Therapeutic potential of celastrol in bacterial infections: Current research advancements and future perspectives

Abstract

Drug-resistant bacterial infections and their associated inflammatory diseases constitute a deadly threat to global health. Celastrol is one of the main effective components extracted from the traditional Chinese medicine Tripterygium wilfordii Hook.F (TWHF). An increasing number of researchers have been focusing on the pharmacological properties of celastrol in the context of bacterial infection and associated inflammatory complications. This paper presents a comprehensive review of the pharmacological activity and mechanisms of celastrol in the treatment of bacterial infectious diseases. Celastrol has been demonstrated to possess a range of antibacterial, anti-biofilm, anti-virulence and synergistic antibacterial properties with antibiotics, mediated through diverse molecular mechanisms. Several potential targets of celastrol, such as Δ¹-Pyrroline-5-Carboxylate Dehydrogenase (P5CDH), Filamenting temperature-sensitive mutant Z (FtsZ), and GdpP, have been identified. By acting on these proteins, celastrol can disrupt bacterial structure (e.g., cell walls and membranes), inhibit macromolecular synthesis (protein, RNA, and DNA), and interfere with metabolic pathways. Furthermore, celastrol exerts dual immunomodulatory effects against bacterial infections through the coordinated regulation of host-pathogen interactions: by suppressing critical bacterial virulence factors staphyloxanthin (STX) and chemotaxis inhibitory protein of S. aureus (CHIPS) to counteract immune evasion mechanisms, while simultaneously activating nuclear respiratory factor 1 (Nrf1), nuclear factor kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), and various signaling pathways of host immune cells to attenuate infection-induced hyperinflammatory responses and immunocyte-derived tissue damage. Finally, a review and discussion of the therapeutic potential of celastrol is presented, with particular attention to its future development as an effective therapeutic agent for treating diseases associated with bacterial infections.