour, anti-microbial, and anti-parasitic properties hence it is being researched for potential use in treatment of cancer and autoimmune diseases. While it has been used in traditional medicine for decades, its mechanisms and modern use haven’t been fully understood yet.