Anti-Inflammatory Effects of Angelica sinensis (Oliv.) Diels Water Extract on RAW 264.7 Induced with Lipopolysaccharide

Nutrients. 2018 May 21;10(5):647. doi: 10.3390/nu10050647.

Abstract

The dry root of Angelica sinensis (Oliv.) Diels, also known as &ldquo;female ginseng&rdquo;, is a popular herbal drug amongst women, used to treat a variety of health issues and cardiovascular diseases. The aim of this study is to evaluate the detailed molecular mechanism for anti-inflammatory effects of Angelica sinensis root water extract (ASW). The anti-inflammatory effect of ASW on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages was evaluated by the tetrazolium-based colorimetric assay (MTT), Griess reagent assay, multiplex cytokine assay, real time reverse transcription polymerase chain reaction (RT-PCR), and Fluo-4 calcium assay. ASW restored cell viability in RAW 264.7 at concentrations of up to 200 &micro;g/mL. ASW showed notable anti-inflammatory effects. ASW exhibited IC50 = 954.3, 387.3, 191.7, 317.8, 1267.0, 347.0, 110.1, 573.6, 1171.0, 732.6, 980.8, 125.0, and 257.0 &micro;g/mL for interleukin (IL)-6, tumor necrosis factor (TNF)-&alpha;, monocyte chemotactic activating factor (MCP)-1, regulated on activation, normal T cell expressed and secreted (RANTES), granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), vascular endothelial growth factor (VEGF), lipopolysaccharide-induced CXC chemokine (LIX), macrophage inflammatory protein (MIP)-1&alpha;, MIP-1&beta;, MIP-2, IL-10, and intracellular calcium, respectively. Additionally, ASW inhibited the LPS-induced production of nitric oxide and the LPS-induced mRNA expression of CHOP (GADD153), Janus kinase 2 (JAK2), signal transducers and activators of transcription 1 (STAT1), first apoptosis signal receptor (FAS), and c-Fos, NOS2, and PTGS2 (COX2) in RAW 264.7 significantly (p < 0.05). Data suggest that ASW exerts an anti-inflammatory effect on LPS-induced RAW 264.7 via NO-bursting/calcium-mediated JAK-STAT pathway.

Keywords: Angelica sinensis; JAK-STAT; anti-inflammatory; calcium; cytokine; macrophage; nitric oxide.

MeSH terms

  • Angelica sinensis / chemistry*
  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • Calcium Signaling / drug effects
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / metabolism
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Regulation
  • Inflammation Mediators / metabolism
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism
  • Lipopolysaccharides / pharmacology*
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Phytotherapy
  • Plants, Medicinal
  • RAW 264.7 Cells
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Solvents / chemistry*
  • Time Factors
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism
  • Water / chemistry*
  • fas Receptor / genetics
  • fas Receptor / metabolism

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Ddit3 protein, mouse
  • Drugs, Chinese Herbal
  • Fas protein, mouse
  • Inflammation Mediators
  • Lipopolysaccharides
  • RNA, Messenger
  • STAT1 Transcription Factor
  • Solvents
  • Stat1 protein, mouse
  • fas Receptor
  • Water
  • Transcription Factor CHOP
  • Nitric Oxide
  • angelicae sinensis extract
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Jak2 protein, mouse
  • Janus Kinase 2