Shikonin: A Review with a Focus on Anti-inflammatory and Anticancer Mechanisms

Abstract

Shikonin (alkannin) is one of the main active components isolated from the Chinese herb Lithospermum Erythrorhizon. Shikonin shows pleiotropic medical properties, such as antibacterial, wound healing, anti-inflammatory, antithrombotic, neuroprotective and antitumor effects. In this article, we discuss recent studies on the activities of shikonin with an emphasis on its effects on the intracellular signaling pathways relevant to anti-inflammatory and anticancer effects. Shikonin has a beneficial feature that it can induce apoptosis in many cancer cells despite its relatively low toxicity to normal cells. The effects of shikonin on many signaling pathways and processes including the NF-B pathway, the PI3K/Akt pathway, the nuclear factor E2 (erythroid-derived 2)-related factor 2(Nrf2) pathway, the reactive oxygen species (ROS) production, and the aerobic glycolysis represent the presence of the multiple target. Similarities between the anti-inflammatory and anticancer mechanisms emerge, but shikonin differentially regulates the ROS levels depending on the cell type. This feature appears to enable shikonin to regulate the cell fate in a manner dependent on the cell context and experimental setting. Further analyses on shikonin are expected to provide insights into the mechanisms by which how cells integrate the ROS signaling in the decision of the cellular outcome, such as survival, autophagy and apoptosis.