Structural Diversity and Biological Potential of Alkaloids from the Genus Hippeastrum, Amaryllidaceae: an Update.

The subfamily Amaryllidoideae, Amaryllidaceae, presents an exclusive group of structures known as Amaryllidaceae alkaloids, which have a broad spectrum of biological activities. These plants are classified into 59 genera, including Hippeastrum Herb., which comprises approximately 60 species distributed mainly in South America, being widely used as ornamental plants due to the beauty of its flowers. This review presents an update about the alkaloid profiling of Hippeastrum extracts published between 2012 and 2021, as well as an approach to the biological potential of these compounds. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43450-021-00211-z.

Prosopis juliflora as a new cosmetic ingredient: Development and clinical evaluation of a bioactive moisturizing and anti-aging innovative solid core.

Prosopis juliflora is an invasive plant distributed throughout the world and presents metabolites of interest for cosmetology. The aim of this work was to develop a new polysaccharide-based ingredient from P. juliflora and analyze its application in a solid core formulation that upon contact with water instantly forms a gel to improve moisturizing and anti-aging skin properties. Purified extracts by gel chromatography were characterized by NMR and LC-DAD-MS-MS. The in vitro and in vivo safety, antioxidant activity, formulation development and clinical evaluation were performed. The extract was characterized as containing an α-glucan and phenolics. It was non-cytotoxic, non-phototoxic and no skin reactions were observed in vivo. Antioxidant activity were present through different mechanisms. Clinical evaluation reinforced the potential of P. juliflora in skin hydration and microrelief improvement. This innovative form proved to be a prototype of a new product and the first study of an α-glucan as a cosmetic ingredient.

Phytochemical study and anti-inflammatory and antioxidant potential of Spondias mombin leaves

Abstract Spondias mombin L., Anacardiaceae, is a plant native of Brazil, where it is known as "cajá". In order to find a potential application for this native species, the anti-inflammatory and antioxidant effects were investigated. The anti-inflammatory activity was evaluated using the in vivo model carrageenan-induced peritonitis in mice. The in vitro antioxidant potential as well the cytotoxicity against 3T3 fibroblast cells also were evaluated. Through High Performance Liquid Chromatography-diode array detector analysis, an analytic method was developed and validated. It allowed the identification and quantification of ellagic acid and chlorogenic acid in hydroethanolic extract of S. mombin leaves. This extract showed anti-inflammatory effect at 100, 200, 300 and 500 mg/kg, however, the ethyl acetate fraction, at 200 mg/kg, showed the highlighted results. Ellagic acid and chlorogenic acid (2.5, 5 and 10 mg/kg) also inhibited the leukocyte migration to the site of inflammation. The extract, fractions and compounds showed significant antioxidant potential when evaluated in different assays. The results shown in this work suggest the anti-inflammatory potential of the leaf extract of S. mombim on peritonitis model induced by carrageenan, it was also observed antioxidant properties associated with an absence of cytotoxicity in cell culture. Further in vivo studies are required to confirm the anti-inflammatories action of S. mombin and its possible anti-inflammatory mechanisms of action.

Natural Green coating inhibits adhesion of clinically important bacteria.

Despite many advances, biomaterial-associated infections continue to be a major clinical problem. In order to minimize bacterial adhesion, material surface modifications are currently being investigated and natural products possess large potential for the design of innovative surface coatings. We report the bioguided phytochemical investigation of Pityrocarpa moniliformis and the characterization of tannins by mass spectrometry. It was demonstrated that B-type linked proanthocyanidins-coated surfaces, here termed Green coatings, reduced Gram-positive bacterial adhesion and supported mammalian cell spreading. The proposed mechanism of bacterial attachment inhibition is based on electrostatic repulsion, high hydrophilicity and the steric hindrance provided by the coating that blocks bacterium-substratum interactions. This work shows the applicability of a prototype Green-coated surface that aims to promote necessary mammalian tissue compatibility, while reducing bacterial colonization.

Assessment of leishmanicidal and trypanocidal activities of aliphatic diamine derivatives.

Leishmanicidal and trypanocidal activity of seventeen lipophilic diamines was evaluated in vitro against Leishmania braziliensis, L. chagasi, and Trypanosoma cruzi. Twelve compounds presented anti-Leishmania and six showed anti-T. cruzi amastigote activity. Compound 14 (N-tetradecyl-1,4-butanediamine) was the most active against both L. braziliensis (IC50  = 2.6 µm) and L. chagasi (IC50  = 3.0 µm) which showed a selectivity index (SI) >100. N-decyl-1,6-hexanediamine (compound 9) presented an IC50  = 1.6 µm and SI >187 and was over six times more potent than the reference drug benznidazole against T. cruzi. Treatment of infected or uninfected macrophages with compounds 9 and 14 did not induce significant TNFα and NO production. Four compounds (15, 16, 22, and 23) inhibited 78.9%, 77.7%, 83.7%, and 70.1% of rTRLb activity, respectively, and compound 23 inhibited 73.3% of rTRTc activity at 100 µm. A concentration-dependent effect on mitochondrial membrane depolarization was observed in T. cruzi epimastigotes treated with compound 9, suggesting this mechanism may be involved in the trypanocidal effect. On the contrary, in L. braziliensis promastigotes treated with compound 14, no mitochondrial depolarization was observed. Our results demonstrate that N-decyl-1,6-hexanediamine and N-tetradecyl-1,4-butanediamine are promising molecules for the development of novel leading compounds against T. cruzi and Leishmania spp., particularly given a possible alternative mechanism of action.

Tannins possessing bacteriostatic effect impair Pseudomonas aeruginosa adhesion and biofilm formation.

Plants produce many compounds that are biologically active, either as part of their normal program of growth and development or in response to pathogen attack or stress. Traditionally, Anadenanthera colubrina, Commiphora leptophloeos and Myracrodruon urundeuva have been used by communities in the Brazilian Caatinga to treat several infectious diseases. The ability to impair bacterial adhesion represents an ideal strategy to combat bacterial pathogenesis, because of its importance in the early stages of the infectious process; thus, the search for anti-adherent compounds in plants is a very promising alternative. This study investigated the ability of stem-bark extracts from these three species to control the growth and prevent biofilm formation of Pseudomonas aeruginosa, an important opportunistic pathogen that adheres to surfaces and forms protective biofilms. A kinetic study (0-72 h) demonstrated that the growth of extract-treated bacteria was inhibited up to 9 h after incubation, suggesting a bacteriostatic activity. Transmission electron microscopy and fluorescence microscopy showed both viable and nonviable cells, indicating bacterial membrane damage; crystal violet assay and scanning electron microscopy demonstrated that treatment strongly inhibited biofilm formation during 6 and 24 h and that matrix production remained impaired even after growth was restored, at 24 and 48 h of incubation. Herein, we propose that the identified (condensed and hydrolyzable) tannins are able to inhibit biofilm formation via bacteriostatic properties, damaging the bacterial membrane and hindering matrix production. Our findings demonstrate the importance of this abundant class of Natural Products in higher plants against one of the most challenging issues in the hospital setting: biofilm resilience.

A steroidal molecule present in the egg wax of the tick Rhipicephalus (Boophilus) microplus inhibits bacterial biofilms.

The cattle tick Rhipicephalus (Boophilus) microplus lays eggs in the soil near the roots of grass, or in similar highly moist environments that are prone to biofilm formation. Tick eggs have a protective wax coating that may be a source of nutrients for microorganisms. However, as the eggs remain viable and show no visible signs of microbial colonization, we hypothesized that the coating might have anti-biofilm properties. We show here that the coating inhibits biofilm formation by both Gram-negative and Gram-positive bacteria, though by different mechanisms. We have identified the anti-biofilm molecule as N-(3-sulfooxy-25-cholest-5-en-26-oyl)-L-isoleucine (boophiline), and we show that it inhibits the expression of fliC (flagellin) and cdrA (biofilm scaffold), whose products are necessary for biofilm formation in Pseudomonas aeruginosa. Boophiline is a novel biofilm inhibitor being also effective against Staphylococcus epidermidis biofilm. In our study we show evidences of the boophiline mode of action in the protection of arthropod eggs against biofilm colonization.

Lycorine derivatives against Trichomonas vaginalis.

Six lycorine derivatives were prepared, characterized, and evaluated for their in vitro anti-Trichomonas vaginalis activity. Compounds bearing an acetyl (2), lauroyl (3), benzoyl (4 and 5), and p-nitrobenzoyl (6 and 7) groups were synthesized. The best activity was achieved with lycorine esterified at C-2 position with lauroyl group. Preliminary structure-activity relationship points that unprotected OH group at C-1 and C-2 is not necessary to the antiparasitic activity, and none of the derivative was less active than lycorine. The lycorine structural requisites required to kill this amitochondriate cell seem to be different in comparison with the derivatives most active against other parasites and tumor cell lines, both mitochondriated cells. This result is an important contribution with our ongoing studies regarding the mechanism of action of the Amaryllidaceae alkaloids on T. vaginalis cell death opening a new perspective to optimize this innovative pharmacological potential.

Alkaloids from Hippeastrum morelianum Lem. (Amaryllidaceae).

The Amaryllidaceae family has proven to be a rich source of active molecules. As part of an ongoing project, we report a phytochemical study of Hippeastrum morelianum (Amaryllidaceae), from which we have isolated two homolycorine-type alkaloids, the new 2α,7-dimethoxyhomolycorine (1) and the poorly described candimine (2), as well as six known alkaloids: tazettine, pretazettine, 3-epimacronine, haemanthamine, hamayne and trisphaeridine. For reference purposes, the NMR of the isolated compounds was unequivocally described, based on 2D NMR measurements including (1)H-(1)H COSY, (1)H-(1)H NOESY, HSQC and HMBC.

Candimine-induced cell death of the amitochondriate parasite Trichomonas vaginalis.

Candimine (1), an alkaloid from the bulbs of Hippeastrum morelianum, was found to be cytotoxic for the amitochondriate parasite Trichomonas vaginalis. Candimine (1) induced cell death with an unprecedented group of effects that failed to fulfill the criteria for apoptosis and apoptosis-like death already reported in trichomonads. Arrest of the parasite cell cycle, and morphologic and ultrastructural alterations, including marked cytoplasmic vacuolization, were induced by 1. The present findings suggest some similarities to paraptotic cell death, described for multicellular organisms. This study contributes to both a better understanding of the biological effects of 1 and T. vaginalis cell biology.

Trichomonas vaginalis nucleoside triphosphate diphosphohydrolase and ecto-5'-nucleotidase activities are inhibited by lycorine and candimine.

Drug discovery from plants plays an important role in the pharmaceutical therapy field and the alkaloids lycorine and candimine are candidates for this purpose. Trichomonas vaginalis is a parasite that infects the human urogenital tract and causes trichomonosis, the most prevalent non-viral sexually transmitted disease. Ecto-nucleotidases including nucleoside triphosphate diphosphohydrolase (NTPDase) members, which hydrolyses extracellular ATP (adenosine triphosphate) and ADP (adenosine diphosphate), and ecto-5'-nucleotidase, which hydrolyses AMP (adenosine monophosphate), have been characterized in T. vaginalis. Because purine nucleotides are released from cells under physiological and stress conditions, the goal of this study was to evaluate the effect of lycorine and candimine on T. vaginalis NTPDase and ecto-5'-nculeotidase activities. The alkaloids (50 to 250microM) were tested against both long-term-grown and clinical isolates. Specific enzymatic activities were expressed as nmolPi released/min/mg protein. The effect of both alkaloids at NTPDase A and B expression levels was investigated. When the alkaloids were added directly to the reaction mixture, no effect on ATP, ADP or AMP hydrolysis was observed. NTPDase and ecto-5'-nucleotidase activities were strongly inhibited by candimine and lycorine on 24h-treated parasites. This effect was abolished when 24-treated parasites were innoculated in a culture medium without alkaloid. Transcript levels of NTPDase A or B were not altered by the alkaloids. Considering the cytotoxic and proinflammatory roles of ATP besides the anti-inflammatory effects of adenosine, the regulation of extracellular nucleotide levels could be relevant in increasing susceptibility of T. vaginalis to host immune response in the presence of lycorine and candimine.

Anti-Trichomonas vaginalis activity of synthetic lipophilic diamine and amino alcohol derivatives.

Taking in account the increased prevalence of metronidazole-resistant infections, alternative drugs are necessary for the treatment of trichomonosis. We report in this work the preparation and the in vitro anti-trichomonads activity of two diamines 1 and 2, and three different lipophilic amino alcohol derivatives 3, 4 and 5. These compounds were tested for in vitro activity against two isolates of Trichomonas vaginalis and displayed inhibition of the parasite growth. Five concentrations of each compound were tested. The butanediamine derivative 1, at a final concentration of 5.85 microM, presented a cytotoxic effect against 47% of T. vaginalis trophozoites. Furthermore, the cytotoxicity of 1 did not present statistically significant difference when compared to metronidazole in the same range of concentration (0.1-1.5 microg/mL).

Avaliação in vitro das atividades antiinflamatória, antioxidante e antimicrobiana do alcalóide montanina / In vitro evaluation of the antioxidant, anti-inflammatory and antimicrobial activities of the montanine alkaloid

Diversas propriedades biológicas, dentre as quais atividade antiparasitária, antitumoral, antiviral e anticolinesterásica são associadas aos extratos e produtos isolados, incluindo alcalóides de espécies de Amarilidáceas. Neste trabalho verificou-se para o alcalóide montanina, isolado dos bulbos de Rhodophiala bifida (Herb.) Traub (Amaryllidaceae), atividade antioxidante e ação inibitória sobre o crescimento de culturas de Saccharomyces cerevisae (ATCC 2601), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 6538), Staphylococcus epidermides (ATCC 12228) e Escherichia coli (ATCC 25922). A atividade antiinflamatória avaliada através da determinação da capacidade antiquimiotáxica da amostra apresentou resultados não significativos na dose empregada.

Several biological properties, such as antiparasite, antitumor, antiviral and anticholinesterasic activities, are associated with extracts and isolated products, including alkaloids from Amaryllidaceae species. In this study, the antioxidant activity and inhibitory action on the growth of cell cultures of Saccharomyces cerevisae (ATCC 2601), Pseudomonas aeruginosa (ATCC 27853), Staphylococcus aureus (ATCC 6538), Staphylococcus epidermides (ATCC 12228) and Escherichia coli (ATCC 25922) were observed to the montanine alkaloid, isolated from the bulbs of Rhodophiala bifida (Herb.) Traub (Amaryllidaceae). The anti-inflammatory activity, which was evaluated through the sample antichemotaxis ability determination, was not significant in the used dose.