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1.
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
2.
J Ethnopharmacol ; 265: 113303, 2021 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32877720

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Silybum marianum (L.) Gaertn. or Milk thistle is a medicinal plant native to Northern Africa, Southern Europe, Southern Russia and Anatolia. It also grows in South Australia, North and South America. In traditional knowledge, people have used S. marianum for liver disorders such as hepatitis, liver cirrhosis and gallbladder diseases. The main active compound of the plant seeds is silymarin, which is the most commonly used herbal supplement in the United States for liver problems. Nowadays, S. marianum products are available as capsules, powders, and extracts. AIM OF STUDY: The aim of our study is to draw a more comprehensive overview of the traditional heritage, pharmacological benefits and chemical fingerprint of S. marianum extracts and metabolites; as well as their metabolism and bioavailability. MATERIALS AND METHODS: An extensive literature search has been conducted using relavant keywords and papers with rationale methodology and robust data were selected and discussed. Studies involving S. marianum or its main active ingredients with regards to hepatoprotective, antidiabetic, cardiovascular protection, anticancer and antimicrobial activities as well as the clinical trials performed on the plant, were discussed here. RESULTS: S. marianum was subjected to thousands of ethnopharmacological, experimental and clinical investigations. Although, the plant is available for use as a dietary supplement, the FDA did not yet approve its use for cancer therapy. Nowadays, clinical investigations are in progress where a global evidence of its real efficiency is needed. CONCLUSION: S. marianum is a worldwide used herb with unlimited number of investigations focusing on its benefits and properties, however, little is known about its clinical efficiency. Moreover, few studies have discussed its metabolism, pharmacokinetics and bioavailability, so that all future studies on S. marianum should focus on such areas.


Assuntos
Cardo-Mariano/química , Extratos Vegetais/farmacologia , Silimarina/farmacologia , Animais , Suplementos Nutricionais , Etnofarmacologia , Humanos , Medicina Tradicional , Sementes , Silimarina/isolamento & purificação
3.
Biomed Environ Sci ; 33(9): 690-700, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-33106214

RESUMO

Objective: To evaluate the efficiency of silymarin (SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus (T1DM). Methods: Diabetes was induced by intraperitoneal injection of alloxan. The diabetic rats were administered with SMN at doses of 50 and 100 mg/kg body weight/d for 30 consecutive days. The rats were divided into the following four groups: vehicle control, diabetic (alloxan-treated), DS50 (alloxan + 50 mg/kg body weight/d of SMN), and DS100 (alloxan + 100 mg/kg body weight/d of SMN) groups. The bodyweight and food and water intake were evaluated. After 30 d, the animals were euthanized and the blood was collected for measuring the serum levels of glucose, triacylglycerol (TAG), urea, and creatinine. The liver and pancreas were collected for measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of carbonylated protein (PC). The pancreas sample was also used for histological analysis. Results: SMN reduced hepatic ( P < 0.001) and pancreatic ( P < 0.001) protein damage and creatinine levels ( P = 0.0141) in addition to decreasing food ( P < 0.001) and water intake ( P < 0.001). However, treatment with SMN did not improve beta-cell function or decrease blood glucose levels in diabetic rats. Conclusion: SMN improved polyphagia and polydipsia, renal function, and protected the liver and pancreas against protein damage without affecting hyperglycemia in diabetic animals.


Assuntos
Antioxidantes/farmacologia , Diabetes Mellitus Experimental/metabolismo , Fígado/metabolismo , Pâncreas/metabolismo , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Aloxano/farmacologia , Animais , Diabetes Mellitus Tipo 1/metabolismo , Fígado/efeitos dos fármacos , Oxirredução , Pâncreas/efeitos dos fármacos
4.
Phytomedicine ; 79: 153320, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32920285

RESUMO

BACKGROUND: Neurodegenerative diseases (NDDs) are primarily characterized by selective neuronal loss in the brain. Alzheimer's disease as the most common NDDs and the most prevalent cause of dementia is characterized by Amyloid-beta deposition, which leads to cognitive and memory impairment. Parkinson's disease is a progressive neurodegenerative disease characterized by the dramatic death of dopaminergic neuronal cells, especially in the SNc and caused alpha-synuclein accumulation in the neurons. Silymarin, an extract from seeds of Silybum marianum, administered mostly for liver disorders and also had anti-oxidant and anti-carcinogenic activities. PURPOSE: The present comprehensive review summarizes the beneficial effects of Silymarin in-vivo and in-vitro and even in animal models for these NDDs. METHODS: A diagram model for systematic review is utilized for this search. The research is conducted in the following databases: PubMed, Web of Science, Scopus, and Science Direct. RESULTS: Based on the inclusion criteria, 83 studies were selected and discussed in this review. CONCLUSION: Lastly, we review the latest experimental evidences supporting the potential effects of Silymarin, as a neuroprotective agent in NDDs.


Assuntos
Doenças Neurodegenerativas/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Silimarina/farmacologia , Doença de Alzheimer/tratamento farmacológico , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Humanos , Transtornos da Memória/tratamento farmacológico , Cardo-Mariano/química , Estresse Oxidativo/efeitos dos fármacos , Doença de Parkinson/tratamento farmacológico
5.
Toxicon ; 185: 97-103, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32622693

RESUMO

Mycotoxins are toxic secondary metabolites produced by fungus which cause worldwide concern regarding food and feed safety. Ochratoxin A (OTA), fumonisin B1 (FB1) and deoxynivalenol (DON) are some of the main mycotoxins and oxidative stress is the main mechanism of toxicity. Thereby, this study investigates the in vitro cytoprotective effects of curcumin (CUR) and silymarin (SIL) - known for their strong antioxidant activity - in PK-15 cells exposed to OTA, FB1 and DON. Pretreatment with CUR and SIL enhanced the viability of cells exposed to the mycotoxins (P < 0.001) and attenuated reactive oxygen species (ROS) formation by DON (P < 0.01), partially reduced ROS formation by FB1 (P < 0.001), but not OTA. CUR significantly decreased apoptosis in cells exposed to DON (P < 0.01) but was not able to prevent apoptosis in cells exposed to OTA and FB1. Whereas SIL was able to prevent apoptosis in PK-15 cells exposed to FB1 and DON (P < 0.01) but was not able to decrease apoptosis in cells exposed to OTA. In summary, these data indicate that curcumin and silymarin are able to provide cytoprotection against toxicity induced by OTA, FB1 and DON in PK-15 cells.


Assuntos
Curcumina/farmacologia , Micotoxinas/toxicidade , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Apoptose , Sobrevivência Celular , Fumonisinas/toxicidade , Fungos , Ocratoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Tricotecenos/toxicidade
6.
An Acad Bras Cienc ; 92(1): e20191121, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32428092

RESUMO

Cadmium, present in the environment, accumulates in different organs of animals and humans, and has deleterious effects on the kidney. In this study, we investigated the protective effects of the methanolic extract of Pleurotus ostreatus in comparison with silymarin on renal function in cadmium-intoxicated rats for five days. Rats intraperitoneally injected with cadmium chloride (1 mg/kg). These rats were treated with either P. ostreatus extract (200 mg/kg) or silymarin to investigate the protective effects of the extract. Cadmium treatment induced significant histopathological impairments and increased cadmium levels, DNA fragmentation, and renal oxidative stress. However, treatment with P. ostreatus extract or silymarin improved the pathology, reduced the level of cadmium in renal tissue, and restored DNA fragmentation. In addition, a significant reduction in lipid peroxidation and reactive oxygen species levels, and a significant increase in the levels of glutathione and catalase activity were observed. Thus, protective effects of P. ostreatus extract to its components. Chromatographic analysis of the P. ostreatus confirmed the presence of five phenolics (gallic acid, chlorogenic acid, catechin, propyl gallate, and cinnamic acid) that exhibit strong antioxidant properties as free radical scavengers. Therefore, our findings demonstrate that treatment with P. ostreatus extract protects against cadmium-induced nephrotoxicity in female rats.


Assuntos
Antioxidantes/farmacologia , Cloreto de Cádmio/toxicidade , Rim/efeitos dos fármacos , Extratos Vegetais/farmacologia , Pleurotus/química , Silimarina/farmacologia , Animais , Apoptose/efeitos dos fármacos , Cloreto de Cádmio/análise , Feminino , Rim/patologia , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Ratos
7.
BMC Complement Med Ther ; 20(1): 97, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32293397

RESUMO

BACKGROUND: The hand, foot and mouth disease (HFMD) is a febrile and exanthematous childhood disease mainly caused by Enterovirus 71 (EV-A71). In severe HFMD, virulent EV-A71 strains can cause acute flaccid paralysis and cardiopulmonary edema leading to death. Currently, no FDA approved antiviral treatment or vaccine is available for EV-A71. Flavonoids such as silymarin and baicalein are known to possess in vitro antiviral properties against viruses. In this study, the cytotoxicity and antiviral activity of silymarin, baicalein and baicalin were investigated. METHODS: The cytotoxic effects of three flavonoids towards rhabdomyosarcoma (RD) cells were first examined using cell proliferation MTS [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium] assay. Compounds found to be non-cytotoxic in RD cells were evaluated for their in vitro antiviral properties against the EV-A71 subgenotype B4 strain 41 (5865/SIN/000009) using antiviral assays. Viral infectivity was determined by reduction of the formation of plaques in RD cells. For the measurement of RNA copy number, the real time quantitative reverse transcription PCR (qRT-PCR) was used. The most potent compound was further evaluated to determine the mode of action of inhibition by time course, virus attachment and entry assays in Vero cells. RESULTS: Silymarin was shown to exert direct extracellular virucidal effects against EV-A71 at 50% inhibitory concentration (IC50) of 15.2 ± 3.53 µg/mL with SI of 10.53. Similarly, baicalein exhibited direct extracellular virucidal effects against EV-A71 at a higher IC50 value of 30.88 ± 5.50 µg/mL with SI of 13.64. Besides virucidal activity, silymarin was shown to block both viral attachment and entry of EV-A71 to inhibit infection in Vero cells. CONCLUSIONS: Silymarin has a stronger inhibition activity against EV-A71 in comparison to baicalein. It could serve as a promising antiviral drug to treat EV-A71 infections.


Assuntos
Enterovirus Humano A/efeitos dos fármacos , Flavanonas/farmacologia , Flavonoides/farmacologia , Silimarina/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Chlorocebus aethiops , Humanos , Células Vero
8.
Biomol Concepts ; 11(1): 57-75, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32229652

RESUMO

Background Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine abnormalities in women. Due to the side effects of drugs, the tendency to use natural antioxidants and anti-inflammatory agents to regulate metabolism, hyperinsulinemia, and hyperlipidemia in PCOS patients has been increased. This review aimed to investigate the role of herbal substances on the treatment of PCOS. Methods The present review was carried out using keywords such as polycystic ovary syndrome and/or PCOS and/or herb. Databases including Web of Science, PubMed, and Science Direct were used to collect all related articles published from 1990 to 2019. We excluded studies unrelated to the PCOS and medical herbs. Results Overall, 361 records were identified through database searching. After primary screening and the full-texts assessment, 323 records were excluded, and 38 articles were finally included. The results indicate that some medicinal herbs may have a key role in treating PCOS. The compounds in these medical herbs can affect lipid profiles (Aloe vera, chamomile, and cinnamon), insulin resistance (cinnamon, chamomile, Aloe vera, and Camellia sinensis), blood glucose (Aloe vera, cinnamon, and Camellia sinensis), hormones (Aloe vera, silymarin, chamomile, fenugreek, Camellia sinensis, Heracleum persicum, Potentilla, Mentha spicata, Foeniculum vulgar, licorice, and Marrubium), and ovarian tissue (Aloe vera, chamomile, Camellia sinensis, Mentha spicata, and silymarin). Conclusion Natural substances such as Aloe vera, cinnamon, green tea, fenugreek, and silymarin can be used as a new supportive care for PCOS. Further clinical trials are warranted to confirm their benefits and safety.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Resistência à Insulina , Plantas Medicinais/química , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Aloe/química , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cinnamomum zeylanicum/química , Feminino , Humanos , Silimarina/química , Silimarina/farmacologia , Silimarina/uso terapêutico , Chá/química , Trigonella/química
9.
BMC Complement Med Ther ; 20(1): 70, 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32143600

RESUMO

BACKGROUND: Post-traumatic stress disorder (PTSD) is an extreme mood disorder that occurs after experiencing extreme stress, and patients with this disorder are known to accompany with symptoms of depression, anxiety, and memory impairments. Silibinin (SIL) is a natural polyphenolic flavonoid and is the main active ingredient of silymarin, which is primarily extracted from the milk thistle. Although some studies have assessed the properties of this flavonoid, the potential of SIL as a treatment for PTSD patients and its mechanisms of action have yet to be fully elucidated. METHODS: After exposure to a model of single prolonged stress (SPS), the open field test (OFT) and forced swimming test (FST), were used to investigate the effects of SIL on anxiety- and depression-like symptoms in male rats. The rats received of SIL (25, 50, and 100 mg/kg) for 14 days following exposure to SPS. RESULTS: Administration of SIL significantly improved anxiety-like behaviors in the OFT, depression-like behaviors in the FST, and freezing behavior in fear conditioning test. SIL also increased levels of serotonin in the hippocampus (Hipp) and amygdala, and enhanced expression of tryptophan hydroxylase-1 mRNA in the Hipp. The administration of SIL also inhibited SPS-induced decreases dopamine levels and increases norepinephrine levels in the Hipp. CONCLUSIONS: Taken together, the present findings suggest that SIL can be a useful therapeutic ingredient for the treatment of trauma stress-associated symptoms, including PTSD-induced anxiety and depression caused by PTSD.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtorno Depressivo/tratamento farmacológico , Silimarina/farmacologia , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Transtornos de Ansiedade/prevenção & controle , Transtorno Depressivo/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo
10.
Int J Mol Sci ; 21(6)2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32178401

RESUMO

BACKGROUND: Autophagy is reported as a survival or death-promoting pathway that is highly debatable in different kinds of cancer. Here, we examined the co-effect of cold atmospheric plasma (CAP) and silymarin nanoemulsion (SN) treatment on G-361 human melanoma cells via autophagy induction. METHODS: The temperature and pH of the media, along with the cell number, were evaluated. The intracellular glucose level and PI3K/mTOR and EGFR downstream pathways were assessed. Autophagy-related genes, related transcriptional factors, and autophagy induction were estimated using confocal microscopy, flow cytometry, and ELISA. RESULTS: CAP treatment increased the temperature and pH of the media, while its combination with SN resulted in a decrease in intracellular ATP with the downregulation of PI3K/AKT/mTOR survival and RAS/MEK transcriptional pathways. Co-treatment blocked downstream paths of survival pathways and reduced PI3K (2 times), mTOR (10 times), EGFR (5 times), HRAS (5 times), and MEK (10 times). CAP and SN co-treated treatment modulates transcriptional factor expressions (ZKSCAN3, TFEB, FOXO1, CRTC2, and CREBBP) and specific genes (BECN-1, AMBRA-1, MAP1LC3A, and SQSTM) related to autophagy induction. CONCLUSION: CAP and SN together activate autophagy in G-361 cells by activating PI3K/mTOR and EGFR pathways, expressing autophagy-related transcription factors and genes.


Assuntos
Autofagia/efeitos dos fármacos , Emulsões/farmacologia , Melanoma/tratamento farmacológico , Nanopartículas/administração & dosagem , Gases em Plasma/farmacologia , Silimarina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Humanos , Transdução de Sinais/efeitos dos fármacos
11.
Mol Cell Biochem ; 468(1-2): 129-142, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32185674

RESUMO

Fibrosis process in the liver is a clinical condition established in response to chronic lesions and may be reversible in many situations. In this process, hepatic stellate cells (HSCs) activate and produce extracellular matrix compounds. During fibrosis, the lipid metabolism is also altered and contributes to the transdifferentiation of the HSCs. Thus, controlling lipid metabolism in HSCs is suggested as a method to control or reverse the fibrotic condition. In the search for therapies that modulate lipid metabolism and treat liver diseases, silymarin has been identified as a relevant natural compound to treat liver pathologies. The present study aimed to evaluate the cellular and molecular effects of silymarin in the transdifferentiation process of HSCs (LX-2) from activated phenotype to a more quiesced-like cells , also focusing on understanding the modulatory effects of silymarin on lipid metabolism of HSCs. In our analyses, 100 µM of silymarin reduced the synthesis of actin filaments in activated cells, the synthesis of the protein level of α-SMA, and other pro-fibrotic factors such as CTGF and PFGF. The concentration of 150 µM silymarin did not reverse the activation aspects of LX-2 cells. However, both evaluated concentrations of the natural compound protected the cells from the negative effects of dimethyl sulfoxide (DMSO). Furthermore, we evaluated lipid-related molecules correlated to the transdifferentiation process of LX-2, and 100 µM of silymarin demonstrated to control molecules associated with lipid metabolism such as FASN, MLYCD, ACSL4, CPTs, among others. In contrast, cellular incubation with 150 µM of silymarin increased the synthesis of long-chain fatty acids and triglycerides, regarding the higher presence of DMSO (v/v) in the solvent. In conclusion, silymarin acts as a hepatoprotective agent and modulates the pro-fibrogenic stimuli of LX-2 cells, whose effects depend on stress levels in the cellular environment.


Assuntos
Transdiferenciação Celular/efeitos dos fármacos , Células Estreladas do Fígado/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Cirrose Hepática/metabolismo , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Actinas/genética , Actinas/metabolismo , Linhagem Celular , Cromatografia Gasosa , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Dimetil Sulfóxido/toxicidade , Ácido Graxo Sintase Tipo I/genética , Ácido Graxo Sintase Tipo I/metabolismo , Células Estreladas do Fígado/enzimologia , Células Estreladas do Fígado/metabolismo , Humanos , Fígado/metabolismo , Fígado/patologia , Cirrose Hepática/genética , Espectrometria de Massas , Triglicerídeos/metabolismo
12.
Med Oncol ; 37(3): 18, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-32062757

RESUMO

Among other cancers, prostate cancer is globally the second most rampant one with the incidence of 29.4% among men. SLIT2/ROBO1 signaling is very crucial pathway causally implicated in many cancers and reported to inhibit a variety of cancer cell types. CXCR4 is a chemokine receptor implicated in cancer progression. Silymarin is a phytochemical, of which anti-carcinogenic activity was suggested in various cancers, including prostate cancer. However, there are no studies examining the effect of silymarin on SLIT2-Robo1-CXCR4 axis. Herein, our goal is to explore cytotoxic and morphological effects of silymarin on DU145 cells and to reveal its role in Slit2/Robo and CXCR1 pathway. First, 24, 48 and 72 h-long cytotoxicity tests were performed for dose analysis of silymarin, followed H-E stain for morphological evaluation with varying doses of silymarin. Afterward, western blot and immunocytochemistry analyses were carried out for SLIT2, ROBO1 and CXCR4 proteins. According to MTT analysis, IC50 concentrations for silymarin were 315, 126 and 70 µM against DU145 cells for 24, 48 and 72 h treatments. In H-E, several apoptotic hallmarks, including, condensed, kidney-shaped and eccentric nuclei, membrane blebbings and apoptotic body formations were observed. Silymarin increased the expressions of SLIT2 and ROBO1 while decreased CXCR4 when compared to control group in immunocytochemistry and Western blot. To summarize, silymarin inhibited DU145 cells dose-dependently by activating SLIT2 protein and inhibiting expression of CXCR4. This study is the first examining the interplay between Slit2-Robo1-CXCR4 proteins and silymarin in DU145 cells. We believe that our study will provide new insights for future studies.


Assuntos
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores CXCR4/metabolismo , Silimarina/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Receptores Imunológicos/metabolismo , Transdução de Sinais/efeitos dos fármacos
13.
Pharmacol Rep ; 72(1): 199-207, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32016841

RESUMO

BACKGROUND: 14 million people are diagnosed with new cancer and approximately 8 million people die from cancer every year. Hepatocellular carcinoma is the most common type of liver cancer and covers almost 5-6% of cancer deaths worldwide. Silybum marianum, a plant that contains silymarin, has been used traditionally in the treatment of liver diseases for centuries. The antioxidant, anti-inflammatory and anti-fibrotic anti-cancer properties of silymarin have been demonstrated in several studies in vivo and in vitro. The Slit/Robo signaling pathway plays a role in many processes such as neurogenesis, angiogenesis, cell proliferation, cell movement, cancer progression, cell invasion, migration and metastasis. In this study, we aimed to investigate the effects of silymarin on HepG2 Hepatocellular carcinoma cells on Slit-2/Robo-1 signaling pathway and CXCR-4 which plays a role in the metastasis process. METHODS: HepG2 Hepatocellular carcinoma cells were used in the study. Different doses of silymarin's effect on HepG2 cells were observed by hematoxylin and eosin staining. Immunoblotting techniques were used to test the expression of Slit-2/Robo-1 and CXCR4 protein level. Immunocytochemistry was used to visualize the localization of Slit-2/Robo-1 and CXCR4 protein within the cells. RESULTS: Silymarin caused apoptosis in HepG2 cells, decreased the level of CXCR-4 protein dose-dependently, and decreased the Slit-2/Robo-1 protein level at low doses and increased it at high doses. CONCLUSIONS: Silymarin doses showed anti-carcinogenic, anti-metastatic and apoptotic effects in a dose-dependent manner on HepG2 cells through the Slit-2/Robo-1 pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Silimarina/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Neoplasias Hepáticas/patologia , Proteínas do Tecido Nervoso/genética , Receptores Imunológicos/genética , Transdução de Sinais/efeitos dos fármacos , Silimarina/administração & dosagem
14.
AAPS PharmSciTech ; 21(3): 81, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31974855

RESUMO

Myocardial infarction (MI) is the principal cause of death in many countries. Silymarin (SM) is a herbal antioxidant and can be efficiently used in preventing cardiovascular diseases (CVDs). The study is aimed to enhance the absorption rate and biological activity of SM by using liquisolids besides investigating the cardioprotective activity of SM and its selected liquisolid formula against isoproterenol prompted cardiotoxicity in rats. Eight formulae were prepared according to (23) full-factorial design. The effect of viscosity increasing agent type and concentration, as well as the carrier/coat ratio on the dissolution rate and angle of repose were studied. All formulae were tested for content uniformity, micromeritic properties, dissolution performance besides the evaluation of its physicochemical properties, and scanning electron microscopy (SEM). Based on the factorial design outcomes, the highest desirability was obtained from F3 with excipient ratio value (R) of 20%, dissolution rate at Q5 min of 26.9%, and angle of repose of 19. Oral administration of F3 liquisolid and SM revealed a significant protective efficacy against the modification of cardiac plasma markers, brain natriuretic peptide (BNP), interleukin-10 (IL-10), vascular endothelial growth factor (VEGF), and transforming growth factor (TGF)-ß1 besides cardiac superoxide dismutase (SOD), malondialdehyde (MDA), and total protein kinase-1 (Akt-1) levels. Additionally, they minimized cardiac inducible nitric oxide synthase (iNOS), microRNA-34a (miR-34a), and p38 mitogen-activated protein kinase (p38-MAPK) levels. In conclusion, F3 liquisolid compact possessed an overall pronounced results over pure SM reckoned to its enhanced solubility and efficacy.


Assuntos
Isoproterenol/toxicidade , Infarto do Miocárdio/tratamento farmacológico , Silimarina/administração & dosagem , Animais , Infarto do Miocárdio/induzido quimicamente , Ratos , Silimarina/química , Silimarina/farmacologia , Solubilidade
15.
Hum Exp Toxicol ; 39(4): 440-450, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31797693

RESUMO

Autophagy and apoptosis are important players in the progression of hepatic fibrosis via activation of hepatic stellate cells (HSCs). Despite the recently depicted antifibrotic effects of alpha-lipoic acid (ALA), however, its modulatory effects on HSCs autophagy remain unverified. Our study aimed to elucidate the underlying antifibrotic mechanisms through which ALA mediates HSC autophagy and apoptosis. Liver fibrosis was induced via thioacetamide (TAA) intoxication in rats; TAA-intoxicated rats were treated with either silymarin or ALA. Effect of ALA on biochemical parameters and immunohistopathological examinations was measured and compared to silymarin. ALA restored normal hepatic architecture (S1 vs. S4), liver functions, hepatic glutathione, and transforming growth factor-ß1 levels. ALA ameliorated hepatic levels of malondialdehyde, platelet-derived growth factor, tissue inhibitor metalloproteinases-1, hydroxyproline, and expression of alpha-smooth muscle actin. Moreover, ALA significantly reduced messenger RNA expression of LC3-II genes and triggered caspase-3 expression. Interestingly, ALA exhibited superior activities over silymarin regarding suppression of proliferation, activation and autophagy of HSCs, collagen deposition, and induction of HSCs apoptosis. In conclusion, treatment of TAA-intoxicated rats with ALA inhibited autophagy and induced apoptotic clearance of activated HSCs. Accordingly, this study provides mechanistic insights into the possible applicability of ALA in the treatment of hepatic fibrosis.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cirrose Hepática/prevenção & controle , Substâncias Protetoras/farmacologia , Ácido Tióctico/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Silimarina/farmacologia , Tioacetamida/toxicidade
16.
J Immunoassay Immunochem ; 41(1): 84-96, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31739724

RESUMO

Acetaminophen is a common analgesic-antipyretic agent, which is safe in therapeutic doses but in higher doses can produce hepatic necrosis. The aim of this study is to investigate the hepatoprotective effects of artichoke, silymarin, and both agents in acetaminophen-induced liver damage in mice. Forty male mice were divided into five main groups, (1) control (2) Acetaminophen (APAP) (3) Artichoke leaf extracts (ALE) and APAP (4) silymarin and APAP group (5) ALE, silymarin and APAP groups. Blood samples were collected for the measurement of liver enzymes (ALT, AST, and ALP). The liver was excised, weighed and dissected into two parts, one used for measurement of malondialdehyde (MDA) and glutathione reductase, and the other part used for histopathological examination and assessment of proliferative cell nuclear antigen (PCNA) immunohistochemical expression. APAP group showed a significant increase in liver weight, ALT, AST, ALP, MDA, and PCNA expression with a significant decrease in glutathione reductase in comparison to control group. All these parameters were significantly improved in the three treated groups when compared to APAP group. APAP group showed marked portal inflammation and parenchyma necrosis. Co-administration of ALE and/or silymarin to acetaminophen treated mice showed a significant reduction in PCNA expression compared to APAP group. Both ALE and silymarin co-treatment showed a significant decrease in PCNA percentage to a level near to control group. Artichoke and/or silymarin are suggested to protect against acetaminophen-induced hepatotoxicity in mice by ameliorating liver enzymes, antioxidant effect, decreasing liver damage and proliferation.Abbreviation: ALT, alanine transaminase. AST, aspartate transaminase. ALP, alkaline phosphatase.MDA, malondialdehyde. PCNA, proliferative cell nuclear antigen.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cynara scolymus/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Substâncias Protetoras/farmacologia , Silimarina/farmacologia , Acetaminofen , Animais , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Silimarina/química
17.
J Mol Neurosci ; 70(2): 276-283, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31732923

RESUMO

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exacerbates mitochondrial impairment and α-synuclein expression leading to Parkinsonism. Impaired mitochondria and over-expressed α-synuclein are degraded and eliminated via macroautophagy and chaperone-mediated autophagy. Owing to multiple properties, silymarin protects from oxidative stress-mediated cellular injury. However, its effect on MPTP-induced changes in autophagy is not yet known. The study aimed to decipher the effect of silymarin on MPTP-induced changes in autophagy. Male mice (20-25 g) were treated with silymarin (intraperitoneally, daily, 40 mg/kg) for 2 weeks. On day 7, a few animals were also administered with MPTP (intraperitoneally, 20 mg/kg, 4 injections at 2-h interval) along with vehicles. Striatal dopamine content was determined. Western blot analysis was done to assess α-synuclein, beclin-1, sequestosome, phosphorylated 5' adenosine monophosphate-activated protein kinase (p-AMPK), lysosome-associated membrane protein-2 (LAMP-2), heat shock cognate-70 (Hsc-70), LAMP-2A, phosphorylated unc-51-like autophagy activating kinase (p-Ulk1), and phosphorylated mechanistic target of rapamycin (p-mTOR) levels in the nigrostriatal tissue. Silymarin rescued from MPTP-induced increase in beclin-1, sequestosome, p-AMPK, and p-Ulk1 and decrease in LAMP-2, p-mTOR, and LAMP-2A levels. Silymarin defended against MPTP-induced increase in α-synuclein and reduction in dopamine content. The results demonstrate that silymarin protects against MPTP-induced changes in autophagy leading to Parkinsonism.


Assuntos
Autofagia , Intoxicação por MPTP/metabolismo , Fármacos Neuroprotetores/farmacologia , Silimarina/farmacologia , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Corpo Estriado/efeitos dos fármacos , Corpo Estriado/metabolismo , Dopamina/metabolismo , Proteína 2 de Membrana Associada ao Lisossomo/metabolismo , Intoxicação por MPTP/tratamento farmacológico , Masculino , Camundongos , Fármacos Neuroprotetores/uso terapêutico , Proteínas Quinases/metabolismo , Silimarina/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , alfa-Sinucleína/metabolismo
18.
Int J Radiat Biol ; 96(2): 220-227, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31692407

RESUMO

Purpose: The present study was undertaken to evaluate the protective and therapeutic effects of silymarin and mesenchymal stem cells (MSCs) to ameliorate the damage caused by gamma radiation.Materials and methods: MSCs were given by intravenous injection to male rats (1.4 × 107 cells), 1 day next to gamma radiation (4Gy). While, silymarin was administered orally at a dose of 70 mg/kg b. wt., 3 days before irradiation and continued for 21 days post irradiation.Results: After 1 and 3 weeks post-irradiation, the results revealed a significant decline in red blood corpuscles (RBCs), white blood corpuscles (WBCs) and platelets count with rising in serum lipid profile [total lipids (TL), total glycerides (TG), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C) and very low density lipoprotein-cholesterol (VLDL-C) levels] and total bilirubin; while significant decreases in serum total protein and high density lipoprotein-cholesterol (HDL-C) levels were observed. In irradiated animals receiving double treatment with MSCs and silymarin; amelioration of the changes observed in hematological and biochemical parameters when comparing with the irradiated group.Conclusions: Treatment with a radio-protector (such as silymarin) in addition to MSCs transplantation was recommended to protect against gamma radiation injury.


Assuntos
Antioxidantes/farmacologia , Raios gama , Células-Tronco Mesenquimais/citologia , Estresse Oxidativo/efeitos da radiação , Protetores contra Radiação/farmacologia , Silimarina/farmacologia , Administração Oral , Animais , Plaquetas/efeitos da radiação , Células da Medula Óssea/citologia , Eritrócitos/efeitos da radiação , Leucócitos/efeitos da radiação , Masculino , Ratos
19.
Nat Prod Res ; 34(6): 759-765, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30445852

RESUMO

Silymarin is a mixture of flavonolignans extracted from the fruit of Silybum marianum (milk thistle). The latter is used as a medicinal plant to treat liver and gallbladder disorders. Recently, silymarin has been investigated for its effects against diabetes mellitus, and shown to reduce serum levels of glucose in model animals and in clinical trials. This effect can be explained mainly by the protective effect of silymarin against pancreatic beta-cells, but the involvement of other mechanisms is possible. We demonstrated the α-amylase inhibitory activity of silymarin and investigated the components responsible for this effect. Two major flavonolignans, silibinin and silychristin, did not show inhibition against α-amylase, but two novel silychristin derivatives conjugated with dehydrodiconiferyl alcohol were isolated as the mildly inhibiting components of silymarin. Further analyses indicated the presence of various silychristin derivatives in silymarin that may act synergistically to show α-amylase inhibitory activity.[Formula: see text].


Assuntos
Álcoois/química , Cardo-Mariano/química , alfa-Amilases Pancreáticas/antagonistas & inibidores , Silimarina/química , Álcoois/farmacologia , Animais , Antioxidantes/farmacologia , Pâncreas/efeitos dos fármacos , Pâncreas/enzimologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Silimarina/farmacologia
20.
Nat Prod Res ; 34(18): 2647-2651, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30663356

RESUMO

A polyphenolic flavonoid, Silymarin isolated from Silybum marianum is widely known for its hepatoprotective action. In the present study anti-plasmodial activity of Silymarin has been demonstrated for the first time having IC50 of 14 ± 0.33 µM against the NF-54 strain of P. falciparum with high selectivity index (>100). The parasitostatic action is exerted through inhibition of ß-hematin/hemozoin formation which is due to the interaction (Kd = 3.63 ± 0.9µM) of silymarin with free heme in a Stoichiometry of 1:1 Silymarin: heme complex resulting into heme-induced membrane damage in the parasite. Silymarin could hinder the glutathione and hydrogen peroxide-induced heme detoxification. Silymarin also induces apoptosis in the parasite through the elevation of caspase-3 level in a dose-dependent manner. Results from the docking studies suggest that Silymarin interacts with heme.


Assuntos
Flavonoides/farmacologia , Heme/metabolismo , Plasmodium falciparum/efeitos dos fármacos , Silimarina/farmacologia , Animais , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Hemeproteínas/antagonistas & inibidores , Concentração Inibidora 50 , Plasmodium falciparum/crescimento & desenvolvimento , Silimarina/química , Silimarina/metabolismo
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