RESUMO
BACKGROUND: Extensive antifungal drug use has enhanced fungal resistance, resulting in persistent mycoses. Combining antifungal plant extracts/compounds with these drugs offers good alternatives to increase the activity of both partners, minimize side effects, and overcome drug resistance. In our previous study, Phytolacca tetramera berries extracts demonstrated activity against Candida spp., correlating with the amount of the main constituent phytolaccoside B and its genin, phytolaccagenin. The extracts and phytolaccagenin altered the fungal plasma membrane by binding to ergosterol, whereas phytolaccoside B increased chitin synthase activity. However, the presence of triterpenoid saponins in Phytolacca spp. has been linked to acute toxicity in humans. PURPOSE: This study aimed to evaluate combinations of P. tetramera berries extracts, phytolaccoside B and phytolaccagenin, together with commercial antifungals [amphotericin B, fluconazole, itraconazole, posaconazole, and caspofungin] against Candida albicans and Candida glabrata, to find synergistic effects with multi-target actions, in which the doses of both partners are reduced, and therefore their toxicity. Additionally, we intended to explore their anti-virulence capacity, thereby hindering the development of drug-resistant strains. METHODS: The effects of these combinations were evaluated using both the checkerboard and isobologram methods. Fractional Inhibitory Concentration Index and Dose Reduction Index were calculated to interpret the combination results. To confirm the multi-target effect, studies on mechanisms of action of synergistic mixtures were performed using ergosterol-binding and quantification assays. The ability to inhibit Candida virulence factors, including biofilm formation and eradication from inert surfaces, was also evaluated. Quantification of active markers was performed using a validated UHPLC-ESI-MS method. RESULTS: Eight synergistic combinations of P. tetramera extracts or phytolaccagenin (but not phytolaccoside B) with itraconazole or posaconazole were obtained against C. albicans, including a resistant strain. These mixtures acted by binding to ergosterol, decreasing its whole content, and inhibiting Candida biofilm formation in 96-well microplates and feeding tubes in vitro, but were unable to eradicate preformed biofilms. CONCLUSIONS: This study demonstrated the synergistic and anti-virulence effects of P. tetramera berries extracts and phytolaccagenin with antifungal drugs against Candida spp., providing novel treatment avenues for fungal infections with reduced doses of both natural products and commercial antifungals, thereby mitigating potential human toxicity concerns.
Assuntos
Antifúngicos , Candida albicans , Sinergismo Farmacológico , Frutas , Testes de Sensibilidade Microbiana , Phytolacca , Extratos Vegetais , Antifúngicos/farmacologia , Antifúngicos/química , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Frutas/química , Candida albicans/efeitos dos fármacos , Phytolacca/química , Candida glabrata/efeitos dos fármacos , Saponinas/farmacologia , Candida/efeitos dos fármacosRESUMO
Magonia pubescens is a natural species from the Brazilian cerrado biome. Its fruits and seeds are used in the treatment of seborrheic dermatitis, a common inflammatory skin disease. In this work, the known compounds lapachol, stigmasterol, maniladiol and scopoletin were isolated from hexane and dichloromethane extracts of M. pubescens branches. The aqueous extract of this material was fractioned through a liquid-liquid partition and the obtained fractions were analyzed by UHPLC-MS/MS. The results obtained were compared with data from three databases, leading to the putative identification of 51 compounds from different classes, including flavonoids, saponins and triterpenes. The cytotoxicity of aqueous fractions was assayed against breast cancer (MDA-MB-231) and leukemia (THP-1 and K562) cells. The best activity was observed for fraction AE3 against MDA-MB-231 cells (IC50 30.72 µg.mL-1).
Assuntos
Antineoplásicos Fitogênicos , Neoplasias da Mama , Compostos Fitoquímicos , Extratos Vegetais , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Neoplasias da Mama/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Linhagem Celular Tumoral , Feminino , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/química , Triterpenos/farmacologia , Triterpenos/química , Brasil , Leucemia/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/química , Células K562 , Cromatografia Líquida de Alta Pressão , Espectrometria de Massas em Tandem , Saponinas/farmacologia , Saponinas/química , Células THP-1 , Estrutura MolecularRESUMO
SUMMARY: This study evaluated the phytochemical screening, antioxidant capacity, and in vitro anticancer activities of four plants namely, Gypsophila capillaris, Anabasis lachnantha, Haloxylon salicornicum, and Horwoodia dicksoniae which belong to four different families: Caryophyllaceae, Amaranthaceae, Chenopodiaceae, Brassicaceae, respectively. The total phenolics, anthocyanins, saponins, total antioxidant capacity (TAC), and DPPH assays were determined by spectrophotometer. In vitro anticancer activity was assessed using two human cancer cell lines; hepatocellular carcinoma (HepG-2) and breast adenocarcinoma (MCF-7) to estimate the inhibition concentration 50 % (IC50). The results showed that H. dicksoniae has the highest concentrations of phenolics and saponins, while H. salicornicum has the highest DPPH. The highest concentration of TAC was found in G. capillaries. Among the tested extracts, G. capillaries and H. salicornicum have the potential activity against MCF-7 and HepG-2 cell lines in vitro. The content of polyphenols in G. capillaries was profiled by high-performance liquid chromatography (HPLC). The highest concentration among the phenolic compounds was chlorogenic (60.8 µg/ml) while the highest concentration among the flavonoid compounds was hesperidin (1444.92 µg/ml). In summary, G. capillaries and H. salicornicum extracts have potent anticancer activity against HepG-2 and MCF-7 cell lines.
Este estudio evaluó la detección fitoquímica, la capacidad antioxidante y las actividades anticancerígenas in vitro de cuatro plantas, Gypsophila capillaris, Anabasis lachnantha, Haloxylon salicornicum y Horwoodia dicksoniae, que pertenecen a cuatro familias diferentes: Caryophyllaceae, Amaranthaceae, Chenopodiaceae y Brassicaceae, respectivamente. Los ensayos de fenólicos totales, antocianinas, saponinas, capacidad antioxidante total (TAC) y DPPH se determinaron mediante espectrofotómetro. La actividad anticancerígena in vitro se evaluó utilizando dos líneas celulares de cáncer humano; carcinoma hepatocelular (HepG-2) y adenocarcinoma de mama (MCF- 7) para estimar la concentración de inhibición del 50 % (IC50). Los resultados indicaron que H. dicksoniae tiene las concentraciones más altas de fenólicos y saponinas, mientras que H. salicornicum tiene el DPPH más alto. La mayor concentración de TAC se encontró en G. capillaries. Entre los extractos probados, G. capillaries y H. salicornicum tienen actividad potencial contra líneas celulares MCF-7 y HepG-2 in vitro. El contenido de polifenoles en G. capillaries se perfiló mediante cromatografía líquida de alta resolución (HPLC). La concentración más alta entre los compuestos fenólicos fue clorogénica (60,8 µg/ml), mientras que la concentración más alta entre los compuestos flavonoides fue la hesperidina (1444,92 µg/ml). En resumen, los extractos de Gypsophila capillaris y H. salicornicum tienen una potente actividad anticancerígena contra las líneas celulares HepG-2 y MCF-7.
Assuntos
Humanos , Plantas Medicinais/química , Antineoplásicos/química , Antioxidantes/química , Fenóis/análise , Saponinas/análise , Arábia Saudita , Técnicas In Vitro , Cromatografia Líquida de Alta Pressão , Metabolômica , Células Hep G2/efeitos dos fármacos , Células MCF-7/efeitos dos fármacos , Compostos Fitoquímicos , Antocianinas/análise , Antineoplásicos/farmacologia , Antioxidantes/farmacologiaRESUMO
Rubus imperialis Chum. Schl. (Rosaceae) have demonstrated some pharmacological activities, including gastroprotective action. However, genotoxic effects of R. imperialis extract was also reported. Since niga-ichigoside F1 (NIF1) is a major compound of this plant species, and which has proven pharmacological properties, it is essential to investigate whether this compound is responsible for the observed toxicity. Therefore, the objective of this study was to analyze the effects of NIF1 on HepG2/C3A cells for possible cytogenotoxicity, cell cycle and apoptosis influence, and expression of genes linked to the DNA damage, cell cycle, cell death, and xenobiotic metabolism. The results showed no cytogenotoxic effects of NIF1 at concentrations between 0.1 and 20 µg/ml. Flow cytometry also showed no cell cycle or apoptosis disturbance. In the gene expression analysis, none of the seven genes investigated showed altered expression. The data indicate that NIF1 has no cytogenotoxic effects, and no interruption of the cell cycle, or induction of apoptosis, apparently not being responsible for the cytotoxic effects observed in the crude extract of R. imperialis.
Assuntos
Apoptose , Ciclo Celular , Humanos , Células Hep G2 , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Rubus/química , Dano ao DNA/efeitos dos fármacos , Extratos Vegetais/toxicidade , Extratos Vegetais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Saponinas/toxicidade , Saponinas/farmacologiaRESUMO
The study investigated Chenopodium berlandieri to analyze its oleanolic acid (OA) content. Response surface methodology with central composite design was used to improve saponin extraction, varying temperature, ethanol, and sample-to-solvent ratio. Best conditions (65 °C, 50% ethanol, 1:10 ratio) yielded 53.45 ± 0.63 mg/g of extract from Huauzontle seeds. Temperature linearly impacted extract yield, while temperature and ethanol influenced total saponin content. Hydrolyzing saponin-rich extracts produced OA-rich extracts. Characterization via HPLC-ELSD and LC-MS identified OA4 as the most concentrated OA saponin (5.54 ± 0.16 mg/g). OA alone reached 2.02 ± 0.12 mg/g. Acid hydrolysis increased OA content by up to 3.27×, highlighting the potential of hydrolyzed Huauzontle extracts as a natural ingredient for various industries due to enhanced OA content.
Assuntos
Chenopodium , Ácido Oleanólico , Extratos Vegetais , Saponinas , Ácido Oleanólico/química , Ácido Oleanólico/análise , Saponinas/química , Hidrólise , Extratos Vegetais/química , Chenopodium/química , Cromatografia Líquida de Alta Pressão , Sementes/químicaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Pfaffia glomerata (Spreng.) Pedersen, Amaranthaceae, is found in South America, mainly in Brazil, where it is considered a species of great medicinal interest owing to its popular use as a tonic, aphrodisiac, anti-inflammatory, and analgesic. These properties can be attributed to the presence of the phytosteroid, 20-Hydroxyecdysone (ß-ecdysone), the main compound found in its roots. AIM OF THE REVIEW: This review aims to provide information about the botanical characteristics, ethnomedicinal uses, the phytochemistry, the biological activities, and the biotechnology of P. glomerata, an important species to local communities and groups researching medicinal plants of South America. MATERIALS AND METHODS: The information available on P. glomerata was collected from scientific databases (ScienceDirect, PubMed/MEDLINE, SciELO, and Scopus) until June 7, 2023, using the search terms "Pfaffia glomerata", "Pfaffia glomerata (Spreng.) Pedersen", and "Brazilian ginseng". The review includes studies that evaluated the botanical, ethnopharmacological, and phytochemical aspects, biological properties, nutraceutical uses, and the application of biotechnology for improving the biosynthesis of metabolites of interest. RESULTS: A total of 207 studies were identified, with 81 articles read in full. Seventy-six studies were included for qualitative synthesis. Overall, 40 compounds belonging to different classes are presented in this review, including ecdysteroids, triterpenes, saponins, flavonoids, anthraquinones, tannins, coumarins, alkaloids, and polysaccharides. Among them, flavonoids, anthraquinones, tannins, coumarins, and alkaloids were only putatively identified. ß-Ecdysone, triterpenes, saponins, and polysaccharides are the chemical components most frequently identified and isolated from P. glomerata and possibly responsible for ethnopharmacological use and the biological activities of this species, with important in vitro and in vivo activities, such as anti-inflammatory, antidepressant, aphrodisiac, analgesic, gastroprotective, antioxidant, and prebiotic. CONCLUSIONS: This review summarizes discussions about the P. glomerata species, highlighting its ethnopharmacological, chemical, biotechnological, and nutraceutical importance. New scientific studies on this species are encouraged in the search for new therapeutic molecules with pharmaceutical potential and nutraceutical applications.
Assuntos
Alcaloides , Amaranthaceae , Afrodisíacos , Botânica , Saponinas , Triterpenos , Etnofarmacologia , Ecdisterona , Taninos , Amaranthaceae/química , Brasil , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico , Prebióticos , Analgésicos , Antraquinonas , Anti-Inflamatórios , Cumarínicos , Flavonoides , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , FitoterapiaRESUMO
Eclipta prostrata Linn. is an annual herbaceous plant used in traditional medicine, commonly known as "Trailing Eclipta" or False Daisy in English, ' Keekirindiya ' in Sinhala and ' Kayyantakara' in Tamil. The aim of this study was to conduct a detailed pharmacognostical evaluation of E. prostrata found in Sri Lanka. Anatomical, physicochemical, phytochemical studies, and quantification of phyto - constituents were performed as per WHO guidelines. Whole plant was sequ entially extracted into solvents with different polarities. Phytochemical screening and Thin Layer Chromatography (TLC) fingerprinting were carried out. Anatomical study and powder microscopy revealed useful diagnostic features. Physicochemical parameters such as moisture content, ash values (total, acid insoluble, water soluble) and extractable matter in water and ethanol were evaluated. Phytochemical screening and TLC fingerprinting revealed the presence of different types of phyto - constituents. Alkaloid, tannin, saponin, total flavonoid and total polyphenol contents were quantified. In conclusion, pharmacognostical study aids in establishing the standardization parameters of E. prostrata found in Sri Lanka.
Eclipta prostrata Linn. es una planta herbácea anual utilizada en la medicina tradicional, comúnmente conocida como "Trailing Eclipta" o False Daisy en inglés, 'Keekirindiya' en sinhala y 'Kayyan takara' en tamil. El objetivo de este estudio fue realizar una evaluación farmacognóstica detallada de E. prostrata encontrada en Sri Lanka. Se llevaron a cabo estudios anatómicos, fisicoquímicos, fitoquímicos y cuantificación de fitoconstituyentes según l as directrices de la OMS. Se extrajo secuencialmente la planta entera en solventes con diferentes polaridades. Se realizaron pruebas de tamizaje fitoquímico y huellas dactilares de cromatografía en capa delgada (TLC). El estudio anatómico y la microscopía en polvo revelaron características diagnósticas útiles. Se evaluaron parámetros fisicoquímicos como el contenido de humedad, los valores de ceniza (total, insoluble en ácido, soluble en agua) y la materia extraíble en agua y etanol. Las pruebas de tamizaje fitoquímico y las huellas dactilares de TLC revelaron la presencia de diferentes tipos de fitoconstituyentes. Se cuantificaron los contenidos de alcaloides, taninos, saponinas, flavonoides totales y polifenoles totales. En conclusión, el estudio farmacogn óstico ayuda a establecer los parámetros de estandarización de E. prostrata encontrada en Sri Lanka.
Assuntos
Eclipta/química , Saponinas/análise , Sri Lanka , Flavonoides/análise , Cromatografia em Camada Fina , Eclipta/anatomia & histologia , Polifenóis/análiseRESUMO
The aim was to report cases and risk factors for hepatogenous photosensitization in lambs kept on Brachiaria spp. pastures and supplemented with levels of extruded urea (EU). The herd consisted of 69 Texel crossbred lambs with known parentage (fathers and mothers adapted to the consumption of forage of the genus Brachiaria), randomly divided into 5 groups and distributed in individual paddocks for each group. The animals were supplemented with increasing levels of EU (Amireia® 200S): 0, 6, 12, 18, and 24 g of EU per 100 kg-1 of body weight (BW). The concentration of protodioscin was estimated in the mixed pastures of Brachiaria spp. (cv. Marandu and cv. Basilisk), structural components (leaf, stem, and dead material), samples of each cultivar, and in the months of December (2018), February, and April (2019). The animals were examined daily, and when behavioral changes were identified, they underwent clinical examinations and anamnesis. Weighing was performed every 14 days, followed by necropsy and serum biochemical analysis, including gamma-glutamyltransferase (GGT). The highest concentrations of protodioscin (p < 0.0001) were found in the pastures used by animals supplemented without extruded urea (7.07 ± 0.56), in the Basilisk cultivar (11.35 ± 0.06), in the leaf blade components (2.08 ± 0.05), and thatch (2.20 ± 0.00), and in the month of April (7.34 ± 0.29) (the month with the lowest rainfall), respectively. Fourteen (20.29%) cases of photosensitization were observed in lambs, of which six recovered, and eight died. Serum GGT levels ranged from 42.2 to 225 IU/L; however, in animals that died, values ranged from 209.4 to 225 IU/L. The use of levels 12 g and 18 g per 100 kg-1 of body weight of extruded urea may contribute to the lower occurrence of photosensitization, as the animals selected pastures with lower protodioscin content, presenting a smaller number of cases.
Assuntos
Brachiaria , Diosgenina , Ureia , Animais , Masculino , Ração Animal/análise , Brasil , Suplementos Nutricionais , Diosgenina/análogos & derivados , gama-Glutamiltransferase/sangue , Transtornos de Fotossensibilidade/veterinária , Saponinas , Ovinos , Doenças dos Ovinos , Ureia/sangue , FemininoRESUMO
Secretory structures in plants play a crucial role in producing bioactive compounds. Despite the potential of the Swartzia genus, comprehensive studies in this context are still scarce. Swartzia is a legume tree (Fabaceae) that occurs in the Brazilian Atlantic Forest, a biodiversity hotspot, and includes species such as Swartzia flaemingii. Therefore, we aim to achieve: (1) identify and characterize the key secretory sites responsible for saponin production in S. flaemingii leaflets; (2) confirm the presence of saponins in S. flaemingii leaves by comparing them with known chemical profiles of other Swartzia species; (3) assess the potential hemolytic and cytotoxic effects of crude leaf extracts. Our investigation unveils the presence of phenolic idioblasts, mucilage cells, and articulate laticifers, which play pivotal roles in defense and adaptation. Notably, we report the first-ever ultrastructural details of laticifers in a legume species. Additionally, oleanane-type saponins were identified in the leaves, giving insights into the chemotaxonomic profile of Swartzia. The crude extracts show low cytotoxicity levels, showcasing as a promising alternative source of saponins. This investigation reinforces the importance of conserving plants in threatened regions like the Atlantic Forest, a global biodiversity hotspot facing substantial anthropogenic pressures.
Assuntos
Fabaceae , Saponinas , Fabaceae/química , Árvores , Saponinas/farmacologia , Saponinas/química , BrasilRESUMO
The present study aimed to determine the biological properties of an extract of Solanum aculeatissimum aqueous extract (SaCE) alone as well as silver nanoparticles (AgNPs) generated by green synthesis utilizing S. aculeatissimum aqueous extract (SaCE). These synthesized SaCE AgNPs were characterized using UV-VIS spectrophotometry, scanning transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), zeta potential (ZP), dynamic light scattering (DLS). Determination of total polyphenols, flavonoids, saponins content was conducted. In addition, high performance liquid chromatography-mass spectrometry (HPLC-MS) was employed to identify constituents in this extract. Antioxidant activity was determined by DPPH radical scavenging and ferric ion reducing power (FRAP) methods. Antiglycation activity was demonstrated through relative mobility in electrophoresis (RME) and determination of free amino groups. The inhibitory activity on tyrosinase was also examined. Molecular docking analyses were performed to assess the molecular interactions with DNA and tyrosinase. The antitumor activity SaCE was also measured. Phytochemical analysis of SaCE and AgNPs showed presence polyphenols (1000.41 and 293.37 mg gallic acid equivalent/g), flavonoids (954.87 and 479.87 mg rutin equivalent/g), saponins (37.89 and 23.01% total saponins), in particular steroidal saponins (aculeatiside A and B). Both SaCE and AgNPs exhibited significant antioxidant (respectively, 73.97%, 56.27% in DPPH test, 874.67 and 837.67 µM Trolox Equivalent/g in FRAP test) and antiglycation activities (72.81 and 67.98% free amino groups, results observed in RME). SaCE and AgNPs presented 33.2, 36.1% inhibitory activity on tyrosinase, respectively. In silico assay demonstrated interaction between steroidal saponins, DNA or tyrosinase. SaCE exhibited antitumor action against various human tumor cells. Data demonstrated that extracts SaCE alone and AgNPs synthesized from SaCE presented biological properties of interest for application in new therapeutic formulations in medicine.