Revisiting the Therapeutic Potential of Lichen Derived Secondary Metabolite Atranorin: From Pharmacological Activities to Mechanism of Action

Abstract

Atranorin, a secondary metabolite predominantly found in the cortical layer of numerous lichen species, has garnered significant attention due to its diverse pharmacological properties, yet a systematic and up-to-date review remains lacking. In this review, we comprehensively summarize the biosynthetic pathway, pharmacokinetics, toxicological profile, and therapeutic potential of atranorin, with particular emphasis on its mechanism of action and therapeutic targets. Atranorin exhibits broad spectrum activities against diverse cancers, including melanoma, prostate cancer, gastric cancer, glioblastoma, breast cancer, cervical cancer, lung cancer, pancreatic cancer, colorectal cancer, ovarian cancer, hepatocellular carcinoma, and leukemia. The underlying mechanism involves the activation of apoptosis and ferroptosis, inhibition of Akt-Bcl-xL mediated aerobic glycolysis, inhibition of Wnt/β-catenin and its downstream pathway. Besides anti-tumor, Atranorin also exerts anti-inflammatory activities through blocking ASC mediated NLRP3 inflammasome activation and protects against inflammatory diseases, including systemic inflammation, gouty arthritis, and ulcerative colitis. Moreover, Atranorin possesses neuroprotective, anti-diabetic complication and antimicrobial activities and the mechanism has been elucidated. Notably, a panel of therapeutic targets of Atranorin have been identified and verified, including DUSP3, PTPN1, Akt, ASC, Decr1 and ZIKV Envelope protein. Still, some issues await further investigation, such as incomplete in vivo pharmacokinetic data, poor aqueous solubility, and insufficiently validated targets. In summary, this review provides a mechanistic and target-based theoretical foundation for the further development and clinical translation of Atranorin as a novel natural therapeutic agent.