Neuroprotective Effect of Halophyte Salicornia herbacea L. Is Mediated by Activation of Heme Oxygenase-1 in Mouse Hippocampal HT22 Cells

Salicornia herbacea L. (glasswort, tungtungmadi in Korean), a halophyte that grows in salt marshes and muddy seashores along the western coast of Korea, has been used as a seasoning vegetable and a folk medicine for intestinal ailments, nephropathy, and hepatitis. As the salt-tolerant herb was reported to contain antioxidants, including tungtungmadic acid, quercetin, and chlorogenic acid, we hypothesized that the ethanolic extract of S. herbacea L. (SH extract) enriched with antioxidative compounds will have neuroprotective activity. The herbal extract and its methylene chloride (MC) fraction showed a strong protective effect against glutamate-induced cell death in murine hippocampal HT22 cells. In addition, SH extract and MC fraction not only scavenged reactive oxygen species efficiently but also caused nuclear translocation of nuclear factor (erythroid-derived 2)-like 2 and subsequently significant induction of antioxidant enzymes such as NAD(P) H: quinone oxidoreductase, heme oxygenase 1 (HO-1), and glutathione reductase. Inhibition of the antioxidant enzyme HO-1 by tin protoporphyrin abolished the neuroprotective effect of the SH extract, suggesting an important role of HO-1 in protection against glutamate-induced neural damage. Metabolite profiling for ethanolic extract and solvent fractions of the herb suggested that diosmetin and a few unidentified compounds were responsible for the neuroprotective effect. Taken together, SH extract and its MC fraction exhibited a neuroprotective effect through Nrf2-mediated induction of antioxidant enzymes, such as HO-1, and warrant further in vivo and clinical studies to confirm its effects and potentially develop a neuroprotective salt substitute or dietary supplement.