Rosmarinus officinalis L. (rosemary) is a medicinal plant native to the Mediterranean region and cultivated around the world. Besides the therapeutic purpose, it is commonly used as a condiment and food preservative. R. officinalis L. is constituted by bioactive molecules, the phytocompounds, responsible for implement several pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, antiproliferative, antitumor and protective, inhibitory and attenuating activities. Thus, in vivo and in vitro studies were presented in this Review, approaching the therapeutic and prophylactic effects of R. officinalis L. on some physiological disorders caused by biochemical, chemical or biological agents. In this way, methodology, mechanisms, results, and conclusions were described. The main objective of this study was showing that plant products could be equivalent to the available medicines.

BackgroundWith the emergence of strains resistant to conventional antibiotics, it is important to carry studies using alternative methods to control these microorganisms causing important infections, such as the use of products of plant origin that has demonstrated effective antimicrobial activity besides biocompatibility. Therefore, this study aimed to evaluate the antimicrobial activity of plant extracts of Equisetum arvense L., Glycyrrhiza glabra L., Punica granatum L. and Stryphnodendron barbatimam Mart. against Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus mutans, Candida albicans, Candida tropicalis, and Candida glabrata, and to analyze the cytotoxicity of these extracts in cultured murine macrophages (RAW 264.7).MethodsAntimicrobial activity of plant extracts was evaluated by microdilution method based on Clinical and Laboratory Standards Institute (CLSI), M7-A6 and M27-A2 standards. The cytotoxicity of concentrations that eliminated the microorganisms was evaluated by MTT colorimetric method and by quantification of proinflammatory cytokines (IL-1β and TNF-α) using ELISA.ResultsIn determining the minimum microbicidal concentration, E. arvense L., P. granatum L., and S. barbatimam Mart. extracts at a concentration of 50 mg/mL and G. glabra L. extract at a concentration of 100 mg/mL, were effective against all microorganisms tested. Regarding cell viability, values were 48% for E. arvense L., 76% for P. granatum L, 86% for S. barbatimam Mart. and 79% for G. glabra L. at the same concentrations. About cytokine production after stimulation with the most effective concentrations of the extracts, there was a significant increase of IL-1β in macrophage cultures treated with S. barbatimam Mart. (3.98 pg/mL) and P. granatum L. (7.72 pg/mL) compared to control (2.20 pg/mL) and a significant decrease of TNF-α was observed in cultures treated with G. glabra L. (4.92 pg/mL), S. barbatimam Mart. (0.85 pg/mL), E. arvense L. (0.83 pg/mL), and P. granatum L. (0.00 pg/mL) when compared to control (41.96 pg/mL).ConclusionsAll plant extracts were effective against the microorganisms tested. The G. glabra L. extract exhibited least cytotoxicity and the E. arvense L. extract was the most cytotoxic.

Rosmarinus officinalis L. extract effectively contributed to in vitro control of important species of microorganisms such as Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans, and Pseudomonas aeruginosa in mono-and polymicrobial biofilms that are responsible for several infections in oral cavity as in other regions of the body. Furthermore, this extract promoted also cell viability above 50% at concentrations 50 mg/mL, excellent anti-inflammatory effect, showing inhibition or reduction of the synthesis of proinflammatory cytokines, being also non-genotoxic to cell lines studied. Thus, this extract may be a promising therapeutic agent that can be added in some medical and dental formulations such as toothpastes, mouthwashes, irrigating root canals, ointments, soaps, in order to control pathogenic microorganisms and biofilms, with anti-inflammatory effect and absence of cytotoxic and genotoxic. AbstractR. officinalis L. is an aromatic plant commonly used as condiment and for medicinal purposes. Biological activities of its extract were evaluated in this study, as antimicrobial effect on mono-and polymicrobial biofilms, cytotoxicity, anti-inflammatory capacity, and genotoxicity. Monomicrobial biofilms of Candida albicans, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mutans and Pseudomonas aeruginosa and polymicrobial biofilms composed of C. albicans with each bacterium were formed in microplates during 48 h and exposed for 5 min to R. officinalis L. extract (200 mg/mL). Its cytotoxic effect was examined on murine macrophages (RAW 264.7), human gingival fibroblasts (FMM-1), human breast carcinoma cells (MCF-7), and cervical carcinoma cells (HeLa) after exposure to different concentrations of the extract, analyzed by MTT, neutral red (NR), and crystal violet (CV) assays. The anti-inflammatory activity was evaluated on RAW 264.7 non-stimulated or stimulated by lipopolysaccharide (LPS) from Escherichia coli and treated with different concentrations of the extract for 24 h. Interleukin-1 beta (IL-1b) and tumor necrosis factor alpha (TNF-a) were quantified by ELISA. Genotoxicity was verified by the frequency of micronuclei (MN) at 1000 cells after exposure to concentrations of the extract for 24 h. Data were analyzed by T-Test or ANOVA and Tukey Test (P 0.05). Thus, significant reductions in colony forming units per milliliter (CFU/mL) were observed in all biofilms. Regarding the cells, it was observed that concentrations 50 mg/mL provided cell viability of above 50%. Production of proinflammatory cytokines in the treated groups was similar or lower compared to the control group. The MN frequency in the groups exposed to extract was similar or less than the untreated group. It was shown that R. officinalis L. extract was effective on mono-and polymicrobial biofilms; it also provided cell viability of above 50% (at 50 mg/mL), showed anti-inflammatory effect, and was not genotoxic.

T. vulgaris L. extract was effective against all biofilms, promoted high cell viability, anti-inflammatory effect and presented no genotoxicity.

CAPE was able to inhibit the gene expression, production and the activity of MMPs induced by LPS and also increased the gene expression of TIMP-1. The present observations suggest that CAPE exerted a positive effect on the regulatory mechanism between MMPs and TIMP, which is important for the control of different diseases.