Целастрол триптерин хімічна сполука виділена з коренів рослин en і en Целастрол є пентациклічним нортритерпеновим хіноно

Целастрол (триптерин) — хімічна сполука, виділена з коренів рослин ^[en] і ^[en]. Целастрол є пентациклічним нортритерпеновим хіноном і належить до родинихінонметидів . У мишей целастрол є агоністом NR4A1, який полегшує запалення та індукує аутофагію. крім того, целастрол посилює експресію IL1R1 — рецептору цитокіну інтерлейкіну-1 (IL-1). Миші з нокаутом IL1R1, які зазнали впливу целастролу, не виявляють ефекту сенсибілізації до лептину або проти ожиріння.

Целастрол

Назва за IUPAC	3-Hydroxy-9β,13α-dimethyl-2-oxo-24,25,26-trinoroleana-1(10),3,5,7-tetraen-29-oic acid
Систематична назва	(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
Інші назви	Tripterine
Властивості
Молекулярна формула	C₂₉H₃₈O₄
Молярна маса	450,61 г/моль
Зовнішній вигляд	Crystalline solid
Т_пл	213
Якщо не зазначено інше, дані наведено для речовин у стандартному стані (за 25 °C, 100 кПа)

Примітки картки

У експериментах in vitro та in vivo на тваринах целастрол виявляє антибактеріальну, антиоксидантну, протизапальну, протиракову, та інсектицидну дію. Було показано, що він контролює ожиріння у мишей шляхом інгібування негативних регуляторів лептину . Целастрол також продемонстрував протидіабетичний ефект

Примітки

Zhang L, Wang Q, Liu W, Liu F, Ji A, Li Y (2018). The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases. J Diabetes Res. 2018: 9363461. doi:10.1155/2018/9363461. PMC 6022324. PMID 30013988.
Feng X, Guan D, Auen T, Choi JW, Salazar Hernández MA, Lee J, Chun H, Faruk F, Kaplun E, Herbert Z, Copps KD, Ozcan U (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. {{}}: Недійсний |displayauthors=6 ()
Padilla-Montaño N, de León Guerra L, Moujir L (March 2021). Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources. Foods. 10 (3): 591. doi:10.3390/foods10030591. PMC 7998816. PMID 33799720.
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.
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.
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.
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.
Lee JH, Choi KJ, Seo WD, Jang SY, Kim M, Lee BW, Kim JY, Kang S, Park KH, Lee YS, Bae S (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. {{}}: Недійсний |displayauthors=6 ()
Tiedemann RE, Schmidt J, Keats JJ, Shi CX, Zhu YX, Palmer SE, Mao X, Schimmer AD, Stewart AK (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. {{}}: Недійсний |displayauthors=6 ()
Zhu H, Liu XW, Cai TY, Cao J, Tu CX, Lu W, He QJ, Yang B (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. {{}}: Недійсний |displayauthors=6 ()
Byun JY, Kim MJ, Eum DY, Yoon CH, Seo WD, Park KH, Hyun JW, Lee YS, Lee JS, Yoon MY, Lee SJ (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. {{}}: Недійсний |displayauthors=6 ()
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.
Kyriakou E, Schmidt S, Dodd GT, et al.
Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, Contreras RE, Kyriakou E, Simonds SE, Tiganis T, Cowley MA, Woods SC, Jastroch M, Clemmensen C, De Angelis M, Schramm KW, Sattler M, Messias AC, Tschöp MH, Pfluger PT (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. {{}}: Недійсний |displayauthors=6 ()
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.
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.
Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, Kim HW, Cha JJ, Hyun YY, Han SY, Han KH, Han JY, Cha DR (2013). Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLOS ONE. 8 (4): e62068. Bibcode:2013PLoSO...862068K. doi:10.1371/journal.pone.0062068. PMC 3637455. PMID 23637966. {{}}: Недійсний |displayauthors=6 ()

[1] Zhang L, Wang Q, Liu W, Liu F, Ji A, Li Y (2018). The Orphan Nuclear Receptor 4A1: A Potential New Therapeutic Target for Metabolic Diseases. J Diabetes Res. 2018: 9363461. doi:10.1155/2018/9363461. PMC 6022324. PMID 30013988.

[2] Feng X, Guan D, Auen T, Choi JW, Salazar Hernández MA, Lee J, Chun H, Faruk F, Kaplun E, Herbert Z, Copps KD, Ozcan U (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. {{}}: Недійсний |displayauthors=6 ()

[3] Padilla-Montaño N, de León Guerra L, Moujir L (March 2021). Antimicrobial Activity and Mode of Action of Celastrol, a Nortriterpen Quinone Isolated from Natural Sources. Foods. 10 (3): 591. doi:10.3390/foods10030591. PMC 7998816. PMID 33799720.

[4] 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.

[5] 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.

[Venkatesha-6] 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.

[7] 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.

[8] Lee JH, Choi KJ, Seo WD, Jang SY, Kim M, Lee BW, Kim JY, Kang S, Park KH, Lee YS, Bae S (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. {{}}: Недійсний |displayauthors=6 ()

[9] Tiedemann RE, Schmidt J, Keats JJ, Shi CX, Zhu YX, Palmer SE, Mao X, Schimmer AD, Stewart AK (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. {{}}: Недійсний |displayauthors=6 ()

[10] Zhu H, Liu XW, Cai TY, Cao J, Tu CX, Lu W, He QJ, Yang B (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. {{}}: Недійсний |displayauthors=6 ()

[11] Byun JY, Kim MJ, Eum DY, Yoon CH, Seo WD, Park KH, Hyun JW, Lee YS, Lee JS, Yoon MY, Lee SJ (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. {{}}: Недійсний |displayauthors=6 ()

[12] 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.

[13] Kyriakou E, Schmidt S, Dodd GT, et al.

[14] Pfuhlmann K, Schriever SC, Baumann P, Kabra DG, Harrison L, Mazibuko-Mbeje SE, Contreras RE, Kyriakou E, Simonds SE, Tiganis T, Cowley MA, Woods SC, Jastroch M, Clemmensen C, De Angelis M, Schramm KW, Sattler M, Messias AC, Tschöp MH, Pfluger PT (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. {{}}: Недійсний |displayauthors=6 ()

[15] 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.

[16] 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.

[17] Kim JE, Lee MH, Nam DH, Song HK, Kang YS, Lee JE, Kim HW, Cha JJ, Hyun YY, Han SY, Han KH, Han JY, Cha DR (2013). Celastrol, an NF-κB inhibitor, improves insulin resistance and attenuates renal injury in db/db mice. PLOS ONE. 8 (4): e62068. Bibcode:2013PLoSO...862068K. doi:10.1371/journal.pone.0062068. PMC 3637455. PMID 23637966. {{}}: Недійсний |displayauthors=6 ()