Irene Iglesias

Antiinflammatory and antioxidant activity of plants used in traditional medicine in Ecuador

Ethanolic extracts from 15 plant species, representing eight different families, used in traditional medicine in Ecuador were evaluated for antiinflammatory and antioxidant activities. Conyza floribunda, Eupatorium articulatum, Bonafousia longituba, Bonafousia sananho, Tagetes pusilla and Piper lenticellosum extracts showed a significant antiinflammatory activity in vivo in the carrageenan-induced paw oedema model in mice. The extracts were also tested in vitro for their ability to inhibit lipid peroxidation and to scavenge superoxide and hydroxyl radicals. E. articulatum extract possesses both activities. Baccharis trinervis, E. articulatum and Phytolacca rivinoides extracts were active as antioxidants.

Antiviral activity of Bolivian plant extracts

Ethanolic and aqueous extracts of seven plant species used in the traditional medicine of Bolivia have been tested for their antiviral activity against herpes simplex type I (HSV-1), vesicular stomatitis virus (VSV), and poliovirus type 1. The aqueous extracts of most of the species investigated showed antiviral activity. Two of these plants-namely, Satureja boliviana and Baccharis genistelloides-were active against two different viruses-HSV-1 and VSV.

Gastric cytoprotection of bolivian medicinal plants.

Several extracts obtained from Bolivian medicinal plants have been evaluated for cytoprotective activity on ethanol-induced ulcer formation in rats. Preliminary results suggest, that the majority of the plants tested showed a significant activity, the aqueous extracts of Phoradendron crassifolium and Franseria artemisioides being the most active, exerting a cytoprotective activity comparable to atropine. The analysis of the chemical constituents of the extracts studied showed the presence of tanins, saponins, flavonoids and coumarins.

Neuropharmacological profile of ethnomedicinal plants of Guatemala

We carried out the Irwins test with some different extracts of the aerial parts of Thidax procumbens L., the leaves of Neurolaena lobata (L.) R. Br., bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp., and root and leaves of Petiveria alliacea L. At dosage of 1.25 g dried plant/kg weight aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. demonstrated the most activity: decrease in motor activity, back tonus, reversible parpebral ptosis, catalepsy and strong hypothermia. These extracts of both plants were assayed for effects on CNS and they caused very significant reductions in spontaneous locomotor activity, exploratory behavior and rectal temperature and they increased the sodium pentobarbital-induced sleeping time.

Preliminary screening of five ethnomedicinal plants of Guatemala.

We performed the Irwin test on some different extracts of the aerial parts of Tridax procumbens L., of the leaves of Neurolaena lobata (L.) R. Br., of the bark and leaves of Byrsonima crassifolia (L.) Kunth. and Gliricidia sepium Jacq. Walp. and of the root and leaves of Petiveria alliacea L. At a dosage of 1.25 g extract/100 g dried plant, the aqueous extracts of bark and leaves of Byrsonima crassifolia (L.) Kunth. and G. sepium Jacq. Walp. showed higher activity: decrease in motor activity, back tonus, reversible parpebral ptosis. catalepsy and strong hypothermia.

Identification of new SNPs associated with severe toxicity to capecitabine

&NA; Predicting individual risk of chemotherapy‐induced severe adverse reaction is a critical issue when selecting the best treatment for cancer patients. SNPs have been identified in genes involved in the pharmacodynamics of fluoropyrimidines, and guidelines even recommend genotyping some DPYD variants in order to estimate the risk of toxicity. However, the predictive value of this approach remains insufficient, thus limiting its clinical implementation. The aim of the present study was to identify new genetic variants by selecting a group of tag SNPs in genes associated with the pharmacodynamics of fluoropyrimidines (CDA, DPYD, ENOSF1, CES1, TYMS, SLC22A7, TYMP, and UMPS). For this purpose, 23 selected SNPs were genotyped on an OpenArray™ platform in a cohort of 301 colorectal cancer patients receiving capecitabine‐based chemotherapy. Univariate and multivariate statistical analysis by logistic regression revealed 10 SNPs associated with severe adverse reactions to capecitabine (P < 0.05): rs1048977, rs12726436, and rs2072671 in CDA; rs12119882 in DPYD; rs2853741 in TYMS; rs699517 in TYMS/ENOSF1; rs2270860 and rs4149178 in SLC22A7; and rs2279199 and rs4678145 in UMPS. Except for rs2072671, no association had previously been reported between these SNPs and the risk of capecitabine‐induced toxicity. The use of tag SNPs to find new polymorphisms related to adverse reactions to capecitabine was successful. These new variants could increase the predictive power of currently available tests and thus prevent severe adverse reactions to capecitabine. Graphical abstract Figure. No caption available.

Ginsenosides Rd and Re co-treatments improve rotenone-induced oxidative stress and mitochondrial impairment in SH-SY5Y neuroblastoma cells

Oxidative stress and mitochondrial dysfunction play key roles in Parkinsons disease (PD) initiation and progression. Ginsenosides are major compounds of Ginseng species and they are responsible for pharmacological activity. The aim of this study was to investigate the potential neuroprotective effects and mechanism of the major ginsenosides Rd and Re in rotenone-induced oxidative stress model in human neuroblastoma SH-SY5Y cells. Co-treatments with both ginsenosides inhibited the increased intracellular ROS production and by-products lipid peroxidation accumulation caused by rotenone. Moreover, these ginsenosides upregulated SOD and aconitase enzymes activities, and glutathione system; these antioxidant properties are related to Nrf2 induction and radical scavenger effect. Additionally, the results showed that both Rd and Re attenuated the extent of depolarization of mitochondrial membrane potential and restored calcium levels. Furthermore, these compounds prevented apoptosis by modulating Bax and Bcl-2 proteins and inhibiting cytochrome c release and caspase-3 activation. The ginsenoside Rd resulted to be more active than ginsenoside Re. These findings highlighted the efficacy of these compounds as neuroprotectant compounds for PD prevention and treatment through reducing oxidative stress, improving mitochondrial integrity and functions, and inhibiting apoptosis.

Use of exome sequencing to determine the full profile of genetic variants in the fluoropyrimidine pathway in colorectal cancer patients affected by severe toxicity

AIM To identify genetic variants associated with capecitabine toxicity in fluoropyrimidine pathway genes using exome sequencing. PATIENTS & METHODS Exomes from eight capecitabine-treated patients with severe adverse reactions (grade >2), among a population of 319, were sequenced (Ion Proton). SNPs in genes classified as potentially damaging (Sorting Intolerant from Tolerant and Polymorphism Phenotyping v2) were tested for association with toxicity in a validation cohort of 319 capecitabine-treated patients. RESULTS A total of 17 nonsynonymous genetic variants were identified. Of these, five putative damaging SNPs in DPYD, ABCC4 and MTHFR were genotyped in the validation cohort. DPYD rs1801160 was associated with the risk of toxicity (p = 0.029) and MTHFR rs1801133 with delayed administration of chemotherapy due to toxicity (p = 0.047). CONCLUSION Exome sequencing revealed two specific biomarkers of the risk of toxicity to capecitabine.

Evaluation of the adaptogenic potential exerted by ginsenosides Rb1 and Rg1 against oxidative stress-mediated neurotoxicity in an in vitro neuronal model

Background Ginseng (Panax sp.) is a drug with multiple pharmacological actions that has been largely used in traditional medicines for the treatment of many health problems. In the therapy of neurodegenerative disorders, it has been employed due to its capacity to strengthen mental processes by enhancing cognitive performance and psychological function. Current work aimed at evaluating the adaptogenic potential of Rb1 and Rg1 against oxidative-stress mediated degeneration in a model of nervous cells. Methods Oxidative stress and mitochondrial dysfunction were achieved by exposing SH-SY5Y cells to the mitochondrial complex I inhibitor rotenone. The cytoprotective activity of pre-treatments with ginsenosides Rb1 and Rg1 against rotenone was assessed by determining biochemical markers regarding oxidative stress (ROS scavenging, glutathione and lipid peroxidation levels, SOD activity and Nrf2 activation) and apoptosis-related alterations (mitochondrial membrane potential, calcium levels, aconitase activity and pro/antiapoptotic proteins). Their capacity to cross the blood brain barrier was also estimated. Results At their optimal doses, ginsenosides Rb1 and Rg1 significantly ameliorated redox status within the cells; they reduced ROS and TBARS levels and improved the glutathione system, as well as they enhanced SOD activity and Nrf2 pathway activation. They protected neuronal cells against MMP loss, calcium homeostasis disruption and aconitase inhibition. Consequently, apoptotic cell death was attenuated by the pre-treatment with ginsenosides, as evidenced by the reduction in caspase-3 and Bax, and the increase in Bcl-2 expressions; also, lower levels of cytochrome C were found in the cytosol. Poor BBB permeation was demonstrated for both ginsenosides. Conclusions In conclusion, ginsenosides Rb1 and Rg1 exhibit neuroprotective potential which is achieved, at least in part, via mitochondrial protection and the plausible involvement of Nrf2 pathway activation. Our results contribute to validate the traditional use of ginseng for cognitive-enhancing purposes and provide basis to encourage further research on the potential of ginsenosides in the treatment of neurodegenerative diseases.

Influence of fraxetin on the lifespan and longevity facing induced stress

This study was conducted to investigate the influence of treatment with fraxetin (7,8‐dihydroxy‐6‐methoxy coumarin), on the lifespan and longevity of Drosophila melanogaster (both sexes), introducing the treatment at different ages and comparing the differences in a situation of stress or not. Different groups were established to determine the maximum longevity (the maximum amount of time that an individual can survive) and the time of life was measured of an homogeneous population until the death of the last individual. This parameter is genetically determined; and is related to the metabolic rate and it appears unchangeable by most environmental factors. From this parameter, the average longevity was determined, establishing an average maximum age between the different subgroups for the same group of treatment, considering the maximum life reached in every subgroup. The third parameter studied is the lifespan (time that 50% of individuals survive), it is affected by both genetic and environmental factors. The object of this investigation was to establish the influence of stress (provoked by an assay of flyingcapacity) in the lifespan of the flies, and to study how treatment can protect individuals against induced stress. The survival values of the individuals submitted to an assay of flying capacity, during its development until the death of the last individual was evaluated. The three parameters for these individuals were established. Fraxetin administration did not reduce the lifespan in male Drosophila, but prolonged the lifespan and longevity in female flies, especially with a 2‐week treatment, both in normal conditions and in a stress situation (the assay of flying capacity was considered as the response to a stress situation). Male Drosophila in a stress situation presented with a reduction of flying capacity, related to age, and also of the maximum life. Whereas, females only presented changes in the flying parameter, without modifications in the lifespan.