Evaluation of Myrcia bella in murine osteosarcoma cells: Effect of the extract and enriched fractions of tannins and flavonoids.

Myrcia bella Cambess (Myrtaceae) is an important and common plant, native to the Brazilian Cerrado, with cytotoxicity, antimicrobial, and antidiabetic properties. Therefore, the effects of crude hydroalcoholic extract (CE) and fractions of ellagitannins (ELT) and flavonoids (FV) from Myrcia bella leaves were evaluated in a UMR-106 murine osteosarcoma cells and MC3T3 (normal cell). Cell viability and migration, production of reactive oxygen species (ROS) and matrix metalloproteinase (MMP) -2 and -9 activities were evaluated. In general, CE (80 µg/mL), ELT (160 µg/mL) and FV (64 µg/mL) reduced cell viability (p < 0.05). FV (64 µg/mL) was more effective in inhibition of cell migration, ROS production, and MMP-2 activity when compared to CE and ELT. Myrcia bella a rich source of phenolic compounds and its fraction of flavonoids have cytotoxic effects on osteosarcoma cells, preserving the viability of normal osteoblasts. Due to its antioxidant capacity, flavonoid may be a new therapeutic strategy for cancer.

Effects of Qualea grandiflora Extract on the Expression of MMP-14 and HIF-1α in Cultured Fibroblasts and Preosteoblasts

Abstract Background: Qualea grandiflora (QG) (Vochysiaceae), also known as "pau-ferro", "pau-terra" or "pau-de-tucano", is a very common deciduous tree in the Brazilian Cerrado used in traditional medicine to treat inflammations, ulcers, diarrhea, and infections. There are reports in the scientific literature that demonstrate the medicinal effects of the bark and leaf of the QG. However, studies involving this plant are rather imited. Aim of the study: To perform the phytochemical analysis of the QG hydroalcoholic extract (HAE) of leaves, and to investigate it effects on fibroblast and preosteoblasts. Methods: Phytochemical analysis was done by HPLC-DAD. Murine NIH/3T3 fibroblasts and MC3T3-E1 preosteoblasts cell lines (ATCC) were used for the experiments. Cell viability was assessed by the MTT colorimetric assay and the expression of MMP-14 and HIF-1α by immunofluorescence. Results and conclusion: The following compounds were identified by HPLC-DAD, such as quinic acid, ethyl galate, ellagic acid derivatives as O-methylellagic acid O-galloyl, O-methylellagic acid O-deoxyhexoside, galloyl derivatives, flavonol glycoside as kaempferol-O-deoxyhexoside, quercetin-O-deoxyhexoside, myricetin-O-deoxyhexoside and the pentacyclic triterpene arjunglucoside. Cell viability results demonstrated no cytotoxic effects in the studied concentrations. We found in QG HAE some compounds with therapeutic properties that can increase the expression of MMP-14 and HIF-1α, in fibroblasts and preosteoblasts. These data suggest that QG HAE has an action on these two molecules widely involved in physiological conditions, such as collagen remodeling, bone development and growth and pathological processes as HIF signaling in cancer metastasis.

Updating the role of matrix metalloproteinases in mineralized tissue and related diseases.

Bone development and healing processes involve a complex cascade of biological events requiring well-orchestrated synergism with bone cells, growth factors, and other trophic signaling molecules and cellular structures. Beyond health processes, MMPs play several key roles in the installation of heart and blood vessel related diseases and cancer, ranging from accelerating metastatic cells to ectopic vascular mineralization by smooth muscle cells in complementary manner. The tissue inhibitors of MMPs (TIMPs) have an important role in controlling proteolysis. Paired with the post-transcriptional efficiency of specific miRNAs, they modulate MMP performance. If druggable, these molecules are suggested to be a platform for development of "smart" medications and further clinical trials. Thus, considering the pleiotropic effect of MMPs on mammals, the purpose of this review is to update the role of those multifaceted proteases in mineralized tissues in health, such as bone, and pathophysiological disorders, such as ectopic vascular calcification and cancer.

An extract from Myracrodruon urundeuva inhibits matrix mineralization in human osteoblasts.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytotherapy based on plant-derived compounds is an alternative medicinal strategy for the relief of symptoms and the curing of diseases. The leaves of Myracrodruon urundeuva a medicinal plant also known as "aroeira", has been used in traditional medicine as healing, antiulcer and anti-inflammatory to treat skeletal diseases in Brazil, but its role in bone cell toxicity, as well as in bone formation, remains to be established. AIM OF THE STUDY: We sought to determine the in vitro osteogenic effects of a hydroalcoholic M. urundeuva leaves extract in primary human osteoblasts. MATERIALS AND METHODS: Cell viability, reactive oxygen species (ROS) production, alkaline phosphatase (ALP) activity and matrix mineralization were evaluated by MTT assay, DCFH-DA probe, colorimetric-based enzymatic assay and Alizarin Red-staining, respectively. Besides, the matrix metalloproteinase (MMP)-2 and progressive ankylosis protein homolog (ANKH) gene expression were determined by real-time RT-qPCR and MMP-2 activity by zymography. RESULTS: Exposure of osteoblasts to M. urundeuva extract significantly decreased viability and increased reactive oxygen species (ROS) production, regardless of the extract concentration. The M. urundeuva extract at 10 µg/mL also downregulated matrix metalloproteinase (MMP)-2, while upregulating progressive ankylosis protein homolog (ANKH) gene expression. By contrast, the MMP-2 activity was unchanged. The M. urundeuva extract at 10 µg/mL also reduced alkaline phosphatase (ALP) activity and mineralization. CONCLUSIONS: Overall, our findings suggest that the inhibition of osteogenic differentiation and matrix mineralization promoted by M. urundeuva may be due more to an increase in oxidative stress than to the modulation of MMP-2 and ANKH expression.