The Promising Therapeutic Potential of Celastrol for Fibrotic Diseases: A Systematic Literature Review on Its Mechanism.

Celastrol is a pentacyclic tripterine sourced from Tripterygium wilfordii hook root. Celastrol can exert certain biological functions such as antitumor, anti-inflammatory, and antiproliferative properties. Celastrol was shown from the previous literature to be capable of attenuating many fibrotic diseases. As the effects of various fibrotic diseases such as atherosclerosis, cancer, and ischemia affect more people with devastating repercussions, this warrants celastrol to be exploited as a phytotherapeutic drug. The purpose of this study is to review previous research and identify the proposed therapeutic mechanisms of celastrol in fibrotic diseases focusing on both the in vitro and in vivo experimental models.  A systematic literature search on Web of Science (WoS), Scopus, and ScienceDirect that included articles published between 2012 and 2022 was carried out using the keywords "celastrol", "tripterine", "fibrotic disease", and "fibrosis". After screening the initial search yield of 405 articles, 25 articles were included in this review.  The study findings summarize the potential therapeutic mechanism of celastrol in the attenuation of fibrotic diseases in in vivo and in vitro experimental models. It shows that celastrol is useful as a treatment means. However, more studies are needed on the effects of celastrol on humans to carry out clinical trials to verify the long-term benefits of celastrol.

Immune-mediated ECM depletion improves tumour perfusion and payload delivery.

High extracellular matrix (ECM) content in solid cancers impairs tumour perfusion and thus access of imaging and therapeutic agents. We have devised a new approach to degrade tumour ECM, which improves uptake of circulating compounds. We target the immune-modulating cytokine, tumour necrosis factor alpha (TNFα), to tumours using a newly discovered peptide ligand referred to as CSG. This peptide binds to laminin-nidogen complexes in the ECM of mouse and human carcinomas with little or no peptide detected in normal tissues, and it selectively delivers a recombinant TNFα-CSG fusion protein to tumour ECM in tumour-bearing mice. Intravenously injected TNFα-CSG triggered robust immune cell infiltration in mouse tumours, particularly in the ECM-rich zones. The immune cell influx was accompanied by extensive ECM degradation, reduction in tumour stiffness, dilation of tumour blood vessels, improved perfusion and greater intratumoral uptake of the contrast agents gadoteridol and iron oxide nanoparticles. Suppressed tumour growth and prolonged survival of tumour-bearing mice were observed. These effects were attainable without the usually severe toxic side effects of TNFα.