Promising natural products for the treatment of cutaneous leishmaniasis: A review of in vitro and in vivo studies.

Although there are available treatments for cutaneous leishmaniasis (CL), the drugs used are far from ideal, toxic, and costly, in addition to the challenge faced by the development of resistance. Plants have been used as a source of natural compounds with antileishmanial action. However, few have reached the market and become phytomedicines with registration in regulatory agencies. Difficulties related to the extraction, purification, chemical identification, efficacy, safety, and production in sufficient quantity for clinical studies, hinder the emergence of new effective phytomedicines against leishmaniasis. Despite the difficulties reported, the major research centers in the world see that natural products are a trend concerning the treatment of leishmaniasis. The present work consists of a literature review of articles with in vivo studies, covering the period from January 2011 to December 2022, providing an overview of promising natural products for CL treatment. The papers show encouraging antileishmanial action of natural compounds with reduced parasite load and lesion size in animal models, suggesting new strategies for the treatment of the disease. The results reported in this review show advances in using natural products as safe and effective formulations, which can stimulate clinical studies to establish clinical therapy. In conclusion, the information in this review article serves as a preliminary basis for establishing a therapeutic protocol for future clinical trials that can validate the safety and efficacy of natural compounds, providing the development of affordable and safe phytomedicines for the treatment of CL.

Nanotechnology Promoting the Development of Products from the Biodiversity of the Asteraceae Family.

Biodiversity is a hallmark of the Asteraceae family. Several species are known for their pharmacological potential. The search for new substances has permeated the chemistry of natural products for years. However, the development of a final product is still a challenge. Plant extracts have physicochemical characteristics that sometimes hinder administration, requiring a formulation. In this context, nanotechnology emerges as a tool to improve the pharmacokinetic parameters of several pharmacologically active substances. Nanoemulsions, liposomes, and nanoparticles are used to carry the active ingredients and thus improve therapeutic action, especially for substances with solubility and absorption problems. This paper aimed at compiling all the studies that used nanotechnology to develop formulations from species of the Asteraceae family from 2010 to 2021 in a literature review. The search showed that nanoemulsions are the most developed formulation associated with essential oils. The use of nanotechnology promoted an improvement in the pharmacokinetic parameters of active substances.

Flavonoids and fractions from Saccharum officinarum L. juice: antinociceptive agents and molecular docking evaluations with µ-opioid receptor.

Opioid receptors mediate antinociceptive effects. Methanolic fractions from sugarcane varieties (MFSCf) were evaluated in classic nociception models. Interactions between bioactive compounds and the µ-opioid receptor (µOR) through docking analysis were also studied. Five methanolic fractions of sugarcane juice were obtained and analysed by LC-ESI-MS/MS. The fractions and standards of phenolic compounds were evaluated in a nociception model using the formalin test. All MFSCfs exhibited antinociceptive activity in the first phase of the formalin test. Docking analyses corroborates with the in vivo test results, suggesting that the phenolic substances are able to activate µOR. These results, for the first time, implicate phenolic constituents from sugarcane juice and other phenolic compounds in the activation of µOR. The antinociceptive activity of fractions from sugarcane juice suggests the potential pharmacological use of this species, widely cultivated in Brazil.

Alkylamides from Acmella oleracea: antinociceptive effect and molecular docking with cannabinoid and TRPV1 receptors.

Alkylamides are secondary metabolites in Acmella oleracea and display wide applications in treating several diseases. Since alkylamides can inhibit pain, this work aims to evaluate the antinociceptive profile of A. Oleracea methanolic extracts used in vivo and in silico assays. The extracts inhibited the neurogenic and inflammatory phases of the formalin test, ratifying the antinociceptive effect of alkylamides. Furthermore, the results from molecular docking demonstrated the interaction of A. oleracea alkylamides with the CB1/CB2 and TRPV1 receptors. Additionally, the crude methanolic extract of flowers did not induce potential side effects related to the classical cannabinoid tetrad: hypolocomotion and catalepsy. In conclusion, this work confirms the potential of the alkylamides of A. Oleracea as antinociceptive agents and, for the first time, correlates its effects with the endocannabinoid and vanilloid systems through in silico assays.

Biological properties of functional flavoring produced by enzymatic esterification of citronellol and geraniol present in Cymbopogon winterianus essential oil.

The chemical composition and biological properties of citronella essential oil were modified by enzymatic esterification reaction of the major monoterpenic alcohols with cinnamic acid. The almost complete conversion of geraniol and citronellol present in the citronella (Cymbopogon winterianus) essential oil, into geranyl (99%) and citronellyl (98%) cinnamates was obtained after 48 hours of reaction using a molar ratio of 3:1 (cinnamic acid/alcohol), lipase concentration (Novozym 435) of 15% (w/w) and 70 °C. The esterified oil showed higher antimicrobial activity against Staphylococcus aureus bacteria resistant to oxacillin and penicillin and also greater larvicidal activity against Aedes aegypti larvae compared to unesterified oil. The results concerning the evaluation of toxicity against Artemia salina and cytotoxicity against monkey kidney epithelial cells also showed the superiority of the esterified oil.

The presence of heavy metals in Avicennia schaueriana Stapf & Leechman ex Moldenke leaf and epicuticular wax from different mangroves around Sepetiba Bay, Rio de Janeiro, Brazil.

This study aimed to investigate the leaf epicuticular wax and the presence of heavy metals in leaves of Avicennia shaueriana, a halophyte found in Brazilian mangroves. We evaluated plants collected in mangroves located around Sepetiba Bay, Rio de Janeiro State. Heavy metals were analyzed by energy dispersive X-ray spectroscopy (EDS or EDX) and inductively coupled plasma optical emission spectrometry (ICP-OES). Chemical analysis of epicuticular wax was made by gas chromatography-mass spectrometry (GC-MS). We also evaluated the micromorphology of leaf surface using scanning electronic and light microscopy. The leaves from each mangrove presented alterations in wax layer. Fagarasterol (lupeol) in high quantity was the main triterpene identified in the leaf wax from plants collected in all mangroves: Coroa Grande (76.43%), Pedra de Guaratiba (38.91%), and Marambaia (62.56%). Al, Fe, Mn, and Zn were the main heavy metals detected in leaves from the three mangroves by ICP-OES. Thus, we show that that plants able to survive in the mangrove swamp can adapt to the exposure of heavy metals, accumulate them in their leaves, and be used in coastal area recovery projects as a phytoremediator.

Evaluation of the chemical composition and antioxidant activity of extracts and fractions of Ocotea notata (Ness) Mez (Lauraceae).

The specie Ocotea notata (Nees & Mart). Mez is a tree with 5 meters high, that can be found in restinga regions in the Brazilian coast. This study describes a phytochemical investigation, total phenolic content and the antioxidant activity of extracts and fractions by DPPH and ORAC. Phenolic content revealed equivalent concentration between evaluated samples, similar to found in the leave extract (66.4 mEq GA/g). By DPPH, extracts and fractions showed effective concentration (EC50) lower than the standards Ginkgo biloba 761® (23.60 ± 0.64 µg/ml) and quercetin (6.06 ± 0, 92 µg/mL); for the ORAC method, ethyl acetate partition showed a value of 2.06 mmol Trolox equivalent g-1 better than obtained in Ginkgo biloba (1.03 ± 0.25 mmol.Trolox equivalent g-1. The butanol partition (0.52 mmol.Trolox equivalent g-1) and the aqueous residue (0.74 mmol Trolox equivalent g-1) have a lesser ORAC potential than ethyl acetate partition. The butanolic partition, investigated by LC-DAD-MS/MS and QTOF-MS, revealed six major compounds: miquelianin (1), isoquercitrin (2), quercitrin (3), kaempferol-3-O-pentose (4), afzelin (5) and isorhamnetin-glucuronide (6).

Marine prebiotics: Polysaccharides and oligosaccharides obtained by using microbial enzymes.

Utilization of marine algae has increased considerably over the past decades, since biodiversity within brown, red and green marine algae offers possibilities of finding a variety of bioactive compounds. Marine algae are rich sources of dietary fibre. The remarkable positive effects of seaweed dietary fibre on human body are related to their prebiotic activity over the gastrointestinal tract (GIT) microbiota. However, dietary modulation of microorganisms present in GIT can be influenced by different factors such as type and source of the dietary fibre, their molecular weight, type of extraction and purification methods employed, composition and modification of polysaccharide and oligosaccharide. This review will demonstrate evidence that polysaccharides and oligosaccharides from marine algae can be used as prebiotics, emphasizing their use in human health, their application as food and other possible applications. Furthermore, an important approach of microbial enzymes employment during extraction, modification or production of those prebiotics is highlighted.

Distinct growth and extractive methods of Acmellaoleracea (L.) R.K. Jansen rising different concentrations of spilanthol: An important bioactive compound in human dietary.

Acmella oleracea, commonly known as jambú, is a great source of spilanthol, a secondary metabolite responsible for different kind of biological activities, such as the antioxidant, antimicrobial, cytotoxic and anti-inflammatory bioactivities. The purpose of this work was to evaluate spilanthol content in A. oleracea plants obtained from three different cultivation conditions - in vitro, acclimatized and in field - and compare two different extraction techniques: maceration and microwave assisted extraction (MAE). Therefore, A. oleracea nodal segments were cultured on Murashige and Skoog medium. After 30days, developed plants were transferred to ex vitro conditions and successfully acclimatized. From all types of culture, the whole plant as well as the flowers, leaves, stems and roots were used, separately, to obtain ethanolic extract (75%) but only the micropropagated whole plant was used on the factorial design 24-1 on the microwave-assisted extraction. All the samples were quantified by HPLC-DAD and analyzed by CG-MS. Results show that the different acclimatized plant parts are the richest in spilanthol content, followed by the in vitro culture and, finally, field material. The MAE was able to extract the highest amount of spilanthol from in vitro whole plant (3.09%) compared to the classical maceration extract (0.98%) and, furnished good crude extracts yields under an optimized study accurately explained by the mathematical model. The antibacterial assay presented a negative result using in vitro samples and bacteria inhibition with field samples against Staphylococcus aureus (ATCC 29213) and Staphylococcus epidermidis (ATCC 12228) standard strains.

Antibacterial activity and cytotoxicity analysis of halistanol trisulphate from marine sponge Petromica citrina.

OBJECTIVES: An aqueous extract and fraction from the marine sponge Petromica citrina have antibacterial activity. We performed a chemical and biological characterization of the antibiotic substance from P. citrina and investigated its mode of action on Staphylococcus aureus cells. METHODS: The inhibitory activity of the aqueous extract of P. citrina was determined against 14 bacteria belonging to type strains and clinical antibiotic-resistant strains. The aqueous extract was fractionated under bioassay guidance and the bioactive substance was identified by its (1)H-NMR, (13)C-NMR and mass spectra. The MIC and the MBC of this substance were determined. This substance was also subjected to cytotoxic bioassays. The mode of action on S. aureus cells was investigated by light and transmission electron microscopy analysis. RESULTS: P. citrina showed a large spectrum of activity against type strains and resistant-bacteria such as S. aureus, Staphylococcus epidermidis, Enterococcus faecalis, Mycobacterium fortuitum and Neisseria gonorrhoeae. The aqueous extract was fractionated and halistanol trisulphate (24ε,25-dimethylcholestane-2ß,3α,6α-triol trisodium sulphate) was isolated for the first time from P. citrina. Halistanol trisulphate had a bactericidal effect on exponentially growing S. aureus cells at the MIC (512 mg/L). Cytotoxicity biossays showed moderate toxicity against cancer cell line L929 (fibrosarcoma). This substance apparently acts by damaging the cell membrane, with subsequent cell lysis. CONCLUSIONS: Halistanol trisulphate is a broad-spectrum antibiotic isolated from P. citrina with a mode of action involving disruption of the cytoplasmic membrane. It is a new candidate for research on antibacterial substances.

Potential use of Piper nigrum ethanol extract against pyrethroid-resistant Aedes aegypti larvae.

Fractionation of Piper nigrum ethanol extract, biomonitored by assays on pyrethroid-resistant Aedes aegypti larvae yielded isolation of the larvicidal amides piperolein-A and piperine. Comparing LC50 values, the ethanol extract (0.98 ppm) was the most toxic, followed by piperolein-A (1.46 ppm) and piperine (1.53 ppm).

Potential use of Piper nigrum ethanol extract against pyrethroid-resistant Aedes aegypti larvae

Fractionation of Piper nigrum ethanol extract, biomonitored by assays on pyrethroid-resistant Aedes aegypti larvae yielded isolation of the larvicidal amides piperolein-A and piperine. Comparing LC50 values, the ethanol extract (0. 98 ppm) was the most toxic, followed by piperolein-A (1. 46ppm) and piperine (1. 53ppm).

O fracionamento do extrato etanólico de Piper nigrum biomonitorado por ensaios em larvas de Aedes aegypti resistentes a piretróides resultou no isolamento das amidas larvicidas piperoleína-A e piperina. Comparando-se os valores de CL50, o extrato etanólico (0. 98ppm) foi o mais tóxico, seguido pela piperoleína-A (1. 46ppm) e piperina (1. 53ppm).