Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ

Astry, Brian; Venkatesha, Shivaprasad H.; Laurence, Arian; Christensen-Quick, Aaron; Garzino-Demo, Alfredo; Frieman, Matthew B.; O’Shea, John J.; Moudgil, Kamal D.

doi:10.1016/j.clim.2015.01.011

Cited by 110 publications

(97 citation statements)

References 32 publications

(46 reference statements)

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“…Celastrol, derived from a traditional Chinese herb celastrus, has anti-inflammatory and anti-oxidant properties [35,37]. We have previously shown in the AA model that celastrol possesses anti-arthritic properties.…”

Section: Introductionmentioning

confidence: 99%

The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response

Dudics

Venkatesha

Moudgil

2018

IJMS

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Rheumatoid arthritis (RA) is a chronic autoimmune disease of the joints affecting about 0.3–1% of the population in different countries. About 50–60 percent of RA patients respond to presently used drugs. Moreover, the current biomarkers for RA have inherent limitations. Consequently, there is a need for additional, new biomarkers for monitoring disease activity and responsiveness to therapy of RA patients. We examined the micro-RNA (miRNA) profile of immune (lymphoid) cells of arthritic Lewis rats and arthritic rats treated with celastrol, a natural triterpenoid. Experimental and bioinformatics analyses revealed 8 miRNAs (miR-22, miR-27a, miR-96, miR-142, miR-223, miR-296, miR-298, and miR-451) and their target genes in functional pathways important for RA pathogenesis. Interestingly, 6 of them (miR-22, miR-27a, miR-96, miR-142, miR-223, and miR-296) were further modulated by celastrol treatment. Interestingly, serum levels of miR-142, miR-155, and miR-223 were higher in arthritic versus control rats, whereas miR-212 showed increased expression in celastrol-treated rats compared with arthritic rats or control rats. This is the first study on comprehensive miRNA expression profiling in the adjuvant-induced arthritis (AA) model and it also has revealed new miRNA targets for celastrol in arthritis. We suggest that subsets of the above miRNAs may serve as novel biomarkers of disease activity and therapeutic response in arthritis.

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Section: Introductionmentioning

confidence: 99%

The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response

Dudics

Venkatesha

Moudgil

2018

IJMS

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“…Celastrol is a herb found in numerous regions of China, with extensive pharmacological effects (10). Celastrol is a pentacyclic triterpene monomer extracted from the root of Tripterygium wilfordii.…”

Section: Introductionmentioning

confidence: 99%

Effects of celastrol on enhancing apoptosis of ovarian cancer cells via the downregulation of microRNA-21 and the suppression of the PI3K/Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma

Zhang

et al. 2016

Molecular Medicine Reports

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Abstract. Celastrol has previously been used to treat rheumatoid arthritis, bruises, back pain and additional diseases. At present, efficacy studies predominantly focus on the anti-inflammatory, antioxidative and antitumor effects of celastrol. However, the effect of celastrol on ovarian cancer cells is not fully elucidated. In the present study, the effects of celastrol were investigated in ovarian cancer cells and the mechanisms involved were explored. In OVCAR3 cells, celastrol was observed to suppress cellular proliferation, induce apoptosis and increase caspase-9 and -3 activity in a dose-and time-dependent manner. The expression levels of microRNA-21 (miRNA-21) were reduced, in addition to a reduction in the levels of phosphoinositide 3-kinase (PI3K)/p-Akt-NF (NF)-κB following treatment with celastrol. Notably, reduced expression of miRNA-21 replicated the effect of celastrol on OVCAR3 cells and inhibited the PI3K/p-Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma. To the best of our knowledge this is the first study to indicate that celastrol may represent a potential agent for the treatment of human ovarian carcinoma, via the induction of apoptosis through the downregulation of miRNA-21 and the PI3K/Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma.

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“…Celastrol has been studied for the treatment of asthma, skin inflammation, arthritis, systemic lupus erythematosus, hypertension, and neurodegenerative disorders [167]. Recent data has shown that celastrol inhibits NF-κB pathway leading to a significant reduction in the expression of IL-6 and IL-1β in myeloid cells [168]. Clinical investigation of this natural compound has identified a number of health benefits including anti-oxidant, anti-cancer, and anti-inflammatory properties [169].…”

Section: Natural Anti-inflammatory Compounds To Modulate Inflammatmentioning

confidence: 99%

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

Yanez

Blanchette

Jabbarzadeh

2018

CPD

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Tissue engineering offers a promising strategy to restore injuries resulting from trauma, infection, tumor resection, or other diseases. In spite of significant progress, the field faces a significant bottleneck; the critical need to understand and exploit the interdependencies of tissue healing, angiogenesis, and inflammation. Inherently, the balance of these interacting processes is affected by a number of injury site conditions that represent a departure from physiological environment, including reduced pH, increased concentration of free radicals, hypoglycemia, and hypoxia. Efforts to harness the potential of immune response as a therapeutic strategy to promote tissue repair have led to the identification of natural compounds with significant anti-inflammatory properties. This article provides a concise review of the body’s inflammatory response to biomaterials and describes the role of oxygen as a physiological cue in this process. We proceed to highlight the potential of natural compounds to mediate inflammatory response and improve host-graft integration. Herein, we discuss the use of natural compounds to map signaling molecules and checkpoints that regulate the cross-linkage of immune response and skeletal repair.

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Celastrol, a Chinese herbal compound, controls autoimmune inflammation by altering the balance of pathogenic and regulatory T cells in the target organ

Cited by 110 publications

References 32 publications

The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response

The Micro-RNA Expression Profiles of Autoimmune Arthritis Reveal Novel Biomarkers of the Disease and Therapeutic Response

Effects of celastrol on enhancing apoptosis of ovarian cancer cells via the downregulation of microRNA-21 and the suppression of the PI3K/Akt-NF-κB signaling pathway in an in vitro model of ovarian carcinoma

Modulation of Inflammatory Response to Implanted Biomaterials Using Natural Compounds

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