Celastrol (tripterine) is a chemical compound isolated from the root extracts of ''
Tripterygium wilfordii
''Tripterygium wilfordii'', or ''léi gōng téng'' (Mandarin) (, Japanese: ''raikōtō''), sometimes called thunder god vine but more properly translated thunder duke vine, is a vine used in traditional Chinese medicine.
''Tripterygium wilfordi ...
'' (Thunder god vine) and ''
Tripterygium regelii'' (Regel's threewingnut). Celastrol is a pentacyclic
nortriterpen quinone and belongs to the family of
quinone methide
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 wit ...
s. In mice, celastrol is an
NR4A1 agonist that alleviates inflammation and induces
autophagy. Also in mice, celastrol increase expression of
IL1R1, which is the receptor for the cytokine
interleukin-1
The Interleukin-1 family (IL-1 family) is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Discovery
Discovery of these cytokines began with studies on t ...
(IL-1). IL1R1 knock-out mice exposed to celastrol exhibit no leptin-sensitizing or anti-obesity effect.
In ''
in vitro
''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called " test-tube experiments", these studies in biology ...
'' and ''
in vivo
Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...
'' animal experiments, celastrol exhibits
antibacterial
An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
,
antioxidant, anti-inflammatory,
anticancer, and insecticidal activities. It has been shown to have obesity-controlling effects in mice by inhibiting negative regulators of
leptin. Celastrol has also shown to possess (by inhibition of
NF-κB
Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a protein complex 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 ...
in the
hypothalamus
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...
)
anti-diabetic effects on
diabetic nephropathy
Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...
and improve whole-body
insulin resistance.
Celastrol inhibits
IKK-NF-κB signaling via multiple molecular targets: direct inhibition of
IKKα and β kinases, inactivation of
CDC37
Hsp90 co-chaperone Cdc37 is a protein that in humans is encoded by the ''CDC37'' gene.
The protein encoded by this gene is highly similar to Cdc 37, a cell division cycle control protein of Saccharomyces cerevisiae. This protein is a HSP90 C ...
and
p23, which are
HSP90
Hsp90 (heat shock protein 90) is a chaperone protein that assists other proteins to fold properly, stabilizes proteins against heat stress, and aids in protein degradation. It also stabilizes a number of proteins required for tumor growth, ...
chaperone proteins, inhibition of
proteasome function and activation of
HSF1
Heat shock factor 1 (HSF1) is a protein that in humans is encoded by the ''HSF1'' gene. HSF1 is highly conserved in eukaryotes and is the primary mediator of transcriptional responses to proteotoxic stress with important roles in non-stress regul ...
, 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.
Celastrol also has demonstrated ''in vitro'' inhibitory effects against the
carbapenemase
Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...
of
CRE ''
Klebsiella pneumoniae
''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar.
Although found in the normal flora of the mo ...
'', in combination with
thymol
Thymol (also known as 2-isopropyl-5-methylphenol, IPMP), , is a natural monoterpenoid phenol derivative of ''p''-Cymene, isomeric with carvacrol, found in oil of thyme, and extracted from ''Thymus vulgaris'' (common thyme), ajwain, and vari ...
, a
monoterpene
Monoterpenes are a class of terpenes that consist of two isoprene units and have the molecular formula C10H16. Monoterpenes may be linear (acyclic) or contain rings (monocyclic and bicyclic). Modified terpenes, such as those containing oxygen func ...
.
References
{{Reflist, 30em
Quinone methides
Triterpenes
Hydroxy acids
Keto acids
Enones
Polyenes
Enols