ABSTRACT
Although traditional use of elderberry flowers is recognized by Medical Agencies, there are not suitable products on the Brazilian market. To overcome poor stability of tinctures of Sambucus nigra flowers, we aimed to develop spray dried microparticles. Statistical experimental design was applied taking inlet temperature and maltodextrin% at five different levels. Next, we applied a stability study for 60 days under accelerated conditions (40 °C/75% RH) and 180 days at room temperature (15-30 °C). We monitored flavonoid content as markers. The best drying condition was 188 °C and 65% of carrier and enabled microparticles with more than 90% of markers recovery. After 180 days, the dried extract remained with 90.8% at room temperature. The markers were released from microparticles in two minutes. In conclusion, the spray drying process and formulation enabled elderberry flowers to be easier to apply in solid pharmaceutical forms.
Subject(s)
Plants, Medicinal , Sambucus nigra , Sambucus , Water , Herbal Medicine , PowdersABSTRACT
BACKGROUND: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. METHODS: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. RESULTS: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. CONCLUSION: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.
Subject(s)
Antineoplastic Agents/therapeutic use , Bone Neoplasms/drug therapy , Breast Neoplasms/pathology , Phthalimides/therapeutic use , Animals , Antineoplastic Agents/toxicity , Bone Neoplasms/secondary , Disease Models, Animal , Female , Humans , Male , Mice , Mice, Inbred C57BL , Phthalimides/toxicityABSTRACT
A series of 3-(triazolyl)-coumarins were synthesized and tested as anti-inflammatory agents. It was possible to infer that these compounds do not alter the interaction of LPS with TLR-4 or TLR-2, as the intracellular pathways involved in the TNF-α secretion and COX-2 activity were not affected. Nevertheless, the compounds inhibited iNOS-derived NO production, without affecting the eNOS activity. The outcome of the docking studies showed that π···π interactions with the heme group are important for the iNOS inhibition, thus making compound 3c a promising lead. Moreover, the efficacy of this compound was visualized by the reduced number of neutrophils in the LPS-inflamed subcutaneous tissue. Together, biological and docking data show that triazolyl-substituted coumarins, that can act on iNOS, are a good scaffold to be explored.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Coumarins/pharmacology , Enzyme Inhibitors/pharmacology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Triazoles/pharmacology , Animals , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/chemistry , Cells, Cultured , Coumarins/chemical synthesis , Coumarins/chemistry , Dose-Response Relationship, Drug , Endothelial Cells/drug effects , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Lipopolysaccharides/antagonists & inhibitors , Lipopolysaccharides/pharmacology , Male , Models, Molecular , Molecular Structure , Neutrophils/drug effects , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Nitric Oxide Synthase Type II/metabolism , Rats , Rats, Wistar , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
A series of 2,5-diaryl substituted furans functionalized with several amino acids were synthesized and evaluated as the cyclooxygenases COX-1 and COX-2 enzymes inhibitors. The proline-substituted compound inhibited PGE(2) secretion by LPS-stimulated neutrophils, suggesting selectivity for COX-2. Molecular docking studies in the binding site of COX-2 were performed.
