title: Downregulation of microglial activation by achillolide A.
abstract: Chronic inflammation has been implicated in the pathogenesis of various neurodegenerative diseases. During the neuroinflammatory process, microglial cells release neurotoxic and proinflammatory mediators. In the present study, using activity-guided fractionation, we have purified an anti-inflammatory compound determined by spectroscopic methods to be a sesquiterpene lactone named achillolide A from Achillea fragrantissima (Forsk.) Sch. Bip. In primary cultures of lipopolysaccharide-activated microglial cells, achillolide A inhibited the lipopolysaccharide-induced levels of proinflammatory and toxic mediators including glutamate, nitric oxide, matrix metalloproteinase-9, cyclooxygenase-2, induced nitric oxide synthase, interleukin-1β, and tumor necrosis factor-α. Achillolide A also exhibited an antioxidant capacity, as was shown in a cell free system as well as by its ability to reduce intracellular reactive oxygen species levels in microglial cells. Thus, achillolide A might have therapeutic potential for treatment of neurodegenerative diseases and deserves further studies.
authors: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Bet Dagan, Israel.
authors: Anat
authors: A
authors: Elmann
authors: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Bet Dagan, Israel.
authors: Alona
authors: A
authors: Telerman
authors: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Bet Dagan, Israel.
authors: Sharon
authors: S
authors: Mordechay
authors: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Bet Dagan, Israel.
authors: Hilla
authors: H
authors: Erlank
authors: Department of Food Quality and Safety, Volcani Center, Agricultural Research Organization, Bet Dagan, Israel.
authors: Miriam
authors: M
authors: Rindner
authors: School of Chemistry, Tel Aviv University, Ramat Aviv, Israel.
authors: Yoel
authors: Y
authors: Kashman
authors: Dead Sea & Arava Science Center and Regenerative Medicine & Stem Cell Research Center, Ben-Gurion University of the Negev, Beer-Sheba, Israel.
authors: Rivka
authors: R
authors: Ofir
mesh_terms: D031162:Achillea / Q000737:chemistry*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D018836:Inflammation Mediators; D007783:Lactones; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012717:Sesquiterpenes