水飞蓟素在慢性疾病中的抗氧化作用研究概述

水飞蓟素(silymarin)作为护肝药物被广泛应用于各类肝病,其护肝作用与水飞蓟素强大的抗氧化、抗炎和抗脂质沉积等作用有关。越来越多研究表明水飞蓟素在氧化应激引发的如心血管疾病、代谢综合征、神经退行性疾病、癌症和并发症等慢性疾病都具有良好治疗效果。本篇列举了近五年水飞蓟素治疗慢性病的通路研究,重点阐述慢性疾病与氧化应激的损伤机制和水飞蓟素的抗氧化能力在其中发挥的关键作用,以期为水飞蓟素的临床使用提供用药思路。     

水飞蓟素抗肿瘤作用及其机制研究进展

水飞蓟素是从植物水飞蓟种子中提取得到的一类生物活性成分,含65%～80%黄酮木脂素(或称水飞蓟素混合物)、少许黄酮、20%～35%脂肪酸和一些多酚。水飞蓟素除用于治疗肝炎和肝硬化等肝脏疾病外,对前列腺癌、皮肤癌、膀胱癌、肺癌和结肠癌等具有抑制作用。近年研究发现,水飞蓟素抗肿瘤的作用机制与其调节细胞周期、诱导细胞凋亡及抑制新生血管形成等作用有关。另外,水飞蓟素具有抗炎、抗肿瘤转移及抗氧化活性,与抗肿瘤药物具有协同增效作用。     

Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes

Silymarin is a polyphenolic plant flavonoid (a mixture of flavonoid isomers such as silibinin, isosilibinin, silidianin and silichristin) derived from Silymarin marianum that has anti-inflammatory, hepatoprotective and anticarcinogenic effects. Our earlier studies have shown that silymarin plays a protective role against the oxidative damage induced by environmental contaminants like benzo(a)pyrene in erythrocyte haemolysates. During the detoxification of these environmental contaminants, the major reactive oxygen species generated is hydrogen peroxide (H(2)O(2)). Because H(2)O(2 )can easily penetrate into the cell and cause damage to biomolecules, the protective role of silymarin was further assessed against this cytotoxic agent in vitro in erythrocyte haemolysates. The protective effect was monitored by assessing the levels of the antioxidant enzymes superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione-s-transferase, glutathione peroxidase and malondialdehyde (LPO) in three groups: vehicle control, H(2)O(2)-exposed groups and drug co-incubation group (H(2)O(2) + silymarin). The protective effect of silymarin on the non-enzymic antioxidant glutathione and haemolysis, methaemoglobin content and protein carbonyl content were also assessed. It was observed that the activities of antioxidant enzymes and glutathione were reduced and the malondialdehyde levels were elevated after H(2)O(2 )exposure. There were also alterations in haemolysis, methaemoglobin content and protein carbonyl content, whereas after the administration of silymarin, the antioxidant enzyme activities reversed to near normal with reduced malondialdehyde content and normalized haemolysis, methaemoglobin content and protein carbonyl content. The results suggest that silymarin possesses substantial protective effect and free radical scavenging mechanism against exogenous H(2)O(2)-induced oxidative stress damages, hence, can be used as a protective drug against toxicity induced by environmental contaminants.     

Silymarin Inhibits Cell Cycle Progression and mTOR Activity in Activated Human T Cells: Therapeutic Implications for Autoimmune Diseases

Silymarin, a complex flavonolignan from the ‘milk thistle’ (Silybum marianum) plant, exhibits anticarcinogenic, anti‐inflammatory and cytoprotective effects. Several reports have demonstrated immunosuppressive activity of silymarin; however, the molecular mechanisms involved in immunomodulatory activities of silymarin are not fully understood yet. In this study, the effect of silymarin on cell cycle and PI3K/Akt/mTOR signalling pathway of activated T lymphocytes was investigated in vitro. Peripheral blood mononuclear cells (PBMC) were isolated from healthy volunteers and activated with anti‐CD3 (5 μg/ml) and anti‐CD28 (2 μg/ml) monoclonal antibodies. Cells were cultured in Complete RPMI medium with 10, 50 and 100 μM silymarin or dimethyl sulphoxide (DMSO) and incubated for 24–96 hrs. Cell cycle analysis was performed by PI staining and flow cytometry. The effect of silymarin on PI3K/AKT signalling pathway and mTOR activity was determined in activated T cells after 72‐hr incubation with silymarin or DMSO. A significant G1 arrest in cell cycle of activated T lymphocytes was found after 96‐hr incubation with 100 μM silymarin without causing cell death. Silymarin also significantly inhibited the level of phospho‐S6 ribosomal protein and mTOR activity in cell lysates of activated T cells after 72‐hr incubation in comparison with DMSO. This study shows that silymarin inhibits cell proliferation through G1 cell cycle arrest and also through the suppression of the mTOR signalling pathway in human activated T lymphocytes in vitro. Characterizing molecular mechanism of such immunomodulatory effects may have a great potential in future practical application of silymarin in transplantation and auoimmunity.     

Protective effect of silymarin against ethanol-induced gastritis in rats: Role of sulfhydryls,nitric oxide and gastric sensory afferents

Silymarin has been known to exert antioxidant, anti-carcinogenic and anti-inflammatory effects. In this study, we examined the effect of silymarin on gastritis in rats. Oral administration of silymarin dose-dependently decreased gastric lesions in ethanol-induced gastritis model. Silymarin also significantly suppressed the development of gastric lesions in aspirin- or water immersion-restraint stress-induced gastritis models. Further study demonstrated that the gastroprotective effect of silymarin was blocked by nitric oxide (NO) synthase inhibitor l-NAME, SH blocker N-ethylmaleimide or TRPV1 antagonist capsazepine in ethanol-induced gastritis model. In addition, ex vivo analysis revealed that ethanol-induced decrease in gastric mucus and non-protein sulfhydryl (NPSH) groups was significantly reversed by silymarin treatment and lipid peroxidation was also suppressed by silymarin in ethanol-induced gastritis model. Taken together, these results suggest that silymarin exerts gastroprotective effects and the gastroprotective effects of silymarin might be related to the protection of gastric mucosal NO and NP-SH and the modulation of capsaicin-sensitive gastric sensory afferents.     

Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway

Cancer is one of the largest causes of death in both men and women. Akt, overexpressed in a number of human malignancies including leukemia, is an important target in cancer prevention and/or therapy. Silymarin, a flavonoid antioxidant, has high human acceptance being used clinically for the treatment of liver diseases. In this study, Akt activity was inhibited by silymarin without changes in total Akt level associated with a prominent caspases-9 and -3 activation as well as PARP cleavage, accompanied by a strong apoptotic death and growth inhibition of K562 cells. These findings suggest that silymarin could serve as a candidate for anti-leukemia drug.     

Physiological responses of a natural antioxidant flavonoid mixture,silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes at high doses

Silymarin is a mixture of bioactive flavonoids isolated from Milk Thistle (Silybum marianum). Crude extracts from this plant have been used for centuries as a natural remedy and silymarin is now effectively used in the treatment of inflammatory liver toxicity and disease in humans. In vitro studies show that silymarin can inhibit the production and damage caused by tumor necrosis factor alpha (TNFalpha) and is a potent antioxidant both in vitro and in vivo. Such findings suggest silymarin may impact the immune system but little information exists following in vivo exposure. Therefore, we tested the hypothesis that exposure to silymarin will modulate the inflammatory immune response. Male BABL/c mice (6/group) were treated intraperitoneally once daily for five days with 0, 10, 50 or 250 mg/kg of silymarin. Silymarin exposure did not produce any signs of overt toxicity or any changes in relative organ weights. Flow cytometric examination of splenic lymphocyte populations showed that the absolute number of CD3+ T-lymphocytes was reduced in the 10 and 50 mg/kg groups although significance was evident only in the 10 mg/kg group. Concomitant decreases in CD4+ and CD8+ T-cell populations were observed but only the CD4+ population in mice treated with 10 mg/kg of silymarin was significantly different from control. Functional examination of secondary lymphoid cells revealed that phytohemagglutinin-induced T-lymphocyte proliferation was increased in the lowest dose group only. B-lymphocyte blastogenesis induced by lipopolysaccharide was increased following exposure to 10 and 50 mg/kg of silymarin. Similarly, expression of TNFalpha, inducible nitric oxide synthase, IL-1beta and IL-6 mRNA were increased dose-dependently. The expression of IL-2 and IL-4 were reduced in mice treated with 10 and 50 mg/kg of silymarin although only the 10 mg/kg group was significantly different from control. The results indicate that in vivo parenteral exposure to silymarin results in suppression of T-lymphocyte function at low doses and stimulation of inflammatory processes at higher doses. Further studies investigating the effects of silymarin on the immune system are warranted.     

水飞蓟素防治实验性肝病的作用及相关临床应用的研究进展

水飞蓟素是一种黄酮类化合物，具有清除活性氧、抗脂质过氧化、抗炎、抗肿瘤等多种药理作用。笔者通过查阅大量相关文献，发现水飞蓟素对各种肝病均具有较好的防治作用。随着基础研究的深入，发现水飞蓟素还可以促进肝细胞的修复与再生，与抗病毒药物及其他护肝药物联用时能更显著地降低血清转氨酶水平及改善肝纤维化，具有安全性高及耐受性好的优点。本文主要对水飞蓟素对不同肝病的防治作用、作用机制及其临床应用现状进行综述，以期为水飞蓟素在防治肝病方面的深入研究、药物开发和临床应用等方面提供参考。     

Protective effect of silymarin in antigen challenge- and histamine-induced bronchoconstriction in in vivo guinea-pigs

The effects of silymarin on bronchoconstriction induced by antigen challenge and on post-antigen challenge hyperresponsiveness to substance P were evaluated in sensitized guinea-pigs. Silymarin significantly decreased the bronchoconstriction due to antigen administration in the early phase of the response. In contrast, the dose-response curve for substance P recorded 1 h after antigen challenge was not modified by pretreatment with silymarin. The influence of the flavonoid on hyperresponsiveness to histamine in propranolol- and PAF (platelet-activating factor)-treated animals was also assessed. Silymarin did not affect hyperresponsiveness to histamine induced by either propranolol or PAF although it had inhibitory activity on the bronchial contractile response to the autacoid. These results suggest that silymarin has a protective effect in the early phase of allergic asthma, an effect, which may be related to a negative influence of the flavonoid on bronchial responsiveness to histamine.     

Potential renoprotective effects of silymarin against nephrotoxic drugs: a review of literature

Drug-induced nephrotoxicity (DIN) accounts for up to sixty percent of hospital acquired acute kidney injury. Several efforts have been made to reduce drug-induced renal damage; however, DIN remains a matter of concern, with substantial impact on patients and the health system. Silymarin is a drug that has been used for many years in alternate and modern medicine for treating hepatic diseases. Its antioxidant, anti-inflammatory and anti-apoptotic effects make it an interesting herbal medicine, and these properties have implicated this compound as a potential renoprotective agent. Based on the findings from animal studies, this review concluded that silymarin might exert significant protective or ameliorative effects against drug-induced kidney disease, especially against cisplatin-induced renal damage. Whether the protective administration of silymarin could be an effective clinical pharmacological strategy to prevent DIN is a question that remains to be answered in clinical trials.     

Silymarin augments human cervical cancer HeLa cell apoptosis via P38/JNK MAPK pathways in serum-free medium

Silymarin was proved to have a protective effect of UV-induced A375-S2 cell apoptosis in our previous research. In this study, its pro-apoptotic and anti-apoptotic activities on human cervical cancer (HeLa) cells in vitro were investigated. Silymarin induced HeLa cell death through both apoptotic and necrotic pathways. At low doses (below 80 micromol l-1), it induced cell apoptosis, but caused necrosis at high dose (160 micromol l-1). Silymarin induced typical chromatin condensation and nuclear fragmentation as a hallmark of apoptosis. In this case, mitochondrial Bcl-2 family, Bcl-2 and Bax, were not involved in apoptotic effects; however, silymarin-induced cell death was regulated by the activation of p38 and JNK MAPKs. We also found that pan-caspase inhibitor and caspase-3 inhibitor could not antagonise silymarin-induced apoptosis. Therefore, silymarin induced and augmented HeLa cell apoptosis through p38/JNK MAPKs in the serum-free medium.     

Topical application of silymarin reduces chemical-induced irritant contact dermatitis in BALB/c mice

Irritant contact dermatitis (ICD) is a non-allergic local inflammatory reaction of a skin and one of the most frequent occupational health problems. Silymarin has been clinically used in Europe for a long time to treat liver diseases and also known to have anti-cancer and anti-inflammatory activities. In the present study, we report that topical application of silymarin reduces chemical-induced ICD. Topical application of 2,4-dinitrochlorobenzene (DNCB) induced an ear swelling in BALB/c mice and silymarin suppressed DNCB-induced increase in ear thickness. Prophylactic and therapeutic application of silymarin showed similar effect on DNCB-induced increase in ear thickness and skin water content. In addition, phobor ester- or croton oil-induced increase in ear thickness was also inhibited by silymarin treatment. Silymarin also blocked neutrophil accumulation into the ear induced by these irritants. Further study demonstrated that DNCB-induced tumor necrosis factor-alpha (TNF-alpha) expression in mouse ear was suppressed by silymarin. DNCB-induced expression of KC, one of the main attractors of neutrophil in mice, and adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1) and E-selectin in mouse ear were also inhibited by silymarin. Moreover, TNF-alpha-induced expression of cytokines, such as TNF-alpha and IL-1beta, and a chemokine, IL-8, were suppressed by silymarin treatment in human keratinocyte cell line, HaCaT. Silymarin also blocked TNF-alpha- and DNCB-induced NF-kappaB activation in HaCaT. Collectively, these results demonstrate that topically applied silymarin inhibits chemical-induced ICD in mice and this might be mediated, at least in part, by blocking NF-kappaB activation and consequently inhibiting the expression of cytokines and adhesion molecules.     

Effects of silymarin MZ-80 on hepatic oxidative stress in rats with biliary obstruction.

This study was designed to evaluate the effects of three pharmaceutical forms of silymarin (silymarin MZ-80, silybinin-beta-cyclodextrin, and silybinin) on the liver oxidative status in vitro and after oral administration to rats with extrahepatic biliary obstruction (EBO) and sham-operated animals. We evaluated thiobarbituric acid-reactive substances (TBARS), glutathione (GSH + GSSG) and their related enzyme activities (GSH peroxidase, GSSG reductase and GSH transferase). All three compounds inhibited the in vitro production of TBARS (IC(50) 56-533 micromol/l). These compounds, mainly silymarin MZ-80, also increased GSH peroxidase and GSH transferase activities. In EBO rats we found increases in TBARS production which was inhibited by 50-70% after treatment. Glutathione was reduced by 55% and elevated by silymarin MZ-80. GSH transferase increased in the group given silymarin MZ-80. We conclude that all three derivatives of silymarin show a clear ability to reduce lipid peroxidation in the liver. Silymarin MZ-80 was the only compound that enhanced the glutathione antioxidant system.     

Autoantibody-induced formation of immune complexes in normal human serum

Intravenous immunoglobulins (IVIg) are concentrated preparations of purified human plasma-derived IgG routinely used in the treatment of many autoimmune diseases. Their precise mechanisms of therapeutic action have remained unclear in most diseases and are attracting much interest due to the rapidly increasing use of this precious plasma-derived product. The presence in IVIg of IgG reactive with various human structures has been known for many years. In this review, we first briefly discuss the formation and role of natural autoreactive human IgG in healthy individuals. A role for IgG autoantibodies in the in vivo immunomodulatory effects of IVIg has been proposed several years ago but the underlying mechanism has remained unclear. Recent work has shown that the large IVIg doses infused in many patients could oversaturate the normal anti-idiotype-dependent inhibition of autoreactive IgG present in the plasma of all healthy individuals since the formation of autoimmune complexes could be observed in normal serum in presence of therapeutic amounts of IVIg. These autoimmune complexes could have potent in vivo immunomodulatory effects by interacting with various IgG and complement receptors. Furthermore the autoreactive IgG can be easily purified from IVIg by affinity chromatography, raising the interesting possibility of further fractionating IVIg into different sub-products for use in the treatment of different diseases. These results indicate that natural autoantibodies have important in vivo roles not only for the protection of the body against infectious agents but also for the efficiency of passive immunotherapy procedures used in the treatment of many diseases.     

Silymarin augments human cervical cancer HeLa cell apoptosis via P38/JNK MAPK pathways in serum-free medium

Silymarin was proved to have a protective effect of UV-induced A375-S2 cell apoptosis in our previous research. In this study, its pro-apoptotic and anti-apoptotic activities on human cervical cancer (HeLa) cells in vitro were investigated. Silymarin induced HeLa cell death through both apoptotic and necrotic pathways. At low doses (below 80 μmol l^? 1), it induced cell apoptosis, but caused necrosis at high dose (160 μmol l^? 1). Silymarin induced typical chromatin condensation and nuclear fragmentation as a hallmark of apoptosis. In this case, mitochondrial Bcl-2 family, Bcl-2 and Bax, were not involved in apoptotic effects; however, silymarin-induced cell death was regulated by the activation of p38 and JNK MAPKs. We also found that pan-caspase inhibitor and caspase-3 inhibitor could not antagonise silymarin-induced apoptosis. Therefore, silymarin induced and augmented HeLa cell apoptosis through p38/JNK MAPKs in the serum-free medium.     

Silymarin as a new hepatoprotective agent in experimental cholestasis: new possibilities for an ancient medication

Silymarin is a purified extract from milk thistle (Silybum marianun (L.) Gaertn), composed of a mixture of four isomeric flavonolignans: silibinin (its main, active component), isosilibinin, silydianin and silychristin. This extract has been empirically used as a remedy for almost 2000 years, and remains being used as a medicine for many types of acute and chronic liver diseases. Despite its routinely clinical use as hepatoprotectant, the mechanisms underlying its beneficial effects remain largely unknown. This review addresses in detail a number of recent studies showing a novel feature of silymarin as a hepatoprotective drug, namely: its anticholestatic properties in experimental models of hepatocellular cholestasis with clinical correlate. For this purpose, this review will cover the following aspects: 1. The chemistry of silymarin, including chemical composition and properties. 2. The current clinical applications of silymarin as a hepatoprotective agent, including the mechanisms by which silymarin is thought to exert its hepatoprotective properties, when known. 3. The physiological events involved in bile formation, and the mechanisms of hepatocellular cholestasis, focusing on cellular targets and mechanisms of action of drugs used to reproduce experimentally cholestatic diseases of clinical interest, in particular estrogens and monohydroxylated bile salts, where anticholestatic properties of silymarin have been tested so far. 4. The recent findings describing the impact of silymarin on normal bile secretion and its novel, anticholestatic properties in experimental models of cholestasis, with particular emphasis on the cellular/molecular mechanisms involved, including modulation of bile salt synthesis, biotransformation/depuration of cholestatic compounds, changes in transporter expression/activity, and evocation of signaling pathways.     

Triptolide in the treatment of psoriasis and other immune-mediated inflammatory diseases

Apart from cancer chronic (auto)immune-mediated diseases are a major threat for patients and a challenge for physicians. These conditions include classic autoimmune diseases like systemic lupus erythematosus, systemic sclerosis and dermatomyositis and also immune-mediated inflammatory diseases such as rheumatoid arthritis and psoriasis. Traditional therapies for these conditions include unspecific immunosuppressants including steroids and cyclophosphamide, more specific compounds such as ciclosporin or other drugs which are thought to act as immunomodulators (fumarates and intravenous immunoglobulins). With increasing knowledge about the underlying pathomechanisms of the diseases, targeted biologic therapies mainly consisting of anti-cytokine or anti-cytokine receptor agents have been developed. The latter have led to a substantial improvement of the induction of long term remission but drug costs are high and are not affordable in all countries. In China an extract of the herb Tripterygium wilfordii Hook F. (TwHF) is frequently used to treat autoimmune and/or inflammatory diseases due to its favourable cost-benefit ratio. Triptolide has turned out to be the active substance of TwHF extracts and has been shown to exert potent anti-inflammatory and immunosuppressive effects in vitro and in vivo. There is increasing evidence for an immunomodulatory and partly immunosuppressive mechanism of action of triptolide. Thus, compounds such as triptolide or triptolide derivatives may have the potential to be developed as a new class of drugs for these diseases. In this review we summarize the published knowledge regarding clinical use, pharmacokinetics and the possible mode of action of triptolide in the treatment of inflammatory diseases with a particular focus on psoriasis.     

Silymarin attenuated mast cell recruitment thereby decreased the expressions of matrix metalloproteinases-2 and 9 in rat liver carcinogenesis

Summary  Liver cancer is the sixth most common cancer worldwide but because of very poor prognosis, it is the third most common cause of death from cancer. There are currently limited therapeutic regimens available for effective treatment of this cancer. Silymarin is a naturally derived polyphenolic antioxidant, is the active constituent in a widely consumed dietary supplement milk thistle (Silybum marianum) extract. Mast cells play an important role in the inflammatory component of a developing neoplasm; they are also a major source for matrix metalloproteinases (MMPs), which are involved in invasion and angiogenesis. In the present study, we investigated whether dietary supplementation of silymarin has any role in mast cell density (MCD) and in the expressions of MMP-2 and MMP-9 in N-nitrosodiethylamine induced (NDEA) liver cancer in Wistar albino male rats. NDEA administered rats showed increased MCD as revealed by toluidine blue staining along with upregulated expressions of MMP-2 and MMP-9. Silymarin treatment inhibited this increase in MCD and downregulated the expressions of MMP-2 and MMP-9 as revealed by Western blotting and immunohistochemistry. In conclusion, silymarin exerted beneficial effects on liver carcinogenesis by attenuating the recruitment of mast cells and thereby decreased the expressions of MMP-2 and MMP-9.     

Hypolipidemic effects of silymarin are not mediated by the peroxisome proliferator-activated receptor alpha

Silymarin is widely used in supportive therapy of liver diseases. It has been shown lately that silymarin has beneficial effects on some risk factors of atherosclerosis owing to its hypolipidemic properties. PPARalpha plays a key role in lipid metabolism and homeostasis as its target genes are involved in catabolism of fatty acids by beta-oxidation (e.g. acyl-CoA oxidase) and by omega-oxidation (e.g. cytochrome P4504A). Here we studied the possibility that hypolipidemic effects of silymarin may be mediated by PPARalpha. Rats fed with a high-cholesterol diet with either silymarin or fenofibrate (as a positive control both for PPARalpha expression as well as for lipid determination) were used. The effects of silymarin on expression of PPARalpha both at the mRNA (including selected target genes) as well as the protein level were determined. In parallel, the levels of cholesterol and triacylglycerols were determined. Our results confirmed the hypolipidemic effects of silymarin and demonstrated that these effects are probably not mediated by PPARalpha because of unchanged mRNA levels of PPARalpha target genes. Furthermore, this work shows for the first time that cholesterol itself inhibits expression of CYP4A mRNA.     

Dietary supplementation of silymarin protects against chemically induced nephrotoxicity,inflammation and renal tumor promotion response

Ferric nitrilotriacetate (Fe-NTA) is a potent nephrotoxicant and a renal carcinogen that induces its effect by causing oxidative stress. The present study was undertaken to explore protective effect of silymarin, a flavonolignan from milk thistle (Silybum marianum), against Fe-NTA mediated renal oxidative stress, inflammation and tumor promotion response along with elucidation of the implicated mechanism(s). Administration of Fe-NTA (10 mg/kg bd wt, i.p.) to Swiss albino mice induced marked oxidative stress in kidney, evident from augmentation in renal metallothionein (MT) expression, depletion of glutathione content and activities of antioxidant and phase II metabolizing enzymes, and enhancement in production of aldehyde products such as 4-hydroxy-2-nonenal. Fe-NTA also significantly activated nuclear factor kappa B (NFκB) and upregulated the expression of downstream genes: cyclooxygenase 2 and inducible nitric oxide synthase and enhancing the production of proinflammatory cytokines: tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). However, feeding of 0.5% and 1% silymarin diet conferred a significant protection against Fe-NTA induced oxidative stress and inflammation. It further augmented MT expression, restored the antioxidant armory, ameliorated NFκB activation and decreased the expression of proinflammatory mediators. Silymarin also suppressed Fe-NTA induced hyperproliferation in kidney, ameliorating renal ornithine decarboxylase activity and DNA synthesis. From these results, it could be concluded that silymarin markedly protects against chemically induced renal cancer and acts plausibly by virtue of its antioxidant, anti-inflammatory and antiproliferative activities.