Reaction of β-alkannin (shikonin) with reactive oxygen species : Detection of β-alkannin free radicals

• Published in: Bioorganic & medicinal chemistry Vol. 8; no. 11; pp. 2561 - 2569
• Main Authors: DAYUAN GAO, KAKUMA, Miyako, OKA, Shigenori, SUGINO, Keiji, SAKURAI, Hiromu
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Science 01.11.2000
• Subjects: Acetonitriles - metabolism; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Deuterium Oxide; Electron Spin Resonance Spectroscopy; Free Radical Scavengers - chemistry; Free Radical Scavengers - metabolism; Free Radicals - analysis; Free Radicals - metabolism; Lipid Peroxidation; Medical sciences; Molecular Structure; Naphthoquinones - chemistry; Naphthoquinones - metabolism; Peroxides - metabolism; Pharmacology. Drug treatments; Plants, Medicinal - chemistry; Plants, Medicinal - metabolism; Potentiometry; Reactive Oxygen Species - metabolism; Spin Trapping; Asia; Japan; Reaction intermediate; MO method; Rat; EPR spectrometry; Dissociation constant; Lipids; Microsome; Diphenols; Free radical; Medicinal plant; Folk medicine; Dicotyledones; Angiospermae; Inhibition; Mechanism of action; Peroxidation; Oriental medicine; Quinone; Rodentia; Antiinflammatory agent; Naphthoquinone derivatives; Antioxidant; Boraginaceae; In vitro; Radical scavenger; Vertebrata; Mammalia; Organic free radical; Animal; Plant origin; Spermatophyta; Redox potential; Physicochemical properties
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/S0968-0896(00)00191-7

beta-Alkannin (shikonin), a compound isolated from the root of Lithospermum erythrorhizon Siebold Zucc., has been used as a purple dye in ancient Japan and is known to exert an anti-inflammatory activity. This study aimed to understand the biological activity in terms of physico-chemical characteristics of beta-alkannin. Several physico-chemical properties including proton dissociation constants, half-wave potentials and molecular orbital energy of beta-alkannin were elucidated. This compound shows highly efficient antioxidative activities against several types of reactive oxygen species (ROS), such as singlet oxygen ((1)O2). superoxide anion radical (.O2), hydroxyl radical (.OH) and tert-butyl peroxyl radical (BuOO.) as well as iron-dependent microsomal lipid peroxidation. During the reactions of beta-alkannin with 1O2, .O2- and BuOO., intermediate organic radicals due to beta-alkannin were detectable by ESR spectrometry. Compared with the radicals due to naphthazarin, the structural skeleton of beta-alkannin, the beta-alkannin radical observed as an intermediate in the reactions with (1)O2, and .O2- was concluded to be a semiquinone radical. On the other hand, during the reactions of beta-alkannin and naphthazarin with BuOO., ESR spectra different from the semiquinone radical were observed, and proposed to result from the abstraction of hydrogen atoms from phenolic hydroxyl groups of beta-alkannin by BuOO.. Based on the ROS-scavenging abilities of beta-alkannin, the compound was concluded to react directly with ROS and exhibits antioxidative activity, which in turn exerts anti-inflammatory activity.