Targeting periodontitis with shikonin: Molecular insights and therapeutic prospects - A narrative review

Shikonin (SHI) is a naturally occurring naphthoquinone predominantly isolated from the roots of Lithospermum erythrorhizon and other species within the Boraginaceae family. Traditionally recognized for its therapeutic potential, SHI has garnered considerable scientific interest due to its broad pharmacological profile and relatively low toxicity. Together with its enantiomer alkannin, SHI shows anti-inflammatory, antibacterial, antioxidant, anticancer, wound-healing, and antithrombotic activities. Recent advancements in extraction technologies, notably ultrasound-assisted ionic liquid-aqueous two-phase systems, have achieved SHI yields of up to 97%, thereby enhancing its accessibility for pharmaceutical applications. SHI is biosynthesized in the endoplasmic reticulum of plant cells through the coordinated activity of the shikimate and mevalonate pathways, with cytochrome P450 enzymes playing a pivotal role in its synthesis. Its relevance in periodontology is increasingly recognized, owing to its capacity to inhibit osteoclastogenesis, promote periodontal tissue and bone regeneration, modulate host immune responses, and suppress pathogenic microorganisms such as Porphyromonas gingivalis. Moreover, SHI's inhibition of pyruvate kinase M2, a key regulator of glycolytic and inflammatory pathways, highlights its potential in the modulation of immunometabolic processes. A systematic search of PubMed, Web of Science, and Scopus using the keywords "shikonin AND periodont*" identified 384 publications. Following screening, 40 studies were selected and thematically categorized: SHI's pharmacological properties, its role in periodontal tissue homeostasis, and its therapeutic potential in clinical periodontology. In summary, SHI appears as a promising candidate for adjunctive periodontal therapy, meriting further investigation into its mechanistic actions and clinical applications in oral health preservation.