Chamaecyparis lawsoniana and Its Active Compound Quercetin as Ca2+ Inhibitors in the Contraction of Airway Smooth Muscle.

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl3. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca2+ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca2+ currents. ASM cells stimulated with Cch produced a transient Ca2+ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca2+ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties.

Photoprotective effect of topical treatment with Lopezia racemosa extract against deleterious UVB irradiation effects in the skin of hairless mice.

Lopezia racemosa is known as a "mosquito flower or perlilla." It is commonly found in corn crops. In traditional Mexican medicine, this plant is used to treat stomach cancer and urinary tract infections. Likewise, compounds and extracts isolated from plants have shown cytotoxic and anti-inflammatory effects. The objective of this study was to evaluate the photochemoprotective effect of topical treatment with the methanolic extract of L. racemosa (MELR) as a photochemoprotective agent against the harmful effects of UV irradiation (UVR) on a bacterial model and hairless mice. The MELR components were separated and analyzed via HPLC-UV-ESI-MS. Antioxidant activity was evaluated by the ability of MERL to scavenge DPPH and ABTS free radicals and by its FRAP capacity. The toxicity of MELR was evaluated in keratinocyte cultures. The photoprotective capacity of MELR was assessed through challenge experiments using models with bacteria and hairless CD1 et/et mice; cytokines related to the damage caused by UVR were also measured. In the methanolic extract of L. racemosa, five metabolites were detected and identified: two isomers of quercetin 6-C glycoside, orientin, quercetin 3-(6″-acetylglycoside) and quercetin 3-(6″-galloylglycoside) 7-(2,3-dihydroxytetrahydro-2H-pyran-4-yl acetate). MELR exhibited DPPH and ABTS radical scavenging properties, in addition to Fe ion reducing activity. MELR showed a photoprotective effect against UVB radiation-induced death in Escherichia coli bacteria. At the histological level, topical treatment of CD-1 et/et mice with MERL reduced the damage caused by UVR. Quantification of interleukins in the blood of mice revealed that the expression of IL-12 was greater in the control group treated with ultraviolet radiation than in the group protected with MELR. The methanolic extract of L. racemosa has photochemoprotective properties.

Unraveling the Neuroprotective Effect of Natural Bioactive Compounds Involved in the Modulation of Ischemic Stroke by Network Pharmacology.

Ischemic stroke (IS) is one of the leading causes of mortality worldwide. It is characterized by the partial or total occlusion of arteries that supply blood to the brain, leading to the death of brain cells. In recent years, natural bioactive compounds (NBCs) have shown properties that ameliorate the injury after IS and improve the patient's outcome, which has proven to be a potential therapeutic strategy due to their neuroprotective effects. Hence, in the present study, we use both systems pharmacology and chemoinformatic analyses to identify which NBCs have the most potential to be used against IS in clinics. Our results identify that flavonoids and terpenoids are the most studied NBCs, and, mainly, salidrosides, ginkgolides A, B, C, and K, cordycepin, curcumin, baicalin, resveratrol, fucose, and cannabidiol, target the main pathological processes occurring in IS. However, the medicinal chemistry properties of such compounds demonstrate that only six fulfill such criteria. However, only cordycepin and salidroside possess properties as leader molecules, suggesting that these compounds may be considered in developing novel drugs against IS.

Epigenetic Factors and ncRNAs in Testicular Cancer.

Testicular cancer is the most prevalent tumor among males aged 15 to 35, resulting in a significant number of newly diagnosed cases and fatalities annually. Non-coding RNAs (ncRNAs) have emerged as key regulators in various cellular processes and pathologies, including testicular cancer. Their involvement in gene regulation, coding, decoding, and overall gene expression control suggests their potential as targets for alternative treatment approaches for this type of cancer. Furthermore, epigenetic modifications, such as histone modifications, DNA methylation, and the regulation by microRNA (miRNA), have been implicated in testicular tumor progression and treatment response. Epigenetics may also offer critical insights for prognostic evaluation and targeted therapies in patients with testicular germ cell tumors (TGCT). This comprehensive review aims to present the latest discoveries regarding the involvement of some proteins and ncRNAs, mainly miRNAs and lncRNA, in the epigenetic aspect of testicular cancer, emphasizing their relevance in pathogenesis and their potential, given the fact that their specific expression holds promise for prognostic evaluation and targeted therapies.

Data-Driven Approaches Used for Compound Library Design for the Treatment of Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease in older individuals worldwide. Pharmacological treatment for such a disease consists of drugs such as monoamine oxidase B (MAO-B) inhibitors to increase dopamine concentration in the brain. However, such drugs have adverse reactions that limit their use for extended periods; thus, the design of less toxic and more efficient compounds may be explored. In this context, cheminformatics and computational chemistry have recently contributed to developing new drugs and the search for new therapeutic targets. Therefore, through a data-driven approach, we used cheminformatic tools to find and optimize novel compounds with pharmacological activity against MAO-B for treating PD. First, we retrieved from the literature 3316 original articles published between 2015-2021 that experimentally tested 215 natural compounds against PD. From such compounds, we built a pharmacological network that showed rosmarinic acid, chrysin, naringenin, and cordycepin as the most connected nodes of the network. From such compounds, we performed fingerprinting analysis and developed evolutionary libraries to obtain novel derived structures. We filtered these compounds through a docking test against MAO-B and obtained five derived compounds with higher affinity and lead likeness potential. Then we evaluated its antioxidant and pharmacokinetic potential through a docking analysis (NADPH oxidase and CYP450) and physiologically-based pharmacokinetic (PBPK modeling). Interestingly, only one compound showed dual activity (antioxidant and MAO-B inhibitors) and pharmacokinetic potential to be considered a possible candidate for PD treatment and further experimental analysis.

Antimicrobial activity of some macroalgae of the Veracruzano Reef System (SAV), Mexico.

The study of macroalgae antimicrobial agents is limited to Mexico and scarce in the Veracruzano Reef System (SAV). It is necessary to devote efforts towards this field of applied phycology. The aim was to evaluate the antimicrobial activity of some phyla of Rhodophyta, Chlorophyta and Ochrophyta from SAV. Methanolic extracts from 23 marine macroalgae species (7 Chlorophyta, 4 Phaeophyta and 12 Rhodophyta) from the Veracruzano Reef System (SAV) (Mexico) were evaluated for antimicrobial activity. Antibacterial and antifungal activity were assessed by agar diffusion and agar dilution methods. The differences between mean values obtained for experimental groups was done by analysis of variance (ANOVA multifactorial model), p-values of 0.001 or less were considered statistically significant. Two new records are recognized for SAV (Laurencia gracilis and Sebdenia flabellata) and Compsothamnion thuioides for the Gulf of Mexico coasts. 16 species showed antibacterial activity, of which Caulerpa sertularioides, Ulva lactuca and Laurencia obtuse had significant activity on Gram-positive bacteria. 43.7% belong to the phyla Chlorophyta (7 species), 50% Rhodophyta (8 species) and 6.25% Ochrophyta (1 species). This indicates that the extracts of the algae of the Rhodophyta and Chlorophyta are the ones that showed the greatest activity. Regarding the yeasts, 16.6% of the total algae collected were active in the different yeast strains. 43.7% belongs to Chlorophyta species and for Rhodophyta were 60%. The macroalgae with the highest antifungal activity were: Cymopolia barbata, Ulva lactuca and Laurencia gracilis. The macroalgae of the Veracruzano Reef System present antimicrobial activity. This study is the first investigation of macroalgae's bioactive components from SAV, where they could be sources for future medical applications.

Chemical profile, antimicrobial activity, and leaf anatomy of Adenophyllum porophyllum var. cancellatum.

Adenophyllum porophyllum var. cancellatum, known as "árnica del monte" in Mexico, is an aromatic annual plant belonging to the Asteraceae family that grows from southern Arizona to central Mexico. The aerial parts of the plant are used in traditional medicine to treat skin diseases such as irritations, infections, and wounds. In this study, the essential oil of this plant was characterized, and its antimicrobial activity was evaluated. This species has large glands in its leaves; therefore, for quality control purposes, an anatomical study of the leaves was performed. The essential oil was isolated from the aerial parts of the plant through hydro-distillation and analyzed using a gas chromatography/mass spectrometry (GC/MS) system. Its anti-yeast activity was evaluated against three Candida species and ten bacterial strains using the disk diffusion technique. The minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), and minimum bactericidal concentration (MBC) were determined using broth microdilution. Anatomical study was performed on the middle part of the leaf. A yield of 0.5% of the essential oil was obtained from the herb, and Eighteen compounds in the essential oil were identified, within them trans pinocamphone (29.5%), limonene (24.7%), pinocarvone (21.8%), and cis pinocamphone (8.0%) were the main components. The inhibition zones were between 10 mm and 20 mm, and the MIC and MFC against the three Candida species ranged from 60 to 500 µg/ml. The leaf anatomy showed anisocytic stomata, simple and glandular trichomes of different types, and large and elliptical-shaped lysigenous glands, which can be used for taxonomic identification. The A. porophyllum var. cancellatum essential oil can serve as an alternative source of natural antimicrobial agents as an affordable approach to control infectious diseases. This is the first study that reports the chemical composition and antimicrobial activity of the essential oil, as well as the leaf anatomy of this species.

Natural marine products as antiprotozoal agents against amitochondrial parasites.

The goal of this work is to compile and discuss molecules of marine origin reported in the scientific literature with anti-parasitic activity against Trichomonas, Giardia, and Entamoeba, parasites responsible for diseases that are major global health problems, and Microsporidial parasites as an emerging problem. The presented data correspond to metabolites with anti-parasitic activity in human beings that have been isolated by chromatographic techniques from marine sources and structurally elucidated by spectroscopic and spectrometric procedures. We also highlight some semi-synthetic derivatives that have been successful in enhancing the activity of original compounds. The biological oceanic reservoir offers the possibility to discover new biologically active molecules as lead compounds to develop new drug candidates. The molecular variety is extensive and must be correctly explored and managed. Also, it will be necessary to take some actions to preserve the source species from extinction or overharvest (e.g., by cryopreservation of coral spermatozoa, oocytes, embryos, and larvae) and coordinate appropriate exploitation to increase the chemical knowledge of the natural products generated in the oceans. Additional initiatives such as the total synthesis of complex natural products and their derivatives can help to prevent overharvest of the marine ecosystems and at the same time contribute to the discovery of new molecules.

Verbascoside-enriched fraction from Buddleja cordata Kunth ameliorates the effects of diabetic embryopathy in an animal model.

BACKGROUND: The deleterious effects of diabetes mellitus (DM) over development are apparently due to an increase in oxidative stress. Some antioxidants could prevent developmental alterations produced by diabetic state. Extracts of plants of the genus Buddleja are used traditionally for Mexican indigens to ameliorate some diseases. The purpose of this work was to evaluate the effect of the extract of Buddleja cordata over diabetic embryopathy. METHODS: Two experimental approaches were used: an in vivo study and an in vitro model. In the first, rats were treated with streptozotocin, streptozotocin plus methanolic extract of B. cordata, or none. Females were sacrificed at gestational day (GD) 19, and biochemical clinical parameters were measured; also, the fetuses were obtained and morphologically analyzed. In the in vitro model, a verbascoside-enriched fraction (VEF) of the extract was used in whole embryo culture in order to search for the mechanisms for embryoprotection effect over hyperglycemia-induced malformations. RESULTS: In the in vivo experiments, B. cordata extract reduces the frequency and severity of fetal malformations produced by chemically induced diabetes, and additionally partially ameliorates the diabetic condition; in the in vitro model, both severity and frequency of embryo dysmorphogenesis were reduced by the VEF; also, this fraction reduces lipoperoxidation without affecting the activity of the antioxidant enzymes. CONCLUSION: The results suggest that verbascoside of methanolic extract and enriched fraction can directly affect the redox state, and thus, prevents the embryotoxicity mediated by oxidative stress, in embryos of diabetic pregnancy.

Verbesina crocata: A pharmacognostic study for the treatment of wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbesina crocata (Cav.) Less. (Arnica or Capitaneja) is an endemic plant from Mexico restricted to the western part of the country. The aerial parts are used in traditional medicine for the treatment of wounds and burns. The objective of this investigation was to carry out a pharmacognostic study of V. crocata and establish markers that allow for the recognition of the characteristics of the plant and validate its traditional use. The study includes anatomical and chemical characteristics of the plant as well as evaluations of its antioxidant capacity and wound healing ability in a murine model. MATERIALS AND METHODS: An anatomical study of V. crocata was performed on the middle part of the leaf and stem. A methanolic extract of this species (VcME) was obtained by methanolic maceration of the aerial parts. Subsequently, a partition of the VcME was made to obtain a hexanic fraction (VcH). The phytochemical preliminary screening and characterization by high-performance liquid chromatography/mass spectrometry (HPLC-ESI/MS) of the VcME and VcH were performed. The antioxidant activity and total phenolic content were quantified. The wound healing capacity of the methanolic extract was determined in CD-1 mice by the healing rate, the tensiometric method, and histological analysis. RESULTS: The anatomical study of V. crocata showed the presence of two types of secretory structures and their position on the leaves. In addition, the characteristics of the middle vein and trichomes are potentially useful for recognition of the species. Chemical compounds detected by HPLC-ESI/MS reveal the presence of sitosterol glycoside and catechin derivatives as principal constituents of V. crocata. The VcME showed low antioxidant capacity and total phenolic. V. crocata had a similar healing effect to Recoveron® in the tensiometric method, but the rate of healing was higher. According to the histological analysis, the treatment of V. crocata promoted the remodelling phase 15 days after the incisional wound. CONCLUSION: This is the first pharmacognostic study of this species that covers the plant anatomy, chemical content and biological properties related to its traditional use. V. crocata favours wound healing according to physical and histological evaluations. In addition, the characteristics of the middle vein, trichomes and catechin glycosides are potentially useful for the recognition of this species.

Efficacy of purified fractions of Artemisia ludoviciana Nutt. mexicana and ultraestructural damage to newly excysted juveniles of Fasciola hepatica in vitro.

The study aimed to evaluate the fasciolicidal efficacy of extracts and fractions of Artemisia ludoviciana and identify the active substance. Extracts from A. ludoviciana were obtained by using hexane, ethyl acetate and methanol. To test the extracts, newly excysted juveniles of Fasciola hepatica were artificially obtained. The extracts were tested at concentrations of 125, 250, 375 and 500 mg/L. In each test run, an untreated control group and control wells containing triclabendazole sulfoxide were also included. The flukes were examined at 24, 48 and 72 h after treatment. Ethyl acetate extract (ALEAE) showed 100 % efficacy at 48 h of exposure (P < 0.05). Then, this extract was fractionated by column chromatography (CC), and the obtained fractions were evaluated in vitro as previously mentioned. The results indicated that fraction 3 yielded 100 % efficacy at 48 h (P < 0.05). Subsequently, the purification of fraction 3 was performed. New fractions were obtained (A-L), with sub-fraction "J" exhibiting 100 % efficacy at 24 h (P < 0.05). These sub-fractions were submitted to phytochemical analysis, demonstrated the presence of sesquiterpene lactones. Likewise, were analyzed by HPLC/MS/DAD, and the results showed that artemisinin was the main compound. In addition, flukes treated were examined by scanning electron microscopy (SEM) showing areas of inflammation throughout the tegument.

Ayahuasca: Uses, Phytochemical and Biological Activities.

Ayahuasca (caapi, yajé), is a psychoactive brew from the Amazon Basin region of South America traditionally considered a "master plant." It is prepared as a decoction from Banisteriopsis caapi and Psychotria viridis, which it is thought that it stimulates creative thinking and visual creativity. Native healers of the Orinoco and Amazon basins have used traditionally ayahuasca as a healing tool for multiple purposes, particularly to treat psychological disorders in the patients, with some beneficial effects experimentally and clinically validated. Recently, several syncretic religions, as the "União de Vegetal" (UDV) group in Brazil, have been spread around the world. The use of ayahuasca has been popularized by internet and smart-shops, bringing the psychoactive substance to new highs, emerging new "ayahuasqueros." Ayahuasca has alkaloids as ß-carbolines and dimethyltryptamines, which inhibit the monoamine oxidase and active the 5-HT2A (5-hydroxytryptamine) receptor, respectively, resulting in hallucinations in the users. Ayahuasca induces a psychedelic change in the anteroposterior coupling of the electrophysiological brain oscillations in humans. Traditional ayahuasca beverage is generating pharmacological, commercial and spiritual interest among the scientific community, government people, and different populations worldwide. The goal of this article is to report about the uses, chemistry and biological activities of ayahuasca.

The Tillandsia genus: history, uses, chemistry, and biological activity / El género Tillandsia: historia, usos, química y actividad biológica

Tillandsia L. genus comprises 649 species, with different uses at different times. T. usneoides L. uses are reported since the late- archaic and pre-Columbian cultures. In XIX-XX centuries, T. usneoides was used in some manufactured products, as polish and packing fruit. Tillandsia has a favorable reputation as medicine: for leucorrhea, rheumatism, ulcers, hemorrhoid treatment, as an anti-diabetic remedy, emetic, analgesic, purgative, contraceptive, antispasmodic and diuretic. Tillandsia chemical composition includes cycloartane triterpenes and hydroxy-flavonoids, which are present in at least 24 species. Several extracts and compounds from Tillandsia spp. have been reported with pharmacological actions, as anti-neoplasia, hypolipidemic, antifungal, anti-HSV-1, hypoglycemic and microbicide. This review communicates the economic importance, ethnobotany, chemistry composition and biological activities of the Tillandsia genus, and analyze its biological and economic perspective. Tillandsia genus has cultural, economic and pharmacological relevance, with a high potential in many essential aspects of the modern society.

El género Tillandsia L. comprende 649 especies, con diferentes usos en diferentes épocas. T. usneoides L. se han reportado desde el arcáico tardío hasta las culturas precolombinas. En los siglos XIX-XX, T. usneoides se usó en productos manufacturados: como abrasivo y embalaje de fruta. Como medicina tradicional, el género Tillandsia se reporta para leucorrea, reumatismo, úlceras, hemorroides, remedio antidiabético, emético, analgésico, purgante, anticonceptivo, antiespasmódico y diurético. Su composición química incluye triterpenos de tipo ciclo-artano e hidroxi-flavonoides, presentes en al menos 24 especies. Los extractos y compuestos del género Tillandsia se han reportado con propiedades antineoplásicas, hipolipidémicas, antifúngicas, anti-HSV-1, hipoglucemiantes y microbicidas. Esta revisión comunica la importancia económica, etnobotánica, composición química y las actividades biológicas del género Tillandsia, y analiza su perspectiva biológica y potencial económica. Tillandsia tiene importancia cultural, económica y farmacológica, con gran potencial en muchos aspectos esenciales de la sociedad moderna.

Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense.

Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree Calophyllum Brasiliense, which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally in vitro on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The in vitro model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.

Volatile organic compounds from pachyrhizus ferrugineus and pachyrhizus erosus (Fabaceae) leaves / Compuestos orgánicos volátiles de las hojas de pachyrhizus ferrugineus y pachyrhizus erosus (Fabaceae)

In México, Pachyrhizus erosus (Fabaceae) commonly called "jícama", is widely known for its edible tubers. It is cultivated since the pre-Columbian period, and the powdered seeds have been used for the treatment of mange, lice, and fleas, due to their content of rotenone, a well-known insecticidal compound. On the other hand, P. ferrugineus, a wild species can only be found in the Tropical Forests, and has no commercial value. It is known that plants release volatile organic compounds (VOCs) showing qualitative and quantitative differences if are wild or cultivated. VOCs are also involved as repelling or attracting chemical signals to insect herbivores, and their natural enemies. Until now, the VOCs of the leaves of P. erosus and P. ferrugineus have not been investigated. In the present contribution the VOCs of both species were characterized by headspace solid-phase (HS-SPME) extraction and gas chromatography-mass spectrometry (GC-MS-TOF). In P. erosus 21 VOCs were found, being the most abundant: cyclohexanone (32.8 percent), 3-hexen-1-ol (Z) (32.7 percent), 3-hexenal (Z) (10.5 percent). The majoritarian compounds were C6 or C5 derivatives In P. ferrugineus, the most abundant VOCs were: 5-hexene-1-ol acetate (51.5 percent), undecanal (22.4 percent), 2-hepten-1-al (14.5 percent). The majoritarian compounds were C6, C7 or C11 derivatives.

En México, Pachyrhizus erosus (Fabaceae) es llamada comúnmente "jícama" y es conocida por sus tubérculos comestibles. Se ha cultivado desde el período pre-Colombino y las semillas se han utilizado para el tratamiento tópico de la sarna, piojos, pulgas; las semillas contienen rotenona, un compuesto insecticida. Por otra parte, P. ferrugineus solo está presente en estado silvestre en los bosques tropicales y carece de valor comercial. Se sabe que las plantas liberan compuestos orgánicos volátiles (COV) y muestran diferencias cualitativas y cuantitativas dependiendo, si son silvestres o cultivadas. Los COV también son señales químicas atrayentes o repelentes de los insectos herbívoros y a sus enemigos naturales. Hasta ahora, los COV en las hojas de P. erosus y P. ferrugineus no han sido investigados. En el presente trabajo, los COV se identificaron mediante la microextracción (HS-SPME) en fase sólida, e identificados por cromatografía de gases acoplada a espectrometría de masas (GC-MS-TOF). En P. erosus se encontraron 21 COV, siendo los más abundantes: ciclohexanona (32.8 por ciento), 3-hexen-1-ol (Z) (32.7 por ciento) y 3-hexenal (Z) (10.5 por ciento). Los compuestos mayoritarios son C6 y C5. En P. ferrugineus los más abundantes fueron: 5-hexen-1-ol acetato (51.5 por ciento), undecanal (22.4 por ciento) y 2-hepten-1-al (14.5 por ciento). Los compuestos mayoritarios son C6, C7 o C11.

Rotenone isolated from Pachyrhizus erosus displays cytotoxicity and genotoxicity in K562 cells.

Pachyrhizus erosus (Fabaceae) is a herb commonly known as 'yam bean', which has been cultivated in México since pre-Columbian times for its edible tubers. The seeds are also known for their acaricidal and insecticidal properties due to rotenone and other isoflavonoid contents. Rotenone has exhibited cytotoxic activity against several human tumour cell lines; however, its mechanism of action is still not fully understood. In this study, we determined the cytotoxicity of rotenone isolated from P. erosus seeds on K562 human leukaemia cells. Rotenone exhibited significant cytotoxic activity (IC50 = 13.05 µM), as determined by the MTT assay. Three other isolated isoflavonoids were not cytotoxic. Rotenone genotoxicity was detected using the comet assay. Rotenone induced cell death, and caspase-3 activation as indicated by TUNEL assay, and immunocytofluorescence. Plasmid nicking assay indicated that rotenone does not interact directly with DNA.

Molecular mechanisms involved in the cytotoxicity induced by coumarins from Calophyllum brasiliense in K562 leukaemia cells.

OBJECTIVES: The aim of this study was to determine the cellular and molecular mechanisms of cell death induced by mammea A/BA and A/BB (3 : 1) on K562 cells. METHODS: These compounds were isolated from Calophyllum brasiliense and its cytotoxicity was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cell death was evaluated by Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and immunocytofluorescence of active caspase-3. Genotoxicity was tested using comet assay. Lastly, a chemoinformatic analysis was performed with Osiris-Molinspiration software. KEY FINDINGS: The mixture of mammea A/BA and A/BB (3 : 1) showed cytotoxic activity against K562 cells (IC50 = 43.5 µm). TUNEL positive cells and active caspase-3 were detected after treatment. Genotoxicity of mammea A/BA and A/BB on K562 was detected since first hour of treatment. Additionally, mammea A/BA and A/BB were found to be in compliance with Lipinski 'rule of 5' suggesting that they possess strong potential of druglikeness. CONCLUSIONS: The overall results confirm and extend the knowledge about coumarins as an important resource of antitumor drugs, and indicate that these compounds could be used in further preclinical studies against leukaemia.