Celastrol

Celastrol (tripterine) is a bioactive chemical compound isolated from the roots of Tripterygium wilfordii (Thunder duke vine) and Tripterygium regelii (Regel's threewingnut). Celastrol is a pentacyclic nortriterpen quinone and belongs to the family of quinone methides. It has been used for centuries as a traditional Chinese medicine. In recent years, celastrol has been widely studied for its anti-inflammatory, anticancer, antioxidant, and antibacterial properties.

In mice, celastrol is an NR4A1 agonist that alleviates inflammation and induces autophagy. It also influences metabolic regulation by enhancing IL1R1 expression, 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 and in vivo animal experiments, celastrol exhibits antibacterial, antioxidant, anti-inflammatory, anticancer, and insecticidal properties. It has been shown to have obesity-controlling effects in mice by inhibiting negative regulators of leptin. Celastrol has also shown to possess anti-diabetic effects on diabetic nephropathy and improve whole-body insulin resistance, through the inhibition of NF-κB signaling in the hypothalamus.

Celastrol inhibits the IKK-NF-κB signaling pathway via multiple molecular mechanisms, including the direct inhibition of IKKα and IKKβ kinases, inactivation of CDC37 and p23 (HSP90 chaperone proteins), suppression of proteasome function and activation of HSF1, which triggers the heat shock response. The available evidence indicates that celastrol covalently binds to the thiol groups of cysteine residues within its molecular targets.

Celastrol also has demonstrated in vitro inhibitory effects against the carbapenemase of carbapenem-resistant Klebsiella pneumoniae (CRE), particularly when used in combination with thymol, a monoterpene.