Therapeutic Effects and Related Molecular Mechanisms of Celastrol, a Triterpenoid Natural Compound and Novel HSP90 Inhibitor Extracted from Plants of the Celastraceae Family

  • Bin Peng
  • Ying Wang
  • Yu-Ting Song
  • Xue Zhang
  • Fan-Fan Cao
  • Li-Min Xu
  • Mei Jiang
  • Xiao-Ling Bo
  • Georges Uzan
  • Deng-Hai Zhang
Part of the Heat Shock Proteins book series (HESP, volume 19)


Celastrol, a triterpenoid compound first identified in the Chinese herbal Tripterygium Wilfordii Hook, f. (TWHF), has attracted much attention in recent years due to its promise in multiple applications. Initially, celastrol was studied mainly as a toxic agent to treat cancer and inflammation. Celastrol’s potential applications have since expanded following findings that it could protect cells due to inducing heat shock proteins via HSF-1 activation (now attributed as caused by HSP90 inhibition). In this paper, we review the therapeutic effects of celastrol towards a variety of abnormalities demonstrated in animal models, including autoimmune and inflammatory diseases, various cancers, neurodegenerative issues, and chronic metabolic disorders. The cellular responses, signaling pathways and proteins reportedly affected by celastrol are also introduced. Moreover, based on celastrol’s chemical structure and properties, as well as reported findings, we present a new molecular model for celastrol’s direct inhibition of the HSP90 chaperone complex, which might be generalized to cover the interactions between celastrol and other targeted proteins. Finally, we suggest future work focusing on clinical translation.


Cancer Celastrol Heat shock protein HSP90 inhibitor Hydrophobicity Inflammation Metabolic disease Michael addition Molecular docking Neurodegenerative disease NF-κB inhibitor 



RAC-alpha serine/threonine-protein kinase


Acute myeloid leukemia


AMP-activated protein kinase

ATF2 or 6

Activating transcription factor 2 or 6


Cell division cycle 37


Cyclin-dependent kinase


Constitutively expressed homology with the viral gene v-myc


Dextran sodium sulfate


Extracellular signal-regulated kinase


Heme oxygenase 1


Heat shock factor 1


Heat shock protein


Heat shock response


Inhibitor of nuclear factor kappa-B kinase


c-Jun N-terminal kinases


Mitogen-activated protein kinase


Myc-associated factor X protein


Lymphocyte antigen 96


Matrix metallopeptidase 9


Manganese-dependent superoxide dismutase




Mammalian target of rapamycin


Nicotinamide adenine dinucleotide


Nuclear factor kappa-light-chain-enhancer of activated B cells


NACHT,LRR and PYD domains-containing protein 3


Nitric oxide


Nuclear factor (erythroid-derived 2)-like 2


Protein kinase R (PKR)-like endoplasmic reticulum kinase


Peroxisome proliferator-activated receptor gamma coactivator 1-alpha


Phosphatidylinositol-4,5-bisphosphate 3-kinase


Receptor activator of nuclear factor kappa-B ligand


Reactive oxygen species


Sterile α- and armadillo-motif-containing protein


Signal transducer and activator of transcription 3


Transforming growth factor beta 1


Toll-like receptor 4


Tumor necrosis factor alpha


Regulatory T cells


Tripterygium Wilfordii Hook, f.


Vascular endothelial growth factor


Vascular endothelial growth factor receptor



Thanks to Mr. Steven Schwab for tidying up the English expressions and grammar. This work was supported in part by the Foundation of Discipline Leader in Health Systems of the Pudong New District (No. PWRd2018-12), the National Natural Science Foundation of China (No. 81102349 and No. 81400793), Shanghai Traditional Chinese Medicine Content Construction Innovation Project (ZY3-CCCX-3-7001), Shanghai health and family planning commission General Program (No. 201540394 and No. 201540395), the Disciplines Group Construction Project of Pu Dong Health Bureau of Shanghai (No. PXZxq2017-15), the Shanghai Gongli Hospital Project (GLRb2018-01 and GLRq2017-01), and Postdoctoral Sustentation Fund of Shanghai Gongli Hospital (No. GLBH2017001).


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Bin Peng
    • 1
  • Ying Wang
    • 1
  • Yu-Ting Song
    • 1
    • 2
  • Xue Zhang
    • 1
  • Fan-Fan Cao
    • 1
  • Li-Min Xu
    • 1
  • Mei Jiang
    • 3
  • Xiao-Ling Bo
    • 4
  • Georges Uzan
    • 1
    • 5
  • Deng-Hai Zhang
    • 1
  1. 1.Sino-French Cooperative Lab, Shanghai Gongli HospitalThe Second Military Medical UniversityShanghaiChina
  2. 2.Postgraduate College of Ning Xiang Medical UniversityYinchuan CityChina
  3. 3.Department of Neurology, Shanghai Gongli HospitalThe Second Military Medical UniversityShanghaiChina
  4. 4.Department of Dermatology, Shanghai Gongli HospitalThe Second Military Medical UniversityShanghaiChina
  5. 5.Inserm 1197 Research Unit, Universite Paris Sud, Paris-Saclay UniversityVillejuifFrance

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