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Molecules (Basel, Switzerland) Jan 2017Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver... (Review)
Review
Silymarin is the extract of , or milk thistle, and its major active compound is silybin, which has a remarkable biological effect. It is used in different liver disorders, particularly chronic liver diseases, cirrhosis and hepatocellular carcinoma, because of its antioxidant, anti-inflammatory and antifibrotic power. Indeed, the anti-oxidant and anti-inflammatory effect of silymarin is oriented towards the reduction of virus-related liver damages through inflammatory cascade softening and immune system modulation. It also has a direct antiviral effect associated with its intravenous administration in hepatitis C virus infection. With respect to alcohol abuse, silymarin is able to increase cellular vitality and to reduce both lipid peroxidation and cellular necrosis. Furthermore, silymarin/silybin use has important biological effects in non-alcoholic fatty liver disease. These substances antagonize the progression of non-alcoholic fatty liver disease, by intervening in various therapeutic targets: oxidative stress, insulin resistance, liver fat accumulation and mitochondrial dysfunction. Silymarin is also used in liver cirrhosis and hepatocellular carcinoma that represent common end stages of different hepatopathies by modulating different molecular patterns. Therefore, the aim of this review is to examine scientific studies concerning the effects derived from silymarin/silybin use in chronic liver diseases, cirrhosis and hepatocellular carcinoma.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antiviral Agents; Chronic Disease; Humans; Liver Diseases; Silybin; Silymarin
PubMed: 28125040
DOI: 10.3390/molecules22020191 -
Advances in Therapy Apr 2020Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative...
Silymarin, an extract from milk thistle seeds, has been used for centuries to treat hepatic conditions. Preclinical data indicate that silymarin can reduce oxidative stress and consequent cytotoxicity, thereby protecting intact liver cells or cells not yet irreversibly damaged. Eurosil 85 is a proprietary formulation developed to maximize the oral bioavailability of silymarin. Most of the clinical research on silymarin has used this formulation. Silymarin acts as a free radical scavenger and modulates enzymes associated with the development of cellular damage, fibrosis and cirrhosis. These hepatoprotective effects were observed in clinical studies in patients with alcoholic or non-alcoholic fatty liver disease, including patients with cirrhosis. In a pooled analysis of trials in patients with cirrhosis, silymarin treatment was associated with a significant reduction in liver-related deaths. Moreover, in patients with diabetes and alcoholic cirrhosis, silymarin was also able to improve glycemic parameters. Patients with drug-induced liver injuries were also successfully treated with silymarin. Silymarin is generally very well tolerated, with a low incidence of adverse events and no treatment-related serious adverse events or deaths reported in clinical trials. For maximum benefit, treatment with silymarin should be initiated as early as possible in patients with fatty liver disease and other distinct liver disease manifestations such as acute liver failure, when the regenerative potential of the liver is still high and when removal of oxidative stress, the cause of cytotoxicity, can achieve the best results.
Topics: Blood Glucose; Diabetes Mellitus; Hepatocytes; Humans; Liver Cirrhosis; Liver Diseases; Liver Diseases, Alcoholic; Non-alcoholic Fatty Liver Disease; Protective Agents; Silymarin
PubMed: 32065376
DOI: 10.1007/s12325-020-01251-y -
Molecules (Basel, Switzerland) Aug 2022Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades.... (Review)
Review
Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture of polyphenolic flavonoids originating from the fruits and akenes of and contains three flavonolignans, silibinins (silybins), silychristin and silydianin, along with taxifolin. Silybins are the major constituents in silymarin with almost 70-80% abundance and are accountable for most of the observed therapeutic activity. Silymarin has also been acknowledged from the ancient period and is utilized in European and Asian systems of traditional medicine for treating various liver disorders. The contemporary literature reveals that silymarin is employed significantly as a neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective and detoxification agent by targeting various cellular and molecular pathways, including MAPK, mTOR, β-catenin and Akt, different receptors and growth factors, as well as inhibiting numerous enzymes and the gene expression of several apoptotic proteins and inflammatory cytokines. Therefore, the current review aims to recapitulate and update the existing knowledge regarding the pharmacological potential of silymarin as evidenced by vast cellular, animal, and clinical studies, with a particular emphasis on its mechanisms of action.
Topics: Antioxidants; Flavonoids; Fruit; Silybum marianum; Silymarin
PubMed: 36014565
DOI: 10.3390/molecules27165327 -
Annals of Medicine Dec 2022Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis,... (Review)
Review
Chronic liver disease (CLD), manifested as hepatic injury, is a major cause of global morbidity and mortality. CLD progresses to fibrosis, cirrhosis, and-ultimately-hepatocellular carcinoma (HCC) if left untreated. The different phenotypes of CLD based on their respective clinical features and causative agents include alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and drug-induced liver injury (DILI). The preferred treatment modality for CLD includes lifestyle modification and diet, along with limited pharmacological agents for symptomatic treatment. Moreover, oxidative stress (OS) is an important pathological mechanism underlying all CLD phenotypes; hence, the use of antioxidants to manage the disease is justified. Based on available clinical evidence, silymarin can be utilized as a hepatoprotective agent, given its potent antioxidant, antifibrotic, and anti-inflammatory properties. The role of silymarin in suppressing OS has been well established, and therefore silymarin is recommended for use in ALD and NAFLD in the guidelines approved by the Russian Medical Scientific Society of Therapists and the Gastroenterology Scientific Society of Russia. However, to discuss the positioning of the original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies, an expert panel of international and Russian medical professionals was convened on 11 November 2020. The panel reviewed approaches for the prevention and treatment of OS, existing guidelines for patient management for CLD, and available evidence on the effectiveness of silymarin in reducing OS, fibrosis, and hepatic inflammation and presented in the form of a narrative review. Key messagesAn expert panel of international and Russian medical professionals reviewed existing guidelines for ALD, NAFLD, MAFLD, and DILI to establish consensus recommendations that oxidative stress is the common pathophysiological mechanism underlying these conditions.The panel also discussed the positioning of original silymarin in clinical guidelines and treatment protocols as a hepatoprotective agent for managing CLD concomitantly with other therapies.The panel reviewed the effectiveness of 140 mg original silymarin three times a day in reducing oxidative stress in chronic liver diseases such as ALD, NAFLD, MAFLD, and DILI.
Topics: Antioxidants; Carcinoma, Hepatocellular; Humans; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; Protective Agents; Silymarin
PubMed: 35635048
DOI: 10.1080/07853890.2022.2069854 -
Biomolecular Concepts Mar 2020Background 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... (Review)
Review
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.
Topics: Aloe; Animals; Anti-Inflammatory Agents; Antioxidants; Cinnamomum zeylanicum; Female; Humans; Insulin Resistance; Plants, Medicinal; Polycystic Ovary Syndrome; Silymarin; Tea; Trigonella
PubMed: 32229652
DOI: 10.1515/bmc-2020-0005 -
PloS One 2019The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its... (Randomized Controlled Trial)
Randomized Controlled Trial
The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist's assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407.
Topics: Adult; Antioxidants; Double-Blind Method; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Silymarin; Treatment Outcome
PubMed: 31536511
DOI: 10.1371/journal.pone.0221683 -
Molecules (Basel, Switzerland) Nov 2017Milk thistle () is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of fruit extract (silymarin) is... (Review)
Review
Milk thistle () is a medicinal plant that has been used for thousands of years as a remedy for a variety of ailments. The main component of fruit extract (silymarin) is a flavonolignan called silybin, which is not only the major silymarin element but is also the most active ingredient of this extract, which has been confirmed in various studies. This compound belongs to the flavonoid group known as flavonolignans. Silybin's structure consists in two main units. The first is based on a taxifolin, the second a phenyllpropanoid unit, which in this case is conyferil alcohol. These two units are linked together into one structure by an oxeran ring. Since the 1970s, silybin has been regarded in official medicine as a substance with hepatoprotective properties. There is a large body of research that demonstrates silybin's many other healthy properties, but there are still a lack of papers focused on its molecular structure, chemistry, metabolism, and novel form of administration. Therefore, the aim of this paper is a literature review presenting and systematizing our knowledge of the silybin molecule, with particular emphasis on its structure, chemistry, bioavailability, and metabolism.
Topics: Biological Availability; Silybum marianum; Silybin; Silymarin
PubMed: 29125572
DOI: 10.3390/molecules22111942 -
Molecules (Basel, Switzerland) Apr 2019Silymarin flavonolignans are well-known agents that typically possess antioxidative, anti-inflammatory, and hepatoprotective functions. Recent studies have also... (Review)
Review
Silymarin flavonolignans are well-known agents that typically possess antioxidative, anti-inflammatory, and hepatoprotective functions. Recent studies have also documented the antiviral activities of silymarin and its derivatives against several viruses, including the flaviviruses (hepatitis C virus and dengue virus), togaviruses (Chikungunya virus and Mayaro virus), influenza virus, human immunodeficiency virus, and hepatitis B virus. This review will describe some of the latest preclinical and clinical studies detailing the antiviral profiles of silymarin and its derivatives, and discuss their relevance for antiviral drug development.
Topics: Antiviral Agents; Chikungunya virus; Dengue Virus; Flavivirus; Flavonolignans; HIV; Hepacivirus; Silymarin; Togaviridae
PubMed: 31010179
DOI: 10.3390/molecules24081552 -
Molecules (Basel, Switzerland) Apr 2020Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present... (Review)
Review
Silymarin extracted from milk thistle consisting of flavonolignan silybin has shown chemopreventive and chemosensitizing activity against various cancers. The present review summarizes the current knowledge on the potential targets of silymarin against various cancers. Silymarin may play on the system of xenobiotics, metabolizing enzymes (phase I and phase II) to protect normal cells against various toxic molecules or to protect against deleterious effects of chemotherapeutic agents on normal cells. Furthermore, silymarin and its main bioactive compounds inhibit organic anion transporters (OAT) and ATP-binding cassettes (ABC) transporters, thus contributing to counteracting potential chemoresistance. Silymarin and its derivatives play a double role, namely, limiting the progression of cancer cells through different phases of the cycle-thus forcing them to evolve towards a process of cell death-and accumulating cancer cells in a phase of the cell cycle-thus making it possible to target a greater number of tumor cells with a specific anticancer agent. Silymarin exerts a chemopreventive effect by inducing intrinsic and extrinsic pathways and reactivating cell death pathways by modulation of the ratio of proapoptotic/antiapoptotic proteins and synergizing with agonists of death domains receptors. In summary, we highlight how silymarin may act as a chemopreventive agent and a chemosensitizer through multiple pathways.
Topics: ATP-Binding Cassette Transporters; Apoptosis; Cell Cycle; Cell Cycle Checkpoints; Chemoprevention; Drug Resistance, Neoplasm; Humans; Protective Agents; Signal Transduction; Silymarin
PubMed: 32344919
DOI: 10.3390/molecules25092009 -
Molecules (Basel, Switzerland) May 2020The past decade has been marked by an intense scientific interest in the use of compounds or micronutrients of natural origin and their potential effects on human...
The past decade has been marked by an intense scientific interest in the use of compounds or micronutrients of natural origin and their potential effects on human health, both from researchers and industry [...].
Topics: Antioxidants; Biological Products; Humans; Micronutrients; Silymarin
PubMed: 32455869
DOI: 10.3390/molecules25102415