Alkannins and Shikonins: From ancient codes to modern medicine

There are few natural products with histories as rich as those of the enantiomeric naphthoquinones alkannin and shikonin (A/S). Their story can be traced back many centuries, where extracts from the roots of Alkanna tinctoria (A.t.) in Europe and Lithospermum erythrorhizon (L.e.) in the Orient have been used independently as natural red dyes and crude drugs with the magic property of accelerating wound healing.

The first recorded use of A.t. roots is found in the works of Hippocrates and Dioscorides for the treatment of ulcers. Since then, the medicinal properties of the plant either have drifted into folklore, or been forgotten.

In 1976 V.P. Papageorgiou revived the study of these plants and discovered the science behind ancient codes. The results of his experiments confirmed the wound healing, antimicrobial and anti-inflammatory properties of A.t. root extracts and was the first to identify alkannin derivatives as the active components. He developed several pharmaceutical preparations, the clinical trials of which proved their outstanding efficacy in patients with indolent ulcers, burns, wounds. These were approved by the National Organization for Medicines (Greece) (Histoplastin Red®, HELIXDERM®).

Since then, our research focuses on chemistry, biology and technology of A/S. The discovery of oligomeric A/S brought new extensions in chemistry of naphthoquinones. The significant antioxidant activity and anti-Leishmanial action of A/S were confirmed. New clinical trials of HELIXDERM® on diabetic and indolent ulcers present impressive results. Drug delivery systems for A/S (microcapsules, liposomes, hyperbranched polymers, chimeric systems, nanofibers) have been formulated.

The ancient medicinal properties claimed for A.t. and L.e. have been confirmed by scientific experimentation the last 35years. A/S are considered a class of medicines that greatly augment the modern therapeutic arsenal, confirming that natural products can be promising for the development of new pharmaceuticals.