Helenalin: a multifaceted sesquiterpene lactone with diverse biological activities-an integrative pharmacological and computational evidence.

Helenalin, a naturally occurring sesquiterpene lactone derived primarily from Arnica montana, has emerged as a promising multitarget therapeutic agent due to its diverse anti-inflammatory, antioxidant, cytotoxic, and antimicrobial activities. The review summarized the pharmacological spectrum and molecular mechanisms underlying helenalin bioactivity. Helenalin exerts anticancer activities by regulating key oncogenic signaling, especially, NF-κB and STAT3/MYC pathway. Helenalin demonstrated Nrf2 antioxidant pathway activation and muted P2X7R-dependent inflammation in osteoarthritis models. It was also found to have antimicrobial activity and was effective in melting the redox and quorum sensing in the pathogens, which were interesting to use in the drug-resistant infections. ADMET predictions support the good drug likeness, pharmacokinetics, and oral bioavailability, and it satisfies the Lipinski Rule of Five. The network pharmacological and GO/KEGG enrichment analyses indicated the implication of helenalin in cancer and inflammation -related pathways. Molecular docking also showed strong binding with COX-1, Bcl-2, and hub target proteins having docking scores of - 9.2 to 11.3, respectively, which confirmed its potential as a pharmacological agent. The learning of this multifaceted pharmacology profile together with the tools of systems biology, however, establishes helenalin as an attractive lead compound towards the development of novel anticancer, anti-inflammatory, antiarthritic, antioxidant, antiviral, antibacterial, and antiangiogenic agents. Its therapeutic index should be further confirmed using future translational research.