Genipin's potential as an anti-cancer agent: from phytochemical origins to clinical prospects.

This comprehensive review delves into the multifaceted aspects of genipin, a bioactive compound derived from medicinal plants, focusing on its anti-cancer potential. The review begins by detailing the sources and phytochemical properties of genipin, underscoring its significance in traditional medicine and its transition into contemporary cancer research. It then explores the intricate relationship between genipin's chemical structure and its observed anti-cancer activity, highlighting the molecular underpinnings contributing to its therapeutic potential. This is complemented by a thorough analysis of preclinical studies, which investigates genipin's efficacy against various cancer cell lines and its mechanisms of action at the cellular level. A crucial component of the review is the examination of genipin's bioavailability and pharmacokinetics, providing insights into how the compound is absorbed, distributed, metabolized, and excreted in the body. Then, this review offers a general and updated overview of the anti-cancer studies of genipin and its derivatives based on its basic molecular mechanisms, induction of apoptosis, inhibition of cell proliferation, and disruption of cancer cell signaling pathways. We include information that complements the genipin study, such as toxicity data, and we differentiate this review by including commercial status, disposition, and regulation. Also, this review of genipin stands out for incorporating information on proposals for a technological approach through its load in nanotechnology to improve its bioavailability. The culmination of this information positions genipin as a promising candidate for developing novel anti-cancer drugs capable of supplementing or enhancing current cancer therapies.

Antiglycation potential and antioxidant activity of genipap (Genipa americana L.) in oxidative stress mediated by hydrogen peroxide on cell culture.

Genipa americana L. is a plant widely used by folk medicine for the prevention and as an aid in the treatment of various diseases. In this work, we evaluated the anti-glycant and antioxidant activities of genipap fruit juice, as well as the influence of different temperatures (-6 °C and -80 °C) on the preservation of phenolic compounds. Purified extract from G. americana showed anti-glycant activity reducing the formation of fructosamine by up to 53% and recovered viability of cells under oxidative stress induced by H2O2. HPLC/UV-Vis analysis identified cinnamic acid as a bioactive substance and possibly responsible for the biological activities described above. Taken together, these results indicate that G. americana is a rich source of cinnamic acid with appreciable antioxidant and anti-glycant potential.

Synergic effect of natural deep eutectic solvent and high-intensity ultrasound on obtaining a ready-to-use genipin extract: Crosslinking and anti-neurodegenerative properties.

In this paper, genipin, an important natural crosslinker and anti-neurodegenerative compound, was extracted from unripe Genipa americana L., combining high-intensity ultrasound (HIUS) and natural deep eutectic solvents (NADESs). The extraction process conditions were evaluated step-by-step to reach the best genipin recovery. The obtained ready-to-use genipin-NADES extract was examined regarding its crosslinking properties and anti-neurodegenerative capacity. For the condictions tested, the highest genipin recovery was obtained using 40 % water and 60 % betaine:lactic acid NADES in molar ratio 1:3 (n/n) as the solvent, a solvent:feed ratio of 19 (w/w), and HIUS acoustic power of 14 ± 1 W. The HIUS-assisted extraction using NADES as solvent showed to be a promising and efficient green extraction technique to obtain genipin. The ready-to-use genipin-NADES extract presented crosslinking capacity and anticholinergic activity. These results indicate that genipin-NADES extract can be directly applied in hydrogels for drug delivery, films, tissue engineering, and others. Moreover, it can be used in food, supplements, and medicine to enhance their neuroprotective effect.

Study of the reaction between genipin and amino acids, dairy proteins, and milk to form a blue colorant ingredient.

Currently, one of the biggest challenges of the colorant industry is to obtain natural blue colorants. Among the different options, a blue pigment can be formed by a crosslinking reaction between genipin and primary amine groups. However, at the industrial level, obtaining an ingredient from pure compounds, such as amino acids, is economically unfeasible. The present work aimed to study the reaction and kinetics of the blue color formation, starting the study with pure compounds (genipin and amino acids) to more complex and cheaper natural sources, such as Genipa americana L. fruits and milk. The reaction kinetics of the monomers/dimers for different amino acids reacting with genipin was evaluated, as well as the preferential amino acid, genipin:amino acid ratio and pH, to obtain the most rapid and intense blue color. Finally, the blue pigment formed using milk and its proteins was characterized by SDS-PAGE. The results suggest that the reaction kinetic is influenced by the type and concentration of the amino acid used and the pH of the medium, which could facilitate the further standardization of the industrial process. We also suggested milk as an excellent reaction medium to obtain the colorant from genipin as it presents an ideal pH and favorable amino acid composition to facilitate the reaction.

Determination of Methyldopa and Paracetamol in Pharmaceutical Samples by a Low Cost Genipa americana L. Polyphenol Oxidase Based Biosensor.

Purpose: Jenipapo fruit (Genipa americana L) is a natural source of polyphenol oxidases (PPOs) whose potential in pharmaceutical analysis is noteworthy. Henceforth, this work reports the electrochemical study of a low-cost PPO-based biosensor produced from the crude extract of Jenipapo fruits and accounts a practical approach to employ this biosensor in the determination of methyldopa and paracetamol in pharmaceutical samples. Methods: In order to investigate the electrochemical properties of the biosensor, theoretical and practical approaches were employed, and both samples and the biosensor were analyzed through electrochemical impedance spectroscopy (EIS) and voltammetric techniques, namely: differential pulse voltammetry (DPV) and cyclic voltammetry (CV). Results: showcased that the biosensor presented good analytical features, as well as low detection limits (8 µmol L-1 for methyldopa and 5 µmol L-1 for paracetamol). The relative standard deviation was less than 5% mid-assay. Conclusion: The use of this biosensor is a reliable, low cost and useful alternative in the pharmaceutic determination of phenolic drugs (e.g. methyldopa and paracetamol).

Induction and growth curve of calli from leaf and nodal explants of genipap / Indução e curva de crescimento de calos obtidos de explantes foliares e nodais de jenipapeiro

The aim of this study was to determine the effect of the auxin 2,4-D (2,4-dichlorophenoxyacetic) in calli formation from leaf and nodal segments of genipap and to characterize its growth curve. Explants obtained from shoots previously established from in vitro seedlings were used for calli induction. The experimental design was completely randomized in a 3x5x2 factorial with three accessions (NB, SA, SAL), five concentrations of 2,4-D (0.0; 2.0; 4.0, 6.0 or 8.0 mg L-1) and two times of measurement for calli fresh weight (30 and 60 days). There was callus formation in all treatments tested. It was observed that the best response for callus induction from leaf segments was with 2.0 mg L-1 of 2,4-D. For the nodal segment, the response among the accessions was different due to 2,4-D concentrations. The growth curve was plotted according to the fresh weight of callus obtained at intervals of 10 days up to 60 days. Through the established growth curve, the nodal-derived calli from accession SA should be transferred to a new medium, after 40 days of culture.

O objetivo desse trabalho foi determinar o efeito da auxina 2,4-D (ácido diclorofenoxiacético) na calogênese de segmentos foliar e nodal de jenipapeiro e caracterizar sua curva de crescimento. Explantes obtidos de brotações pré-estabelecidas a partir de plântulas in vitro foram utilizados na indução de calos. O delineamento experimental utilizado foi o inteiramente casualizado em esquema fatorial 3x5x2, com três acessos (NB, SA e SAL), cinco concentrações de 2,4-D (0,0; 2,0; 4,0; 6,0 ou 8,0 mg L-1) e dois tempos de avaliação (30 e 60 dias) da massa fresca de calos. Houve formação de calos em todos os tratamentos testados. Observou-se que a melhor resposta de indução ocorreu na concentração de 2,0 mg L-1 para calos oriundos de segmentos foliares. Para o segmento nodal a resposta entre os acessos foi diferenciada em função das concentrações de 2,4-D. A curva de crescimento foi plotada a partir da massa fresca dos calos obtida em intervalos de 10 dias até os 60 dias. Através da curva de crescimento estabelecida, os calos derivados de segmentos nodais do acesso SA devem ser transferidos para um novo meio de cultura, 40 dias após à inoculação.

Development of a Polyphenol Oxidase Biosensor from Jenipapo Fruit Extract (Genipa americana L.) and Determination of Phenolic Compounds in Textile Industrial Effluents.

In this work, an innovative polyphenol oxidase biosensor was developed from Jenipapo (Genipa americana L.) fruit and used to assess phenolic compounds in industrial effluent samples obtained from a textile industry located in Jaraguá-GO, Brasil. The biosensor was prepared and optimized according to: the proportion of crude vegetal extract, pH and overall voltammetric parameters for differential pulse voltammetry. The calibration curve presented a linear interval from 10 to 310 µM (r² = 0.9982) and a limit of detection of 7 µM. Biosensor stability was evaluated throughout 15 days, and it exhibited 88.22% of the initial response. The amount of catechol standard recovered post analysis varied between 87.50% and 96.00%. Moreover, the biosensor was able to detect phenolic compounds in a real sample, and the results were in accordance with standard spectrophotometric assays. Therefore, the innovatively-designed biosensor hereby proposed is a promising tool for phenolic compound detection and quantification when environmental contaminants are concerned.

Physiological potential of jenipapo seeds stored in different packages / Potencial fisiológico de sementes de jenipapo armazenadas em diferentes embalagens

Seed storage through the reduction of its water content is an important strategy for the conservation of many plant species, but some, such as the jenipapo, are susceptible to desiccation, which may lead to loss of viability and even death, in case its water content is reduced to a critical level. The aim of this work was to evaluate the interference of different packaging conditions in the conservation of the physiological potential of jenipapo seeds stored for 105 days. Specifically, this research sought to analyze the feasibility of the use of vacuum conditions and the coating of the seed with biofilm. The evaluated treatments were: storage in paper bag, plastic bag, plastic with vacuum, plastic with seeds coated with biofilm and plastic with seeds with biofilm and vacuum condition for 15, 45, 75 and 105 days, besides the control. Seeds with biofilm were treated with cassava starch at 3% of the mass to volume ratio. The following tests were performed: water content, germination, germination speed, aerial part and root lengths, wet and dry mass of the aerial part and root. It was concluded that plastic packaging, vacuum condition and biofilm coating are not recommended for storage of jenipapo seeds. Storage in paper bags, when at 24 ºC and with 65% relative humidity for 46 days, is capable of conserving the seeds of jenipapo with germination of 60%.

O armazenamento de sementes por meio da redução do seu teor de água é uma importante estratégia para a conservação de muitas espécies vegetais, porém, algumas, como o jenipapeiro, são sensíveis à dessecação, podendo haver a perda da sua viabilidade, e até a morte, caso o seu teor de água seja reduzido a um nível considerado crítico. Neste trabalho, o objetivo foi avaliar a interferência de diferentes condições de embalagens na conservação do potencial fisiológico de sementes de jenipapo armazenadas por 105 dias. De forma específica, buscou-se analisar a viabilidade do uso de condições de vácuo e do revestimento da semente com biofilme. Os tratamentos avaliados foram: armazenamento em saco de papel, saco plástico, plástico com vácuo, plástico com sementes revestidas com biofilme e plástico com sementes com biofilme e condição de vácuo por 15, 45, 75 e 105 dias, além da testemunha. As sementes com biofilme receberam tratamento com fécula de mandioca a 3% da relação massa por volume. Os seguintes testes foram realizados: teor de água, germinação, velocidade de germinação, comprimento da parte aérea e radicular, massa úmida e seca da parte aérea e da raiz. Concluiu-se que a embalagem plástica, a condição de vácuo e o revestimento com biofilme não são recomendados para o armazenamento de sementes de jenipapo. O armazenamento em saco de papel quando realizado em ambiente com 24 ºC e 65% de umidade relativa do ar durante 46 dias é capaz de conservar as sementes de jenipapo com germinação de 60%.

Extraction of bioactive compounds from genipap (Genipa americana L.) by pressurized ethanol: Iridoids, phenolic content and antioxidant activity.

The search for compounds with functional properties from natural sources has grown in recent years as people have developed healthier habits. Therefore, the aim of this study was to evaluate the extraction of bioactive compounds from various parts of unripe genipap fruit (Genipa americana L.) by using pressurized ethanol to verify which part of the fruit provides the greatest recovery of the iridoids genipin and geniposide. Two process variables were studied: temperature (50 and 80°C) and pressure (2, 12 and 20 bar). The whole fruit and the peel, mesocarp, endocarp, endocarp+seeds and seeds of the fruit were studied. The endocarp presented with the highest recovery of genipin (48.6±0.6mg/g raw material) and the extraction from the mesocarp allowed a greater recovery of geniposide (59±1mg/g raw material). The highest values of total phenolic content were obtained with mesocarp extracts. The endocarp and mesocarp extracts presented the highest antioxidant activity as measured by FRAP and DPPH. These results are promising and support the use of unripe genipap fruit as a source of iridoids and natural antioxidants.

Allergic contact dermatitis caused by a new temporary blue-black tattoo dye - sensitization to genipin from jagua (Genipa americana L.) fruit extract.

BACKGROUND: Temporary tattoos made with an extract of the jagua fruit (Genipa americana L.) are becoming increasingly popular. It is claimed that it is 'dermatologically tested' and does not contain p-phenylenediamine. Extracts of jagua and gardenia fruits have been used by indigenous people in South America, as well as in traditional Chinese medicine, for centuries. Genipin is currently used for its cross-linking effect in the manufacture of polysaccharides, and is being investigated for its anti-inflammatory and other properties. OBJECTIVES: To report the presence of the allergenic substance genipin in a self-administered temporary tattoo dye made from the fruit juice of jagua (Genipa americana L.). PATIENTS AND METHODS: A 39-year-old female who repeatedly applied 'completely natural and 100% safe' Earth Jagua® tattoo, obtained via the internet, to her left hand developed allergic contact dermatitis within 6 weeks. Analysis of the dye showed the presence of geniposide and genipin. RESULTS: Patch tests with the dye and with its main components, including genipin, gave strong positive reactions to the latter. There was no sensitization to other ingredients or p-amino compounds. CONCLUSIONS: We report an extensively evaluated case of allergic contact dermatitis caused by a temporary Earth Jagua® tattoo. The allergen identified is genipin, a substance that is increasingly used for tattoos and as a therapeutic agent in medicine. This could result in an increase in the number of allergic reactions in the future.

One pot phytosynthesis of gold nanoparticles using Genipa americana fruit extract and its biological applications.

In this article, rapid one pot synthesis of gold nanoparticles (GNPs) using an eco-friendly extract of Genipa americana L. fruit is described. Electrospray ionization mass spectrometry (ESI-MS) and Fourier transform infrared (FTIR) spectroscopic studies demonstrated that small molecules such as genipin, genipaol, geniposide and ranolazine can act as reducer as well as stabilizers. The monodispersed, spherical GNPs were further characterized by UV-vis spectroscopy at λmax=535 nm, transmission electron microscopy (TEM), dynamic light scattering (DLS) and X-ray diffraction (XRD) analysis. This synthetic approach offers a greener and alternate route to the preparation of GNPs free from toxic chemical components and stable for 6-7 months under room temperature. The green synthesized GNPs showed weak antioxidant efficacy against 1,1-diphenyl-2-picrylhydrazyl and no cytotoxicity against A-549 and HeLa human cancer cell lines, from lung and cervix. This study opens a new industrial scope of G. americana fruit in nanoscience and as surface modified GNPs can be developed into a successful drug carrier for future pharmaceutical products.

Influence of the composition of unripe genipap (Genipa americana L.) fruit on the formation of blue pigment.

The physical and chemical characteristics of unripe genipap fruits and the proximate and amino acid compositions of the endocarp and mesocarp of the unripe fruits were determined, placing special emphasis on the possible role of the protein-amino acid fraction on the formation of the typical blue pigment of the matrix. The two parts of the fruit analyzed have low energy (49.88 kcal/100 g for mesocarp and 43.48 kcal/100 g for endocarp) and high fiber content (7.88 % for mesocarp and 16.76 % for endocarp). The endocarp showed protein content (3.19 %) five times higher than the mesocarp (0.62 %), which may explain in part the greater amounts of blue pigment formed in the endocarp when compared to the mesocarp. Furthermore, the pH found in mesocarp (4.49) and endocarp (5.21) is within the optimum range for the formation of the blue pigment. A significant color change (ΔE (*) = 26.45) was observed in endocarp during its exposure to the air for 2 h. Free aspartic and glutamic acids and cystine were the predominant amino acids in the mesocarp, while glutamic and aspartic acids and leucine were predominant in the endocarp. According to the results, the formation of blue pigment does not cause any change in the amino acid composition.

Influence of the stage of ripeness on the composition of iridoids and phenolic compounds in genipap (Genipa americana L.).

Genipap fruits, native to the Amazon region, were classified in relation to their stage of ripeness according to firmness and peel color. The influence of the part of the genipap fruit and ripeness stage on the iridoid and phenolic compound profiles was evaluated by HPLC-DAD-MS(n), and a total of 17 compounds were identified. Geniposide was the major compound in both parts of the unripe genipap fruits, representing >70% of the total iridoids, whereas 5-caffeoylquinic acid was the major phenolic compound. In ripe fruits, genipin gentiobioside was the major compound in the endocarp (38%) and no phenolic compounds were detected. During ripening, the total iridoid content decreased by >90%, which could explain the absence of blue pigment formation in the ripe fruits after their injury. This is the first time that the phenolic compound composition and iridoid contents of genipap fruits have been reported in the literature.

Efecto estimulante del extracto hidroalcohólico de Genipa americana L. (huito) en la musculatura uterina de ratas Holtzman estrogenizadas sin preñar / Stimulatory effect of the hydroalcoholic extract of Genipa americana L. (huito) in the uterine musculature of Holtzman rats estrogenized nonpregnant

Objetivo: Demostrar el efecto estimulante que presenta el extracto hidroalcohólico de Genipa americana L. (Huito) en la musculatura uterina de ratas Holtzman estrogenizadas sin preñar. Método: Se utilizaron 15 ratas Holtzman adultas hembras de pesos entre 250 y 300g con 2 a 2.5 meses de vida, previa estrogenización con valerato de estradiol 17B 10mg/ml a concentración de 10 mg/kg. Se extrajo 30 muestras de útero, colocados en equipo de órgano aislado (Tissue-Organ Bath System TM). Luego se realizó la medición basal de las 3 variables de estudio: Tensión máxima, frecuencia y máxima duración de la contracción uterina, posterior a esto se administró sucesivamente diferentes concentraciones del extracto hidroalcohólico de Genipa americana L. (10 mg/ml, 25 mg/ml, 50 mg/ml, 100 mg/ml, 500 mg/ml y 1 g/ml). Los datos obtenidos fueron estudiados a través del análisis estadístico usando el programa estadístico SPSS 19.0 para Microsoft Windows. Se determinó las medidas de tendencia central y de dispersión para las tres variables de estudio, y en cada una de las concentraciones se trabajó con un intervalo de confianza para la media al 95 por ciento. Resultados: Se realizó un análisis de varianza (ANOVA) para máxima tensión y máxima duración de la contracción uterina para cada concentración administrada con un p<0.05, y se demostró que existen diferencias significativas; por lo tanto el huito causa efecto estimulante de las variables de máxima tensión y máxima duración respecto a la medición basal. En frecuencia mediante el Test de Kruskal-Wallis (p<0.05) mostró que el huito si afectan en la frecuencia de las contracciones. Se realizaron pruebas pareadas T-Student (p<0.05) para analizar respuestas del basal versus administración del huito en los tres parámetros observados de la contracción mostrando que existe un efecto diferenciado entre los basales y las concentraciones de huito. En los resultados obtenidos de los gráficos de concentración-respuesta comparando los tres...

Objective: To demonstrate the stimulating effect that hydroalcoholic extract of Genipa americana L. (Huito) has in the uterine musculature Holtzman rats estrogenized nonpregnant. Method: were used 15 female Holtzman adult rats weighing between 250 and 300 g with 2 to 2.5 months of life, prior estrogenization by estradiol valerate 17B at 10mg/ml concentration of 10mg/kg. 30 samples of uterus were extracted, placed in isolated organ equipment (Tissue - Organ Bath System TM). Then, the baseline measurement of the 3 study variables was performed: Subsequent to this is successively administered different concentration of the hydroalcoholic extract of Genipa americana L (10 mg/ml, 25 mg/ml, 50 mg/ml, 100 mg/ml, 500 mg/ml and 1 g/ml). The data obtained were studied by statistical analysis using the SPSS v.19.0 for Microsoft Windows. Measures of central tendency and dispersion for the three study variables was determined, and in each of the concentrations worked with a confidence interval for the average 95 per cent. Results: Analysis of variance (ANOVA) for maximum voltage and maximum duration of uterine contraction for each concentration delivered with a p<0.05 was performed and it demonstrated that significant differences exist, therefore huito causes stimulating effect the variables maximum voltage and maximum duration from baseline measurement. In frequency, the Kruskal-Wallis test (p<0.05) showed that huito affects the frequency of contractions. Paired t- Student test (p<0.05) were performed for analyzing responses from baseline versus administration in the three parameters observed of huito concentrations, showing that there is a differential effect between the baseline and huito concentrations. In the results of the graphs of concentration-response comparing the three parameters noted that for each increase in concentration huito the stimulus obtained by the administration of huito tends to be lower. Conclusion: The hydroalcoholic extract of Genipa americana...