In vitro and in vivo inhibition of skin matrix metalloproteinases by Pothomorphe umbellata root extract.
Exposure to UV radiation up-regulates the synthesis of matrix metalloproteinases (MMPs), a group of matrix-degrading enzymes. MMPs are regarded as promising therapeutic targets and the development of effective inhibitors is an important research focus. The plant Pothomorphe umbellata has been shown to exert a potent antioxidant activity on the skin and to delay the onset and reduce the incidence of UVB-induced chronic skin damage. The aim of the present study was to determine the effect of P. umbellata ethanolic root extract on MMP-2 and MMP-9. The in vitro inhibition of MMP-2 and MMP-9 was measured by gelatin zymography in the presence of different concentrations of P. umbellata extract, as well as in the presence of its isolated active principle 4-nerolidylcatechol (4-NC). The inhibitory effect of the P. umbellata extract was stronger than that of 4-NC. Gelatin zymography and histological analysis revealed that P. umbellata was able to inhibit constitutive MMP-9 activity in vivo in mice sacrificed 2 h after UVB irradiation. The intensity of the MMP-2 band was unchanged. Our data contribute to the elucidation of the mechanism of prevention of photoaging by P. umbellata and may provide a rational basis for the use of this plant in prophylaxis against and treatment of skin cancer.
Ropke
Cristina D
CD
Departamento de Análises Clínicas e Toxicológicas, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. cdropke@usp.br
da Silva
Vanessa V
VV
Kera
Clarissa Z
CZ
Miranda
Denise V
DV
de Almeida
Rebeca L
RL
Sawada
Tânia C H
TC
Barros
Silvia B M
SB
D000818:Animals; D002396:Catechols / Q000302:isolation & purification; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005780:Gelatin / Q000737:chemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000378:metabolism; D051379:Mice; D008812:Mice, Hairless; D008517:Phytotherapy / Q000379:methods; D026321:Piperaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D011833:Radiation Injuries, Experimental / Q000473:pathology / Q000517:prevention & control; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012867:Skin / Q000201:enzymology*; D013997:Time Factors; D014466:Ultraviolet Rays
C110583:4-nerolidylcatechol; D002396:Catechols; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D010936:Plant Extracts; D011837:Radiation-Protective Agents; D005780:Gelatin; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9