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1.
Int J Nanomedicine ; 16: 6983-7022, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703224

RESUMO

Nowadays, medicinal herbs and their phytochemicals have emerged as a great therapeutic option for many disorders. However, poor bioavailability and selectivity might limit their clinical application. Therefore, bioavailability is considered a notable challenge to improve bio-efficacy in transporting dietary phytochemicals. Different methods have been proposed for generating effective carrier systems to enhance the bioavailability of phytochemicals. Among them, nano-vesicles have been introduced as promising candidates for the delivery of insoluble phytochemicals. Due to the easy preparation of the bilayer vesicles and their adaptability, they have been widely used and approved by the scientific literature. The first part of the review is focused on introducing phytosome technology as well as its applications, with emphasis on principles of formulations and characterization. The second part provides a wide overview of biological activities of commercial and non-commercial phytosomes, divided by systems and related pathologies. These results confirm the greater effectiveness of phytosomes, both in terms of biological activity or reduced dosage, highlighting curcumin and silymarin as the most formulated compounds. Finally, we describe the promising clinical and experimental findings regarding the applications of phytosomes. The conclusion of this study encourages the researchers to transfer their knowledge from laboratories to market, for a further development of these products.


Assuntos
Curcumina , Silimarina , Disponibilidade Biológica , Composição de Medicamentos , Compostos Fitoquímicos
2.
Expert Rev Clin Pharmacol ; 14(11): 1445-1453, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34486906

RESUMO

Background and aim: We conducted a systematic review to apprise the efficacy of silymarin in conjunction with standard iron chelators on iron overload for transfusion-dependent ß-thalassemia (TDT) patients.Methods: We searched PubMed, Web of Science, Scopus, Sciencedirect, the Cochrane Library (the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials (CENTRAL) to 1 May 2020. All randomized controlled trials (RCTs) studies comparing the effect of iron chelators alone versus silymarin plus standard routine treatment on iron burden amid TDT were included in this review. Primary outcomes comprised serum ferritin level (ng/mL), liver iron concentration (LIC Fe/kg dry weight), and total iron binding capacity (TIBC mcg/dL)Results: Combination therapy of silymarin and iron chelators showed a significant improvement in serum ferritin level in TDT patients, compared to nonsilymarin users [eight studies, n = 477]; weighted mean difference (WMD) -1.79, 95% confidence interval [CI] -2.86 to -0.72, I2 96.1%; P = 0.001. Concurrent treatment with silymarin failed to significantly decrease LIC in TDT patients [two studies, n = 106]; WMD 0.74, 95% CI -1.62 to 3.10, I2 96.6%; P = 0.54.Conclusion: There is no evidence of the effectiveness of adding silymarin to standard iron chelators to reduce iron load in TDT.


Assuntos
Quelantes de Ferro/administração & dosagem , Silimarina/administração & dosagem , Talassemia beta/terapia , Transfusão de Sangue , Quimioterapia Combinada , Ferritinas/sangue , Humanos , Sobrecarga de Ferro/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
Ceska Slov Farm ; 70(3): 102-108, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34418947

RESUMO

In this experimental study, the effects of the combined herbal drug Pancreo-Plant® at a dose of 72 mg/kg and the comparison drug silymarin at a dose of 25 mg/ kg on animal mortality, cytolysis activity, free radical oxidation, and functional activity of the liver in the conditions of acute experimental ischemia have been studied. A pronounced antioxidant effect of the studied agent has been found which was manifested in the reduction of the lipid peroxidation products content, namely thiobarbituric acid products and diene conjugates and normalization of the enzymatic and non-enzymatic chains of endogenous antioxidant protection (reduced glutathione, catalase). In the case of acute liver failure, Pancreo-Plant® exhibited a significant anti-cytolytic effect, restored carbohydrate metabolism and protein-synthetic function of the liver. It was found that the total hepatoprotective activity of the combined herbal drug Pancreo-Plant® exceeded the activity of the comparison drug silymarin.


Assuntos
Antioxidantes , Silimarina , Animais , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Isquemia/metabolismo , Peroxidação de Lipídeos , Fígado , Silimarina/metabolismo , Silimarina/farmacologia
4.
Int J Mol Sci ; 22(16)2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34445463

RESUMO

Enterovirus A71 (EV-A71) is a major neurovirulent agent capable of causing severe hand, foot and mouth disease (HFMD) associated with neurological complications and death. Currently, no FDA-approved antiviral is available for the treatment of EV-A71 infections. The flavonoid silymarin was shown to exert virucidal effects, but the binding site on the capsid was unknown. In this study, the ligand interacting site of silymarin was determined in silico and validated in vitro. Moreover, the potential of EV-A71 to develop resistance against silymarin was further evaluated. Molecular docking of silymarin with the capsid of EV-A71 indicated that silymarin binds to viral protein 1 (VP1) of EV-A71, specifically at the GH loop of VP1. The in vitro binding of silymarin with VP1 of EV-A71 was validated using recombinant VP1 through ELISA competitive binding assay. Continuous passaging of EV-A71 in the presence of silymarin resulted in the emergence of a mutant carrying a substitution of isoleucine by threonine (I97T) at position 97 of the BC loop of EV-A71. The mutation was speculated to overcome the inhibitory effects of silymarin. This study provides functional insights into the underlying mechanism of EV-A71 inhibition by silymarin, but warrants further in vivo evaluation before being developed as a potential therapeutic agent.


Assuntos
Antivirais/química , Proteínas do Capsídeo/química , Capsídeo/química , Enterovirus Humano A/química , Simulação de Acoplamento Molecular , Silimarina/química , Proteínas do Capsídeo/genética , Linhagem Celular Tumoral , Farmacorresistência Viral Múltipla/genética , Enterovirus Humano A/genética , Humanos , Mutação , Estrutura Secundária de Proteína
5.
Trop Anim Health Prod ; 53(4): 442, 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410508

RESUMO

The aim of this study was to determine whether the inclusion of silymarin in broiler feed was able to mitigate the adverse effects of mycotoxin on growth performance, health status, liver oxidative stress, and meat fatty acid profiles. A completely randomized design with four treatments, four repetitions, and 15 chicks per repetition was used, with the following groups: (a) feed without additives (NoMyc-NoSil), (b) feed supplemented with silymarin (NoMyc-Sil), (c) feed contaminated with mycotoxin (Myc-NoSil), and (d) feed contaminated with mycotoxin and supplemented with silymarin (Myc-Sil). Growth performance, intestinal and liver health, and meat quality were assessed. The consumption of feed contaminated with mycotoxin delayed weight gain and increased the feed conversion ratio; however, the addition of silymarin prevented these adverse effects on the chicken industry. Serum ALT activity was higher in Myc-NoSil broilers than in other groups. Intake of silymarin in healthy birds increased serum globulin concentration and reduced albumin concentration and ALT and AST serum activities compared to the Myc-NoSil group. The NoMyc-Sil birds had greater villus heights and crypt depths. Luminosity and water loss by cooking were affected by mycotoxin ingestion, changes that did not occur in the meat of birds that were supplemented with silymarin. The sum of saturated and monounsaturated fatty acids in the meat did not change among treatments, unlike the sum of polyunsaturated fatty acids higher in the meat of birds that consumed silymarin. We conclude that silymarin is a potential additive in broiler feed; it reduces impairment of growth performance at the end of the productive cycle, prevents oxidative stress, improves meat quality, and increases polyunsaturated fatty acids.


Assuntos
Micotoxinas , Silimarina , Ração Animal/análise , Animais , Antioxidantes , Galinhas , Dieta/veterinária , Suplementos Nutricionais , Ácidos Graxos , Carne/análise
6.
J Biomed Nanotechnol ; 17(6): 1123-1130, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34167626

RESUMO

Alzheimer's disease (AD) is strongly associated with oxidative stress which can damage neural cells. Silibinin has shown potential antioxidative effects. However, due to its low solubility in water, silibinin provides low biological activity and bioavailability. Therefore, to increase its pharmacological effects, silibilin was encapsulated into human serum albumin (HSA) nanoparticles and well-characterized by DLS and TEM techniques. The antioxidant activity of silibinin-HSA nanoparticles was evaluated on LPS-induced oxidative stress in neuron-like cells (SH-SY5Y) through MTT, antioxidant activity and apoptotic assay. It was shown that the mean diameter of HSA and silibinin-HSA nanoparticles were 88 and 105 nm, respectively with a drug loading of 24.08%, drug encapsulation rate of 94.72%, and the yield of silibinin-HSA nanoparticles of around 83.41% and the HSA nano-formulation released silibinin for 15 h. The results displayed that cell viability was reduced by LPS (10 µg/mL), who's also determined to stimulate oxidative stress and apoptosis. However, co-incubation of cells with silibinin (50 µg/mL) or silibinin-HSA nanoparticles led to the recovery of cell viability, activation of SOD and CAT, increase of GSH content, and reduction of ROS level, Caspase-3 activity and fragmentation of DNA. It was also indicated that the neuroprotective and antioxidant activities of silibinin-HAS nanoparticles was greater than free silibinin, indicating that using albumin can be a potential formulation approach for improving the antioxidant efficacy of silibinin.


Assuntos
Doença de Alzheimer , Nanopartículas , Silimarina , Albuminas , Doença de Alzheimer/tratamento farmacológico , Linhagem Celular Tumoral , Humanos , Nanopartículas/toxicidade , Estresse Oxidativo , Silibina , Silimarina/farmacologia
7.
Toxins (Basel) ; 13(6)2021 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064255

RESUMO

The present study was designed to determine the efficacy of a novel multicomponent mycotoxin detoxifying agent (MMDA) containing modified zeolite (Clinoptilolite), Bacillus subtilis, B. licheniformis, Saccharomyces cerevisiae cell walls and silymarin against the deleterious effects of Aflatoxin B1 (AFB1) and Ochratoxin A (OTA) in broiler chicks. A total of 160 one-day-old Ross 308® broiler chicks were randomly allocated in four treatment groups, with four replicates, according to the following experimental design for 42 days. Group A received a basal diet; Group B received a basal diet contaminated with AFB1 and OTA at 0.1 mg/kg and 1 mg/kg, respectively; Group C received a basal diet contaminated with AFB1 and OTA and MMDA at 1 g/kg feed, and Group D received a basal diet contaminated with AFB1 and OTA and MMDA at 3 g/kg feed. Results showed that ingested mycotoxins led to significant (p ≤ 0.05) reduction in body weight and feed conversion from 25 days of age, induced histopathological changes, increased the pH of the intestinal content, and altered the biochemical profile of birds with significantly (p ≤ 0.05) increased aspartate aminotransferase (AST) values (p ≤ 0.05). On the other hand, the supplementation of MMDA significantly (p ≤ 0.05) improved the feed conversion ratio (FCR) during the second part of the study, diminished biochemical alterations, reduced pH in jejunal and ileal content, and E. coli counts in the caeca of birds (p ≤ 0.05). It may be concluded that the dietary supplementation of the MMDA partially ameliorated the adverse effects of AFB1 and OTA in broilers and could be an efficient tool in a mycotoxin control program.


Assuntos
Aflatoxina B1/envenenamento , Micotoxicose/tratamento farmacológico , Ocratoxinas/envenenamento , Silimarina/administração & dosagem , Zeolitas/administração & dosagem , Ração Animal , Animais , Bacillus licheniformis , Bacillus subtilis , Galinhas , Micotoxicose/metabolismo , Micotoxicose/patologia , Distribuição Aleatória , Saccharomyces cerevisiae
8.
Environ Sci Pollut Res Int ; 28(41): 57997-58006, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34100211

RESUMO

This study assessed prophylactic potentials of silymarin against lead-induced hepatorenal toxicity in rats with the respect to its antioxidant and anti-apoptotic activities. Forty male albino rats were distributed into four groups. Control group is provided with distilled water. Lead acetate group was given lead acetate (100 mg/kg bwt) orally for 10 weeks. The third and fourth groups administered silymarin at doses of 50 or 100 mg/kg bwt, respectively, 1 h before administration of lead acetate for 10 weeks. Lead acetate altered liver structure and function that represented by significant elevation of the activities of serum aspartate and alanine aminotransferases and serum levels of urea and creatinine. Hepatic and renal tissues' malondialdehyde concentrations were increased, while reduced glutathione content and superoxide dismutase and catalase activities were reduced in the lead acetate group. Also, lead acetate increased caspase-3 mRNA expression and inhibited alpha-fetoprotein mRNA expression in hepatic tissues, as well as it altered liver and kidney tissues' architectures. In contrast, silymarin ameliorated in a dose dependent mannar the toxic effects of lead acetate on the liver and kidneys through modulation of lead acetate which altered liver and kidney function and structures via reducing lipid oxidation and pathological changes of hepatic and renal tissue structure, improving antioxidant defense system of liver and kidneys, and decreasing pro-apoptotic gene expression in hepatic tissue. This study indicated that silymarin ameliorated lead acetate-induced hepatorenal toxicity via its antioxidant and cytoprotective potentials.


Assuntos
Antioxidantes , Silimarina , Animais , Antioxidantes/metabolismo , Glutationa/metabolismo , Rim/metabolismo , Chumbo/metabolismo , Peroxidação de Lipídeos , Fígado/metabolismo , Masculino , Estresse Oxidativo , Ratos , Silimarina/metabolismo , Silimarina/farmacologia
9.
J Biochem Mol Toxicol ; 35(8): e22800, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33934443

RESUMO

Multiple sclerosis (MS) is a chronic disease that affects the central nervous system and is characterized by inflammation, demyelination, and degenerative changes. Relapsing-remitting MS (RRMS) is the most common form of MS. Fingolimod (FTY720) is a once-daily disease-modifying agent approved to treat RRMS, and it binds to sphingosine 1-phosphate receptors. Milk thistle (silybum marianum; SM) is an herb generally used to protect the liver with antioxidant and antifibrotic effects. The purpose of this study was to evaluate the effects of silymarin on reducing liver complications of FTY720 in patients with RRMS and decrease the oxidative stress that plays an important role in the pathogenesis of this disease. Forty-eight patients with RRMS were divided into two groups using random assignment: the placebo and drug-treated groups. Participants of intervention and control groups took FTY720 with silymarin and placebo without silymarin per day for six months. Findings showed a significant reduction in the level of ALT and AST, reduction of main pathogenic factors in MS containing malondialdehyde, and also a significant rise in total antioxidant capacity, and total thiol groups in the serum of patients treated with silymarin as compared with the placebo group. Our outcomes propose the practical effects of silymarin in multiple sclerosis and reduction of hepatic side effects of fingolimod.


Assuntos
Antioxidantes/administração & dosagem , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Cloridrato de Fingolimode , Esclerose Múltipla/sangue , Esclerose Múltipla/tratamento farmacológico , Adulto , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Método Duplo-Cego , Feminino , Cloridrato de Fingolimode/administração & dosagem , Cloridrato de Fingolimode/efeitos adversos , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva , Silimarina
10.
Biomed Pharmacother ; 139: 111673, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33965729

RESUMO

Zingiber roseum is native to Bangladesh and widely used in folk medicine. This present study was designed to assess the ameliorative potential of Zingiber roseum rhizome extract in carbon tetrachloride (CCl4) induced hepatotoxicity in mice model. Seven phenolic compounds were identified and quantified by HPLC analysis in the plant extract, including quercetin, myricetin, catechin hydrate, trans-ferulic acid, trans-cinnamic acid, (-) epicatechin, and rosmarinic acid. Hepatotoxicity was induced by administrating a single intraperitoneal injection of CCl4 (10 mL/kg) on 7th day of treatment. The results revealed that plant extract at all doses (100, 200 and 400 mg/kg) significantly reduced (p < 0.05) the elevated serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) concentrations, and these effects were comparable to that of standard drug silymarin. Histopathological examination also revealed the evidence of recovery from CCL4 induced cellular damage when pretreated with Z. roseum rhizome extract. The in-vivo hepatoprotective effects were further investigated by the in-silico study of the aforementioned compounds with liver-protective enzymes such as superoxide dismutase (SOD), peroxiredoxin, and catalase. The strong binding affinities (ranging from -7.3359 to -9.111 KCal/mol) between the phenolic compounds (except trans-cinnamic acid) and oxidative stress enzymes inhibit ROS production during metabolism. The compounds were also found non-toxic in computational prediction, and a series of biological activities like antioxidant, anticarcinogen, cardio-protectant, hepato-protectant have been detected.


Assuntos
Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Polifenóis/química , Polifenóis/farmacologia , Rizoma/química , Zingiberaceae/química , Animais , Intoxicação por Tetracloreto de Carbono/patologia , Catalase/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Cromatografia Líquida de Alta Pressão , Feminino , Fígado/enzimologia , Fígado/patologia , Testes de Função Hepática , Camundongos , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , Peroxirredoxinas/metabolismo , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Espécies Reativas de Oxigênio , Silimarina/uso terapêutico , Superóxido Dismutase/metabolismo
11.
Gene ; 790: 145700, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-33964378

RESUMO

The aim of this study was to investigate secondary metabolite production in Silybum marianum L. cell suspension cultures obtained from seeds treated with gamma rays (200 and 600 Gy) and 0.05% colchicine. The effects of these treatments on callus induction, growth, viability, and silymarin production were studied, along with the changes in the transcriptome and DNA sequence of chalcone synthase (CHS) genes. The effect of gamma radiation (200 and 600 Gy) on silymarin production in S. marianum dry seeds was also studied using HPLC-UV. All three treatments induced high callus biomass production from leaf segments. The viability of the cell suspension cultures was over 90%. The flavonolignan content measured in the extracellular culture medium of the S. marianum cell suspension was highest after treatment with 600 Gy, followed by 0.05% colchicine, and finally, 200 Gy, after a growth period of 12 days. In general, an increased expression of CHS1, CHS2, and CHS3 genes, accompanied by an increase of silymarin content, was observed in response to all the studied treatments, although the effect was greatest on CHS2 expression. Bioinformatics analysis confirmed that the three CHS2 clones exhibited the highest genetic variation, both in relation to each other and to the CHS1 and CHS3 clones. Based on the results, S. marianum plants obtained from seeds previously exposed to 600 and 200 Gy as well as colchicine constitute a renewable resource with the potential to obtain large amounts of silymarin.


Assuntos
Colchicina/farmacologia , Raios gama , Regulação da Expressão Gênica de Plantas , Cardo-Mariano/metabolismo , Silimarina/metabolismo , Transcriptoma/efeitos dos fármacos , Transcriptoma/efeitos da radiação , Vias Biossintéticas , Biologia Computacional , Cardo-Mariano/efeitos dos fármacos , Cardo-Mariano/genética , Cardo-Mariano/efeitos da radiação , Moduladores de Tubulina/farmacologia
12.
Oncol Res ; 28(7): 801-809, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34030768

RESUMO

Irinotecan, a topoisomerase inhibitor, is a common cytotoxic agent prescribed for metastatic colorectal cancer (mCRC) patients. Diarrhea is the most common adverse event (AE). The underlying mechanism of irinotecan-induced diarrhea is intestinal mucosal damage caused by SN-38 (active metabolite of irinotecan) hydrolyzed from SN-38G (inactive metabolite) by bacterial -glucuronidase (G). According to an animal study, silymarin reduces the activity of bacterial G without impairing antitumor efficacy. We conducted a prospective open-label pilot study to evaluate the effect of silymarin as supplementation in reducing toxicities of mCRC patients undergoing irinotecan-based chemotherapy. We enrolled and randomized 70 mCRC patients receiving first-line FOLFIRI (5-fluorouracil/leucovorin/irinotecan) plus bevacizumab. In each treatment cycle, the study group was administered silymarin capsules (150 mg) three times daily for 7 days. The study group experienced less AEs in diarrhea (5.7% vs. 14.6%, p=0.002) and nausea (27.0% vs. 40.2%, p=0.005) in comparison with the control group, but no significant differences in hepatic toxicities were observed. In conclusion, simultaneous administration of silymarin is a potential effective supplementation for reducing toxicities in mCRC patients undergoing first-line FOLFIRI plus bevacizumab, especially in diarrhea and nausea.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , Silimarina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Diarreia/etiologia , Suplementos Nutricionais , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Irinotecano/efeitos adversos , Irinotecano/uso terapêutico , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/etiologia , Projetos Piloto , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
13.
Drug Des Devel Ther ; 15: 1903-1914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33976540

RESUMO

Aim: Silymarin contains various flavonoids and exhibits antioxidative, anti-inflammatory, and anticancer effects, in addition to other pharmacological properties. This study explored the alleviating effect of silymarin on multiple-organ damage induced by D-galactose/lipopolysaccharide in Kunming mice. Methods: Kunming mice were injected intraperitoneally with D-galactose (30 mg/kg·BW)/LPS (3 µg/kg·BW) and then treated using silymarin with different doses (75 mg/kg·bw and 150 mg/kg·bw) via intragastric administration. Changes in organ indexes, pathological changes, liver-function index, biochemical indexes, molecular biological indexes, and genes related to the oxidation and inflammation of main organs were evaluated. Results: After the mice were treated with silymarin, their body weight showed no significant change, and the liver, kidney, and lung indexes of the treated mice were higher than those of the model group; meanwhile, the corresponding histopathological formation was reduced. Compared with the model group, the silymarin-treated group showed reductions in ALT, AST, and liver function indexes in the mouse serum. Silymarin treatment also increased the SOD, CAT, GSH, GSH-Px, T-AOC, IL-10, and IL-12 levels, as well as reduced the MDA, NO, IL-6, IL-1ß, TNF-α, IFN-γ levels in the mouse serum and liver tissues. In addition, quantitative polymerase chain reaction analysis indicated that the mRNA expression levels of SOD1, SOD2, CAT, GSH-Px, IL-10, Nrf2, HO-1, NQO1, Trx, and IκB-α were higher in the liver tissue of the silymarin-treated mice than in those of the model group; meanwhile, the mRNA expression levels of IL-6, IL-1ß, TNF-α, IFN-γ, NF-κB, NLRP3, COX2, and p38 were lower than those in the model group. Conclusion: Silymarin, which exhibits antioxidative and anti-inflammatory effects, can alleviate the liver, lung, and kidney damage induced by D-galactose/lipopolysaccharide. High-dose (150 mg/kg·bw) silymarin can more effectively inhibit organ damage, compared with low-dose silymarin (75 mg/kg·bw) in Kunming mice.


Assuntos
Galactose/antagonistas & inibidores , Inflamação/tratamento farmacológico , Lipopolissacarídeos/antagonistas & inibidores , Fígado/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Administração Oral , Animais , Inflamação/induzido quimicamente , Masculino , Camundongos , Camundongos Endogâmicos , Substâncias Protetoras/administração & dosagem , Silimarina/administração & dosagem
14.
Toxicol In Vitro ; 74: 105162, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33839235

RESUMO

Silymarin is a flavonoid complex isolated from the plant Silybum marianum which is well known for its antioxidant, hepatoprotective and immunomodulatory effects. Since little is known about its anti-inflammatory properties and healing effects, our study focused on whether or not silymarin components reduce inflammation and support epidermis regeneration. Lipopolysaccharides (LPS) and sodium dodecyl sulfate (SDS) were used to induce inflammation in normal human epidermal keratinocytes (NHEKs) and reconstructed epidermis (RHE), respectively. The expression of pro-inflammatory cytokines (IL-1, IL-6 and IL-8) in NHEKs and RHE was measured by enzyme - linked immunosorbent assay (ELISA). The expression of cytokeratin 14 and loricrin in RHE was detected by immunofluorescent analysis. Hematoxylin and eosin staining was used for the morphological evaluation of RHE. It was determined that 2, 3 - dehydrosilybin (DHSB) downregulated the production of selected pro-inflammatory cytokines produced by NHEKs. Although all layers of RHE displayed full thickness, when SDS was applied, cell detachment was seen in the stratum corneum and loricrin expression was diminished.


Assuntos
Anti-Inflamatórios/farmacologia , Epiderme/efeitos dos fármacos , Queratinócitos/efeitos dos fármacos , Quercetina/farmacologia , Silimarina/farmacologia , Citocinas/metabolismo , Epiderme/metabolismo , Humanos , Inflamação/induzido quimicamente , Queratina-14/metabolismo , Queratinócitos/metabolismo , Lipopolissacarídeos/toxicidade , Proteínas de Membrana/metabolismo , Dodecilsulfato de Sódio/toxicidade
15.
Molecules ; 26(5)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807773

RESUMO

In late 2019, a global pandemic occurred. The causative agent was identified as a member of the Coronaviridae family, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we present an analysis on the substances identified in the human metabolome capable of binding the active site of the SARS-CoV-2 main protease (Mpro). The substances present in the human metabolome have both endogenous and exogenous origins. The aim of this research was to find molecules whose biochemical and toxicological profile was known that could be the starting point for the development of antiviral therapies. Our analysis revealed numerous metabolites-including xenobiotics-that bind this protease, which are essential to the lifecycle of the virus. Among these substances, silybin, a flavolignan compound and the main active component of silymarin, is particularly noteworthy. Silymarin is a standardized extract of milk thistle, Silybum marianum, and has been shown to exhibit antioxidant, hepatoprotective, antineoplastic, and antiviral activities. Our results-obtained in silico and in vitro-prove that silybin and silymarin, respectively, are able to inhibit Mpro, representing a possible food-derived natural compound that is useful as a therapeutic strategy against COVID-19.


Assuntos
Antivirais/farmacologia , Proteases 3C de Coronavírus/metabolismo , Metaboloma , Inibidores de Proteases/farmacologia , SARS-CoV-2/enzimologia , Silimarina/farmacologia , Antivirais/química , Antivirais/metabolismo , Sítios de Ligação , COVID-19/tratamento farmacológico , Domínio Catalítico/efeitos dos fármacos , Simulação por Computador , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/química , Bases de Dados de Compostos Químicos , Descoberta de Drogas , Ensaios Enzimáticos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Inibidores de Proteases/química , Inibidores de Proteases/metabolismo , SARS-CoV-2/efeitos dos fármacos , Silimarina/química , Silimarina/metabolismo , Software
16.
Life Sci ; 277: 119460, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811899

RESUMO

BACKGROUND AND AIMS: The normal functioning of Kelch-like ECH-associated protein-1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) complex is necessary for the cellular protection against oxidative stress. We investigated the effect of chlorogenic acid (CGA), quercetin (Qt), coenzyme Q10 (Q10) and silymarin on the expression of Keap1/Nrf2 complex and its downstream target; heme oxygenase-1 (HO-1) as well as inflammation and apoptosis in an acute liver toxicity model induced by thioacetamide (TAA). MAIN METHODS: Wistar rats were divided into 13 groups: Control, silymarin, CGA, Qt, Q10, TAA (single dose 50 mg/kg, i.p.), TAA + silymarin (400 mg/kg, p.o.), TAA + CGA (100 & 200 mg/kg, p.o.), TAA + Qt (200 &300 mg/kg, p.o.) and TAA+ Q10 (30&50 mg/kg, p.o.) and treated for 8 days. KEY FINDINGS: The results showed improved liver functions and hepatic tissue integrity in all tested doses of TAA + silymarin, TAA + CGA, TAA + Qt and TAA + Q10 groups compared to the TAA group. Furthermore, these groups showed significantly lower ROS, malondialdehyde and nitric oxide levels but higher glutathione content and superoxide dismutase activity compared to the TAA group, p < 0.05. In these groups, Keap1 expression was significantly decreased while Nrf2 expression and HO-1 activity were increased. In addition, the number of apoptotic cells and the expression level of TNF-α in the liver tissues were significantly decreased compared to the TAA group. SIGNIFICANCE: CGA, Qt, Q10 and silymarin protect against TAA-induced acute liver toxicity via antioxidant, anti-inflammatory, anti-apoptotic activities and regulating Keap1-Nrf2/HO-1 expression.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Heme Oxigenase (Desciclizante)/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Ácido Clorogênico/metabolismo , Ácido Clorogênico/farmacologia , Heme Oxigenase (Desciclizante)/fisiologia , Heme Oxigenase-1/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/fisiologia , Fígado/metabolismo , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/fisiologia , Quercetina/metabolismo , Quercetina/farmacologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Silimarina/metabolismo , Silimarina/farmacologia , Tioacetamida/efeitos adversos , Tioacetamida/farmacologia , Tioacetamida/toxicidade , Ubiquinona/análogos & derivados , Ubiquinona/metabolismo , Ubiquinona/farmacologia
17.
Trop Biomed ; 38(1): 22-27, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33797519

RESUMO

This work was carried out to investigate the effect of silymarin combination in the therapeutic plane of schistosomiasis with praziquantel or mirazid to enhance the liver and reduce fibrosis. Mice were divided into 2 main groups, the 1st uninfected group served as control and the 2nd group infected subcutaneously with 60 cercaria of S. mansoni per each. The infected group was subdivided into 5 subgroups, the 1st kept untreated, the 2nd and 3rd treated at the 7th week of infection with (600 mg/kg) of PZQ orally for 3 consecutive days, while the 3rd treated also orally with (150 mg/kg) of silymarin daily for 11 weeks. The 4th and 5th groups treated orally at the 7th week of infection with 600 mg/kg of MZ for 3 consecutive days, while the 5th group treated orally also with 150 mg/kg of silymarin daily for 11weeks. IgG determination showed high level in the untreated infected group. Furthermore, the infected groups treated with PZQ and PZQ with silymarin displayed the lower levels than treated with MZ. Additionally, the untreated infected group showed severe pathological changes as hyaline degeneration, inflammation, presence of worm burdens in dilated portal veins, granulomas as well as depositions of collagenous and reticular fibers indicated intense fibrosis. Treatment with PZQ alone resulted in reduction of pathological signs and decreasing of granulomas. Combination with silymarin to PZQ therapy revealed more improvement for liver besides to lowering of granulomas areas and volumes and decreasing of fibrosis. Whereas, treatment with MZ was less effective than PZQ to reduce granulomas areas, volumes and fibrosis. Although, combination of silymarin to MZ treatment resulted in more curative signs and reduction of granulomas areas, volumes and fibrosis. Furthermore, the present study concluded that PZQ still the more effective drug of schistosomiasis treatment than MZ. The silymarin is very useful in schistosomiasis treatment when combined with PZQ or MZ due to its anti-fibrotic effect.


Assuntos
Praziquantel/farmacologia , Resinas Vegetais/farmacologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomicidas/farmacologia , Silimarina/farmacologia , Animais , Quimioterapia Combinada , Granuloma/tratamento farmacológico , Granuloma/parasitologia , Fígado/parasitologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/parasitologia , Masculino , Camundongos
18.
Phytother Res ; 35(8): 4246-4257, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33817867

RESUMO

Coronavirus disease 2019 (COVID-19) triggered by a new viral pathogen, named severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), is now a global health emergency. This debilitating viral pandemic not only paralyzed the normal daily life of the global community but also spread rapidly via global travel. To date there are no effective vaccines or specific treatments against this highly contagious virus; therefore, there is an urgent need to advocate novel prophylactic or therapeutic interventions for COVID-19. This brief opinion critically discusses the potential of Silymarin, a flavonolignan with diverse pharmacological activity having antiinflammatory, antioxidant, antiplatelet, and antiviral properties, with versatile immune-cytokine regulatory functions, that able to bind with transmembrane protease serine 2 (TMPRSS2) and induce endogenous antiviral cytokine interferon-stimulated gene 15, for the management of COVID-19. Silymarin inhibits the expression of host cell surface receptor TMPRSS2 with a docking binding energy corresponding to -1,350.61 kcal/mol and a full fitness score of -8.11. The binding affinity of silymarin with an impressive virtual score exhibits significant potential to interfere with SARS-CoV-2 replication. We propose in-depth pre-clinical and clinical review studies of silymarin for the development of anti-COVID-19 lead, based on its clinical manifestations of COVID-19 and multifaceted bioactivities.


Assuntos
Antivirais , COVID-19 , Silimarina , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , COVID-19/prevenção & controle , Humanos , Pandemias , SARS-CoV-2/efeitos dos fármacos , Silimarina/farmacologia , Silimarina/uso terapêutico
19.
Biomolecules ; 11(3)2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33801090

RESUMO

For maize, the potential preventive role of foliar spraying with an extract derived from maize grain (MEg, 2%), silymarin (Sm, 0.5 mM), or silymarin-enriched MEg (MEg-Sm) in attenuating the stress effects of cadmium (Cd, 0.5 mM) was examined using a completely randomized design layout. Under normal conditions, foliar spraying with MEg, Sm, or MEg-Sm was beneficial (with MEg-Sm preferred) for maize plants, whereas the benefit was more pronounced under Cd stress. The use of Cd through irrigation water decreased plant growth traits, photosynthetic efficiency, including instantaneous carboxylation efficiency, Fv/Fm, and pigment contents, and hormonal contents (e.g., auxin, gibberellins, cytokinins including trans-zeatin, and salicylic acid). These undesired findings were due to an increase in Cd content, leading to increased levels of oxidative stress (O2•- and H2O2), ionic leakage, and lipid peroxidation. Therefore, this damage resulted in an increase in the activities of nonenzymatic antioxidants, Sm, antioxidative enzymes, and enzyme gene expression. However, under Cd stress, although foliar spray with MEg or Sm had better findings than control, MEg-Sm had better findings than MEg or Sm. Application of MEg-Sm greatly increased photosynthesis efficiency, restored hormonal homeostasis, and further increased the activities of various antioxidants, Sm, antioxidative enzymes, and enzyme gene expression. These desired findings were due to the suppression of the Cd content, and thus the levels of O2•-, H2O2, ionic leakage, and lipid peroxidation, which were positively reflected in the growth and accumulation of dry matter in maize plants. The data obtained in this study recommend applying silymarin-enriched maize grain extract (MEg-Sm at 0.24 g Sm L-1 of MEg) as a spray solution to maize plants when exposed to excess Cd in soil or irrigation water.


Assuntos
Cádmio/toxicidade , Extratos Vegetais/farmacologia , Silimarina/farmacologia , Zea mays/efeitos dos fármacos , Zea mays/metabolismo , Antioxidantes/metabolismo , Clorofila/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fotossíntese/efeitos dos fármacos
20.
Int J Mol Sci ; 22(4)2021 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-33670070

RESUMO

The present study aimed to investigate the enzymatic potential of Silybum marianum leaves to bioconvert phenolic acids produced in S. marianum callus into silymarin derivatives as chemopreventive agent. Here we demonstrate that despite the fact that leaves of S. marianum did not accumulate silymarin themselves, expanding leaves had the full capacity to convert di-caffeoylquinic acid to silymarin complex. This was proven by HPLC separations coupled with electrospray ionization mass spectrometry (ESI-MS) analysis. Soaking the leaf discs with S. marianum callus extract for different times revealed that silymarin derivatives had been formed at high yield after 16 h. Bioconverted products displayed the same retention time and the same mass spectra (MS or MS/MS) as standard silymarin. Bioconversion was achieved only when using leaves of a specific age, as both very young and old leaves failed to produce silymarin from callus extract. Only medium leaves had the metabolic capacity to convert callus components into silymarin. The results revealed higher activities of enzymes of the phenylpropanoid pathway in medium leaves than in young and old leaves. It is concluded that cotyledon-derived callus efficiently produces compounds that can be bio-converted to flavonolignans in leaves tissue of S. marianum.


Assuntos
Cardo-Mariano/química , Compostos Fitoquímicos/farmacologia , Folhas de Planta/química , Silimarina/farmacologia , Extratos Vegetais/química , Folhas de Planta/enzimologia , Espectrometria de Massas por Ionização por Electrospray , Temperatura
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