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Objective: This study aims to evaluate the effect of silymarin on insulin resistance and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs)., Methods: We searched PubMed, Embase, Web of Science, and Cochrane Library up to September 2024 for relevant RCTs. The intervention required silymarin supplementation for at least 4 weeks. Primary outcomes were homeostatic model assessment of insulin resistance (HOMA-IR) and fasting insulin (FI), while secondary outcomes included quantitative insulin sensitivity check index (QUICKI). Bias risk was assessed using Cochrane RoB 2. Subgroup analyses were based on disease type, duration, and dosage. Sensitivity and publication bias analyses were conducted using Egger's and Begg's tests. Statistical analysis and meta-analysis were performed using Stata 15.1., Results: Six studies with 673 participants from Iran, Egypt, and Italy were included. All studies had low risk of bias. Meta-analysis showed that Silybum marianum significantly improved HOMA-IR (WMD = -2.29, 95 % CI: -4.55 to -0.03, p = 0.047) but had no effect on FI (WMD = -2.56, 95 % CI: -7.60 to 2.48, p = 0.862). Subgroup analyses revealed improvements in HOMA-IR for T2DM and diabetics with alcoholic cirrhosis, but no effect in non-alcoholic fatty liver disease (NAFLD) patients. QUICKI did not show significant changes in any group. Only one study reported changes in QUICKI. The results indicated that, compared to the placebo, silymarin improved insulin sensitivity in patients with type 2 diabetes mellitus (T2DM)., Conclusion: In conclusion, the results of this study indicate that there is limited evidence supporting the effectiveness of silymarin in improving HOMA-IR and FI levels in metabolic diseases, and it generally does not appear to significantly improve these parameters. Future studies should aim to increase the number of high-quality RCTs to further validate the efficacy and safety of silymarin, as well as to explore its underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Liver disease represents a significant global public health concern. Silybin, derived from Silybum marianum, has been demonstrated to exhibit a range of beneficial properties, including anti-inflammatory, antioxidative, antifibrotic, antiviral, and cytoprotective effects. These attributes render it a promising candidate for the treatment of liver fibrosis, cirrhosis, liver cancer, viral hepatitis, non-alcoholic fatty liver disease, and other liver conditions. Nevertheless, its low solubility and low bioavailability have emerged as significant limitations in its clinical application. To address these limitations, researchers have developed a number of silybin formulations. This study presents a comprehensive review of the results of research on silybin for the treatment of liver diseases in recent decades, with a particular focus on novel formulations based on the pathogenesis of the disease. These include approaches targeting the liver via the CD44 receptor, folic acid, vitamin A, and others. Furthermore, the study presents the findings of studies that have employed nanotechnology to enhance the low bioavailability and low solubility of silybin. This includes the use of nanoparticles, liposomes, and nanosuspensions. This study reviews the application of silybin preparations in the treatment of global liver diseases. However, further high-quality and more complete experimental studies are still required to gain a more comprehensive understanding of the efficacy and safety of these preparations. Finally, the study considers the issues that arise during the research of silybin formulations., (© 2024 John Wiley & Sons Ltd.)

Introduction: Postoperative atrial fibrillation is a frequent complication after coronary artery bypass grafting and is associated with increased mortality. The effects of various drugs on the occurrence of postoperative atrial fibrillation have been studied, but no one has looked into the effect of silymarin on the occurrence of postoperative atrial fibrillation., Methods: This prospective experimental study included 160 patients undergoing coronary artery bypass grafting. The experimental group received 400 mg of silymarin orally three days before the surgery, while the control group did not. The occurrence of postoperative atrial fibrillation was monitored. Patients' clinical data and postoperative characteristics were investigated to elucidate their impact on postoperative atrial fibrillation., Results: Postoperative atrial fibrillation occurred in significantly fewer patients in the experimental group (14 vs. 30, P=0.008). There were also lower mean values of postoperatively measured C-reactive protein (P<0.0005) and aspartate aminotransferase (P=0.001) in the experimental group. Within the multivariate regression model, a non-silymarin group (odds ratio 0.296 [0.109-0.807], P=0.005), postoperative red blood cell transfusion (odds ratio 5.218 [1.930-14.107], P=0.001), left atrial diameter (odds ratio 7.800 [2.122-28.672], P=0.002), postoperative C-reactive protein (odds ratio 1.020 [1.008-1.032], P=0.001), and CHA₂DS₂-VASc score (standing for congestive heart failure, hypertension, age ≥ 75 years [doubled], diabetes, stroke [doubled], vascular disease, age 65 to 74 years, and sex category [female]) (odds ratio 1.873 [1.279-2.743], P=0.001) proved to be independently associated with the development of postoperative atrial fibrillation., Conclusion: This study showed that preoperative administration of silymarin significantly reduces the development of atrial fibrillation after coronary artery bypass grafting.

Introduction: Benign prostatic hyperplasia (BPH) mainly leads to lower urinary tract symptoms (LUTS) in aging men. The present study investigates the role of cholecalciferol, Silymarin, and their combined administration in patients with BPH suffering from LUTS., Methods: This double-blind, randomized, controlled trial enrolled 80 participants (50-80 years) diagnosed with BPH, from March 2019 to March 2020. Based on serum 25-(OH) vitamin D levels we formed subgroups, each receiving specific interventions. Measurements of International Prostate Symptom Score (IPSS), Maximal Urinary Flow Rate (Q-max), Prostate Volume (PV), Post-Void Residual (PVR), and Prostate-Specific Antigen (PSA) were recorded at baseline and following 3 months of follow-up., Results: Participants with serum concentration of 25-(OH) vitamin D below 20 ng/ml simultaneously received cholecalciferol and Silymarin that significantly improved IPSS, irritation, obstruction, PV, and PVR. In those with concentrations ⩾20 ng/ml, a single use of Silymarin significantly reduced IPSS, irritation, obstruction, and PVR. Adjustment of confounding variables revealed independent and significant effects of both cholecalciferol and Silymarin on PVR, IPSS, and obstruction. Cholecalciferol also improved irritation, while Silymarin reduced prostate volume. These findings highlight potential therapeutic benefits for BPH-associated LUTS, encouraging further exploration and clinical consideration., Conclusions: In this investigation, combination therapy with cholecalciferol at 50,000 IU/w for 8 weeks and Silymarin at a dosage of 480 mg for 3 months resulted in a notable improvement in the IPSS score, PV, and PVR, as well as both irritative and obstructive symptoms. However, the total PSA and free PSA amounts did not reach a significant difference., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C 25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, β-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Silibinin, or silybin, is a polyphenolic flavonoid and the main active component of silymarin, isolated from the seeds of the milk thistle plant (Silybum marianum). It has been shown to have antioxidant, antineoplastic, hepatoprotective, neuroprotective, anti-inflammatory, antimicrobial, and antidiabetic effects. In this systematic review, a literature search was conducted from inception until January 2024 on major electronic databases (PubMed, Scopus, Web of Science, and Google Scholar) to identify studies assessing the effects of silibinin on diabetes and its associated complications in different molecular, cellular, animal, and clinical studies. Silibinin has been shown to improve diabetic conditions through a variety of mechanisms, including reducing insulin resistance (IR), lowering reactive oxygen species (ROS) levels, and affecting glycolysis, gluconeogenesis, and glycogenolysis. Silibinin treatment reduced blood glucose (BG) levels, oxidative stress markers, and inflammatory cytokines while increasing glycosylated hemoglobin (HbA1C) and antioxidative marker levels in various cellular and animal models of diabetes. It also ameliorated levels of triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Furthermore, silibinin has been identified as an effective treatment for diabetic complications, including hepatic damage, endothelial dysfunction, neuropathy, nephropathy, retinopathy, and osteoporosis. The promising anti-inflammatory, antioxidant, antidiabetic, and insulin-sensitizing activities of silibinin were also supported in clinical studies. The administration of silibinin could possess multiple protective impacts in improving DM and its complications. Nevertheless, further well-designed investigations are necessary to better understand its mechanisms., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Silymarin as an herbal medicine has shown anticancer effects on tumor cells, while having low toxicity in normal cells. In this study, the effects of Silymarin on proliferation and apoptosis of colorectal cancer cells and its impact on immune response against cancer cells were evaluated in vitro and in vivo., Methods and Materials: The effect of Silymarin on CT-26 and Caco-2 cells proliferation and apoptosis were demonstrated by MTT assay and PI staining. A subcutaneous tumor of colorectal cancer was developed. Silymarin and Doxorubicin were administrated by intravenous injection. qRT-PCR analyses was performed on blood samples and tumor tissues. Spleen tissue was used to evaluate CD8+ T cell immune responses. Histological study was carried out on tumor tissues., Results: Silymarin showed anti-proliferative effects on CT-26 and Caco-2 cells. The markers of immunogenic cell death (Calreticulin exposure, ATP secretion, and HMGB1 secretion) significantly increased in both cell lines in the presence of silymarin. The expression of genes related to cell proliferation particularly β-Catenin and Cycline D1, and also anti-apoptotic ones such as Bcl-2 significantly reduced in mice treated with Silymarin while the expression of pro-apoptotic Bax increased. The RNA level of PD-L1 decreased in tumor tissues exposed by Silymarin. Moreover, the number of CTLs increased in the spleen of mice treated with Silymarin in comparison with untreated mice. Decreased tumor size and also survival of colorectal cancer cells in Silymarin-treated mice were observed in histological analysis., Conclusion: Silymarin treatment showed a suppressive role on colorectal cancer cells almost as much as Doxorubicin. Our study indicated that having a low toxicity profile, cost-effectiveness, and availability of raw materials, plant-derived Silymarin can be a good candidate for further investigation to treat CRC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: Brain tissue in Alzheimer's patients is exposed to oxidative stress. Silymarin is an adjunct drug that has anti-inflammatory and antioxidant properties., Objective: This study aimed to evaluate the effect of silymarin on biomarkers of oxidative stress, inflammation, and disease severity in Alzheimer's patients., Methods: This randomized, single-blind clinical trial study was performed on 33 patients with Alzheimer's disease (AD) whose disease was confirmed by DSM-5 criteria and by brain imaging. Patients in the case group received three 250 mg silymarin capsules daily (each containing 150 mg silymarin), as an adjunctive medication in addition to the routine medication regimen. In the placebo group (control), patients received the same amount of placebo. All patients underwent Mini Mental State Exam (MMSE) and a panel of blood tests including malondialdehyde, neopterin, catalase, paraoxonase-1, total oxidative status, and total antioxidant capacity to reevaluate the changes pre/postintervention at the end of the trimester., Results: The catalase and MDA serum levels after the adjunctive silymarin treatment decreased significantly (Catalase before silymarin  = 9.29 ± 7.02 vs Catalase after silymarin  = 5.32 ± 2.97, p  = 0.007 and MDA before silymarin  = 4.29 ± 1.90 vs MDA after silymarin  = 1.66 ± 0.84, p  < 0.001) while MMSE increased notably (MMSE before silymarin  = 10.39 ± 6.42 vs MMSE after silymarin  = 13.37 ± 6.81, p  < 0.001)., Conclusion: Silymarin can be effective as an adjunct drug and a powerful antioxidant in reducing oxidative stress and improving the course of AD.

Background: Breast cancer is one of the most common diseases globally that may have side effects on liver and renal function. Pharmacological treatments to reduce adverse liver and renal effects are still limited. It has been proposed that silymarin may possess hepatoprotective and anti-inflammatory properties. The present trial aims to assess the hepatorenal protective efficacy of silymarin supplementation in cancer patients receiving chemotherapy in an outpatient setting., Method: This is a randomized, placebo-controlled clinical trial that recruited female breast cancer patients. Participants were randomly assigned to one placebo group and two intervention groups. The control group received 140 mg of placebo daily, while the two intervention groups received 140 mg silymarin daily. Follow-up assessments were conducted at baseline, 3 weeks, and 6 weeks. At the beginning of the study, the patients were subjected to a computed tomography (CT) scan, and the liver and renal parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), bilirubin, Blood urea nitrogen (BUN) and Creatinine (Cr) were examined through laboratory tests., Results: Despite two deaths and three dropouts, 100 patients completed the study. Silymarin showed significant effects on liver enzymes in the levels of ALP and bilirubin (P < 0.05), with no significant impact on renal function in the levels of Blood urea nitrogen (BUN) and Creatinine (Cr) (P > 0.05). The medication was well-tolerated, with minimal reported side effects (P > 0.05)., Discussion: The study suggests that silymarin may have hepato-renal protective potential in breast cancer patients and improve patient tolerance to chemotherapy. The data presented on the efficacy and safety of silymarin may provide stronger foundation for further trials and for a possible use in clinical practice., Trial Registration Information: Registration Number: IRCT20201123049474N2, First Trial Registration: 16/08/2021, Access: https://www.irct.behdasht.gov.ir/trial/57641., (© 2024. The Author(s).)

This randomized clinical trial was conducted to evaluate the effects of silymarin supplementation on glycemic indices and serum lipid profile in type 2 diabetes mellitus (T2DM) patients. In this open-label randomized clinical trial study, 48 patients with T2DM were eligible to participate for 12 weeks and were divided into two groups randomly: 24 subjects in the intervention (received three 140 mg silymarin capsules daily and diet plan) and 24 in control (received a diet plan). Fasting blood samples and anthropometric data were collected, and glycemic indices and lipid profiles were determined at baseline and at the end of the study. Out of 60 patients included in the clinical trial, 48 people completed the study. In comparing silymarin and control groups before and after the study, a significant reduction was observed in weight and body mass index. However, after adjustment, no significant difference was seen between the two groups. Furthermore, daily consumption of three capsules of 140 mg silymarin for 12 weeks did not show any significant difference on the level of fasting blood sugar (p = 0.789), HbA1c (p = 0.719), and lipid profile. The findings of the present study show that silymarin did not lead to changes in the level of glycemic index and lipid profile in patients with T2DM., (© 2024 John Wiley & Sons Ltd.)

Antioxidants play an important role in protecting cardiac arrhythmias. Silymarin, strong antioxidant, is effective in reducing the complications caused by arrhythmias. This study was conducted to determine the effect of silymarin on the prevention and treatment of calcium chloride-induced arrhythmia. In total, 48 male rats were randomly divided into six groups: the first control group for acute administration received intravenous injection of 0.2 mL of dimethylsulfoxide, a cosolvent, immediately after induction of arrhythmia; the second control group for chronic administration, daily gavage of dimethylsulfoxide for 2 weeks before induction of arrhythmia; acute silymarin group, 100 mg/kg intravenous, immediately after the occurrence of arrhythmia; chronic silymarin group, daily gavage of 50 mg/kg for 2 weeks before induction of arrhythmia; amiodarone standard treatment, 5 mg/kg intravenous, immediately after induction of arrhythmia; and quinidine standard treatment, 10 mg/kg intravenous, immediately after induction of arrhythmia. Calcium chloride (140 mg/kg, i.v.) was used to induce arrhythmia. Electrocardiogram was recorded and monitored by PowerLab™ system. The incidence rates of premature ventricular beat (PVB), ventricular tachycardia (VT), and ventricular fibrillation (VF) were calculated. The antiarrhythmic effect of silymarin was observed with a significant decrease in the incidence of premature ventricular beat (22.56 ± 1.04%, P < 0.001), ventricular tachycardia (34.150 ± 1.59%, P < 0.001), and ventricular fibrillation (24.31 ± 1.02%, P < 0.001) compared with the control group (100%). These effects were comparable to antiarrhythmic drugs such as quinidine (29.23% ± 1.24%, 52.23% ± 1.13%, 66.31% ± 1.81%) and amiodarone (22.91% ± .72%, 41.09% ± 1.66%, 61.59% ± 1.11%). Silymarin exerts a potent antioxidant effect, thereby mitigating the risk of VT, VF, and PVC., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2024 Fereshteh Toghroli et al.)

Background: Despite centuries of traditional use of silymarin for hepatoprotection, current randomized controlled trial (RCT) studies on the effectiveness of silymarin in managing metabolic dysfunction-associated steatotic liver disease (MASLD) are limited and inconclusive, particularly when it is administered alone. The low bioavailability of silymarin highlights the possible influence of gut microbiota on the effectiveness of silymarin; however, no human studies have investigated this aspect., Objective: To determine the potential efficacy of silymarin in improving MASLD indicators and to investigate the underlying mechanisms related to gut microbiota., Method: In this 24-week randomized, double-blind, placebo-controlled trial, 83 patients with MASLD were randomized to either placebo (n = 41) or silymarin (103.2 mg/d, n = 42). At 0, 12, and 24 weeks, liver stiffness and hepatic steatosis were assessed using FibroScan, and blood samples were gathered for biochemical detection, while faecal samples were collected at 0 and 24 weeks for 16S rRNA sequencing., Results: Silymarin supplementation significantly reduced liver stiffness (LSM, -0.21 ± 0.17 vs. 0.41 ± 0.17, P = 0.015) and serum levels of γ-glutamyl transpeptidase (GGT, -8.21 ± 3.01 vs. 1.23 ± 3.16, P = 0.042) and ApoB (-0.02 ± 0.03 vs. 0.07 ± 0.03, P = 0.023) but had no significant effect on the controlled attenuation parameter (CAP), other biochemical indicators (aminotransferases, total bilirubin, glucose and lipid parameters, hsCRP, SOD, and UA), physical measurements (DBP, SBP, BMI, WHR, BF%, and BMR), or APRI and FIB-4 indices. Gut microbiota analysis revealed increased species diversity and enrichment of Oscillospiraceae in the silymarin group., Conclusion: These findings suggest that silymarin supplementation could improve liver stiffness in MASLD patients, possibly by modulating the gut microbiota., Trial Registration: The trial was registered at the Chinese Clinical Trial Registry (ChiCTR2200059043)., (© 2024. The Author(s).)

Aim: This study aimed to evaluate the impact of silibinin as a therapeutic agent on ligature-induced periodontitis in rats with liver cirrhosis., Materials and Methods: Twenty-five Wistar rats were enrolled in this study. Group A (Control) included eight rats. The other 17 rats received CCl4 to develop cirrhosis, which was confirmed by sacrificing one of the rats and performing a histological examination of its liver tissue. Periodontitis was induced in the remaining 16 rats then they were allocated into ( n = 8) group B-periodontitis with cirrhosis and group C-silibinin-treated group, 5 times/week starting from week 11 till week 14. Animals of the three groups were euthanized, and biochemical analysis comprising of liver functions assessment (serum levels of glutamate-pyruvate transaminase, serum levels of glutamate-oxalate transaminase, TIMP1) and oxidative stress index [MDA, nitric oxide (NO), superoxide dismutase (SOD), and catalase (CAT)] and histological examination were conducted by the end of week 14., Results: Group C revealed a more organized orientation of the periodontal ligament (PDL) collagen fibers with a marked regain of the alveolar bone height compared to group B. Biochemical analysis confirmed the potent therapeutic effect of silibinin manifested by a significant improvement in the biochemical parameters: tissue inhibitor of metalloproteinase-1, MDA, NO levels, and antioxidant enzymes., Conclusion: Group B was associated with the most unfavorable biochemical findings and the maximum periodontal destruction. Group C demonstrated a positive osteogenic capacity and a noteworthy improvement in biochemical findings, which were comparable to those of group A, which displayed normal and healthy findings., Clinical Significance: The study highlights the potential use of silibinin as a natural remedy with minimal side effects for treating periodontitis in rats with liver cirrhosis. The findings could be translated to human clinical trials, which may lead to new treatment strategies using silibinin as a targeted therapy or as adjunctive therapy to conventional periodontal treatment for patients with liver cirrhosis who are more susceptible to periodontitis. How to cite this article: Shawky HA, Ahmed NM, Essawy MM, et al. Histological and Biochemical Evaluation of Silibinin in Treatment of Periodontitis Induced in Rats with Liver Cirrhosis. J Contemp Dent Pract 2024;25(7):631-638.

Background and Objectives : Coadministration of natural products to enhance the potency of conventional antirheumatic treatment is of high interest. This study aimed to assess the impact of administration of silymarin (a nutritional supplement) in patients with active rheumatoid arthritis under treatment with conventional disease-modifying antirheumatic drugs. Materials and Methods : One-hundred and twenty-two patients diagnosed with active rheumatoid arthritis and treated with conventional disease-modifying antirheumatic drugs were randomly assigned to either control or intervention groups; the latter was supplemented with silymarin (300 mg/day) for 8 weeks. Indicators of disease activity, inflammatory markers, disease activity and disability indices, European League Against Rheumatism responses, fatigue, depression, and anxiety scores were determined at baseline and week 8. Results : Silymarin supplementation significantly reduced the number of tender and swollen joints, duration of morning stiffness, severity of pain, disease activity and disability indices, European League Against Rheumatism responses, levels of fatigue, depression, and anxiety. According to our results, silymarin substantially improved patients' general condition. Conclusions : Our study provides evidence for the benefits of silymarin supplementation to disease-modifying antirheumatic drugs in patients with active rheumatoid arthritis.

In the landscape of cancer treatments, the efficacy of coadjuvant molecules remains a focus of attention for clinical research with the aim of reducing toxicity and achieving better outcomes. Most of the pathogenetic processes causing tumour development, neoplastic progression, ageing, and increased toxicity involve inflammation. Inflammatory mechanisms can progress through a variety of molecular patterns. As is well known, the ageing process is determined by pathological pathways very similar and often parallel to those that cause cancer development. Among these complex mechanisms, inflammation is currently much studied and is often referred to in the geriatric field as 'inflammaging'. In this context, treatments active in the management of inflammatory mechanisms could play a role as adjuvants to standard therapies. Among these emerging molecules, Silibinin has demonstrated its anti-inflammatory properties in different neoplastic types, also in combination with chemotherapeutic agents. Moreover, this molecule could represent a breakthrough in the management of age-related processes. Thus, Silibinin could be a valuable adjuvant to reduce drug-related toxicity and increase therapeutic potential. For this reason, the main aim of this review is to collect and analyse data presented in the literature on the use of Silibinin, to better understand the mechanisms of the functioning of this molecule and its possible therapeutic role.

Background: Paclitaxel (PAX) is a widely used chemotherapy drug for various cancer types but often induces significant toxicity in multiple organ systems. Silymarin (SIL), a natural flavonoid, has shown therapeutic potential due to its multiple benefits., Aims: To evaluate the therapeutic efficacy of SIL in mitigating liver and kidney damage induced by PAX in rats, focusing on oxidative stress, inflammation, and apoptosis pathways., Study Design: Experimental animal model., Methods: The study included 28 male Wistar rats aged 12-14 weeks weighing 270-300 g. The rats were divided into four groups: control, SIL, PAX, and PAX + SIL, with seven in each group. The rats received intraperitoneal (i.p.) injections at a dose of 2 mg per kilogram of body weight of PAX for 5 successive days, followed by oral gavage with 200 mg/kg body mass of SIL for 10 uninterrupted days. We examined the effect of SIL on specific serum biochemical parameters using an autoanalyzer and rat-specific kits. The spectrophotometric methods was used to investigate oxidative stress indicators in kidney and liver tissues. Aquaporin-2 (AQP-2), B-cell lymphoma-2 (Bcl-2), cysteine aspartate-specific protease-3 (caspase-3), interleukin-6 (IL-6), nuclear factor kappa B (NF-κB), and streptavidin-biotin staining were used to assess immunoreactivity in PAX-induced liver and kidney injury models., Results: SIL treatment significantly reduced serum levels of alanine aminotransferase, aspartate aminotransferase, creatinine, urea, and C-reactive protein, indicating its effectiveness in treating PAX-induced liver and kidney injury. SIL treatment significantly reduced oxidative stress by increasing essential antioxidant parameters, such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione. It also reduced malondialdehyde levels in liver and kidney tissues of SIL-PAX groups ( p < 0.05). SIL administration reduced NF-κB, caspase-3, and IL-6 expression while increasing Bcl-2 and AQP2 levels in liver and kidney tissues of rats treated with SIL and PAX ( p < 0.05)., Conclusion: Our findings indicate the potential of SIL to alleviate PAX-induced liver and kidney damage in rats by reducing oxidative stress, inflammation, and apoptotic processes., Competing Interests: Conflict of Interest: The authors declare that they have no conflict of interest.

Background: Silymarin is an antioxidant that can protect against free radicals that cause premature signs of aging and oil oxidation that may contribute to breakouts., Aims: The objective of these studies was to evaluate a silymarin antioxidant serum alone and in combination with a prescription acne treatment regimen in improving facial appearance in blemish-prone skin.&nbsp; Methods: Two international studies were conducted. A 12-week study in Brazil enrolled 56 subjects to examine the effect of silymarin antioxidant serum on facial acne. Clinical grading on acne lesions, skin tone, clarity, and postinflammatory hyperpigmentation (PIH) were conducted. In addition, consumer self-assessment, analysis for markers of lipid peroxidation, and sebumeter analysis were completed. Another Unites States (US)/German study enrolled 40 subjects who were on topical prescription acne medications to which silymarin antioxidant serum was added. Acne lesion counts, tolerability, and facial appearance assessments were conducted in this study., Results: The Brazilian study demonstrated a 45% reduction in inflammatory lesions and a 43% reduction in noninflammatory lesions after 12 weeks of silymarin antioxidant serum use. In addition, sebumeter testing showed a 16% reduction in oiliness at week 1. The US/German study showed the benefits of the serum in persons already on prescription acne therapy by reducing facial erythema by 60%, dryness by 49%, and scaling by 67%., Conclusion: Silymarin is shown in clinical testing to have significant benefits in reducing lipid peroxidation, oiliness, and PIH, and in improving key markers of skin aging. Additionally, the serum can be used alone or as an adjunctive treatment in acne therapy to further benefit aging, acne-prone skin. J Drugs Dermatol. 2024;23(4):&nbsp; &nbsp; &nbsp;doi:10.36849/JDD.8120.

Background: Owing to the rich phytochemical content of Silymarin, it may effectively manage inflammation and oxidative stress. We, therefore, aimed to examine the existing evidence on the effect of Silymarin consumption on inflammation and oxidative stress factors by conducting a systematic review and meta-analysis of randomized controlled trials., Methods: A systematic literature search up to September 2023 was completed in PubMed/Medline, Scopus, and Web of Science, to identify eligible RCTs. Heterogeneity tests of the selected trials were performed using the I 2 statistic. Random effects models were assessed based on the heterogeneity tests, and pooled data were determined as weighted mean differences with a 95% confidence interval., Results: Fifteen RCTs were included in this meta-analysis. Our findings showed that Silymarin consumption significantly decreased CRP (WMD, - 0.50 mg/L; 95% CI, (- 0.95 to - 0.04); p = 0.03), MDA (WMD, - 1.19 nmol/mL; 95% CI, (- 1.99 to - 0.38); p = 0.004), and IL-6 (WMD, - 0.44 pg/ml; 95% CI, (- 0.75 to - 0.12); p = 0.006). Silymarin consumption had no significant effects on IL-10, TAC, and GSH. A significant non-linear relationship was observed between the duration of the intervention and MDA changes., Conclusions: Silymarin can help reduce inflammation in patients with diabetes and thalassemia by reducing MDA as an oxidative stress marker and CRP and IL-6 as inflammatory markers., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objective: Data on the pharmacological treatment of gambling disorder are limited. Silymarin (derived from milk thistle) has antioxidant properties. The goal of the current study was to determine the efficacy and tolerability of silymarin in adults with gambling disorder., Methods: Forty-three individuals (18 [41.9%] women; mean age=49.61 [±13.1] years) with gambling disorder entered an 8-week, double-blind, placebo-controlled study. Dosing of silymarin ranged from 150 to 300 mg twice a day. The primary outcome measure was the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS). Secondary outcome measures comprised the Gambling Symptom Assessment Scale and measures of depression and anxiety. Outcomes were examined using mixed-effect models., Results: Silymarin did not statistically differentiate from the placebo on any of the outcome measures of interest, in terms of treatment group×time interactions. There was a robust response in the placebo group (57% reduction on the PG-YBOCS), and on average there was a 56% reduction in YBOCS score for the milk thistle., Conclusions: The findings of this study do not support the use of silymarin/milk thistle in the treatment of gambling disorder but highlight the large placebo response seen in gambling disorder. Treatment interventions for gambling disorder need to better understand and address the placebo response., Trial Registration: ClinicalTrials.gov identifier: NCT02337634., Competing Interests: Conflicts of interest and source of funding: There was no funding for this study. Dr Grant has received research grants from Biohaven and Janssen Pharmaceuticals. Dr Grant receives yearly compensation from Springer Publishing for acting as Editor-in-Chief of the Journal of Gambling Studies and has received royalties from Oxford University Press, American Psychiatric Publishing, Inc, Norton Press, and McGraw Hill. Dr Chamberlain's role and research is funded by the NHS. Dr Chamberlain receives honoraria from Elsevier for his role as associate editor at journals. Dr Driessens reports no conflicts of interest. Dr Driessens' role in this study was supported by the National Institute for Health and Care Research ARC Wessex, UK. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health and Care Research or the Department of Health and Social Care, UK., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Liver cirrhosis is the consequence of chronicisation and of the evolution of untreated liver diseases. The complexity of the disease and the complications it can cause have been and are still intensively researched, aiming to discover new therapies or improve existing ones for the effective management of liver cirrhosis. Currently, the treatment used is directed against the cause that caused the disease, if it is known; in advanced cases, liver transplantation is the only valid therapeutic option. Hepatoprotectors that are currently on the market are numerous, having as common properties the antioxidant, anti-inflammatory, stabilizing properties of the hepatocytic membrane; A few examples: the ethanolic extract of Curcuma longa, the extract from the plant called Sophora flavescens, the extract of Glycyrrhiza glabra, silymarin (extracted from Sylibum marianum), the extract of Ganoderma lucidum, etc. Liver cirrhosis is accompanied by generalized hypovitaminosis, so supplementing the diet with hydro- and liposoluble vitamins is mandatory. Protein-caloric malnutrition can be prevented by a hyperprotein diet, especially beneficial being the supplementation with branched-chain amino acids, which are also applicable in the prophylaxis and treatment of hepatic encephalopathy. Nanoparticles are a state-of-the-art therapeutic option, proving increased bioavailability, for example polydopamine nanoparticles loaded with l-arginine have been tested as therapy in liver cirrhosis. Among the innovative treatment directions in liver cirrhosis are hybrid products (e.g. hybrid polymer nanoparticles loaded with caffeic acid), cell cultures and artificial or bioartificial liver support.

Silymarin has ameliorated obesity, type 2 diabetes (T2DM), and insulin resistance (IR) in combination with standard therapy, diet, or exercise in recent studies. Obesity and IR are the main risk factors for developing T2DM and other metabolic disorders. Today, there is a need for new strategies to target IR in patients with these metabolic diseases. In the present longitudinal study, a group of non-diabetic insulin-resistant women with type 1 and type 2 obesity were given silymarin for 12 weeks, with no change in habitual diet and physical activity. We used the Homeostatic Model Assessment for Insulin Resistance Index (HOMA-IR) to determine IR at baseline and after silymarin treatment (t = 12 weeks). We obtained five timepoint oral glucose tolerance tests, and other biochemical and clinical parameters were analyzed before and after treatment. Treatment with silymarin alone significantly reduced mean fasting plasma glucose (FPG) and HOMA-IR levels at 12 weeks compared to baseline values ( p < 0.05). Mean fasting plasma insulin (FPI), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (Tg), indirect bilirubin, and C-reactive protein (CRP) levels decreased compared to baseline values, although changes were non-significant. The overall results suggest that silymarin may offer a therapeutic alternative to improve IR in non-diabetic individuals with obesity. Further clinical trials are needed in this type of patient to strengthen the results of this study.

Background: β-thalassemia imposes significant complications on affected patients. Silymarin, a natural flavonoid complex, has potential therapeutic properties., Objective: This systematic review aims to comprehensively evaluate the literature on the mechanistic effects of Silymarin on β-thalassemia outcomes in children and adolescents., Methods: A systematic search of electronic databases, including MEDLINE/PubMed, Embase, Scopus, Cochrane Library, and Web of Science (WOS), was done to identify relevant clinical trials before January 2024. Various data were extracted, including study characteristics, outcomes measured (hematological parameters, oxidative stress markers, iron metabolism, and other outcomes), proposed mechanisms, and safety., Results: By iron chelation effects, Silymarin can reduce reactive oxygen species (ROS) production, increase intracellular antioxidant enzyme glutathione (GSH), and insert antioxidant effects. It also attenuated inflammation through reduced tumor necrosis factor-alpha (TNF-α), transforming growth factor-β1 (TGF-β1), interferon-gamma (IFNγ), C-reactive protein (CRP), interleukin 6 (IL-6), IL-17, and IL-23 levels and increase in IL-4 and IL-10 levels. By reducing iron overload conditions, Silymarin indicates modulatory effects on immune abnormalities, inhibits red blood cell (RBC) hemolysis, increases RBC count, and minimizes the need for a transfusion. Moreover, it reduces myocardial and hepatic siderosis, improves liver function tests, and modifies abnormal enzymes, particularly for aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin, and total protein levels. Silymarin also reduces iron overload, increases antioxidant and anti-inflammatory capacity in cardiomyocytes, and reveals antioxidant effects., Conclusion: Silymarin indicates promising effects on various aspects of children and adolescents with β-thalassemia and has no serious side effects on the investigated dosage., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: To evaluate the effectiveness of herbal agents in the prevention and therapy of radiodermatitis in breast cancer patients., Methods: Randomized controlled trials were searched from databases such as PubMed, Web of Science, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) to assess the effectiveness of herbal agents compared to a standard medication or placebo in prevention or treatment of radiodermatitis in breast cancer., Results: Data from 16 studies involving 1994 patients were included. This meta-analysis included 10 clinical trials of 562 breast cancer patients treated with calendula, silymarin, or aloe vera for the prevention of radiodermatitis. Silymarin showed positive effects in ameliorating the damage of radiodermatitis, whereas the efficacy of calendula and aloe vera in the treatment of radiodermatitis lacks sufficient evidence., Conclusions: Herbal medicine may show therapeutic effects on radiodermatitis in breast cancer, but more comprehensive investigations and clinical trials are required in the future., (© 2023 Japan Academy of Nursing Science.)

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are the most common forms of skeletal disease worldwide., Objective: The current systematic review investigated the mechanisms of Silybum marianum , silymarin, and silibinin on RA and OA symptoms., Methods: The PRISMA 2020 statement was used for reporting Items in this systematic review. The result was a list of five databases, including Web of Science, Cochrane Library, Embase, PubMed, and Scopus. After determining the inclusion and exclusion criteria, of 437 records identified, 21 studies were eligible. The data were extracted from the studies and imported into an Excel form, and finally, the effects, outcomes, and associated mechanisms were surveyed., Results: Silybum marianum and its main constituents revealed immunomodulatory, anti-inflammatory, antioxidant, and anti-apoptotic properties in humans and laboratory animals. Moreover, they protect the joints against the cartilage matrix's hypocellularity and fibrillation, reduce synovitis, and inhibit degeneration of aggrecan and collagen-II in human chondrocytes. They also, through reducing inflammatory cytokines, show an analgesic effect. Although silymarin and silibinin have low absorption, their bioavailability can be increased with nanoparticles., Conclusion: In experimental studies, Silybum marianum , silymarin, and silibinin revealed promising effects on RA and OA symptoms. However, more clinical studies are needed in this field to obtain reliable results and clinical administration of these compounds., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Hepatocellular carcinoma is a particularly dangerous and severe kind of liver cancer. Many anticancer drugs fail to complete the treatment of hepatocellular carcinoma without any side effects. There should be appropriate and without side effective treatments for hepatocellular carcinoma., Objective: The objective of the current study was to evaluate how quercetin and silymarin in a niosomal formulation affected hepatocyte carcinoma caused by diethylnitrosamine., Methods: Five groups were created from the thirty male rats. Normal control (untreated group), tumor group (administered dimethylnitrosoamine 200 mg/kg), treatment group I (administered 50 mg/kg of niosomal encapsulated quercetin), treatment group II (administered 50 mg/kg of niosomal encapsulated silymarin), and treatment group III (administered 50 mg/kg of niosomal encapsulated quercetin + silymarin). Then, biochemical estimation, serum analysis, and histopathological examination were carried out., Results: Treatment group III, treated with niosomal encapsulation of a combination of quercetin + silymarin 50 mg/kg, demonstrated the significant restoration of alpha-fetoprotein and carcinoembryonic antigen and also antioxidants like superoxide dismutase and nitric oxide. The histopathological examination showed improved liver architecture in this group compared to other treatment groups., Conclusion: Our findings revealed that a potent anticancer effect was observed in treatment group III as niosomal formulation increased the bioavailability of the drug within the body. In order to completely understand the underlying processes and evaluate the therapeutic effectiveness of these chemicals in the therapy of hepatocellular carcinoma, further investigation and clinical trials are required., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Medicinal plants possess therapeutic potential for reducing reactive oxygen species (ROS)-mediated cellular damage. Hydroxytyrosol is one of the most potent antioxidants that served as control in the current study, including other synthetic antioxidants to computationally identify the antioxidant properties of Silymarin. The sequences of the receptors IκB kinase (IKK), Kelch-like ECH-associated protein 1 (Keap-1) and mitochondrial transcription factor A (Tfam) were retrieved from UniProtKB and homology modeling was performed using Swiss-Model server. Thereof the molecular docking and dynamic simulation studies were performed using Schrödinger's software version 11.5. From the current study, it was reported that on comparison of the binding energy of silymarin, hydroxytyrosol, α-tocopherol, ascorbic acid, butylated hydroxy anisole (BHA) and butylated hydroxytoluene (BHT), Silymarin exhibited better affinities with IKK receptor followed by Hydroxytyrosol suggesting it as the best or comparable of all other known antioxidants that could potentially suppress inflammation and other diseases. Also, Silymarin exhibited poorest binding affinity with Tfam promoting mitochondrial biogenesis, thereby scavenging ROS. However, with Keap-1, Silymarin is ranked 4 th in the list, whereas hydroxytyrosol exhibited highest binding affinity to release oxidative stress. The stability of docked complexes made us conclude that Silymarin has comparable antioxidant properties to hydroxytyrosol, better anti-inflammatory potential and mitochondrial biogenesis enhancing properties to ultimately reduce oxidative stress. Now it can be tested further for in vitro or in vivo studies as potential drug against oxidative insult.Communicated by Ramaswamy H. Sarma.

Background: Ethanol (Eth.) abuse induces memory impairment. Oxidative damage and apoptosis are considered the likely causes of memory impairment. Silymarin (Sil.) is a flavonoid isolated from the plant Silymarin marianum (milk thistle). While studies have reported the neuroprotective effect of Sil. against neurodegenerative processes, the precise mechanism of action of Sil. in Eth.-induced memory impairment remains unclear., Methods: Twenty-eight rats were equally divided into four groups: Control (saline 1 ml/rat); Sil. (200 mg/kg for 30 days); Eth. (2 g/kg/day for 30 days); and Sil. + Eth. Behavioral tests including inhibitory avoidance and open field were used to investigate memory and locomotion. Brain antioxidant parameters, including catalase, superoxide dismutase, total antioxidant capacity and total thiol group, plus oxidative parameters, including malondialdehyde and total oxidant status, followed by hippocampal apoptosis (Bax/Bcl2, cleaved caspase) and histopathological changes were evaluated in the groups., Results: While the administration of Eth. impaired memory, Sil. significantly reversed Eth-induced memory deficits. Eth. administration also augmented brain oxidative and hippocampal apoptosis parameters. In contrast, a marked reduction in brain antioxidant and anti-apoptotic parameters was observed in the Eth. group. At the tissue level, hippocampal sections from Eth.-treated animals revealed severe neuronal damage. The administration of Sil. to Eth.-treated rats remarkably alleviated all the said Eth.-induced biochemical and histopathological effects. On the contrary, Sil. alone did not change the behavior and biochemical/molecular parameters., Conclusion: The memory-enhancing effect of Sil. in Eth.-induced demented rats may be partly mediated by the augmented antioxidant effects and amelioration of apoptotic and histopathological changes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Memory impairment is a result of multiple factors including amyloid-beta (Aβ) accumulation. Several receptors are mediated for Aβ transport and signaling. Moreover, blood lipids are involved in Aβ signaling pathway through these receptors. Mediated blood lipid level by statins aims to regulate Aβ signaling cascade. First, the structure of receptors was taken from the RCSB PDB database and prepared with MGLTools and AutoDock tool 4. Second, the ligand was prepared for docking through AutoDock Vina. The binding affinity was calculated, and the binding sites were determined through LigPlot+ software. Besides, pharmacokinetic properties were calculated through multiple software. Finally, a molecular dynamics (MD) simulation was conducted to evaluate ligands stability along with clustering analysis to evaluate proteins connection. Our molecular docking and dynamic analyses revealed silymarin as a potential inhibitor of acetylcholinesterase (AChE), P-glycoprotein, and angiotensin-converting enzyme 2 (ACE2) with 0.704, 0.85, and 0.83 Å for RMSD along with -114.27, -107.44, and -122.51 kcal/mol for free binding energy, respectively. Moreover, rosuvastatin and quercetin have more stability compared to silymarin and donepezil in complex with P-glycoprotein and ACE2, respectively. Eventually, based on clustering and pharmacokinetics analysis, silymarin, rosuvastatin, and quercetin are suggested to be involved in peripheral clearance of Aβ. The bioactivity effects of mentioned statins and antioxidants are predicted to be helpful in treating memory impairment in Alzheimer's disease (AD). Nevertheless, mentioned drug effect could be improved by nanoparticles to facilitate penetration of the blood-brain barrier (BBB)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Peritoneal dialysis (PD) is the mainstay of treatment for renal failure replacement therapy. Although PD has greatly improved the quality of life of end-stage renal disease (ESRD) patients, long-term PD can lead to ultrafiltration failure, which in turn causes peritoneal fibrosis (PF). Silymarin (SM) is a polyphenolic flavonoid isolated from the milk thistle (Silybum marianum) species that has a variety of pharmacological actions, including antioxidant, anti-inflammatory, antiviral, and anti-fibrotic pharmacological activities. However, the effect of SM on PF and its potential mechanisms have not been clarified. The aim of this study was to investigate the preventive effect of SM on PF in vitro and in vivo as well as elucidate the underlying mechanisms. We established PF mouse models and human pleural mesothelial cell fibrosis in vitro by intraperitoneal injection of high-glucose peritoneal dialysis solution (PDS) or transforming growth factor-β1 (TGF-β1), and evaluated the effect of SM on peritoneal fibrosis in vivo and in vitro. We found that SM alleviated peritoneal dysfunction. Meanwhile, SM inhibited the expression of fibrotic markers (TGF-β1, collagen I, fibronectin) and restored the expression of E-cadherin, BMP-7 in PF mice and TGF-β1-treated Met-5A cells. Furthermore, SM markedly down-regulated the expression of TGF-β1, p-Smad2, and p-Smad3 and up-regulated the expression of smad7. In conclusion, these findings suggested that SM may be an efficient and novel therapy for the prevention of PF through inhibition of TGF-β/Smad signaling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aggression, a highly prevalent behavior among all the psychological disorders having strong association with psychiatric imbalance, neuroendocrine changes and neurological disturbances (including oxidative stress & neuroinflammation) require both pharmacological and non-pharmacological treatments. Focusing the preclinical neuroendocrine determinants of aggression, this interventional study was designed to elucidate the curative effect of antioxidants on aggression in male mice. Adult albino male mice (n = 140) randomly divided into two main treatment groups for α-lipoic acid (ALA) and silymarin with 5 subgroups (n = 10) for each curative study, namely control, disease (aggression-induced), standard (diazepam, 2.5 mg/kg), low dose (100 mg/kg) and high dose (200 mg/kg) treatment groups of selected antioxidants. Resident-intruder paradigm and levodopa (L-dopa 375 mg/kg, p.o.) induced models were used for aggression. Effect of antioxidant treatment (i.e., 21 days bid) on aggression was assessed by evaluating the changes in aggressive behavior, oxidative stress biomarkers superoxide dismutase, catalase, glutathione, nitrite and malondialdehyde (SOD, CAT, GSH, nitrite & MDA), neurotransmitters (dopamine, nor-adrenaline and serotonin), pro-inflammatory cytokines tumor necrosis factor-α and interleukin- 6 (TNF-α & IL-6) along with serum testosterone examination. This study showed potential ameliorative effect on aggressive behavior with both low (100 mg/kg) and high (200 mg/kg) doses of antioxidants (ALA & silymarin). Resident-intruder or L-dopa induced aggression in male mice was more significantly tuned with ALA treatment than silymarin via down regulating both oxidative stress and inflammatory biomarkers. ALA also exhibited notable effects in managing aggression-induced disturbances on plasma testosterone levels. In conclusion, ALA is more effective than silymarin in attenuating aggression in mice., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Overuse of the antipyretic agent Paracetamol (PCM) is linked to hepatotoxicity, which limits its clinical use. The goal of this investigation was to find out how well Balsamodendron mukul (B. mukul) extract protects the liver from acute PCM poisoning. B. mukul extract was procured from a standard crude drug supplier in the local market. The PCM-induced hepatotoxicity was screened in experimental animals. Animals that were treated only with excessive PCM (2g/kg) had changes in their serum biomarkers (i.e., serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, alkaline phosphatase, and serum total bilirubin), oxidative stress, Tumor Necrosis Factor-α (TNF-α), and Interleukin-1 proteins. B. mukul extracts of 245μg and 332μg revealed 50% of hydroxyl radical scavenging and lipid peroxidation inhibiting, respectively, which was found to be more significant when compared to ascorbic acid treatment. The outcomes confirmed that B. mukul extract has strong antioxidant activity, which leads to the inhibition of reactive oxygen species (ROS). Treatment with B. mukul extract at doses of 300 and 600mg/kg produced a dose-dependent reduction in the PCM-induced rise of the biochemical parameters. Silymarin at 100mg/kg body weight significantly prevented such rise in the study. Finally, the findings confirmed that the B. mukul extract has more potent than silymarin and revealed higher antioxidant and hepatoprotective activity, which could consider a novel approach for the reduction of PCM-induced liver toxicity., (Copyright © 2023 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Radiodermatitis in breast cancer patients varies from mild irritation to life-threatening lesions. Several studies suggest a role for topical corticosteroid ointments in the treatment of radiodermatitis. Yet, to avoid the adverse effects of corticosteroids, many authors recommend the use of topical herbal products instead. The therapeutic role of herbal treatments has yet to be fully understood. This systematic review evaluates the role of topical or oral herbal medicines in radiodermatitis prevention and treatment. A systematic search of four databases (Embase, PubMed, Web of Science, and Scopus) was performed without language and time restrictions from their inception until April 2023. The bibliographies of potential articles were also searched manually. Studies evaluated and compared the effects of herbal preparations with the control group, on dermatitis induced by radiotherapy for breast cancer. The Cochrane risk of bias tool was used to assess the included studies. Thirty-five studies were included in the systematic review. Studies which used herbal drugs including topical and oral formulations were evaluated. Herbal monotherapy and combination therapy were reported, and their effects on radiodermatitis were explained in the systematic review. In conclusion, henna ointments, silymarin gel, and Juango cream were reported to reduce the severity of radiodermatitis. These agents should be considered for radiodermatitis prophylaxis and treatment. The data on aloe gel and calendula ointment were conflicting. Further randomized controlled trials of herbal medications and new herbal formulations are required to determine their effects on breast cancer radiodermatitis., (© 2023 John Wiley & Sons Ltd.)

One of the biggest factors that negatively affect the cancer treatment plan is the toxic effects of chemotherapeutics on non-target cells and tissues. This information prompted us to investigate the protective effects of silymarin (SL), a hepatoprotective agent, against the hepatotoxic effects of the anticancer drug paclitaxel (PAC). Four groups were formed from 28 rats as control, PAC (2 mg/kg), SL (100 mg/kg) and PAC + SL (combination of PAC with SL). After completing the experimental procedures, the tissues collected after anesthesia were analyzed by Western blot, qRT-PCR, biochemical, stereological, immunohistochemical, and histopathological techniques. Administration of PAC significantly increased the expression of tumor necrosis factor-alpha (TNF-α), Bax, cytochrome-c (cyt-c), and active caspase-3, as well as malondialdehyde (MDA) levels in liver tissue and decreased glutathione (GSH) levels compared with the control group. PAC also resulted in a significant increase in serum triglyceride (TG), cholesterol (CH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with the control group. Pathological changes such as microvesicular steatosis, the formation of Councilman bodies, an increase in total sinusoidal volume, and a decrease in the total number of hepatocytes were observed in the liver tissue of the PAC group. Almost all analysis results in the PAC + SL group were similar to those in the control group, and no significant pathological alterations were observed in this group. The data obtained show that SL protects the liver from the harmful effects of PAC, especially thanks to its TNF-α suppressor, anti-inflammatory, anti-apoptotic and antioxidant effects. Based on this result, in cases where PAC is used in cancer treatment, it can be recommended to be used together with SL to prevent harmful effects on healthy liver tissue and to continue treatment uninterruptedly and effectively., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Medicinal plants with minimal side effects, low cost, and liver-protective effects can be a suitable treatment option for cirrhosis. Therefore, this systematic review aimed to determine the effectiveness of herbal medicines on cirrhosis, a life-threatening liver disease. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for clinical trials that investigated the effect of medicinal plants on cirrhosis. This review includes 11 clinical trials, of which eight studies including 613 patients assessed the effect of silymarin on cirrhosis. Three of six studies showed the beneficial effects of silymarin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Two studies including 118 patients investigated the effect of curcumin on cirrhosis, one showing improvement in quality of life and the other showing improvements in alkaline phosphatase (ALP), bilirubin, prothrombin time (PT), and the international normalized ratio (INR). An article including four patients investigated the effect of ginseng on cirrhosis; two patients reported improvement in the Child-Pugh score, and ascites decreased in two. All studies included here reported no or negligible side effects. Results showed that medicinal plants including silymarin, curcumin, and ginseng have beneficial effects on cirrhosis. However, due to the limited number of studies, further high-quality studies are warranted., (© 2023 John Wiley & Sons Ltd.)

Insulin resistance (IR) and the associated hyperinsulinemia are early pathophysiological changes which, if not well treated, can lead to type 2 diabetes, endothelial dysfunction and cardiovascular disease. While diabetes care is fairly well standardized, the prevention and treatment of IR lacks a single pharmaceutical approach and many lifestyle and dietary interventions have been proposed, including a wide range of food supplements. Among the most interesting and well-known natural remedies, alkaloid berberine and the flavonol quercetin have particular relevance in the literature, while silymarin-the active principle of the Silybum marianum thistle-was traditionally used for lipid metabolism disorders and to sustain liver function. This review describes the major defects of insulin signaling leading to IR and the main properties of the three mentioned natural substances, their molecular targets and synergistic action mechanisms. The actions of berberine, quercetin and silymarin are partially superimposable as remedies against reactive oxygen intermediates generated by a high-lipid diet and by NADPH oxidase, which is triggered by phagocyte activation. Furthermore, these compounds inhibit the secretion of a battery of pro-inflammatory cytokines, modulate intestinal microbiota and are especially able to control the various disorders of the insulin receptor and post-receptor signaling systems. Although most of the evidence on the effects of berberine, quercetin and silymarin in modulating insulin resistance and preventing cardiovascular disease derive from experimental studies on animals, the amount of pre-clinical knowledge strongly suggests the need to investigate the therapeutic potential of these substances in human pathology.

Various therapeutic approaches are conducted for regression of liver fibrosis and prevent possible further carcinogenic transformation. This study was aimed to assess the prospective therapeutic potential of bromelain against thioacetamide (TAA)-induced liver fibrosis using in-vitro and in vivo approaches. In vitro study, HSC-T6 cell line was used to evaluate the effect of bromelain on HSC-T6 cell viability and apoptosis. In vivo, Rats were treated by TAA for 6 weeks for induction of hepatic fibrosis followed by post treatment by different doses of bromelain and silymarin for further 4 weeks to assess the regression of hepatic fibrosis. The in-vitro findings indicated that bromelain hindered the proliferation of HSCs in concentration dependent manner compared with the untreated cells. The in vivo study revealed that treatment of TAA fibrotic rats with different doses of bromelain and silymarin induced a significant restoration in liver function biomarkers, attenuation of oxidative stress, upregulation of total antioxidant capacity and thereby decline of fibrotic biomarkers and improving histopathological and immunohistochemical changes. In conclusion, This study indicates that bromelain can regress TAA induced hepatic fibrosis in rats via inhibiting HSCs activation, α-SMA expression and the ECM deposition in hepatic tissue in addition to its antioxidants pathway, these findings prove the promising therapeutic potential of bromelain as a novel therapeutic approach for chronic hepatic fibrotic diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Carvacrol is a natural phenolic monoterpenoid, and cilostazol is a selective phosphodiesterase-3 inhibitor with antioxidant, anti-inflammatory and antiapoptotic effects. This experiment aimed to explore the hepatoprotective effects of carvacrol and cilostazol alone and in combination against alcoholic liver fibrosis (ALF), and the underlying mechanisms, using silymarin as a reference anti-fibrotic product. ALF was induced by oral administration of ethanol (1 ml/100 g/day) thrice per week. Silymarin (100 mg/kg), carvacrol (70 mg/kg), cilostazol (50 mg/kg), or carvacrol + cilostazol combination were administered daily and concurrently with ethanol for six weeks. Hepatic changes were evaluated by quantifying serum biomarkers of liver injury, hepatic MDA, GSH and NOx as oxidative stress markers, interleukin (IL)-10 as an anti-inflammatory cytokine, 4-hydroxyproline (4-HYP) as a collagen synthesis indicator, transforming growth factor (TGF)-β1 as a profibrogenic cytokine, α-smooth muscle actin (α-SMA) as a marker of hepatic stellate cells (HSCs) activation, histopathological (necroinflammation and fibrosis) scores and hepatic sirtuin-1 (SIRT1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and hemeoxygenase-1 (HO-1) mRNA levels. Our results showed that carvacrol, cilostazol, and their combination significantly ameliorated ethanol-induced hepatic fibrosis manifested as improving hepatic functions and histopathological features, attenuating α-SMA immunostaining, reducing TGF-β1 and 4-HYP levels, suppressing oxidativeinjury and elevating IL-10 contents. Such effects were accompanied by upregulating SIRT1, Nrf2 and HO-1 genes. This work disclosed for the first time the hepatoprotective effect of carvacrol against ALF and, to a greater extent, with carvacrol + cilostazol combination that could be partially accredited to SIRT1/Nrf2/HO-1 pathway with consequent antioxidant, anti-inflammatory, and anti-fibrotic features., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Arsenic toxicity is one of the most trending reasons for several malfunctions, particularly reproductive toxicity. The exact mechanism of arsenic poisoning is a big question mark. Exposure to arsenic reduces sperm count, impairs fertilization, and causes inflammation and genotoxicity through interfering with autophagy, epigenetics, ROS generation, downregulation of essential protein expression, metabolite changes, and hampering several signaling cascades, particularly by the alteration of NF-ĸB pathway. This work tries to give a clear idea about the different aspects of arsenic resulting in male reproductive complications, often leading to infertility. The first part of this article explains the implications of arsenic poisoning and the crosstalk of the NF-ĸB pathway in male reproductive toxicity. Silymarin is a bioactive compound that exerts anti-cancer and anti-inflammatory properties and has demonstrated hopeful outcomes in several cancers, including colon cancer, breast cancer, and skin cancer, by downregulating the hyperactive NF-ĸB pathway. The next half of this article thus sheds light on silymarin's therapeutic potential in inhibiting the NF-ĸB signaling cascade, thus offering protection against arsenic-induced male reproductive toxicity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing for financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Wilson's disease causes copper accumulation in the liver and extrahepatic organs. The available therapies aim to lower copper levels by various means. However, a potent drug that can repair the damaged liver and brain tissue is needed. Silymarin has hepatoprotective, antioxidant, and cytoprotective properties. However, poor oral bioavailability reduces its efficacy. In this study, a "thin film hydration method" was used for synthesizing silymarin-encapsulated liposome nanoparticles (SLNPs) and evaluated them against copper toxicity, associated liver dysfunction and neurobehavioral abnormalities in Wistar rats. After copper toxicity induction, serological and behavioral assays were conducted to evaluate treatment approaches. Histological examination of the diseased rats revealed severe hepatocyte necrosis and neuronal vacuolation. These cellular degenerations were mild in rats treated with SLNPs and a combination of zinc and SLNPs (ZSLNPs). SLNPs also decreased liver enzymes and enhanced rats' spatial memory significantly ( p = 0.006) in the diseased rats. During forced swim tests, SLNPs treated rats exhibited a 60-s reduction in the immobility period, indicating reduced depression. ZSLNPs were significantly more effective than traditional zinc therapy in decreasing the immobility period ( p = 0.0008) and reducing liver enzymes, but not in improving spatial memory. Overall, SLNPs enhanced oral silymarin administration and managed copper toxicity symptoms.

This study investigated the effect of eight weeks of aerobic training (AT) combined with silymarin (S)consumption on glycemic indices and liver enzymes in men with type 2 diabetes (T2D). In this clinical trial, 60 middle-aged male volunteers were randomly divided into 4 groups, including: (1) C + placebo(C) (2) AT + placebo (3), S and (4) AT + S. AT was performed for eight weeks, three sessions per week, each session for 20-45 minutes at an intensity of 60-85% of maximal heart rate reserve, and S receiving groups consumed 140 mg/kg S daily (in two servings). AT reduced glycemic indices and liver enzymes in men with T2D ( p  ≤ .05). S decreased blood glucose, insulin, HOMA-IR, AST, ALT and ALP in men with T2D ( p  ≤ .05). Exercise along with silymarin decreased blood glucose, insulin, HOMA-IR, AST, ALT and ALP. Also, reduction of AST and blood glucose in the AT + S group was more favourable than the effect of S alone ( p  ≤ .05). It seems that simultaneous AT and S has interactive effects on reducing glycemic indices and liver enzymes in men with T2D.

Purpose: It is known that obesity has a multifactorial etiology that involves genetic and environmental factors. The WHO estimates the worldwide prevalence of 1.9 billion overweight adults and more than 650 million people with obesity. These alarming data highlight the high and growing prevalence of obesity and represent a risk factor for the development and aggravation of other chronic diseases, such as nonalcoholic fatty liver disease (NAFLD) that is frequently considered the hepatic outcome of type 2 diabetes. The use of non-pharmacological therapies such as food supplements, nutraceuticals, and natural integrative therapies has grown as an alternative tool for obesity-related diseases compared to conventional medications. However, it is a still little explored research field and lacks scientific evidence of therapeutic effectiveness. Considering this, the aim is to evaluate whether a new nutraceutical supplement composition can improve and supply essential mineral nutrients, providing an improvement of obesity-related metabolic and endocrine parameters., Methods: Sedentary volunteers (women and men) with body mass index (BMI) ≤34.9 kg/m 2 were divided into two groups: Novel Nutraceutical Supplement&#95;(S) (n = 30) and Novel Nutraceutical Supplement (n = 29), differing in the absence (S) or presence of silymarin, respectively. Volunteers were instructed to take two capsules in the morning and two capsules in the evening. No nutritional intervention was performed during the study period. The data (anthropometrics and anamneses) and harvest blood (biochemistry and hormonal exams) were collected at three different time points: baseline time [day 0 (T0)], day 90 (T90), and day 180 (T180) post-supplementation., Results: In the anthropometric analysis, the waist circumference in middle abdomen (WC-mid) and waist circumference in iliac crest (WC-IC) were reduced. Also, the waist-to-height ratio (WHt R) and waist-to-hip ratio (WHR) seem to slightly decrease alongside the supplementation period with both nutraceutical supplements tested as well as transaminase enzyme ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR)], a known as a biomarker of NAFLD, and endocrine hormones cortisol and thyroid-stimulating hormone (TSH) at 90 and 180 days post-supplementation., Conclusions: In a condition associated with sedentary and no nutritional intervention, the new nutraceutical supplement composition demonstrated the ability to be a strong and newfangled tool to improve important biomarkers associated with obesity and its comorbidities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nehmi-Filho, Santamarina, de Freitas, Trarbach, de Oliveira, Palace-Berl, de Souza, de Miranda, Escamilla-Garcia, Otoch and Pessoa.)

The reproductive system is extremely vulnerable to chemotherapy drugs, ionizing radiation, toxic heavy metals, chemicals, and so on. These harmful stimuli are able to induce oxidative damage, apoptosis, inflammation, and other mechanisms in the reproductive organs, leading to different adverse reproductive effects. It was shown that using medicinal plants (medicinal herbs) can be an effective medication for the prevention and treatment of multiple health conditions. Silymarin is a medicinal herb extract, obtained from the seeds of Silybum marianum. This herbal agent is a nontoxic agent even at relatively high physiological dose values, which suggests that it is safe for use in the treatment of different diseases. The hepato-, neuro-, cardio- and nephro-protective effects of silymarin have been assessed previously. The protective activities of silymarin can point to anti-oxidant, anti-apoptotic, anti-inflammatory, anti-fibrotic, immunomodulatory, and membrane-stabilizing properties. In this review, we aim to summarize current studies on the protective potentials of silymarin against reproductive toxicity. The molecular mechanisms of silymarin protection against cellular toxicity are also studied. Moreover, the findings obtained from improved formulations and delivery systems of silymarin have been addressed., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Although radiotherapy is one of the main cancer treatment modalities, exposing healthy organs/tissues to ionizing radiation during treatment can lead to different adverse effects. In this regard, it has been shown that the use of radioprotective agents may alleviate the ionizing radiation-induced toxicities., Objective: The present study aims to review the radioprotective potentials of silymarin/silibinin in the prevention/reduction of ionizing radiation-induced adverse effects on healthy cells/tissues., Methods: Based on PRISMA guidelines, a comprehensive and systematic search was performed for identifying relevant literature on the "potential protective role of silymarin/silibinin in the treatment of radiotherapy-induced toxicities" in the different electronic databases of Web of Science, PubMed, and Scopus up to April 2022. Four hundred and fifty-five articles were obtained and screened in accordance with the inclusion and exclusion criteria of the current study. Finally, 19 papers were included in this systematic review., Results: The findings revealed that the ionizing radiation-treated groups had reduced survival rates and body weight in comparison with the control groups. It was also found that radiation can induce mild to severe adverse effects on the skin, digestive, hematologic, lymphatic, respiratory, reproductive, and urinary systems. Nevertheless, the administration of silymarin/silibinin could mitigate the ionizing radiation-induced adverse effects in most cases. This herbal agent exerts its radioprotective effects through anti-oxidant, anti-apoptosis, anti-inflammatory activities, and other mechanisms., Conclusion: The results of the current systematic review showed that co-treatment of silymarin/silibinin with radiotherapy alleviates the radiotherapy-induced adverse effects in healthy cells/tissues., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Thus far, silymarin has been examined in several studies for prevention or treatment of various chemotherapy or radiotherapy-induced adverse reactions. In this review, we try to collect all available human, animal, and pre-clinical data in this field., Methods: The search was done in Scopus, PubMed, Medline, and systematic reviews in the Cochrane database, using the following keywords: "Cancer," "Chemotherapy," "Radiotherapy," "Mucositis," "Nephrotoxicity," "Dermatitis," "Ototoxicity," "Cardiotoxicity," "Nephrotoxicity," "Hepatotoxicity," "Reproductive system," "Silybum marianum," "Milk thistle," and "Silymarin" and "Silybin." We included all relevant in vitro, in vivo, and human studies up to the date of publication., Results: Based on 64 included studies in this review, silymarin is considered a safe and well-tolerated compound, with no known clinical drug interaction. Notably, multiple adverse reactions of chemotherapeutic agents are effectively managed by its antioxidant, anti-apoptotic, anti-inflammatory, and anti-immunomodulatory properties. Clinical trials suggest that oral silymarin may be a promising adjuvant with cancer treatments, particularly against hepatotoxicity (n = 10), nephrotoxicity (n = 3), diarrhea (n = 1), and mucositis (n = 3), whereas its topical formulation can be particularly effective against radiodermatitis (n = 2) and hand-foot syndrome (HFS) (n = 1)., Conclusion: Further studies are required to determine the optimal dose, duration, and the best formulation of silymarin to prevent and/or manage chemotherapy and radiotherapy-induced complications., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Depression and anxiety are the most common mental disorders worldwide., Objective: We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment., Methods: The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed., Results: Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1β, and IL-12β, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation., Conclusion: Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and-ultimately-hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.

Background: Rheumatoid Arthritis (RA) is a systemic chronic autoimmune disease. Several inflammatory agents play key roles in RA pathogenesis, among which tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1β) are of great importance. Silymarin is a potent anti-oxidant extracted from Silybummarianum L. seeds., Objective: To study the effect of silymarin on serum levels of TNF-α and IL-1β in patients with RA., Methods: Patients with stable RA received 140 mg of silymarin, 3 times a day, for 3 months. Serum samples were collected before and after the treatment. Both TNF-α and IL-1β serum levels were measured by ELISA., Results: 42 patients (14.3% male, and 85.7% female, with a mean age of 47.59±12.8 years old) completed the treatment course. There was no significant difference in the overall mean concentration of either TNF-α (p=0.14) or IL-1β (p=0.27) in all 42 patients after the treatment with silymarin., Conclusion: The addition of silymarin to the treatment regimen of patients with stable RA has no significant effect on the serum levels of TNF-α and IL-1β, however, this study needs further evaluation with a larger sample size.

Purpose: To evaluate the effectiveness of antioxidants in the prevention and management of oral mucositis in adults undergoing radiotherapy and/or chemotherapy with diagnosed head and neck cancer (HNC) compared to placebo intervention., Methods: Cochrane, EMBASE, PubMed, and Web of Science databases were used to search for randomized controlled trials (RCTs) comparing oral or topical antioxidants with placebo in clinically diagnosed HNC adult patients receiving radiotherapy with/without chemotherapy. The primary outcome was to assess the efficacy of the antioxidant to prevent and decrease the incidence/prevalence and severity of oral/oropharyngeal mucositis. The risk of bias was assessed following Cochrane's guidelines., Results: The database search resulted in 203 records up to February 19, 2021. Thirteen RCTs were included with 650 HNC-diagnosed patients. Included studies showed a statistically significant improvement in mucositis severity score for all antioxidants except melatonin. However, further studies are needed as only one study reported outcomes for zinc, propolis, curcumin, and silymarin. Patients receiving vitamin E were 60% less likely to develop severe mucositis grade 2 or higher than those receiving placebo in one study (P = 0.040). Patients receiving zinc were 95% less likely to develop severe mucositis (grades 3-4) in one study compared to placebo (P = 0.031). One meta-analysis showed no statistical difference in the risk of having severe mucositis (grades 3-4) with 199 patients compared to placebo for honey (n = 2 studies, P = 0.403). Meta-analyses could not be conducted for zinc, propolis, curcumin, melatonin, silymarin, and selenium due to the lack of studies reporting similar outcomes for the same intervention., Conclusion: Though oral and topical antioxidants significantly improved mucositis severity scores in HNC patients receiving radiotherapy with/without chemotherapy in individual studies, the quality of the evidence was low due to the small number of studies and unclear/high-risk bias. Additionally, large RCTs are needed to confirm these results., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

To study the effect of silymarin on the Interleukin-6 (IL-6) level, size of endometrioma lesion, pain, sexual function, and Quality of Life (QoL) in women diagnosed with endometriosis. This randomized, double-blind placebo-controlled clinical trial was performed on 70 women with endometriosis which was divided into two groups of intervention and control. The intervention was 140 mg silymarin (or matching placebo) administered twice daily for 12 weeks. The volume of endometrioma lesions, the level of IL-6 concentration in serum, pain, sexual function, and QoL were analyzed before and after the intervention. The means of endometrioma volume (P = 0.04), IL-6 (P = 0.002), and pain (P < 0.001) were reduced significantly in the silymarin group after intervention. However, the QoL and female sexual function did not improve substantially in the two groups (P > 0.05). Silymarin significantly reduced interleukin-6 levels, sizes of endometrioma lesions, and pain-related symptoms. The trial has been registered in the Iranian Registry of Clinical Trials (IRCT20150905023897N5) on 4th February 2020 (04/02/2020) ( https://en.irct.ir/trial/42215 ) and the date of initial participant enrollment was 2nd March 2020 (02/03/2020)., (© 2022. The Author(s).)