Impact Of Silymarin Research Articles

The Impact of Silymarin on Inflammation and Oxidative Stress: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Numerous studies have investigated into the antioxidant and anti‐inflammatory properties of silymarin, as well as its ability to reduce reactive oxygen species and inflammation biomarkers. The effect of silymarin on inflammation and oxidative stress was investigated using the keywords “milk thistle” OR “Silybum marianum” OR “Silybum” OR “silymarin” OR “Silibinin” AND “MDA” OR “Malondialdehyde” OR “TAC” OR “total antioxidant capacity” OR “IL‐10” OR “Interleukin‐10” OR “IL‐6” OR “Interleukin‐6” OR “TNF‐α” OR “tumor necrosis factor alpha” on the Web of Science, Scopus, Embase, PubMed, and Cochrane Library, up until March 2023. Data were combined using a random‐effects model, and the weighted/standardized mean differences (WMDs/SMDs) with a 95% confidence interval (CI) were used as the overall effect size. Our meta‐analysis indicated that silymarin supplementation resulted in a significant decrease in levels of C‐reactive protein (CRP) (WMD: −3.39 mg/L, 95% CI: −5.99, −0.79, p = 0.01) and malondialdehyde (MDA) (SMD: −1.69, 95% CI: −2.62, −0.76, p < 0.001). Furthermore, silymarin significantly increases IL‐10 (WMD: 2.03 pg/mL; 95% CI: 1.04, 3.01, p < 0.001), superoxide dismutase (SOD) (SMD: 3.39, 95% CI: 1.42, 5.37, p = 0.001), and glutathione peroxidase (GPx) (SMD: 1.94; 95% CI, 0.89 to 2.99; p < 0.001) level. However, silymarin supplementation did not have significant effects on TAC (SMD: 2.91; 95% CI: −0.30, 6.11, p = 0.076) and IL‐6 (WMD: −0.70 pg/mL; 95% CI: −1.42, 0.02, p < 0.056) level. Silymarin supplementation may significantly improve oxidative stress and inflammation in adults by decreasing CRP and MDA and increasing IL‐10, SOD, and GPx. However, additional studies with longer study periods are required to ascertain the long‐term effects of silymarin on oxidative stress and chronic inflammation.

The effect of silymarin on ischemia-reperfusion injury in skeletal muscles of rats silymarin and ischemia-reperfusion injury

Aim: Although the precise process is not entirely elucidated, it is well-known that oxidative stress mediators contribute to ischemia-reperfusion (I/R) injury. The impact of silymarin on I/R injury in many different tissues has been examined. For this purpose, we planned to see the effect of silymarin on muscle tissue in rats subjected to lower extremity I/R injury. Material and Methods: We used 18 male Wistar albino rats weighing 225-275 g. Each of the three groups of rats [Control (C), Ischemia-Reperfusion (I/R), and Silymarin-Ischemia/Reperfusion (S-I/R)] consisted of six rats. Silymarin was administered intraperitoneally 30 minutes before the procedure. (100 mg/kg-1) In Group I/R, the infrarenal abdominal aorta was clamped with a microvascular clamp. The clamp was removed after 120 minutes, and reperfusion was achieved for the next 120 minutes. At the end of the reperfusion period, muscle tissue samples were collected, and Malondialdehyde (MDA), catalase (CAT) enzyme activity levels and histopathological parameters were compared. Results: In the histopathological examination, no degeneration was observed in the muscle fibers in the Group C, while findings of striated muscle damage such as muscle atrophy/hypertrophy, muscle degeneration/congestion, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization and leukocyte cell infiltration were seen in the Group I/R. In Group S-I/R, muscle atrophy /hypertrophy, internalization of the muscle nucleus/oval/central nucleus, fragmentation/hyalinization, and leukocyte cell infiltration were observed to improve these damaged areas compared to Group I/R. MDA levels in the Group I/R were significantly higher compared to Group C and S-I/R. The activity of the CAT enzyme was much higher in Group I/R compared to Group C. Conclusion: Our study revealed that 100 mg/kg-1 silymarin administered by intraperitoneal injection 30 minutes before ischemia effectively decreased lipid peroxidation, oxidative stress, and the injury caused by I/R in muscle histology in rats.

Silymarin reduced cisplatin-induced hyperalgesia bysuppressing oxidative stress in male rats

Introduction: Cisplatin is an antineoplastic agent which is used in treatment of various cancers. However its clinical use is associated with oxidative stress-mediated neuropathic pain. This research aimed to explore the effect of silymarin on cisplatin-induced hyperalgesia (CIH) and oxidative stress biomarkers in male rats. Methods: Fifty-six male rats were allocated into seven equal groups. Hyperalgesia was caused by intraperitoneal single dose administration of cisplatin (1mg/kg) and assessed by utilizing tail-flick method. The impact of silymarin (25, 50 and 100 mg/kg/day for 15 days) on CIH was investigated on days 1, 5, 10 and 15. Blood samples were collected to assess malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD) and total antioxidant status (TAS) on day fifteen. Results: Single dose injection of cisplatin (1mg/kg) could cause a significant hyperalgesia on days 5, 10 and 15. CIH was abolished by daily administration of silymarin (50 and 100mg/kg) on days 10 and 15. Serum MDA level was decreased in cisplatin and silymarin (100 mg/kg) co-treated rats, while there was an increase in GPx, SOD as well as TAS parameters. Conclusion: The results of this study revealed that silymarin prevents from CIH possibly by improving lipid peroxidation and oxidative stress biomarkers. Other clinical studies should be performed to establish possible use of silymarin for treatment of CIH in susceptible individuals.

Impact of Silymarin in individuals with nonalcoholic fatty liver disease: A systematic review and meta-analysis.

Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease affecting a significant proportion of the general population. Recently, randomized clinical trials have been conducted examining the efficacy of silymarin in individuals with NAFLD, with conflicting results. The aim of this meta-analysis was to evaluate the efficacy of silymarin in the treatment of NAFLD by examining changes in liver biochemistry, body mass index, and liver histology. We searched major electronic databases PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials, as well as gray-literature sources, up to June 2020 for randomized clinical trials examining the efficacy of treatment with silymarin in individuals with NAFLD compared to placebo. The primary outcomes were changes in the mean values of transaminases (alanine aminotransferase and aspartate aminotransferase). Secondary outcomes included changes in body mass index and liver histology. Quality analysis was performed with the risk-of-bias tool 2.0. We synthesized results using weighted mean differences for continuous outcomes, along with 95% confidence intervals. In the meta-analysis, eight randomized clinical trials were included. A cutoff level of 0.05 was considered to provide statistically significant results. Silymarin treatment led to a statistically significant greater reduction in the levels of transaminases compared to placebo, irrespective of weight loss. Silymarin seems to be effective in reducing transaminase levels in individuals with NAFLD. Despite the statistical benefits, we call attention to potential flaws related to the quality of the included studies. Further well-designed studies should be carried out to examine whether this reduction in transaminase levels corresponds to histologic improvement.

The impact of silymarin in patients with non-alcoholic fatty liver disease: A systematic review and meta-Analysis

Rationale: Non-Alcoholic Fatty Liver Disease (NAFLD) is a chronic liver disease affecting a significant proportion of the general population. Recently, randomized clinical trials (RCTs) have been conducted examining the efficacy of silymarin in patients with NAFLD with encouraging results. The aim of our study was to evaluate the efficacy of silymarin in patients with NAFLD

Impact of silymarin on cadmium-induced apoptosis in human spermatozoa.

Oxidative stress-induced apoptosis in spermatozoa may lead to male infertility. Environmental pollutants and heavy metals such as cadmium cause harmful effects on the reproductive system and sperm parameters through the induction of oxidative stress. Silymarin, as a potent antioxidant, is able to inhibit oxidative stress. This study was performed to investigate the protective effects of silymarin on cadmium-induced toxicity in human spermatozoa. Sperm samples were divided into the following five groups: (a) spermatozoa at 0min, (b) spermatozoa in the control group, (c) spermatozoa treated with cadmium chloride (20μM), (d) spermatozoa treated with silymarin (2μM)+ cadmium chloride (20μM) and (e) spermatozoa treated with silymarin (2μM). Sperm parameters related to apoptosis, such as DNA fragmentation, nucleus diameter, mitochondrial membrane potential (MMP) and expression of caspase-3, were evaluated in all groups. After 180min, spermatozoa treated with cadmium chloride showed a significant decrease in nucleus diameter and MMP but a significant increase in DNA fragmentation; however, caspase-3 expression remained unchanged. At this time point, silymarin in the silymarin + cadmium chloride group could significantly reverse the adverse effects of cadmium chloride on these parameters.Silymarn could partly compensate for the caspase-independent apoptosis in the spermatozoa. Therefore, oxidative stress could be a consequence for cadmium toxicity.

The impact of silymarin on antioxidant and oxidative status in patients with β-thalassemia major: A crossover, randomized controlled trial

Background & aimsBlood transfusion therapy is lifesaving for individuals with β-thalassemia major (β-TM). Iron burden following blood transfusion is the main cause of oxidative stress (OS) and organ dysfunction in these patients. The aim of this study was to evaluate the effects of silymarin on serum antioxidant and oxidative status in patients with β-TM. MethodsA crossover, randomized controlled trial was performed on 82 thalassemia patients. In two periods of 12 weeks, patients received 420mg silymarin (divided into three equal 140-mg daily doses) and placebo. The washout period between the two phases was two weeks. Serum malondialdehyde (MDA), protein carbonyl (CO), total antioxidant capacity (TAC), and reduced glutathione (GSH) were measured before and after both periods. ResultsSixty-nine patients completed the study. Mean serum MDA and protein CO significantly decreased in all patients with β-TM after three months of treatment with silymarin. At the end of the study, serum MDA decreased from 20.36±20.11 to 4.79±4.71μmol/l (compared to 17.81±16.05μmol/l after administration of placebo), and protein CO dropped from 0.31±0.28 to 0.11±0.09mM/l (compared to 0.24±0.17mM/l with placebo). Additional laboratory parameters (such as serum TAC and plasma GSH) were also significantly elevated after therapy with silymarin. At the end of the study, serum TAC increased in all patients from 620.7±202.64 to 971.83±328.16μmol FeSO4/l (compared to 672.22±206.88μmol FeSO4/l with placebo), and GSH increased from 46.16±41.68 to 195.35±210.98nM/l (compared to 58.52±48.95nM/l with placebo). The treatment effect of silymarin was measured using a mixed-effects model of variance analysis for changes in MDA, protein CO, TAC, and GSH, with significant effects being demonstrated for each laboratory parameter (P<0.001, P=0.002, P<0.001, and P<0.001, respectively). ConclusionsSilymarin was effective in decreasing serum OS and enhancing serum antioxidant capability in patients with β-thalassemia major. Silymarin given as an adjuvant therapy to standard iron chelators may provide an improvement in the OS measurements obtained in these patients, with accompanying benefit.

Silymarin alleviates hepatic oxidative stress and protects against metabolic disorders in high-fat diet-fed mice

ABSTRACTSilymarin is a potent antioxidant medicine and has been widely used for the treatment of liver diseases over 30 years. Recent studies suggest that silymarin may benefit patients with glucose intolerance. However, the mechanism underlying the action of silymarin is not clarified. The aim of this work was to assess the impact of silymarin on glucose intolerance in high-fat diet (HFD)-fed mice, and explore the potential therapeutic mechanisms. C57BL/6 mice were fed with HFD for 12 weeks, randomized, and treated orally with vehicle saline or silymarin (30 mg/kg) daily for 30 days. We found that silymarin significantly improved HFD-induced body weight gain, glucose intolerance, and insulin resistance in mice. Silymarin treatment reduced HFD-increased oxidative stress indicators (reactive oxygen species, lipid peroxidation, protein oxidation) and restored HFD-down-regulated activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase) in the plasma and/or liver of the HFD-fed mice. Furthermore, silymarin decreased HFD-up-regulated hepatic NADPH oxidase expression and NF-κB activation in mice. Additionally, silymarin treatment mitigated HFD-increased plasma IL-1β, TNF-α levels, and HFD-enhanced hepatic NO, TLR4, and iNOS expression in mice. These novel data indicate that silymarin has potent anti-diabetic actions through alleviating oxidative stress and inflammatory response, partially by inhibiting hepatic NADPH oxidase expression and the NF-κB signaling.

Effect of Silymarin in the Treatment of Allergic Rhinitis

Although the role of oxidative stresses has been confirmed in the pathophysiology of allergic rhinitis and the protective effect of silymarin against oxidative stresses has been proven in different organs, no study has yet been conducted on the impact of silymarin on allergic rhinitis treatment. A randomized clinical trial study. Two tertiary referral centers with otorhinolaryngology-head and neck surgery and allergy and immunology departments. In a randomized clinical trial, 94 patients with the signs and symptoms of allergic rhinitis and a positive skin prick test were selected and randomly divided into 2 groups. Their signs and symptoms, eosinophil percentage on nasal smear, serum IgE, and interleukin (IL-4, IL-5, interferon-γ) levels were recorded. The study group was treated with silymarin, whereas the control group received placebo, both for 1 month, along with routine antihistamine treatment. At the end of the treatment course, clinical and laboratory findings were statistically analyzed. Sixty patients completed the trial. Based on the Sino-Nasal Outcome Test 20 (SNOT-20), a significant improvement in clinical symptom severity was observed in both groups (9.23 ± 5.14 vs 2.20 ± 2.69; P < .001), which was statistically significantly higher in the study group (P < .001). Posttreatment percentage of nasal eosinophils and cytokine levels showed no significant difference (P > .05). Rise in serum IgE level was seen after treatment with silymarin (P = .003). Considering the statistically effective role of silymarin in alleviating the severity of allergic rhinitis symptoms, applying this herbal antioxidant along with other medications may result in better management.