Possible Uses for Silymarin in Human Health: Systematic Review

Silymarin, from the fruit of Silybum marianum, is known for its hepatoprotective action. The aim of this study was to review the mechanisms of action of the silymarin phytocomplex to expand the possibilities for its application in human health. The search for published articles was carried out on the CAPES Journals Portal platform, which covers worldwide scientific databases. Publications from 2010 to 2022 were included. Of the 311 articles retrieved, 21 were included. The articles discuss the diversity of silymarin’s applications and the possibility of optimizing its bioavailability using drug delivery systems. Silymarin shows promise in numerous diseases, such as liver, kidney, cardiovascular, respiratory and others. Its antiviral action has been demonstrated in studies and silymarin has the potential to be used as a complementary therapy in the treatment of many diseases, with the expectation that, in the future, it will be used in therapeutic protocols for exclusive use.

Commentary: Discussing the antidepressant potential of silymarin

The therapeutic potential of diet,dietary supplements,herbal remedies,and nutraceuticals for treatment of depression and anxiety is being increasingly explored.In this commentary,we discuss the recent findings on the antidepressant potential of silymarin(SILY)in mice and present an alternative approach.We highlight the extensive research on another phytochemical,curcumin,for the treatment of depression and anxiety.Finally,we suggest a future application,which investigates the potential synergistic effects of combined treatment with SILY and curcumin for depression.

Preparation and Characterization of Solid Dispersions of Silymarin with Polyethylene Glycol 6000

Aim To prepare and characterize solid dispersions of silymarin with the intention of improving their dissolution properties. Methods The solid dispersions were prepared by the fusion method with polyethylene glycol 6000(PEG 6000) as the carrier. Evaluation of the properties of the dispersions was performed using dissolution studies, X ray powder diffraction and Fourier transform infrared (FT IR) spectroscopy. Results The rate of dissolution of silymarin was considerably improved as compared with pure silymarin when formulated in solid dispersions with PEG 6000. The data of the X ray diffraction showed some changes in the parameters of lattice spacing [ d ], peak position and relative intensities. FT IR together with those from X ray diffraction showed the absence of well defined drug polymer interactions. Conclusion The dissolution improvement of poorly soluble silymarin could be illuminated by the changes of the lattice parameters of PEG 6000 and the drug.

Hepatoprotective effect of silymarin

The use of medicinal plants in treating illnesses has been reported since ancestral times.In the case of hepatic diseases,several species such as Silybum marianum,Phyllanthus niruri,and Panus giganteus(Berk.)have been shown to ameliorate hepatic lesions.Silymarin is a natural compound derived from the species Silybum marianum,which is commonly known as Milk thistle.This plant contains at least seven flavoligands and the flavonoid taxifolin.The hepatoprotective and antioxidant activity of silymarin is caused by its ability to inhibit the free radicals that are produced from the metabolism of toxic substances such as ethanol,acetaminophen,and carbon tetrachloride.The generation of free radicals is known to damage cellular membranes and cause lipoperoxidation.Silymarin enhances hepatic glutathione and may contribute to the antioxidant defense of the liver.It has also been shown that silymarin increases protein synthesis in hepatocytes by stimulating RNA polymerase I activity.A previous study on humans reported that silymarin treatment caused a slight increase in the survival of patients with cirrhotic alcoholism compared with untreated controls.

Alterations of mast cells and TGF-β1 on the silymarin treatment for CCl_4-induced hepatic fibrosis

AIM: Silymarin is a potent antioxidant, antiinflammatory and anti-fibrogenic agent in the liver, which is mediated by alteration of hepatic Kupffer cell function, lipid peroxidation, and collagen production. Especially, in hepatic fibrogenesis, mast cells are expressed in chronic inflammatory conditions, and promote fibroblast growth and stimulate production of the extracellular matrix by hepatic stellate cells. METHODS: We examined the inhibitory mechanism of silymarin on CCI4-induced hepatic cirrhosis in rats. At 4, 8, and 12 wk, liver tissues were examined histopathologically for fibrotic changes produced by silymarin treatment. RESULTS: In the silymarin with CCU-treated group, increase of hepatic stellate cells and TGF-β1 production were lower than in the CCI4-treated group at early stages. Additionally, at the late fibrogenic stage, expressions of TGF-β1 were weaker and especially not expressed in hepatocytes located in peripheral areas. Moreover, the number of mast cell in portal areas gradually increased and was dependent on the fibrogenic stage, but those of CCI4+silymarin-treated group decreased significantly. CONCLUSION: Anti-fibrotic and antiinflammatory effects of silymarin were associated with activation of hepatic stellate cells through the expression of TGF-β1 and stabilization of mast cells. These results suggest that silymarin prevent hepatic fibrosis through suppression of inflammation and hypoxia in the hepatic fibrogenesis.

Silymarin in non alcoholic fatty liver disease

AIM: This study was undertaken to evaluate the hepatic effects of silybum marianum on non alcoholic fatty liver disease (NAFLD). METHODS: In 72 patients affected by NAFLD, main metabolic, hepatic and anti-inflammatory parameters were assayed after 3 mo of a restricted diet and before silymarin treatment (twice a day orally). The brightness of liver echography texture (hepatorenal ratio brightness) was also defined at same time. These evaluations were repeated after 6 mo of treatment. RESULTS: Serum levels of some metabolic and anti-inflammatory data nonsignificantly lowered after 6 mo of silymarin. On the contrary, Steato test, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase were significantly (P < 0.001) reduced. Instead, the AST/ALT ratio unchanged. Finally, the hepatorenal brightness ratio, as an index of hepatic steatosis, significantly (P < 0.05) dropped. CONCLUSION: The obtained results indicate that silymarin appears to be effective to reduce the biochemical, inflammatory and ultrasonic indices of hepatic steatosis. Some parameters indicative of early stage of atherosclerosis were also lowered.

Effect of silymarin on biochemical indicators in patients with liver disease: systematic review with meta-analysis

To evaluate the effect of silymarin on the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (γGT) in patients with liver diseases. METHODSA systematic review with meta-analysis of ramdomized and controlled clinical trials was performed, evaluating the effects of sylimarin in patients with hepatic diseases, published by January 31, 2016. Clinical trials were sought on the basis of The Cochrane Central Register of Controlled Trials in the Cochrane Library, PubMed/Medline, Scopus, Web of Science, Lilacs and Clinical Trials. The trials with adult and elderly patients of both sexes, with Liver Diseases who took oral silymarin supplementation, as extract or isolated, as well as Silymarin combined with other nutrients, were included. The trials should provide information about the intervention, such as dosages and detailing of the product used, besides the mean and standard deviation of serum levels of ALT, AST and γGT of the baseline and at the end of the intervention. RESULTSAn amount of 10904 publications were identified. From those, only 17 were included in the systematic review and 6 in the meta-analysis, according to the used selection criteria. In this meta-analysis, the results indicated a reduction of 0.26 IU/mL (95%CI: -0.46-0.07, P = 0.007) at the level of ALT and 0.53 IU/mL (95%CI: -0.74-0.32, P = 0.000) at the serum levels of AST after using the silymarin, both, statistically significant, but with no clinical relevance. There was no significant change in the γGT levels. Subgroup analyzes were also performed for the biochemical markers in relation to the type of intervention, whether silymarin isolated or associated with other nutrients and the time of intervention (whether ≥ 6 mo or < 6 mo). Significant differences were not found. The evaluated studies presented a high degree of heterogeneity and low methodological quality in the carried out analysis. CONCLUSIONSilymarin minimally reduced, but without clinical relevance, the serum levels of ALT and AST. It is necessary to carry out studies with more appropriate methodological designs.

Kinetic Mechanisms for Preparing Silymarin via Microwave-assisted Extraction

The kinetic mechanism for the preparation of silymarin from milk thistle seeds was studied during the microwave-assisted extraction （MAE） process. The results showed that the transfer rate of silymarin from milk thistle seeds increased with the microwave output power and temperature during MAE processing. The apparent extraction rate constant k （s-1） was 1.2028×10-2 , 1.2248×10-2 , and 1.2485×10-2 , and diffusion coefficient D （m2·s-1 ） was 4.21×10-10, 4.29×10-10 , and 4.37×10-10 at the microwave temperatures of 383, 393, and 403 K, respectively, in the silymarin MAE process. With the help of scanning electron microscopy （SEM）, the microstructures of the samples extracted by MAE were observed. The results revealed that the increased efficiency and rate of MAE of silymarin could be attributed mainly to the subsequent cell change resulting from superheating effects during MAE.

Silymarin-laden PVP-PEG polymeric composite for enhanced aqueous solubility and dissolution rate: Preparation and in vitro characterization

The aim of this work was to develop, optimize and characterize a silymarin-laden polyvinylpyrrolidone(PVP)-polyethylene glycol(PEG) polymeric composite to resolve low aqueous solubility and dissolution rate problem of the drug. A number of silymarin-laden polymeric formulations were fabricated with different quantities of PVP K-30 and PEG 6000 by the solvent-evaporation method. The effect of PVP K-30 and PEG 6000 on the aqueous solubility and dissolution rate was investigated. The optimized formulation and its constituents were characterized using powder X-ray diffraction(PXRD), differential scanning calorimetry(DSC), scanning electron microscopy(SEM) and Fourier transform infrared spectroscopy(FTIR) techniques. Both the PEG 6000 and PVP K-30 positively affected the aqueous solubility and dissolution rate of the drug. In particular, a formulation consisting of silymarin, PVP K-30 and PEG 6000(0.25/1.5/1.5, w/w/w) furnished the highest solubility(24.3972.95 mg/mL) and an excellent dissolution profile( $100% in 40 min). The solubility enhancement with this formulation was $ 1150-fold as compared to plain silymarin powder. Moreover, all the constituents existed in the amorphous state in this silymarin-laden PVP-PEG polymeric composite. Accordingly, this formulation might be a promising tool to administer silymarin with an enhanced effect via the oral route.

Improved dissolution and bioavailability of silymarin delivered by a solid dispersion prepared using supercritical fluids

The objective of this study was to improve the dissolution and bioavailability of silymarin(SM).Solid dispersions(SDs)were prepared using solution-enhanced dispersion by supercritical fluids(SEDS)and evaluated in vitro and in vivo,compared with pure SM powder.The particle sizes,stability,and contents of residual solvent of the prepared SM-SDs with SEDS and solvent evaporation(SE)were investigated.Four polymer matrix materials were evaluated for the preparation of SM-SD-SEDS,and the hydrophilic polymer,polyvinyl pyrrolidone K17,was selected with a ratio of 1:5 between SM and the polymer.Physicochemical analyses using X-ray diffraction and differential scanning calorimetry indicated that SM was dispersed in SD in an amorphous state.The optimized SM-SD-SEDS showed no loss of SM after storage for 6 months and negligible residual solvent(ethanol)was detected using gas chromatography.In vitro drug release was increased from the SM-SDSEDS,as compared with pure SM powder or SM-SD-SE.In vivo,the area under the rat plasma SM concentration-time curve and the maximum plasma SM concentration were 2.4-fold and 1.9-fold higher,respectively,after oral administration of SM-SD-SEDS as compared with an aqueous SM suspension.These results illustrated the potential of using SEDS to prepare SM-SD,further improving the biopharmaceutical properties of this compound.

Silymarin: An option to treat non-alcoholic fatty liver disease

We have read with a great interest the review published by Singh et al, on the treatment options in alcoholic and non-alcoholic fatty liver disease, including various new targeted therapies that are currently under investigation. Recently, we described the health effects of the Mediterranean diet associated to an antioxidant complex rich in silymarin, to improve in overweight patients anthropometric parameters, glucose and lipid metabolism and intra-hepatic fat accumulation.

Protective Effects of Combined Therapy of Rutin with Silymarin on Experimentally-Induced Diabetic Neuropathy in Rats

The management of diabetic neuropathy (DN) is still a challenge for physicians. Hyperglycemia induced oxidative stress involves in the development of diabetic neuropathy, which could be reversed by supplementation of antioxidants. In the present study, it has targeted the oxidative stress mediated nerve damage in DN by using combined therapy of rutin (RT) and silymarin (SM). Diabetes was induced by single streptozotocin (STZ, 65 mg/kg i.p.) injection. The diabetic rats were treated daily with RT (100 mg/kg), SM (60 mg/kg) and RT (50 mg/kg) + SM (30 mg/kg) for 6 consecutive weeks. Pain-related behavior tests were performed including tail flick, paw-pressure analgesia and Rota-rod treadmill performance. Serum glucose, insulin, tumor necrosis factor-α (TNF-α), interleukine-6 (IL-6) and interleukine-1β (IL-β) levels were estimated. Thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) levels and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GPx) were measured. Diabetic rats that developed neuropathy were revealed by decreased tail-flick latency, paw-withdrawal latency and motor coordination. RT (100 mg/kg/day) and SM (60 mg/kg/day) dosed to diabetic rats, ameliorated hyperalgesia, analgesia and led to improved motor coordination. However, the combined therapy of RT (50 mg/kg/day) with SM (30 mg/kg/day) showed more significant effects in these parameters. STZ significantly increased TBARS and decreased GSH levels in sciatic nerve whereas combined therapy of RT and SM produced higher significant protection compared to individual. Similarly, combined therapy showed more significant amelioration in decreased levels of SOD, CAT, GST, GS and GPx activities in sciatic nerve of diabetic rats. Present results concluded that the combined therapy of phenolic compounds such as RT and SM had higher protective effects than their individual supplementations against DM.

Modulations in Anti-Oxidant Activities of Selected Gastro-Intestinal Tissues in Alloxan-Induced, Silymarin Treated Diabetic Wistar Rats

Diabetes mellitus (DM) is reportedly the commonest metabolic disorder with multi organ involvement. By inducing DM (with Alloxan) in Wistar rats, current study investigated the changes in antioxidant activities of selected gastrointestinal (GI) tissues [stomach, duodenum, pancreas and liver], upon treatment with Silymarin and/or Vitamin C. One hundred and twenty five (125) adult male wistar rats of between 130 to 180 grams were procured for the study. Five units of one control and four experimental units were designated with twenty five (25) rats per group (n = 25);Unit 1: Control rats, Unit 2 were DM induced, Silymarin untreated rats, and Units 3, 4 and 5 were DM induced, vitamin C, Silymarin and Vitamin C + Silymarin treated respectively. Following four (4) weeks of administration of test substance(s), rats were euthanized and blood samples obtained for biochemical and antioxidant assay on aforementioned GI tissues. One way analysis of variance (ANOVA) and Students t-test at p p < 0.05) at comparison of extract treated unit to control. Study also observed a significant change in pancreatic, liver, and duodenal anti-oxidant marker levels with Vitamin C, Silymarin and Vitamin C + Silymarin co-administrations to diabetic rats. It can therefore be said, that DM caused a destructive alteration pancreatic histo-architecture with improved functional capabilities in wistar rats at administration of Silymarin and vitamin C. Thus, Silymarin posed antioxidant potentials, with ameliorated pancreatic dysfunctions.

Evaluation of silymarin extract from Silybum marianum in mice: anti-fatigue activity

Silymarin has been used for centuries for its hepatoprotective properties. The specific objective of this study was to evaluate the anti-fatigue properties of silymarin. The silymarin was administered orally at doses of 50, 100, and 200 mg/kg for 4 weeks;the fatigue level and exercise performance were evaluated using exhaustive swimming time and pole-climbing time, as well as levels of plasma lactate, ammonia, glucose, creatine kinase(CK), serum urea nitrogen(SUN), blood lactic acid(BLA), muscle glycogen(MG), and liver glycogen(LG) contents after an intensive swimming session. The results demonstrated that silymarin treatment decreased the BLA and SUN levels while increased the LG and MG levels. In addition, silymarin decreased plasma lactate and ammonia levels and CK activity after swimming test, this is related to the mechanism that increases energy storage(as glycogen) and release(as blood glucose), and decreases plasma levels of lactate, ammonia, and CK. The observation of the skeletal muscle structures of mice also confirmed that skeletal muscles became more damaged in the control group compared with the silymarin-treated mice after prolonged endurance exercise. Therefore, it is reasonable to infer that silymarin may bear potential pharmacological effects in combating fatigue.

The Potential of Duck Hepatitis Virus(DHV-1) Stimulating the Body Weight Gain and the Effects of Silymarin on It in Duckling

To evaluate the effects of duck hepatitis virus-1 （DHV-1） on the body weight gain in duck and the effects of silymarin on it in vivo, 100 10-d-old ducks, both male and female, were collected to be subjected to the test. The experiments were conducted in 8 groups： in group 1-3, the animals were inoculated with 1：105 diluted duck hepatitis virus （DHV-1） infected allantoic fluid and given 0, 30, and 50 mg kg^-1 BW d^-1 silymarin orally, respectively. In group 4-6, the animals were inoculated with 1：5 × 105 diluted DHV-1 infected allantoic fluid and given 0, 10, and 30 mg kg^-1 BW d^-1 silymarin orally, respectively. In group 7, the animals were given 10 mg kg^-1 BW d^-1 silymafin only. Group 8 was the control one treated by injecting sterillized saline into the leg muscles. All the silymarin was given from 0 to 4 d after inoculation of the virus. By the 5th d after inoculation, the vein blood was drawn from the dorsal foot vein and the plasma samples were collected and stored at -20℃. The body weight gain （BWG） was measured from 0 to 10 d after inoculation. The plasma IGF-I, T3, and T4 concentrations were measured by radioimmunoassay （RIA）. At the virus dose of 1：5 ×105 diluted virus infected allantoic fluid, the inoculation of the virus enhanced the BWG significantly compared with that of the control （P〈 0.01）, while 10-50 mg kg^-1 BW d^-1 silymarin could counteract the effects of the virus on the BWG dose-dependently. The plasma IGF-I levels showed no correlation with the BWG, but the T3 levels showed a same tropism with the body weight gain. The present results indicated that sublethal DHV-1 enhanced the body weight gain of ducklings significantly, and the silymarin could counteract this effect in vivo.

Silymarin Attenuates Hepatic and Pancreatic Redox Imbalance Independent of Glycemic Regulation in the Alloxan-induced Diabetic Rat Model

Objective To evaluate the efficiency of silymarin(SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus(T1 DM).Methods Diabetes was induced by intraperitoneal injection of alloxan. The diabetic rats were administered with SMN at doses of 50 and 100 mg/kg body weight/d for 30 consecutive days. The rats were divided into the following four groups: vehicle control, diabetic(alloxan-treated), DS50(alloxan +50 mg/kg body weight/d of SMN), and DS100(alloxan + 100 mg/kg body weight/d of SMN) groups. The bodyweight and food and water intake were evaluated. After 30 d, the animals were euthanized and the blood was collected for measuring the serum levels of glucose, triacylglycerol(TAG), urea, and creatinine. The liver and pancreas were collected for measuring the activities of superoxide dismutase(SOD) and catalase(CAT), and the levels of carbonylated protein(PC). The pancreas sample was also used for histological analysis.Results SMN reduced hepatic(P < 0.001) and pancreatic(P < 0.001) protein damage and creatinine levels(P = 0.0141) in addition to decreasing food(P < 0.001) and water intake(P < 0.001). However,treatment with SMN did not improve beta-cell function or decrease blood glucose levels in diabetic rats.Conclusion SMN improved polyphagia and polydipsia, renal function, and protected the liver and pancreas against protein damage without affecting hyperglycemia in diabetic animals.

Fish Nutrition Additives in SHK-1 Cells: Protective Effects of Silymarin

In nutrition for productive species, additives play an important role in boosting physiological processes. Only in recent years studies include models of the effects on fish cells of these additives. We observed effects of silymarin, a compound highly utilized in aquaculture. The cell line SHK-1 was used derived from the upper liver of the Atlantic salmon as a biological model. Samples were exposed to silymarin in incrementing time and concentrations, to evaluate by MTT and number of cells, the effects on cell viability. Also, oxidative stress models were used to find the protector effects of silymarin against these agents. Our data indicate that a dose of 100 ppm of silymarin is sufficient to stimulate cellular proliferation. Cultures were exposed to high glucose (15 mM) or H2O2 (0.1 mM) in presence of or absence of silymarin at 100 ppm. We observed that the toxic effects of both compounds were blocked by the presence of silymarin. Our results indicate that it is important to evaluate additive effects at a cellular level. Also, silymarin does have proliferative effects, and protect against cellular injury in our models. Our study helps to generate more rational applications of additives in the industry and presents new challenges in order to better manipulate the model in the laboratory, allowing us to obtain new evidence regarding the microalgae’s biology through in vitro studies.

Dietary silymarin ameliorating reproductive and lactation performance of sows via regulating body antioxidant and metabolism

Objective The experiment was conducted to explore the effects of silymarin on reproductive and lactation performance,serum antioxidants,and body metabolism of sows.Methods Sixty pregnant sows(85 d,Large×Landrace)with similar genetic background,body condition,and parity were randomly divided into three groups,and each group has 20 individually housed sows.The sows in the control group(CG)were fed with basal diet,and those in the experimental group A(EGA)and B(EGB)were fed with basal diet containing 250 and 500 mg/kg silymarin,respectively.The experiment lasted 46 days from day 85 of gestation to the end of lactation(weaning on day 17).The milk composition and serum biochemical para-meters were determined by a milk composition analyzer and a blood biochemical analyzer,respectively.Serum antioxidant indexes and plasma hormone levels were measured using the biochemical kits.The gas chromatograph was applied to detect the fecal short chain fatty acids.Results Compared with the CG,the total feed intake(TFI)and average daily feed intake(ADFI)were significantly increased(P<0.01),and the urea content in regular milk tended to increase(P=0.095)in the EG.The serum malondialdehyde(MDA)contents were decreased on day 90 of gestation and the day of farrowing(P<0.01),and the serum contents of total antioxidant capacity(T-AOC)tended to increase on day 17 of lactation(P=0.099)compared with the CG.Compared with the CG,the serum triglyceride(TG)concentrations in the EG tended to increase on day 90 of gestation(P=0.062),and the content of serum total protein(TP)and albumin(ALB)reduced on day 17 of lactation(P<0.01).Compared with the CG,plasm D-lactic acid content was decreased(P<0.05),and the plasma prostaglandin(PG)level tended to increase(P=0.088)in the EG on the day of farrowing and day 17 of lactation.Compared with the CG,fecal isobutyric acid concentration in the EG significantly decreased on the day of farrowing(P<0.05).Conclusion Adding 250-500 mg/kg silymarin to diets from the late gestation to the end of lactation could improve reproductive and lactation performance of sows via the regulation of nutrient metabolism and serum antioxidant.

Amelioration of paracetamol hepatotoxicity and oxidative stress on mice liver with silymarin and Nigella sativa extract supplements

Objective: To evaluate the ameliorator property of silymarin or/and Nigella sativa(N. sativa) extract against N-acetyl-p-aminophenol(APAP)-induced injury in male mice at the biochemical, histological and ultrastructural levels.Methods: The mice were divided into seven groups(10/group). The first group was served as control. While, the second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa extract alone respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa extract respectively. The seventh group was treated with combination of both ameliorative compounds(silymarin and N. sativa extract) with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose to mice led to an alteration of liver functions, increased the alanine transaminase, aspartate aminotransferase and lactate dehydrogenase levels, decreased total protein level as well as the increasing the superoxide dismutase and malondialdehyde while decreased catalase, glutathione peroxidase and glutathione reduced activities. The effects of APAP on the biochemical parameters of mice were dose-dependent. Administration of silymarin or/and N. sativa extract to APAP-treated mice attenuates the toxicity of this compound, objectified by biochemical, histological and ultrastructural improvement of liver. But the alleviation was more pronounced with the both antioxidants. Conclusions: The synergistic effect of silymarin and N. sativa extract is the most powerful in reducing the toxicity induced by APAP and improving the liver functions and antioxidant capacities of mice.

Estimation of the novel antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects of silymarin in Albino rats and mice

Objective: To evaluate the other pharmacological actions of silymarin in Albino rats and mice such as antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects. Methods: Rats were injected intramuscularly with pyrogenic dose of brewer's yeast for the antipyretic test of silymarin. Another group of rats injected with 0.1 mL of 1% carrageenan solution in saline at the subplanter area of the right hind paw for the anti-inflammatory test of silymarin. Another group of mice tested by hot plate method for determination of antinociceptive effect of silymarin. Hyperlipidemia was induced using high fat diet for 2 months to estimate the antihyperlipidemic activity of silymarin. Results: Silymarin showed a significant antipyretic effect of both doses(50 and 100 mg/kg) compared with control untreated group. Moreover, silymarin elucidated a significant anti-inflammatory effect of both doses reflected on the decrease of the rat paw edema every hour interval for 4 h after administration in comparison with control positive group. By the same taken, both doses of silymarine revealed a significant antinociceptive action in hot plate method at 30 and 60 min post administration. Besides, it lowered significantly the serum levels of prostaglandin E2, tumor necrosis factor alpha and interleukin 1 beta after 2 h of silymarin administration in carrageenan induced rat paw edema besides the significant decrease of total cholesterol, triglycerides, low density lipoprotein and significantly elevated high density lipoprotein after 2 weeks of silymarin administration. Conclusions: These outcomes delivered a new vision into the possible pharmacological mechanisms by which silymarin advances antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects.