title: Evidence of biological activity of Mentha species extracts on apoptotic and autophagic targets on murine RAW264.7 and human U937 monocytic cells.
abstract: BACKGROUND
  Mints (Lamiaceae) are used as traditional remedies for the treatment of several diseases. Their extracts are recognized as anti-inflammatory compounds.
  
  
  OBJECTIVE
  This study characterized the cytotoxic effects of Mentha spicata L. (MS), Mentha pulegium L. (MP) and Mentha rotundifolia (L). Huds (MR) on macrophage cells (RAW264.7; U937) and determined their impact on apoptosis and autophagy, which can play a role in controlling inflammation.
  
  
  METHODS
  The extracts were prepared in culture medium and tested from 25 to 400 μg/mL after 24-48 h of treatment. To show the effect of the aqueous ethanol (50%) extracts on apoptosis and authophagy, the presence of cleaved caspase-3, and the conversion of LC3-I to LC3-II was evaluated by Western blotting.
  
  
  RESULTS
  Compared with the MTT assay, crystal violet showed a pronounced decrease in the number of cells with all extracts at 48 h. Calculated IC50values were 257.31, 207.82 and 368.02 μg/mL for MS, MP and MR, respectively. A significant increase in PI positive cells was observed with all extracts at 200-400 μg/mL. Mitochondrial dysfunctions and nuclear morphological changes were detected with MS and MR extracts at 400 μg/mL. At this concentration, no cleaved caspase-3 was found whereas stabilized caspase-3 in its dimeric form was identified. MS and MR extracts also favour LC3-I to LC3-II conversion which is a criterion of autophagy.
  
  
  CONCLUSIONS
  The cytotoxic profiles depend on the extracts considered; MS extract showed the strong activity. However, all the mint extracts studied interact with the apoptotic and autophagic pathways at elevated concentrations.
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.|b Laboratory of 3BS, Faculty of Life and Nature Sciences , Universty of Bejaia , Bejaia , Algeria.
authors.forename: Fatiha
authors.initials: F
authors.lastname: Brahmi
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.|c Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health' , University Monastir , Monastir , Tunisia.
authors.forename: Samia
authors.initials: S
authors.lastname: Hadj-Ahmed
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.|c Faculty of Medicine, LR12ES05, Lab-NAFS 'Nutrition - Functional Food & Vascular Health' , University Monastir , Monastir , Tunisia.|d Laboratory Biochemistry, Faculty of Medicine , University of Sousse , Sousse , Tunisia.
authors.forename: Amira
authors.initials: A
authors.lastname: Zarrouk
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.|e Laboratory of 'Venoms and Therapeutic Biomolecules' , University of Tunis El Manar - Pasteur Institut , Tunis , Tunisia.
authors.forename: Maryem
authors.initials: M
authors.lastname: Bezine
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Nury
authors.affiliation: b Laboratory of 3BS, Faculty of Life and Nature Sciences , Universty of Bejaia , Bejaia , Algeria.
authors.forename: Khodir
authors.initials: K
authors.lastname: Madani
authors.affiliation: f Faculty of Life, Nature and Earth Sciences , University of Akli Mohand Oulhadj , Bouira , Algeria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Chibane
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vejux
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Andreoletti
authors.affiliation: b Laboratory of 3BS, Faculty of Life and Nature Sciences , Universty of Bejaia , Bejaia , Algeria.
authors.forename: Lila
authors.initials: L
authors.lastname: Boulekbache-Makhlouf
authors.affiliation: a Team 'Biochemistry of the Peroxisome, Inflammation and Lipid Metabolism' EA 7270/INSERM, Faculté des Sciences Gabriel , University Bourgogne Franche Comté , Dijon , France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Lizard
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D027541:Mentha / Q000737:chemistry*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D000067996:RAW 264.7 Cells; D013997:Time Factors; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D010936:Plant Extracts; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Mentha spicata; mentha pulegium; mentha rotundifolia; mitochondria