Physiological and biochemical characteristics of milk thistle (Silybum marianum (L.) Gaertn) as affected by some plant growth regulators.

Milk thistle (Silybum marianum (L.) Gaertn) is a globally and widely used medicinal plant that contains silymarin. This plant has antioxidant, antimicrobial, anticancer, hepatoprotective, cardiovascular-protective, and neuroprotective effects. Plant quality, yield, and phytochemicals, especially silymarin content, change under various conditions like drought stress. Therefore, this research studied plant growth regulators (PGRs) like salicylic acid, spermidine, and brassinosteroid to increase plant tolerance to drought stress. Experimental treatments include different levels of irrigation (25%, 50%, 75%, and 90% field capacity), and foliar spraying including salicylic acid (75 and 150 mg/L), spermine (70 and 140 mg/L), and brassinosteroid (1 and 1.2 µM), separately, and water as a control and a secondary factor. The results revealed that the highest amount of leaf phenolic compounds was observed in the highest drought stress level (25%) and 75 mg/L salicylic acid application. Furthermore, brassinosteroid at different concentrations and salicylic acid (75 mg/L) increased leaf flavonoid content compared to other treatments. In 50% field capacity, foliar application of salicylic acid (150 mg/L) significantly increased seed yield by approximately 75% compared to control under the same stress level. Brassinosteroid application (1 µM) under 75% field capacity significantly increased the seed's taxifolin amount by 159%. Additionally, salicylic acid noticeably increased the silychristin concentration. The concentration of silydianin in the seed has also been increased under drought stress and foliar spraying with PGRs. Compared to the control, using spermidine below 75% field capacity caused an increase in its concentrations by over seven times. The highest silybin A amount was obtained in 50% field capacity and foliar150 mg/L salicylic acid. Taxifolin, silychristin, silydianin, silybinin B, iso-silybinin A, and iso-silybinin B compounds were identified in the seed extract. Generally, foliar spraying using plant growth regulators increased the number of silymarin compounds under drought stress conditions and field cultivation conditions.

The comparison of the effects of nano-silymarin and silymarin on high-fat diet-induced fatty liver of adult male rats.

Objective: Considering the high prevalence of non-alcoholic fatty liver disease and its complications, this study aims to determine and compare the effect of nano-silymarin and silymarin on non-alcoholic fatty liver in rats. Materials and Methods: Rats were divided into 5 groups: Control, high-fat diet, high-fat diet and atorvastatin, high-fat diet and silymarin, and high-fat diet and nano-silymarin. After 12 weeks, blood samples were taken to measure cholesterol, triglyceride, HDL, LDL, ALT and AST. The animals were killed and the liver tissue was removed to examine the histopathological changes. Results: Feeding with a high-fat diet caused a significant increase in cholesterol, triglyceride and LDL-C in serum of rats compared to the control. Nano-silymarin and silymarin could significantly reduce serum triglyceride compared to negative group but the reduction of cholesterol, LDL-C, AST and ALT by nano-silymarin was not significant as compared to silymarin. The liver histology evaluation mainly showed that in the group receiving nano-silymarin, a significant decrease in the percentage of fat vacuoles and degree of steatosis was observed compared to the negative group. In the positive group, the percentage of fat vacuoles and the degree of steatosis showed a significant decrease compared to the negative group. Group receiving atorvastatin showed a greater protective effect than silymarin and nano-silymarin. Conclusion: The use of nano-silymarin similar to silymarin in rats treated with a high-fat diet led to a decrease in the percentage of fat vacuoles and the degree of hepatic steatosis mainly and can be used to prevent non-alcoholic fatty liver disease.

Silymarin ameliorates motor function and averts neuroinflammation-induced cell death in the rat model of Huntington's disease.

Huntington's disease (HD) is a scarce neurodegenerative disorder defined by chorea (unusual involuntary movements), behavioral presentations, psychiatric features, and cognitive deterioration. Although the precise pathogenic mechanism behind HD has not yet been identified, the most widely acknowledged pathways include excitotoxicity, mitochondrial malfunction, neuroinflammation, neurochemical imbalance, oxidative stress, and apoptosis HD has no efficient therapy. Current medications have drawbacks. Silymarin, a compound made up of standardized extracts obtained from the seeds of the Silybum marianum and polyphenolic flavonolignan, is utilized in therapeutic settings to treat a variety of experimental disorders in animals. Silymarin's key pharmacological activities include anti-cancer, hepatoprotection, antioxidant, cardioprotection, and anti-inflammatory. It also has no adverse side effects on people or animals. The current study aims to provide Silymarin's neuro-pharmacological activities or therapeutic qualities in HD. In this study, Thirty-six male Sprague-Dawley rats (200-220g, 8 weeks) at the initial of the study were used. Silymarin solution (100mg/Kg) was administered by oral gavage for 21 days to ameliorate neural damage in rats injected with 3-nitropropionicacid (3-NP) in a preliminary rat model of HD. The results showed that administration of silymarin to HD rats reduced gliosis, improved motor coordination and muscle activity, and increased striatal volume and the number of neurons and glial cells. Our results suggest that silymarin provides a protective environment for nerve cells and can have beneficial effects against the harmful effects of HD.

Hybrid Nanoparticles Based on Mesoporous Silica and Functionalized Biopolymers as Drug Carriers for Chemotherapeutic Agents.

Mesoporous silica nanoparticles (MSNs) are promising drug carriers for cancer therapy. Their functionalization with ligands for specific tissue/cell targeting and stimuli-responsive cap materials for sealing drugs within the pores of MSNs is extensively studied for biomedical and pharmaceutical applications. The objective of the present work was to establish MSNs as ideal nanocarriers of anticancer drugs such as 5-FU and silymarin by exploiting characteristics such as their large surface area, pore size, and biocompatibility. Furthermore, coating with various biopolymeric materials such as carboxymethyl chitosan-dopamine and hyaluronic acid-folic acid on their surface would allow them to play the role of ligands in the process of active targeting to tumor cells in which there is an overexpression of specific receptors for them. From the results obtained, it emerged, in fact, that these hybrid nanoparticles not only inhibit the growth of glioblastoma and breast cancer cells, but also act as pH-responsive release systems potentially useful as release vectors in tumor environments.

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624 nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6 mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Exercise-activated hepatic autophagy combined with silymarin is associated with suppression of apoptosis in rats subjected to dexamethasone induced- fatty liver damage.

AIM: There is a need for effective treatments for non-alcoholic fatty liver disease (NAFLD) that are economically inexpensive, and have few side effects. The present study aimed to investigate exercise training and silymarin on hepatocyte death factors in rats with liver damage. METHODS: Forty-nine male Wistar rats were assigned to seven groups: sedentary control, fatty liver control (DEX), fatty liver + high-intensity interval training (HIIT), fatty liver + HIIT + silymarin (HIIT + SILY), fatty liver + continuous training (CT), fatty liver + CT + silymarin (CT + SILY), and fatty liver + silymarin (SILY). A subcutaneous injection of dexamethasone for 7 days was used to induce fatty liver in rats. Masson's trichrome and hematoxylin-eosin staining were done to evaluate hepatic injury. The hepatocyte apoptosis was determined by TUNEL assay. Real-Time PCR was conducted to evaluate the gene expressions of caspase-9, adenosine monophosphate-activated protein kinase (AMPKα1), mitofusin 2 (Mfn2), and damage-regulated autophagy modulator (DRAM). Liver tissue changes and serum levels of liver enzymes were also evaluated. RESULTS: Liver apoptosis was decreased in the CT, HIIT, HIIT + SILY and CT + SILY groups compared to the DEX group. Both continuous and high-intensity training models produced beneficial alterations in liver morphology and hepatic injuries that were significant in exercise training + silymarin group. This impact was accompanied by increased AMPKα1 and DRAM gene expression and decreased caspase-9 and Mfn2 gene expression. Liver enzyme levels were high in the DEX group and treatment with silymarin significantly reduced it. CONCLUSION: Silymarin supplementation combined with interval or continuous training substantially improves DEX-induced hepatic steatosis and hepatocyte injury mostly through suppressing liver apoptosis and upregulating autophagy, which may provide a novel perspective for NAFLD treatment.

Design and development of multibiocomponent hybrid alginate hydrogels and lipid nanodispersion as new materials for medical and cosmetic applications.

The multibiocomponent hybrid alginate hydrogels based on brown and sea algae, containing 100 % ingredients of natural origin were prepared by ionic crosslinking reaction of a polymeric matrix with lipid nanodispersion. To the best of the Authors' knowledge such multicomponent biobased hydrogel of promising medical and cosmetical applications for the first time was obtained in the environment of flower water, received earlier as a waste by-product from various chemical processes. An innovative hybrid alginate hydrogel that is completely biodegradable and eco-friendly was obtained following waterless and upcycling trends that are in line with the principles of sustainable development. The optimal composition of the lipid nanodispersion and the polymeric matrix was selected using the statistical method of design of the experiment. Based on obtained results, multibiocomponent hybrid alginate hydrogels with various ratios of lipid nanodispersion were obtained. Subsequently, the porous structure and elasticity of the hybrid hydrogels were analyzed. Moreover, to confirm the safety of the multibiocomponent alginate hybrid hydrogels the cytotoxic tests were carried out using human fibroblasts and keratinocytes cell lines. As the final product hybrid of hydrolate-swollen alginate hydrogel and lipid nanodispersion containing several active ingredients (silymarin, bakuchiol, spirulina) was obtained.

Unlocking the possibilities of therapeutic potential of silymarin and silibinin against neurodegenerative Diseases-A mechanistic overview.

Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, ß-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules.

Silymarin in combination with hair follicle transplantation as a potential treatment for refractory vitiligo: A double-blind randomized controlled trial.

BACKGROUND: There is still no certain effective treatment for vitiligo as a common chronic skin disorder characterized by depigmented patches and loss of skin melanocytes. OBJECTIVES: This study evaluates the efficacy of oral silymarin combined with hair follicle transplantation compared to follicle transplantation alone in the treatment of refractory vitiligo. MATERIALS AND METHODS: Twenty refractory vitiligo patients were enrolled in this randomized controlled clinical trial, following up for 3 months. One group underwent hair transplantation plus oral silymarin, while the other group underwent follicle transplantation alone. We assessed the progress with Vitiligo Extent Tensity Index (VETI) in both groups and the peri-follicular pigmentation diameter was estimated monthly. The Friedman test for comparing two groups at the end and the Mann-Whitney test for comparing two groups during each month was used. RESULTS: The mean age was 30.22 (18-59) years, with the male to female ratio of 1:1. The decrease in the VETI and increase in the perifollicular pigmentation was statistically significant between silymarin and another group in monthly follow-up (p-value: 0.019, 0.019, and 0.035, respectively). Finally, the re-pigmentation was notable in silymarin group (p-value <0.001 vs. 0.029, respectively). In addition, both genders had a significant increase in peri-follicular re-pigmentation in the last follow-up (p-value: 0.012 and 0.044, respectively); although the improvement was not statistically significant between genders in each month. CONCLUSION: According to our study, silymarin in combination with hair transplantation could be a potential medical treatment for vitiligo; however, further trials are needed to establish the efficacy of combination therapies.

Antiparasitic Effects of Niosomal Formulations of Curcumin and Silymarin Against Toxoplasma gondii In Vitro.

Background: Toxoplasmosis is caused by infection with Toxoplasma gondii. No Symptoms in healthy people. Notably, very dangerous symptoms in immunocompromised, or patients with immune diseases. Previous research has shown that the parasite's resistance to drugs continues to emerge and has indicated this resistance as a cause for concern. In this context, researchers have a great responsibility to search for alternative treatments, as well as to develop existing ones. Essentially, this improves the therapeutic efficacy of drugs and prevents the emergence of resistance to them. The present study aims to evaluate antitoxoplasma effects of niosomal loaded curcumin and silymarin and their synergistic effects with clindamycin against T. gondii RH strain in vitro. Materials and Methods: Experiments were conducted on the tachyzoites of T. gondii RH-strain, based on: the free and nieosomal compounds of curcumin and silymarin, in addition to the drug clindamycin. Data were collected to estimate parasite viability during exposure to the therapeutic compounds under study using a special MTT assay ((3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolioum bromide) assay: is a colorimetric assay for measuring cellular growth) kit provided by (Bio Idea Company, Tehran, Iran). Hence, the effect of the therapeutic compounds on the parasite load was studied using the quantitative molecular technique real-time PCR. Results: The results indicate that the combination of N-silymarin and N-curcumin with clindamycin has active synergistic effects against T. gondii leading to complete elimination of the parasite. Data revealed that curcumin and silymarin in both their free and nisomal forms had inhibitory effects on the parasite, and minimal toxic effects on normal cells. Conclusions: The results highlight the successful synergistic effect of clindamycin and the niosomal compounds curcumin and silymarin in completely eradicating the T. gondii RH-strain. This finding contributes positively to the field of safe and effective treatments.

Effect of silymarin on lipid profile and glycemic control in patients with type 2 diabetes mellitus.

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

Silymarin decreases liver stiffness associated with gut microbiota in patients with metabolic dysfunction-associated steatotic liver disease: a randomized, double-blind, placebo-controlled trial.

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

Evaluation of oral silymarin formulation efficacy in prevention of doxorubicin induced hepatotoxicity in patients with non-metastatic breast cancer.

INTRODUCTION: Chemotherapy-induced hepatotoxicity is a common complication in breast cancer patients, especially with doxorubicin-containing regimens. Liver enzyme abnormality is reported in 34.8% of patients undergoing AC-T regimen and fatty liver is reported in 30% to 50% of cases. Antioxidant and anti-inflammatory properties of silymarin, a polyphenolic flavonoid extract derived from Silybum marianum, may be useful in preventing chemotherapy-induced hepatotoxicity. This study evaluated the effect of oral silymarin for preventing doxorubicin induced hepatotoxicity in non-metastatic breast cancer patients. METHODS: In this triple-blind, placebo-controlled clinical trial, 50 patients with non-metastatic breast cancer were assigned to receive either 140 mg silymarin tablets or the placebo three times daily for 63 days and were evaluated for liver function test before the study and at the end of each chemotherapy cycle (every 3 weeks) for 4 cycles. In addition, an ultrasonography assessment was performed upon entry and the end of the study. RESULTS: Based on ultrasonography, the fatty liver grade was significantly higher in the placebo group at the end of the study. Moreover, the serum levels of aspartate aminotransferase (p = 0.015) and alkaline phosphatase (p = 0.004) at 6-week intervals, and the serum level of alkaline phosphatase (p = 0.002) at 9-week intervals were significantly lower in the silymarin group. CONCLUSION: Oral formulation of silymarin 420 mg/day for 63 days significantly prevented hepatotoxicity caused by doxorubicin in patients with non-metastatic breast cancer mostly based on liver ultrasonography but not laboratory parameters. Further investigations are suggested on different doses, durations and formulations of silymarin, particularly nano-formulations for increasing its oral bioavailability.

Silymarin ameliorates diazinon-induced subacute nephrotoxicity in rats via the Keap1-Nrf2/heme oxygenase-1 signaling pathway.

PURPOSE: The goal of the current study was to clarify the potential molecular mechanism underlying the protective effects of silymarin (SIL) administration against diazinon-induced subacute nephrotoxicity, with a special emphasis on the role of the Kelch-like-associated protein-1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2)-heme oxygenase-1 (HO-1) signaling pathway in minimizing the oxidative stress induced by diazinon (DZN). METHODS: Five equal groups of thirty adult male Wistar rats were created at random. Group 1 (G1) was maintained under typical control conditions and administered saline intragastrically (I/G) once daily for 4 weeks; G2 was administered olive oil I/G for 4 weeks; G3 was I/G administered silymarin daily for 4 weeks; G4 was I/G administered diazinon daily for 4 weeks. G5 was I/G administered silymarin daily 1 h before the I/G administration of the diazinon for 4 weeks. Blood samples were collected at the end of the experiment for the determination of complete blood cell count, and kidney function tests. Kidney specimens were collected for the evaluation of the oxidative markers, mRNA gene expression, protein markers, and histopathological examination. RESULTS: SIL reduced the renal dysfunction caused by DZN by restoring urea and creatinine levels, as well as oxidative indicators. Although the expression of Keap-1 was also elevated, overexpression of Nrf2 also enhanced the expression of HO-1, a crucial target enzyme of Nrf2. CONCLUSIONS: SIL is hypothesized to potentially aid in the prevention and management of nephrotoxicity caused by DZN.

Effects of micelle silymarin in corn-soybean meal-based diet on laying hens' performance, egg quality, and blood profile, with comparative assessment of blood absorption rates between powdered and micelle silymarin.

Micelle silymarin (MS) is recognized for its diverse range of beneficial properties, which encompass anti-inflammatory, antioxidant, hepatoprotective, and antidiabetic effects. The main objective of this study was to examine the effects of micelle silymarin on the performance, egg quality, blood profile, and absorption rate of silymarin in laying hens. In experiment 1: 288 Hy-Line brown laying hens, 28 wk old, were utilized for this experiment. The hens were randomly allocated into 3 dietary treatment groups, with each group comprising eight replicates of 12 hens, each housed in individual pens with access to feed and water. Over a 12-wk feeding trial, the hens were provided with a basal diet supplemented with different levels of MS: 0, 0.03, and 0.06%. In experiment 2: For this experiment, 192 Hy-Line Brown laying hens were divided into 2 dietary treatment groups, with each group comprising eight replications of 12 hens. The dietary treatments were: TRT1, basal diet + powder silymarin 4%; TRT2, basal diet + MS 4%. From the first experiment, the findings revealed that incorporating micelle silymarin (MS) into the hens' diet significantly increased egg weight at wk 6 (P < 0.05). Similarly, at wk 12 and throughout the entire experiment, significant effects were observed on downgraded egg count, egg production, egg weight, and feed conversion ratio (FCR) (P < 0.05). Moreover, Haugh Units (HU) and albumen height showed a linear improvement (P < 0.05) at wk 4 with MS supplementation. Furthermore, there was a linear increase in egg yolk color, albumen height, and eggshell thickness at wk 8 with MS supplementation (P < 0.05). Furthermore, a layers-fed diet supplemented with MS showed a linear increase (P < 0.05) in HU, egg weight, yolk color, albumen height, eggshell strength, and eggshell thickness in wk 12. Regarding blood profile parameters, the study revealed linear reductions for aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) (P < 0.05), whereas there was a tendency for albumin, triglyceride, and cholesterol (P < 0.10). In the second experiment, it was observed that the blood absorption rate of silymarin was higher in TRT2 compared to TRT1 at 2- and 4-h intervals following administration. In summary, increasing MS supplementation in the diet of laying hens enhanced egg production, egg quality, and blood profile. Additionally, silymarin absorption was higher in its micelle form than in its powder form.

Unlocking milk thistle's anti-psoriatic potential in mice: Targeting PI3K/AKT/mTOR and KEAP1/NRF2/NF-κB pathways to modulate inflammation and oxidative stress.

Silybum marianum, known as milk thistle (MT), is traditionally used to manage liver diseases. This study aimed to investigate the role of MT extract topical application as a potential treatment for imiquimod (IMQ)-induced psoriatic lesions in mice with particular emphasis on phosphoinositol-3 Kinase (PI3K)/ protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) and Kelch-like ECH-associated protein 1 (KEAP1)/ nuclear factor erythroid-2-related factor (NRF2)/ nuclear factor-kappa B (NF-κB) molecular cascades involvement. To address this aim, forty male Swiss albino mice were subdivided into four groups (n = 10 mice/group): control, IMQ model, standard group where mice were treated topically with IMQ, then the anti-psoriatic mometasone cream, and MT extract-treated group where mice were treated topically with IMQ followed by MT extract. In most measured parameters, MT extract, rich in silymarin, exhibited potent anti-psoriatic activity comparable to the standard cortisone treatment. MT extract mitigated dorsal skin erythema, scaling, and epidermal thickening, reflected by lowering the Psoriasis Area Severity Index (PASI) score. Moreover, it alleviated IMQ-induced splenomegaly. Mechanistically, the PI3K/AKT/mTOR pathway was the main functional pathway behind such improvements, where it was significantly inhibited by MT extract application. This led to NRF2 activation via KEAP1 downregulation with subsequent anti-inflammatory effect proven by reducing NF-κB, interleukin (IL)-23, and IL-17A and antioxidant ability proven by boosting the antioxidant glutathione and heme oxygenase-1. Such improvements were confirmed by alleviating the histopathological alteration. Thus, MT extract could be a promising therapeutic agent for psoriasis treatment by inhibiting PI3K/AKT/mTOR cascade, along with NRF2 signaling activation.

Exploring the therapeutic potential of silymarin-based herbal remedy (prebiotic) and probiotic blend in a mouse model of NAFLD: Insights into gut microbiota modulation and liver health.

Non-alcoholic fatty liver disease (NAFLD) is a significant consequence of metabolic dysfunction, often associated with changes in the intestinal microbiota. Prebiotics and probiotics have shown promise in NAFLD management. This study evaluated a silymarin-based herbal remedy with piperine and fulvic acid, alongside a probiotic blend of Bifidobacterium adolescentis, Bifidobacterium bifidum, Lactobacillus casei, and Lactobacillus rhamnosus. Using a NAFLD mouse model induced by a high-fat and high-fructose diet, we assessed biochemical parameters, liver function, glucose levels, and conducted histological analysis. Stool samples underwent 16S rRNA metagenomic analysis to explore changes in microbiota composition. Mice on the high-fat diet exhibited elevated lipids, liver enzymes, and glucose, with reduced high-density lipoprotein levels (with p value < 0.001). Treatment, particularly with F3 (silymarin-piperine-fulvic acid herbal remedy and probiotic blend), significantly reduced hepatic fat accumulation and improved gut microbiota composition. This study highlights the potential of silymarin-based therapy combined with probiotics in attenuating NAFLD progression.

Dietary silymarin improves performance by altering hepatic lipid metabolism and cecal microbiota function and its metabolites in late laying hens.

BACKGROUND: Liver lipid dysregulation is one of the major factors in the decline of production performance in late-stage laying hens. Silymarin (SIL), a natural flavonolignan extracted from milk thistle, is known for its hepatoprotective and lipid-lowering properties in humans. This study evaluates whether SIL can provide similar benefits to late-stage laying hens. A total of 480 68-week-old Lohmann Pink laying hens were randomly assigned into 5 groups, each group consisting of 6 replicates with 16 hens each. The birds received a basal diet either without silymarin (control) or supplemented with silymarin at concentrations of 250, 500, 750, or 1,000 mg/kg (SIL250, SIL500, SIL750, SIL1000) over a 12-week period. RESULTS: The CON group exhibited a significant decline in laying rates from weeks 9 to 12 compared to the initial 4 weeks (P = 0.042), while SIL supplementation maintained consistent laying rates throughout the study (P > 0.05). Notably, the SIL500 and SIL750 groups showed higher average egg weight than the CON group during weeks 5 to 8 (P = 0.049). The SIL750 group had a significantly higher average daily feed intake across the study period (P < 0.05), and the SIL500 group saw a marked decrease in the feed-to-egg ratio from weeks 5 to 8 (P = 0.003). Furthermore, the SIL500 group demonstrated significant reductions in serum ALT and AST levels (P < 0.05) and a significant decrease in serum triglycerides and total cholesterol at week 12 with increasing doses of SIL (P < 0.05). SIL also positively influenced liver enzyme expression (FASN, ACC, Apo-VLDL II, FXR, and CYP7A1; P < 0.05) and altered the cecal microbiota composition, enhancing species linked to secondary bile acid synthesis. Targeted metabolomics identified 9 metabolites predominantly involved in thiamin metabolism that were significantly different in the SIL groups (P < 0.05). CONCLUSIONS: Our study demonstrated that dietary SIL supplementation could ameliorate egg production rate in late stage laying hens, mechanistically, this effect was via improving hepatic lipid metabolism and cecal microbiota function to achieve. Revealed the potentially of SIL as a feed supplementation to regulate hepatic lipid metabolism dysregulation. Overall, dietary 500 mg/kg SIL had the best effects.

Hepatoprotective efficacy of quinoa seed extract against CCl4- induced acute liver toxicity in rat model.

The current research explored the possible protective effect of chenopodium quinoa extract against CCl4 acute liver toxicity in Sprague Dawley rats. Thirty rats were divided into five groups with six rats in each group. CCl4 (Carbon tetrachloride) was administered at a dose rate of 2 mL/kg b.w. intra-peritoneally once a week for 3 weeks. The plant extract was given through oral gavage for a period of 21 days. Group I served as a normal group which was given with basal diet. Group II was referred to as a positive control group and received CCl4 2 mL/kg body weight (i.p.). Group III was the standard treatment group and received 2 mL/kg CCl4 (i.p.) and 16 mg/kg body weight (p.o.) silymarin. Group IV was the plant treatment group, which received 2 mL/kg CCl4 (i.p.) and 600 mg/kg body weight of quinoa seed extract (p.o.). Group V was the combined treatment group, which received 2 mL/kg CCl4 (i.p.) accompanied with a combination of silymarin (p.o.) 16 mg/kg body weight and quinoa seed extract (p.o.) 600 mg/kg body weight. The liver biomarkers were assessed along with histopathological analysis to observe the changes in the liver. The outcome suggested that the treatment, which was given with the combination of silymarin and quinoa seed extract, significantly enhanced the antioxidant levels, reduced the oxidative stress, and restored the liver function as evidenced by biochemical parameters histopathological studies. The hepatoprotective potential may be due to the antioxidant and anti-inflammatory properties of quinoa seed extract.

Phytolacca Dodecandra (L' Herit) (Phytolaccaceae) Methanol Root Extract Protects Liver from Acetaminophen-Induced Injury in Rats.

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury.