title: Achillolide A Protects Astrocytes against Oxidative Stress by Reducing Intracellular Reactive Oxygen Species and Interfering with Cell Signaling.
abstract: Achillolide A is a natural sesquiterpene lactone that we have previously shown can inhibit microglial activation. In this study we present evidence for its beneficial effects on astrocytes under oxidative stress, a situation relevant to neurodegenerative diseases and brain injuries. Viability of brain astrocytes (primary cultures) was determined by lactate dehydrogenase (LDH) activity, intracellular ROS levels were detected using 2',7'-dichlorofluorescein diacetate, in vitro antioxidant activity was measured by differential pulse voltammetry, and protein phosphorylation was determined using specific ELISA kits. We have found that achillolide A prevented the H₂O₂-induced death of astrocytes, and attenuated the induced intracellular accumulation of reactive oxygen species (ROS). These activities could be attributed to the inhibition of the H₂O₂-induced phosphorylation of MAP/ERK kinase 1 (MEK1) and p44/42 mitogen-activated protein kinases (MAPK), and to the antioxidant activity of achillolide A, but not to H₂O₂ scavenging. This is the first study that demonstrates its protective effects on brain astrocytes, and its ability to interfere with MAPK activation. We propose that achillolide A deserves further evaluation for its potential to be developed as a drug for the prevention/treatment of neurodegenerative diseases and brain injuries where oxidative stress is part of the pathophysiology.
authors.affiliation: Department of Food Quality and Safety, The Volcani Center, Agricultural Research Organization, Bet Dagan 50250, Israel. aelmann@volcani.agri.gov.il.
authors.forename: Anat
authors.initials: A
authors.lastname: Elmann
authors.affiliation: Department of Food Quality and Safety, The Volcani Center, Agricultural Research Organization, Bet Dagan 50250, Israel. alonat@volcani.agri.gov.il.
authors.forename: Alona
authors.initials: A
authors.lastname: Telerman
authors.affiliation: Department of Food Quality and Safety, The Volcani Center, Agricultural Research Organization, Bet Dagan 50250, Israel. hilla_erlank@walla.com.
authors.forename: Hilla
authors.initials: H
authors.lastname: Erlank
authors.affiliation: Dead Sea &amp; Arava Science Center and Regenerative Medicine &amp; Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheba 84105, Israel. rivir@bgu.ac.il.
authors.forename: Rivka
authors.initials: R
authors.lastname: Ofir
authors.affiliation: Raymond and Beverly Sackler Faculty of Exact Sciences, School of chemistry, Tel Aviv University, Ramat Aviv 69978, Israel. kashman@post.tau.ac.il.
authors.forename: Yoel
authors.initials: Y
authors.lastname: Kashman
authors.affiliation: Clinical Biochemistry and Pharmacology Department, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheba 84105, Israel. bye@bgu.ac.il.
authors.forename: Elie
authors.initials: E
authors.lastname: Beit-Yannai
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006861:Hydrogen Peroxide / Q000009:adverse effects; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology
chemical_list: D007783:Lactones; D018696:Neuroprotective Agents; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes; D006861:Hydrogen Peroxide
keywords: Achillea fragrantissima; achillolide A; astrocytes; mitogen-activated protein kinases (MAPK); neurodegenerative diseases; oxidative stress; reactive oxygen species