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.
1 School of Food Science and Biotechnology and BK21 Plus Program, Kyungpook National University , Daegu, Republic of Korea.
Min Sun
MS
Kim
1 School of Food Science and Biotechnology and BK21 Plus Program, Kyungpook National University , Daegu, Republic of Korea.
Ji Yeon
JY
Seo
1 School of Food Science and Biotechnology and BK21 Plus Program, Kyungpook National University , Daegu, Republic of Korea.
Jisun
J
Oh
2 Department of Bioscience and Biotechnology, Konkuk University , Seoul, Republic of Korea.
Yu Kyung
YK
Jang
2 Department of Bioscience and Biotechnology, Konkuk University , Seoul, Republic of Korea.
Choong Hwan
CH
Lee
1 School of Food Science and Biotechnology and BK21 Plus Program, Kyungpook National University , Daegu, Republic of Korea.
Jong-Sang
JS
Kim
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019663:Chenopodiaceae / Q000737:chemistry*; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D056910:Republic of Korea; D055051:Salt-Tolerant Plants / Q000737:chemistry*
D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1
HO-1; Nrf2; Salicornia herbacea L.; diosmetin; neuroprotection