PMID- 27643502
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20190212
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 9
DP  - 2016
TI  - Anti-Inflammatory, Anti-Osteoclastogenic and Antioxidant Effects of Malva 
      sylvestris Extract and Fractions: In Vitro and In Vivo Studies.
PG  - e0162728
LID - 10.1371/journal.pone.0162728 [doi]
LID - e0162728
AB  - Given their medical importance, natural products represent a tremendous source of 
      drug discovery. The aim of this study was to investigate Malva sylvestris L. 
      extract and fractions and their pharmacological activities followed by chemical 
      identification. The aqueous fraction (AF) was identified as the bioactive 
      fraction in the in vitro and in vivo assays. The AF controlled the neutrophil 
      migration to the peritoneal cavity by 66%, inhibited the antiedematogenic 
      activity by 58.8%, and controlled IL-1beta cytokine expression by 54%. The in vitro 
      viability tests showed a concentration-dependent effect, where the MSE and 
      fractions at concentrations under 10 mug/mL were non-toxic to cells. 
      Transcriptional factors of carbonic anhydrase II (CAII), cathepsin K (Ctsk) and 
      tartrate-resistant acid phosphatase (TRAP) were analyzed by qPCR in RAW 264.7 
      cell lines. The gene expression analysis showed that the AF was the only 
      treatment that could downregulate all the study genes: CAII, Ctsk and TRAP 
      (p<0.05). TRAP staining was used to evaluate osteoclast formation. AF treatments 
      reduced the number of osteoclastogenesis 2.6-fold compared to the vehicle control 
      group. Matrix metalloproteinase 9 (MMP-9) activity decreased 75% with the AF 
      treatment. Moreover, the bioactive fraction had the ability to regulate the 
      oxidation pathway in the ABTS (2,2-Azino-bis (3-ethylbenzthiazoline-6-sulfonic 
      acid) assay with an activity equivalent to 1.30 mumol Trolox/g and DPPH 
      (2,2-diphenyl-1-picrylhydrazyl) radicals 1.01 g/L. Positive ion ESI-mass 
      spectrometry for molecular ions at m/z 611 and 633 confirmed rutin as the major 
      compound in the AF. The AF of M. sylvestris presented anti-inflammatory, 
      controlled osteoclastogenic mechanisms and antioxidant abilities in different in 
      vitro and in vivo methods. In addition, we suggest that given its multi-target 
      activity the bioactive fraction may be a good candidate in the therapy of chronic 
      inflammatory diseases.
FAU - Benso, Bruna
AU  - Benso B
AUID- ORCID: 0000-0002-4425-5174
AD  - Department of Physiological Sciences, Piracicaba Dental School, State University 
      of Campinas, Piracicaba, SP, Brazil.
AD  - School of Dentistry, Faculty of Medicine, Universidad Austral de Chile, Valdivia, 
      Chile.
FAU - Franchin, Marcelo
AU  - Franchin M
AD  - Department of Physiological Sciences, Piracicaba Dental School, State University 
      of Campinas, Piracicaba, SP, Brazil.
FAU - Massarioli, Adna Prado
AU  - Massarioli AP
AD  - Department of Agri-food Industry, Food and Nutrition, "Luiz de Queiroz" College 
      of Agriculture, University of Sao Paulo, Piracicaba, SP, Brazil.
FAU - Paschoal, Jonas Augusto Rizzato
AU  - Paschoal JA
AD  - Department of Physics and Chemistry, School of Pharmaceutical Sciences of 
      Ribeirao Preto, University of Sao Paulo, Riberao Preto, SP, Brazil.
FAU - Alencar, Severino Matias
AU  - Alencar SM
AD  - Department of Agri-food Industry, Food and Nutrition, "Luiz de Queiroz" College 
      of Agriculture, University of Sao Paulo, Piracicaba, SP, Brazil.
FAU - Franco, Gilson Cesar Nobre
AU  - Franco GC
AD  - Department of General Biology, Laboratory of Physiology and Pathophysiology, 
      State University of Ponta Grossa, Ponta Grossa, PR, Brazil.
FAU - Rosalen, Pedro Luiz
AU  - Rosalen PL
AD  - Department of Physiological Sciences, Piracicaba Dental School, State University 
      of Campinas, Piracicaba, SP, Brazil.
LA  - eng
PT  - Journal Article
DEP - 20160919
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Antioxidants)
RN  - 0 (Cytokines)
RN  - 0 (Plant Extracts)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*chemistry/isolation & purification/*pharmacology
MH  - Antioxidants/*chemistry/isolation & purification/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cytokines/analysis
MH  - Edema/drug therapy
MH  - Male
MH  - Malva/*chemistry
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neutrophils/cytology/drug effects
MH  - Osteoclasts/cytology/*drug effects
MH  - Plant Extracts/chemistry/isolation & purification/pharmacology
MH  - RAW 264.7 Cells
PMC - PMC5028055
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/20 06:00
MHDA- 2017/08/15 06:00
PMCR- 2016/09/19
CRDT- 2016/09/20 06:00
PHST- 2016/02/04 00:00 [received]
PHST- 2016/08/26 00:00 [accepted]
PHST- 2016/09/20 06:00 [entrez]
PHST- 2016/09/20 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2016/09/19 00:00 [pmc-release]
AID - PONE-D-16-02647 [pii]
AID - 10.1371/journal.pone.0162728 [doi]
PST - epublish
SO  - PLoS One. 2016 Sep 19;11(9):e0162728. doi: 10.1371/journal.pone.0162728. 
      eCollection 2016.