Antitumor Effect of Manool in a Murine Melanoma Model.

The manool diterpene, found in abundance in Salvia officinalis L., showed a selective cytotoxic effect against murine melanoma cells. Therefore, the present study aimed to evaluate the antitumor potential of manool in a murine melanoma model, administered by three routes: oral, subcutaneous, and intraperitoneal. In addition, the antimelanoma effect of manool (orally) combined with cisplatin (subcutaneous) was evaluated. The results obtained revealed that manool, administered by the three routes, was able to significantly decrease the mass and frequency of mitosis of the tumor tissue. The data obtained revealed that manool, at a dose of 20 mg/kg, was able to significantly decrease the tumor mass when administered by the three routes, with the percentages of reduction being equivalent to 62.4% (oral), 48.5% (intraperitoneal), and 38.8% (subcutaneous), without toxic effects. The treatment of manool plus cisplatin led to 86.7% reduction in tumor mass, higher than that observed in treatment with manool or cisplatin alone (50.7%), although signs of toxicity have been observed. The results also showed that treatments with manool (20 mg/kg orally) and/or cisplatin did not alter the activity of caspase 3 cleaved in tumor tissue. Therefore, manool revealed a promising antimelanoma effect, but without involvement of the caspase 3 cleaved pathway.

Investigation of Copaifera genus as a new source of antimycobaterial agents.

AIM: This paper reports on the antimycobacterial activity of the oleoresins and extracts obtained from Copaifera spp. MATERIALS & METHODS: The minimum inhibitory concentration (MIC) and fractional inhibitory concentration index techniques helped to evaluate the effect of these oleoresins and extracts against six strains of mycobacteria that cause tuberculosis. RESULTS & CONCLUSION: Among the assayed oleoresins and plant extracts, the Copaifera langsdorffii, Copaifera duckei, Copaifera reticulata and Copaifera trapezifolia oleoresins provided the lowest MIC values against some of the tested strains. The combination of Copaifera spp. samples with isoniazid did not evidence any synergistic action. Some Copaifera spp. oleoresins may represent a future source for the discovery of new antimycobacterial drugs due to their low MIC values.

Occurrence, chemical composition, biological activities and analytical methods on Copaifera genus-A review.

Copaifera is a genus of large trees found in Brazil, mainly in Amazon forest, but also in Atlantic forest and cerrado biomes. It has also been found in other countries in South America. In Africa, it is found mainly in Congo, Cameroon, Guinea and Angola. Its oleoresin has been used in folk medicine in the treatment of numerous healthy disorders, such as urinary, respiratory, skin and inflammatory diseases, for which there are several studies corroborating its ethnopharmacological uses. It is also extensively employed in the pharmaceutical and cosmetic industries in the development of ointments, pills, soaps, perfumes, among others. Copaifera oleoresin contains mainly diterpenes, such as: kaurenoic acid, kaurenol, copalic acid, agathic acid, hardwiickic acid, polyalthic acid, and sesquiterpenes, comprising ß-caryophyllene, caryophyllene oxide, α-copaene, α-humulene, γ-muurolene and ß-bisabolol, among other compounds. On the other hand, Copaifera leaves contain mainly phenolic compounds, such as flavonoids and methylated galloylquinic acid derivatives. Therefore, considering the economic importance of Copaifera oleoresin, its ethnopharmacological uses, the need to develop new pharmaceuticals for the treatment of many diseases, as well as the pharmacological potential of the compounds found in Copaifera spp., it was undertaken a review covering mostly the last two decades on the distribution, chemistry, pharmacology, quality control and safety of Copaifera species.

Mikania glomerata Sprengel extract and its major compound ent-kaurenoic acid display activity against bacteria present in endodontic infections.

The search for new, effective and safe antimicrobial compounds from plant sources has continued to play an important role in the maintenance of human health since ancient times. Such compounds can be used to help to eradicate microorganisms from the root canal system, preventing/healing periapical diseases. Mikania glomerata (Spreng.), commonly known as "guaco," is a native climbing plant from Brazil that displays a wide range of pharmacological properties. Many of its activities have been attributed to its phytochemical composition, which is mainly composed of diterpenes, such as ent-kaurenoic acid (KA). The present study evaluated the potential activity of an ent-kaurenoic-rich (KA) extract from Mikania glomerata (i.e. Mikania glomerata extract/MGE) and its major compound KA against bacteria that can cause endodontic infections. Time-kill assays were conducted and the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), anti-biofilm activity, and synergistic antimicrobial activity of MGE and KA were determined. The MGE exhibited MIC and MBC values, which ranged from 6.25 to 100 µg/mL and 12.5 to 200 µg/mL respectively. The MIC and MBC results obtained for the KA, ranged from 3.12 to 100 µg/mL and 3.12 to 200 µg/mL respectively. Time-kill and anti-biofilm activity assays conducted for KA at concentrations between 3.12 and 12.5 µg/mL exhibited bactericidal activity between 6 and 72 h of incubation and 50% inhibition of biofilm formation for Porphyromonas gingivalis (clinical isolate), Propionibacterium acnes (ATCC 6919), Prevotella nigrescens (ATCC 33563), P. melaninogenica (ATCC 25845), Aggregatibacter actinomycetemcomitans (ATCC 43717). For synergistic antimicrobial activity, KA combined with chlorhexidine dichlorohydrate (CHD) had an additive effect with increased efficacy against P. gingivalis (clinical isolate) compared to CHD alone. It was concluded that M. glomerata extract and its major compound ent-kaurenoic acid (KA) showed in vitro antibacterial activity, the latter being a potential biofilm inhibitory agent. They may play important roles in the search for novel sources of agents that can act against bacteria present in endodontic infections.

Antibacterial activity of Pinus elliottii against anaerobic bacteria present in primary endodontic infections.

Endodontic infections have a polymicrobial nature, but anaerobic bacteria prevail among the infectious microbes. Considering that it is easy to eliminate planktonic bacteria, biofilm-forming bacteria still challenge clinicians during the fight against endodontic diseases. The chemical constituents of the oleoresin of Pinus elliottii, a plant belonging to the family Pinaceae, stand out in the search for biologically active compounds based on natural products with potential application in the treatment of endodontic infections. Indeed, plant oleoresins are an abundant natural source of diterpenes that display significant and well-defined biological activities as well as potential antimicrobial action. In this context, this study aimed to (1) evaluate the in vitro antibacterial activity of the oleoresin, fractions, and subfractions of P. elliottii as well as the action of dehydroabietic acid against 11 anaerobic bacteria that cause endodontic infection in both their planktonic and biofilm forms and (2) assess the in vitro antibiofilm activity of dehydroabietic acid against the same group of bacteria. The broth microdilution technique helped to determine the minimum inhibitory concentration (MIC) of the oleoresin and fractions. This same technique aided determination of the MIC values of nine subfractions of Fraction 1, the most active fraction. The MIC, minimum bactericidal concentration, and antibiofilm activity of dehydroabietic acid against the tested anaerobic bacteria were also examined. The oleoresin and fractions, especially fraction PE1, afforded promising MIC values, which ranged from 0.4 to 50 µg/mL. Concerning the nine evaluated subfractions, PE1.3 and PE1.4 furnished the most noteworthy MIC values, between 6.2 and 100 µg/mL. Dehydroabietic acid displayed antibacterial activity, with MIC values lying from 6.2 to 50 µg/mL, as well as bactericidal effect for all the investigated bacteria, except for Prevotella nigrescens. Assessment of the antibiofilm activity revealed significant results--MICB50 lay between 7.8 and 62.5 µg/mL, and dehydroabietic acid prevented all the evaluated bacteria from forming a biofilm. Hence, the chemical constituents of P. elliottii are promising biomolecules to develop novel therapeutic strategies to fight against endodontic infections.