Decreasing Superoxide Radicals with Zingerone

The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 9 No. 1 • January 2006

Decreasing Superoxide Radicals with Zingerone

As noted in the article above, when nitric oxide synthase becomes “uncoupled” from the production of nitric oxide, it generates superoxide radicals. One of the things superoxide radicals do is react with nitric oxide (thereby preventing it from dilating blood vessels), with the resultant creation of peroxynitrite, a powerful oxidant that accounts for many of the deleterious effects of superoxide radicals and of nitric oxide. Earlier studies1,2 have found a correlation between serum superoxide levels and lifespan, with mammals that live longer having higher serum levels of superoxide dismutase (SOD), an antioxidant enzyme that scavenges superoxide radicals. Hence, if you intend to live a long time, increasing protective SOD and decreasing superoxide radical production is a very good idea.

Zingerone is a major flavonoid in ginger. A recent paper3 reports that zingerone treatment (it was injected i.p.) at doses of 6.5 nmol/kg body weight or 65 nmol/kg body weight protected mouse brain from the toxicity of 6-hydroxydopamine by increasing SOD activity. Although zingerone acted as an antioxidant and did scavenge superoxide directly, it was very weak (its superoxide scavenging capability was said to be about 3.1 × 106 times weaker than that of Cu-Zn-SOD). Thus, it induced SOD activity rather than producing its protective effects by scavenging the superoxide itself. An inhibitor of SOD, DDC, eliminated the protective effect of zingerone, showing that its protection was mediated by increased SOD activity. The authors note another paper that reported that SOD transgenic mice (that overexpressed SOD) had resistance to 6-hydroxydopamine-induced dopaminergic neuronal damage. They also note an earlier paper of theirs in which they showed that ropinirole (Requip®, a dopaminergic agonist) prevented 6-hydroxydopamine-induced dopamine depression in the striatum through activation of SOD.


  1. Cutler. Antioxidants and longevity of mammalian species. Basic Life Sci 35:15-73 (1985).
  2. Cutler. Antioxidants and aging. Am J Clin Nutr 53 (1 Suppl):373S-9S (1991).
  3. Kabuto et al. Zingerone [4-(4-hydroxy-3-methoxyphenyl)-2-butanone] prevents 6-hydroxydopamine-induced dopamine depression in mouse striatum and increases superoxide scavenging activity in serum. Neurochem Res 30(3):325-32 (2005).

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