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BRUCEA JAVANICA (L.) MERR. EXTRACT DOWNREGULATES MMP2 EXPRESSION AND REDUCES ENDOTHELIAL DENUDATION-INDUCED ARTERIAL NEOINTIMAL HYPERPLASIA IN MICE

CANDRA DWIPAYANA HAMDIN 1*, VANIA AISYAH AULIA SYAHDA HARIS 1, ANDRI FREDIANSYAH 2, ANGGIT L. SUNARWIDHI 1, EKA SUNARWIDHI PRASEDYA ³

¹ Study Program of Pharmacy, Faculty of Medicine and Health Sciences, University of Mataram, Mataram, Indonesia
2 Research Center for Food Technology and Processing (PRTPP), National Research and Innovation Agency (BRIN), Yogyakarta, Indonesia
3 Study Program of Biology, Faculty of Mathematics and Natural Sciences, University of Mataram, Mataram, Indonesia

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This study evaluated the therapeutic potential of Brucea javanica (L.) Merr. (BJ) extract against vascular smooth muscle cell (VSMC) proliferation and migration, and endothelial denudation-induced neointimal hyperplasia in mice. Primary VSMCs isolated from mouse embryonic aortas were used, while guidewire injury-induced neointimal hyperplasia was utilized. In VSMCs, BJ (10 - 30 µg/mL) treatment reduced VSMC proliferation, migration, and lamellipodia formation. Further, Western blot showed reduced matrix metalloproteinase-2 (MMP2) expression, without affecting total or phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Meanwhile, in mice, BJ (30 mg/kg/day) treatment mitigated neointimal formation, as indicated by the artery intima-to-media ratio (0.313 ± 0.056) compared to injured controls (0.630 ± 0.089, p = 0.013). Interestingly, the reduction of the intima-to-media ratio was followed by a reduction in matrix MMP2 expression in the area (1.342 ± 0.085-fold compared to control) compared to untreated (1.687 ± 0.056-fold compared to control, p = 0.0071). Taken together, BJ extract contains predominantly flavonoids, with quercetin as the major constituent, and inhibited VSMC proliferation and migration; this was accompanied by reduced MMP2 expression without changes in ERK1/2 expression or activation. In mice, BJ extract reduced neointimal hyperplasia and MMP2 expression in intimal and medial arteries.