Hepatotoxicity-induced by the therapeutic dose of acetaminophen and the ameliorative effect of oral co-administration of selenium/Tribulus terrestris extract in rats / Hepatotoxicidad inducida por la dosis terapéutica de acetaminofén y el efecto de mejora de la administración conjunta de extracto de selenio Tribulus terrestris en ratas

SUMMARY: Over dose or long-term clinical use of therapeutic doses of acetaminophen (APAP) causes hepatotoxicity. Various strategies attempted to ameliorate APAP-hepatotoxicity have been found to be unsuitable for clinical practice. This study was aimed to illustrate the histopathological changes induced by therapeutic dose of APAP and investigate the hepatoprotective role of oral co-administration of selenium/ Tribulus terrestris (TT) extract concurrently against hepatotoxicity induced by APAP in rats. Fifty-four healthy male albino Wistar rats were randomized into nine groups (G1-G9) of six rats each, and administered with APAP and TT orally for 30 days as follows: Control (2ml normal saline), APAP (470 mg/kg), APAP (470 mg/kg) + selenium (2 mg/kg), APAP (470 mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + selenium (2mg/kg) + TT (98 mg/kg), APAP (470 mg/kg) + silymarin (200 mg/kg), selenium (2 mg/ kg), TT (98 mg/kg) and silymarin (200 mg/kg) groups. The results demonstrated that exposure of rats to therapeutic dose of APAP for 30 days caused significant histopathological changes parallel to elevated blood chemistry parameters. Co-administration of selenium/TT extract showed significantly reduced histopathological lesions and, restored or decreased levels of the examined blood chemistry parameters. Liver histology in selenium/TT extract showed normal hepatic architecture with mild changes and silymarin treated rats showed no histopathological changes. Histochemically PAS staining, showed that APAP-induced hepatotoxicity was characterized by hepatocytes glycogen depletion. Selenium/TT co-supplementation plays a potential role in preventing APAP-induced glycogen depletion by increasing detoxification and scavenging the reactive metabolites. Selenium/TT extract oral co-administration possesses a significant hepatoprotective property and mitigates APAP-induced hepatotoxicity by enhancing its antioxidant role and improving tissue integrity. Selenium/TT supplementation could represent an effective treatment against APAP-induced hepatotoxicity. Further studies are needed to elucidate the exact mechanism underlying the protective role of TT extract.

RESUMEN: La dosis excesiva o el uso clínico a largo plazo de dosis terapéuticas de acetaminofeno (APAP) causa hepatotoxicidad. Se ha descubierto que varias estrategias que intentaron mejorar la hepatotoxicidad por APAP no son adecuadas para la práctica clínica. Este estudio tuvo como objetivo ilustrar los cambios histopatológicos inducidos por la dosis terapéutica de APAP e investigar el papel hepatoprotector de la administración conjunta de extracto de selenio / Tribulus terrestris (TT) simultá- neamente contra la hepatotoxicidad inducida por APAP en ratas. Cincuenta y cuatro ratas Wistar albino machos sanas se aleatorizaron en nueve grupos (G1 - G9) de seis ratas cada una, y se administraron con APAP y TT por vía oral durante 30 días de la siguiente manera: Control (2 ml de solución salina normal), APAP (470 mg / kg), APAP (470 mg / kg) + selenio (2 mg / kg), APAP (470 mg / kg) + TT (98 mg / kg), APAP (470 mg / kg) + selenio (2 mg / kg) + TT (98 mg / kg), APAP (470 mg / kg) + silimarina (200 mg / kg), selenio (2 mg / kg), TT (98 mg / kg) y silimarina (200 mg / kg). Los resultados demostraron que la exposición de las ratas a la dosis terapéutica de APAP durante 30 días causó cambios histopatológicos significativos paralelos a parámetros elevados de química sanguínea. La administración conjunta de extracto de selenio / TT mostró lesiones histopatológicas significativamente reducidas y niveles restaurados o disminuidos de los parámetros de química sanguínea. La histología hepática en el extracto de selenio / TT mostró una arquitectura hepática normal con cambios leves y las ratas tratadas con silimarina no mostraron cambios histopatológicos. La tinción histoquímica de PAS mostró que la hepatotoxicidad inducida por APAP se caracterizó por la pérdida de glucógeno de los hepatocitos. La suplementación con selenio / TT juega un papel potencial en la prevención de la pérdida de glucógeno inducido por APAP al aumentar la desintoxicación y eliminar los metabolitos reactivos. La administración conjunta de extracto de selenio / TT posee una propiedad hepatoprotectora significativa y mitiga la hepatotoxicidad inducida por APAP al mejorar su papel antioxidante y la integridad del tejido. La suplementación con selenio / TT podría representar un tratamiento efectivo contra la hepatotoxicidad inducida por APAP. Se necesitan más estudios para dilucidar el mecanismo exacto que subyace a la función protectora del extracto TT.

Tribulus terrestris for female sexual dysfunction: a systematic review / Tribulus terrestris para disfunção sexual feminina: uma revisão sistemática

Abstract Objective We performed a systematic review to assess the effectiveness and safety of Tribulus terrestris to treat female sexual dysfunction (FSD). Data sources We performed unrestricted electronic searches in the MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO,WHO-ICTR, Clinicaltrials.gov and OpenGrey databases. Selection of studies We included any randomized controlled trials (RCTs) that compared T. terrestris versus inactive/active interventions. After the selection process, conducted by two reviewers, 5 RCTs (n = 279 participants) were included. Data collection Data extraction was performed by two reviewers with a preestablished data collection formulary. Data synthesis Due to lack of data and clinical heterogeneity, we could not perform meta-analyses. The risk of bias was assessed by the Cochrane Risk of Bias (RoB) tool, and the certainty of evidence was assessed with Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Results After 1 to 3 months of treatment, premenopausal and postmenopausal women randomized to T. terrestris had a significant increase in sexual function scores. Three months of treatment with T. terrestris showed a significant increase in the serum testosterone levels of premenopausal women. There was no report of serious adverse events, and none of the studies assessed health-related quality of life. The certainty of the evidence was very low, whichmeans that we have very little confidence in the effect estimates, and future studies are likely to change these estimates. Conclusion MoreRCTs are needed to supportor refute the use of T. terrestris. The decision to use this intervention should be shared with the patients, and the uncertainties around its effects should be discussed in the clinical decision-making process. Number of Protocol registration in PROSPERO database: CRD42019121130

Resumo Objetivo Nós realizamos uma revisão sistemática para avaliar a efetividade e a segurança do Tribulus terrestris no tratamento da disfunção sexual feminina (DSF). Fontes de dados Nós realizados uma busca eletrônica irrestrita nas seguintes bases de dados: MEDLINE, CENTRAL, EMBASE, LILACS, CINAHL, PsycINFO, WHO-ICTR, Clinicaltrials.gov, e OpenGrey. Seleção dos estudos Nós incluímos todos os ensaios clínico randomizados (ECR) que comparou T. terrestris com controles ativos/inativos. Após o processo de seleção, conduzido por 2 revisores, 5 ECRs (n = 279 participantes) foram incluídos. Extração de dados O processo de extração de dados foi realizado por dois revisores, utilizando-se um formulário de extração de dados pré-estabelecido. Síntese de dados Devido à falta de dados disponíveis e à heterogeneidade clínica entre os estudos incluídos, nós não realizamos meta-análises. O risco de viés foi avaliado pela tabela de risco de viés da Cochrane e, a certeza do corpo da evidência foi avaliada pelo Grading of Recommendations, Assessment, Development and Evaluations (GRADE). Resultados Após 1 a três 3 meses de tratamento, mulheres na pré e pós-menopausa randomizadas ao T. terrestris tiveram um aumento significante nos escores de função sexual. O grupo com 3 meses de tratamento com T. terrestris exibiu um aumento significante dos níveis séricos de testosterona emmulheres pré-menopausa. Não houve relato de eventos adversos graves, e nenhum estudo avaliou qualidade de vida das participantes. A certeza da evidência foi considerada muito baixa, o que significa que existe pouca certeza na estimativa dos efeitos e que é provável que futuros estudos mudem estas estimativas. Conclusão Mais ECRs são importantes para apoiar ou refutar o uso do T. terrestris. A decisão de usar essa intervenção deve ser compartilhada com pacientes, e as incertezas sobre seus efeitos devem ser discutidas durante o processo de decisão clínica.

Simultaneous use of oxalate-degrading bacteria and herbal extract to reduce the urinary oxalate in a rat model: A new strategy

ABSTRACT Objective: Urinary stones with oxalate composition can cause kidney failure. Recent findings evidenced that probiotics are effective in reducing oxalate absorption in these subjects based on their high colonic absorption levels at baseline. The purpose of this study was to evaluate the effect of the simultaneous use of oxalate-degrading bacteria, Urtica dioica and T. terrestris extract in reducing urinary oxalate. Materials and Methods: Anti-urolithiatic activity of Urtica dioica and T. terrestris extract and probiotic by using ethylene glycol induced rat model. In this study, 4 strains of Lactobacillus and 2 strains of Bifidobacterium and also 2 strains of L. paracasei (that showed high power in oxalate degrading in culture media) were used. Male Wistar rats were divided into four groups (n=6). The rats of group-I received normal diet (positive control group) and groups-II (negative control group), III, IV rats received diet containing ethylene glycol (3%) for 30 days. Groups III rats received Urtica dioica and T. terrestris extract. Groups IV rats received extracts + probiotic for 30 days. Findings: The results show that the use of herbal extracts (Urtica dioica and T. terrestris) reduced the level of urinary oxalate and other parameters of urine and serum. Also, the accumulation of calcium oxalate crystals in the kidney tissue was significantly reduced. Conclusion: Considering that the formation of calcium oxalate crystals can cause inflammation and tissue damage in the kidney, the use of herbal extracts with oxalate degrading bacteria can be a new therapeutic approach to preventing the formation of kidney stones.

Improvement of fertility parameters with tribulus terrestris and anacyclus pyrethrum treatment in male rats

ABSTRACT Objective Anacyclus Pyrethrum (AP) and Tribulus Terrestris (TT) have been reported as male infertility treatment in several studies; however, in Iranian traditional medicine these two plants are prescribed simultaneously. In this study, we aimed to determine the effects of AP and TT extracts both separately and simultaneously on the male Wistar rat fertility parameters. Materials and Methods 32 male Wistar rats were divided into 4 groups: Control, TT, AP, and AT treated groups. Treatment continued for 25 days and rats were weighed daily. Their testes were dissected for histological studies. Sperm analysis including sperm count, viability and motility were performed. Serum was obtained to evaluate testosterone, LH and FSH levels. Histological studies were conducted to study Leydig, and Sertoli cells, spermatogonia and spermatid cell numbers, and to measure seminiferous diameter and epithelium thickness. Results Sperm count increased in all the treatment groups. Sperm viability and motility in AT and AP groups were elevated. TT and AT groups showed significantly increased testosterone level compared to control group (P=004, P=0.000, respectively) and TT, AP and AT treatment groups showed increased LH level (P=0.002, P=0.03 and P=0.000, respectively) compared to control, while only AT group showed increased FSH (p=0.006) compared to control. Histological studies showed significant increase of spermatogonia, Leydig and Sertoli cell numbers and epithelial thickness in AT group compared to other groups. All the treatment groups had higher number of Leydig, spermatogonia and spermatid cells. Conclusion TT and AP improved sexual parameters; however, their simultaneous administration had higher improving effects on studied parameters.

Hepatoprotective effects of Tibulus terrestris hydro-alcholic extract on non-alcoholic fatty liver- induced rats / Efectos hepatoprotectores del extracto hidro-alcohólico de Tribulus terrestris en ratas con inducción de hígados grasos no alcólicos

Non-alcoholic fatty liver induces many complications to the liver tissue and also serum related parameters. Medicinal plants are the safe therapeutic strategy for the treatment of diseases. In this regards, the present study was conducted to evaluate the effect of Tribulus terrestris (T. terrestris) extract on non-alcoholic fatty liver in rats. In this experimental study, thirty male Wistar rats were divided into five groups (n=6). Animals in experimental groups were received high fructose diet (70 %) (HDF) daily alone or in combined with daily intraperitoneal injection of 500, 700 and 1000 mg/kg extract of T. terrestris. Control group of rats was feed with standard chow. The serum levels of biomarkers of liver and serum lipid profiles were assessed, also histopathological examination of liver tissue done. Data were analyzed using One-way ANOVA method followed by Tukey's post-hoc multiple comparison test and P<0.05 was considered statistically significant. There were significant improvements for biomarkers of liver tissue (P<0.05) and serum lipid profiles (P<0.01) in the HFD-fed rats that were treated with T. terrestris extract compare to HFD-fed group. In addition, accumulation of lipids in hepatocytes was significantly reduced in the HFD-fed + extract administrated groups in comparison to HFD-fed rats (P<0.01). T. terrestris extract has protective effects against non-alcoholic fatty liver by changing biomarkers of liver tissue, serum lipid profiles and histopathological anomalies of liver tissue, to normal range.

El hígado graso no alcohólico induce muchas complicaciones al tejido hepático y también en ciertos parámetros relacionados con el suero. Las plantas medicinales son la estrategia terapéutica segura para el tratamiento de enfermedades. En este sentido, el presente estudio se realizó para evaluar el efecto del extracto de Tribulus terrestris (T. terrestris) sobre el hígado graso no alcohólico en ratas. En este estudio experimental se dividieron 30 ratas macho Wistar en cinco grupos (n = 6). Los animales de los grupos experimentales recibieron dietas altas en fructosa (70 %) (HDF) al día o en combinación con inyección intraperitoneal diaria de 500, 700 y 1000 mg / kg de extracto de T. terrestris. El grupo control de ratas fue alimentado con alimento estándar. Se evaluaron los niveles séricos de biomarcadores hepáticos y perfiles de lípidos séricos, así como un examen histopatológico del tejido hepático. Los datos se analizaron utilizando el método ANOVA de una vía seguido de la prueba de comparación múltiple post-hoc de Tukey y el P<0,05 se consideró estadísticamente significativo. Hubo mejoras significativas en los biomarcadores del tejido hepático (P <0,05) y en los perfiles de lípidos séricos (P <0,01) en las ratas alimentadas con HFD que se trataron con extrato de T. terrestris comparado con el grupo alimentado con HFD. Además, la acumulación de lípidos en los hepatocitos se redujo significativamente en los grupos alimentados con HFD + extracto, en comparación con las ratas alimentadas con HFD (P <0,01). El extracto de T. terrestris tiene efectos protectores sobre el hígado graso no alcohólico, provocando modificaciones en los marcadores biológicos del tejido hepático, los perfiles lipídicos del suero y las anomalías histopatológicas del tejido hepático, hasta un rango normal.

Protective effect of Tribulus terrestris hydroalcoholic extract against cisplatin-induced cytotoxicity on sperm parameters in male mice / Efecto protector del extracto hidroalcohólico de Tribulus terrestris contra la citotoxicidad inducida por cisplatino sobre parámetros espermáticos en ratones macho

Cisplatin is an anti-cancer drug used in chemotherapy. One of the limiting side effects of cisplatin is decreasing genital gland function, azoospermia and oligospermia. Tribulus terrestris has been used as an aphrodisiac. The present study amid to investigate protective effect of Tribulus terrestris hydroalcoholic extract against cisplatin-induced cytotoxicity on sperm parameters in mice. Male adult mice (n=30) were divided into control and 4 experimental groups (n=6). Control group received saline, first experimental group received cisplatin (5.5 mg/kg) and other three experimental groups received cisplatin (5.5 mg/kg) and different doses of hydroalcoholic extact of Tribulus terrestris (100, 300 and 500 mg/kg/i.p) respectively. On the day after the last injection, blood samples were collected for serum Nitric oxide (NO) assay. Also weights of body and testis, sperm parameters and seminiferous tubules diameter were assessed. Data analysis was performed using one-way ANOVA followed by Tukeys' test. The results showed that cisplatin lead to a reduction in the weight of body and testes, sperm parameters and increased level serum of NO significantly compared to the control group (P<0.05), while in treated groups with Tribulus terrestris, the weights of body and testes, sperm parameters, seminiferous tubules diameter were significantly higher compared with cisplatin group (P<0.05), but serum level of NO did not show significant differences. The study demonstrates that extract of Tribulus terrestris could protective effect against cisplatin- induced cytotoxicity on sperm parameters that may be related to the presence of antioxidant components acting via a multitude of central and peripheral mechanisms.

El cisplatino es un medicamento contra el cáncer utilizado en la quimioterapia. Uno de los efectos secundarios limitantes de cisplatino es la decreciente función glándular genital, azoospermia y oligospermia. Tribulus terrestris ha sido utilizado como un afrodisíaco. En el presente estudio se investiga el efecto protector del extracto hidroalcohólico de Tribulus terrestris (TT) contra la citotoxicidad inducida por cisplatino en los parámetros espermáticos en ratones. Ratones adultos machos (n = 30) fueron divididos en 4 grupos control y experimentales (n = 6). En el grupo control se administró solución salina, el primer grupo experimental recibió cisplatino (5,5 mg/kg) mientras que otros tres grupos experimentales recibieron cisplatino (5.5 mg/kg) además de diferentes dosis de extracto hidroalcohólico de TT (100, 300 y 500 mg/kg/IP) respectivamente. El día siguiente de la última inyección, se analizaron muestras de sangre para expresión de óxido nítrito (ON). Además, fueron evaluados el peso del cuerpo y testículos, los parámetros espermáticos y el diámetro de los túbulos seminíferos. Los datos fueron analizados mediante análisis ANOVA y la prueba de Tukey. El uso de cisplatino causó reducción del peso corporal y testicular, parámetros espermáticos y aumento significativo de los valores de ON en comparación con el grupo control (P<0,05), mientras que los grupos tratados con TT, fue significativamente mayor el peso corporal y testicular, parámetros espermáticos y diámetro de los túbulos seminíferos en comparación al grupo tratado con cisplatino (P<0,05). No se observaron diferencias significativas en los valores ON. El extracto de TT puede tener un efecto protector frente a la citotoxicidad inducida por el cisplatino sobre los parámetros espermáticos, al estar relacionado a la presencia de componentes antioxidantes que actúan mediante mecanismos centrales y periféricos.

Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris

PURPOSE: Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as “gokhru” which is often used in ayurveda to treat various urinary diseases including urolithiasis. MATERIALS AND METHODS: The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx) crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. RESULTS: Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. CONCLUSION: The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.

Hypoglycemic and hypolipidemic effects of alcoholic extract of Tribulus alatus in streptozotocin-induced diabetic rats: a comparative study with T. terrestris (Caltrop).

The extracts of both T. alatus and T. terrestris significantly decrease fasting glucose level in diabetic rats. After 4 and 6 hr, T. alatus extract showed significant reduction in glucose level as compared to T. terrestris. After 3 weeks of treatment with T. alatus extract, glucose level was significantly decreased to the normal level. Both the extracts also caused a significant decrease in the levels of glycosylated hemoglobin, total cholesterol, triglycerides and LDL-cholesterol. The percent of reduction in rats treated with T. alatus extract was significantly higher than that of the rats treated with T. terrestris. The results indicate that alcoholic extract of T. alatus possesses hypoglycemic activity in type-1 model of diabetes.

Free serum testosterone level in male rats treated with tribulus alatus extracts

OBJECTIVE: The present study was undertaken to investigate the effect of Tribulus alatus extracts on free serum testosterone in male rats. MATERIALS AND METHODS: Free serum testosterone level was measured in male rats treated with alcoholic extracts of the aerial part without fruits, fruits of Tribulus alatus and their fractions. RESULTS: All tested extracts showed significant increase in the level of free serum testosterone when compared to that of corresponding control, p < 0.05. Statistical comparison of all groups revealed that the maximum level was found in groups treated with chloroformic and ethanolic fractions of fruits extract. CONCLUSION: Tribulus alatus extract appears to possess aphrodisiac activity due to its androgen increasing property.