Celastrol and Its Role in Controlling Chronic Diseases.
Celastrol, a triterpenoid derived from traditional Chinese medicinal plants, has anti-inflammatory, antioxidant, and anticancer activities. Celastrol has shown preventive/therapeutic effects in experimental models of several chronic diseases. These include, chronic inflammatory and autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, and psoriasis), neurodegenerative disorders (e.g., Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis), atherosclerosis, obesity, Type 2 diabetes, and cancer. Celastrol modulates intricate cellular pathways and networks associated with disease pathology, and it interrupts or redirects the aberrant cellular and molecular events so as to limit disease progression and facilitate recovery, where feasible. The major cell signaling pathways modulated by celastrol include the NF-kB pathway, MAPK pathway, JAK/STAT pathway, PI3K/Akt/mTOR pathway, and antioxidant defense mechanisms. Furthermore, celastrol modulates cell proliferation, apoptosis, proteasome activity, heat-shock protein response, innate and adaptive immune responses, angiogenesis, and bone remodeling. Current understanding of the mechanisms of action of celastrol and information about its disease-modulating activities in experimental models have set the stage for testing celastrol in clinical studies as a therapeutic agent for several chronic human diseases.
Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite-380, Baltimore, MD, 21201, USA.
Shivaprasad H
SH
Venkatesha
Department of Microbiology and Immunology, University of Maryland School of Medicine, 685 W. Baltimore Street, HSF-1, Suite-380, Baltimore, MD, 21201, USA. kmoudgil@som.umaryland.edu.|Division of Rheumatology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, 21201, USA. kmoudgil@som.umaryland.edu.
Kamal D
KD
Moudgil
D020533:Angiogenesis Inhibitors / Q000494:pharmacology; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000188:drug therapy; D002908:Chronic Disease; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol
Autoimmune diseases; Celastrol; Immune modulation; Inflammation; Metabolic disorders; Natural products; Neurodegenerative diseases; Traditional Chinese medicine
Biochem Biophys Res Commun. 1990 Oct 30;172(2):890-7
2241977
Exp Mol Pathol. 2015 Jun;98(3):313-27
25818165
J Ethnopharmacol. 2008 Aug 13;118(3):479-84
18577440
Zhongguo Zhong Yao Za Zhi. 2015 Mar;40(6):1129-33
26226758
Am J Chin Med. 2013;41(3):615-28
23711145
Am J Alzheimers Dis Other Demen. 2014 Mar;29(2):177-82
24226465
J Rheumatol. 2001 Oct;28(10):2160-7
11669150
PLoS One. 2014 Nov 10;9(11):e112470
25383959
Eur J Pharmacol. 2011 Nov 30;670(2-3):399-408
21951963
Int Immunopharmacol. 2012 Dec;14(4):422-31
22954486
Blood. 2007 Apr 1;109(7):2727-35
17110449
Biochim Biophys Acta. 2005 Dec 30;1754(1-2):253-62
16198162
Biochim Biophys Acta. 2015 Aug;1850(8):1607-21
25445706
Pharmacol Ther. 2014 May;142(2):164-75
24333502
Oncol Rep. 2014 Jul;32(1):235-42
24859482
Eur J Clin Invest. 2009 Sep;39(9):819-27
19549173
Int J Clin Exp Med. 2014 Jul 15;7(7):1684-91
25126165
BMC Neurosci. 2009 Sep 01;10:109
19723328
BMC Cancer. 2011 May 14;11:170
21569548
Eur J Pharmacol. 2005 Apr 11;512(2-3):231-7
15840409
Sheng Li Xue Bao. 2015 Jun 25;67(3):341-7
26109308
Ann Intern Med. 2009 Aug 18;151(4):229-40, W49-51
19687490
Cancer Lett. 2011 Apr 1;303(1):9-20
21168266
EMBO J. 1996 Sep 2;15(17):4629-42
8887554
Arthritis Rheum. 2002 Jul;46(7):1735-43
12124856
Pharmacology. 2014;93(1-2):39-46
24434352
Mol Cell Biol. 2009 May;29(10):2570-81
19273585
Autoimmun Rev. 2009 Mar;8(5):388-93
19121415
J Nat Prod. 2002 Jan;65(1):89-91
11809076
Pest Manag Sci. 2005 Jan;61(1):85-90
15593077
BMB Rep. 2015 Mar;48(3):172-7
25059279
Cell Stress Chaperones. 2010 Nov;15(6):939-46
20480272
Autoimmunity. 2009 Nov;42(7):563-73
19863375
J Biol Chem. 2010 Apr 9;285(15):11498-507
20154087
Science. 1997 Sep 12;277(5332):1630-5
9287210
Neurodegener Dis. 2005;2(5):246-54
16909005
Int Immunopharmacol. 2013 Dec;17(4):1028-36
24144813
PLoS One. 2014 Mar 24;9(3):e93151
24664372
Eur J Pharmacol. 2009 Jun 10;612(1-3):131-42
19356729
Toxins (Basel). 2010 Oct;2(10):2428-66
22069560
Proc Natl Acad Sci U S A. 1999 May 11;96(10):5668-73
10318942
J Clin Rheumatol. 2010 Dec;16(8):375-8
21085018
Cancer Res. 2010 Mar 1;70(5):1951-9
20160026
Yao Xue Xue Bao. 1990;25(8):573-7
2082679
Eur J Pharmacol. 2009 Jun 10;612(1-3):98-105
19356734
Chin Med J (Engl). 1986 Apr;99(4):317-20
3098512
Anticancer Agents Med Chem. 2015;15(6):681-93
25783963
Int J Hyperthermia. 2009 Dec;25(8):647-54
20021225
J Cardiovasc Pharmacol. 2009 Sep;54(3):240-5
19661812
Cell Stress Chaperones. 2007 Autumn;12(3):237-44
17915556
Gut. 2003 Jan;52(1):144-51
12477778
Annu Rev Genet. 1988;22:631-77
2853609
Chin Med J (Engl). 2009 Jul 20;122(14):1666-73
19719969
Bioorg Med Chem. 2014 Nov 1;22(21):6053-6061
25284249
Biochem Pharmacol. 2006 Nov 15;72(10):1311-21
16984800
Eur J Pharmacol. 2014 Dec 5;744:52-8
25300680
J Biol Chem. 1998 Nov 6;273(45):29661-71
9792677
J Neurochem. 2014 Jan;128(2):256-266
24111524
Arthritis Res Ther. 2007;9(4):R70
17645785
Int Immunopharmacol. 2015 Feb;24(2):239-246
25529994
Clin Rheumatol. 2010 Sep;29(9):1067-72
20563618
PLoS One. 2013 Apr 26;8(4):e62068
23637966
J Pharmacol Exp Ther. 2010 Aug;334(2):489-99
20472666
Cancer Prev Res (Phila). 2008 Nov;1(6):485-93
19138996
Int Immunopharmacol. 2015 May;26(1):221-8
25858875
J Leukoc Biol. 2006 Aug;80(2):309-19
16769766
Cancer Lett. 2013 May 28;332(2):304-12
20685036
Chem Biol Interact. 2014 Mar 5;210:26-33
24384223
Clin Immunol. 2015 Apr;157(2):228-38
25660987
J Mol Biol. 2011 Jul 29;410(5):972-83
21763500
Biomed Res Int. 2015;2015:308475
25866772
J Mol Med (Berl). 2010 Dec;88(12):1243-53
20798912
Oncol Rep. 2014 Dec;32(6):2527-32
25310109
Curr Protein Pept Sci. 2008 Jun;9(3):227-39
18537678
Apoptosis. 2011 Oct;16(10):1028-41
21786165
Proc Nutr Soc. 1987 Feb;46(1):13-26
3575319
Expert Rev Clin Immunol. 2014 Jul;10(7):819-22
24820012
Cell Death Dis. 2015 Jan 22;6:e1604
25611379
Cancer Prev Res (Phila). 2012 Apr;5(4):631-43
22369852
Nat Rev Mol Cell Biol. 2014 Jun;15(6):411-21
24854789
Chem Biol Interact. 2016 Feb 25;246:52-62
26768587
Zhongguo Yao Li Xue Bao. 1997 May;18(3):270-3
10072949
PLoS One. 2014 Nov 24;9(11):e113783
25419573
J Cell Physiol. 2012 May;227(5):2196-206
21866552
Cell Stress Chaperones. 2014 Nov;19(6):845-51
24700193
Int J Radiat Oncol Biol Phys. 2009 Jul 15;74(4):1217-25
19545787
Int J Cancer. 2014 Oct 1;135(7):1721-32
24615207
Curr Cancer Drug Targets. 2014;14(6):517-36
25092212
J Biol Chem. 2004 Dec 31;279(53):56053-60
15509580
Cell Death Dis. 2011 Aug 25;2:e195
21866174
Cell. 2015 May 21;161(5):999-1011
26000480
Mol Biol Cell. 2008 Mar;19(3):1104-12
18199679
Br J Pharmacol. 2011 Nov;164(5):1506-21
21506956
Pharmacol Res. 2011 Nov;64(5):501-8
21683142
Free Radic Biol Med. 1994 Sep;17(3):201-7
7982625
J Neuroinflammation. 2010 Mar 08;7:17
20211007
J Biol Chem. 2012 Jun 22;287(26):22216-26
22549786
Prog Neuropsychopharmacol Biol Psychiatry. 2001 Oct;25(7):1341-57
11513350
Curr Pharm Biotechnol. 2010 Feb;11(2):158-66
20170473
Eur J Pharmacol. 2014 Nov 5;742:102-12
25218987
Neurochem Res. 2014 Jan;39(1):84-96
24214023
Nat Rev Immunol. 2003 Nov;3(11):900-11
14668806
J Neurochem. 2005 Aug;94(4):995-1004
16092942
Ann Rheum Dis. 2000 Nov;59 Suppl 1:i65-71
11053092
PLoS One. 2013 Jul 04;8(7):e68905
23861949
Zhonghua Jie He He Hu Xi Za Zhi. 2004 Mar;27(3):165-8
15130326
Ann Rheum Dis. 2015 Jun;74(6):1078-86
24733191
Clin Exp Pharmacol Physiol. 2012 Mar;39(3):311-20
21834865
Acta Haematol. 2014;131(2):102-11
24157922
Cell Biochem Funct. 2007 Sep-Oct;25(5):501-7
16929507
PLoS One. 2010 Dec 10;5(12):e14153
21170316
Zhonghua Nei Ke Za Zhi. 2002 May;41(5):317-21
12133425
Clin Exp Metastasis. 2016 Feb;33(2):197-210
26620208
Toxicol Appl Pharmacol. 2014 Oct 1;280(1):42-52
25064159
Br J Pharmacol. 2009 Jul;157(6):1014-23
19508391
Mol Cell Biol. 2002 Oct;22(20):7004-14
12242281
Cancer Lett. 2008 Jun 8;264(1):101-6
18343027
Molecules. 2011 Jun 23;16(6):5283-97
21701438
J Biol Chem. 2011 Apr 29;286(17):15138-46
21402700
Bioorg Med Chem Lett. 2006 Apr 15;16(8):2274-7
16455245
Cancer Metastasis Rev. 2010 Sep;29(3):405-34
20737283
Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):249-54
24351928
Pharmacotherapy. 2012 Dec;32(12):1095-111
23208836
Biochim Biophys Acta. 2014 Oct;1840(10):3145-52
24954307
Altern Med Rev. 2001 Oct;6(5):460-71
11703166
J Clin Invest. 2001 Jan;107(1):7-11
11134171
Exp Mol Med. 2007 Dec 31;39(6):715-21
18160842
Int J Mol Med. 2011 Mar;27(3):407-15
21249310
Biochem Biophys Res Commun. 2012 Jul 6;423(3):467-72
22683631
Biochem Biophys Res Commun. 2010 Apr 9;394(3):439-42
20226165
PLoS One. 2013 Jun 17;8(6):e65477
23799016
Mol Cancer. 2010 Apr 16;9:79
20398364
Nat Rev Neurosci. 2005 Jan;6(1):11-22
15611723
Food Chem Toxicol. 2011 Feb;49(2):527-32
21134410
Gynecol Oncol. 2015 Apr;137(1):173-9
25677064
Autoimmun Rev. 2012 Oct;11(12):856-62
22415021
Mol Cancer. 2013 Aug 02;12:86
23915189
J Cell Mol Med. 2009 Sep;13(9A):2780-6
19674190
Anticancer Drugs. 2009 Nov;20(10):880-92
19745720
Mol Cancer Ther. 2009 Aug;8(8):2339-47
19671767
J Neuroimmune Pharmacol. 2015 Sep;10(3):506-16
25773257
Rheumatology (Oxford). 2008 May;47(5):584-90
18234712