Effect of Silymarin as an Adjunct Therapy in Combination with Sofosbuvir and Ribavirin in Hepatitis C Patients: A Miniature Clinical Trial.

Silymarin is proclaimed to be a blend of flavonolignans or phytochemicals. An era of new generation of direct-acting antivirals (DAAs) has commenced to have facet effect in swaying of the hepatitis C virus (HCV). Nonetheless, this therapy has serious side effects that jeopardize its efficacy. This study is aimed at probing the effects of ribavirin (RBV) and sofosbuvir (SOF) along with silymarin as an adjunct therapy on hematological parameters and markers of obscured oxidative stress. The effect of DAAs along with silymarin was also examined on variable sex hormone level and liver function markers such as alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and bilirubin. The study was followed to determine viral load and viral genotypes. A total of 30 patients were randomly divided into two equal groups comprising the control group (n = 15) and treatment group (n = 15). The control group was solely administered with DAAs (SOF and RBV; 400 mg/800 mg each/day). Conversely, the treatment group was dispensed with DAAs, but with adjunct therapy of silymarin (400 mg/day) along with DAAs (400/800 mg/day) over period of 8 weeks. Sampling of blood was performed at pre- and posttreatment levels for the evaluation of different propound parameters. Our data showed that silymarin adjunct therapy enhances the efficiency of DAAs. A decrease in menace level of liver markers such as ALT, ALP, AST, and bilirubin was observed (p > 0.05). The adjunct therapy concurrently also demonstrated an ameliorative effect on hematological indices and oxidative markers, for instance, SOD, TAS, GSH, GSSG, and MDA (p < 0.05), diminishing latent viral load. The silymarin administration was also found to revamp the fluster level of sex hormones. Our outcomes provide evidence that systematic administration of silymarin effectively remits deviant levels of hematological, serological, hormonal, and antioxidant markers. This demonstrates a possibly unique role of silymarin in mitigating hepatitis C.

Tackling of Renal Carcinogenesis in Wistar Rats by Silybum marianum Total Extract, Silymarin, and Silibinin via Modulation of Oxidative Stress, Apoptosis, Nrf2, PPARγ, NF-κB, and PI3K/Akt Signaling Pathways.

The present work was designed to assess the efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally induced renal carcinogenesis in male Wistar rats and their roles in regulating oxidative stress, inflammation, apoptosis, and carcinogenesis. The diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4)-administered rats were orally treated with STE (200 mg/kg b.w.), Sm (150 mg/kg b.w.), and Sb (5 mg/kg b.w.) every other day either from the 1st week or from the 16th week of carcinogen administration to the end of 25th week. The treatments with STE, Sm, and Sb attenuated markers of toxicity in serum, decreased kidney lipid peroxidation (LPO), and significantly reinforced the renal antioxidant armory. The biochemical results were further confirmed by the histopathological alterations. The treatments also led to suppression of proinflammatory mediators such as NF-κß, p65, Iκßα, and IL-6 in association with inhibition of the PI3K/Akt pathway. Furthermore, they activated the expressions of PPARs, Nrf2, and IL-4 in addition to downregulation of apoptotic proteins p53 and caspase-3 and upregulation of antiapoptotic mediator Bcl-2. The obtained data supply potent proof for the efficacy of STE, Sm, and Sb to counteract renal carcinogenesis via alteration of varied molecular pathways.

Dietary Polyphenols and Non-Alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), which is emerging as a major public health issue worldwide, is characterized by a wide spectrum of liver disorders, ranging from simple fat accumulation in hepatocytes, also known as steatosis, to non-alcoholic steatohepatitis (NASH) and cirrhosis. At present, the pharmacological treatment of NAFLD is still debated and dietary strategies for the prevention and the treatment of this condition are strongly considered. Polyphenols are a group of plant-derived compounds whose anti-inflammatory and antioxidant properties are associated with a low prevalence of metabolic diseases, including obesity, hypertension, and insulin resistance. Since inflammation and oxidative stress are the main risk factors involved in the pathogenesis of NAFLD, recent studies suggest that the consumption of polyphenol-rich diets is involved in the prevention and treatment of NAFLD. However, few clinical trials are available on human subjects with NAFLD. Here, we reviewed the emerging existing evidence on the potential use of polyphenols to treat NAFLD. After introducing the physiopathology of NAFLD, we focused on the most investigated phenolic compounds in the setting of NAFLD and described their potential benefits, starting from basic science studies to animal models and human trials.

The therapeutic effects of silymarin for patients with glucose/lipid metabolic dysfunction: A meta-analysis.

BACKGROUND: To comprehensively evaluate the treatment efficacy and safety of silymarin for patients with glucose/lipid metabolic dysfunction using a meta-analysis. METHODS: A systematic literature search in PubMed, EMBASE and Cochrane Library databases was performed up to October 1, 2019. STATA 13.0 software was used to estimate pooled standardized mean difference (SMD) and 95% confidence interval (95% CI). RESULTS: Sixteen studies involving 1358 patients were identified. Overall meta-analysis showed that compared with control, silymarin significantly reduced levels of fasting blood glucose (SMD: -1.27, 95% CI = [-1.78, -0.76]; P < .001), homeostatic model assessment for insulin resistance (SMD: -0.41, 95% CI = [-0.70, -0.12]; P = .005), hemoglobin A1c (SMD: -1.88, 95% CI = [-2.57, -1.20]; P < .001), total cholesterol (SMD: -1.13, 95% CI = [-1.82, -0.77]; P < .001), triglyceride (SMD: -0.37, 95% CI = [-0.69, -0.05]; P = .025), low-density lipoprotein-cholesterol (SMD: -1.30, 95% CI = [-1.93, -0.67]; P < .001), C-reactive protein (SMD: -0.63, 95% CI = [-1.01, -0.27]; P = .001), and increased high-density lipoprotein-cholesterol (SMD: 0.17, 95% CI = [0.05, 0.29]; P = .005), but had no impacts on function indicators of liver and kidney (alanine transaminase, aspartate aminotransferase, creatinine phosphokinase, creatinine) and the complication rate. Subgroup analyses indicated that insulin (which was negative in overall analysis) was significantly decreased in patients undergoing silymarin monotherapy (SMD: -2.03, 95% CI = [-3.03, -1.04]; P = .044) for more than 3 months (SMD: -0.01, 95% CI = [-0.25, -0.24]; P = .035). CONCLUSION: Supplementation of silymarin may be effective and safe for the management of diabetes mellitus and hyperlipidemia.

Development of an HPLC-MS/MS Method for the Determination of Silybin in Human Plasma, Urine and Breast Tissue.

Silybin is a flavonolignan extracted from Silybum marianum with chemopreventive activity against various cancers, including breast. This study was designed to develop an HPLC-MS/MS method for the determination of silybin in human plasma, urine and breast tissue in early breast cancer patients undergoing Siliphos® supplementation, an oral silybin-phosphatidylcholine complex. The determination of silybin was carried out by liquid-liquid extraction with methyl-tert-butyl ether (MTBE); total silybin concentration was determined by treating the samples with ß-glucuronidase, while for the determination of free silybin, the hydrolytic step was omitted. Naringenin and naproxen were selected as internal standards. The detection of the analyte was carried out by mass spectrometry and by chromatography. The HPLC-MS/MS method was evaluated in terms of selectivity, linearity, limit of quantification, precision and accuracy, and carryover. The method proved to be selective, linear, precise and accurate for the determination of silybin. To the best of our knowledge, this presents the first analytical method with the capacity to quantify the major bioactive components of milk thistle in three different biological matrices with a lower limit of quantification of 0.5 ng/mL for plasma. Silybin phosphatidylcholine, taken orally, can deliver high blood concentrations of silybin, which selectively accumulates in breast tumor tissue.

Neuronal degeneration and oxidative stress in the SNc of 6-OHDA intoxicated rats; improving role of silymarin long-term treatment.

Progressive loss in dopaminergic neurons (DA) of substantia nigra pars compacta (SNc) leads to Parkinson's disease with a hypothesis of oxidative stress generation. The present study was conducted to determine the long-term efficacy of silymarin (SM) post-treatment on 6-OHDA-induced oxidative stress in the SNc of male rats. Male Wistar rats were received 6-OHDA (8 µg/rat) into SNc. After 3 weeks, as recovery period, the animals were treated with i.p. injection of SM at different doses of 100, 200, or 300 mg/kg for 15 days. At the end of the treatment, motor function, neuronal cell count, antioxidant enzymes, and lipid peroxidation and tyrosine hydroxylase (TH) activities were evaluated in the ventral midbrain tissue. The 6-OHDA significantly decreased (p ≤ 0.05) motor function, antioxidant enzyme activity, GSH level, and GSH/GSSG ratio and caused an augmentation in GSSG and lipid peroxidation level. The 6-OHDA also reduced the population of neurons and TH expression. The SM repaired the 6-OHDA-induced motor impairment, antioxidant enzyme suppression, and TH down-regulation. All three doses of SM could restore the MDA level to the normal range in the 6-OHDA-lesioned rats and could reversed the effect of 6-OHDA on GSH, GSSG level, and GSH/GSSG ratio. The SM treatment significantly and dose-dependently increased (p ≤ 0.001) the total number of surviving neurons in the SNc. Silymarin chronic treatment restored the brain's antioxidant capacity and salvaged neurons from oxidative stress-induced neurodegeneration. The SM could also improve motor function in parkinsonian animals by increasing TH expression. These results recommend that application of SM over initial clinical stages may depict a hopeful approach versus PD. However, more research is needed to confirm this issue.

Co-administration of silymarin elevates the therapeutic effect of praziquantel through modulation of specific antibody profiles, Th1/Th2/Tregs cytokines and down-regulation of fibrogenesis in mice with Mesocestoides vogae (Cestoda) infection.

Silymarin (SIL) represents a natural mixture of polyphenols showing an array of health benefits. The present study, carried out on a model cestode infection induced by Mesocestoides vogae tetrathyridia in the ICR strain of mice, was aimed at investigating the impact of SIL as adjunct therapy on the activity of praziquantel (PZQ) in relation to parasite burden, immunity and liver fibrosis within 20 days post-therapy. In comparison with PZQ alone, co-administration of SIL and PZQ stimulated production of total IgG antibodies to somatic and excretory-secretory antigens of metacestodes and modified the expression patterns of immunogenic molecules in both antigenic preparations. The combined therapy resulted in the elevation of IFN-γ and a decline of TNF-α and TGF-ß1 in serum as compared to untreated group; however, SIL attenuated significantly the effect of PZQ on IL-4 and stimulated PZQ-suppressed phagocytosis of peritoneal macrophages. In the liver, SIL boosted the effect of PZQ on gene expression of the same cytokines in a similar way as was found in serum, except for down-regulation of PZQ-stimulated TNF-α. Compared to PZQ therapy, the infiltration of mast cells into liver after SIL co-administration was nearly abolished and correlated with suppressed activities of genes for collagen I, collagen III and α-SMA. In conclusion, co-administration of SIL modified the effects of PZQ therapy on antigenic stimulation of the immune system and modulated Th1/Th2/Tregs cytokines. In liver this was accompanied by reduced fibrosis, which correlated with significantly higher reduction of total numbers of tetrathyridia after combined therapy as compared with PZQ treatment.

Silymarin effect on experimental bone defect repair in rat following implantation of the electrospun PLA/carbon nanotubes scaffold associated with Wharton's jelly mesenchymal stem cells.

In this study, the ability of silymarin to heal rat calvarial bone critical defects with mesenchymal stem cells isolated from human Wharton's jelly (HWJMSC) cultured on the electrospun scaffold of poly (lactic acid)/carbon nanotube (PLA/CNT) has been examined. In this study, 20 adult male Wistar rats were divided into four groups of five each. Under general anesthesia, 8 mm defects were created in the calvarial bone of the rats. Then, study groups were defined as no treatment group, the scaffold alone, the scaffold and HWJMSCs, and the scaffold/cells plus oral silymarin, respectively. The histomorphometric study was performed using H&E staining and Goldner's Masson trichrome as specific staining. The results of this study showed that the electrospun PLA/CNT scaffold is a biocompatible scaffold and HWJMSCs can considerably attach and proliferate on this scaffold, and the scaffold itself is also a suitable option for improving the bone repair process. The results of the histomorphometric analysis also showed a significantly higher amount of recently formed bone in the silymarin group plus scaffold/cells compared to the scaffold and cell group alone (p < .05). Utilizing silymarin plus HWJMSCs cultured on PLA/CNT scaffold can be used as a suitable method for the process of osteogenesis and bone repair.

Silymarin as Supportive Treatment in Liver Diseases: A Narrative Review.

Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. Eurosil 85® is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Most of the clinical research on silymarin has used this formulation. Silymarin acts as a free radical scavenger and modulates enzymes associated with the development of cellular damage, fibrosis and cirrhosis. These hepatoprotective effects were observed in clinical studies in patients with alcoholic or non-alcoholic fatty liver disease, including patients with cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liver-related deaths. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Patients with drug-induced liver injuries were also successfully treated with silymarin. Silymarin is generally very well tolerated, with a low incidence of adverse events and no treatment-related serious adverse events or deaths reported in clinical trials. For maximum benefit, treatment with silymarin should be initiated as early as possible in patients with fatty liver disease and other distinct liver disease manifestations such as acute liver failure, when the regenerative potential of the liver is still high and when removal of oxidative stress, the cause of cytotoxicity, can achieve the best results.

The effect of combined diet containing n-3 polyunsaturated fatty acids and silymarin on metabolic syndrome in rats.

The risk of development of metabolic syndrome can be increased by hypertriglyceridemia. A search for effective therapy is a subject of considerable attention. Therefore, our hypothesis is that the fish oil (containing polyunsaturated fatty acids; n-3 PUFA) in a combination with silymarin can more effectively protect against hypertriglyceridemia-induced metabolic disturbances. The study was conducted using a unique non-obese strain of rats with hereditary hypertriglyceridemia an accepted model of metabolic syndrome. Adult male rats were treated with n-3 PUFA (300 mg/kg/day) without or with 1 % micronized silymarin in a diet for 4 weeks. The treatment with the diet containing n-3 PUFA and silymarin significantly reduced concentrations of serum triglycerides (-45 %), total cholesterol (-18 %), non-esterified fatty acids (-33 %), and ectopic lipid accumulation in skeletal muscle (-35 %) compared to controls. In addition, an increase in Abcg5 and Abcg8 mRNA expression (as genes affecting lipid homeostasis) as well as in protein content of ABCG5 (+78 %) and ABCG8 (+232 %) transporters have been determined in the liver of treated rats. Our findings suggest that this combined diet could be used in the prevention of hypertriglyceridemia-induced metabolic disorders.

Efficacy and safety of oral silymarin in comparison with oral doxycycline and their combination therapy in the treatment of acne vulgaris.

Two factors of oxidative stress and inflammatory processes are implicated in pathogenesis of acne vulgaris. Silymarin has antioxidant and anti-inflammatory activities. This study was done to evaluate the effect of oral silymarin in the treatment of acne vulgaris compared to doxycycline and also their combination therapy. This randomized controlled trial was performed on 60 patients with acne vulgaris were divided into three groups of 20 patients, including: Silymarin (Group 1), Doxycycline (Group 2), and both compounds (Group 3). The patients' response was monitored every month and the lesions were evaluated using photography and two methods of Global Acne Grading system (GAGS) and Acne Severity Index (ASI). According to the results, the response to silymarin was not significantly different with doxycycline in the GAGS index (p = .260), but was lower in the ASI (p = .021). In this study, the synergistic effects of silymarin and doxycycline combination have been investigated in comparison with doxycycline. Although the improvement was more favorable in combination group, there was no statistically significant difference (p = .9 in ASI and p = .5 in GAGS). The results of our study suggest that although the silymarin monotherapy is not as effective as doxycycline for the treatment of acne vulgaris, it can be a therapeutic option.

Evaluating the protective potency of Acacia hydaspica R. Parker on histological and biochemical changes induced by Cisplatin in the cardiac tissue of rats.

BACKGROUND: Increase oxidative trauma is the main cause behind Cisplatin (CP) induced cardiotoxicity which restricts its clinical application as anti-neoplastic prescription. Acacia hydaspica is a natural shrub with diverse bioactivities. Acacia hydaspica ethyl acetate extract (AHE) ameliorated drug-induced cardiotoxicity in animals with anti-oxidative mechanisms. Current study aimed to evaluate the protective potential of A. hydaspica against cisplatin-induced myocardial injury. METHODS: Rats were indiscriminately distributed into six groups (n = 6). Group 1: control; Groups 2: Injected with CP (7.5 mg/kg bw, i.p, single dose) on day 16; Group 3: Treated for 21 days with AHE (400 mg/kg b.w, oral); Group 4: Received CP injection on day 16 and treated with AHE for 5 days post injection; Group 5: Received AHE (400 mg/kg b.w/day, p.o.) for 21 days and CP (7.5 mg/kg b.w., i.p.) on day 16; Group 6: Treated with silymarin (100 mg/kg b.w., p.o.) after 1 day interval for 21 days and CP injection (7.5 mg/kg b.w., i.p.) on day 16. On 22nd day, the animals were sacrificed and their heart tissues were removed. Cisplatin induced cardiac toxicity and the influence of AHE were evaluated by examination of serum cardiac function markers, cardiac tissue antioxidant enzymes, oxidative stress markers and histology. RESULTS: CP inoculation considerably altered cardiac function biomarkers in serum and diminished the antioxidant enzymes levels, while increased oxidative stress biomarkers in cardiac tissues AHE treatment attenuated CP-induced deteriorations in creatine kinase (CK), Creatine kinase isoenzymes MB (CK-MB), cardiac Troponin I (cTNI) and lactate dehydrogenase (LDH) levels and ameliorated cardiac oxidative stress markers as evidenced by decreasing lipid peroxidation, H2O2 and NO content along with augmentation in phase I and phase II antioxidant enzymes. Additionally, CP inoculation also induced morphological alterations which were ameliorated by AHE. In pretreatment group more significant protection was observed compared to post-treatment group indicating preventive potential of AHE. The protective potency of AHE was comparable to silymarin. CONCLUSION: Results demonstrate that AHE attenuated CP induce cardiotoxicity. The polyphenolic metabolites and antioxidant properties of AHE might be responsible for its protective influence.

Hepatoprotective efficacy of Premna integrifolia L. leaves against aflatoxin B1-induced toxicity in mice.

The present study evaluated the hepatoprotective role of ethanol extract of P. integrifolia leaves (EEPL) on aflatoxin B1 (AFB1)-induced toxicity in mice. Mice were administered with AFB1 (0.1 mg/kg b. wt., orally) for 90 days, EEPL (400 and 600 mg/kg b. wt., orally) and silymarin (100 mg/kg b. wt., orally) in combination with AFB1. The study shows the protective effect of EEPL by the restoration of altered hematological indices and liver marker enzymes. Restoration of lipid peroxidation and glutathione content, along with activities of antioxidant enzymes, suggest amelioration of oxidative stress in AFB1-intoxicated mice. In addition, EEPL attenuated apoptosis and histopathological alterations in liver tissue. In conclusion, the current study suggests that EEPL protect mice liver against AFB1 toxicity by inhibiting oxidative stress and apoptosis. The protective activity of EEPL may be due to the enrichment of flavonoids (neohesperidin, apigenin-7-O-glucoside, catechin hydrate, cyanidin chloride, quercetin-3-galactoside, diosmin, genistein, malvin chloride, 4-hydroxy-3-methoxycinnamic acid, kaempferol-3-O-alpha-L-arabinoside, myricitrin, poncirin, vitexin and tiliroside) in the extract as identified by UPLC-QTOF-MS/MS.

Silymarin-loaded nanostructured lipid carrier gel for the treatment of skin cancer.

Aim: The present study was aimed at determining the antiproliferative, antioxidant, anti-inflammatory and antitumor activity of developed silymarin-nanostructured lipid carrier (NLC) gel. Materials & methods: B16 melanoma cell line and albino mice were used as ex vivo and in vivo models, respectively, to evaluate the aforementioned pharmacological activities. Results: The volume of large tumors significantly (p < 0.05) reduced from 5.02 to 3.05 mm3, levels of IL-1α and TNF-α were significantly (p < 0.001) lower and levels of superoxide dismutase (SOD), catalase (CAT) and glutathione (GSH) significantly (p < 0.0001) increased in the group treated with silymarin-NLC gel. Furthermore, in skin treated with placebo and conventional gels, a basosquamous carcinoma and squamous cell carcinoma were noticed, respectively. Conclusion: Silymarin-NLC gel presented better treatment outcomes compared with silymarin-conventional gel.

Effects of silymarin supplementation on blood lipids: A systematic review and meta-analysis of clinical trials.

Dyslipidemia is a leading cause of endothelial dysfunction and cardiovascular disease. Several studies used silymarin as an herbal supplement in hyperlipidemic subjects. The aim of the present systematic review and meta-analysis was to examine the effect of silymarin supplementation on blood lipids. PubMed, Scopus, Ovid (Cochrane library), ISI Web of Science, and Google Scholar were systematically searched until March 2018 to find intervention studies that examined the impact of silymarin supplementation on blood lipids in adults. Changes in blood lipids and potential sources of between-study variation were extracted. We run a subgroup analysis to determine potential sources of inter-study heterogeneity. Ten clinical trials fulfilled the eligibility criteria. Meta-analysis indicated that silymarin supplementation in combination with other treatments (not silymarin alone) reduced total cholesterol (change: -25.45 mg/dl; 95% confidence interval [CI] [-47.89, -3.01 mg/dl]) and low-density lipoprotein (change: -28.25 mg/dl; 95% CI [-53.09, -3.42 mg/dl]). Also, silymarin increased high-density lipoprotein concentration (change: 4.82 mg/dl; 95% CI [2.01, 7.63 mg/dl]). Blood concentration of triglyceride was significantly after silymarin supplementation in comparison with controls (change: -22.55 mg/dl; 95% CI [-44.32, -0.78 mg/dl]). Present systematic review and meta-analysis revealed that silymarin supplementation in combination with other treatments had a favorable effect on blood lipids.

Ginger potentiates the effects of silymarin on liver fibrosis induced by CCL4: the role of galectin-8.

OBJECTIVE: The liver is an important organ that is actively involved in metabolic functions and targeted by a number of toxicants. Galectin-8 (Gal-8) is downregulated in liver fibrosis. Reduced Gal-8 expression correlates with inflammation and metastasis. Therefore, this study aimed to further investigate the benefits of combined administration of silymarin and ginger for CCl4-induced liver injuries in mice. We also investigated the mechanisms underlying the hepatoprotective activity of these herbal drugs and evaluated the role of Gal-8 and apoptosis in liver fibrosis. MATERIALS AND METHODS: Eighty male albino mice were used in this study. Animals were divided into the following groups: control group, fibrotic group, silymarin and ginger group. The CCL4 model was used for the induction of liver fibrosis. RESULTS: Gal-8 expression was reduced in the fibrotic group, while Gal-8 expression was increased in the ginger group and silymarin and ginger group. Tissue levels of nitric oxide (NO) and malondialdehyde (MDA) were markedly increased in the fibrotic group but decreased in the silymarin and ginger group. Additionally, tissue caspase-3 activity and antioxidant markers were decreased in the fibrotic group. However, these markers were increased in the silymarin and ginger group. CONCLUSIONS: Gal-8 is a diagnostic and/or prognostic glycoprotein for liver fibrosis. The combination of silymarin and ginger has protective liver action and reduces the severity and incidence of liver fibrosis.

Metabolic effect of berberine-silymarin association: A meta-analysis of randomized, double-blind, placebo-controlled clinical trials.

The aim of this study is to assess the impact of a combination of berberine and silymarin on serum lipids and fasting plasma glucose (FPG) through a systematic review of literature and meta-analysis of the available randomized, double-blind, placebo-controlled clinical trials (RCTs). A systematic literature search in SCOPUS, PubMed-Medline, ISI Web of Science, and Google Scholar databases was conducted up to October 2, 2018, in order to identify RCTs assessing changes in plasma concentrations of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and FPG during treatment with berberine and silymarin in combination. Two review authors independently extracted data on study characteristics, methods, and outcomes. Quantitative data synthesis was performed using a random-effects model. We identified five eligible RCTs, with 497 subjects overall included. Berberine and silymarin combination treatment exerted a positive effect on TC (mean difference [MD]: -25.3, 95% CI [-39.2, -11.4] mg/dl; p < 0.001), TG (MD: -28, 95% CI [-35.3, -20.6] mg/dl; p < 0.001), HDL-C [MD: 6, 95% CI [3.2, 8.8] mg/dl; p < 0.001), LDL-C (MD: -29.1, 95% CI [-39.7, -18.6] mg/dl; p < 0.001), and FPG (MD: -7.5, 95% CI [-13, -1.9] mg/dl; p = 0.008). The present findings suggest that the coadministration of berberine and silymarin is associated with an advantageous improvement in lipid and glucose profile, suggesting the possible use of this nutraceutical combination in order to promote the cardiometabolic health.

Milk Thistle Treatment for Children and Adults with Trichotillomania: A Double-Blind, Placebo-Controlled, Crossover Negative Study.

BACKGROUND: Data on the pharmacological treatment of trichotillomania are limited. Milk thistle has antioxidant properties and showed promise in trichotillomania in a prior case report. The goal of the current study was to determine the efficacy and tolerability of silymarin in children and adults with trichotillomania. METHODS: Twenty individuals (19 [95.0%] women; 16 adults; mean age, 27.9 [11.5] years) with trichotillomania entered a 12-week, double-blind, placebo-controlled crossover study (6 weeks of milk thistle and 6 weeks of placebo with a 1-week wash-out in between). Dosing of milk thistle ranged from 150 mg twice a day to 300 mg twice a day. Subjects were assessed with the National Institute of Mental Health Trichotillomania Severity Scale (primary outcome), the Massachusetts General Hospital Hair Pulling Scale, Clinical Global Impression scale, and measures of depression, anxiety, and psychosocial functioning. Outcomes were examined using linear mixed models with a random intercept for subject and t tests. RESULTS: There were no statistically significant treatment type-by-time interactions for the main outcome measure, but significant effects were seen for secondary measures (eg, time spent pulling per day for the past week). From baseline to week 6, there was a significant decrease in Clinical Global Impression severity for the milk thistle group but not in the placebo group. CONCLUSIONS: This trial failed to show that milk thistle was more effective than placebo on the main outcome measure, but milk thistle did demonstrate significant improvements on select secondary outcome measures. These findings may shed light on important neurochemical targets worthy of future investigation.

Topical silymarin administration for prevention of acute radiodermatitis in breast cancer patients: A randomized, double-blind, placebo-controlled clinical trial.

Radiation-induced dermatitis is one of the most common side effects of radiotherapy. Silymarin, a flavonoid extracted from the Silybum marianum, exhibits antioxidant and anti-inflammatory activities. The purpose of this study was to investigate the efficacy of silymarin gel in prevention of radiodermatitis in patients with breast cancer. During this randomized, double-blinded, placebo-controlled clinical trial, the preventive effect of silymarin 1% gel was assessed in comparison with placebo, on radiodermatitis occurrence. Forty patients randomly received silymarin gel or placebo formulation on chest wall skin following modified radical mastectomy, once daily starting at the first day of radiotherapy for 5 weeks. Radiodermatitis severity was assessed weekly based on Radiation Therapy Oncology Group (RTOG) and National Cancer Institute Common Terminology for Adverse Events (NCI-CTCAE) criteria radiodermatits grading scale for 5 weeks. The median NCI-CTCAE and RTOG scores were significantly lower in silymarin group at the end of the third to fifth weeks (p value < 0.05). The scores increased significantly in both placebo and silymarin groups during radiotherapy, but there was a delay in radiodermatitis development and progression in silymarin group. Prophylactic administration of silymarin gel could significantly reduce the severity of radiodermatitis and delay its occurrence after 5 weeks of application.

Synergistic therapeutic effects of Vitis vinifera extract and Silymarin on experimentally induced cardiorenal injury: The pertinent role of Nrf2.

BACKGROUND: Cardiorenal crosstalk has gained growing scientific curiosity recently. Clinical observations have approved that heart and kidney performances are intimately interrelated; acute or chronic dysfunction of either is inevitably mirrored on the other. This coexistence usually has the poor prognosis and worsened outcome. METHODS: We designed this study to explore therapeutic potentials of combined Vitis vinifera and Silymarin extracts on histopathological alterations of experimentally induced cardiorenal injury model. Moreover, to examine the pertinent role of Nrf2 in their bio-molecular actions. Sixty adult male Wistar albino rats were utilized, further subdivided into control, doxorubicin (DXR), DXR + Silymarin, DXR + Aqueous Vitis, DXR + Ethanolic Vitis, DXR + Ethanolic Vitis + Silymarin. Left ventricle and renal cortex sections from all groups were processed for histopathological examination, biochemical estimation of serum Urea, Creatinine, BUN, lipid profile and hs-CRP and real-time PCR of Nrf2 expression in cardiac and renal tissue homogenate were performed. RESULTS: Our results proved that combined ethanolic extract of Vitis vinifera and Silymarin restored normal renal and cardiac histomorphology. Significant improvement of Creatinine, BUN, lipid profile and hs-CRP cardiac and renal biochemical indicators confirmed our results. Moreover, significant elevation of mRNA expression levels of Nrf2 proved that combined Vitis vinifera and Silymarin action was directly related to the redox-sensitive regulator pathway. CONCLUSIONS: We concluded that synergistic therapeutic effect of Vitis vinifera extract and Silymarin on experimental cardiorenal injury model owes principally to promoting activation of the Keap1/Nrf2 signaling pathway.