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1.
Article in Chinese | WPRIM | ID: wpr-879012

ABSTRACT

To evaluate the effects of Hydroxypropyl methylcellulose acetate succinate(HPMCAS MF) on absorption of silybin(SLB) from supersaturable self-nanoemulsifying drug delivery system which was pre-prepared at the early stage experiment. The cell toxicity of self-emulsifying preparation was evaluated by the MTT method, and the in vitro membrane permeability and absorption promoting effect of the self-emulsifying preparation were evaluated by establishing a Caco-2 cell monolayer model. The in vivo and in vitro supersaturation correlation was evaluated via the blood concentration of SLB. The results of MTT showed that the concentration of the preparation below 2 mg·mL~(-1)(C_(SLB) 100 μg·mL~(-1)) was not toxic to Caco-2 cells, and the addition of polymer had no significant effect on Caco-2 cells viability. As compared with the solution group, the transport results showed that the P_(app)(AP→BL) of the self-emulsifying preparation had a very significant increase; the transport rate of silybin can be reduced by polymer in 0-30 min; however, there was no difference in supersaturated transport between supersaturated SLB self-nanoemulsion drug delivery system(SLB-SSNEDDS) and SLB self-nanoemulsion drug delivery system(SLB-SNEDDS) within 2 hours. As compared with SLB suspension, pharmacokinetic parameters showed that the blood concentration of both SLB-SNEDDS and SLB-SSNEDDS groups were significantly increased, and C_(max) was 5.25 times and 9.69 times respectively of that in SLB suspension group, with a relative bioavailability of 578.45% and 1 139.44% respectively. C_(max) and relative bioavailability of SLB-SSNEDDS were 1.85 times and 197% of those of SLB-SNEDDS, respectively. Therefore, on the one hand, SSNEDDS can increase the solubility of SLB in gastrointestinal tract by maintaining stability of SLB supersaturation state; on the other hand, the osmotic transport process of SLB was regulated through the composition of its preparations, and both of them could jointly promote the transport and absorption of SLB to improve the oral bioavailability of SLB.


Subject(s)
Administration, Oral , Biological Availability , Caco-2 Cells , Drug Delivery Systems , Emulsions , Humans , Methylcellulose/analogs & derivatives , Nanoparticles , Particle Size , Silymarin , Solubility
2.
Int. j. morphol ; 38(6): 1767-1778, Dec. 2020. tab, graf
Article in English | LILACS | ID: biblio-1134510

ABSTRACT

SUMMARY: Acrylamide (ACR) is a cytotoxic and carcinogenic material. It is a product of a Maillard reaction during the cooking of many types of fried fast food, e.g. potato chip fries, and chicken nuggets. ACR has a severe toxic effect on different body organs. This study investigates the hepatotoxic effect of ACR, and the protective effect of ascorbic acid and silymarin. For this purpose, forty adult, male, albino rats were divided into four groups and received the following treatments for fourteen days: Group I: (the control) normal saline; Group II: ACR only; Group III: ACR and ascorbic acid; and Group IV: ACR and silymarin. Under a light microscope, the liver from rats treated with ACR only presented disturbed liver architecture, degenerated hepatocytes, reduced glycogen contents, congested central vein, and increased collagen fibres with areas of fibrosis. Immunohistochemical examination revealed an increased mean number of CD68-, and α-SMA-positive cells. This indicates the presence of large numbers of stellate macrophages (Kupffer cells) and Hepatic stellate cells (HSCs). The combination of ACR with either ascorbic acid or silymarin resulted in less hepatic degeneration, less fibrosis and fewer CD68 and α-SMA positive cells compared to the ACR only group. In conclusion, treatment with silymarin or ascorbic acid along with ACR appears to alleviate ACR-induced hepatotoxicity with more protection in silymarin treated rats.


RESUMEN: La acrilamida (ACR) es un material citotóxico y cancerígeno. Es producto de la reacción de Maillard durante la cocción de muchos tipos de comida rápida y frita, por ejemplo: papas fritas y nuggets de pollo. ACR tiene un efecto tóxico severo en diferentes órganos del cuerpo. Este estudio investigó el efecto hepatotóxico del ACR y el efecto protector del ácido ascórbico y la silimarina. Con este fin, cuarenta ratas albinas machos adultas se dividieron en cuatro grupos y recibieron los siguientes tratamientos durante catorce días: Grupo I (control), solución salina normal; Grupo II, solo ACR; Grupo III, ACR y ácido ascórbico; y Grupo IV, ACR y silimarina. Bajo microscopio óptico, el hígado de ratas tratadas con ACR solo presentó alteración de su arquitectura, entre ellos hepatocitos degenerados, contenido reducido de glucógeno, vena central congestionada y aumento de fibras de colágeno con áreas de fibrosis. El examen inmunohistoquímico reveló un aumento del número medio de células CD68 y α-SMA positivas. Esto indica la presencia de un gran número de macrófagos estrellados (células de Kupffer) y células estrelladas hepáticas (HSC). La combinación de ACR con ácido ascórbico o silimarina resultó en menos degeneración hepática, menos fibrosis y menos células positivas para CD68 y α-SMA en comparación con el grupo de ACR solo. En conclusión, el tratamiento con silimarina o ácido ascórbico junto con ACR parece aliviar la hepatotoxicidad inducida por ACR.


Subject(s)
Animals , Male , Rats , Ascorbic Acid/pharmacology , Silymarin/pharmacology , Acrylamide/toxicity , Liver/drug effects , Immunohistochemistry , Antigens, CD/analysis , Actins/analysis , Hepatocytes , Hepatic Stellate Cells , Liver/metabolism , Liver/pathology
3.
Arq. bras. med. vet. zootec. (Online) ; 72(4): 1248-1257, July-Aug. 2020. tab, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1131497

ABSTRACT

Bidens pilosa L. is a medicinal plant popularly used for treatment of liver diseases. In this study, the dry extract of aerial parts of Bidens pilosa and Silymarin, a phytocomplex obtained from the Silybum marianum fruits and marketed as hepatoprotective, were tested in dogs experimentally acutely intoxicated with carbon tetrachloride. The liver activity was evaluated by hematological and biochemical profiles, and histological and ultrasound analyzes. It was observed that the lowest serum activities of ALT and serum concentrations of total bilirubin occurred in the groups treated with the dry extract of Bidens pilosa, while only decreased serum concentrations of total bilirubin occurred in the group treated with Silymarin. Best liver recovery was also observed for the dry extract of B. pilosa at a 400mg/Kg dose by ultrasonography. This study showed that the dry extract of Bidens pilosa acted more efficiently in the treatment of acute toxic hepatitis induced in dogs than Silymarin.(AU)


Bidens pilosa L. é uma planta medicinal utilizada popularmente para tratamento de doenças hepáticas. Neste trabalho, o extrato seco das partes aéreas da Bidens pilosa e a silimarina, um fitocomplexo obtido dos frutos da Silybum marianum e comercializado como hepatoprotetor, foram testados em cães intoxicados experimentalmente de forma aguda com tetracloreto de carbono. A atividade hepática foi avaliada por meio dos perfis hematológico e bioquímico, análises histológica e ultrassonográfica. Observou-se que, nos grupos tratados com o extrato seco da Bidens pilosa, ocorreram as menores atividades séricas da ALT e de concentrações séricas de bilirrubina total, enquanto no grupo tratado com silimarina, ocorreu apenas diminuição de concentrações séricas de bilirrubina total. Melhor recuperação hepática também foi verificada para o extrato seco de B. pilosa na dose de 400mg/kg por ultrassonografia. Este estudo evidenciou que o extrato seco da Bidens pilosa atuou de forma mais eficiente no tratamento da hepatite aguda tóxica induzida em cães do que a silimarina.(AU)


Subject(s)
Animals , Dogs , Carbon Tetrachloride Poisoning/therapy , Carbon Tetrachloride Poisoning/veterinary , Bidens/chemistry , Hepatitis, Animal/therapy , Plants, Medicinal , Silymarin/therapeutic use
4.
Braz. arch. biol. technol ; 62: e19170754, 2019. tab, graf
Article in English | LILACS | ID: biblio-1055383

ABSTRACT

Abstract The aim of the present research was to develop a silymarin-laden PVP-nanocontainer providing ameliorated aqueous solubility and dissolution of the drug. Several silymarin-laden formulations were formed with varying quantities of PVP and SDS via the solvent evaporation method using the electrospraying technique. The influence of the hydrophilic carriers on solubility and dissolution was explored. The solid-state characterization was carried out by particle-size analysis, PXRD, DSC, FTIR and SEM. All of the formulations demonstrated better solubility and dissolution than did silymarin plain powder. Both the SDS and PVP had positive effects on solubility and dissolution of silymarin in the aqueous media. An increased solubility was attained as the drug/PVP ratio was 1/4; however, further increase in PVP did not provide significant improvement. In particular, a nanocontainer formulation prepared with silymarin, PVP and SDS (1/4/0.5, w/w/w) exhibited the best solubility (26432.76 ± 1749.00 μg/mL) and an excellent dissolution (~92 % in 20 min) than did silymarin plain powder. Also, it demonstrated similar dissolution profiles compared to a commercial product; therefore, might be bioequivalent to the commercial product (f 1 = 3 and f 2 = 69). Moreover, cumulative undersize distribution values as represented by X10, X50 and X90 were 201 ± 21.01 nm, 488 ± 36.05 nm and 392 ± 48.10 nm, respectively. The drug existed in the amorphous state in the PVP-nanocontainers with no strong chemical bonding with other excipients. Thus, this formulation might be used for more effective administration of silymarin via the oral route.


Subject(s)
Silymarin/administration & dosage , Spectrometry, Mass, Electrospray Ionization , Dissolution , Nanoparticles
5.
Article in English | WPRIM | ID: wpr-761790

ABSTRACT

Hydrogen sulfide is well-known to exhibit anti-inflammatory and cytoprotective activities, and also has protective effects in the liver. This study aimed to examine the protective effect of hydrogen sulfide in rats with hepatic encephalopathy, which was induced by mild bile duct ligation. In this rat model, bile ducts were mildly ligated for 26 days. Rats were treated for the final 5 days with sodium hydrosulfide (NaHS). NaHS (25 µmol/kg), 0.5% sodium carboxymethyl cellulose, or silymarin (100 mg/kg) was administered intraperitoneally once per day for 5 consecutive days. Mild bile duct ligation caused hepatotoxicity and inflammation in rats. Intraperitoneal NaHS administration reduced levels of aspartate aminotransferase and alanine aminotransferase, which are indicators of liver disease, compared to levels in the control mild bile duct ligation group. Levels of ammonia, a major causative factor of hepatic encephalopathy, were also significantly decreased. Malondialdehyde, myeloperoxidase, catalase, and tumor necrosis factor-α levels were measured to confirm antioxidative and anti-inflammatory effects. N-Methyl-D-aspartic acid (NMDA) receptors with neurotoxic activity were assessed for subunit NMDA receptor subtype 2B. Based on these data, NaHS is suggested to exhibit hepatoprotective effects and guard against neurotoxicity through antioxidant and anti-inflammatory actions.


Subject(s)
Alanine Transaminase , Ammonia , Animals , Aspartate Aminotransferases , Bile Ducts , Carboxymethylcellulose Sodium , Catalase , Hepatic Encephalopathy , Hydrogen Sulfide , Inflammation , Ligation , Liver , Liver Diseases , Malondialdehyde , Models, Animal , N-Methylaspartate , Necrosis , Peroxidase , Rats , Silymarin , Sodium
6.
Int. j. morphol ; 36(2): 661-669, jun. 2018. graf
Article in English | LILACS | ID: biblio-954169

ABSTRACT

Thioacetamide (TAA) is one of the common fungicidal agents that induce liver injury varying from inflammation, necrosis, and fibrosis to cirrhosis. Many recent studies reported the beneficial effect of probiotics and silymarin on hepatotoxicity regardless the causative agents. Therefore, the present study aimed to evaluate the ameliorative role of probiotics and/or silymarin on TAA induced hepatotoxicity in rats via histological, and immunohistochemical methods. Twenty five male albino rats were used for this experiment and were divided into five groups (n=5 rats/group); group I acts as negative control, group II was orally administrated distilled water for six weeks, then injected with TAA (200 mg/kg b.wt./ 5 ml physiological saline/ I.P.) twice a week for another six weeks, group III was treated with probiotics at a dose of 135 mg/ kg b.wt. orally in drinking water daily for six weeks, then injected with TAA (dosage of group II), twice weekly for another six weeks, group IV was treated with silymarin at a dose of 200 mg/ kg b.wt orally 4 times per week for six weeks, then injected with TAA (dosage of group II), twice weekly for another six weeks and group V was treated with combination of both probiotics and silymarin, at the same dosage in groups III and IV respectively then injected with TAA (dosage of group II), twice weekly for another six weeks. Histologically, TAA induced hepatocytes degeneration, inflammatory cells infiltration, and pseudolobular parenchyma as well as, high apoptosis and low proliferation rates that were proved by immunohistochemical staining for caspase 3 and ki-67 respectively. Probiotics and/or silymarin improved the histological feature of hepatocytes, reduced apoptosis and stimulated proliferation. Based on these results, we concluded that the use of probiotics and silymarin combination ameliorates the hepatotoxic effect of TAA in rats more than the use of probiotics or silymarin alone.


La tioacetamida (TAA) es uno de los agentes fungicidas más comunes que inducen lesiones hepáticas que varían desde inflamación, necrosis y fibrosis hasta cirrosis. Muchos estudios recientes informaron el efecto beneficioso de los probióticos y la silimarina sobre la hepatotoxicidad independientemente de los agentes causantes. Por lo tanto, el presente estudio tuvo como objetivo evaluar el papel paliativo de los probióticos y / o silimarina en la hepatotoxicidad inducida por TAA en ratas a través de métodos histológicos e inmunohistoquímicos. Para este experimento se usaron veinticinco ratas albinas y se dividieron en cinco grupos (n = 5 ratas / grupo); el grupo I se usó como control negativo; en el grupo II se administró por vía oral agua destilada durante seis semanas y luego se inyectó TAA (200 mg / kg b.wt./ 5 ml solución salina fisiológica / IP) dos veces por semana durante otras seis semanas; el grupo III se trató con probióticos, dosis diaria de 135 mg / kg b.wt. por vía oral en agua potable, durante seis semanas y luego fue inyectado con TAA (dosis del grupo II), dos veces por semana durante otras seis semanas; el grupo IV se trató con silimarina, con una dosis de 200 mg / kg b.wt por vía oral 4 veces por semana durante seis semanas, luego se inyectó TAA (dosificación del grupo II), dos veces por semana durante otras seis semanas; y el grupo V, se trató con una combinación de ambos probióticos y silimarina con la misma dosis que en los grupos III y IV, respectivamente, luego fueron inyectados con TAA (dosificación del grupo II), dos veces por semana durante otras seis semanas. Histológicamente, la TAA indujo la degeneración de los hepatocitos, la infiltración de células inflamatorias y el parénquima pseudolobular, así como también una apoptosis alta y tasas de proliferación bajas que se probaron mediante tinción inmunohistoquímica para caspasa 3 y ki-67, respectivamente. Los probióticos y / o la silimarina mejoraron la característica histológica de los hepatocitos, redujeron la apoptosis y estimularon la proliferación. En base a estos resultados, concluimos que el uso de la combinación de probióticos y silimarina mejora el efecto hepatotóxico del TAA en ratas más que el uso de probióticos o silimarina individualmente.


Subject(s)
Animals , Male , Rats , Silymarin/administration & dosage , Thioacetamide/toxicity , Probiotics/administration & dosage , Chemical and Drug Induced Liver Injury/drug therapy , Immunohistochemistry , Chemical and Drug Induced Liver Injury/pathology , Liver/drug effects
7.
Braz. J. Pharm. Sci. (Online) ; 54(1): e17529, 2018. tab, graf
Article in English | LILACS | ID: biblio-951902

ABSTRACT

Abstract The present study aimed to investigate the protective effects of silymarin (SMN), an antioxidant, on methotrexate (MTX)-induced damage in rat testes. Thirty-two Wistar albino rats were divided into four groups (n = 8): control, MTX (20 mg/kg, i.p. on days 1 and 5), SMN (200 mg/kg, orally), and MTX + SMN (20 mg/kg, i.p. on days 1 and 5 and SMN 200 mg/kg orally) groups. At the end of the 6-week trial period, histopathological, immunohistochemical, biochemical, and spermatological analyses were performed on testes tissues. Histopathologically, MTX-induced damage, including depletion of germ cell and loos of spermatozoa, was significantly improved with SMN treatment. Immunohistochemically, the immunoreactivity of glutathione peroxidase 1 (GPx1) and manganese superoxide dismutase 2 (SOD2) were detected more intensely in the MTX + SMN group than in the MTX group. Biochemical examinations revealed that SMN supplementation decreased the lipid peroxidation and increased enzymatic antioxidants in the SMN-treated rats. Spermatologically, significant differences were found in the density, motility, dead-to-live sperm ratio, and abnormal sperm rate in the MTX + SMN group compared to the MTX group. In conclusion, SMN seems to have protective effects as an antioxidant against MTX-induced damage in rat testes.


Subject(s)
Animals , Male , Rats , Silymarin/adverse effects , Testis/abnormalities , Protective Agents/analysis , Methotrexate/analysis
8.
Braz. J. Pharm. Sci. (Online) ; 54(3): e17596, 2018. tab, graf
Article in English | LILACS | ID: biblio-974416

ABSTRACT

Citral is a small molecule present in various citrus species, with reported anti-hyperlipidemic and anti-inflammation effects. Here, the effect of intraperitoneal (IP) administration of citral is evaluated in a mouse model of non-alcoholic steatosis. Male NMRI mice were divided into the following groups (n = 12): normal control group (NC) receiving a normal diet; high-fat emulsion group (HF) receiving high fat diet for four weeks; positive control group (C+) receiving HF diet for four weeks and then shifted to normal diet with IP-administered silymarin (80 mg/kg) for four weeks; sham group receiving HF diet for four weeks and then shifted to normal diet for four weeks; and EC1, EC2, and EC3 groups receiving HF diet for four weeks and then shifted to normal diet with IP-administered citral doses of 5, 10, and 20 mg/kg, respectively. HF diet resulted in steatohepatitis with impaired lipid profile, high glucose levels and insulin resistance, impaired liver enzymes, antioxidants, adiponectin and leptin levels, decreased PPARα level, and fibrosis in the liver tissue. Upon treatment with citral, improvement in condition was observed in a dose-dependent manner-both at histological level and in the serum of treated animals. and the PPARα level was also increased.


Subject(s)
Animals , Male , Rats , Gene Expression/physiology , PPAR gamma/analysis , End Stage Liver Disease/diagnosis , Silymarin/pharmacology , Citrus , Non-alcoholic Fatty Liver Disease/diagnosis
9.
Article in English | WPRIM | ID: wpr-741613

ABSTRACT

Silymarin is the standardized extract from Silybum marianum which consists mainly of flavonoids and polyphenols. It is highly regarded for its hepatoprotective ability. Silybin B is a flavonolignan and one of the active components of silymarin. The content of silybin B in various parts of S. marianum was analyzed by HPLC-UV. Results show that the extract of seeds contain the highest amount of silybin B (7.434 mg/g DW). The petioles of S. marianum showed a low content of silybin B. This study revealed that seeds of S. marianum contain high amount of silybin B and could be a good source of the compound.


Subject(s)
Flavonoids , Milk Thistle , Polyphenols , Silymarin
10.
Article in English | WPRIM | ID: wpr-713617

ABSTRACT

The liver is an essential organ for the detoxification of exogenous xenobiotics, drugs and toxic substances. The incidence rate of non-alcoholic liver injury increases due to dietary habit change and drug use increase. Our previous study demonstrated that Ecklonia stolonifera (ES) formulation has hepatoprotective effect against alcohol-induced liver injury in rat and tacrine-induced hepatotoxicity in HepG2 cells. This present study was designated to elucidate hepatoprotective effects of ES formulation against carbon tetrachloride (CCl₄)-induced liver injury in Sprague Dawley rat. Sixty rats were randomly divided into six groups. The rats were treated orally with ES formulation and silymarin (served as positive control, only 100 mg/kg/day) at a dose of 50, 100, or 200 mg/kg/day for 21 days. Seven days after treatment, liver injury was induced by intraperitoneal injection of CCl₄ (1.5 ml/kg, twice a week for 14 days). The administration of CCl₄ exhibited significant elevation of hepatic enzymes (like AST and ALT), and decrease of antioxidant related enzymes (superoxide dismutase, glutathione peroxidase and catalase) and glutathione. Then, it leaded to DNA damages (8-oxo-2′-deoxyguanosine) and lipid peroxidation (malondialdehyde). Administration of ES formulation inhibited imbalance of above factors compared to CCl₄ induced rat in a dose dependent manner. Real time PCR analysis indicates that CYP2E1 was upregulated in CCl₄ induced rat. However, increased gene expression was compromised by ES formulation treatment. These findings suggests that ES formulation could protect hepatotoxicity caused by CCl₄ via two pathways: elevation of antioxidant enzymes and normalization of CYP2E1 enzyme.


Subject(s)
Animals , Carbon Tetrachloride , Cytochrome P-450 CYP2E1 , DNA Damage , Feeding Behavior , Gene Expression , Glutathione , Glutathione Peroxidase , Hep G2 Cells , Incidence , Injections, Intraperitoneal , Lipid Peroxidation , Liver , Rats , Rats, Sprague-Dawley , Real-Time Polymerase Chain Reaction , Silymarin , Xenobiotics
11.
Article in English | WPRIM | ID: wpr-739679

ABSTRACT

Cirsium japonicum belongs to the Asteraceae or Compositae family and is a medicinal plant in Asia that has a variety of effects, including tumour inhibition, improved immunity with flavones, and antidiabetic and hepatoprotective effects. Silymarin is synthesized by 4-coumaroyl-CoA via both the flavonoid and phenylpropanoid pathways to produce the immediate precursors taxifolin and coniferyl alcohol. Then, the oxidative radicalization of taxifolin and coniferyl alcohol produces silymarin. We identified the expression of genes related to the synthesis of silymarin in C. japonicum in three different tissues, namely, flowers, leaves, and roots, through RNA sequencing. We obtained 51,133 unigenes from transcriptome sequencing by de novo assembly using Trinity v2.1.1, TransDecoder v2.0.1, and CD-HIT v4.6 software. The differentially expressed gene analysis revealed that the expression of genes related to the flavonoid pathway was higher in the flowers, whereas the phenylpropanoid pathway was more highly expressed in the roots. In this study, we established a global transcriptome dataset for C. japonicum. The data shall not only be useful to focus more deeply on the genes related to product medicinal metabolite including flavolignan but also to study the functional genomics for genetic engineering of C. japonicum.


Subject(s)
Asia , Asteraceae , Cirsium , Dataset , Estrone , Flavones , Flowers , Gene Expression Profiling , Genetic Engineering , Genomics , Humans , Plants, Medicinal , Sequence Analysis, RNA , Silymarin , Transcriptome
12.
Article in Korean | WPRIM | ID: wpr-715162

ABSTRACT

PURPOSE: This study was conducted to evaluate the clinical efficacy of pharmacologic treatment of amatoxin poisoning patients. METHODS: Literature was accessed through PubMed, EMBASE, Cochrane library, KoreaMed, KISS and KMBASE. Studies relevant to human use of pharmacologic therapy including silymarin, penicillin and N-acetylcysteine (NAC) for amanita poisoning were included. Case reports, letters, editorials and papers with insufficient information were excluded. Comparison of clinical outcomes (especially mortality and liver transplantation rate) in each study was analyzed. RESULTS: The final analysis included 13 retrospective studies. None of these studies showed direct comparisons of individual agents. Among 12 studies comparing silymarin vs penicillin, eight showed clinical superiority of silymarin. Among eight studies comparing silymarin with NAC, six showed clinical superiority of silymarin. Among seven studies of NAC vs penicillin, five showed clinical superiority of NAC. CONCLUSION: This systematic review suggested that clinical superiority of various pharmacological agents used to treat amatoxin poisoning is debatable. Nevertheless, the available evidence suggests it is reasonable to consider combinations of multiple agents for patients with amanita poisoning. Further studies are required to establish a treatment regimen for amanita poisoning.


Subject(s)
Acetylcysteine , Amanita , Humans , Liver Transplantation , Mortality , Penicillins , Poisoning , Retrospective Studies , Silymarin , Treatment Outcome
13.
Int. j. morphol ; 35(2): 723-732, June 2017. ilus
Article in English | LILACS | ID: biblio-893046

ABSTRACT

Tumor necrosis factor alpha (TNF-a) and interleukin (IL)-6, are prominent mediators of inflammation and have been confirmed to be elevated in at least a subgroup of women with polycystic ovary syndrome (PCOS). In this study, the effects of Silymarin (SLM) on the expression TNF-a, IL-6, CRP and symptoms of PCOS were studied. In this research, PCOS was induced by injection of Estradiol Valerate. PCOS rats were divided into control and experimental groups received intraperitoneal injection SLM extract daily. After syndrome induction, ovaries were collected for histological and immunohistochemical evaluations. Serum IL-6 was detected by the ELISA kit. The results indicated the significant reduction in inflammatory markers and significant changes follicular layers thickness in the treatment group as compared with control. It can be concluded that having anti-inflammatory substances, Silymarin is effective in symptoms of this syndrome and metabolic syndrome.


El factor de necrosis tumoral alfa (TNF-a) y la interleucina (IL) -6 son mediadores prominentes de la inflamación y se ha confirmado que están elevados en al menos un subgrupo de mujeres con síndrome de ovario poliquístico (SOP). En este estudio se estudiaron los efectos de Silymarin (SLM) en la expresión TNF-a, IL-6, PCR y síntomas de SOP. El SOP fue inducido por inyección de valerato de estradiol. Las ratas SOP se dividieron en grupos control y los grupos experimentales recibieron diariamente un extracto de SLM por inyección intraperitoneal. Después de la inducción del síndrome, los ovarios se analizaron mediante histología e inmunohistoquímica. Se detectó IL-6 en suero mediante el kit ELISA. Los resultados indicaron una reducción significativa en los marcadores inflamatorios y cambios significativos en el espesor de las capas foliculares en el grupo de tratamiento en comparación con el control. Se puede concluir que con sustancias anti-inflamatorias, Silymarin es eficaz en los síntomas de este síndrome y el síndrome metabólico.


Subject(s)
Animals , Female , Rats , Anti-Inflammatory Agents/pharmacology , Polycystic Ovary Syndrome/metabolism , Silymarin/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Immunohistochemistry , Inflammation , Interleukin-6/metabolism , Rats, Wistar , Tumor Necrosis Factor-alpha/drug effects
14.
Acta cir. bras ; 32(6): 407-417, June 2017. tab, graf
Article in English | LILACS | ID: biblio-886210

ABSTRACT

Abstract Purpose: To investigate the hepatoprotective and antioxidant effeicacies of Silybum marianum's (silymarin, S) on University of Wisconsin (UW) and histidinetryptophan-ketoglutarate (HTK) preservation solutions. Methods: Thirty two Wistar albino adult male rats were used. Group 1: UW group, Group 2: UW + Silymarin group(S), Group 3: HTK group, Group 4: HTK + silymarin group (S), respectively. Silymarin was enforced intraperitoneally before the surgery. Biopsies were enforced in 0, 6 and 12.hours to investigate. Results: Biochemical parameters examined in alanine aminotransferase (ALT), furthermore superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) in rats were also evaluated. Detected histopathological changings were substantially declining in the groups that received silymarin, cellular damage was decreased significantly in HTK + Silymarin group, according to other groups. It has been identified as the most effective group was HTK + silymarin group in evaluation of ALT, electron microscopic results, also decreased MDA and elevated in SOD, and CAT activity. Caspase 3 analysis showed a substantial lower apoptosis ratio in the silymarin groups than in the non-performed groups (p<0.05). Conclusion: Histidinetryptophan-ketoglutarate+silymarin group provides better hepatoprotection than other groups, by decreasing the hepatic pathologic damage, delayed changes that arise under cold ischemic terms.


Subject(s)
Animals , Male , Rats , Silymarin/therapeutic use , Organ Preservation Solutions , Protective Agents/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Antioxidants/therapeutic use , Potassium Chloride , Procaine , Raffinose , Immunohistochemistry , Adenosine , Allopurinol , Rats, Wistar , Disease Models, Animal , Glucose , Glutathione , Insulin , Mannitol
15.
Pakistan Journal of Pharmaceutical Sciences. 2017; 30 (4): 1203-1211
in English | IMEMR | ID: emr-189683

ABSTRACT

This study was designed to evaluate the effects of sylimarin supplementation on different biochemical parameters in thioacetamide induced cirrhotic rats. For this purpose 24 male Albino wistar rats were divided into four groups [n=6]. Group I, remained healthy control rats, Group II, received thioacetamide [at a dose of 200mg/kg b.w, i.p, for 12 weeks, twice a week] in first phase and saline in second phase, Group III, received thioacetamide [200mg/kg b.w, i.p for 12 weeks, twice a week] in first phase and silymarin [orally at a dosage of 200mg/kg b.w, twice a week, for 8 weeks] in second phase and Group IV, received silymarin [orally at a dosage of 200mg/kg b.w, twice a week, for 8 weeks] in first phase and saline in second phase. Biochemical analysis was evaluated by total and direct bilirubin [Retiman and Franhel, 1957, Sherlock, 1951], liver specific enzymes, antioxidant enzymes [SOD [Kono et a/., 1978], Catalase [Sinha et al, 1979], Glutathione reductase [Calberg and Mannervik, 1985] and MDA [Okhawa et al, 1979]] and plasma and intraerythrocyte sodium and potassium [Tabssum et #/., 1996]. Marked increase in total and direct bilirubin and ALT activity was the indicative markers of liver cirrhosis while reduced antioxidant activity [SOD and GSH] and increased MDA and Catalase levels and disturbed electrolyte homeostasis were observed in cirrhotic group. Silymarin supplementation markedly reduced total bilirubin and ALT activity and restored the antioxidant enzymes [SOD and GSH], MDA and catalase activity and electrolyte homeostasis. These results indicate that silymarin successively attenuates the thioacetamide induced liver cirrhosis


Subject(s)
Animals, Laboratory , Silymarin/therapeutic use , Rats, Wistar , Thioacetamide , Glutathione Reductase , Antioxidants
16.
Article in English | WPRIM | ID: wpr-728589

ABSTRACT

The present study aimed to show that pro-inflammatory cytokines [tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-1β] synergistically induce the production of nitric oxide (NO) production in mouse mesangial cells, which play an important role in inflammatory glomerular injury. We also found that co-treatment with cytokines at low doses (TNF-α; 5 ng/ml, IFN-γ; 5 ng/ml, and IL-1β; 1.25 U/ml) synergistically induced NO production, whereas treatment with each cytokine alone did not increase NO production at doses up to 100 ng/ml or 50 U/ml. Silymarin, a polyphenolic flavonoid isolated from milk thistle (Silybum marianum), attenuates cytokine mixture (TNF-α, IFN-γ, and IL-1β)-induced NO production. Western blot and RT-PCR analyses showed that silymarin inhibits inducible nitric oxide synthase (iNOS) expression in a dose-dependent manner. Silymarin also inhibited extracellular signal-regulated protein kinase-1 and -2 (ERK1/2) phosphorylation. Collectively, we have demonstrated that silymarin inhibits NO production in mouse mesangial cells, and may act as a useful anti-inflammatory agent.


Subject(s)
Animals , Blotting, Western , Cytokines , Interferons , Interleukins , Mesangial Cells , Mice , Milk Thistle , Necrosis , Nitric Oxide , Nitric Oxide Synthase Type II , Phosphorylation , Silymarin
17.
Article in English | WPRIM | ID: wpr-27728

ABSTRACT

BACKGROUND/OBJECTIVE: Orostachys japonicus A. Berger (Crassulaceae) has been used in traditional herbal medicines in Korea and other Asian countries to treat various diseases, including liver disorders. In the present study, the anti-fibrotic effects of O. japonicus extract (OJE) in cellular and experimental hepatofibrotic rat models were investigated. MATERIALS/METHODS: An in vitro hepatic stellate cells (HSCs) system was used to estimate cell viability, cell cycle and apoptosis by MTT assay, flow cytometry, and Annexin V-FITC/PI staining techniques, respectively. In addition, thioacetamide (TAA)-induced liver fibrosis was established in Sprague Dawley rats. Briefly, animals were divided into five groups (n = 8): Control, TAA, OJE 10 (TAA with OJE 10 mg/kg), OJE 100 (TAA with OJE 100 mg/kg) and silymarin (TAA with Silymarin 50 mg/kg). Fibrosis was induced by treatment with TAA (200 mg/kg, i.p.) twice per week for 13 weeks, while OJE and silymarin were administered orally two times per week from week 7 to 13. The fibrotic related gene expression serum biomarkers glutathione and hydroxyproline were estimated by RT-PCR and spectrophotometry, respectively, using commercial kits. RESULTS: OJE (0.5 and 0.1 mg/mL) and silymarin (0.05 mg/mL) treatment significantly (P < 0.01 and P < 0.001) induced apoptosis (16.95% and 27.48% for OJE and 25.87% for silymarin, respectively) in HSC-T6 cells when compared with the control group (9.09%). Further, rat primary HSCs showed changes in morphology in response to OJE 0.1 mg/mL treatment. In in vivo studies, OJE (10 and 100 mg/kg) treatment significantly ameliorated TAA-induced alterations in levels of serum biomarkers, fibrotic related gene expression, glutathione, and hydroxyproline (P < 0.05-P < 0.001) and rescued the histopathological changes. CONCLUSIONS: OJE can be developed as a potential agent for the treatment of hepatofibrosis.


Subject(s)
Animals , Apoptosis , Asian Continental Ancestry Group , Biomarkers , Cell Cycle , Cell Survival , Fibrosis , Flow Cytometry , Gene Expression , Glutathione , Hepatic Stellate Cells , Humans , Hydroxyproline , In Vitro Techniques , Korea , Liver , Liver Cirrhosis , Models, Animal , Rats , Rats, Sprague-Dawley , Silymarin , Spectrophotometry , Thioacetamide
18.
Experimental Neurobiology ; : 266-277, 2017.
Article in English | WPRIM | ID: wpr-18846

ABSTRACT

Silibinin, an active constituent of silymarin extracted from milk thistle, has been previously reported to confer protection to the adult brain against neurodegeneration. However, its effects against epileptic seizures have not been examined yet. In order to investigate the effects of silibinin against epileptic seizures, we used a relevant mouse model in which seizures are manifested as status epilepticus, induced by kainic acid (KA) treatment. Silibinin was injected intraperitoneally, starting 1 day before an intrahippocampal KA injection and continued daily until analysis of each experiment. Our results indicated that silibinin-treatment could reduce seizure susceptibility and frequency of spontaneous recurrent seizures (SRS) induced by KA administration, and attenuate granule cell dispersion (GCD), a morphological alteration characteristic of the dentate gyrus (DG) in temporal lobe epilepsy (TLE). Moreover, its treatment significantly reduced the aberrant levels of apoptotic, autophagic and pro-inflammatory molecules induced by KA administration, resulting in neuroprotection in the hippocampus. Thus, these results suggest that silibinin may be a beneficial natural compound for preventing epileptic events.


Subject(s)
Adult , Animals , Brain , Dentate Gyrus , Epilepsy , Epilepsy, Temporal Lobe , Hippocampus , Humans , Kainic Acid , Mice , Milk Thistle , Neuroprotection , Seizures , Silymarin , Status Epilepticus
19.
Article in English | WPRIM | ID: wpr-220963

ABSTRACT

BACKGROUND: The first line of anti-tuberculosis (TB) drugs are the most effective standard of drugs for TB. However, the use of these drugs is associated with hepatotoxicity. Silymarin has protective effects against hepatotoxicity of anti-TB drugs in animal models. This study aims to investigate the protective effect of silymarin on hepatotoxicity caused by anti-TB drugs. METHODS: This is a prospective, randomized, double-blind and placebo-controlled study. Patients were eligible if they were 20 years of age or order and started the first-line anti-tuberculosis drugs. Eligible patients were randomized for receiving silymarin or a placebo for the first 4 weeks. The primary outcome was the proportion of patients who showed elevated serum liver enzymes more than 3 times the upper normal limit (UNL) or total bilirubin (TBil) > 2× UNL within the first 8 weeks of anti-TB treatment. RESULTS: We enrolled a total of 121 patients who silymarin or a placebo to start their anti-TB treatment, for the first 8 weeks. The proportions of elevated serum liver enzymes more than 3 times of UNL at week 2, week 4, and week 8 did not show any significant difference between the silymarin and placebo groups, at 0% versus 3.6% (p>0.999); 4.4% versus 3.6% (p>0.999); and 8.7% versus 10.8% (p=0.630), respectively. However, patients with TBil >2× ULN at week 8 were significantly low in the silymarin group (0% versus 8.7%, p=0.043). CONCLUSION: Our findings did not show silymarin had any significant preventive effect on the hepatotoxicity of anti-TB drugs.


Subject(s)
Bilirubin , Humans , Liver , Models, Animal , Prospective Studies , Silymarin , Tuberculosis
20.
Rev. bras. cir. cardiovasc ; 31(6): 434-439, Nov.-Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-843455

ABSTRACT

Abstract Objective: To determine whether intraperitoneal silymarin administration has favorable effects on the heart, lungs, kidney, and liver and on oxidative stress in a rat model of supraceliac aorta ischemia/reperfusion injury. Methods: Thirty male Wistar albino rats were divided equally into three groups: sham, control, and silymarin. The control and silymarin groups underwent supraceliac aortic occlusion for 45 min, followed by a 60 min period of reperfusion under terminal anesthesia. In the silymarin group, silymarin was administered intraperitoneally during ischemia at a dose of 200 mg/kg. Rats were euthanized using terminal anesthesia, and blood was collected from the inferior vena cava for total antioxidant capacity, total oxidative status, and oxidative stress index measurement. Lungs, heart, liver and kidney tissues were histologically examined. Results: Ischemia/reperfusion injury significantly increased histopathological damage as well as the total oxidative status and oxidative stress index levels in the blood samples. The silymarin group incurred significantly lesser damage to the lungs, liver and kidneys than the control group, while no differences were observed in the myocardium. Furthermore, the silymarin group had significantly lower total oxidative status and oxidative stress index levels than the control group. Conclusion: Intraperitoneal administration of silymarin reduces oxidative stress and protects the liver, kidney, and lungs from acute supraceliac abdominal aorta ischemia/reperfusion injury in the rat model.


Subject(s)
Animals , Male , Rats , Aorta, Abdominal , Silymarin/administration & dosage , Reperfusion Injury/drug therapy , Oxidative Stress , Protective Agents/administration & dosage , Reperfusion Injury/pathology , Rats, Wistar , Disease Models, Animal , Injections, Intraperitoneal
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