جستجوی مقالات مرتبط با کلیدواژه « silibinin » در نشریات گروه « پزشکی »

Triple-negative breast cancer (TNBC) with a poor prognosis and survival is the most invasive subtype of breast cancer.  Usually, TNBC requires a chemotherapy regimen at all stages, but chemotherapy drugs have shown many side effects. We assumed that combination therapy of vinblastine and silibinin might reduce the vinblastine toxicity and dose of vinblastine.

The MDA-MB-231 were cells subjected to MTT assay for IC50 determination and combination effects, which were measured based on  Chou-Talalay's method. The type of cell death was determined by using a Flow-cytometric assay. Cell death pathway markers, including Bcl-2, Bax, and caspase-3 were analyzed by western blot and Real-Time PCR.

The treatment of MDA-MB-231 cells exhibited IC50 and synergism at the combination of 30 µM of silibinin and 4 µm of vinblastine in cell viability assay (CI=0.69). YO-PRO-1/PI double staining results showed a significant induction of apoptosis when MDA-MB-231 cells were treated with a silibinin and vinblastine combination (p<0.01). Protein levels of Bax and cleaved caspase-3 were significantly upregulated, and Bcl-2 downregulated significantly. Significant upregulation of Bax (2.96-fold) and caspase-3 (3.46-fold) while Bcl-2 was downregulated by 2-fold.

Findings established a preclinical rationale for the combination of silibinin and vinblastine. This combination produces synergistic effects in MDA-MB-231 cells by altering pro- and anti-apoptotic genes, which may reduce the toxicity and side effects of vinblastine.

According to availability of natural products, lower cost and less toxic effects compared to synthetic drugs make them an easy and excellent choice in the treatment of diseases. Silymarin “milk thistle” has been used for many years. Silymarin has antioxidant, anti-lipid peroxidation, anti-fibrotic, anti-inflammatory, and immunomodulatory properties. These effects are due to the addition of endogenous antioxidant enzymes, inhibition of neutrophil infiltration, and a reduction in serum malondialdehyde as an end product of myocardial lipid peroxide. The antioxidant and anti-inflammatory properties of silymarin may also have a protective role against carcinogens. Studies have shown that Silymaran can have protective effects against hepatotoxicity, nephrotoxicity and cardiotoxicity caused by chemical agents. A notable feature is the prowess of silymarin in shielding against reperfusion injury and inflammation, sustained by its unwavering support of anti-inflammatory and antioxidant functions .This review provides a comprehensive survey of the potentials of silymarin in cardio-protection, nephroprotection, and hepatoprotection.

Silibinin has exhibited antitumor activities. However, there are few reports about the immunomodulatory properties of silibinin on T lymphocyte function in the tumor microenvironment. Here, we determined the effects of silibinin on T cells of peripheral blood mononuclear cells (PBMCs), cultivated alone or with a human cell line of glioblastoma (U-87 MG).

The proliferation of T lymphocytes was assessed by MTT test in the presence of silibinin (15 and 45 µM). Also, total antioxidant capacity (TAC), the activity of superoxide dismutase-3 (SOD3), and the levels of two cytokines interferon gamma (IFN-γ) and tumor growth beta (TGF-β) were compared between treated and untreated PBMCs alone or co-cultured with U-87 cells.

According to our results, silibinin raised the TAC levels and SOD3 activity in the PBMCs and in the co-culture condition. Moreover, silibinin-treated PBMCs showed higher IFN-γ levels and lower TGF-β levels. Interestingly, silibinin protected PBMCs against the U-87-induced suppression.

Altogether, these results proposed the immunomodulatory potential of silibinin on T cells of PBMCs, as well as its partially protective effects on PBMCs against the suppression induced by U-87 MG cells.

 Silibinin, an herbal polyphenolic flavonolignan, has antioxidant and anticancer properties.

 This study aimed to evaluate some cellular and molecular effects of silibinin on the human ovarian cancer SKOV-3 cell line.

 For cytotoxicity investigations of silibinin, MTT assay was used at 24, 48, and 72 hours. Apoptosis and cell cycle were studied by flow cytometry. The effect of silibinin on mRNA expression of B-cell lymphoma 2 (Bcl-2), cyclin E, and S-phase kinase-associated protein 2 (SKP2) was determined by Quantitative reverse transcription polymerase chain reaction (QRT-PCR).

 Silibinin administration in lower concentrations (12.5 and 25 µg/mL) did not lead to significant (P < 0.05) changes in cell viability and even slightly increased cell growth after 72 hours. However, silibinin in higher concentrations (≥ 50µg/mL) inhibited SKOV-3 cell proliferation in a dose- and time-dependent manner. The mode of cell growth inhibition was apoptosis induction and G2/M cell cycle arrest. Silibinin caused down-regulation of the anti-apoptotic gene, namely Bcl-2. Additionally, silibinin resulted in down-regulation of the major genes in the cell cycle, including cyclin E and SKP2.

 Overall, this study confirmed the ability of silibinin to suppress ovarian cancer progression through the induction of apoptosis and inhibition of G2/M phase transition. Silibinin may be considered an efficient and safe herbal medication for ovarian cancer.

Almost all diseases of the nervous system are related to neuroinflammation, oxidative stress, neuronal death, glia activation, and increased pro-inflammatory cytokines. Cognitive disorders are one of the common complications of nervous system diseases. The role of some plant compounds in reducing or preventing cognitive disorders has been determined. Silibinin is a plant bioflavonoid and exhibits various effects on cognitive functions. This article discusses the different mechanisms of the effect of silibinin on cognitive disorders in experimental studies.

Databases, including ISI, , Google Scholar, Scopus, Medline  and PubMed, were investigated from 2000 to 2021, using related keywords to find required articles.

Silibinin can improve cognitive disorders by different pathways such as reducing neuroinflammation and oxidative stress, activation of reactive oxygen species- Brain-derived neurotrophic factor- Tropomyosin receptor kinase B (ROS–BDNF–TrkB) pathway in the hippocampus, an increase of dendritic spines in the brain, inhibition of hyperphosphorylation of tau protein and increasing the expression of insulin receptor (IR) and insulin-like growth factor receptor 1 (IGF-1R), inhibiting inflammatory responses and oxidative stress in the hippocampus and amygdala, and decrease of Homovanillic acid/Dopamine (HVA/DA) ratio and 3,4-Dihydroxyphenylacetic acid + Homovanillic acid/Dopamine (DOPAC+ HVA/DA) ratio in the prefrontal cortex and 5-hydroxyindoleacetic acid/5-hydroxytryptamine (5-HIAA/5-HT) ratio in the hippocampus.

These results suggest that silibinin can be considered a therapeutic agent for the symptom reduction of cognitive disorders, and it acts by affecting various mechanisms such as inflammation, programmed cell death, and oxidative stress.

Alzheimer’s disease (AD), the most common cause of dementia, is one of the leading causes of morbidity and death in the world. Currently, treatment mostly used to slow down the disease progression. Herbal remedies are considered by many in the community as a natural and safe treatment with fewer side effects. Silibinin, the active ingredient of Silybum marionum, has anti-oxidant, neurotrophic and neuroprotective characteristics. Therefore, here, the effect of different doses of Silibinin extract on oxidative stress and expression of neurotrophic factors was investigated.  Forty eight male Wistar rats were randomly divided into sham, lesion; Aβ1-40 injection, lesion-treatment; Aβ1-40 injection followed by different doses of silibinin (50, 100, 200 mg / kg) through gavage and lesion-vehicle group; Aβ1-40 injection + vehicle of silibinin. Morris water Maze (MWM) was done 28 days after the last treatment. Hippocampal tissue was removed for biochemical analysis. Production of nitric oxide (NO) and reactive oxygen species (ROS), expression of BDNF/VEGF and cell viability were measured using Griess, fluorimetry, Western blotting and MTT techniques.   Different concentrations of silibinin improved behavioral performance in animals. Higher doses of Silibinin could improve memory and learning function through MWM. Also, increasing the concentration of silibinin resulted in decreased ROS and NO production in a dose-dependent manner. Consequently, silibinin may act as a potential candidate for alleviating symptoms of AD.

Colorectal Cancer (CRC) is the most common malignant gastrointestinal cancer. Cancer stem cells (CSCs) are the major cause of cancer recurrenceand cancer drug resistance. Silibinin, as an herbal compound, has anticancer properties.

The present study aimed to evaluate the antiproliferative effects of silibinin on HT29 stem-like cells (spheroids).

In this study, antiproliferative and apoptotic properties of Silibinin encapsulated in Polymersome Nanoparticles (SPNs) were evaluated by MTT assay, propidium iodide(PI)/AnnexinV assay, cell cycle analysis, and DAPI (4',6-diamidino-2-phenylindole) staining. The expression of some miRNAs and their potential targets was evaluated by real-time reverse transcription-polymerase chain reaction (qRT-PCR).

IC50 of SPNs was determined at 28.13±0.78μg/ml after 24 h. SPNs (28μg/ml) induced apoptosis by 32.36% in HT29 cells after 24 h. DAPI staining indicated a decrease instained nuclei after SPNs induction.SPNs treatment increased the expression of miR-34a, as well as P53, BAX, CASP9, CASP3, and CASP8. The downregulation of miR-221 and miR-222 was observed in SPNs treated cells. Moreover, SPNs decrease the expression level of CD markers inHT29 spheroids (cancer stem cells) compared to untreated spheroids.Spheroids were completely destroyed after 72 h treatment with SPNs (28μg/ml).

As evidenced by the obtained results, SPNs can be used as an effective anticancer agent in multi-layer (cancer stem cells) and mono-layer cancerous cells with the upregulation of tumor suppressive miRs and genes, as well as downregulation of oncomiRs and oncogenes.

 Silibinin is a natural flavonoid compound known to induce apoptosis in cancer cells. Despite silibinin's safety and efficacy as an anticancer drug, its effects on inducing immunogenic cell death (ICD) are largely unknown. Herein, we have evaluated the stimulating effects of silibinin on ICD in cancer cells treated with silibinin alone or in combination with chemotherapy.

 The anticancer effect of silibinin, alone or in combination with doxorubicin or oxaliplatin (OXP), was assessed using the MTT assay. Compusyn software was used to analyze the combination therapy data. Western blotting was conducted to examine the level of STAT3 activity. Flow cytometry was used to analyze calreticulin (CRT) and apoptosis. The heat shock protein (HSP70), high mobility group box protein1 (HMGB1), and IL-12 levels were assessed by ELISA.

 Compared to the negative control groups, silibinin induced ICD in CT26 and B16F10 cells and significantly enhanced the induction of this type of cell death by doxorubicin, and these changes were allied with substantial increases in the level of damage-associated molecular patterns (DAMPs) including CRT, HSP70, and HMGB1. Furthermore, conditioned media from cancer cells exposed to silibinin and doxorubicin was found to stimulate IL-12 secretion in dendritic cells (DCs), suggesting the link of this treatment with the induction of Th1 response. Silibinin did not augment the ICD response induced by OXP.

 Our findings showed that silibinin can induce ICD and it potentiates the induction of this type of cell death induced by chemotherapy in cancer cells.

This study aimed to investigate the radioprotective effect of liposomal silibinin (Lip-SIL) on human lymphocytes in the treatment of non-small lung cancer cells using a combined method of cell viability assay and cytokinesis-block micronucleus assay for a better evaluation of whether one active compound is suitable to be used as a radioprotector in radiotherapy or not.

Firstly, Lip-SIL was prepared by the lipid film hydration method combined with sonication. Secondly, penetration of Lip-SIL into cells was observed by fluorescence microscopy. Finally, the potential application of Lip-SIL as a radioprotector of human lymphocytes in the treatment of non-small cell lung cancer was evaluated using the above combined method with A549 cell line as a model.

The successfully prepared Lip-SIL had a spherical shape and good physical characteristics (particle size of approximately 83.9 nm, zeta potential of -20.6 mV, encapsulation efficiency of 28.8 % and payload of 5.1 %). At a SIL concentration of 10 µg/mL, Lip-SIL exhibited the highest radioprotection for lymphocytes, but showed no radioprotection or even increased genotoxicity in human lung cancer A549 cells.

Lip-SIL is a potential protector of human lymphocytes during radiotherapy in the treatment of non-small lung cancer. Moreover, the results of this study also imply that the radioprotection ability of bioactive compounds for normal cells is not only based on their scavenging activity on reactive oxygen species (ROS) but also on their mechanisms of intracellular activations.

Signal transduction of mitogen-activated protein kinases (MAPKs) is activated during ischemia. In this study, c-Jun N-terminal Kinase (JNK) and p38 MAPK (p38) gene and protein expression were evaluated as two members of the MAPK family during liver ischemia-reperfusion in rats.

Thirty-two male Wistar rats were divided into four groups of eight: Vehicle, ischemia-reperfusion (IR), ischemia-reperfusion+silibinin (IR+SILI), and SILI. The IR and IR+SILI groups differed from the other two groups in that they underwent one hour of ischemia followed by three hr of reperfusion. The Vehicle and IR groups received normal saline while the SILI and IR+SILI groups were treated with silibinin (50 mg/kg). At the end of the reperfusion time, blood and ischemic liver tissue were collected for further experiments.

The expression of JNK and p38 gene, the amount of serum hepatic injury indices, and malondialdehyde (MDA) in the IR group increased significantly compared with the vehicle group. The JNK and p38 gene expression decreased significantly in the IR + SILI group compared with the IR group. Glutathione peroxidase (GPx) and total antioxidant capacity (TAC) levels decreased in the IR group while increasing in the IR+SILI group. Histological examination showed that silibinin significantly reduced the severity of hepatocyte degradation. Western blot results were completely consistent with real-time PCR results.

The possible pathways of the protective effect of silibinin against hepatic ischemia damages is to reduce the expression of the p38 and JNK gene and protein.

Malignant breast cancer (BC) frequently contains a rare population of cells called cancer stem cells which underlie tumor relapse and metastasis, and targeting these cells may improve treatment options and outcomes for patients with BC. The aim of the present study was to determine the effect of silibinin on the self-renewal capacity, tumorgenicity, and metastatic potential of mammospheres.

The effect of silibinin on viability and proliferation of MCF-7, MDA-MB-231 mammospheres, and MDA-MB-468 cell aggregation was determined after 72-120 hours of treatment. Colony and sphere formation ability, and the expression of stemness, differentiation, and epithelial-mesenchymal-transition (EMT)-associated genes were assessed by reverse transcription-quantitative polymerase chain reaction (qRT-PCR) in mammospheres treated with an IC50 dose of silibinin. Additionally, the antitumor capacity of silibinin was assessed in vivo, in mice.

The results of the present study showed that silibinin decreased the viability of all mammospheres derived from MCF-7, MDA-MB-231, and MDA-MB-468 cell aggregation in a dose-dependent manner. Colony and sphere-forming ability, as well as the expression of genes associated with EMT were reduced in mammospheres treated with silibinin. Additionally, the expression of genes associated with stemness and metastasis was also decreased and the expression of genes associated with differentiation were increased. Intra-tumoral injection of 2 mg/kg silibinin decreased tumor volumes in mice by 2.8 fold.

The present study demonstrated that silibinin may have exerted its anti-tumor effects in BC by targeting the BC stem cells, reducing the tumorgenicity and metastasis. Therefore, silibinin may be a potential adjuvant for treatment of BC.

Ovarian cancer is one of the deadliest genital cancers among females and mainly originates from epithelial cells. The cancer generally remains asymptomatic until metastasis. Silibinin, a derivative of Silybum marianum, is a flavonoid with anticancer effects against many tumor cells. The sortilin1 (SORT1) gene has been shown to be overexpressed in ovarian tumors. Here, we investigated the effects of silibinin on SORT1 gene expression and the viability of ovarian A2780s cancer cell line.

The A2780s ovarian cancer cell line was treated with silibinin at the concentrations of 50, 100, and 200 μM for 24 hours, and IC50 (half-maximal inhibitory concentration) was determined. Then the viability percentage of the cells treated with 100 μM silibinin was determined at 24, 48, and 72 hours. After 24 and 48 hours exposure to 100 μM silibinin, RNA was extracted, followed by cDNA synthesis and SORT1 gene expression analysis using glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as the reference gene by real-time Polymerase chain reaction (PCR).

Silibinin in a dose- and time-dependent manner reduced the viability of ovarian cancer cells (P < 0.05), accompanied by a reduction in SORT1 gene expression.

The present study showed that silibinin had toxic effects against the A2780s ovarian cancer cell line, suggesting this compound as a potential anticancer agent.

Recently, there is a significant focus on combination chemotherapy for cancer using a cytotoxic drug and a phytochemical compound. We investigated the effect of silibinin on etoposide-induced apoptosis in MCF-7 and MDA-MB-231 breast carcinoma cell lines. The cytotoxic effects of silibinin and etoposide were determined using MTT assay after 24 and 48 hr incubation with these drugs individually and combined. The mRNA expression of Bax and Bcl2, and protein levels of P53, phosphorylated p53 (P-P53), and P21 were determined using real-time PCR and western blot analysis, respectively. The caspase 9 activity was measured using an ELISA kit. Silibinin and etoposide alone and combined significantly inhibit cell growth in a dose and time-dependent manner in both cell lines. The strongest synergistic effects in terms of MCF-7 cell growth inhibition [combination index (CI) = 0.066] were evident. The silibinin-etoposide combinations cause a much powerful apoptotic death (47% and 40%) compared with each compound individually in MCF-7 and MDA-MB 231 cells, respectively. Additionally, the silibinin-etoposide combinations significantly increased the expression of P53, P-P53, and P21 in MCF-7 cells. Neither silibinin nor etoposide individually increased the level of P53 and P-P53 in MDA-MB-231 cells, but both of them individually and combined increased the level of P21. Since the silibinin-etoposide combination induces apoptosis in both cell lines with and without expression of p53, thus, it is suggested that this combination may be a successful therapeutic strategy for breast cancer regardless of P53 status.

This research examined silibinin's anti-inflammatory outcomes on the NOD-like receptor protein-3 (NLRP3) and NF-κB gene expression, which plays a notable role in inciting inflammatory pathways.

Hepatic ischemia-reperfusion (I/R) is a common phenomenon in many clinical cases, including liver surgery and transplantation. Inflammatory mediators are vital contributors to the expansion of hepatic damage after I/R injury (I/RI), and therefore, targeting inflammation is a considerable candidate for the management of hepatic I/RI and its complications.

Thirty-two male Wistar rats were divided equally into four groups: 1) Control (Vehicle) group, in which rats underwent laparotomy and received normal saline; 2) SILI group, in which rats underwent laparotomy, and 30 mg/kg silibinin was injected intraperitoneal (IP); 3) I/R group, in which rats underwent I/R and received normal saline; and 4) I/R + SILI group, who encountered I/R after laparotomy and received silibinin. After one hour of ischemia and three hours of reperfusion, blood and liver tissue samples were assembled for future biochemical, histological, and gene expression studies.

In vivo analysis attested that serum AST and ALT activities were significantly lessened by silibinin in the SILI + I/R group (p <0.001). Silibinin ameliorated inflammatory liver tissue injuries, including neutrophil and macrophage infiltration, hepatocyte degeneration, cytoplasmic vacuolation, vascular endothelial damages, and sinusoid dilation observed in the I/R group. During I/R, NLRP3 and NF-κB gene expression showed a significant increment compared to the control group (p <0.001), which could be alleviated by silibinin (p <0.01).

The results evidence that adjusting the expression of NLRP3 and NF-κB genes during I/R is probably one of the mechanisms of the anti-inflammatory effects of silibinin.

Silibinin (silibinin A) is the most active silymarin component, which acts both as a hepatoprotective [1] and an antiviral agent. The present study investigated the silibinin effect on IFN-related innate immune genes in PBMCs from HCV-infected patients.

22 chronic HCV patients, including 10 IFN responders and 12 non-responders, were included. Their isolated PBMCs were treated for 6 hours in the presence of silibinin, IFN-α, or their combination. The transcription level of TLR7, ISG15, and SOCS1 genes was compared using real-time PCR.

Our result showed that IFN-α induced a significant up-regulation of TLR7 and ISG15 in PBMCs of both responder and non-responder groups. Nevertheless, the SOCS1 gene was not significantly changed in the non-responder group (P=0.32). The combination of IFNα- and silibinin showed a similar pattern to IFN-α alone. By itself, silibinin did not leave a significant change on the expression level of the studied genes.

The results indicated that silibinin did not enhance or suppress the expression level of TLR7, ISG15, and SOCS1 genes.  Therefore, it has been suggested that its anti-inflammatory role might be devoid of IFN pathways.

Ischemia-reperfusion injury (IRI) is an injurious phenomenon that is the primary determinant of liver dysfunction after surgery and transplantation. The present evidence demonstrated that connexin 43(Cx43), Cx32, and Cx26are the essential gap junction proteins involved in the liver IRI.

This study aimed to characterize the beneficial effects of silibinin on Cx43, Cx32, and Cx26gene expression during warm hepatic ischemia-reperfusion (IR).

A total of 32 male Wistar rats weighing 250-300 g were randomly divided into four equal groups of eight animals in each group as follows:1) control (laparotomy+normal saline), 2) laparotomy+silibinin (30 mg/kg) (SILI), 3) liver IR procedure+normal saline (IR), and 4) liver IR procedure+silibinin (30 mg/kg) (IR+SILI). After 1 h of ischemia followed by 3 h of reperfusion, blood samples and tissue sections were gathered to assess the serum liver markers and evaluate the liver histological changes as well as gene expression, respectively.

The obtained data proved no considerable differences between control and SILI groups in all experiments. Furthermore, the gene expression of Cx26, Cx32, and Cx43was significantly induced in the IR group, compared to the control group. Silibinin markedly reduced Cx26and Cx32mRNA expression, whereas increased Cx43mRNA expression. Moreover, serum alanine aminotransferase and aspartate aminotransferase levels were markedly elevated in the IR group (P<0.001), compared to the control group. However, in the IR+SILI group, silibinin could significantly decline these elevations, compared to the IR group. In addition, silibinin diminished hepatic tissue damages during IR.

Silibinin could attenuate liver injury through better cell-to-cell communication via lowering Cx32and Cx26, as well as increasing Cx43gene expression, respectively

Metastasis of cancer cells is the primary responsible for death in patients with colorectal cancer (CRC). Transforming growth factor-β (TGF-β)-induced matrix metalloproteinases (MMPs) are essential for the metastasis process. Silibinin is a natural compound extracted from the Silybum marianum that exhibits anti-neoplastic activity in cancer cell lines. In this study, we evaluated the effects of silibinin on MMP-2 and MMP-9 induced by TGF-β in human HT-29 CRC cell line and the potential mechanism underlying the effects.

The present in vitro study was done on the HT-29 cell line. The HT-29 cell line was cultured in RPMI1640 and exposed to TGF- β (5 ng/ml) in the absence and presence of different concentrations of silibinin (10, 25, 50, and 100 μM). The effect of silibinin on HT-29 cell viability was measured with the MTT assay. A real-time polymerase chain reaction (Real-Time PCR) determined the relative mRNA expression of MMP-2 and MMP-9. Western blotting was employed to examine MMP-2 and MMP 9 protein expression and Smad2 phosphorylation.

Silibinin inhibits cell viability of HT-29 cell line at 24 hours in a dose-dependent manner. TGF-β increased the mRNA and protein expression of MMP-2, MMP-9, and phosphorylated Smad2 compared to controls. Pharmacological inhibition with silibinin markedly blocked TGF-β–induced MMP-2 and MMP-9 mRNA and protein expression and Smad2 phosphorylation.

Silibinin decreased the cell viability of HT-29 cancer cells in a dose-dependent manner. Silibinin also inhibited TGF-β-stimulated MMP-2 and MMP-9 expression in HT-29 cells, possibly mediated with the Smad2 signaling pathway.