Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3+ T-lymphocyte expression in a relapsing–remitting model of multiple sclerosis in rats

Abdin, Amany A.; Hasby, Eiman Adel

doi:10.1016/j.ejphar.2014.09.001

Cited by 38 publications

(34 citation statements)

References 91 publications

(84 reference statements)

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“…This ability of celastrol to interfere with Th17 cells in favor of an anti-inflammatory response was also found in the context of arthritis, as described above. In the EAE mice model, Abdin et al (155) have further proven that celastrol ameliorates disease signs and relapse and causes a shift in the cytokine profile from Th1 towards Th2 cell pattern. Authors have also shown that it reduces NF-kB expression, nitrites levels, TLR2 expression, and CD3+ T cell count (155).…”

Section: Neuroprotective Properties Of Celastrolmentioning

confidence: 99%

“…In the last decade, some studies have reported that celastrol is a promising neuroprotective agent in animal models of neurodegenerative diseases, such as Parkinson disease (149), Huntington disease (149–151), Alzheimer disease (152), and amyotrophic lateral sclerosis (153–155). Neurodegenerative diseases have been termed “protein misfolding disorders” and are characterized by the neuronal accumulation of protein aggregates (156–158).…”

Section: Neuroprotective Properties Of Celastrolmentioning

confidence: 99%

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Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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The identification of new bioactive compounds derived from medicinal plants with significant therapeutic properties has attracted considerable interest in recent years. Such is the case of the Tripterygium wilfordii (TW), an herb used in Chinese medicine. Clinical trials performed so far using its root extracts have shown impressive therapeutic properties but also revealed substantial gastrointestinal side effects. The most promising bioactive compound obtained from TW is celastrol. During the last decade, an increasing number of studies were published highlighting the medicinal usefulness of celastrol in diverse clinical areas. Here we systematically review the mechanism of action and the therapeutic properties of celastrol in inflammatory diseases, namely, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel diseases, osteoarthritis and allergy, as well as in cancer, neurodegenerative disorders and other diseases, such as diabetes, obesity, atherosclerosis, and hearing loss. We will also focus in the toxicological profile and limitations of celastrol formulation, namely, solubility, bioavailability, and dosage issues that still limit its further clinical application and usefulness.

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Section: Neuroprotective Properties Of Celastrolmentioning

confidence: 99%

Section: Neuroprotective Properties Of Celastrolmentioning

confidence: 99%

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

2017

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“…Several studies pointed out the role of celastrol in altering the balance between T helper 17 (Th17) and regulatory T cells (Treg) by suppressing Th17 cell induction and promoting the generation of Treg cells [91][92][93]. Celastrol also increased Th2 cells while decreased Th1 cells accompanied by a significant reduction in NF-κB expression in multiple sclerosis in rats [94]. In order to clarify the exact role of celastrol in the hematopoietic system, our future work may examine the individual cell types of lymphocytes after celastrol treatment in mice.…”

Section: Discussionmentioning

confidence: 99%

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Wang

Ahn

Alharbi

et al. 2020

IJMS

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The present study aimed to explore the possible radioprotective effects of celastrol and relevant molecular mechanisms in an in vitro cell and in vivo mouse models exposed to gamma radiation. Human keratinocytes (HaCaT) and foreskin fibroblast (BJ) cells were exposed to gamma radiation of 20 Gy, followed by treatment with celastrol for 24 h. Cell viability, reactive oxygen species (ROS), nitric oxide (NO) and glutathione (GSH) production, lipid peroxidation, DNA damage, inflammatory cytokine levels, and NF-κB pathway activation were examined. The survival rate, levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in blood, and p65 and phospho-p65 expression were also evaluated in mice after exposure to gamma radiation and celastrol treatment. The gamma irradiation of HaCaT cells induced decreased cell viability, but treatment with celastrol significantly blocked this cytotoxicity. Gamma irradiation also increased free radical production (e.g., ROS and NO), decreased the level of GSH, and enhanced oxidative DNA damage and lipid peroxidation in cells, which were effectively reversed by celastrol treatment. Moreover, inflammatory responses induced by gamma irradiation, as demonstrated by increased levels of IL-6, TNF-α, and IL-1β, were also blocked by celastrol. The increased activity of NF-κB DNA binding following gamma radiation was significantly attenuated after celastrol treatment. In the irradiated mice, treatment with celastrol significantly improved overall survival rate, reduced the excessive inflammatory responses, and decreased NF-κB activity. As a NF-κB pathway blocker and antioxidant, celastrol may represent a promising pharmacological agent with protective effects against gamma irradiation-induced injury.

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“…In in ammatory disease, celastrol had been found to ameliorate myelin oligodendrocyte glycoprotein (MOG)-induced EAE development by reducing Th17 responses in both the periphery and central nervous system (CNS) (20). Celastrol also switches T-cell responses from a predominantly Th1 to Th2 type (16). Moreover, celastrol may also reduce NF-κB expression and T-cell accumulation in the CNS, indicating its anti-in ammatory properties (20,21).…”

Section: Discussionmentioning

confidence: 99%

“…EAN was induced by immunization via subcutaneous injection of 0.3 ml of inoculum to the base of the tail. For celastrol treatments, rats were induced by intragastric administration with celastrol at a dose of 1 mg/kg (16). Celastrol was prepared as a 0.2-mg/ml solution in 1% dimethyl sulfoxide (DMSO).…”

Section: Induction Of Ean and Celastrol Treatmentsmentioning

confidence: 99%

Celastrol ameliorates experimental autoimmune neuritis by shifting the polarization of M1/M2 macrophages via the hypoxic response pathway

Qian¹,

Tang²,

Min-hai³

et al. 2020

Preprint

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BackgroundGBS is an autoimmune disease characterized by inflammatory infiltration and demyelination of peripheral nerves. Macrophage polarization is involved in different stages of GBS. Altering the polarization of macrophages may be an effective therapeutic strategy for GBS. Celastrol was previously shown to contribute to anti-neuroinflammation. However, the mechanism underlying the effect of celastrol in GBS animal model experimental autoimmune neuritis (EAN) is unclear. We hypothesized that celastrol may shift the polarization of macrophages through the NRF /HIF-1αpathway.MethodsClinical scores, weight and histological changes were assessed to investigate the effects of celastrol on EAN. To detect the polarization state of macrophages, flow cytometry and immunofluorescence staining were applied. Inflammation cytokines were evaluated by ELISA. The expression of NRF2 and HIF-1α were detected by western-blot and immunofluorescence staining.ResultsCelastrol treatment significantly ameliorates the severity and neuroinflammation of EAN. The polarization state of macrophages from M1 to M2 was observed upon celastrol application. Consistently, pro-inflammatory cytokines were decreased, whereas anti-inflammatory cytokines were increased upon celastrol treatment. Furthermore, we found that celastrol treatment may increase expression of Nrf2 and decrease the expression of HIF-1α. ConclusionTaken together, these data demonstrate that celastrol may ameliorate the severity and neuroinflammation of EAN via promoting the polarization state of macrophages into M2, likely by modulating the hypoxic response. Celastrol may therefore serve as a novel therapeutic agent for GBS.

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Modulatory effect of celastrol on Th1/Th2 cytokines profile, TLR2 and CD3+ T-lymphocyte expression in a relapsing–remitting model of multiple sclerosis in rats

Cited by 38 publications

References 91 publications

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Celastrol Alleviates Gamma Irradiation-Induced Damage by Modulating Diverse Inflammatory Mediators

Celastrol ameliorates experimental autoimmune neuritis by shifting the polarization of M1/M2 macrophages via the hypoxic response pathway

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