Celastrol (tripterine) is a chemical compound isolated from the root extracts of ''
Tripterygium wilfordii'' (Thunder god vine) and ''
Tripterygium regelii
''Tripterygium regelii'', or Regel's threewingnut (Pinyin: Dongbei Leigongteng), is a rambling, shrubby perennial deciduous yellow vine native to Korea, Japan and Manchuria. It grows to about . Small very pretty yellowish white or white flowers ...
'' (Regel's threewingnut). Celastrol is a pentacyclic
nortriterpen quinone and belongs to the family of
quinone methides. In mice, celastrol is an
NR4A1
The nuclear receptor 4A1 (NR4A1 for "nuclear receptor subfamily 4 group A member 1") also known as Nur77, TR3, and NGFI-B is a protein that in humans is encoded by the ''NR4A1'' gene.
Nuclear receptor 4A1 (NR4A1) is a member of the '' NR4A'' nucl ...
agonist that alleviates inflammation and induces
autophagy
Autophagy (or autophagocytosis; from the Ancient Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent re ...
. Also in mice, celastrol increase expression of
IL1R1
Interleukin 1 receptor, type I (IL1R1) also known as CD121a (Cluster of Differentiation 121a), is an interleukin receptor. IL1R1 also denotes its human gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to de ...
, 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.
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 ...
'' 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 hypothalamus ...
)
anti-diabetic effects on
diabetic nephropathy and improve whole-body
insulin resistance
Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin.
Insulin is a hormone that facilitates the transport of glucose from blood into cells, thereby reducing blood glucose (blood suga ...
.
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
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, 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 of
CRE ''
Klebsiella pneumoniae'', in combination with
thymol, 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
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Quinone methides
Triterpenes
Hydroxy acids
Keto acids
Enones
Polyenes
Enols