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Advisor(s)
Abstract(s)
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) are regarded as important clinical
targets due to their nodal-point role in inflammatory and oncological diseases. Here, we aimed at
isolating and characterizing am MMP-2 and-9 inhibitor (MMPI) from Lupinus albus and at assessing its
efficacy in vitro and in vivo. The protein was isolated using chromatographic and 2-D electrophoretic
procedures and sequenced by using MALDI-TOF TOF and MS/MS analysis. In vitro MMP-2 and
9 inhibitions were determined on colon adenocarcinoma (HT29) cells, as well as by measuring
the expression levels of genes related to these enzymes. Inhibitory activities were also confirmed
in vivo using a model of experimental TNBS-induced colitis in mice, with oral administrations of
15 mg kg1. After chromatographic and electrophoretic isolation, the L. albus MMP-9 inhibitor
was found to comprise a large fragment from -conglutin and, to a lower extent, small fragments
of -conglutin. In vitro studies showed that the MMPI successfully inhibited MMP-9 activity in
a dose-dependent manner in colon cancer cells, with an IC50 of 10 g mL1 without impairing
gene expression nor cell growth. In vivo studies showed that the MMPI maintained its bioactivities
when administered orally and significantly reduced colitis symptoms, along with a very significant
inhibition of MMP-2 and -9 activities. Overall, results reveal a novel type of MMPI in lupine that is
edible, proteinaceous in nature and soluble in water, and effective in vivo, suggesting a high potential
application as a nutraceutical or a functional food in pathologies related to abnormally high MMP-9
activity in the digestive system
Description
Keywords
Lupinus albus protein MMP-9 MMP-2 gelatinases MMP inhibitor nutraceutical gastrointestinal diseases
Pedagogical Context
Citation
Mota, J.; Direito, R.; Rocha, J.; Fernandes, J.; Sepodes, B.; Figueira, M.E.; Raymundo, A.; Lima, A.; Ferreira, R.B. Lupinus albus Protein Components Inhibit MMP-2 and MMP-9 Gelatinolytic Activity In Vitro and In Vivo. Int. J. Mol. Sci. 2021, 22, 13286
Publisher
MDPI