Research Advances in the Structural Characterization and Biological Activity Assessment of Neocryptotanshinone

Neocryptotanshinone (NCTS), a rare diterpene quinone bioactive compound isolated from Salvia miltiorrhiza, was first reported in 1941 and structurally characterized in 1987. The phenanthraquinone core has been extensively characterized in terms of structural confirmation and synthesis. Due to its low natural abundance, NCTS is challenging to extract but can be obtained through semisynthesis. Mechanistically, NCTS was identified in 2015 as an inhibitor of the nuclear factor kappa-B (NF-κB) pathway, inducing a cascade of downstream effects. Its low cytotoxicity, minimal induction of cyclooxygenase-2 (COX-2) expression, and other favorable pharmacological properties suggest therapeutic potential. Recent research has focused on NCTS's therapeutic applications. By modulating multiple pathways, it exerts beneficial effects on heart failure, myocardial ischemia/ reperfusion injury, cerebral ischemia, and type 2 diabetes mellitus. Pharmacokinetic studies are progressing; its promising bioavailability and absorption kinetics require validation. This review summarizes research progress on NCTS and its derivative 16-Ooleoylneocryptotanshinone, covering structural characterization, synthetic routes, structural modifications, pharmacological activities, traditional Chinese medicine applications, and pharmacokinetics. Our goal is to provide a reference for further development of NCTS, which remains in its nascent research phase.