Celastrol is a quinone methide triterpenoid extracted from the root bark of Hook F, and it exhibits extensive biological activities such as anti-cancer effects. However, narrow therapeutic window together with undesired side effects limit its clinical application. In this study, we explore celastrol's cardiotoxicity using the methods of histology and cell biology. The results show that celastrol administration dose-dependently induces cardiac dysfunction in mice as manifested by left ventricular dilation, myocardial interstitial fibrosis, and cardiomyocyte hypertrophy. Exposure to celastrol greatly decreases neonatal rat ventricular myocyte (NRVM) viability and promotes its apoptosis. More importantly, we demonstrate that celastrol exerts its pro-apoptotic effects through endoplasmic reticulum (ER) stress and unfolded protein response. Furthermore, siRNA targeting C/EBP homologous protein, a pivotal component of ER stress-mediated apoptosis, effectively prevents the pro-apoptotic effect of celastrol. Taken together, our results demonstrate the potential cardiotoxicity of celastrol and a direct involvement of ER stress in the celastrol-induced apoptosis of NRVMs. Thus, we recommend careful evaluation of celastrol's cardiovascular effects when using it in the clinic.
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http://dx.doi.org/10.3724/abbs.2022104 | DOI Listing |
Inflamm Res
January 2025
Henan International Joint Laboratory for Nuclear Protein Regulation, School of Basic Medical Sciences, Henan University, Kaifeng, 475004, Henan, China.
Celastrol is one of the main active ingredients extracted from the plant Tripterygium wilfordii Hook F. A growing number of studies have shown that celastrol has various pharmacological effects, including anti-inflammation, anti-rheumatism, treatment of neurodegenerative diseases, and anti-tumor. This article systematically summarized the mechanism and role of celastrol in lipid metabolism and obesity, rheumatoid arthritis (RA), osteoarthritis (OA), gouty arthritis, inflammatory bowel disease, neurodegenerative diseases, and cancer and other diseases (such as diabetes, respiratory-related diseases, atherosclerosis, psoriasis, hearing loss, etc.
View Article and Find Full Text PDFAntibiotics (Basel)
January 2025
Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Facultad de Farmacia, Universidad de La Laguna, Avenida Astrofísico Fco Sánchez s/n, 38206 La Laguna, Spain.
: The emergence of antibiotic-resistant bacteria, including , underscores the need for novel antimicrobial agents. Celastrol, a natural compound derived from the plants of the Celastraceae family, has demonstrated promising antibacterial and antibiofilm properties against various pathogens. This study aims to evaluate the antibacterial effects, mechanism of action, and antibiofilm activity of celastrol against , an emerging opportunistic pathogen.
View Article and Find Full Text PDFInt J Pharm
January 2025
Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405 China. Electronic address:
Breast cancer and its lung metastases pose significant threats to women's health worldwide, impacting their quality of life. Although several therapeutic strategies against breast cancer have been developed, they often cause serious side effects due to their high toxicity and low specificity. Therefore, novel therapeutic strategies that offer potent anti-tumor activity with minimal toxicity are urgently needed to combat the threat of breast cancer and lung metastases.
View Article and Find Full Text PDFLancet Diabetes Endocrinol
January 2025
Division of Diabetes & Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, UK; Catholic University of the Sacred Heart, Rome, Italy; University Polyclinic Foundation Agostino Gemelli IRCCS, Rome, Italy.
Zhongguo Zhong Yao Za Zhi
December 2024
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences Beijing 100700, China.
This study aimed to investigate the potential role of Colquhounia Root Tablets against bone destruction in rheumatoid arthritis(RA) and its molecular mechanism. The study used ultra-performance liquid chromatography-mass spectrometry to analyze the major components of Colquhounia Root Tablets and predicted its candidate target gene set based on the major components. The key targets of RA bone destruction were obtained through GeneCards and the Database of Genetics and Medical Literature(OMIM), protein-protein interaction(PPI) network was constructed, and the key targets were identified by topological analysis.
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