Oral toxicity of the acetone extract of Coffea arabica var. Oro Azteca leaves in CD-1 mice.

The investigation of coffee leaves as a source of bioactive principles represents a relatively unexplored area of research. The study assesses the potential adverse effects of an aqueous acetone extract derived from Coffea arabica var. Oro Azteca leaves. The phenolic composition of the extract was identified and quantified by UPLC-MS/MS, and its acute and repeated-dose effects were evaluated in six-week-old CD-1 mice (n = 11 for acute evaluation and n = 20 female and n = 20 male for repeated-dose evaluation). The extract demonstrated no significant toxicity, maintaining consistent body weight and exhibiting a hepatoprotective effect by reducing ALT levels at a dose of 500 mg/kg. Some hyperactivity was observed at the highest doses, but overall, the extract enhanced the immune response and showed no histological alterations, except for mild inflammation in certain organs. The extract, which contains abundant quinic acid, chlorogenic acid, epicatechin, procyanidin B2, and mangiferin, has been deemed safe for consumption.

On a deterministic mathematical model which efficiently predicts the protective effect of a plant extract mixture in cirrhotic rats.

In this work, we propose a mathematical model that describes liver evolution and concentrations of alanine aminotransferase and aspartate aminotransferase in a group of rats damaged with carbon tetrachloride. Carbon tetrachloride was employed to induce cirrhosis. A second groups damaged with carbon tetrachloride was exposed simultaneously a plant extract as hepatoprotective agent. The model reproduces the data obtained in the experiment reported in [Rev. Cub. Plant. Med. 22(1), 2017], and predicts that using the plants extract helps to get a better natural recovery after the treatment. Computer simulations show that the extract reduces the damage velocity but does not avoid it entirely. The present paper is the first report in the literature in which a mathematical model reliably predicts the protective effect of a plant extract mixture in rats with cirrhosis disease. The results reported in this manuscript could be used in the future to help in fighting cirrhotic conditions in humans, though more experimental and mathematical work is required in that case.

Effects of Banana (Musa spp.) Bract Flour on Rats Fed High-Calorie Diet.

Research background: The extensive cultivation of bananas (Musa sp.) is related to producing tons of residues, such as leaves, pseudostems and bracts (inflorescences). The banana bract is a commercially interesting residue due to its dietary fibre content and high antioxidant potential. With this in mind, this study evaluates the effects of administering banana bract flour in animal models fed a cafeteria diet. Experimental approach: Thirty-two male rats were divided into 4 groups: (i) control diet, (ii) control diet with 10 % banana bract flour, (iii) hypercaloric diet, and (iv) hypercaloric diet with 10 % bract banana flour. The study was conducted for 12 weeks and included analysis of phenolic compounds, assessment of the antioxidant effect of banana bract flour, determination of serum biochemical parameters (glucose, total cholesterol, triglycerides, aspartate aminotransferase (AST), alanine transaminase (ALT), amylase, albumin, uric acid, creatine, total protein, and oral glucose), determination of faecal fat content, and histomorphological analysis of the liver, pancreas and adipose tissue. In addition, molecular parameters such as IL6, total and phosphorylated JNK, total and phosphorylated IKKß, TNFα, TLR4 and HSP70 were determined. Results and conclusions: The banana bract flour showed a high content of phenolic compounds and an antioxidant effect. The in vivo results suggest that the supplementation of a hypercaloric diet with banana bract flour prevented pathological damage by reducing total cholesterol and glucose amounts, which may imply a hepatoprotective effect of this supplement. Thus, using banana bract flour as a supplement can increase the consumption of fibre, antioxidants and bioactive compounds. Novelty and scientific contribution: The development of flour from banana waste and its inclusion in the diet can prevent and/or help treat obesity. In addition, the use of banana bracts can help protect the environment, as they are considered a source of waste by the food industry.

Caffeine attenuates liver damage and improves neurologic signs in a rat model of hepatic encephalopathy.

INTRODUCTION AND AIMS: Cirrhosis is the common outcome of liver diseases. It can be decompensated and lead to the development of complications, such as encephalopathy. Hyperammonemia that develops due to liver dysfunction is etiopathologically related to hepatic encephalopathy. Caffeine increases the activity of the urea cycle in the liver, augmenting ammonia degradation. By antagonizing adenosine receptors, it also has a hepatoprotective effect, impeding the formation of fibrosis, as well as having a stimulating effect on the central nervous system. The present study analyzed the effects of caffeine on the progression of cholestatic liver fibrosis and hepatic encephalopathy. MATERIALS AND METHODS: An experimental model of cholestatic liver fibrosis, through common bile duct ligature, and of hepatic encephalopathy, through the administration of a high-protein diet, was constructed. Male Wistar rats (n=32) were equally divided into 4 groups. The experiment lasted 28 days, with the administration of 50mg/kg/day of caffeine. Laboratory tests, histologic analyses of the liver and encephalon, open field tests (OFTs), and daily behavioral analyses were carried out. RESULTS: The ligated animals treated with caffeine had lower mean transaminase levels and improved histologic aspects of the liver and encephalon. The untreated ligated animals were clearly lethargic and apathetic at the last week of the experiment, confirmed by reduced exploratory activity during the OFT. CONCLUSION: Caffeine improved the microarchitecture of the liver and encephalon of the cirrhotic animals and prevented the decrease in exploratory behavior of the animals during the OFT.

Effect of low-fat diets enriched with fruit purees on the biochemical markers of metabolic syndrome analogy induced-rats / Efecto de dietas bajas en grasa enriquecida con purés de frutas sobre marcadores bioquímicos en ratas inducidas con analogia a sindrome metabólico

Fruit purees can be added to diet as alternative sources of bioactive compounds for the prevention and/or improvement of the complications of metabolic syndrome. In this work we evaluated the effect of the intake of low-fat diets enriched with fruit purees (guava-strawberry, guava-blackberry, guava-soursop, guava-passion fruit) on the body weight and biochemical markers in metabolic syndrome analogy (MSA)-induced rats. The rats (n=6 for each treatment) were induced with a high fat diet and were injected with streptozotocin, one dose every week for 4 consecutive weeks after fasting overnight, then healthy rats were fed with standard diet and MS rats were fed with standard diet plus each of the fruit puree, for 4 weeks. As novel findings, the diet enriched with fruit purees was associated with a reduction in body weight (~13-21 %) and a control in the metabolism of glucose by decreasing plasma glucose (~5963 %). Also, there was a reduction in the total cholesterol, triacylglycerols, low-density lipoproteins, and low enzymatic activities of alanine aminotransferase, alkaline phosphatase and γ-glutamyl transferase, useful metabolites in the control of inflammatory processes in the liver. A notable improvement in the liver morphology was observed indicating that the treatments had a hepatoprotective effect. The diet enriched with guava-blackberry puree caused the best results on most biochemical markers of MS rats. Therefore, diets enriched with fruit purees can be an alternative for MS individuals for the control and improvement of the complications caused by this syndrome.

Los purés de frutas se pueden agregar a la dieta como fuentes alternativas de compuestos bioactivos para la prevención y / o mejora de las complicaciones del síndrome metabólico. En este trabajo evaluamos el efecto de la ingesta de dietas bajas en grasas, enriquecidas con purés de frutas (guayaba-fresa, guayaba-mora, guayaba-guanábana, guayaba-maracuyá) sobre el peso corporal y los marcadores bioquímicos en el síndrome metabólico (SM) inducido en ratas. Las ratas (n = 6 para cada tratamiento) fueron inducidas con una dieta alta en grasas y se les inyectó estreptozotocina, una dosis cada semana durante 4 semanas consecutivas después de ayunar durante la noche. Luego, las ratas sanas fueron alimentadas con una dieta estándar; y las ratas con SM fueron alimentadas con dieta estándar más cada uno de los purés de frutas, durante 4 semanas. Como hallazgos novedosos, la dieta enriquecida con purés de frutas se asoció con una reducción en el peso corporal (~ 13-21 %) y un control en el metabolismo de la glucosa al disminuir la glucosa en plasma (~ 59-63 %). Además, hubo una reducción en el colesterol total, triacilgliceroles, lipoproteínas de baja densidad, y bajas actividades enzimáticas de alanina aminotransferasa, fosfatasa alcalina y gama-glutamil transferasa, metabolitos útiles en el control de los procesos inflamatorios en el hígado. Se observó una mejora notable en la morfología del hígado, lo que indica que los tratamientos tuvieron un efecto hepatoprotector. La dieta enriquecida con puré de guayaba y mora causó los mejores resultados en la mayoría de los marcadores bioquímicos de las ratas con SM. Por lo tanto, las dietas enriquecidas con purés de frutas pueden ser una alternativa para las personas con SM, para el control y la mejora de las complicaciones causadas por este síndrome.

Antioxidant and Hepatoprotective Effects of Croton hypoleucus Extract in an Induced-Necrosis Model in Rats.

The aim of this study was to evaluate the antioxidant and hepatoprotective activity of Croton hypoleucus (EC). The present work reports the first pharmacological, toxicological, and antioxidant studies of EC extract on liver injury. Liver necrosis was induced by thioacetamide (TAA). Five groups were established: Croton Extract (EC), thioacetamide (TAA), Croton extract with thioacetamide (EC + TAA), vitamin E with thioacetamide (VE + TAA) and the positive control and vehicle (CT). For EC and EC + TAA, Wistar rats (n = 8) were intragastrically pre-administered for 4 days with EC (300 mg/kg.day) and on the last day, EC + TAA received a single dose of TAA (400 mg/kg). At 24 h after damage induction, animals were sacrificed. In vitro activity and gene expression of superoxide dismutase (SOD), catalase (Cat), and Nrf2 nuclear factor were measured. The results show that EC has medium antioxidant properties, with an IC50 of 0.63 mg/mL and a ferric-reducing power of 279.8 µM/mg. Additionally, EC reduced hepatic damage markers at 24 h after TAA intoxication; also, it increased SOD and Cat gene expression against TAA by controlling antioxidant defense levels. Our findings demonstrated the hepatoprotective effect of EC by reducing hepatic damage markers and controlling antioxidant defense levels. Further studies are necessary to identify the mechanism of this protection.

Effect of Extract and Ellagic Acid from Geranium schiedeanum on the Antioxidant Defense System in An Induced-Necrosis Model.

Geranium schiedeanum has been used in traditional therapies as an antiseptic, antipyretic, and as analgesic. The present study was designed to evaluate the pretreatment with G. schiedeanum total extract (GS) and its active metabolites on stimulating the endogenous antioxidant defense system (EADS): catalase (Cat), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione reduction index (RI GSH/GSSG) in rat liver treated with a sublethal dose (6.6 mmol/Kg) of thioacetamide (TAA) in order to probe the capacity of GS and the active compounds to reduce liver injury. This was assessed by measuring aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (BILT) in rats pretreated or not with TAA, and pretreated or not with GS and its metabolites. The results showed that GS was able to induce the production of EADS enzymes, increasing redox index GSH/GSSG at 24 and 48 h after intoxication, and both the extract and the ellagic acid exhibited a significant reduction of hepatic damage markers. Our data confirmed the hepatoprotective effect of GS and its metabolites, like ellagic acid, support the possible use of this extract in the treatment of liver injury.

Hepatoprotective effect of Alhagi sparsifolia against Alcoholic Liver injury in mice

Overconsumption of alcohol leads to alcoholic liver disease (ALD). Natural compounds have been investigated previously for their hepatoprotective activities against liver injury. This study investigated the protective effect of Alhagi sparsifolia on ALD. Alcohol was administered to mice for three consecutive days; either alone or in combination with Alhagi sparsifolia extract (150, 300, 600 mg/kg). Serum aspartate aminotransferase and alanine transaminase as biomarkers of liver injury, the content of malonaldehyde, hydrogen peroxide (H2O2) and glutathione which indicated the redox status of liver and the antioxidant enzyme activity of super oxide dismutase were detected, respectively. Moreover, the expression of protein cytochrome P450 2E1 (CYP2E1) the key enzyme of alcohol metabolism, and also tested by western blot experiment. Subsequently, the mRNA levels of inflammatory factors including TNF- α and TLR4 was determined real-time PCR. Results showed that Alhagi sparsifolia significantly alleviated alcohol-induced liver injury by reducing serum ALT and AST, inhibiting MDA and H2O2 content, increasing SOD, and GSH level in the liver (P< 0.05). In addition, the Alhagi sparsifolia treatment inhibited the expression of CYP2E1 (P< 0.05). The results suggest that Alhagi sparsifolia could be a promising natural substance for ameliorating acute alcohol-induced oxidative stress and hepatic injury

Efecto hepatoprotector de una mezcla de siete plantas en cirrosis inducida con tetracloruro de carbono / Hepatoprotective effect of a mixture of seven plants in carbon tetrachloride induced cirrhosis

Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

Hepatoprotective effect of Maytenus robusta Reiss extract on CCl4-induced hepatotoxicity in mice and HepG2 cells.

We investigated the hepatoprotective effect of methanolic extract from Maytenus robusta leaves in mice and HepG2 cells. The administration of CCl4 in mice promoted a deep destruction of the histological lobular structure and increased the alanine aminotransferase (ALT) serum levels by 46.25% compared with the control group (p < 0.05). The M. robusta extract reduced the hepatic histological changes and normalization the ALT levels. The antioxidant effect of M. robusta in liver tissue promoted the reduction in 31.5% on lipoperoxides levels (p < 0.05), increased by 101.5% the reduced glutathione content (p < 0.05) and increased the activity of superoxide dismutase, catalase, and glutathione-S-transferase by 21.3% (p < 0.05), 49.3% (p < 0.05), and 27.6% (p < 0.05), respectively, compared with the vehicle group. Moreover, the extract reduced hepatic inflammation by diminishing myeloperoxidase activity, TNF and interleukin-6 levels by 29.4% (p < 0.05), 46.1% (p < 0.01), and 59.5% (p < 0.0001), respectively, compared with the vehicle group. The viability of HepG2 cells after incubation with CCl4 was 29.56± 3.07%, whereas the extract (300 µg/mL) restored the viability to 65.27± 8.75% and aspartate aminotransferase levels to 41.82 ± 4.41 U/L. The extract scavenged DPPH (IC50 = 14.44 µg/mL) and ABTS (IC50 = 3.00 µg/mL) radicals and did not produce acute toxicity in mice at 2000 mg/kg. In conclusion, was confirmed the hepatoprotective potential of M. robusta by its antioxidant effects.

Efecto hepatoprotector de una mezcla de siete plantas en cirrosis inducida con tetracloruro de carbono / Hepatoprotective effect of a mixture of seven plants in carbon tetrachloride induced cirrhosis

Introducción: las plantas medicinales han sido utilizadas con fines terapéuticos desde tiempos antiguos sobre diversas enfermedades, en este sentido, se han reportado por la medicina tradicional una gran variedad de plantas con actividad gastrointestinal y efecto hepatoprotector. Las plantas utilizadas en este estudio fueron Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. y Linum usitatissimum L. Objetivo: demostrar el efecto hepatoprotector de una mezcla de siete plantas (EHAM7) en ratas cirróticas inducidas con tetracloruro de carbono (CCl4). Métodos: se utilizaron las semillas de L. usitatissimum y las hojas y flores secas del resto de las plantas. Se formaron grupos de ratas control y ratas cirróticas con y sin tratamiento con la mezcla. A los animales cirróticos se les indujo el daño hepático intraperitonealmente con 0,2 mL de una mezcla de CCl4 y aceite mineral. Por otra parte, se les administraron oralmente 200 mg/kg del EHAM 7 re-suspendido en solución salina durante una semana y posteriormente cada tercer día durante ocho semanas. Los animales fueron sacrificados y se determinó el perfil hepático (transaminasas, bilirrubina y proteínas) y lipídico (triglicéridos, colesterol y lipoproteínas) en muestras de suero sanguíneo; el hígado se utilizó para los estudios histológicos. Resultados: el EHAM7 mostró efecto hepatoprotector en los animales cirróticos sobre los parámetros séricos correspondientes al perfil hepático y al perfil lipídico, lo cual se correlaciona con las características histológicas del hígado. Conclusión: el EHAM7 presenta efecto hepatoprotector en ratas cirróticas inducidas con CCl4, debido a que dicha mezcla presenta compuestos polifenólicos con actividad antioxidante(AU

Introduction: Medicinal plants have been used for therapeutic purposes against a great variety of diseases since ancient times. A large number of plants with gastrointestinal activity and hepatoprotective effect have been used in traditional medicine. The plants examined in the present study were Bidens odorata Cav. L., Tecoma stans L., Equisetum hyemale L., Rosmarinus officinalis L., Cynaya scolymus L., Peumus boldus L. and Linum usitatissimum L. Objective: Demonstrate the hepatoprotective effect of a mixture of seven plants (EHAM7) in carbon tetrachloride (CCl4) induced cirrhotic rats. Methods: The study used seeds of L. usitatissimum and dry flowers and leaves of the remaining plants. Groups were formed of control and cirrhotic rats with and without treatment with the mixture. Hepatic damage was induced intraperitoneally into the cirrhotic animals with 0.2 ml of a mixture of CCl4 and mineral oil. The rats were also administered 200 mg/kg EHAM7 resuspended in saline solution orally during a week and then every third day during eight weeks. The animals were sacrificed and determination was made of the hepatic profile (transaminases, bilirubin and proteins) and lipid profile (triglycerides, cholesterol and lipoproteins) in blood serum samples. The liver was preserved for histological examination. Results: EHAM7 was found to have an hepatoprotective effect on the serum parameters corresponding to the hepatic and lipid profiles of cirrhotic animals, which correlates with the histological characteristics of the liver. Conclusion: EHAM7 has a hepatoprotective effect in CCl4 induced cirrhotic rats, since the mixture contains polyphenolic compounds with antioxidant activity(AU)

Inulin-type fructan and infusion of Artemisia vulgaris protect the liver against carbon tetrachloride-induced liver injury.

BACKGROUND: Infusions of aerial parts of Artemisia vulgaris L. (Asteraceae) are used in herbal medicine to treat several disorders, including hepatosis. PURPOSE: Evaluation of in vivo hepatoprotective effects of A. vulgaris infusion (VI) and inulin (VPI; i.e., the major polysaccharide of VI). STUDY DESIGN: The hepatoprotective effect of A. vulgaris extracts on carbon tetrachloride (CCl4)-induced hepatotoxicity and the probable mechanism involved in this protection were investigated in mice. METHODS: A. vulgaris infusion (VI) was prepared according to folk medicine using the aerial parts of the plant. Carbohydrate, protein, and total phenolic content was determined in VI, and its phenolic profile was determined by high-performance liquid chromatography (HPLC). Male Swiss mice were orally pretreated for 7 days with VI or VPI (once per day). On days 6 and 7 of treatment, the mice were intraperitoneally challenged with CCl4. Liver and blood were collected and markers of hepatic damage in plasma and oxidative stress in the liver were analyzed. Hepatic histology and inflammatory parameters were also studied in the liver. The scavenging activity of VI and VPI were evaluated in vitro using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. RESULTS: VI contained 40% carbohydrates, 2.9% proteins and 9.8% phenolic compounds. The HPLC fingerprint analysis of VI revealed chlorogenic, caffeic and dicaffeoylquinic acids as major low-molar-mass constituents. Oral pretreatment with VI and VPI significantly attenuated CCl4-induced liver damage, reduced the activity of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) in plasma, and prevented reactive oxygen species accumulation and lipid peroxidation in the liver. Comparisons with the CCl4-treated group showed that VI and VPI completely prevented necrosis, increased the levels of reduced glutathione (GSH), and reduced tumor necrosis factor alpha (TNF-α) level in the liver. VI and VPI also exhibited high radical scavenging activity in vitro. CONCLUSION: VI and VPI had remarkable hepatoprotective effects in vivo, which were likely attributable to antioxidant and immunomodulatory properties. The present findings support the traditional use of A. vulgaris infusion for the treatment of hepatic disorders.