Iron chelation mitigates mitochondrial dysfunction and oxidative stress by enhancing nrf2-mediated antioxidant responses in the renal cortex of a murine model of type 2 diabetes.

Renal iron overload is a common complication of diabetes that leads to oxidative stress and mitochondrial dysfunction in the kidneys. This study investigated the effects of iron chelation using deferiprone on mitochondrial dysfunction and oxidative stress in the renal cortex of a murine model of type 2 diabetes. Diabetic rats were treated with deferiprone (50 mg/kg BW) for 16 weeks. Our results show that iron chelation with deferiprone significantly increased the nuclear accumulation of Nrf2, a transcription factor that regulates the expression of antioxidant enzymes. This led to enhanced antioxidant capacity, reduced production of reactive oxygen species, and improved mitochondrial bioenergetic function in diabetic rats. However, chronic iron chelation led to altered mitochondrial respiration and increased oxidative stress in non-diabetic rats. In conclusion, our findings suggest that iron chelation with deferiprone protects mitochondrial bioenergetics and mitigates oxidative stress in the renal cortex, involving the NRF2 pathway in type 2 diabetes.

Antioxidant Effect of the Ethyl Acetate Extract of Potentilla indica on Kidney Mitochondria of Streptozotocin-Induced Diabetic Rats.

Diabetes mellitus (DM) is a metabolic disorder characterized by persistent hyperglycemia. This state may lead to an increase in oxidative stress, which contributes to the development of diabetes complications, including diabetic kidney disease. Potentilla indica is a traditional medicinal herb in Asia, employed in the treatment of several diseases, including DM. In this study, we investigated the antioxidant effect of the ethyl acetate extract of Potentilla indica both in vitro and on kidneys of streptozotocin-induced diabetic male rats. Firstly, phytochemicals were identified via UPLC-MS/MS, and their in vitro antioxidant capabilities were evaluated. Subsequently, male Wistar rats were assigned into four groups: normoglycemic control, diabetic control, normoglycemic treated with the extract, and diabetic treated with the extract. At the end of the treatment, fasting blood glucose (FBG) levels, creatinine, blood urea nitrogen (BUN), and uric acid were estimated. Furthermore, the kidneys were removed and utilized for the determination of mitochondrial reactive oxygen species (ROS) production, mitochondrial respiratory chain complex activities, mitochondrial lipid peroxidation, glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. The in vitro findings showed that the major phytochemicals present in the extract were phenolic compounds, which exhibited a potent antioxidant activity. Moreover, the administration of the P. indica extract reduced creatinine and BUN levels, ROS production, and lipid peroxidation and improved mitochondrial respiratory chain complex activity and GSH-Px, SODk, and CAT activities when compared to the diabetic control group. In conclusion, our data suggest that the ethyl acetate extract of Potentilla indica possesses renoprotective effects by reducing oxidative stress on the kidneys of streptozotocin-induced diabetic male rats.

An Ethyl Acetate Extract of Eryngium carlinae Inflorescences Attenuates Oxidative Stress and Inflammation in the Liver of Streptozotocin-Induced Diabetic Rats.

Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from streptozotocin (STZ)-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver triacylglycerides (TG) levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. We hypothesize that solvent polarity and consequently chemical composition of the ethyl acetate extract of E. carlinae, exert the beneficial effects due to phenolic compounds. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

Antifungal Activity of Avocado Seed Recombinant GASA/Snakin PaSn.

The avocado fruit (Persea americana) has become a significant fruit in the human diet for its nutritional properties. However, the seed is a source of bioactive molecules and has been poorly utilized. Previously, we reported that the PaSn gene is expressed in the avocado seeds, a cysteine-rich antimicrobial peptide (GASA/Snakin), and demonstrated its antibacterial activity. In this work, we report the recombinant production of PaSn in the Escherichia coli system and evaluate its antifungal activity against plant and human pathogen fungi. The recombinant peptide showed antifungal activity at 200 µg/mL against phytopathogens Colletotrichum gloeosporioides and Fusarium oxysporum and human pathogens Candida albicans and C. glabrata. Our results demonstrate the usefulness of a prokaryotic expression system for avocado antimicrobial peptide production. In conclusion, the snakin PaSn could be helpful in the control of postharvest avocado and other fruits' fungal diseases and human fungal pathogens.

Gallic, ellagic acids and their oral combined administration induce kidney, lung, and heart injury after acute exposure in Wistar rats.

Gallic (GA) and ellagic (EA) acids are present in foods, medicinal plants, teas, and dietary supplements. An acute toxicological study was conducted by oral administration of both compounds alone (200, 1000, and 2000 mg/kg) and combined (2000 mg/kg) and their effects on the electron transport chain (ETC) and the ROS production in kidney mitochondria further evaluated. All treatments induced a dose-dependent heart, lung, and kidney injury. However, the intensity of these effects varied according to the substance, with greater cardiac and renal toxicity for EA and pulmonary injury for GA, while the combination attenuated the toxicity of the isolated molecules. All substances inhibited the activity of complexes II, III, and IV of the ETC from renal mitochondria. However, no changes were observed regarding mitochondrial ROS production. These compounds have a non-negligible inherent deleterious potential, so their uncontrolled use at high doses (≥200 mg/kg) could cause undesirable effects.

In vitro selection of blackberry (Rubus fruticosus 'Tupy') plants resistant to Botrytis cinerea using gamma ray-irradiated shoot tips.

Blackberry is an economically important crop in Mexico, and its yield is substantially reduced by gray mold, a disease caused by Botrytis cinerea. One of the means to obtain B. cinerea-resistant plants is gamma irradiation. Shoot tips of in vitro-micropropagated blackberry plants (Rubus fruticosus 'Tupy') were irradiated with five doses of Cobalt-60 gamma radiation (0, 15, 30, 45, and 60 Gy) and cultured on Murashige and Skoog basal medium containing 1.0 mg l-1 benzylaminopurine and 0.06 mg l-1 indole-3-butyric acid (MSB medium). After 28 days of culture, survival was evaluated to determine mean lethal dose (LD50), and 200 shoots were further irradiated at the determined LD50 (30.8 Gy). After 28 days, the surviving shoots were micropropagated on MSB medium for 60 days. Non-irradiated shoots were screened for the in vitro selection of resistant B. cinerea, exposing them to different concentrations of sterile culture filtrate of B. cinerea (0, 2, 4, 6, 8, and 10 g l-1) for 28 days to determine mean lethal concentration (LC50), and the irradiated surviving shoots were further exposed to the determined LC50 (4.6 g l-1). Three surviving lines (rfgum5, rfgum6, and rfgum17) that did not present changes compared with the control shoots were micropropagated to obtain plantlets, which were further subjected to in vitro resistance assays using detached leaves inoculated with B. cinerea (1×103 spores ml-1). Plants of rfgum5 and rfgum6 mutant lines were highly resistant and presented similar growth to control plants. Therefore, this methodology is useful to obtain B. cinerea-resistant blackberry plants.

Antilipidemic and Hepatoprotective Effects of Ethanol Extract of Justicia spicigera in Streptozotocin Diabetic Rats.

Oxidative stress is a factor that contributes to the development of complications in diabetes; however, its effects can be counteracted using exogenous antioxidants that are found in some plants, which is why people turn to traditional medicines in the search for therapeutic treatment. Justicia spicigera has been demonstrated to have the capacity to reduce glycemic levels; however, its effects on non-insulin-dependent organs such as the liver have not been reported. During 30 days of administration of Justicia spicigera ethanol extract, the blood glucose and weight of rats were measured every 5 days. Once the treatment was concluded, the rats were sacrificed. Corporal weight, blood glucose, cholesterol, very-low-density lipoprotein (VLDL), triglycerides, total lipids, and liver profile were reduced in the diabetic condition and normalized with the application of ethanol extract from J. spicigera (EJS). Additionally, there was a significant increase in catalase and superoxide dismutase activity in the control diabetic rats, a decrease in their activity with the extract administration, and no effect on normoglycemic rats. In conclusion, EJS is considered to be capable of reducing oxidative stress by maintaining diminished lipid and liver function profiles in male Wistar rats with streptozotocin-induced diabetes.

Metabolomics studies of allelopathy: a review

SUMMARY Introduction: Allelopathy is a harmful effect indirectly or directly produced by one plant to another through the production of chemical substances that enter the environment. Allelopathy has a pertinent significance for systems of ecological, sustainable, and integrated management. These natural reactions have multiple effects, ranging from processes of inhibition and stimulation of growth in neighbor plants to inhibition of seed germination. Metabolomics is a discipline integral that studies all the metabolites in a particular tissue, organ, or organism in a specific developmental stage or under particular environmental conditions, and it allows for the assessment of the contribution of genetic and environmental factors to the modification of metabolism. With the growing number of "omics", new approaches can be used to understand metabolic changes that occur in plants, especially in proteomics and metabolomics, and thus those analyses could be profiled in coming years with the objective of knowing the allelopathome of a larger number of plant species and their interactions. Aim: To provide a recent update on the science of allelopathy in the context of physiology, practical application of metabolomics in allelopathic studies, allelochemicals analyzed by metabolomics in alfalfa, rice, canola, sorghum, rye, wheat and other crops and finally mentionated the biological activity of allelopathic secondary metabolites. Methods: A recent comprehensive literature search of allelopathy and metabolomics in journal databases was carried out. Results: The concept of allelopathy, allelopathic mechanisms, metabolomic studies in allelopathy, allelochemicals analysed by metabolomics in alfalfa, rice, canola, rye sorghum, wheat and other agro-industrially important crops, and the biological activity of allelopathic secondary metabolites are detailed. Conclusions: These studies suggest that a combination of secondary metabolites can be used to attack weeds. In situ and In vitro culture of secondary metabolites (allelochemical types) is recommended to be used as organics compounds in weed organic control in the future.

Introducción: la alelopatía es un efecto nocivo producido directa o indirectamente por una planta a otra a través de la producción de sustancias químicas que ingresan al medio ambiente. La alelopatía es importante para los sistemas de manejo ecológico, sostenible e integrado. Estas reacciones naturales tienen múltiples efectos, que van desde procesos de inhibición y estimulación del crecimiento en plantas vecinas hasta la inhibición de la germinación de semillas. La metabolómica es una disciplina integral que estudia todos los metabolitos en un determinado tejido, órgano u organismo en una determinada etapa de desarrollo o en determinadas condiciones ambientales, y permite evaluar la contribución de los factores genéticos y ambientales a la modificación del metabolismo. Con el creciente número de "ómicas", se pueden utilizar nuevos enfoques para comprender los cambios metabólicos que ocurren en las plantas, especialmente en proteómica y metabolómica, y así esos análisis podrían perfilarse en los próximos años con el objetivo de conocer el alelopatoma de un mayor número. de las especies de plantas y sus interacciones. Objetivo: proporcionar una actualización reciente sobre la ciencia de la alelopatía en el contexto de la fisiología, la aplicación práctica de la metabolómica en los estudios alelopáticos, los aleloquímicos analizados por metabolómica en alfalfa, arroz, canola, sorgo, centeno, trigo y otros cultivos y, finalmente, mencionar los aspectos biológicos. actividad de los metabolitos secundarios alelopáticos. Métodos: se realizó una búsqueda bibliográfica exhaustiva reciente sobre alelopatía y metabolómica en bases de datos de revistas. Resultados: se detalla el concepto de alelopatía, los mecanismos alelopáticos, los estudios metabolómicos en alelopatía, los aleloquímicos analizados por metaboló-mica en alfalfa, arroz, canola, sorgo de centeno, trigo y otros cultivos de importancia agroindustrial, y la actividad biológica de los metabolitos secundarios alelopáticos. Conclusiones: estos estudios sugieren que se puede utilizar una combinación de metabolitos secundarios para atacar a las malas hierbas. Se recomienda el cultivo in situ e in vitro de metabolitos secundarios (de tipo aleloquímico) para ser utilizados como compuestos orgánicos en el control orgánico de las malas hierbas en el futuro.

Introdução: A alelopatia é um efeito nocivo produzido de forma indireta ou direta por uma planta a outra por meio da produção de substâncias químicas que adentram o meio ambiente. A alelopatia é importante para sistemas de manejo ecológico, sustentável e integrado. Essas reações naturais têm múltiplos efeitos, que vão desde processos de inibição e estimulação do crescimento em plantas vizinhas até a inibição da germinação de sementes. A metabolômica é uma disciplina integral que estuda todos os metabólitos em um determinado tecido, órgão ou organismo em um estágio de desenvolvimento específico ou condições ambientais particulares, e permite avaliar a contribuição de fatores genéticos e ambientais para a modificação do metabolismo. Com o crescente número de "ômicas", novas abordagens podem ser utilizadas para entender as alterações metabólicas que ocorrem nas plantas, principalmente em proteômica e metabolómica, e assim essas análises poderão ser perfiladas nos próximos anos com o objetivo de conhecer o alelopatoma de um número maior das espécies vegetais e suas interações. Objetivo: fornecer uma atualização recente sobre a ciência da alelopatia no contexto da fisiologia, aplicação prática da metabolômica em estudos alelopáticos, aleloquímicos analisados por metabolômica em alfafa, arroz, canola, sorgo, centeio, trigo e outras culturas e, finalmente, mencionar atividade de metabólitos secundários alelopáticos. Métodos: uma pesquisa bibliográfica abrangente recente sobre alelopatia e metabolismo foi conduzida em bancos de dados de periódicos. Resultados: o conceito de alelopatia, mecanismos alelopáticos, estudos metabólicos em alelopatia, aleloquímicos analisados por metabolômicos em alfafa, arroz, canola, sorgo de centeio, trigo e outros cultivos agroindustriais importantes, e a atividade biológica dos metabólitos secundários alelopáticos são detalhados. Conclusões: esses estudos sugerem que uma combinação de metabólitos secundários pode ser usada para atacar ervas daninhas. Recomenda-se o cultivo in situ e in vitro de metabólitos secundários (tipo alquímico) para uso como compostos orgânicos no controle de ervas daninhas orgânicas no futuro.

Cytotoxicity of a Lipid-Rich Extract from Native Mexican Avocado Seed (Persea americana var. drymifolia) on Canine Osteosarcoma D-17 Cells and Synergistic Activity with Cytostatic Drugs.

Osteosarcoma is the most common malignant bone tumor in both children and dogs. It is an aggressive and metastatic cancer with a poor prognosis for long-term survival. The search for new anti-cancer drugs with fewer side effects has become an essential goal for cancer chemotherapy; in this sense, the bioactive compounds from avocado have proved their efficacy as cytotoxic molecules. The objective of this study was to determine the cytotoxic and antiproliferative effect of a lipid-rich extract (LEAS) from Mexican native avocado seed (Persea americana var. drymifolia) on canine osteosarcoma D-17 cell line. Also, the combined activity with cytostatic drugs was evaluated. LEAS was cytotoxic to D-17 cells in a concentration-dependent manner with an IC50 = 15.5 µg/mL. Besides, LEAS induced caspase-dependent cell apoptosis by the extrinsic and intrinsic pathways. Moreover, LEAS induced a significant loss of mitochondrial membrane potential and increased superoxide anion production and mitochondrial ROS. Also, LEAS induced the arrest of the cell cycle in the G0/G1 phase. Finally, LEAS improved the cytotoxic activity of cisplatin, carboplatin, and in less extension, doxorubicin against the canine osteosarcoma cell line through a synergistic effect. In conclusion, avocado could be a potential source of bioactive molecules in the searching treatments for osteosarcoma.

Quantitative Analysis of Rutin by HPTLC and In Vitro Antioxidant and Antibacterial Activities of Phenolic-Rich Extracts from Verbesina sphaerocephala.

Verbesina sphaerocephala A. Gray, like other wild plants of the genus Verbesina, has been used in herbal medicine. There is information for other species of the genus related to their phenolic content, antioxidant capacity, and isolation of bioactive compounds with antimicrobial activity. However, there are no reports for V. sphaerocephala, although it has an important presence in the state of Michoacán, México. In this study, the phenolic composition, quantification of rutin, and in vitro antioxidant and antibacterial activities of methanolic extracts from V. sphaerocephala leaves and flowers were determined. The results showed that all the investigated extracts have high phenolic and flavonoid contents. The flavonoid rutin was identified in all the extracts from V. sphaerocephala by high-performance thin-layer chromatography (HPTLC). The V. sphaerocephala extracts showed scavenging activity against DPPH• and ABTS•+ radicals (IC50 and 5.83 ± 0.50 and 0.93 ± 0.01 mg/mL, respectively) as well as relevant antioxidant capacity (51.05 ± 0.36 mg of ascorbic acid/g of dry tissue). The experimental results show that V. sphaerocephala extracts possessed a strong antimicrobial activity against Escherichia coli and Staphylococcus aureus bacteria. This research indicates that V. sphaerocephala could be considered as a potential source of natural compounds from the point of ethnopharmacological usage.