Celastrol: A Spectrum of Treatment Opportunities in Chronic Diseases

Abstract

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.

Ca2+ signalling plays a role in celastrol‐mediated suppression of synovial fibroblasts of rheumatoid arthritis patients and experimental arthritis in rats

“…Although celastrol has exhibited anti‐arthritic effect in vivo (Li et al, ; Venkatesha, Yu, Rajaiah, Tong, & Moudgil, ) through inhibition of cytokines, chemokines, and inflammatory mediators (Cascao, Fonseca, & Moita, ), the role of celastrol‐mediated Ca 2+ in RA therapy remains unclear. Therefore, the possible anti‐arthritic effect of celastrol via Ca 2+ mobilization was examined in the AIA rat model.…”

“…RA pathogenesis factor colours are only linked to their coloured asterisks ( * ) and are independent of the gene and pathway colour-coding & Moudgil, 2011; Li et al, 2012;Nanjundaiah et al, 2012;Li et al, 2013;Astry et al, 2015;Jiang et al, 2015;Lv et al, 2015). Although the molecular targets responsible for the celastrol-mediated antiarthritic effect have been identified (Cascao et al, 2012;Li et al, 2012;Li et al, 2013;Astry et al, 2015;Cascao, Fonseca, & Moita, 2017 (Wang et al, 2016). The blockade of store-operated Ca 2+ release-activated channels with the use of neutralizing antibodies can also effectively suppress the activity of T cells and B cells derived from RA patients (Liu et al, 2017).…”

“…Li et al, 2013;Venkatesha, Yu, Rajaiah, Tong, & Moudgil, 2011) through inhibition of cytokines, chemokines, and inflammatory mediators(Cascao, Fonseca, & Moita, 2017), the role of celastrol-mediated Ca 2+ in RA therapy remains unclear. Therefore, the possible anti-arthritic effect…”

Activation of nicotinamide adenine dinucleotide phosphate oxidase is the primary trigger of epileptic seizures in rodent models

“…The therapeutic usefulness and anti-inflammatory properties of celastrol have been studied in several inflammatory diseases, including rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus, inflammatory bowel disease, osteoarthritis, allergy, and skin inflammation. 49 However, despite the therapeutic potential of celastrol, clinical applications are limited by low water solubility, reduced oral bioavailability, narrow window of dosage, and adverse side effects. 50 In contrast, GSK2795039 is not cytotoxic at concentrations efficacious for NOX2 inhibition.…”

Comparative Proteome Analysis of Celastrol-TreatedHelicobacter pylori

“…After 2-dimensional electrophoresis analysis, spot intensities were analyzed and then each spot was identified using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) or peptide sequencing using Finnigan LCQ ion trap mass spectrometer (LC-MS/MS). The results show that celastrol has multiple effects on protein expression in H. pylori.Key Words: Helicobacter pylori, 2 dimensional electrophoresis, Celastrol, MALDI-TOF-MS Recently, interest in celastrol has renewed again as a new candidate drug for obesity and various chronic diseases (Cascao et al, 2017). Celastrol has been reported primarily to exhibit inhibitory effects on several cancers, such as breast cancer, prostate cancer and colorectal cancer (Shrivastava et al, 2015;Guo et al, 2015;Lin et al, 2016).…”