title: Cytopiloyne, a polyacetylenic glucoside from Bidens pilosa, acts as a novel anticandidal agent via regulation of macrophages.
abstract: BACKGROUND
  Bidens pilosa, a tropical and sub-tropical herbal plant, is used as an ethnomedicine for bacterial infection or immune modulation in Asia, America and Africa. It has been demonstrated that cytopiloyne (CP), a bioactive polyacetylenic glucoside purified from B. pilosa, increases the percentage of macrophages in the spleen but the specific effects on macrophages remain unclear.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the effects of CP on macrophage activity and host defense in BALB/c mice with Candida parapsilosis infection and investigate the likely mechanisms.
  
  
  METHODS
  RAW264.7 cells, a mouse macrophage cell line, were used to assess the effects of CP on macrophage activity by phagocytosis assay, colony forming assay and acridine orange/crystal violet stain. To evaluate the activity of CP against C. parapsilosis, BALB/c mouse infection models were treated with/without CP and histopathological examination was performed. The role of macrophages in the infection model was clarified by treatment with carrageenan, a selective macrophage-toxic agent. RAW264.7 macrophage activities influenced by CP were further investigated by lysosome staining, phagosomal acidification assay, lysosome enzyme activity and PKC inhibitor GF109203X.
  
  
  RESULTS
  The results showed that CP in vitro enhances the ability of RAW264.7 macrophages to engulf and clear C. parapsilosis. In the mouse model, CP treatment improved the survival rate of Candida-infected mice and lowered the severity of microscopic lesions in livers and spleens via a macrophage-dependent mechanism. Furthermore, with CP treatment, the fusion and acidification of phagolysosomes were accelerated and the lysosome enzyme activity of RAW264.7 macrophages was elevated. PKC inhibitor GF109203X reversed the increase in phagocytic activity by CP demonstrating that the PKC pathway is involved in the macrophage-mediated phagocytosis of C. parapsilosis.
  
  
  CONCLUSIONS
  Our data suggested that CP, as an immunomodulator, enhances macrophage activity against C. parapsilosis infections.
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Chih-Yao
authors.initials: CY
authors.lastname: Chung
authors.affiliation: Agricultural Biotechnology Research Center, Academia Sinica, Taipei 11529, Taiwan; Department of Aquaculture, National Taiwan Ocean University, Keelung 202, Taiwan; Institute of Pharmacology, Yang-Ming University, Taipei 112, Taiwan; Department of Life Sciences, National Chung-Hsing University, Taichung 402, Taiwan.
authors.forename: Wen-Chin
authors.initials: WC
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung 402, Taiwan.
authors.forename: Chih-Lung
authors.initials: CL
authors.lastname: Liang
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Hsien-Yueh
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan.
authors.forename: Shih-Kai
authors.initials: SK
authors.lastname: Lai
authors.affiliation: Department of Veterinary Medicine, National Chung Hsing University, Taichung 402, Taiwan. Electronic address: ltchang@nchu.edu.tw.
authors.forename: Cicero Lee-Tian
authors.initials: CL
authors.lastname: Chang
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D031176:Bidens; D002177:Candidiasis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D002351:Carrageenan / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D005960:Glucosides / Q000494:pharmacology* / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000187:drug effects; D008517:Phytotherapy; D053279:Polyynes / Q000494:pharmacology* / Q000627:therapeutic use*; D011493:Protein Kinase C / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology
chemical_list: D000935:Antifungal Agents; D005960:Glucosides; C520271:cytopiloyne; D053279:Polyynes; D002351:Carrageenan; D011493:Protein Kinase C
keywords: Bidens pilosa; Candida; Cytopiloyne; Macrophage; PKC