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Celastrol

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Celastrol
Names
IUPAC name
3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
Other names
Tripterine
Identifiers
3D model (JSmol)
ChemSpider
ECHA InfoCard 100.164.266 Edit this at Wikidata
UNII
  • InChI=1S/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
    Key: KQJSQWZMSAGSHN-JJWQIEBTSA-N
  • InChI=1/C29H38O4/c1-17-18-7-8-21-27(4,19(18)15-20(30)23(17)31)12-14-29(6)22-16-26(3,24(32)33)10-9-25(22,2)11-13-28(21,29)5/h7-8,15,22,31H,9-14,16H2,1-6H3,(H,32,33)/t22-,25-,26-,27+,28-,29+/m1/s1
    Key: KQJSQWZMSAGSHN-JJWQIEBTBS
  • CC1=C(C(=O)C=C2C1=CC=C3[C@]2(CC[C@@]4([C@@]3(CC[C@@]5([C@H]4C[C@](CC5)(C)C(=O)O)C)C)C)C)O
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 Celastrus regelii. Celastrol is a pentacyclic triterpenoid and belongs to the family of quinone methides.

In mice, celastrol increase expression of IL1R1, which is the receptor for the cytokine interleukin-1 (IL-1). This suggests that celastrol exhibits its anti-obesity effects via a pro-inflammatory signaling pathway, as IL1R1 knock-out mice exposed to celastrol exhibit no leptin-sensitizing or anti-obesity effect.[2]

In in vitro and in vivo animal experiments, celastrol exhibits antioxidant,[3] anti-inflammatory,[4][5] anticancer,[6][7][8][9][10] and insecticidal [11] activities. It has been shown to have obesity-controlling effects in mice.[12][13] Celastrol has also shown to possess (by inhibition of NF-κB in the hypothalamus[14]) anti-diabetic effects on diabetic nephropathy and improve whole-body insulin resistance.[15]

References

  1. ^ Ryu YB, Park SJ, Kim YM, Lee JY, Seo WD, Chang JS, et al. (March 2010). "SARS-CoV 3CLpro inhibitory effects of quinone-methide triterpenes from Tripterygium regelii". Bioorganic & Medicinal Chemistry Letters. 20 (6): 1873–6. doi:10.1016/j.bmcl.2010.01.152. PMC 7127101. PMID 20167482.
  2. ^ Feng X, Guan D, Auen T, Choi JW, Salazar Hernández MA, Lee J, et al. (April 2019). "IL1R1 is required for celastrol's leptin-sensitization and antiobesity effects". Nature Medicine. 25 (4): 575–582. doi:10.1038/s41591-019-0358-x. PMC 7158951. PMID 30833749.
  3. ^ Allison AC, Cacabelos R, Lombardi VR, Alvarez XA, Vigo C (October 2001). "Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer's disease". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 25 (7): 1341–57. doi:10.1016/S0278-5846(01)00192-0. PMID 11513350. S2CID 21569585.
  4. ^ Kim DH, Shin EK, Kim YH, Lee BW, Jun JG, Park JH, Kim JK (September 2009). "Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated from Celastrus regelii". European Journal of Clinical Investigation. 39 (9): 819–27. doi:10.1111/j.1365-2362.2009.02186.x. PMID 19549173.
  5. ^ Venkatesha SH, Yu H, Rajaiah R, Tong L, Moudgil KD (April 2011). "Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced cellular and humoral effector responses". The Journal of Biological Chemistry. 286 (17): 15138–46. doi:10.1074/jbc.M111.226365. PMC 3083183. PMID 21402700.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  6. ^ Metselaar DS, Meel MH, Benedict B, Waranecki P, Koster J, Kaspers GJL, Hulleman E (November 2019). "Celastrol-induced degradation of FANCD2 sensitizes pediatric high-grade gliomas to the DNA-crosslinking agent carboplatin". EBioMedicine. 50: 81–92. doi:10.1016/j.ebiom.2019.10.062. PMC 6921187. PMID 31735550.
  7. ^ Lee JH, Choi KJ, Seo WD, Jang SY, Kim M, Lee BW, et al. (March 2011). "Enhancement of radiation sensitivity in lung cancer cells by celastrol is mediated by inhibition of Hsp90". International Journal of Molecular Medicine. 27 (3): 441–6. doi:10.3892/ijmm.2011.601. PMID 21249311.
  8. ^ Tiedemann RE, Schmidt J, Keats JJ, Shi CX, Zhu YX, Palmer SE, et al. (April 2009). "Identification of a potent natural triterpenoid inhibitor of proteosome chymotrypsin-like activity and NF-kappaB with antimyeloma activity in vitro and in vivo". Blood. 113 (17): 4027–37. doi:10.1182/blood-2008-09-179796. PMC 3952546. PMID 19096011.
  9. ^ Zhu H, Liu XW, Cai TY, Cao J, Tu CX, Lu W, et al. (August 2010). "Celastrol acts as a potent antimetastatic agent targeting beta1 integrin and inhibiting cell-extracellular matrix adhesion, in part via the p38 mitogen-activated protein kinase pathway". The Journal of Pharmacology and Experimental Therapeutics. 334 (2): 489–99. doi:10.1124/jpet.110.165654. PMID 20472666.
  10. ^ Byun JY, Kim MJ, Eum DY, Yoon CH, Seo WD, Park KH, et al. (October 2009). "Reactive oxygen species-dependent activation of Bax and poly(ADP-ribose) polymerase-1 is required for mitochondrial cell death induced by triterpenoid pristimerin in human cervical cancer cells". Molecular Pharmacology. 76 (4): 734–44. doi:10.1124/mol.109.056259. PMID 19574249. S2CID 6541041.
  11. ^ Avilla J, Teixidò A, Velázquez C, Alvarenga N, Ferro E, Canela R (January 2000). "Insecticidal activity of Maytenus species (Celastraceae) nortriterpene quinone methides against codling moth, Cydia pomonella (L.) (Lepidoptera: tortricidae)". Journal of Agricultural and Food Chemistry. 48 (1): 88–92. doi:10.1021/jf990008w. PMID 10637057.
  12. ^ Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, et al. (November 2018). "Celastrol-Induced Weight Loss Is Driven by Hypophagia and Independent From UCP1". Diabetes. 67 (11): 2456–2465. doi:10.2337/db18-0146. PMID 30158241.
  13. ^ Liu J, Lee J, Salazar Hernandez MA, Mazitschek R, Ozcan U (May 2015). "Treatment of obesity with celastrol". Cell. 161 (5): 999–1011. doi:10.1016/j.cell.2015.05.011. PMC 4768733. PMID 26000480.
  14. ^ Lee JH, Koo TH, Yoon H, Jung HS, Jin HZ, Lee K, Lee JJ (2006). "Inhibition of NF-κB activation through targeting IκB kinase by celastrol, a quinone methide triterpenoid". Biochemical Pharmacology. 72 (10): 1311–1321. doi:10.1016/j.bcp.2006.08.014. PMID 16984800.
  15. ^ Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, et al. (2013). "Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice". PLOS ONE. 8 (4): e62068. doi:10.1371/journal.pone.0062068. PMC 3637455. PMID 23637966.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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