Coumarins from Rutaceae: Chemical diversity and biological activities.

Rutaceae is a family expressed by approximately 2100 species distributed in 154 genera widespread in tropical and temperate regions of Australasia, America, and South Africa. Substantial species of this family are employed as folk medicines. The literature describes the Rutaceae family as a great source of natural and bioactive compounds like terpenoids, flavonoids, and, especially, coumarins. To data, 655 coumarins were isolated and identified from Rutaceae in the past twelve years and, most of them, showed different biological and pharmacological activities. There are studies with coumarins from Rutaceae indicating that these compounds showed activity against cancer, inflammation, infectious diseases, and in the treatment of endocrinal and gastrointestinal conditions. Although coumarins are considered versatile bioactive molecules, until the present, there is no compiled information about coumarins from the Rutaceae family demonstrating the potency of these compounds in all dimensions and chemical similarities among the genera. The present review covers the relevant studies dealing with isolation of Rutaceae coumarins from 2010 until 2022 and outlines the current data on pharmacological activities these coumpounds. Additionally, the chemical disposition and similarity among Rutaceae genera are also statistically discussed employing PCA and HCA methods.

The genus Erythrina L.: A review on its alkaloids, preclinical, and clinical studies.

Erythrina L. genus (Fabaceae) comprises about 115 species, and it has been extensively studied, mainly because of its alkaloids, which have pharmacological properties. References demonstrated that Erythrina spp. have a potential to act in the central nervous system, presenting anxiolytic and anticonvulsant properties already established. Phytochemical investigations confirmed the presence of tetracyclic alkaloids as the major compounds. However, other alkaloid classes have also been reported, including dimeric and trimeric substances, coupled through direct polymerization or two erythrinine units via an acetyl glucose. The present review covers the relevant literature from 1990 until 2017 and outlines the current data on chemical composition and preclinical and clinical studies on Erythrina species. Additionally, the quite striking analogy in the biosynthetic route of erythrin, morphinans, and Amaryllidaceae family alkaloids was also discussed.

Potential use of secondary products of the agri-food industry for topical formulations and comparative analysis of antioxidant activity of grape leaf polyphenols.

The aim of the present study was to develop a phytocosmetic using Vitis waste by-products, for use as a topical formulation for skin protection against ultraviolet radiation damage. The study also evaluates the free radical scavenger activity of the crude extracts of dried leaves of Vitis vinifera and Vitis labrusca, as well as the anthocyanins, flavonoid fraction and isolated compounds. Next, release and permeation studies of hydrogels were performed using Franz-type diffusion cells. Flavonoid acted more intensively in TRAP and conjugated dienes antioxidant assays, whereas anthocyanins had higher antioxidant activity in hydroxyl and nitric oxide assay. Only quercetin-3-O-glucuronide (5) was released from hydrogels, and the flavonoid retention in porcine ear skin after eight hours of permeation was below of limit of quantification for this compound. The polyphenols present in Vitis are capable of absorbing UV and visible light, justifying their potential as sunscreens for the development of a phytocosmetic.

Toxicological profile and acetylcholinesterase inhibitory potential of Palicourea deflexa, a source of ß-carboline alkaloids.

Palicourea genus is chemically and taxonomically close to Psychotria genus, a well-known source of neuroactive alkaloids. It has been previously reported the pharmacological potential of these alkaloids in some targets related to the neurodegenerative process. In this context, this study was carried out in order to evaluate the toxic effects and acetylcholinesterase (AChE) inhibitory potential of Palicourea deflexa fraction of total alkaloids (FTA). P. deflexa FTA was analyzed by means of HPLC-DAD and HRMS-ESI. We performed toxicological screening through Fish Embryo Toxicity (FET) test using zebrafish embryo and abnormal developmental phenotypes were recorded daily. For AChE inhibition, zebrafish brains were used as enzymatic source and formation of thiolate dianion of 5,5'-Dithiobis(2-nitrobenzoic acid) (DTNB) was used to monitor acetylthiocholine hydrolysis. Lineaweaver-Burk double reciprocal plots were used to indicate mode of inhibition. Chemical analysis of the P. deflexa FTA allowed the identification of the main compound as harman-3-carboxylic acid. This fraction was evaluated in vivo for its toxicological effect. The zebrafish embryo test indicated that the FTA has a lethal concentration of 50% (LC50)=72.18µg/mL. Further, the FTA was evaluated for its AChE inhibitory profile, demonstrating an inhibitory concentration of 50% (IC50) of 50.65µg/mL. Lineaweaver-Burk double reciprocal plots indicated a mixed mode of inhibition. It is reported for the first time the toxicological and pharmacological profile of the alkaloid fraction of Palicourea deflexa in zebrafish models.

In vitro Antioxidant and Enzymatic Approaches to Evaluate Neuroprotector Potential of Blechnum Extracts without Cytotoxicity to Human Stem Cells.

BACKGROUND: Investigation of selected plant extracts on multi-targets related to neurodegeneration, such as monoamine oxidases (MAO), cholinesterase enzymes, and antioxidant activities (AOA) is a useful tool for identification of new scaffolds. OBJECTIVE: This work investigated biological effects of three Blechnum methanol extracts from Brazil and chemical profile of the most active sample. MATERIALS AND METHODS: AOA included scavenging of hydroxyl and nitric oxide radicals, also lipid peroxidation inhibition. Enzymatic modulation of Blechnum binervatum, Blechnum brasiliense, and Blechnum occidentale extracts on MAO and cholinesterases was conducted. Moreover, total phenol content was performed with all samples, and high-performance liquid chromatography-diode array detection mass spectrometry HPLC-DAD-MS analysis was carried out with B. brasiliense. Possible toxic effects were evaluated on Wistar rats polymorphonuclear cells (PMN) and human stem cells. RESULTS: B. brasiliense extract presented the highest phenolic amount (9.25 g gallic acid equivalent/100 g extract) and lowest IC50 values (112.3 ± 2.61 and 176.1 ± 1.19 µg/mL) against hydroxyl radicals and on lipid peroxidation, respectively, showing strong AO effects. On nitric oxide assay and cholinesterase inhibition, all extracts were considered inactive. MAO-A selective action was evidenced, being B. brasiliense powerful against this enzyme (IC50: 72.7 µg/mL), followed by B. occidentale and B. binervatum (IC50: 130.85 and 165.2 µg/mL). No cytotoxic effects were observed on PMN and human stem cells treated with Blechnum extracts. HPLC-DAD-MS analysis of B. brasiliense allowed the identification of chlorogenic and rosmarinic acids. CONCLUSION: Our results especially highlight B. brasiliense, with pronounced phenols content and strong effects on selected targets related to neurodegeneration, being characterized as a natural safe source of bioactive hydroxycinnamic acids. SUMMARY: Blechnum crude extracts showed high phenolic amounts and valuable IC50 values on targets related with neurodegenerative disordersBlechnum brasiliense was the most active sample, with strong radical scavenging and lipid peroxidation inhibition, also with monoamine oxidases: A selective modulationNo cytotoxic effects were observed on polymorphonuclear cells rat cells and human stem cells treated with Blechnum extractsHigh-performance liquid chromatography-diode array detection-mass spectrometry analysis of Blechnum brasiliense allowed the identification of hydroxycinnamic derivatives: Chlorogenic and rosmarinic acids. Abbreviations used: IC50: half maximal inhibitory concentration; MAO: monoamine oxidase; MAO-A: monoamine oxidase isoform A; MAO-B: monoamine oxidase isoform B; HO•: hydroxyl radical.

pH-dependent cytotoxic effects of extracts of the marine sponge Polymastia janeirensis on cancer cell lines.

The purpose of this work was to study the cytotoxic effects of marine sponge Polymastia janeirensis, which has been observed in the field to release an orange substance that is toxic to fish. The result showed that aqueous extract (pH 7.0) was highly cytotoxic to glioma (U87) and neuroblastoma (SHSY5Y) cancer cell lines (IC50 < 1.0 µg/mL). In addition, this extract showed potent antioxidant and procoagulant (decreased the clotting time by 1.7-fold) activities. Interestingly, the cytotoxic effects were pH-dependent since the viability of the cancer cells was not affected with the extract (pH 5.5). The close similarity between the aqueous extract (pH 7.0) and the orange liquid that is released by the sponge indicates that this potential chemical defence of P. janeirensis deserves further investigation.

Sphingosines Derived from Marine Sponge as Potential Multi-Target Drug Related to Disorders in Cancer Development.

Haliclona tubifera, marine sponge species abundant in Brazilian coastline, presents only a few papers published in the literature. Recently, we have reported the isolation of two modified C18 sphingoid bases: (2R,3R,6R,7Z)-2-aminooctadec-7-ene-1,3, 6-triol and and (2R,3R,6R)-2-aminooctadec-1,3,6-triol. In order to continue our research, in this work aimed at the biological investigation of fractions that led to the isolation of these compounds. We evaluated the cytotoxic effect of marine sponge H. tubifera fractions in glioma (U87) and neuroblastoma (SH-SY5Y) human cell lines. In addition, considering the link between cancer, imbalance of reactive oxygen species and coagulation disorders, we also investigated the in vitro effects on blood coagulation and their redox properties. We showed that the ethyl acetate (EtOAc) fraction, rich in sphingoid bases, had important cytotoxic effects in both cancer cell lines with an IC50 < 15 µg/mL and also can inhibit the production of peroxyl radicals. Interestingly, this fraction increased the recalcification time of human blood, showing anticoagulant properties. The present study indicates the sphingosines fraction as a promising source of chemical prototypes, especially multifunctional drugs in cancer therapy.

Cytotoxic effects on tumour cell lines of fatty acids from the marine sponge Scopalina ruetzleri.

OBJECTIVES: Marine sponges are among the most promising sources of chemically diversified fatty acids (FAs). In addition, several studies have shown the effect of polyunsaturated FAs on cancer therapy. This research carried out a biological and chemical evaluation of the sponge Scopalina ruetzleri collected on the South Brazilian coastline. METHODS: Bioassay-guided fractionation of S. ruetzleri was performed in human glioma (U87) and neuroblastoma (SH-SY5Y) cell lines, and the in-vitro effects on free radicals were evaluated. KEY FINDINGS: The ethyl acetate fraction of S. ruetzleri showed promising cytotoxic effects in cancer cell lines, with IC50 < 20 µg/ml. Fingerprint (1) H Nuclear Magnetic Resonance (NMR) analysis showed that this fraction is mainly constituted of FAs. Through FA methyl ester analysis, it was possible to identify 32 FAs. In addition, some minor unusual FAs for the marine biosphere were identified. The results of conjugated dienes method showed that FAs fraction, at concentrations above 50 µg/ml, has a pro-oxidant effect, indicating that lipid peroxidation may be partially responsible for the mechanism of cytotoxicity on cancer cells. CONCLUSION: This work also contributes to studies that focus on the application of FAs on cancer therapy as a new adjuvant to radio or chemotherapy, or as a chemotherapeutic agent.

Morphoanatomical identification and physicochemical parameters of the drug Erythrina verna Vell. trunk bark / Identificación morfoanatómica y parámetros físico-químicos de la cortezadel leño de Erythrina verna Vell

“Mulungu” (Erythrina verna Vell., Fabaceae.) is an arboreal specie native to southeastern Brazil, used for medicinal purposes. This plant is characterized by the presence of alkaloids that have demonstrated anxiolytic activity. Due to this activity, this plant is listed by the Brazilian National Program of Medicinal Plants and Herbal Medicines. However, bibliographic information is lacking regarding this species. This study aims to describe E. verna barks, macro and microscopically, as well as some physicochemical parameters for the quality control of its raw material. In addition, the chromatographic profile of its alkaloid fraction and optimization of extraction methods for crude extract production has also been performed.

“Mulungu” (Erythrina verna Vell., Fabaceae.) es una especie arborea nativa del sudeste de Brasil, utilizada con fines medicinales. Esta planta se caracteriza por la presencia de alcaloides que han demostrado actividad ansiolítica. Debido a esta actividad, esta planta se encuentra en la lista del Programa Nacional Brasileño de las Plantas Medicinales y Medicinas Herbarias. Sin embargo, la información bibliográfica es escasa con respecto a esta especie. Este estudio tiene como objetivo describir E. Verna corteza, macro y microscópicamente, así como algunos parámetros físico-químicos para el control de la calidad de la materia prima fresca. Además, el perfil cromatográfico de la fracción alcaloidica y la optimización de métodos de extracción para la producción de extracto crudo también fue realizada.

Halisphingosines A and B, modified sphingoid bases from Haliclona tubifera. Assignment of configuration by circular dichroism and van't Hoff's principle of optical superposition.

Halisphingosines A (1) and B (2), modified long-chain sphingoid bases, from the marine sponge Haliclona tubifera collected in Brazil, were characterized after conversion to their N-Boc derivatives. The 2R,3R,6R configuration of halisphingosine A, a compound first reported from Haliclona sp. from South Korea, was confirmed using a novel CD approach: deconvolution of exciton coupling from mono- and trinaphthoyl derivatives obtained by derivatization of the natural product. The sensitive CD deconvolution method, applicable to submilligram samples, simultaneously predicted the relative and absolute configuration of three stereocenters in halisphingosine A with precision and accuracy. Halisphingosine B was assigned by correlation to halisphingosine A.

Comparative analysis of the chemical composition and antioxidant activity of red (Psidium cattleianum) and yellow (Psidium cattleianum var. lucidum) strawberry guava fruit.

UNLABELLED: Strawberry guava (Psidium cattleianum Sabine) is a native fruit of Brazil widely consumed fresh and used in the food industry. In this context, the present study deals with the chemical characterization and the antioxidant activity of the red (Psidium cattleianum) and yellow (P. cattleianum var. lucidum Hort.) strawberry guava fruits, cultivars Irapuã and Ya-Cy, respectively. Knowledge of chemical composition is fundamental to human nutrition, contributing to the quality of foods. Phenolic compounds in both fruits were analyzed by HPLC-DAD and the total flavonoid content was determined by the Folin-Ciocalteu assay. The antioxidant activity was evaluated by the total reactive antioxidant (TRAP) method. Psidium cattleianum presented a higher content of polyphenolic compounds than P. cattleianum var. lucidum (501.33 and 292.03 mg/100 g, respectively), with hyperoside being one of the major flavonoids identified for both cultivars. In addition to flavonoids, P. cattleianum presented an anthocyanin, identified as cyanidin. The antioxidant activity varied in a concentration-dependent manner for both strawberry guava species. The volatile oils in fruits and fatty acids in seeds were quantified by GC-EM. The analysis of the essential oil of yellow strawberry guava was compared with a previous study on the red cultivar, revealing ß-caryophyllene as the main component in both oils. The fatty acid composition was also quite similar and was especially characterized by the presence of unsaturated fatty acids (86.25% and 76%, respectively), among which linoleic acid as the most abundant. PRACTICAL APPLICATION: In this study, the chemical characterization and the antioxidant activity of the red (Psidium cattleianum) and yellow (P. cattleianum var. lucidum Hort.) strawberry guava fruits were investigated. This is important for potential application of strawberry guava as functional food. Moreover, it may be the experimental basis for further development and use in food industry.

Optimization and validation of an alternative method to evaluate total reactive antioxidant potential.

The total reactive antioxidant potential (TRAP) is one of the methods most employed to estimate the antioxidant capacity of samples in vitro. This method is based on the quenching of luminol-enhanced chemiluminescence derived from the thermolysis of 2,2'-azo-bis(2-amidinopropane)dihydrochloride (AAPH) as the free radical source. However, this method can present limitations when the sample does not present a lag phase. In addition, there are no studies regarding TRAP assay validation. In this context, the aim of this work was to optimize and validate this method and to propose another evaluation method using the area under the curve (AUC). The main condition established was the need for the stabilization of the system, at 7000s, before the addition of the antioxidant to be tested. Both evaluation methods were validated using Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid) as a calibrator in the range of 50 to 250nM, and all parameters showed satisfactory results: specificity, linearity (r>0.99), precision (intra and interassay relative standard deviations <5%), robustness, and the limits of detection and quantitation (low and similar for both methods). The main advantage of the use of AUC is to evaluate the antioxidant potential of samples that do not present lag phase.