title: Anti-inflammatory effects of Perilla frutescens in activated human neutrophils through two independent pathways: Src family kinases and Calcium.
abstract: The leaves of Perilla frutescens (L.) Britt. have been traditionally used as an herbal medicine in East Asian countries to treat a variety diseases. In this present study, we investigated the inhibitory effects of P. frutescens extract (PFE) on N-formyl-Met-Leu-Phe (fMLF)-stimulated human neutrophils and the underlying mechanisms. PFE (1, 3, and 10 μg/ml) inhibited superoxide anion production, elastase release, reactive oxygen species formation, CD11b expression, and cell migration in fMLF-activated human neutrophils in dose-dependent manners. PFE inhibited fMLF-induced phosphorylation of the Src family kinases (SFKs), Src (Tyr416) and Lyn (Tyr396), and reduced their enzymatic activities. Both PFE and PP2 (a selective inhibitor of SFKs) reduced the phosphorylation of Burton's tyrosine kinases (Tyr223) and Vav (Tyr174) in fMLF-activated human neutrophils. Additionally, PFE decreased intracellular Ca(2+) levels ([Ca(2+)]i), whereas PP2 prolonged the time required for [Ca(2+)]i to return to its basal level. Our findings indicated that PFE effectively regulated the inflammatory activities of fMLF-activated human neutrophils. The anti-inflammatory effects of PFE on activated human neutrophils were mediated through two independent signaling pathways involving SFKs (Src and Lyn) and mobilization of intracellular Ca(2+).
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yann-Lii
authors.initials: YL
authors.lastname: Leu
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
authors.forename: Chwan-Fwu
authors.initials: CF
authors.lastname: Lin
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Division of General Surgery, Department of Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Liang-Mou
authors.initials: LM
authors.lastname: Kuo
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Wei-Che
authors.initials: WC
authors.lastname: Sung
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Yung-Fong
authors.initials: YF
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Pei-Jen
authors.initials: PJ
authors.lastname: Chung
authors.affiliation: Brion Research Institute of Taiwan, New Taipei City 231, Taiwan.
authors.forename: Ming-Chung
authors.initials: MC
authors.lastname: Lee
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
authors.forename: Hsuan-Wu
authors.initials: HW
authors.lastname: Yang
authors.affiliation: Graduate Institute of Natural Products, School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.|Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Kweishan, Taoyuan 333, Taiwan.|Department of Cosmetic Science and Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan.
authors.forename: Tsong-Long
authors.initials: TL
authors.lastname: Hwang
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D039481:CD11b Antigen / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010196:Pancreatic Elastase / Q000378:metabolism; D031344:Perilla frutescens / Q000737:chemistry*; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D039481:CD11b Antigen; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D013481:Superoxides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D019061:src-Family Kinases; D010196:Pancreatic Elastase; D002118:Calcium