Justicidin: A Versatile Arylnaphthalene Lignan with Broad-Spectrum Anticancer and Chronic Disease Potential.

Justicidins are naturally occurring arylnaphthalene lignans, mainly from Justicia, Phyllanthus, and Linum species. Justicidin and its derivatives have gained scientific attention for their structural adaptability and wide-ranging pharmacological activities. Their rigid arylnaphthalene core, featuring hydroxyl, methoxy, dioxymethylene groups, and a five-membered lactone ring, offers chemical stability and scope for modification, enabling targeted drug design. Preclinical studies show that justicidin has potent cytotoxicity against breast, lung, leukemia, colorectal, and bladder cancer cells through mechanisms such as apoptosis induction via mitochondrial pathways, topoisomerase inhibition, cell cycle modulation, angiogenesis suppression, and interference with metastasis-related signaling. Beyond oncology, it demonstrates anti-inflammatory, antiviral, neuroprotective, antibacterial, antiplatelet, and antiangiogenic effects. Its multi-target activity involves modulation of NF-κB, MAPK, and PI3K/Akt pathways, as well as DNA damage induction, mitochondrial membrane potential disruption, and regulation of caspases. Low toxicity in normal cells and favorable pharmacokinetics in experimental models strengthen its therapeutic promise. Advances in total synthesis and biotechnological production further enhance its research value. This review compiles current insights into the chemistry, biosynthesis, biotechnological production, pharmacology, and molecular mechanisms of justicidin, underscoring its dual potential as an anticancer lead and a versatile agent for chronic diseases. Understanding structure-activity relationships and optimizing drug-like properties may enable the development of novel, multi-target therapeutics inspired by this natural product.