In silico approach of secondary metabolites from Brazilian herbal medicines to search for potential drugs against SARS-CoV-2.

The new severe acute respiratory syndrome coronavirus (SARS-CoV-2) recently emerged as a worrying pandemic, with many confirmed cases and deaths globally. Therefore, there is a clear need for identifying effective therapeutic options and a review of secondary metabolites related to Brazilian herbal medicines was performed as a strategy for the discovery of new antiviral agents. To confirm this potential, an in silico screening of the identified compounds identified was also evaluated. The review was performed by the PubMed database and the selected natural compounds were subjected to in silico analysis such as QSAR, molecular docking and ADMET. 497 secondary metabolites were identified from 23 species. The in silico assays indicated 19 potential anti-SARS-CoV-2 compounds, being triterpenes and phenolic compounds. The indicated compounds showed a high affinity with proteins considered as the main molecular targets against SARS-CoV-2 and parameters indicated low toxicity. In addition to Brazilian medicinal plants, these compounds can be found in other species and they can be a base for the synthesis of other anti-COVID-19 drugs. Therefore, this review is important to conduct researches that address the emerging need for drugs in COVID-19 treatment.

Nanostructured Systems Improve the Antimicrobial Potential of the Essential Oil from Cymbopogon densiflorus Leaves.

The physicochemical characteristics of nanostructured suspensions are important prerequisites for the success of new drug development. This work aimed to develop nanometric systems containing Cymbopogon densiflorus leaf essential oil and to evaluate their antimicrobial activity. The essential oil was isolated by hydrodistillation from leaves and analyzed by GC-MS. The main constituents were found to be trans-p-mentha-2,8-dien-1-ol, cis-p-mentha-2,8-dien-1-ol, trans-p-mentha-1(7),8-dien-2-ol, cis-piperitol, and cis-p-mentha-1(7),8-dien-2-ol. In silico prediction analysis suggested that this oil possesses antimicrobial potential and the main mechanism of action might be the peptidoglycan glycosyltransferase inhibition. Nanoemulsions were prepared by the phase inversion method, and liposomes were made by the film hydration method. Qualitative evaluation of the antimicrobial activity was performed by the diffusion disk assay with 24 microorganisms; all of them were found to be sensitive to the essential oil. Subsequently, this property was quantified by the serial microdilution technique, where the nanoformulations demonstrated improved activity in comparison with the free oil. Bactericidal action was tested by the propidium iodide method, which revealed that free essential oil and nanoemulsion increased cytoplasmic membrane permeability, while no difference was observed between negative control and liposome. These results were confirmed by images obtained using transmission electron microscopy. This study has shown an optimization in the antimicrobial activity of C. densiflorus essential oil by a nanoemulsion and a liposomal formulation of the active substances.

Aqueous extract of Baccharis trimera improves redox status and decreases the severity of alcoholic hepatotoxicity

ABSTRACT The metabolism of ethanol occurs mainly in the liver, promoting increase of reactive oxygen species and nitrogen, leading to redox imbalance. Therefore, antioxidants can be seen as an alternative to reestablish the oxidizing/reducing equilibrium. The aim of this study was to evaluate the antioxidant and hepatoprotective effect of aqueous extract of Baccharis trimera (Less.) DC., Asteraceae, in a model of hepatotoxicity induced by ethanol. The extract was characterized and in vitro tests were conducted in HepG2 cells. It was evaluated the cells viability exposed to aqueous extract for 24 h, ability to scavenging the radical DPPH, besides the production of reactive oxygen species and nitric oxide, and the influence on the transcriptional activity of transcription factor Nrf2 (12 and 24 h) after exposure to 200 mM ethanol. The results showed that aqueous extract was non-cytotoxic in any concentration tested; moreover, it was observed a decrease in ROS and NO production, also promoting the transcriptional activity of Nrf2. In vivo, we pretreatment male rats Fisher with 600 mg/kg of aqueous extract and 1 h later 5 ml/kg of absolute ethanol was administrated. After two days of treatment, the animals were euthanized and lipid profile, hepatic and renal functions, antioxidant status and oxidative damage were evaluated. The treatment with extract improved liver function and lipid profile, reflecting the reduction of lipid microvesicules in the liver. It also promoted an increase of glutathione peroxidase activity, decrease of oxidative damage and MMP-2 activity. These results, analyzed together, suggest the hepatoprotective effect of B. trimera aqueous extract.

Hydroalcoholic extracts of Vellozia squamata: study of its nanoemulsions for pharmaceutical or cosmetic applications

Some species of plants are notable for the wide range of biologically active constituents in their tissues. Chemical and pharmacological studies of Vellozia squamata Pohl, Velloziaceae, popularly known in Brasil as "canela-de-ema" are scarce, but showed the presence of di-and triterpenoid that may be of scientific interest. In the present study the hydroalcoholic extracts from leafs and stems of V. squamata were submitted to phytochemical prospection to identify the principal groups of constituents, and the antioxidant activity was determined by DPPH method. The hydroethanolic extracts presented higher antioxidant activity. Thus, nanoemulsion formulations were prepared using the method of phase inversion. Accelerated stability tests, such as heat stress and centrifugation were made, and physical and chemical properties of the nanoemulsions were established. Stable formulations were obtained from both extracts from leafs and stems. By the results was possible to establish the potential application of hydroalcoholic extracts from V. squamata in development of products with antioxidant properties and demonstrate a promising pharmaceutical product.

Preparation and in vitro evaluation of α and ß-amyrins loaded nanoemulsions.

The triterpenes α- and ß-amyrins display important pharmacological activities. As a result of their high hydrophobia, they present low water solubility and reflect poor oral bioavailability. Different techniques can be used for the improvement of amyrins solubility, one of them is the use of nanoemulsions. Therefore, the method of direct emulsification was used to develop a nanoemulsion of these triterpenes and the resulting drug delivery system was characterized by an in vitro release assay. Encapsulation efficiency higher than 99% was achieved with total release around 30% in 24 h, which suggests that this system could be useful for the administration of α- and ß-amyrins by different routes in an efficient way.

Chemical composition of the essential oil from Microlicia graveolens growing wild in Minas Gerais

The chemical composition of the essential oil of the aerial parts of Microlicia graveolens DC., Melastomataceae, growing wild in the mountains of Minas Gerais, Brazil, was investigated for the first time. A pale orange to colourless oil was obtained in a yield of 4.8%. The oil was analyzed by GC-MS. The main components were (+)-trans-pinocarvyl acetate (78.9%), (-)-trans-pinocarvyl acetate (5.5%) and β-pinene (3.8%).

Co-processed extracts of Cassia angustifolia Vahl, Fabaceae, and Maytenus ilicifolia (Schrad.) Planch., Celastraceae, for production of high load tablets

The aim of this study was to investigate the feasibility of a co-processing technique for improving the manufacturing properties of Maytenus ilicifolia (Schrad.) Planch., Celastraceae, and Cassia angustifolia Vahl, Fabaceae, extracts in order to obtain tablets containing a high dose of such extracts. An experimental mixture design was used to optimise the formulation composition. Flowability parameters, such as compressibility index, time flow and angle of repose, were determined. Additional important industrial parameters, such as granulometry, bulk density and moisture stability, were also studied. The results demonstrated that co-processing technique was able to improve the flowability of vegetal extracts, making these materials suitable for a direct compression process. The contour plots revealed that formulations with a higher amount of lactose produced the best flow results as well as a larger particle size and a greater bulk density. Tablets from co-processed extracts containing lactose as majority diluent showed appropriate physical-chemical characteristics and presented a more stable moisture sorption behaviour compared to commercial gelatine capsules.

Anti-inflammatory and analgesic properties of water-ethanolic extract from Pothomorphe umbellata (Piperaceae) aerial parts.

Anti-inflammatory and analgesic activities as well as the median lethal dose (LD50) of water-ethanolic extract (PHE) of the aerial parts of Pothomorphe umbellata were evaluated in animal models. The ED(50) (oral) for the inhibition of carrageenan-induced rat paw edema assay was determined to be 550 mg/kg, while the LD(50) was higher than 2.0 g/kg. At a dose of 550 mg/kg, PHE inhibited the inflammatory process by 48.7% (P < 0.05) on the third hour of the assay (edema peak) when compared to the untreated control. Indomethacin, the positive control used in this test, inhibited the edema by 58.6% at a dose of 10 mg/kg, when compared to the untreated control (P < 0.05). All three fractions--hexane, methylene chloride and ethyl acetate--obtained by partition of PHE with respective solvents also showed inhibition of the edema induced by carrageenan over a period of 4h but the methylene chloride fraction showed the best activity. The activity shown by the methylene chloride fraction at 200 mg/kg was comparable to that exhibited by indomethacin at a dose of 10mg/kg. The number of writhings induced by a 0.6% acetic acid solution intraperitoneal injection was decreased by 22% (P < 0.05) in the group treated orally with Pothomorphe umbellata crude extract. PHE also inhibited the granulomatous tissue formation in rats by 6.2% (P < 0.05). In the same assay, topically applied dexamethasone decreased the granuloma formation by 14.2%. The above results suggest that Pothomorphe umbellata crude extract has analgesic and anti-inflammatory properties supporting its folkloric use for the treatment of these conditions.

Synthesis and biological activity evaluation of lignan lactones derived from (-)-cubebin.

The anti-inflammatory and analgesic effects of three dibenzylbutyrolactone lignans, (-)-hinokinin (2), (-)-6,6'-dinitrohinokinin (3), and (-)-6,6'-diaminohinokinin (4), obtained by partial synthesis from (-)-cubebin (1), were investigated using different animal models. It was observed that compounds (1) and (2) inhibited the edema formation in the rat paw edema assay at the same level and that all responses were dose dependent. Also, at the dose of 30 mg/kg, compounds 1, 2, 3, and 4 inhibited the edema formation by 53%, 63%, 54%, and 82%, respectively, at the third hour of the experiment. In the acetic acid-induced writhing test in mice, compounds 2 and 4 produced inhibition levels of 97% and 92%, respectively, while 3 displayed lower effect (75%), which was still higher than 1. The assayed compounds neither displayed activity in the cell migration test nor in the hot plate test.

Trypanocidal activity of (-)-cubebin derivatives against free amastigote forms of Trypanosoma cruzi.

Five (-)-cubebin derivative compounds, (-)-O-acetyl cubebin (3), (-)-O-benzyl cubebin (4), (-)-O-(N,N-dimethylaminoethyl)-cubebin (5), (-)-hinokinin (6) and (-)-6,6'-dinitrohinokinin (7), previously synthesised by our research group, were evaluated on in vitro assay against free amastigote forms of Trypanosoma cruzi, the asogic agent of Chagas' disease. It was observed that 6 was the most active compound (IC(50)=0.7 microM), and that 4 and 5 displayed moderate activity against the parasite, giving IC(50) values of 5.7 and 4.7 microM, respectively. In contrast, it was observed that compound 3 was inactive and that 7 displayed low activity with IC(50) values of congruent with 1.5 x 10(4) and 95.3 microM, respectively.