Five Underutilized Ecuadorian Fruits and Their Bioactive Potential as Functional Foods and in Metabolic Syndrome: A Review.

The Ecuadorian Amazon harbors numerous wild and cultivated species used as food, many of which are underutilized. This review explores the bioactive potential of five such fruits-Borojó (Alibertia patinoi); Chonta (Bactris gasipaes); Arazá (Eugenia stipitata); Amazon grape (Pourouma cecropiifolia), a wild edible plant; and Cocona (Solanum sessiliflorum)-and their applications against metabolic syndrome. This study highlights their health-promoting ingredients and validates traditional medicinal properties, emphasizing their significance in improving health and mitigating the effects of the Western diet. These fruits, integral to Ecuadorian cuisine, are consumed fresh and processed. Chonta is widely cultivated but less prominent than in pre-Hispanic times, Borojó is known for its aphrodisiac properties, Cocona is traditional in northern provinces, Arazá is economically significant in food products, and Amazon grape is the least utilized and researched. The fruits are rich in phenolics (A. patinoi, E. stipitata) and carotenoids (B. gasipaes, E. stipitata), which are beneficial in controlling metabolic syndrome. This study advocates for more research and product development, especially for lesser-known species with high phenolic and anthocyanin content. This research underscores the economic, cultural, and nutritional value of these fruits, promoting their integration into modern diets and contributing to sustainable agriculture, cultural preservation, and public health through functional foods and nutraceuticals.

Synthesis and Evaluation of Biological Activities of Bis(spiropyrazolone)cyclopropanes: A Potential Application against Leishmaniasis.

This work focuses on the search and development of drugs that may become new alternatives to the commercial drugs currently available for treatment of leishmaniasis. We have designed and synthesized 12 derivatives of bis(spiropyrazolone)cyclopropanes. We then characterized their potential application in therapeutic use. For this, the in vitro biological activities against three eukaryotic models-S. cerevisiae, five cancer cell lines, and the parasite L. mexicana-were evaluated. In addition, cytotoxicity against non-cancerous mammalian cells has been evaluated and other properties of interest have been characterized, such as genotoxicity, antioxidant properties and, in silico predictive adsorption, distribution, metabolism, and excretion (ADME). The results that we present here represent a first screening, indicating two derivatives of bis(spiropyrazolone)cyclopropanes as good candidates for the treatment of leishmaniasis. They have good specificity against parasites with respect to mammalian cells.

Natural Compounds as Modulators of Cell Cycle Arrest: Application for Anticancer Chemotherapies.

Natural compounds from various plants, microorganisms and marine species play an important role in the discovery novel components that can be successfully used in numerous biomedical applications, including anticancer therapeutics. Since uncontrolled and rapid cell division is a hallmark of cancer, unraveling the molecular mechanisms underlying mitosis is key to understanding how various natural compounds might function as inhibitors of cell cycle progression. A number of natural compounds that inhibit the cell cycle arrest have proven effective for killing cancer cells in vitro, in vivo and in clinical settings. Significant advances that have been recently made in the understanding of molecular mechanisms underlying the cell cycle regulation using the chemotherapeutic agents is of great importance for improving the efficacy of targeted therapeutics and overcoming resistance to anticancer drugs, especially of natural origin, which inhibit the activities of cyclins and cyclin-dependent kinases, as well as other proteins and enzymes involved in proper regulation of cell cycle leading to controlled cell proliferation.

Cytotoxic, antioxidative, genotoxic and antigenotoxic effects of Horchata, beverage of South Ecuador.

BACKGROUND: "Horchata" is an herbal mixture infusion consumed in Southern Ecuador; 66% of its plants are anti-inflammatory medicinal plant, and 51% are analgesics. Anti-inflammatory substances can prevent carcinogenesis mediated by cytotoxic effects and can prevent DNA damage. The aim of this study was to evaluate the cytotoxicity and apoptotic/antigenotoxic effects of horchata as well as its mechanism. METHODS: Nine different varieties of horchata were prepared in the traditional way and then freeze-dried. Phytochemical screening tested for the presence of secondary metabolites using standard procedures and antioxidant activities. The cytotoxic activity was evaluated on cerebral astrocytoma (D-384), prostate cancer (PC-3), breast cancer (MCF-7), colon cancer (RKO), lung cancer (A-549), immortalized Chinese hamster ovary cells (CHO-K1), and human peripheral blood lymphocytes via a MTS assay. The pro-apoptotic effects were evaluated with Anexin V/Propidium Iodide and western blot of Bax, Bcl-2, TP53, and TP73. Induction and reduction of ROS were assessed by fluorimetry. Genotoxic and antigenotoxic effects were evaluated with a comet assay and micronuclei on binucleated cells. RESULTS: Five of nine horchatas had cytotoxic effects against D-384 while not affecting normal cells. These horchatas induce cell death by apoptosis modulated by p53/p73. In CHO-K1 cells, the horchatas decrease the damage induced by hydrogen peroxide and Mitomycin C measured in the comet and micronucleus assay respectively. CONCLUSIONS: The IC50 range of effective horchatas in D-384 was 41 to 122 µg·mL-1. This effect may be related to its use in traditional medicine (brain tonic). On the other hand, immortalized Chinese hamster ovary cells (CHO-K1) and lymphocytes did not show a cytotoxic effect. The most potent horchata induced apoptosis via a p53/p73-mediated mechanism. The horchatas present antigenotoxic properties, which may be related to the antioxidant capacity. Future studies on horchata components are necessary to understand the interactions and beneficial properties.

Development of anticancer drugs based on the hallmarks of tumor cells.

Cancer remains a public health problem with a high unmet medical demand. However, in recent decades, the knowledge of several functional molecular and biological traits that distinguish tumor cells from normal cells, known as the hallmarks of cancer as described by Hannahan and Weinberg, has led to new and modern therapeutic approaches against this disease. Most cancer drugs are deliberately developed for specific molecular targets that involve these hallmarks. In this review, we address the currently available cancer drugs and development of new drugs from the perspective of their interaction with these hallmarks as well as the pathways and mechanisms involved.

Exploring the Antioxidant Potential of Tragia volubilis L.: Mitigating Chemotherapeutic Effects of Doxorubicin on Tumor Cells.

Several plants of the genus Tragia L. have shown antibacterial, fungicidal, and antiproliferative activity, among other types of activities; however, most species of the genus have not been investigated. Tragia volubilis L. is native to tropical America and Africa, and although it has been reported as medicinal in the literature, it has not been thoroughly investigated. In this study, the phytochemical screening, isolation, and identification of compounds and the determination of the antioxidant activity of the aqueous extract of Tragia volubilis L. and its partitions were carried out. Ethyl acetate and n-butanol partitions of the extract present high antioxidant activity according to the Antioxidant Activity Index. Due to their activity, these partitions were tested on RKO cells as a representative model, both individually and in combination with Doxorubicin. It was found that the partitions significantly reduced the effect of Doxorubicin, as well as the expression of proteins involved in DNA damage and cell death. While the reduction of the chemotherapeutic effect of Doxorubicin on tumor cells may not be a desired outcome in therapeutic settings, the findings of the study are valuable in revealing the antioxidant potential of Tragia volubilis L. and its partitions. This highlights the importance of carefully regulating the application of antioxidants, especially in the context of cancer chemotherapy.

Chenopodium quinoa Willd. and Amaranthus hybridus L.: Ancestral Andean Food Security and Modern Anticancer and Antimicrobial Activity.

The species Chenopodium quinoa Willd. and Amaranthus hybridus L. are Andean staples, part of the traditional diet and gastronomy of the people of the highlands of Colombia, Ecuador, Peru, Bolivia, northern Argentina and Chile, with several ethnopharmacological uses, among them anticancer applications. This review aims to present updated information on the nutritional composition, phytochemistry, and antimicrobial and anticancer activity of Quinoa and Amaranth. Both species contribute to food security due to their essential amino acid contents, which are higher than those of most staples. It is highlighted that the biological activity, especially the antimicrobial activity in C. quinoa, and the anticancer activity in both species is related to the presence of phytochemicals present mostly in leaves and seeds. The biological activity of both species is consistent with their phytochemical composition, with phenolic acids, flavonoids, carotenoids, alkaloids, terpenoids, saponins and peptides being the main compound families of interest. Extracts of different plant organs of both species and peptide fractions have shown in vitro and, to a lesser degree, in vivo activity against a variety of bacteria and cancer cell lines. These findings confirm the antimicrobial and anticancer activity of both species, C. quinoa having more reported activity than A. hybridus through different compounds and mechanisms.

Peach Palm (Bactris gasipaes Kunth.): Ancestral Tropical Staple with Future Potential.

A pre-Columbian staple, Bactris gasipaes Kunth. is a palm tree domesticated around 4000 years ago, so appreciated that a Spanish chronicler wrote in 1545, "only their wives and children were held in higher regard" by the Mesoamerican natives. The peach palm is an integral part of the foodways and gastronomy of Ecuador, Colombia, Bolivia, Peru, Brazil, and other tropical American countries; meanwhile, it is almost unknown in the rest of the world, except for hearts of palm. Although abundant, the species faces anthropogenic threats. The purpose of this study is to describe and summarize the physicochemical, nutritional, and bioactive characteristics of the peach palm and its two main alimentary products: hearts of palm and fruits, highlighting the functional and antioxidant potential of the latter, showing both ancestral and modern uses. There is active research on peach palm products and coproducts that aim for better, more sustainable uses of its traditional and recently found properties. The review and presentation of studies on this strategically relevant species can motivate the protection of endangered populations and stimulate new lines of research to advance development in the food, pharmaceutical, and cosmetic industries, with fair trade, sustainable development goals, and adaptation to climate change in mind.

Is the anemia in men an effect of the risk of crude oil contamination?

Pollution from oil spills can seriously affect many ecosystem processes and human health. Many articles have evaluated the impact of oil spills on human health. However, most of these articles focus on occupational exposure. The effect on people living in the areas affected by oil pollution is rarely studied. Approximately 640 million people worldwide live in areas at risk of oil pollution. Thus, studying the impact of this pollution on human health should be a priority. Here, we evaluate the presence of anemia in relation to crude oil exposure in men living in areas at risk of oil contamination in the Ecuadorian Amazon (Orellana and Napo). We evaluated the hematological and biochemical parameters of 135 participants. We divided the participants into three groups according to exposure: low, medium, and high. Our results showed a significant association between exposure risk and hemoglobin and hematocrit concentration. Groups with medium- and high- contamination exposure had levels below normal values in hemoglobin and hematocrit in more than 30% and 26% of the population, respectively. In conclusion, we found that crude oil affected human health, and the prevalence of the anemia in men was dependent of the level of contamination.

Onoseriolide, from Hedyosmum racemosum, induces cytotoxicity and apoptosis in human colon cancer cells.

The number of colon cancer patients is increasing, and new alternatives for treatment are important. We focused on the sesquiterpene lactone onoseriolide from Hedyosmum racemosum, which is widely used in traditional medicine. This compound was evaluated to determine its cytotoxic effect and the mechanism of cell death that is induced in the human colon cancer cell line RKO. A dose-dependent decrease in cell viability was observed. p53 expression increased followed by an increase in p21 expression, which is involved in cell cycle arrest in the G2/M phase. Caspase-3 activation and PARP-1 cleavage, which are apoptotic markers, were also monitored. Autophagy markers were also studied, and Beclin 1 was downregulated, while LC-3II increased in a dose-dependent manner. There were no changes in SQSTM1/p62 regulation. Onoseriolide exerts cytotoxic and cytostatic effects, activating the autophagy pathway as a protective mechanism and apoptosis as the cell death pathway.

Synthesis of 4,4'-(arylmethylene)bis(3-methyl-1-phenyl-1H-pyrazol-5-ols) and evaluation of their antioxidant and anticancer activities.

BACKGROUND: Pyrazoles have attracted particular attention due to the diverse biological activities associated with this heterocyclic system, and some have been shown to be cytotoxic to several human cell lines. Several drugs currently on the market have this heterocycle as the key structural motif, and some have been approved for the treatment of different types of cancer. RESULTS: 4,4'-(Arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized by a three components reaction of 3-methyl-1-phenyl-5-pyrazolone (1) with various benzaldehydes 2 catalyzed by sodium acetate at room temperature. The structures of all synthesized compounds were characterized by physicochemical properties and spectral means (IR and NMR) and were evaluated for their radical scavenging activity by DPPH assay and tested in vitro on colorectal RKO carcinoma cells in order to determine their cytotoxic properties. All 4,4'-(arylmethylene)bis(1H-pyrazol-5-ols) derivatives 3a-q were synthetized in high to excellent yield, and pure products were isolated by simple filtration. All compounds have good radical scavenging activity, and half of them are more active than ascorbic acid used as standard. CONCLUSION: Several derivatives proved to be cytotoxic in the RKO cell line. In particular, compound 3i proved to be a very potent scavenger with an IC50 of 6.2 ± 0.6 µM and exhibited an IC50 of 9.9 ± 1.1 µM against RKO cell. Autophagy proteins were activated as a survival mechanism, whereas the predominant pathway of death was p53-mediated apoptosis.

Cytotoxic Property of Grias neuberthii Extract on Human Colon Cancer Cells: A Crucial Role of Autophagy.

Traditional herbal medicine has become an important alternative in the treatment of various cancer types, including colon cancer, which represents one of the main health problems around the world. Therefore, the search for new therapies to counteract this disease is very active. Grias neuberthii is an endemic plant located in the Ecuadorian Amazon region, which has been used in traditional medicine for its pharmacological properties, including its ability to inhibit tumor cell growth, although scientific studies are limited. We have analyzed the effect of this plant on two colon carcinoma cell lines, that is, RKO (normal p53) and SW613-B3 (mutated p53) cells. Among several extracts obtained from various parts of G. neuberthii plant, we identified the extract with the greatest cytotoxic potential, derived from the stem bark. The cytotoxic effect was similar on both cell lines, thus indicating that it is independent of the status of p53. However, significant differences were observed after the analysis of colony formation, with RKO cells being more sensitive than SW613-B3. No evidence for apoptotic markers was recorded; nevertheless, both cell lines showed signs of autophagy after the treatment, including increased Beclin-1 and LC3-II and decreased p62. Finally, three chemical compounds, possibly responsible for the effect observed in both cell lines, were identified: lupeol (1), 3'-O-methyl ellagic acid 4-O-ß-D-rhamnopyranoside (2), and 19-α-hydroxy-asiatic acid monoglucoside (3).

Biochemical and genotoxic effects in women exposed to pesticides in Southern Ecuador.

Toxicity refers to the potential of a substance such as a pesticide to cause damage to the structure or functions of an exposed organism. Pesticides can lead to harmful biological effects in exposed animals and their offspring over the medium and long term. They can affect the immunological, nervous, endocrine, and reproductive systems. DNA damage has also been linked to exposure to pesticides, and this damage can cause abortions, degenerative diseases, and cancer. The aim of this work was to establish whether women who are indirectly exposed to pesticides exhibit a compromised health status, including genotoxic effect. Women exposed indirectly to pesticides in Chimchanga and Colaisaca in the south of Ecuador underwent hematological and biochemical tests and micronucleus assay in buccal cells. The subjects were also genotyped for GSTM1, GSTT1, GSTP1, and PON1 polymorphisms, which can modify an individual's capacity to metabolize pesticides and relation with damage of DNA. The study revealed hepatic toxicity in Colaisaca women (AST and ALT) and an increase in the rate of micronucleus (MN) in Colaisaca individuals. In addition, genetic polymorphisms in PON1 and GSTP1 showed effects of modulating the frequency of karyolytic cells, karyorrhectic cells, and condensed chromatin cells.

Phytochemical Study and Evaluation of the Cytotoxic Properties of Methanolic Extract from Baccharis obtusifolia.

Some species of the Baccharis genus have been shown to possess important biomedical properties, including cytotoxic activity. In this study, we examined the cytotoxic effect of methanol extract from Baccharis obtusifolia (Asteraceae) in cancer cell lines of prostate (PC-3), colon (RKO), astrocytoma (D-384), and breast (MCF-7). The methanolic extract displayed the largest substantial cytotoxic effect in lines of colon cancer (RKO) and cerebral astrocytoma (D-384). Chromatographic purification of the B. obtusifolia methanolic extract led to the isolation and identification of 5,4'-dihydroxy-7-methoxyflavone (1) and 5-hydroxy-7,4'-dimethoxyflavone (2) compounds of the flavonoid type.

Contamination by oil crude extraction - Refinement and their effects on human health.

The harmful effects of oil on various species of flora and fauna have been studied extensively; however, few studies have studied the effects of oil exposure on human health. The objective of this research was to collect information on the acute health effects and serious psychological symptoms of the possible consequences of such exposure to crude oil. Some studies focused on the composition of different chemicals used in the extraction process, and wastes generated proved to be highly harmful to human health. Thus, studies have shown that individuals who live near oil fields or wells - or who take part in activities of cleaning oil spills - have presented health conditions, such as irritation to the skin, eyes, mucous membranes, kidney damage, liver, reproductive, among others. In Ecuador, this reality is not different from other countries, and some studies have shown increased diseases related with oil crude and oil spills, like skin irritation, throat, liver, lung, infertility, and abortions, and it has been linked to childhood leukemia. Other studies suggest a direct relationship between DNA damage because of oil resulting in a genetic instability of the main enzymes of cellular metabolism as well as a relationship with some cancers, such as leukemia.

Medicinal plants used as anthelmintics: Ethnomedical, pharmacological, and phytochemical studies.

Intestinal parasites delay mental and physical development in children. Infection with these parasites can result in complications during pregnancy and alter the health of newborns, which has long-term effects on educational attainment and economic productivity. The appearance of resistance against classical drug treatments generates interest in the development of new deworming alternatives. We think that research of new plants species may reveal potential antiparasitic compounds. This review is focused on the use of plants and secondary metabolites against intestinal parasites. We discuss the use of plants in traditional medicine and the use of plant secondary metabolites tried in in vitro and in vivo models when available.

Correction: Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

[This corrects the article DOI: 10.1371/journal.pone.0136527.].

Phytometabolite Dehydroleucodine Induces Cell Cycle Arrest, Apoptosis, and DNA Damage in Human Astrocytoma Cells through p73/p53 Regulation.

Accumulating evidence supports the idea that secondary metabolites obtained from medicinal plants (phytometabolites) may be important contributors in the development of new chemotherapeutic agents to reduce the occurrence or recurrence of cancer. Our study focused on Dehydroleucodine (DhL), a sesquiterpene found in the provinces of Loja and Zamora-Chinchipe. In this study, we showed that DhL displayed cytostatic and cytotoxic activities on the human cerebral astrocytoma D384 cell line. With lactone isolated from Gynoxys verrucosa Wedd, a medicinal plant from Ecuador, we found that DhL induced cell death in D384 cells by triggering cell cycle arrest and inducing apoptosis and DNA damage. We further found that the cell death resulted in the increased expression of CDKN1A and BAX proteins. A marked induction of the levels of total TP73 and phosphorylated TP53, TP73, and γ-H2AX proteins was observed in D384 cells exposed to DhL, but no increase in total TP53 levels was detected. Overall these studies demonstrated the marked effect of DhL on the diminished survival of human astrocytoma cells through the induced expression of TP73 and phosphorylation of TP73 and TP53, suggesting their key roles in the tumor cell response to DhL treatment.

Molecular Docking Studies of the Antitumoral Activity and Characterization of New Chalcone.

Phytochemical investigation of Azorella madreporica led to the isolation of four known compounds and an unknown chalcone. The structure of the new compound was identified by spectroscopy, including two-dimensional NMR techniques and comparison with published spectral data. The antioxidant activity of chalcone (compound 1) was measured using the 1,2-diphenyl-2-picryl-hydrazyl (DPPH) free radical scavenging assay, and the bioactivity was evaluated against five bacteria (Mycobacterium smegmatis ATCC 14468, clinical isolates of Staphylococcus aureus, Klebsiella granulomatis, Morganella morganii and Escherichia coli) and four cancer cell lines. Docking studies with the tested cancer related proteins revealed nearby values of energy between doxorubicin and compound 1. Besides, protein-ligand interactions correlate with these energy values.

Phytochemical study and evaluation of cytotoxic and genotoxic properties of extracts from Clusia latipes leaves

Abstract Some species of the Clusia genus have been shown to have important biomedical properties, including the ability to inhibit tumor growth in vitro and the usefulness for skin care. In this study, we examined the cytotoxic effect of hexane, ethyl acetate and methanol extracts from Clusia latipes Planch. & Triana, Clusiaceae, leaves on survival of human prostate cancer cells (PC-3), colon cancer cells (RKO), astrocytoma cells (D-384), and breast cancer cells (MCF-7). The ethyl acetate extract displayed the most substantial cytotoxic effect. However, using a Comet assay, we observed that the hexane extract induced a genotoxic effect (DNA damage) on human lymphocytes in an in vitro model. Chromatographic purification of the C. latipes hexane extract led to the isolation and identification of friedelin, friedolan-3-ol, and hesperidin as active cytotoxic compounds in hexane extract, while β-amyrine was identified as an active cytotoxic compound in the ethyl acetate extract of C. latipes, thereby supporting further studies of the molecular mechanisms underlying the effect of these secondary metabolites on cancer cell survival.