Correction: Diniz et al. Silver Nanoparticles-Composing Alginate/Gelatine Hydrogel Improves Wound Healing In Vivo. Nanomaterials 2020, 10, 390.

In the original publication, there was a mistake in Figure 6 as published [...].

Brazilian Red Propolis: Extracts Production, Physicochemical Characterization, and Cytotoxicity Profile for Antitumor Activity.

Brazilian red propolis has been proposed as a new source of compounds with cytotoxic activity. Red propolis is a resinous material of vegetal origin, synthesized from the bees of the Appis mellifera family, with recognized biological properties. To obtain actives of low polarity and high cytotoxic profile from red propolis, in this work, we proposed a new solvent accelerated extraction method. A complete 23 factorial design was carried out to evaluate the influence of the independent variables or factors (e.g., temperature, number of cycles, and extraction time) on the dependent variable or response (i.e., yield of production). The extracts were analyzed by gas chromatography coupled with mass spectrometry for the identification of chemical compounds. Gas chromatography analysis revealed the presence of hydrocarbons, alcohols, ketones, ethers, and terpenes, such as lupeol, lupenone, and lupeol acetate, in most of the obtained extracts. To evaluate the cytotoxicity profile of the obtained bioactives, the 3-(4,5-dimethyl-2-thiazole)-2,5-diphenyl-2-H-tetrazolium bromide colorimetric assay was performed in different tumor cell lines (HCT116 and PC3). The results show that the extract obtained from 70 °C and one cycle of extraction of 10 min exhibited the highest cytotoxic activity against the tested cell lines. The highest yield, however, did not indicate the highest cytotoxic activity, but the optimal extraction conditions were indeed dependent on the temperature (i.e., 70 °C).

Evaluation of the antioxidant profile and cytotoxic activity of red propolis extracts from different regions of northeastern Brazil obtained by conventional and ultrasound-assisted extraction.

Propolis is a complex mixture of resinous and balsamic material collected from the exudates of plants, shoots, and leaves by bees. This study evaluated red propolis extracts obtained by conventional (ethanolic) extraction and ultrasound-assisted extraction of six samples from different regions of northeastern Brazil. The total phenolic compounds and flavonoids, in vitro antioxidant activity, concentration of formononetin and kaempferol and the cytotoxicity against four human tumor cell lines were determined for all twelve obtained extracts. Significant variations in the levels of the investigated compounds were identified in the red propolis extracts, confirming that the chemical composition varied according to the sampling region. The extraction method used also influenced the resulting propolis compounds. The highest concentration of the compounds of interest and the highest in vitro antioxidant activity were exhibited by the extracts obtained from samples from state of Alagoas. Formononetin and kaempferol were identified in all samples. The highest formononetin concentrations were identified in extracts obtained by ultrasound, thus indicating a greater selectivity for the extraction of this compound by this method. Regarding cytotoxic activity, for the HCT-116 line, all of the extracts showed an inhibition of greater than 90%, whereas for the HL-60 and PC3 lines, the minimum identified was 80%. In general, there was no significant difference (p>0.05) in the antiproliferative potential when comparing the extraction methods. The results showed that the composition of Brazilian red propolis varies significantly depending on the geographical origin and that the method used influences the resulting compounds that are present in propolis. However, regardless of the geographical origin and the extraction method used, all the red propolis samples studied presented great biological potential and high antioxidant activity. Furthermore, the ultrasound-assisted method can be efficiently applied to obtain extracts of red propolis more quickly and with high concentration of biomarkers of interest.

Use of pharmaceutical nanotechnology for the treatment of leishmaniasis.

INTRODUCTION: Leishmaniasis is a global public health concern. Currently available treatments are associated with considerable side effects. The use of nanotechnology has shown promise for improving efficacy and bioavailability and minimizing side effects. METHODS: This study investigated available literature, including patents and scientific articles, to identify advances in the use of nanotechnology for the treatment of leishmaniasis. RESULTS: Our findings revealed a stable number of patents and scientific articles published over the past five years. CONCLUSIONS: There is a need to intensify research on the use of nanotechnology for the treatment of leishmaniasis.

Innovative nanocompounds for cutaneous administration of classical antifungal drugs: a systematic review.

Nanomedicine manipulates materials at atomic, molecular, and supramolecular scale, with at least one dimension within the nanometer range, for biomedical applications. The resulting nanoparticles have been consistently shown beneficial effects for antifungal drugs delivery, overcoming the problems of low bioavailability and high toxicity of these drugs. Due to their unique features, namely the small mean particle size, nanoparticles contribute to the enhanced drug absorption and uptake by the target cells, potentiating the therapeutic drug effect. The topical route is desirable due to the adverse effects arising from oral administration. This review provides a comprehensive analysis of the use of nano compounds for the current treatment of topical fungal infections. A special emphasis is given to the employment of lipid nanoparticles, due to their recognized efficacy, versatility, and biocompatibility, attracting the major attention as novel topical nanocompounds used for the administration of antifungal drugs.

Anti-Leishmania and cytotoxic activities of perillaldehyde epoxide synthetic positional isomers.

Leishmaniasis belongs to a complex of zoonotic disease caused by protozoa of the genus Leishmania and is considered a major public health problem. Several essential oil chemical components have inhibitory effect against protozoa, including Leishmania donovani. Thus, the aim of this study was to evaluate for the first time the anti-Leishmania activity of two p-menthane monoterpene isomers (EPER-1: perillaldehyde 1,2-epoxide and EPER-2: perillaldehyde 8,9-epoxide) against L. donovani promastigotes as well as evaluating cytotoxic effect on mononuclear peripheral blood cells. Results of anti-Leishmania assay revealed that EPER-2 (IC50 = 3.8 µg.mL-1) was 16-fold more potent than its isomer EPER-1 (IC50 = 64.6 µg.mL-1). In contrast to PBMC cells, EPER-2 was not cytotoxic (IC50 > 400 µg.mL-1) when compared to positive control. These data suggest that the disposition of epoxide group into the p-menthane skeleton affects the anti-Leishmania activity, being that the presence of the exocyclic epoxide group considerably increased potency. Thus, it was possible to observe that the location of the epoxide group into the p-menthane skeleton resulted in different potencies.

Use of pharmaceutical nanotechnology for the treatment of leishmaniasis

Abstract INTRODUCTION: Leishmaniasis is a global public health concern. Currently available treatments are associated with considerable side effects. The use of nanotechnology has shown promise for improving efficacy and bioavailability and minimizing side effects. METHODS: This study investigated available literature, including patents and scientific articles, to identify advances in the use of nanotechnology for the treatment of leishmaniasis. RESULTS: Our findings revealed a stable number of patents and scientific articles published over the past five years. CONCLUSIONS: There is a need to intensify research on the use of nanotechnology for the treatment of leishmaniasis.

Antioxidant, antimicrobial, antiparasitic, and cytotoxic properties of various Brazilian propolis extracts.

Propolis is known for its biological properties and its preparations have been continuously investigated in an attempt to solve the problem of their standardization, an issue that limits the use of propolis in food and pharmaceutical industries. The aim of this study was to evaluate in vitro antioxidant, antimicrobial, antiparasitic, and cytotoxic effects of extracts of red, green, and brown propolis from different regions of Brazil, obtained by ethanolic and supercritical extraction methods. We found that propolis extracts obtained by both these methods showed concentration-dependent antioxidant activity. The extracts obtained by ethanolic extraction showed higher antioxidant activity than that shown by the extracts obtained by supercritical extraction. Ethanolic extracts of red propolis exhibited up to 98% of the maximum antioxidant activity at the highest extract concentration. Red propolis extracts obtained by ethanolic and supercritical methods showed the highest levels of antimicrobial activity against several bacteria. Most extracts demonstrated antimicrobial activity against Staphylococcus aureus. None of the extracts analyzed showed activity against Escherichia coli or Candida albicans. An inhibitory effect of all tested ethanolic extracts on the growth of Trypanosoma cruzi Y strain epimastigotes was observed in the first 24 h. However, after 96 h, a persistent inhibitory effect was detected only for red propolis samples. Only ethanolic extracts of red propolis samples R01Et.B2 and R02Et.B2 showed a cytotoxic effect against all four cancer cell lines tested (HL-60, HCT-116, OVCAR-8, and SF-295), indicating that red propolis extracts have great cytotoxic potential. The biological effects of ethanolic extracts of red propolis revealed in the present study suggest that red propolis can be a potential alternative therapeutic treatment against Chagas disease and some types of cancer, although high activity of red propolis in vitro needs to be confirmed by future in vivo investigations.

In Vivo Anti-Tumor Activity and Toxicological Evaluations of Perillaldehyde 8,9-Epoxide, a Derivative of Perillyl Alcohol.

Recent studies have revealed the high cytotoxicity of p-menthane derivatives against human tumor cells. In this study, the substance perillaldehyde 8,9-epoxide, a p-menthane class derivative obtained from (S)-(-)-perillyl alcohol, was selected in order to assess antitumor activity against experimental sarcoma 180 tumors. Toxicological effects related to the liver, spleen, kidneys and hematology were evaluated in mice submitted to treatment. The tumor growth inhibition rate was 38.4%, 58.7%, 35.3%, 45.4% and 68.1% at doses of 100 and 200 mg/kg/day for perillaldehyde 8,9-epoxide, perillyl alcohol and 25 mg/kg/day for 5-FU intraperitoneal treatments, respectively. No toxicologically significant effect was found in liver and kidney parameters analyzed in Sarcoma 180-inoculated mice treated with perillaldehyde 8,9-epoxide. Histopathological analyses of the liver, spleen, and kidneys were free from any morphological changes in the organs of the animals treated with perillaldehyde 8,9-epoxide. In conclusion, the data suggest that perillaldehyde 8,9-epoxide possesses significant antitumor activity without systemic toxicity for the tested parameters. By comparison, there was no statistical difference for the antitumor activity between perillaldehyde 8,9-epoxide and perillyl alcohol.

Sesquiterpenes from Essential Oils and Anti-Inflammatory Activity.

This review is aimed at presenting relevant information on the therapeutic potential of essential oil sesquiterpenes with anti-inflammatory activity. The data reviewed provide a basis for seeking new anti-inflammatory drugs from natural products that do not exhibit the undesirable side effects often displayed by anti-inflammatory drugs. In this review the experimental models, possible mechanisms of action, and chemical structures of 12 sesquiterpenes are presented.

Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers.

Stereoisomers of the monoterpene epoxycarvone (EC), namely (+)-cis-EC, (-)-cis-EC, (+)-trans-EC, and (-)-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ)-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg) increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES) test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+) and (-)-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+) and (-)-trans-EC (at 300 mg/kg) showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+)-cis-EC and (+)-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+)-cis-EC, (+)-trans-EC, and (-)-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.

A Systematic Review of the Anxiolytic-Like Effects of Essential Oils in Animal Models.

The clinical efficacy of standardized essential oils (such as Lavender officinalis), in treating anxiety disorders strongly suggests that these natural products are an important candidate source for new anxiolytic drugs. A systematic review of essential oils, their bioactive constituents, and anxiolytic-like activity is conducted. The essential oil with the best profile is Lavendula angustifolia, which has already been tested in controlled clinical trials with positive results. Citrus aurantium using different routes of administration also showed significant effects in several animal models, and was corroborated by different research groups. Other promising essential oils are Citrus sinensis and bergamot oil, which showed certain clinical anxiolytic actions; along with Achillea wilhemsii, Alpinia zerumbet, Citrus aurantium, and Spiranthera odoratissima, which, like Lavendula angustifolia, appear to exert anxiolytic-like effects without GABA/benzodiazepine activity, thus differing in their mechanisms of action from the benzodiazepines. The anxiolytic activity of 25 compounds commonly found in essential oils is also discussed.

Evaluation of the cytotoxicity of structurally correlated p-menthane derivatives.

Compounds isolated from essential oils play an important role in the prevention and treatment of cancer. Monoterpenes are natural products, and the principal constituents of many essential oils. The aim of this study was to investigate the cytotoxic potential of p-menthane derivatives. Additionally, analogues of perillyl alcohol, a monoterpene with known anticancer activity, were evaluated to identify the molecular characteristics which contribute to their cytotoxicity, which was tested against OVCAR-8, HCT-116, and SF-295 human tumor cell lines, using the MTT assay. The results of this study showed that (-)-perillaldehyde 8,9-epoxide exhibited the highest percentage inhibition of cell proliferation (GI = 96.32%-99.89%). Perillyl alcohol exhibited high cytotoxic activity (90.92%-95.82%), while (+)-limonene 1,2-epoxide (GI = 58.48%-93.10%), (-)-perillaldehyde (GI = 59.28%-83.03%), and (-)-8-hydroxycarvotanacetone (GI = 61.59%-94.01%) showed intermediate activity. All of the compounds tested were less cytotoxic than perillyl alcohol, except (-)-perillaldehyde 8,9-epoxide (IC50 = 1.75-1.03 µL/mg). In general, replacement of C-C double bonds by epoxide groups in addition to the aldehyde group increases cytotoxicity. Furthermore, stereochemistry seems to play an important role in cytotoxicity. We have demonstrated the cytotoxic influence of chemical substituents on the p-menthane structure, and analogues of perillyl alcohol.

Antitumor phenylpropanoids found in essential oils.

The search for new bioactive substances with anticancer activity and the understanding of their mechanisms of action are high-priorities in the research effort toward more effective treatments for cancer. The phenylpropanoids are natural products found in many aromatic and medicinal plants, food, and essential oils. They exhibit various pharmacological activities and have applications in the pharmaceutical industry. In this review, the anticancer potential of 17 phenylpropanoids and derivatives from essential oils is discussed. Chemical structures, experimental report, and mechanisms of action of bioactive substances are presented.

Anti-ulcer activity of essential oil constituents.

Essential oils have attracted considerable worldwide attention over the last few decades. These natural products have wide-ranging pharmacological activities and biotechnological applications. Faced with the need to find new anti-ulcer agents and the great effort on the development of drugs for the treatment of ulcers, in this review, the anti-ulcer activities of 21 bioactive compounds found in essential oils are discussed.

A review on anti-inflammatory activity of phenylpropanoids found in essential oils.

The search for alternative drugs capable of disrupting the inflammatory process has become an important issue in scientific research, especially with reference to the use of natural substances and the reduction of undesirable side effects. Essential oils represent an important source of such substances, since their active constituents often exhibit an array of pharmacological properties, including anti-inflammatory activity. This review presents an overview of the anti-inflammatory action exerted by phenylpropanoids from essential oils and discusses possible mechanisms of action involved in the anti-inflammatory response, assessed through specific experimental models.

A review on anti-inflammatory activity of monoterpenes.

Faced with the need to find new anti-inflammatory agents, great effort has been expended on the development of drugs for the treatment of inflammation. This disorder reduces the quality of life and overall average productivity, causing huge financial losses. In this review the anti-inflammatory activity of 32 bioactive monoterpenes found in essential oils is discussed. The data demonstrate the pharmacological potential of this group of natural chemicals to act as anti-inflammatory drugs.

Anthelmintic activity of carvacryl acetate against Schistosoma mansoni.

Blood flukes of the genus Schistosoma are the causative agents of human schistosomiasis, a debilitating disease that afflicts over 200 million people worldwide. Praziquantel is the drug of choice but concerns over praziquantel resistance have renewed interest in the search for alternative drug therapies. Carvacrol, a naturally occurring monoterpene phenol and food additive, has been shown high medicinal importance, including antimicrobials activities. The aim of this study was to evaluate in vitro effect of carvacryl acetate, a derivative of carvacrol, on Schistosoma mansoni adult worms. We demonstrated that carvacryl acetate at 6.25 µg/mL has antischistosomal activity, affecting parasite motility and viability. Additionally, confocal laser scanning microscopy pictures revealed morphological alterations on the tegumental surface of worms, where some tubercles appeared to be swollen with numerous small blebs emerging from the tegument around the tubercles. Furthermore, experiments performed using carvacryl acetate at sub-lethal concentrations (ranging from 1.562 to 6.25 µg/mL) showed an inhibitory effect on the daily egg output of paired adult worms. Thus, carvacryl acetate is toxic at high doses, while at sub-lethal doses, it significantly interferes with the reproductive fitness of S. mansoni adult worms. Due to its safety and wide use in the industry, carvacryl acetate is a promising natural product-derived compound and it may represent a step forward in the search for novel anthelmintic agents, at a time when there is an urgent need for novel drugs.