Cynaropicrin: A promising sesquiterpene lactone with multifaceted therapeutic potential for various diseases

Cynaropicrin is a guaianolide-type sesquiterpene lactone primarily derived from plants within the Asteraceae family. Structurally, it features a distinctive 5-7-5 tricyclic framework, four exocyclic double bonds, and two hydroxyl groups. Due to its broad pharmacological activities, cynaropicrin garnered considerable scientific interest, with well-established protocols for its extraction and synthesis. Extensive studies have demonstrated that cynaropicrin exhibits remarkable antitumor activities by effectively inhibiting the proliferation of various malignancies, such as lung cancer, melanoma, and breast cancer. The underlying mechanisms are primarily associated with the regulation of cell cycle progression and apoptosis-related pathways. Moreover, cynaropicrin significantly enhances the efficacy of chemotherapeutic agents including temozolomide, cisplatin, and docetaxel, suggesting promising potential for combination therapy. Beyond its antitumor properties, cynaropicrin exhibits a broad spectrum of bioactivities, including antioxidant, antiviral, antiparasitic, and immunomodulatory effects, primarily via the modulation of signaling pathways like NF-κB. Structure-activity relationship (SAR) studies further indicate that the side chain, hydrophilicity of the OH-3 and OH-19 substituents, and the C17-C18 exo-olefin structure critically influence its NF-κB inhibitory activity. This review comprehensively synthesizes current knowledge regarding the mechanisms of action and SAR insight of cynaropicrin across various pathophysiological processes, evaluates its prospects for clinical application, and aims to provide a foundational framework to guide future research and development efforts involving this compound.