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Aim To investigate the mechanism of action of paeonol based on JAK2/STAT3 signaling pathway to ameliorate liver inflammation and oxidative stress injury induced by acute alcohol stimulation in mice. Methods C57BL/6 mice were randomly divided into normal group, model group, silibinin group (36. 8 mg • kg
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Silibinin is a kind of flavonoid extracted from the dried ripe fruit of Silybum marianum，a plant of compositae. It has a variety of pharmacological activities and can effectively prevent and treat diabetes and its complications. This paper reviews the research progress on the mechanism of silibinin in the prevention and treatment of diabetes and its complications. It is found that silibinin can prevent and treat diabetes by up-regulating the expression of estrogen receptor-α，activating the duodenum-brain-liver axis pathway and stabilizing the protein structure. It can prevent and cure the nervous system diseases of diabetes by activating glucagon-like peptide-1 receptor/protein kinase A signal pathway and inhibiting the hyperphosphorylation of tau protein. It can prevent and treat diabetic retinopathy by down-regulating the expression and activity of pro-inflammatory，pro-oxidative factors and histone deacetylase 6. It can prevent diabetic nephropathy by activating protein kinase B signal pathway and reducing the level of transforming growth factor-β1，and prevent and treat diabete’s obesity by inhibition of hepatobiliary transporter CD36 expression， and suppressing nuclear factor-κB pathway and its downstream expression of pro-inflammatory cytokines（tumor necrosis factor-α and interleukin-1β），etc.
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Amyloid fibrils are characteristic of several disorders including Alzheimer's disease (AD), with no cure or preventive therapy. Diminishing amyloid deposits using aromatic compounds is an interesting approach toward AD treatment. The present study examined the anti-fibrillogenic effects of silibinin and trans-chalcone in vitro, in vivo, and in silico on insulin amyloids. In vitro incubation of insulin at 37°C for 24 h induced amyloid formation. Addition of trans-chalcone and silibinin to insulin led to reduced amounts of fibrils as shown by thioflavin S fluorescence and Congo red absorption spectroscopy, with a better effect observed for silibinin. In vivo bilateral injection of fibrils formed by incubation of insulin in the presence or absence of silibinin and trans-chalcone or insulin fibrils plus the compounds in rats' hippocampus was performed to obtain AD characteristics. Passive avoidance (PA) test showed that treatment with both compounds efficiently increased latency compared with the model group. Histological investigation of the hippocampus in the cornu ammonis (CA1) and dentate gyrus (DG) regions of the rat's brain stained with hematoxylin-eosin and thioflavin S showed an inhibitory effect on amyloid aggregation and markedly reduced amyloid plaques. In silico, a docking experiment on native and fibrillar forms of insulin provided an insight onto the possible binding site of the compounds. In conclusion, these small aromatic compounds are suggested to have a protective effect on AD.
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Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.
Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.
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Candida albicans , Silymarin , Proteins , Invasive Fungal InfectionsABSTRACT
Aim To evaluate the therapeutic effect of apigenin on liver fibrosis in mice anrl the pharmacologi¬cal mechanism.Methods Carbon tetrachloride ( CC14) -induced liver fibrosis mouse model was estab¬lished.The mice were divided into six groups of con¬trol, model, silibinin(55 mg • kg 1 • d 1 ) , apigenin in high dosage (60 mg • kg 1 • d 1 ) , apigenin in mid¬dle dosage( 30 mg • kg 1 • d 1 ) and apigenin in low dosage( 15 mg • kg 1 • d 1 ).The general life status, body weight and liver coefficient of the mice in every group were recorded.HE staining, Masson staining, immunohistochemistry and Western blot were used to e- valuate the effect of apigenin on the pathological chan¬ges, the markers related to epithelial-mesenchymal transition and signaling pathways of liver tissues.Re¬sults In CCI4-induced liver fibrosis mice, middle and high-dosage of apigenin could improve the general life status, increase body weight, decrease liver coeffi¬ cient, and significantly improve liver lesions.Middle and high-dosage of apigenin significantly increased the expression of the epithelial marker protein E-cadherin and significantly decreased the expression of the mes¬enchymal marker protein Vimentin in liver tissues of mice with the disease.The further results showed that middle and high-dosage apigenin could significantly in¬hibit the expression of phosphorvlated PDK1 and phos- phorvlated AKT protein in liver tissues of model mice.Conclusions Apigenin can inhibit EMT by inhibiting PDK1/AKT signaling pathway, which plays an anti-fi- brosis role.The apigenin has the potential to be further developed as a drug to protect the liver and treat liver fibrosis.
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ObjectiveTo conduct a meta-analysis of the articles on the effect of silibinin on aminotransferases in patients with nonalcoholic fatty liver disease (NAFLD), and to investigate the liver-protecting effect of silibinin in patients with NAFLD. MethodsCNKI, Wanfang Data, VIP, SinoMed, PubMed, MEDLINE, Embase, and ScienceDirect were searched for randomized controlled trials (RCTs) on the treatment of NAFLD patients with silibinin, The articles were screened according to inclusion and exclusion criteria, and then quality assessment and data extraction were performed. RevMan 5.3 was used to perform the meta-analysis. ResultsA total of 8 articles with 665 patients were included. After 8 weeks to 3 months of silibinin treatment, there were significant reductions in the serum levels of alanine aminotransferase (ALT) (weighted mean difference ［WMD］=-11.60, 95% confidence interval ［CI］: -18.68 to -4.51, P=0.001) and aspartate aminotransferase (AST) (WMD=-11.56, 95% CI: -16.93 to -6.18, P＜0.001). Conclusion Silibinin can significantly reduce the serum levels of ALT and AST in patients with NAFLD.
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Objective To investigate the in vitro antibacterial spectrum of silibinin and its isomers and the combined antibacterial effect of silibinin and commonly-used clinical antibiotics. Methods Micro-broth dilution method was used to determine the minimum inhibitory concentration (MIC) of silibinin and its isomers against six standard strains and six clinical isolates (74 strains) of common bacteria infections. Plate count method was used to measure the growth inhibition curves of different concentrations of silibinin against six standard strains. Checkerboard micro-broth dilution method was used to carry out the combined susceptibility test of silibinin and clinical antibiotics. The fractional inhibitory concentration (FIC) was calculated to determine the combined antibacterial effect of silibinin and antibiotics. Results The MICs of silibinin against standard strains of Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium were between 50 μg/mL and 400 μg/mL, and those of silibinin for standard strains of Escherichia coli and Pseudomonas aeruginosa were both greater than 400 μg/mL. The MICs of silibinin for clinical strains, Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium were all within the range of 100 μg/mL to 400 μg/mL, and MICs of silibinin against clinical strains of Escherichia coli and Pseudomonas aeruginosa were greater than 400 μg/mL. The MICs of other isomers of silibinin against six standard strains were greater than or equal to 400 μg/mL. Silibinin had a significant inhibitory effect on the growth curve of standard strains of Staphylococcus epidermidis, Staphylococcus aureus, Enterococcus faecalis, and Enterococcus faecium, which increased with increasing drug concentration, and it had no effect on that of Escherichia coli and Pseudomonas aeruginosa. The FIC of silibinin combined with penicillin/erythromycin for gram-positive test bacteria was in the range of 0.5 2 or 1 < FIC ≤ 2. Conclusion Silibinin has a notable antibacterial activity to gram-positive bacteria with the best inhibitory effect on Staphylococcus epidermidis. The antibacterial activities of silibinin is higher than those of other isomers. The combined antibacterial effect of silibinin and penicillin/erythromycin is mainly additive and irrelevant, while that of silibinin and ciprofloxacin or gentamicin is mainly antagonistic or irrelevant.
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It is known that silibinin has antioxidant, anti-tumor, anti-inflammatory and immunomodulatory effects, and which is widely used for liver damage caused by a variety of reasons. In recent years, it is found that silibinin has potential anti-allergic reactions. However, even larger doses of silibinin still show no significant side effects . The rare literature reports that silibinin can cause allergic reactions. The paper reports a middle-aged patient who orally took silibinin for the prevention of tuberculosis chemotherapy-induced liver damage, and he occurred symptoms of lip pain and anabrosis, foreign body sensation, and difficulty eating one day after treatment. The patient was misdiagnosed as"vesicular stomatitis"and was treated by anti-viral therapy. The patient was discharged from the hospital after treating allergic reactions. As a safe and effective drug for prevention of liver damages in clinic, silibinin should be alert to induce possible allergies when there are local skin manifestations such as lip pain and anabrosis.
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BACKGROUND/AIMS: Hepatic steatosis is caused by an imbalance between free fatty acids (FFAs) uptake, utilization, storage, and disposal. Understanding the molecular mechanisms involved in FFAs accumulation and its modulation could drive the development of potential therapies for Nonalcoholic fatty liver disease. The aim of the current study was to explore the effects of picroside II, a phytoactive found in Picrorhiza kurroa, on fatty acid accumulation vis-à-vis silibinin, a known hepatoprotective phytoactive from Silybum marianum. METHODS: HepG2 cells were loaded with FFAs (oleic acid:palmitic acid/2:1) for 20 hours to mimic hepatic steatosis. The FFAs concentration achieving maximum fat accumulation and minimal cytotoxicity (500 μM) was standardized. HepG2 cells were exposed to the standardized FFAs concentration with and without picroside II pretreatment. RESULTS: Picroside II pretreatment inhibited FFAs-induced lipid accumulation by attenuating the expression of fatty acid transport protein 5, sterol regulatory element binding protein 1 and stearoyl CoA desaturase. Preatreatment with picroside II was also found to decrease the expression of forkhead box protein O1 and phosphoenolpyruvate carboxykinase. CONCLUSIONS: These findings suggest that picroside II effectively attenuated fatty acid accumulation by decreasing FFAs uptake and lipogenesis. Picroside II also decreased the expression of gluconeogenic genes.
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Fatty Acid Transport Proteins , Fatty Acids, Nonesterified , Hep G2 Cells , Lipogenesis , Silybum marianum , Non-alcoholic Fatty Liver Disease , Phosphoenolpyruvate , Picrorhiza , Stearoyl-CoA Desaturase , Sterol Regulatory Element Binding Protein 1ABSTRACT
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.
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Humans , Acetylcysteine , Amanita , Liver Transplantation , Mortality , Penicillins , Poisoning , Retrospective Studies , Silymarin , Treatment OutcomeABSTRACT
OBJECTIVE: To investigate the effects of Silibinin capsules combined with routine therapy on serum oxidative injury and liver function of patients with alcoholic liver disease (ALD) complicated with early liver fibrosis.METHODS: The patients with ALD complicated with early liver fibrosis selected from our hospital during Apr. 2013-Jan. 2015 were divided into control group and study group according to random number table, with 38 cases in each group. Control group received routine symptomatic treatment [temperance, oral administration of Inosine tablets (0. 4 g/times, bid), vitamin and microelement supplementation, etc. ]. Study group was additionally given Silibinin capsule (70 mg/time, bid) orally, for consecutive 48 weeks, on the basis of control group. The clinical efficacies and the incidence of ADR were compared between 2 groups. The changes of serum oxidative injury indexes (SOD, MDA), liver fibrosis indexes [laminin (LN), hyaluronic acid (HA), type IV collagen (IV-C), type Ⅲ procollagen (PC Ⅲ)] and liver function indexes (ALT, AST) were recorded before and after treatment. RESULTS: Before treatment, there was no statistical significance in baseline information between 2 groups (P>0. 05). After treatment, total response rate of study was significantly higher than that of control group (P<0. 05), but there was no statistical significance in the incidence of ADR between 2 groups (P>0. 05). Compared with before treatment, serum levels of MDA, liver fibrosis indexes and liver function indexes in 2 groups were decreased significantly (P<0. 05), while SOD levels were increased significantly (P<0. 05); the improvement of study group was more significant than control group (P<0. 05). CONCLUSIONS: Silibinin capsules combined with routine treatment can enhance clinical efficacy of ALD patients with early liver fibrosis, mainly manifesting as improving oxidative stress, regulating liver function and inhibiting the development of liver fibrosis.
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Objective@#To explore the synergistic effect of silibinin combined with crizotinib on anaplastic lymphoma kinase positive (ALK+ ) non-small cell lung cancer (NSCLC) cells and its mechanism.@*Methods@#H2228 and H3122 cells were treated with silibinin, crizotinib alone or in combination. Cell proliferation was measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and colony formation assay. Migration or invasion ability was tested by wound healing assay or transwell assay, respectively. Expressions of E-Cadherin and vimentin protein were examined by immunofluorescence staining. The protein expressions of ALK, p-ALK, E-Cadherin and Vimentin were detected by western blotting.The anti-cancer effect of silibinin combined with crizotinib in vivo was determined by subcutaneously injecting 2×106 H2228 cells into immunodeficient nude mice.@*Results@#The result of MTT assay showed that the cell viability of H2228 or H3122 treated with 100 μmol/L silibinin was (88.38±4.10)% or (72.27±3.62)%, respectively, marginally decreased compared with that of the control. The 50% inhibitory concentration (IC50) of H2228 cells treated with crizotinib alone or combined with 100 μmol/L silibinin was (917.10±7.75) nmol/L or (238.73±7.67) nmol/L, respectively. The IC50 of H3122 cells treated with crizotinib alone or combined with 100 μmol/L silibinin was (472.50±15.70) nmol/L or (206.10±12.01) nmol/L, respectively. The IC50s of H2228 and H3122 cells were significantly decreased by combined treatment of crizotinib and silibinin compared to crizotinib treatment alone (P<0.01). When compared with the control group, colony forming ratios of H2228 cells were (83.34±2.72)% in 100 μmol/L silibinin treatment group, (69.42±3.06)% in 400 nmol/L crizotinib treatment group and (27.32±1.42)% in combined treatment group. When compared with the control group, colony forming ratios of H3122 cells were (84.45±5.67)% in 100 μmol/L silibinin treatment group, (45.02±5.83)% in 400 nmol/L crizotinib treatment group and (17.43±3.83)% in combined treatment group. Silibinin combined with crizotinib treatment significantly inhibited the colony formation ability of H2228 and H3122 cells (P<0.01). Migration and invasion results showed that combined treatment of crizotinib and silibinin markedly inhibited the migration and invasion ability of H2228 cells (P<0.01). Western blot results indicated that treated with silibinin alone or in combination of crozitinib for 48 hours, the protein level of E-cadherin in H2228 cells was upregulated, while the expressions of p-ALK and vimentin were downregulated, without obvious alteration of ALK protein expression. In the xenograft model, the mean tumor weight was (9.40±2.58)g in crizotinib treatment group and (4.58±1.07)g in the combined treatment group. The inhibitory effect of tumor growth in vivo of combined treatment was significantly superior to that of crizotinib treatment alone (P<0.05).@*Conclusion@#Silibinin enhances the inhibitory effect of crizotinib on ALK positive NSCLC cells, which may be associated with suppression of ALK activity and mesenchymal-epithelial transition.
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Objective To study the protection of silibinin sunscreen on chronic UVB induced guinea pig skin apoptosis. Methods A total of 60 guinea pigs were randomly divided into four groups, blank group, UVB group, silibinin sunscreen group, anti-wrinkle day cream group (positive control), and 15 in each group. The UVB ultraviolet phototherapy instrument was used to irradiate guinea pig skin for 30 min once and twice per day, and then up to 15 days before the apoptosis of skin model has been set up. The silibinin sunscreen and anti-wrinkle day cream groups received silibinin sunscreen and anti-wrinkle day cream as intervetion, respectively. But the other two groups received nothing for intervention. The GSH-Px and SOD, and MDA kit were detected and compared. The westerrn blot detected caspase-3, Bax, Bcl-2 protein expression in each group. Results Compared with the UVB group, the contents of GSH-Px (8.79 ± 1.57 mg/g, 8.25 ± 2.07 mg/g vs. 4.66 ± 1.82 mg/g) and SOD (24.52 ± 5.43 U/mg, 27.81 ± 2.13 U/mg vs. 10.82 ± 3.40 U/mg) in the silibinin sunscreen group and anti-wrinkle day cream group increased significantly, and the content of MDA (7.91 ± 2.80 nmol/mg, 6.45 ± 1.86 nmol/mg vs. 13.57 ± 2.63 nmol/mg) decreased significantly (P<0.05, P<0.01). The expression ofcaspase-3 (0.44 ± 0.04, 0.38 ± 0.03 vs. 0.56 ± 0.06) and Bax (0.46 ± 0.05, 0.40 ± 0.06 vs. 0.75 ± 0.06) in the silibinin sunscreen group and anti-wrinkle day cream group decreased significantly, and the expression of Bcl-2 (0.39 ± 0.04, 0.43 ± 0.06 vs. 0.25 ± 0.05) increased significantly (P<0.05, P<0.01). Conclusions Protection of Silibinin Sunscreen on Chronic UVB Induced Guinea Pig Skin Apoptosis, mainly through enhancing GSH-Px and SOD activity and reducing MDA content, reducing the caspase-3, Bax protein expression and increasing the Bcl-2 protein expression.
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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.
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Adult , Animals , Humans , Mice , Brain , Dentate Gyrus , Epilepsy , Epilepsy, Temporal Lobe , Hippocampus , Kainic Acid , Silybum marianum , Neuroprotection , Seizures , Silymarin , Status EpilepticusABSTRACT
Objective:To investigate the efficacy of Silybinin meglumine on hepatic fibrosis rats and possible mecha -nisms.Methods:The liver fibrosis rats were randomly divided into 4 groups,the model group,Silybinin meglumine 120 mg/kg group, Silybinin meglumine dose group 60 mg/kg and Silybinin meglumine low dose group 30 mg/kg,and the control group.All groups had been treated for 4 groups.Results:No deaths rat.Compared with the control group ,the reduced body weight ,less dynamic,dark hair, decreased liver and spleen indexes ,increased ALT,AST,TBIL,TG,TC and LDLC,and the decreased ALB, and the increased LXRαand SREBP1c had been observed in the model group (P<0.05).Compared with the model group ,better activity and body weight ,the in-creased liver and spleen indexs decreased ALT ,AST,TBIL,TG,TC and LDLC,and the increased ALB , and the decreased LXRαand SREBP1c had been observed in the Silybinin meglumine groups (P<0.05),in a way of dose-depended.Conclusion: The Silibinin meglumine can treat liver fibrosis ,by improving liver function,lowing lipid and decreaseing LXRαand SREBP1c expression in liver tis-sue.But the mechanism of two proteins reduced remains for further investigation .
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Objective To investigate the lipid hepatoprotective effect of silibinin on high fat diet-induced nonalcoholic fatty liver (NAFL) rat model and provide a theoretical basis for the treatment of silibinin on NAFL.Methods The NAFL rat model was established by administration of high fat emulsion and high fat diet.Rats in control group was treated with saline and normal diet.The model rats were randomly divided into model group,simvastatin (positive drug,1.8 mg/kg) group,Silibinin groups with low,middle and high doses (18.9,37.8 and 75.6 mg/kg).From the fifth week,NAFLrats were treated with different drugsonce a day for eight weeks.All rats were anaesthetized after final administration,Livertissues were weighed for the calculation of hepatic coefficient The hepatic morphology was observed through HE staining.Serum was obtained from abdominal aortic blood for detection of triglyceride separation (TG),total cholesterol (TC),high density lipoprotein (HDL),low-density lipoprotein (LDL),aspartate aminotransferase (AST),and alanine aminotransferase (ALT) levels.Results After eight-week treatment,compared with model group,middle and high doses of silibinin could significantly improve the hepatic steatosis.The levels of hepatic coefficient,serum TC,TG,AST and ALT in rats treated with individual dose of Silibinin were significantly decreased (P ＜ 0.05,0.01).Particularly,high dose of silibinin significantly reduced LDL level whereas elevated HDL level in serum (P ＜ 0.01).Conclusion Silibinin has a therapeutic effect on nonalcoholic fatty liver rats,and possible mechanism is related to lipid-lowering and hepatic protection.
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Epidermal Growth Factor Receptor (EGFR) is mostly deregulated and over expressed in ovarian cancer, which is directly linked with STAT3 activation that leads to the accumulation of anti-apoptotoc events and thus, platinum drug resistance occurs. Regarding this, increasing of platinum drug sensitivity by targeting EGFR receptor along with platinum drugs is one of the major strategies in ovarian cancer treatment. In this context, using molecular simulation studies, the present study described the structural and functional properties of silibinin as a potential inhibitor of EGFR tyrosine kinase, and also its metabolic profile had been investigated by SOM prognosis. According to the results, silibinin have shown the significant binding energy by interacting with important residues in the active site. Again, it also processed medium absorption profile with no Fe accessibility. Furthermore, the study is also useful for further clinical based studies and also for the validation of toxicological and pharmacokinetic study.
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The present study was designed to evaluate the hepatoprotective and antioxidant potentials of silibinin (SBN) against N-nitrosodimethylamine (DMN)-induced toxic insults in the rat liver. The liver damage was induced in Wistar albino rats by repeated administration of DMN (10 mg·kg(-1) b.w., i.p.) on 3 consecutive days per week for 3 weeks. SBN (100 mg·kg(-1) b.w., p.o.) was given daily to the DMN treated rats for two weeks. The marker enzymes of liver toxicity and second-line enzymic and non-enzymic antioxidants were evaluated in serum and liver tissues before and after SBN treatment. Histopathology of the liver was evaluated by H & E staining. The DMN treatment produced a progressive increase in all the serum marker enzymes (AST, ALT, ALP, LDH, and γ-GT), peaking on Day 21. This treatment produced highly significant decreases in all the second-line antioxidant parameters (GSH, GST, GR, GPx, and vitamins C and E). The SBN treatment significantly reversed the DMN-induced damages, towards normalcy. Histopathological studies confirmed the development of liver toxicity in DMN-treated rats, which was reversed by SBN treatment in corroboration with the aforementioned biochemical results, indicating the hepatoprotective and antioxidant properties of SBN. In conclusion, the DMN-induced degenerative changes in the liver were alleviated by SBN treatment and this protective ability may be attributed to its antioxidant, free radical scavenging, and membrane stabilizing properties.
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Animals , Female , Male , Rats , Antioxidants , Pharmacology , Chemical and Drug Induced Liver Injury , Drug Therapy , Dimethylnitrosamine , Toxicity , Glutathione , Metabolism , Protective Agents , Pharmacology , Rats, Wistar , Silymarin , Silymarin , PharmacologyABSTRACT
Objective To study the physical and chemical properties of silibinin; To lay foundation for optimal formulation design.Methods The high performance liquid chromatography method was used to detect the equilibrium solubility of silibininin in various solutions. The partition coefficients of silibinnin in the n-octalution-water and n-octalution-buffer solution systems were determined by shaking flask method. The destructive tests were carried out on silibinin.Results The equilibrium solubility of silibininin at 25℃ was 1.352 mg/L in water and the largest in acetonitrile, and increased in basic buffer solutions and after adding surfactants, of which sodium dodecyl benzene sulfonate was the strongest in solubilizing ability. The apparent oil-water partition coefficient of silibinnin was 61.39. Silibinnin was unstable in the acidic, basic, oxidizing and reducing solutions.Conclusion The experiment results can provide references for designing new preparations of silibinin.
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The present study investigated the effect of silibinin, the principal potential anti-inflammatory flavonoid contained in silymarin, a mixture of flavonolignans extracted from Silybum marianum seeds, on palmitate-induced insulin resistance in C2C12 myotubes and its potential molecular mechanisms. Silibinin prevented the decrease of insulin-stimulated 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose) uptake and the downregulation of glutamate transporter type 4 (GLUT4) translocation in C2C12 myotubes induced by palmitate. Meanwhile, silibinin suppressed the palmitate-induced decrease of insulin-stimulated Akt Ser473 phosphorylation, which was reversed by wortmannin, a specific inhibitor of phosphatidylinositol-3-kinase (PI3K). We also found that palmitate downregulated insulin-stimulated Tyr632 phosphorylation of insulin receptor substrate 1 (IRS-1) and up-regulated IRS-1 Ser307 phosphorylation. These effects were rebalanced by silibinin. Considering several serine/threonine kinases reported to phosphorylate IRS-1 at Ser307, treatment with silibinin downregulated the phosphorylation of both c-Jun N-terminal kinase (JNK) and nuclear factor-κB kinase β (IKKβ), which was increased by palmitate in C2C12 myotubes mediating inflammatory status, whereas the phosphorylation of PKC-θ was not significantly modulated by silibinin. Collectively, the results indicated that silibinin prevented inhibition of the IRS-1/PI3K/Akt pathway, thus ameliorating palmitate-induced insulin resistance in C2C12 myotubes.