Biochemical, morphological and molecular assessments of n butanol fraction of Phoenix dactylifera L. following exposure to inorganic mercury on the liver of Wistar rats.

BACKGROUND: Mercury chloride (HgCl2) damages tissues it comes in contact with in sufficient concentration. This study evaluated the protective effects of n-butanol fraction of Phoenix dactylifera (BFPD) on mercury-triggered liver toxicity in Wistar rats. 25 male rats were divided into 5 groups of 5 rats each. Group I was administered 2 ml/kg of distilled water; group II was administered 5 mg/kg of HgCl2; group III was administered 500 mg/kg of BFPD + 5 mg/kg of HgCl2; group IV was administered 1000 mg/kg of BFPD + 5 mg/kg of HgCl2, while group V was administered 100 mg/kg of silymarin + 5 mg/kg of HgCl2. orally for 2 weeks. The rats were euthanized and liver tissue blood samples were collected for histological, histochemical, stereological, immunohistochemical, molecular, and biochemical studies. RESULTS: The results revealed that HgCl2 induced oxidative stress in the rats evident by histoarchitectural distortions and altered levels of liver enzymes, proteins, and oxidative stress biomarkers when compared to the control. However, BFPD treatment restored these changes. Glutathione peroxidase levels decreased (p < 0.05) in the HgCl2-treated group when compared to the control and BFPD-treated groups. HgCl2 group revealed reduced reactivity with histochemical and immunohistochemical stains (Masson's Trichrome and B cell Lymphoma 2) when compared to the control, with a significant decrease in quantified liver Bcl-2 stain intensity when compared to the silymarin-treated group. BFPD administration revealed normal staining intensity comparable to the control. HgCl2 administration revealed a remarked decrease in the number of hepatocytes when compared to the control, BFPD, and silymarin groups. BFPD preserved (p < 0.05) the stereological features when compared to the HgCl2-treated group. GPx activity in the liver decreased (p < 0.05) with HgCl2 administration when compared to the control and silymarin-treated groups. BFPD attenuated GPx gene activity to levels similar to the control indicating some level of amelioration against HgCl2-induced toxicity. CONCLUSIONS: The ability of BFPD to mitigate HgCl2 triggered liver alterations could be attributed to the antioxidant property of its flavonoid content. Therefore, BFPD may be a potential candidate for treating and managing liver-induced mercury intoxication.

Modulation of the gut microbiome and Firmicutes phylum reduction by a nutraceutical blend in the obesity mouse model and overweight humans: A double-blind clinical trial.

Overweight and obesity are closely linked to gut dysbiosis/dysmetabolism and disrupted De-Ritis ratio [aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio], which may contribute to chronic noncommunicable diseases onset. Concurrently, extensive research explores nutraceuticals, and health-enhancing supplements, for disease prevention or treatment. Thus, sedentary overweight volunteers were double-blind randomized into two groups: Novel Nutraceutical_(S) (without silymarin) and Novel Nutraceutical (with silymarin). Experimental formulations were orally administered twice daily over 180 consecutive days. We evaluated fecal gut microbiota, based on partial 16S rRNA sequences, biochemistry and endocrine markers, steatosis biomarker (AST/ALT ratio), and anthropometric parameters. Post-supplementation, only the Novel Nutraceutical group reduced Clostridium clostridioforme (Firmicutes), Firmicutes/Bacteroidetes ratio (F/B ratio), and De-Ritis ratio, while elevating Bacteroides caccae and Bacteroides uniformis (Bacteroidetes) in Brazilian sedentary overweight volunteers after 180 days. In summary, the results presented here allow us to suggest the gut microbiota as the action mechanism of the Novel Nutraceutical promoting metabolic hepatic recovery in obesity/overweight non-drug interventions.

Metabolic profiling of Verbena bonariensis L. extract by LC/MS and evaluation of the hepatoprotective potential with isoniazid- and rifampicin-induced hepatotoxicity in rats.

The study explored the hepatoprotective activity and metabolic profile of Verbena bonariensis L. methanol extract (VBM) and fractions using isoniazid as well as rifampicin-triggered liver toxicity in Wistar albino rats. Metabolite profiling of VBM using HPLC-PDA-ESI-MS identified 12 compounds, mainly iridoids, phenylpropanoids, and flavonoids, where verbascoside represents the major compound. Different biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP), bilirubin, and total protein levels were used to assess liver functions. All the evaluated samples exhibited hepatoprotective potential, but VBM exhibited maximum activity and a notable decline in ALP (p < 0.05, significant), even better than the standard drug (silymarin). VBM significantly reduced the elevated ALT, AST, ALP, and total bilirubin. It also triggered a significant elevation in total proteins compared with diseased animals. This was further consolidated by histopathological studies. Verbena bonariensis L. could serve as a potent hepatoprotective agent and may alleviate liver ailments.

Protective effects of silymarin-loaded chitosan nanoparticles in the diet-induced hyperlipidemia rat model.

Objectives: Obesity is a metabolic syndrome that leads to many chronic diseases worldwide. In this study, we investigate the antihyperlipidemic activities of chitosan nanoparticles (CH NPs) on silymarin (SIL) as a carrier in the drug delivery system that can improve some biochemical parameters and hormones in the model of hyperlipidemic rats receiving a high-fat diet (HFD). Materials and Methods: Physicochemical characterization of silymarin-loaded chitosannanoparticles (CH-SIL NPs) was done by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and drug loading efficiency (LE). Diet-induced hyperlipidemic rats were treated with SIL (15 mg/kg/day) and CH-SIL NPs(15 mg/kg/day) for twelve weeks orally daily. The body weight loss (BW), food consumption, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), levels of fasting blood glucose (FBG) in serum, serum insulin, cortisol, testosterone, and brain neuropeptide Y (NPY), Y1 and Y5 receptor mRNA expression were analyzed. Results: A significant reduction in BW and food consumption from 417 ± 16 g and 33 ± 1.03 in group HFD to 338 ± 10 g and 17.33 ± 1.02 in group CHS+HFD was observed, respectively. This data revealed that CH-SIL NPs improved hyperlipidemia, hyperinsulinemia, and hyperglycemia, reduced serum cortisol, and down-regulated NPY and Y1R with a significant increase in HDL and testosterone hormones compared to the control group. Conclusion: The developed Sil-loaded CH NPs were good agents for improving efficacy. It is the first report of the proposed weight loss mechanism of SIL CH NPs, thereby providing information about the anti-hyperlipidemic and antihyperglycemic effects of silymarin-loaded chitosan nanoparticles, a natural food with proper effects against metabolic disorders in case of hyperlipidemia that may lead to obesity and up-regulation of brain NPY.

Evaluation of the efficacy of silymarin and dexmedetomidine on kidney and lung tissue in the treatment of sepsis in rats with cecal perforation.

Sepsis is a systemic inflammatory response syndrome that develops in the host against microorganisms. This response develops away from the primary infection site and results in end-organ damage. The present study aimed to investigate the protective and therapeutic effects on lung and kidney tissue of silymarin (S) and dexmedetomidine (DEX) applied 1 h before and after sepsis induced by the cecal ligation and puncture (CLP) method in rats. A total of 62 rats was randomly divided into eight groups: i) Control (n=6); ii) cecal perforation (CLP; n=8); iii) S + CLP (n=8; S + CLP; S administered 1 h before CPL); iv) CLP + S (n=8; S administered 1 h after CLP); v) DEX + CLP (n=8; D + CLP; DEX administered 1 h before CLP); vi) CLP + D (n=8; DEX administered 1 h after CLP); vii) SD + CLP (n=8; S and DEX administered 1 h before CLP) and viii) CLP + SD (n=8; S and DEX administered 1 h after CLP). After the cecum filled with stool, it was tied with 3/0 silk under the ileocecal valve and the anterior surface of the cecum was punctured twice with an 18-gauge needle. A total of 100 mg/kg silymarin and 100 µg/kg DEX were administered intraperitoneally to the treatment groups. Lung and kidney tissue samples were collected to evaluate biochemical and histopathological parameters. In the histopathological examination, all parameters indicating kidney injury; interstitial edema, peritubular capillary dilatation, vacuolization, ablation of tubular epithelium from the basement membrane, loss of brush border in the proximal tubule epithelium, cell swelling and nuclear defragmentation; were increased in the CLP compared with the control group. Silymarin administration increased kidney damage, including ablation of tubular epithelium from the basement membrane, compared with that in the CLP group. DEX significantly reduced kidney damage compared with the CLP and silymarin groups. The co-administration of DEX + silymarin decreased kidney damage, although it was not as effective as DEX-alone. To conclude, intraperitoneal DEX ameliorated injury in CLP rats. DEX + silymarin partially ameliorated injury but silymarin administration increased damage. As a result, silymarin has a negative effects with this dosage and DEX has a protective effect. In the present study, it was determined that using the two drugs together had a greater therapeutic effect than silymarin and no differences in the effects were not observed any when the application times of the agents were changed.

Mitigation of haemato-genotoxic and stress response effects in Cyprinus carpio via silymarin dietary supplementation following deltamethrin exposure.

The study examined the potential of Silymarin, a blend of bioactive flavonolignans extracted from the milk thistle Silybum marianum, to mitigate Deltamethrin-induced toxicity in the blood of Cyprinus carpio. Fish were exposed to Deltamethrin (0.66 µg/L), the plant extract, or a combination of both for a duration of thirty days. Various parameters, including serum biochemical markers, erythrocytic abnormalities, and genotoxicity endpoints, were assessed. Results indicated a significant (p < 0.05) increase in the levels of AST, ALT, ALP, blood urea nitrogen, creatinine, glucose, cholesterol, and TLC in the fish exposed to the pesticide. Conversely, total protein, TEC, and Hb showed a notable decrease. There was also a notable rise in micronuclei and erythrocytic abnormalities such as acanthocytes, microcytes, and notched cells. Under ultrastructural examination, phenotypic deformities like spherocytosis, discocytes, and clumped erythrocytes were observed. However, dietary supplementation of silymarin (1 g/kg) significantly restored the biochemical, genetic, and cellular parameters, resembling those of the control group. This suggests the potential of this plant extract in protecting the common carp, Cyprinus carpio, from Deltamethrin-induced damage by scavenging free radicals and reducing DNA oxidative stress.

Silymarin and MSC-exosomes ameliorate thioacetamide-evoked renal fibrosis by inhibiting TGF-ß/SMAD pathway in rats.

BACKGROUND: TGF-ß1 and SMAD3 are particularly pathogenic in the progression of renal fibrosis. AIM: This study aimed to evaluate the kidney protective potentials of silymarin (SM) and exosomes of mesenchymal stem cells against the nephrotoxin thioacetamide (TAA) in rats. METHODS: 32 female rats were randomly assigned into four groups: the control group, the TAA group, the TAA + SM group, and the TAA + Exosomes group. The kidney homogenates from all groups were examined for expression levels of TGF-ß receptors I and II using real-time PCR, expression levels of collagen type I and CTGF proteins using ELISA, and the expression levels of nuclear SMAD2/3/4, cytoplasmic SMAD2/3, and cytoplasmic SMAD4 proteins using the western blot technique. RESULTS: Compared to the control group, the injection of TAA resulted in a significant increase in serum levels of urea and creatinine, gene expression levels of TßRI and TßRII, protein expression levels of both collagen I and CTGF proteins, cytoplasmic SMAD2/3 complex, and nuclear SMAD2/3/4 (p-value < 0.0001), with significantly decreased levels of the co-SMAD partner, SMAD4 (p-value < 0.0001). Those effects were reversed considerably in both treatment groups, with the superiority of the exosomal treatment regarding the SMAD proteins and the expression levels of the TßRI gene, collagen I, and CTGF proteins returning to near-control values (p-value > 0.05). CONCLUSION: Using in vitro and in vivo experimental approaches, the research discovered a reno-protective role of silymarin and exosomes of BM-MSCs after thioacetamide-induced renal fibrosis in rats, with the advantage of exosomes.

Thymoquinone protects thioacetamide-induced chronic liver injury by inhibiting TGF-ß1/Smad3 axis in rats.

Chronic liver injury due to various etiological factors results in excess secretion and accumulation of extracellular matrix proteins, leading to scarring of liver tissue and ultimately to hepatic fibrosis. If left untreated, fibrosis might progress to cirrhosis and even hepatocellular carcinoma. Thymoquinone (TQ), an active compound of Nigella sativa, has been reported to exhibit antioxidant, anti-inflammatory and anticancer activities. Therefore, the effect of TQ against thioacetamide (TAA)-induced liver fibrosis was assessed in rats. Fibrosis was induced with intraperitoneal administration of TAA (250 mg/kg b.w.) twice a week for 5 weeks. TQ (20 mg/kg b.w.) and silymarin (50 mg/kg b.w.) were orally administered daily for 5 weeks separately in TAA administered groups. Liver dysfunction was reported by elevated liver enzymes, increased oxidative stress, inflammation and fibrosis upon TAA administration. Our study demonstrated that TQ inhibited the elevation of liver marker enzymes in serum. TQ administration significantly increased antioxidant markers, such as superoxide dismutase, catalase, glutathione, glutathione peroxidase and glutathione reductase in the liver tissue of rats. Further, TQ significantly attenuated liver fibrosis, as illustrated by the downregulation of TAA-induced interleukin-ß, tumour necrosis factor-α, inducible nitric oxide synthase and fibrosis markers like transforming growth factor-ß (TGF-ß), α-smooth muscle actin, collagen-1, Smad3 and 7. Therefore, these findings suggest that TQ has a promising hepatoprotective property, as indicated by its potential to effectively suppress TAA-induced liver fibrosis in rats by inhibiting oxidative stress and inflammation via TGF-ß/Smad signaling.

Effects of silymarin use on liver enzymes and metabolic factors in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis.

Background: Fatty liver disease comprises a wide range of related liver disorders affecting mainly people who drink no or minimal amounts of alcohol. Silymarin is a member of the Carduus marianum family that has been used for centuries to treat different diseases. There is little evidence supporting its efficacy in humans. Objectives: To evaluate the effects of Silymarin in patients with non alcoholic fatty liver disease (NAFLD) or recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: We searched PubMed, SCOPUS, Web of Science, and Cochrane Library for relevant clinical trials assessing the use of silymarin in patients with NAFLD. A risk of bias assessment was performed using Cochrane's risk of bias tool. We included the following outcomes: alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transferase (GGT), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) (mg/dL), degree of fibrosis resolution, low-density lipoprotein (LDL), and HOMA-IR. We analyzed continuous data using mean difference (MD) and relative 95% confidence interval (CI). Results: We included nine clinical trials. We found that silymarin significantly reduced the levels of ALT (MD= -17.12 [-28.81, -4.43]), (P < 0.004), AST (MD= -12.56 [-19.02, -6.10]), (P < 0.0001) and TG (MD = -22.60 [-23.83, -21.38]) (p < 0.00001). It also improved HDL (MD= 2.13 [1.60, 2.66]), (P < 0.01)). There was no significant difference regarding GGT (P=o.07), TC (P= 0.52), LDL (P= 0.06), HOMA-IR (P= 0.06) and BMI (p=0.1).One study reported significant improvement in the degree of fibrosis (P = 0.023). Conclusion: Silymarin treatment significantly reduces biochemical and transaminase levels in patients with MASLD.

Silymarin Synergizes with Antiviral Therapy in Hepatitis B Virus-Related Liver Cirrhosis: A Propensity Score Matching Multi-Institutional Study.

Hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC) presents a substantial mortality and hepatocellular carcinoma (HCC) risk. While antiviral therapy (AVT) is the standard, complete HBV clearance remains elusive and may not reduce the risk of death in patients with decompensated cirrhosis. Silymarin, a centuries-old herbal remedy, has shown promise against HBV infection and as an antifibrosis therapy. This study explores the potential of silymarin combined with AVT to reduce mortality and HCC incidence in patients with HBV-LC. This research, spanning from 2001 to 2019, entailed a multi-institutional retrospective cohort study which included 8447 HBV-LC patients all undergoing AVT. After applying inclusion and exclusion criteria, the study comprised two cohorts: a case cohort receiving silymarin alongside AVT for at least 30 days, and a control cohort on AVT alone. Propensity score matching, based on baseline parameters including HBV-DNA levels, comorbidity, and an important LC medication, namely, non-selective ß-blockers, was employed to ensure balanced groups, resulting in 319 patients in each cohort for subsequent analyses. Overall mortality was the primary outcome, with HCC occurrence as a secondary outcome. Among 319 patients in both cohorts, the case cohort exhibited significant improvements in the international normalized ratio (INR), model for end-stage liver disease (MELD) score and the Charlson comorbidity index (CCI) one year after the index date. A competing risk survival analysis demonstrated superior one-year and two-year mortality outcomes in the case cohort. However, no significant impact on one-year and two-year HCC occurrence was observed in either cohort. The combination of silymarin and AVT in HBV-LC patients demonstrated a synergistic effect, leading to decreased overall mortality and an improved comorbidity index. While the incidence of HCC remained unchanged, our results suggested promising potential for further clinical trials investigating the synergistic role of silymarin in the treatment of HBV-LC.

Synthesis, physiochemical characterization, molecular docking study, and anti-breast cancer activity of silymarin loaded zein nanoparticles.

Breast cancer is a major cause of death in women worldwide leading to requirement of new therapeutic strategies. Silymarin demonstrated the anti-cancer activity however, due to low bioavailability its use is restricted. This study aimed to improve the solubility of silymarin by developing a silymarin loaded zein nanoparticles (SLNPs) which was stabilized by beta cyclodextrin. Comprehensive physiochemical characterization studies based on DLS, FTIR, UV-Vis Spectroscopy, FE-SEM, TEM, XRD, DSC, NMR and TGA confirmed the successful synthesis of SLNPs via an anti-solvent precipitation method. FE-SEM and TEM images demonstrated the uniform size and spherical shape of nanoparticles with encapsulation and loading efficiencies of 84.32 ± 1.9 % and 15.25 ± 2.4 % respectively. The zein protein interaction with silymarin, and ß-cyclodextrin was shown to be beneficial via the use of molecular simulations and binding energy calculations. Cellular studies demonstrated dose and time dependent cytotoxicity of SLNPs on MCF-7 breast cancer cell. FACS, qRT-PCR and Western blotting showed Bax (pro-apoptotic) upregulation while Bcl-2 (anti-apoptotic) downregulation. Our findings suggest that these loaded nanoparticles are more efficient than pure drug, enhancing its bioavailability and paving the path for developing it as a promising nutraceutical to treat breast cancer.

Synergistic effects of citicoline and silymarin nanomicelles in restraint stress-exposed mice.

This study evaluated the effects of citicoline and silymarin nanomicelles (SMnm) in repeated restraint stress (RRS). METHOD: Mice were exposed to RRS for four consecutive days, 2 hrs. daily. On day 5 of the study, SMnm (25 and 50 mg/kg, i.p.) and citicoline (25 and 75 mg/kg), and a combination of them (25 mg/kg, i.p.) were initiated. On day 18, anxiety-like behavior, behavioral despair, and exploratory behavior were evaluated. The prefrontal cortex (PFC) and the hippocampus were dissected measuring brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), and tumor necrosis factor-alpha (TNF-α) through Western Blot and ELISA, respectively. RESULTS: In RR-exposed mice, anxiety-like behavior in the elevated plus maze (EPM) was enhanced by reductions in open arm time (OAT%) P < 0.001, and open arm entry (OAE%) P < 0.001. In the forced swimming test (FST), the immobility increased P < 0.001 while the swimming and climbing reduced P < 0.001. In the open field test (OFT), general motor activity was raised P < 0.05. Further, body weights reduced P < 0.001, and tissue BDNF and pCREB expressions decreased P < 0.001 while TNF-α increased P < 0.001. Conversely, SMnm, citicoline and their combination could reduce anxiety-like behavior P < 0.001. The combination group reduced the depressive-like behaviors P < 0.001. Moreover, body weights were restored P < 0.001. Besides, BDNF and pCREB expressions increased while TNF-α reduced, P < 0.001. CONCLUSION: The combination synergistically improved emotion-like behaviors, alleviating the inflammation and upregulating the hippocampal BDNF-mediated CREB signaling pathway.

Camel milk or silymarin could improve the negative effects that experimentally produced by aflatoxin B1 on rat's male reproductive system.

BACKGROUND: Camel milk and silymarin have many different beneficial effects on several animal species. Meanwhile, Aflatoxins are mycotoxins with extraordinary potency that pose major health risks to several animal species. Additionally, it has been documented that aflatoxins harm the reproductive systems of a variety of domestic animals. The present design aimed to investigate the impact of aflatoxin B1 (AFB1) on rat body weight and reproductive organs and the ameliorative effects of camel milk and silymarin through measured serum testosterone, testes pathology, and gene expression of tumor necrosis factor (TNF-α), luteinizing hormone receptor (LHR), and steroidogenic acute regulatory protein (StAR) in the testes. A total of sixty mature male Wister white rats, each weighing an average of 83.67 ± 0.21 g, were used. There were six groups created from the rats. Each division had ten rats. The groups were the control (without any treatment), CM (1 ml of camel milk/kg body weight orally), S (20 mg silymarin/kg b. wt. suspension, orally), A (1.4 mg aflatoxin/kg diet), ACM (aflatoxin plus camel milk), and AS (aflatoxin plus silymarin). RESULTS: The results indicated the positive effects of camel milk and silymarin on growth, reproductive organs, and gene expression of TNF-α, LHR, and StAR with normal testicular architecture. Also, the negative effect of AFB1 on the rat's body weight and reproductive organs, as indicated by low body weight and testosterone concentration, was confirmed by the results of histopathology and gene expression. However, these negative effects were ameliorated by the ingestion of camel milk and silymarin. CONCLUSION: In conclusion, camel milk and silymarin could mitigate the negative effect of AFB1 on rat body weight and reproductive organs.

Nephroprotective effects of silymarin and its fabricated nanoparticles against aluminum-induced oxidative stress, hyperlipidemia, and genotoxicity.

BACKGROUND: Aluminum (Al) is a ubiquitous element with proven nephrotoxicity. Silymarin (SM) is a mixture of polyphenolic components extracted from Silybum marianum and exhibited protective influences. However, SM bioactivity can be enhanced by its incorporation in chitosan (CS) through the use of nanotechnology. This work proposed to assess the protective influence of SM and its loaded chitosan nanoparticles (SM-CS-NPs) on aluminum chloride (AlCl3)-induced nephrotoxicity. METHODS: Six groups were created randomly from 42 male Wistar rats and each one contains 7 rats (n = 7). Group I, acted as a control and received water. Group II received SM (15 mg/kg/day) and group III administered with SM-CS-NPs (15 mg/kg/day). Group IV received AlCl3 (34 mg/kg) and groups V and VI were treated with SM and SM-CS-NPs with AlCl3 respectively for 30 days. RESULTS: AlCl3 administration significantly elevated TBARS, H2O2, and kidney function levels besides LDH activity. Whereas GSH, CAT, SOD, GPx, GST, and GR values were all substantially reduced along with protein content, and ALP activity. Additionally, significant alterations in lipid profile, hematological parameters, and renal architecture were observed. Moreover, TNF-α, TGF-ß, and MMP9 gene expression were upregulated in kidney tissues. The administration of SM or its nanoparticles followed by AlCl3 intoxication attenuated renal dysfunction replenished the antioxidant system, and downregulated TNF-α, TGF-ß, and MMP9 gene expression in renal tissues compared to the AlCl3 group. CONCLUSION: SM-CS-NPs have more pronounced appreciated protective effects than SM and have the proficiency to balance oxidant/antioxidant systems in addition to their anti-inflammatory effect against AlCl3 toxicity.

Effects of Six Natural Compounds and Their Derivatives on the Control of Coccidiosis in Chickens.

Chicken coccidiosis costs the poultry industry over GBP 10 billion per year. The main method of preventing and controlling coccidiosis in chickens continues to be the use of drugs. Unfortunately, the prevalence of drug resistance in the field reduces or even eliminates the effectiveness of drugs, and drug residues in the food supply chain can also can be harmful to humans. Therefore, safe and effective anticoccidial drugs are urgently needed. Natural products have many advantages such as being safe, effective and inexpensive and are a sustainable way to control coccidiosis. In this study, the anticoccidial effects of six natural compounds were tested by Eimeria tenella infection. Oocyst production, cecum lesion, body weight gain, feed conversion ratio, and intestinal microbiota were measured. The results showed that nerolidol had a moderate effect on maintaining both body weight gain and feed conversion ratio. Silymarin and dihydroartemisinin showed significant anticoccidial effects by reducing total oocyst output. Dihydroartemisinin also significantly reduced the cecum lesion caused by Eimeria infection, but this compound may be toxic to the host at such informed doses because it decreases growth and survival rates. In addition, both silymarin and dihydroartemisinin partly restored the microbiota after challenge. This indicates that silymarin, dihydroartemisinin, and nerolidol are effective in the control of chicken coccidiosis. Our data provide basic knowledge about the anticoccidial effects of such natural compounds/derivates.

Silymarin enriched gelatin methacrylamide bioink imparts hepatoprotectivity to 3D bioprinted liver construct against carbon tetrachloride induced toxicity.

Three-dimensional liver bioprinting is an emerging technology in the field of regenerative medicine that aids in the creation of functional tissue constructs that can be used as transplantable organ substitutes. During transplantation, the bioprinted donor liver must be protected from the oxidative stress environment created by various factors during the transplantation procedure, as well as from drug-induced damage from medications taken as part of the post-surgery medication regimen following the procedure. In this study, Silymarin, a flavonoid with the hepatoprotective properties were introduced into the GelMA bioink formulation to protect the bioprinted liver against hepatotoxicity. The concentration of silymarin to be added in GelMA was optimised, bioink properties were evaluated, and HepG2 cells were used to bioprint liver tissue. Carbon tetrachloride (CCl4) was used to induce hepatotoxicity in bioprinted liver, and the effect of this chemical on the metabolic activities of HepG2 cells was studied. The results showed that Silymarin helps with albumin synthesis and shields liver tissue from the damaging effects of CCl4. According to gene expression analysis, CCl4 treatment increased TNF-α and the antioxidant enzyme SOD expression in HepG2 cells while the presence of silymarin protected the bioprinted construct from CCl4-induced damage. Thus, the outcomes demonstrate that the addition of silymarin in GelMA formulation protects liver function in toxic environments.

Dietary inclusion of micelle silymarin enhances egg production, quality, and lowers blood cholesterol in Hy-line brown laying hens.

This study aimed to evaluate the effect of micelle silymarin (MS) supplementation on productive performance, egg quality, and blood biochemical parameters in laying hens. A total of 384 (Hy-Line brown, 28-week-old) laying hens were randomly distributed into one of four dietary treatment groups (eight replication per treatment; 12 hens per replicate) for a 12-week long feeding trial. Hens were fed a basal diet with the addition of 0%, 0.02%, 0.04%, and 0.06% of MS respectively. The results expressed that egg production percentage and egg weight were linearly (p < 0.05) enhanced at Weeks 0-6, 7-12, and 0-12, when 0%, 0.02%, 0.04%, and 0.06% of MS were added to laying hen diets. The feed conversion ratio and feed intake improved (p < 0.05) linearly at Weeks 0-6, 7-12, and 0-12 with increasing levels of MS supplementation in laying hens. The eggshell thickness and eggshell strength were linearly (p < 0.05) improved at weeks 4, 8, and 12 with an MS-supplemented diet. Additionally, eggshell colour, Haugh unit, and albumin height had no significant (p > 0.05) difference throughout the experimental period with different levels of MS-supplemented diet. The yolk colour of eggs showed significant (p < 0.05) differences at weeks 8 and 12 with levels of the MS-supplemented diet. However, at the end of the trial, the blood profile indicated that cholesterol levels decreased (p < 0.05) linearly, and triglyceride levels showed a tendency to decrease (p < 0.10) with MS supplementation. In conclusion, increasing the level of MS addition in the laying hen diet improved the egg production percentage and egg quality, reducing cholesterol levels in Hy-Line brown hens. However, this study indicates that MS can be added to the diet of laying hens up to 0.06% for improved egg production and egg quality.

Effects of silymarin supplementation on liver and kidney functions: A systematic review and dose-response meta-analysis.

It is suggested that supplementation with silymarin (SIL) has beneficial impacts on kidney and liver functions. This systematic review and dose-response meta-analysis assessed the impact of SIL administration on certain hepatic, renal, and oxidative stress markers. A systematic search was conducted in various databases to identify relevant trials published until January 2023. Randomized controlled trials (RCTs) that evaluated the effects of SIL on kidney and liver markers were included. A random-effects model was used for the analysis and 41 RCTs were included. The pooled results indicated that SIL supplementation led to a significant reduction in serum levels of alkaline phosphatase, alanine transaminase, creatinine, and aspartate aminotransferase, along with a substantial elevation in serum glutathione in the SIL-treated group compared to their untreated counterparts. In addition, there was a nonsignificant decrease in serum levels of gamma-glutamyl transferase, malondialdehyde (MDA), total bilirubin, albumin (Alb), total antioxidant capacity, and blood urea nitrogen. Sub-group analyses revealed a considerable decline in MDA and Alb serum values among SIL-treated participants with liver disease in trials with a longer duration (≥12 weeks). These findings suggest that SIL may ameliorate certain liver markers with potential hepatoprotective effects, specifically with long-term and high-dose supplementation. However, its nephroprotective effects and impact on oxidative stress markers were not observed. Additional high-quality RCTs with longer durations are required to determine the clinical efficacy of SIL supplementation on renal and oxidative stress markers.

Silymarin prevents endothelial dysfunction by upregulating Erk-5 in oxidized LDL exposed endothelial cells.

Extracellular signal-regulated kinase (Erk)-5 is a key mediator of endothelial cell homeostasis, and its inhibition causes loss of critical endothelial markers leading to endothelial dysfunction (ED). Circulating oxidized low-density lipoprotein (oxLDL) has been identified as an underlying cause of ED and atherosclerosis in metabolic disorders. Silymarin (Sym), a flavonolignan, possesses various pharmacological activities however its preventive mechanism in ED warrants further investigation. Here, we have examined the effects of Sym in regulating the expression of Erk-5 and ameliorating ED using in vitro and in vivo models. Primary human umbilical vein endothelial cells (pHUVECs) viability was measured by MTT assay; mRNA and protein expression by RT-qPCR and Western blotting; tube-formation assay was performed to examine endothelialness. In in-vivo experiments, normal chow-fed mice (control) or high-fat diet (HFD)-fed mice were administered Sym or Erk-5 inhibitor (BIX02189) and body weight, blood glucose, plasma-LDL, oxLDL levels, and expression of EC markers in the aorta were examined. Sym (5 µg/ml) maintained the viability and tube-formation ability of oxLDL exposed pHUVECs. Sym increased the expression of Erk-5, vWF, and eNOS and decreased ICAM-1 at transcription and translation levels in oxLDL-exposed pHUVECs. In HFD-fed mice, Sym reduced the body weight, blood glucose, LDL-cholesterol, and oxLDL levels, and increased the levels of vWF and eNOS along with Erk-5 and decreased the level of ICAM-1 in the aorta. These data suggest that Sym could be a potent anti-atherosclerotic agent that could elevate Erk-5 level in the ECs and prevent ED caused by oxidized LDL during HFD-induced obesity in mice.

Adjunctive silymarin supplementation and its effects on disease severity, oxidative stress, and inflammation in patients with Alzheimer's disease.

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 (Catalasebefore silymarin = 9.29 ± 7.02 vs Catalaseafter silymarin = 5.32 ± 2.97, p = 0.007 and MDAbefore silymarin = 4.29 ± 1.90 vs MDAafter silymarin = 1.66 ± 0.84, p < 0.001) while MMSE increased notably (MMSEbefore silymarin = 10.39 ± 6.42 vs MMSEafter 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.