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Wang X. The Effects of Silibinin Combined With EGFR-TKIs in the Treatment of NSCLC. Cancer Med 2025; 14:e70643. [PMID: 39907159 DOI: 10.1002/cam4.70643] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 01/16/2025] [Accepted: 01/24/2025] [Indexed: 02/06/2025] Open
Abstract
BACKGROUND Currently, the most effective oral targeted therapies for NSCLC in clinical practice are EGFR-TKIs. However, acquired drug resistance often leads to tumor progression and recurrence. EGFR overexpression and activation of its downstream pathways are primary contributors to both mutations in tumor cells and their development of drug resistance. Silibinin has been identified as a promising agent that can suppress EGFR signaling through multiple mechanisms. However, its poor water solubility and difficulty penetrating cell membranes result in rapid metabolism in vivo, and significantly affect its concentration in the blood. METHODS We conducted a comprehensive search of the English PubMed database using various combinations of keywords, including "silibinin," "epidermal growth factor receptor," "phosphorylation," "chemotherapy," "nano," and "non-small cell lung cancer." The results were then filtered for their relevance and impact on current treatment paradigms. RESULTS This review presents a comprehensive exploration of the mechanisms underlying the EGFR autophosphorylation pathways that contribute to acquire drug resistance in. Additionally, this study delves into the potential of silibinin as a novel therapeutic agent for NSCLC, evaluating its advantages and limitations on the basis of existing research. The majority of the available data suggest that combining silibinin with first-generation TKIs would yield promising outcomes because of additive or synergistic effects, suggesting that optimizing the time and dosage of each of these treatments is crucial for achieving the best results. CONCLUSION The existing evidence is inadequate to endorse the clinical application of nano silibinin for NSCLC treatment. Developing multifunctional nanomedicines that incorporate silibinin, EGFR-TKIs, and other bioactive compounds is a recommended future strategy for NSCLC treatment.
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Affiliation(s)
- Xiaocen Wang
- School of Health Medicine, University of Sanya, Hainan, China
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Ashique S, Mohanto S, Kumar N, Nag S, Mishra A, Biswas A, Rihan M, Srivastava S, Bhowmick M, Taghizadeh-Hesary F. Unlocking the possibilities of therapeutic potential of silymarin and silibinin against neurodegenerative Diseases-A mechanistic overview. Eur J Pharmacol 2024; 981:176906. [PMID: 39154829 DOI: 10.1016/j.ejphar.2024.176906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2024] [Revised: 07/28/2024] [Accepted: 08/15/2024] [Indexed: 08/20/2024]
Abstract
Silymarin, a bioflavonoid derived from the Silybum marianum plant, was discovered in 1960. It contains C25 and has been extensively used as a therapeutic agent against liver-related diseases caused by alcohol addiction, acute viral hepatitis, and toxins-inducing liver failure. Its efficacy stems from its role as a potent anti-oxidant and scavenger of free radicals, employed through various mechanisms. Additionally, silymarin or silybin possesses immunomodulatory characteristics, impacting immune-enhancing and immune-suppressive functions. Recently, silymarin has been recognized as a potential neuroprotective therapy for various neurological conditions, including Parkinson's and Alzheimer's diseases, along with conditions related to cerebral ischemia. Its hepatoprotective qualities, primarily due to its anti-oxidant and tissue-regenerating properties, are well-established. Silymarin also enhances health by modifying processes such as inflammation, β-amyloid accumulation, cellular estrogenic receptor mediation, and apoptotic machinery. While believed to reduce oxidative stress and support neuroprotective mechanisms, these effects represent just one aspect of the compound's multifaceted protective action. This review article further delves into the possibilities of potential therapeutic advancement of silymarin and silibinin for the management of neurodegenerative disorders via mechanics modules.
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Affiliation(s)
- Sumel Ashique
- School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India; Department of Pharmaceutics, Bengal College of Pharmaceutical Sciences & Research, Durgapur, 713212, West Bengal, India.
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India.
| | - Nitish Kumar
- SRM Modinagar College of Pharmacy, SRM Institute of Science and Technology (Deemed to Be University), Delhi-NCR Campus, Modinagar, Ghaziabad, Uttar Pradesh, 201204, India
| | - Sagnik Nag
- Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor, Malaysia.
| | - Anuradha Mishra
- Amity Institute of Pharmacy, Amity University Lucknow Campus, Uttar Pradesh, 226010, India
| | - Aritra Biswas
- Department of Microbiology, Ramakrishna Mission Vivekananda Centenary College, Rahara Akhil Mukherjee Road, Khardaha, West Bengal, 700118, India; UNESCO Regional Centre for Biotechnology, Department of Biotechnology, Government of India, NCR Biotech Science Cluster, Faridabad, 121001, Haryana, India.
| | - Mohd Rihan
- Department of Pharmacology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab, 160062, India
| | - Shriyansh Srivastava
- Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, 203201, India; Department of Pharmacology, Delhi Pharmaceutical Sciences and Research University (DPSRU), Sector 3 Pushp Vihar, New Delhi, 110017, India
| | - Mithun Bhowmick
- Department of Pharmaceutics, Bengal College of Pharmaceutical Sciences & Research, Durgapur, 713212, West Bengal, India
| | - Farzad Taghizadeh-Hesary
- ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
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Ashique S, Mohanto S, Kumar N, Nag S, Mishra A, Biswas A, Rihan M, Srivastava S, Bhowmick M, Taghizadeh-Hesary F. Unlocking the possibilities of therapeutic potential of silymarin and silibinin against neurodegenerative Diseases-A mechanistic overview. Eur J Pharmacol 2024; 981:176906. [DOI: https:/doi.org/10.1016/j.ejphar.2024.176906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2025]
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Zadeh BSM, Akbari H, Salimi A. Preparation and in vitro evaluation of protective effects of Silibinin-loaded polymeric micelles on human hair against UV-B radiation. J Cosmet Dermatol 2024; 23:1816-1827. [PMID: 38193246 DOI: 10.1111/jocd.16176] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 10/20/2023] [Accepted: 12/28/2023] [Indexed: 01/10/2024]
Abstract
BACKGROUND The purpose of this study was to investigate the protective effect of Silibinin-loaded polymeric micelles from human hair against UV-B radiation. METHODS Eight formulations with different concentrations of Silibinin, Pluronic F-127, and Labrasol-Labrafil were made by a solvent evaporation method, and the selected formulation was chosen by examining their properties like particle size and loading efficiency. Six groups of human hair, including a group that received the selected formulation, were exposed to UV-B radiation and by calculating its factors such as peak-to-valley roughness, RMS roughness, FTIR, and the amount of protein loss, the protective effect of the selected formulation was judged. RESULTS According to the results, the loading efficiency and particle size of the selected formulation were 45.34% and 43.19 nm. The Silibinin release profile had two parts, fast and slow, which were suitable for creating a drug depot on hair. Its zeta potential also confirmed the minimum electrostatic interference between the formulation and hair surface. The zeta potential of selected formulation was -5.9 mv. Examination of AFM images showed that the selected formulation was able to prevent the increase in peak-to-valley roughness and RMS roughness caused by UV-B radiation. RMS roughness after 600 h of UV radiation in Groups 5 and 6 was significantly lower than the negative control group and the amount of this factor did not differ significantly between 0 and 600, so it can be concluded that the selected formulation containing Silibinin and the positive control group was able to prevent the increase of RMS roughness and hair destruction. In other hands, the two positive control groups and the selected formulation containing Silibinin were able to effectively reduce hair protein loss. CONCLUSION Silibinin-loaded polymeric micelles were able to effectively protect hair from structural and chemical changes caused by UV-B radiation.
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Affiliation(s)
- Behzad Sharif Makhmal Zadeh
- Department of Phamaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Hamed Akbari
- Department of Phamaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Anayatollah Salimi
- Department of Phamaceutics, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Nanotechnology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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Bechtold BJ, Lynch KD, Oyanna VO, Call MR, White LA, Graf TN, Oberlies NH, Clarke JD. Pharmacokinetic Effects of Different Models of Nonalcoholic Fatty Liver Disease in Transgenic Humanized OATP1B Mice. Drug Metab Dispos 2024; 52:355-367. [PMID: 38485280 PMCID: PMC11023818 DOI: 10.1124/dmd.123.001607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 03/05/2024] [Accepted: 03/07/2023] [Indexed: 03/21/2024] Open
Abstract
Organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 (collectively, OATP1B) transporters encoded by the solute carrier organic anion transporter (SLCO) genes mediate uptake of multiple pharmaceutical compounds. Nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease (NAFLD), decreases OATP1B abundance. This research characterized the pathologic and pharmacokinetics effects of three diet- and one chemical-induced NAFLD model in male and female humanized OATP1B mice, which comprises knock-out of rodent Oatp orthologs and insertion of human SLCO1B1 and SLCO1B3. Histopathology scoring demonstrated elevated steatosis and inflammation scores for all NAFLD-treatment groups. Female mice had minor changes in SLCO1B1 expression in two of the four NAFLD treatment groups, and pitavastatin (PIT) area under the concentration-time curve (AUC) increased in female mice in only one of the diet-induced models. OATP1B3 expression decreased in male and female mice in the chemical-induced NAFLD model, with a coinciding increase in PIT AUC, indicating the chemical-induced model may better replicate changes in OATP1B3 expression and OATP substrate disposition observed in NASH patients. This research also tested a reported multifactorial pharmacokinetic interaction between NAFLD and silymarin, an extract from milk thistle seeds with notable OATP-inhibitory effects. Males showed no change in PIT AUC, whereas female PIT AUC increased 1.55-fold from the diet alone and the 1.88-fold from the combination of diet with silymarin, suggesting that female mice are more sensitive to pharmacokinetic changes than male mice. Overall, the humanized OATP1B model should be used with caution for modeling NAFLD and multifactorial pharmacokinetic interactions. SIGNIFICANCE STATEMENT: Advanced stages of NAFLD cause decreased hepatic OATP1B abundance and increase systemic exposure to OATP substrates in human patients. The humanized OATP1B mouse strain may provide a clinically relevant model to recapitulate these observations and predict pharmacokinetic interactions in NAFLD. This research characterized three diet-induced and one drug-induced NAFLD model in a humanized OATP1B mouse model. Additionally, a multifactorial pharmacokinetic interaction was observed between silymarin and NAFLD.
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Affiliation(s)
- Baron J Bechtold
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - Katherine D Lynch
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - Victoria O Oyanna
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - M Ridge Call
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - Laura A White
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - Tyler N Graf
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - Nicholas H Oberlies
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
| | - John D Clarke
- Department of Pharmaceutical Sciences (B.J.B., K.D.L., V.O.O., M.R.C., J.D.C.) and Washington Animal Disease Diagnostic Laboratory (L.A.W.), Washington State University, Pullman, Washington; and Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (T.N.G., N.H.O.)
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Inai M, Sagara H, Ueno Y, Ouchi H, Yoshimura F, Asakawa T, Hamashima Y, Kan T. Total Synthesis of (+)-Silybin A. Chem Pharm Bull (Tokyo) 2024; 72:570-573. [PMID: 38910121 DOI: 10.1248/cpb.c24-00276] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/25/2024]
Abstract
We report the first total synthesis of silybin A (1). Key synthetic steps include the construction of the 1,4-benzodioxane neolignan skeleton, a modified Julia-Kocienski olefination reaction between m-nitrophenyltetrazole sulfone (m-NPT sulfone) 10 and aldehyde 21, the formation of the flavanol lignan skeleton 28 via a quinomethide intermediate under acidic conditions, and stepwise oxidation of the benzylic position of flavanol 29.
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Affiliation(s)
- Makoto Inai
- School of Pharmaceutical Sciences, University of Shizuoka
| | - Hiroto Sagara
- School of Pharmaceutical Sciences, University of Shizuoka
| | - Yoshinori Ueno
- School of Pharmaceutical Sciences, University of Shizuoka
| | - Hitoshi Ouchi
- School of Pharmaceutical Sciences, University of Shizuoka
| | | | | | | | - Toshiyuki Kan
- School of Pharmaceutical Sciences, University of Shizuoka
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Gros Q, Wolniaczyk M, Duval J, Horie S, Funada Y, Hayakawa Y, West C, Lesellier E. Facilitated on-line supercritical fluid extraction - supercritical fluid chromatography for nonpolar and polar compounds from milk thistle seeds. J Chromatogr A 2023; 1705:464168. [PMID: 37348225 DOI: 10.1016/j.chroma.2023.464168] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2023] [Revised: 06/15/2023] [Accepted: 06/16/2023] [Indexed: 06/24/2023]
Abstract
Plant seeds, as those from milk thistle (Silybum marianum), are a valuable source of nonpolar and polar compounds with potentially interesting biological activity. The main nonpolar compounds are triglycerides, which are also the main components of all vegetable oils. In addition, specific polar compounds - flavonolignans, called silymarin, have been found in large amounts in milk thistle seeds extract. These flavonoids derivatives have different biological activity, for instance hepatoprotective effects. In order to extract and analyze both nonpolar (triglycerides) and polar compounds (flavonolignans) from milk thistle seeds through a sequential methodology, an on-line supercritical fluid extraction - supercritical fluid chromatography (SFE-SFC) method was developed. Different ways of transferring the extracts from SFE to SFC (i.e. direct on-column transfer and loop transfer) were compared, and particularly for their effect on chromatographic quality. In this respect, nonpolar and polar compounds caused different issues, especially as polar compounds required a significant portion of co-solvent in the extraction step, favoring early elution in the chromatographic column. First, on-line SFE-SFC was used for triglycerides analysis and allowed the comparison of transfer modes. Then, on-line kinetics were performed to measure defatting time before polar molecules extraction. Finally, the eventual benefit of loop transfer was also investigated for the analysis of flavonolignans, polar molecules whose analysis can be difficult by on-line SFE-SFC. The aim of this paper is to discuss the versatility of on-line SFE-SFC and how challenging the coupling can be, especially when both non-polar and polar molecules must be analyzed independently in a single sample.
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Affiliation(s)
- Quentin Gros
- University of Orleans, ICOA, CNRS UMR 7311, Pôle de Chimie, Rue de Chartres - BP 6759 45067, Cedex 2, Orléans, France; Shimadzu France, Le luzard 2, Bat A, Bd Salvador Allende Noisiel, Marne-la-Vallée 77448, France
| | - Marta Wolniaczyk
- University of Orleans, ICOA, CNRS UMR 7311, Pôle de Chimie, Rue de Chartres - BP 6759 45067, Cedex 2, Orléans, France; Faculty of Chemistry, Jagiellonian University, Gronostajowa 2, Kraków 30-387, Poland
| | - Johanna Duval
- Shimadzu France, Le luzard 2, Bat A, Bd Salvador Allende Noisiel, Marne-la-Vallée 77448, France
| | - Shinnosuke Horie
- Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan; Shimadzu Europa Gmbh, Albert-Hahn-Straße 6, Duisburg 47269, Germany
| | - Yasuhiro Funada
- Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan
| | - Yoshihiro Hayakawa
- Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho, Nakagyo-ku, Kyoto 604-8511, Japan
| | - Caroline West
- University of Orleans, ICOA, CNRS UMR 7311, Pôle de Chimie, Rue de Chartres - BP 6759 45067, Cedex 2, Orléans, France.
| | - Eric Lesellier
- University of Orleans, ICOA, CNRS UMR 7311, Pôle de Chimie, Rue de Chartres - BP 6759 45067, Cedex 2, Orléans, France
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Raclariu-Manolică AC, Mauvisseau Q, Paranaiba R, De Boer HJ, Socaciu C. Authentication of milk thistle commercial products using UHPLC-QTOF-ESI + MS metabolomics and DNA metabarcoding. BMC Complement Med Ther 2023; 23:257. [PMID: 37480124 PMCID: PMC10360273 DOI: 10.1186/s12906-023-04091-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Accepted: 07/13/2023] [Indexed: 07/23/2023] Open
Abstract
BACKGROUND Milk thistle is one of the most popular hepatoprotectants, and is often sold in combination with other ingredients. Botanical supplements are known to be vulnerable to contamination and adulteration, and emerging technologies show promise to improve their quality control. METHODS Untargeted and semi-targeted metabolomics based on UHPLC-QTOF-ESI+MS techniques, UV spectrometry, and DNA metabarcoding using Illumina MiSeq were used to authenticate eighteen milk thistle botanical formulations (teas, capsules, tablets, emulsion). RESULTS Untargeted metabolomics separated 217 molecules and by multivariate analysis the discrimination between the different preparations was established. The semi-targeted metabolomics focused on 63 phytochemicals, mainly silymarin flavonolignans and flavonoids, that may be considered as putative biomarkers of authenticity. All formulations contained molecules from silymarin complexes at different levels. The quantitative evaluation of silybins was done using in parallel UV spectrometry and UHPLC-QTOF-ESI+MS and their correlations were compared. DNA metabarcoding detected milk thistle in eleven out of sixteen retained preparations, whereas two others had incomplete evidence of milk thistle despite metabolomics validating specific metabolites, e.g., silymarin complex, identified and quantified in all samples. Meanwhile, the DNA metabarcoding provided insights into the total species composition allowing the interpretation of the results in a broad context. CONCLUSION Our study emphasizes that combining spectroscopic, chromatographic, and genetic techniques bring complementary information to guarantee the quality of the botanical formulations.
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Affiliation(s)
- Ancuța Cristina Raclariu-Manolică
- Stejarul Research Centre for Biological Sciences, National Institute of Research and Development for Biological Sciences, Alexandru cel Bun Street, 6, Piatra Neamț, 610004, Romania.
- Natural History Museum, University of Oslo, P.O. Box 1172, Blindern, Oslo, 0318, Norway.
| | - Quentin Mauvisseau
- Natural History Museum, University of Oslo, P.O. Box 1172, Blindern, Oslo, 0318, Norway
| | - Renato Paranaiba
- Natural Products Laboratory, School of Health Sciences, University of Brasília, Campus Universitário Darcy Ribeiro, Brasília, DF, 70910-900, 70910-900, Brazil
- DNA Laboratory, National Institute of Criminalistics, Brazilian Federal Police, SAIS Quadra 7, Lote 23, Brasília, DF, 70610-200, Brazil
| | - Hugo J De Boer
- Natural History Museum, University of Oslo, P.O. Box 1172, Blindern, Oslo, 0318, Norway
| | - Carmen Socaciu
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine, Mănăştur Street, nr. 3-5, Cluj Napoca, 400372, Romania
- BIODIATECH- Research Center for Applied Biotechnology in Diagnosis and Molecular Therapy, Trifoiului Street 12G, Cluj-Napoca, 400478, Romania
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Raclariu-Manolică AC, Socaciu C. Detecting and Profiling of Milk Thistle Metabolites in Food Supplements: A Safety-Oriented Approach by Advanced Analytics. Metabolites 2023; 13:440. [PMID: 36984880 PMCID: PMC10052194 DOI: 10.3390/metabo13030440] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/14/2023] [Accepted: 03/15/2023] [Indexed: 03/30/2023] Open
Abstract
Milk thistle (Silybum marianum (L.) Gaertn.) is among the top-selling botanicals used as a supportive treatment for liver diseases. Silymarin, a mixture of unique flavonolignan metabolites, is the main bioactive component of milk thistle. The biological activities of silymarin have been well described in the literature, and its use is considered safe and well-tolerated in appropriate doses. However, commercial preparations do not always contain the recommended concentrations of silymarin, failing to provide the expected therapeutic effect. While the poor quality of raw material may explain the low concentrations of silymarin, its deliberate removal is suspected to be an adulteration. Toxic contaminants and foreign matters were also detected in milk thistle preparations, raising serious health concerns. Standard methods for determination of silymarin components include thin-layer chromatography (TLC), high-performance thin-layer chromatography (HPTLC), and high-performance liquid chromatography (HPLC) with various detectors, but nuclear magnetic resonance (NMR) and ultra-high-performance liquid chromatography (UHPLC) have also been applied. This review surveys the extraction techniques of main milk thistle metabolites and the quality, efficacy, and safety of the derived food supplements. Advanced analytical authentication approaches are discussed with a focus on DNA barcoding and metabarcoding to complement orthogonal chemical characterization and fingerprinting of herbal products.
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Affiliation(s)
- Ancuța Cristina Raclariu-Manolică
- Stejarul Research Centre for Biological Sciences, National Institute of Research and Development for Biological Sciences, 610004 Piatra Neamț, Romania
| | - Carmen Socaciu
- Faculty of Food Science and Technology, University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca, 400372 Cluj-Napoca, Romania
- BIODIATECH—Research Center for Applied Biotechnology in Diagnosis and Molecular Therapy, 400478 Cluj-Napoca, Romania
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Elmowafy M, Shalaby K, Elkomy MH, Alsaidan OA, Gomaa HAM, Abdelgawad MA, Mostafa EM. Polymeric Nanoparticles for Delivery of Natural Bioactive Agents: Recent Advances and Challenges. Polymers (Basel) 2023; 15:1123. [PMID: 36904364 PMCID: PMC10007077 DOI: 10.3390/polym15051123] [Citation(s) in RCA: 51] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Revised: 02/16/2023] [Accepted: 02/20/2023] [Indexed: 02/25/2023] Open
Abstract
In the last few decades, several natural bioactive agents have been widely utilized in the treatment and prevention of many diseases owing to their unique and versatile therapeutic effects, including antioxidant, anti-inflammatory, anticancer, and neuroprotective action. However, their poor aqueous solubility, poor bioavailability, low GIT stability, extensive metabolism as well as short duration of action are the most shortfalls hampering their biomedical/pharmaceutical applications. Different drug delivery platforms have developed in this regard, and a captivating tool of this has been the fabrication of nanocarriers. In particular, polymeric nanoparticles were reported to offer proficient delivery of various natural bioactive agents with good entrapment potential and stability, an efficiently controlled release, improved bioavailability, and fascinating therapeutic efficacy. In addition, surface decoration and polymer functionalization have opened the door to improving the characteristics of polymeric nanoparticles and alleviating the reported toxicity. Herein, a review of the state of knowledge on polymeric nanoparticles loaded with natural bioactive agents is presented. The review focuses on frequently used polymeric materials and their corresponding methods of fabrication, the needs of such systems for natural bioactive agents, polymeric nanoparticles loaded with natural bioactive agents in the literature, and the potential role of polymer functionalization, hybrid systems, and stimuli-responsive systems in overcoming most of the system drawbacks. This exploration may offer a thorough idea of viewing the polymeric nanoparticles as a potential candidate for the delivery of natural bioactive agents as well as the challenges and the combating tools used to overcome any hurdles.
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Affiliation(s)
- Mohammed Elmowafy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Khaled Shalaby
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Mohammed H. Elkomy
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Omar Awad Alsaidan
- Department of Pharmaceutics, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Hesham A. M. Gomaa
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Mohamed A. Abdelgawad
- Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
| | - Ehab M. Mostafa
- Department of Pharmacognosy, College of Pharmacy, Jouf University, Sakaka P.O. Box 2014, Saudi Arabia
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Das PK, Saha J, Pillai S, Lam AKY, Gopalan V, Islam F. Implications of estrogen and its receptors in colorectal carcinoma. Cancer Med 2023; 12:4367-4379. [PMID: 36207986 PMCID: PMC9972078 DOI: 10.1002/cam4.5242] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Revised: 08/18/2022] [Accepted: 09/01/2022] [Indexed: 11/08/2022] Open
Abstract
Estrogens have been implicated in the pathogenesis of various cancer types, including colorectal carcinoma (CRC). Estrogen receptors such as ERα and ERβ activate intracellular signaling cascades followed by binding to estrogen, resulting in important changes in cellular behaviors. The nuclear estrogen receptors, i.e. ERβ and ERα are responsible for the genomic actions of estrogens, whereas the other receptor, such as G protein-coupled estrogen receptor (GPER) regulates rapid non-genomic actions, which lead to secondary gene expression changes in cells. ERβ, the predominant estrogen receptor expressed in both normal and non-malignant colonic epithelium, has protective roles in colon carcinogenesis. ERβ may exert the anti-tumor effect through selective activation of pro-apoptotic signaling, increasing DNA repair, inhibiting expression of oncogenes, regulating cell cycle progression, and also by changing the micro-RNA pool and DNA-methylation. Thus, a better understanding of the underlying mechanisms of estrogen and its receptors in CRC pathogenesis could provide a new horizon for effective therapeutic development. Furthermore, using synthetic or natural compounds as ER agonists may induce estrogen-mediated anti-cancer activities against colon cancer. In this study, we report the most recent pre-clinical and experimental evidences related to ERs in CRC development. Also, we reviewed the actions of naturally occurring and synthetic compounds, which have a protective role against CRC development by acting as ER agonist.
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Affiliation(s)
- Plabon Kumar Das
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.,Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
| | - Joti Saha
- Department of Applied Chemistry and Chemical Engineering, University of Rajshahi, Rajshahi, Bangladesh
| | - Suja Pillai
- School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
| | - Alfred K-Y Lam
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia
| | - Vinod Gopalan
- School of Medicine & Dentistry, Griffith University, Gold Coast, Queensland, Australia
| | - Farhadul Islam
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, Bangladesh.,Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia
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12
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Nejabati F, Ebrahimzadeh H. Electrospun nanofibers for extraction of thymoquinone from Nigella-Stevia prior to detection using electrochemical biosensor based on GCE/rGO/CuO. Microchem J 2023. [DOI: 10.1016/j.microc.2023.108545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/22/2023]
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13
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In Vitro Antioxidant Capacity of Purified Bioactive Compounds in Milk Thistle Seed (Silybum marianum) Along with Phenolic Profile. FOOD ANAL METHOD 2023. [DOI: 10.1007/s12161-023-02449-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
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14
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Henriet E, Abdallah F, Laurent Y, Guimpied C, Clement E, Simon M, Pichon C, Baril P. Targeting TGF-β1/miR-21 pathway in keratinocytes reveals protective effects of silymarin on imiquimod-induced psoriasis mouse model. JID INNOVATIONS 2022; 3:100175. [PMID: 36968096 PMCID: PMC10034514 DOI: 10.1016/j.xjidi.2022.100175] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Revised: 11/10/2022] [Accepted: 11/11/2022] [Indexed: 12/23/2022] Open
Abstract
Epidermal cells integrate multiple signals that activate the signaling pathways involved in skin homeostasis. TGF-β1 signaling pathway upregulates microRNA (miR)-21-5p in keratinocytes and is often deregulated in skin diseases. To identify the bioactive compounds that enable to modulate the TGF-β1/miR-21-5p signaling pathway, we screened a library of medicinal plant extracts using our miR-ON RILES luciferase reporter system placed under the control of the miR-21-5p in keratinocytes treated with TGF-β1. We identified silymarin, a mixture of flavonolignans extracted from Silybum marianum (L.) Gaertn., as the most potent regulator of miR-21-5p expression. Using Argonaute 2 immunoprecipitation and RT-qPCR, we showed that silymarin regulates the expression of miR-21-5p through a noncanonical TGF-β1 signaling pathway, whereas RNA-sequencing analysis revealed three unexpected transcriptomic signatures associated with keratinocyte differentiation, cell cycle, and lipid metabolism. Mechanistically, we demonstrated that SM blocks cell cycle progression, inhibits keratinocyte differentiation through repression of Notch3 expression, stimulates lipid synthesis via activation of PPARγ signaling and inhibits inflammatory responses by suppressing the transcriptional activity of NF-κB. We finally showed that topical application of silymarin alleviates the development of imiquimod-induced psoriasiform lesions in mice by abrogating the altered expression levels of markers involved in inflammation, proliferation, differentiation, and lipid metabolism.
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Park SM, He YC, Gong C, Gao W, Bae YS, Si C, Park KH, Choi SE. Effects of taxifolin from enzymatic hydrolysis of Rhododendron mucrotulatum on hair growth promotion. Front Bioeng Biotechnol 2022; 10:995238. [PMID: 36159701 PMCID: PMC9492874 DOI: 10.3389/fbioe.2022.995238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Accepted: 08/04/2022] [Indexed: 11/22/2022] Open
Abstract
Flavonoid aglycones possess biological activities, such as antioxidant and antidiabetic activities compared to glycosides. Taxifolin, a flavonoid aglycones, is detected only in trace amounts in nature and is not easily observed. Therefore, in this study, to investigate the hair tonic and hair loss inhibitors effect of taxifolin, high content of taxifolin aglycone extract was prepared by enzymatic hydrolysis. Taxifolin effectively regulates the apoptosis of dermal papilla cells, which is associated with hair loss, based on its strong antioxidant activities. However, inhibition of dihydrotestosterone (DHT), which is a major cause of male pattern hair loss, was significantly reduced with taxifolin treatment compared with minoxidil, as a positive control. It was also confirmed that a representative factor for promoting hair growth, IGF-1, was significantly increased, and that TGF-β1, a representative biomarker for hair loss, was significantly reduced with taxifolin treatment. These results suggest that taxifolin from enzymatic hydrolysis of RM is a potential treatment for hair loss and a hair growth enhancer.
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Affiliation(s)
- Sun-Min Park
- Department of Forest Biomaterials Engineering, College of Forest and Environmental Sciences, Kangwon National University, Kangwon, South Korea
| | - Yi-Chang He
- Key Lab of Agricultural Resources and Ecology of Poyang Lake Basin, College of Land Resources and Environment, Jiangxi Agricultural University, Nanchang, Jiangxi, China
- Jiangxi Academy of Forestry, Nanchang, Jiangxi, China
| | - Chun Gong
- Jiangxi Academy of Forestry, Nanchang, Jiangxi, China
| | - Wei Gao
- Jiangxi Academy of Forestry, Nanchang, Jiangxi, China
| | - Young-Soo Bae
- Department of Forest Biomaterials Engineering, College of Forest and Environmental Sciences, Kangwon National University, Kangwon, South Korea
- Jiangxi Academy of Forestry, Nanchang, Jiangxi, China
| | - Chuanling Si
- Tianjin Key Laboratory of Pulp and Paper, Tianjin University of Science and Technology, Tianjin, China
| | - Kwang-Hyun Park
- Department of Emergency Medicine and BioMedical Science Graduate Program (BMSGP), Chonnam National University, Hwasun, South Korea
- Department of Emergency Medical Rescue, Nambu University, Gwangju, South Korea
| | - Sun-Eun Choi
- Department of Forest Biomaterials Engineering, College of Forest and Environmental Sciences, Kangwon National University, Kangwon, South Korea
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16
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Abderrezag N, Montenegro ZJS, Louaer O, Meniai AH, Cifuentes A, Ibáñez E, Mendiola JA. One-step sustainable extraction of Silymarin compounds of wild Algerian milk thistle (Silybum marianum) seeds using Gas Expanded Liquids. J Chromatogr A 2022; 1675:463147. [PMID: 35640448 DOI: 10.1016/j.chroma.2022.463147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Revised: 05/10/2022] [Accepted: 05/12/2022] [Indexed: 11/25/2022]
Abstract
This work reports the application of Gas Expanded Liquid (GXL) extraction to concentrate the flavonolignan fraction (silymarin) and taxifolin from Silybum marianum seeds, which have proven to be highly valuable health-promoting compounds. GXL using green solvents was used to isolate silymarin with the objective of replacing conventional methods. In one hand, the effect of different compositions of solvents, aqueous ethanol (20%, 50% or 80% (v/v)) at different CO2/liquid (25, 50 and 75%) ratios, on the GXL extraction was investigated. The obtained extracts have been chemically and functionally characterized by means of UHPLC-ESI-MS/MS (triple quadrupole) and in-vitro assays such as anti-inflammatory, anti-cholinergic and antioxidant. Results revealed that the operating conditions influenced the extraction yield, the total phenolic content and the presence of the target compounds. The best obtained yield was 55.97% using a ternary mixture of solvents composed of CO2:EtOH:H2O (25:60:15) at 40 °C and 9 MPa in 160 min. Furthermore, the results showed that obtained extracts had significant antioxidant and anti-inflammatory activities (with best IC50 value of 8.80 µg/mL and 28.52 µg/mL, respectively) but a moderate anti-cholinesterase activity (with best IC50 value of 125.09 µg/mL). Otherwise, the concentration of silymarin compounds in extract can go up to 59.6% using the present one-step extraction method without further purification, being silybinA+B the predominant identified compound, achieving value of 545.73 (mg silymarin/g of extract). The obtained results demonstrate the exceptional potential of GXL to extract high-added values molecules under sustainable conditions from different matrices.
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Affiliation(s)
- Norelhouda Abderrezag
- Laboratory of Environmental Processes Engineering, University of Salah Boubnider Constantine 3, Ali Mendjli, 25000 Constantine, Algeria; Profesora Facultad de Ingeniería Agroindustrial, Universidad de Nariño (UdeNar), Pasto, Colombia
| | | | - Ouahida Louaer
- Laboratory of Environmental Processes Engineering, University of Salah Boubnider Constantine 3, Ali Mendjli, 25000 Constantine, Algeria
| | - Abdeslam-Hassen Meniai
- Laboratory of Environmental Processes Engineering, University of Salah Boubnider Constantine 3, Ali Mendjli, 25000 Constantine, Algeria
| | - Alejandro Cifuentes
- Foodomics Laboratory, Bioactivity and Food Analysis Department, Institute of Food Science Research CIAL (CSIC-UAM), Nicolas Cabrera 9, 28049 Madrid, Spain
| | - Elena Ibáñez
- Foodomics Laboratory, Bioactivity and Food Analysis Department, Institute of Food Science Research CIAL (CSIC-UAM), Nicolas Cabrera 9, 28049 Madrid, Spain
| | - Jose A Mendiola
- Foodomics Laboratory, Bioactivity and Food Analysis Department, Institute of Food Science Research CIAL (CSIC-UAM), Nicolas Cabrera 9, 28049 Madrid, Spain.
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Kirdeeva Y, Fedorova O, Daks A, Barlev N, Shuvalov O. How Should the Worldwide Knowledge of Traditional Cancer Healing Be Integrated with Herbs and Mushrooms into Modern Molecular Pharmacology? Pharmaceuticals (Basel) 2022; 15:868. [PMID: 35890166 PMCID: PMC9320176 DOI: 10.3390/ph15070868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2022] [Revised: 07/04/2022] [Accepted: 07/11/2022] [Indexed: 12/04/2022] Open
Abstract
Traditional herbal medicine (THM) is a "core" from which modern medicine has evolved over time. Besides this, one third of people worldwide have no access to modern medicine and rely only on traditional medicine. To date, drugs of plant origin, or their derivates (paclitaxel, vinblastine, vincristine, vinorelbine, etoposide, camptothecin, topotecan, irinotecan, and omacetaxine), are very important in the therapy of malignancies and they are included in most chemotherapeutic regimes. To date, 391,000 plant and 14,000 mushroom species exist. Their medical and biochemical capabilities have not been studied in detail. In this review, we systematized the information about plants and mushrooms, as well as their active compounds with antitumor properties. Plants and mushrooms are divided based on the regions where they are used in ethnomedicine to treat malignancies. The majority of their active compounds with antineoplastic properties and mechanisms of action are described. Furthermore, on the basis of the available information, we divided them into two priority groups for research and for their potential of use in antitumor therapy. As there are many prerequisites and some examples how THM helps and strengthens modern medicine, finally, we discuss the positive points of THM and the management required to transform and integrate THM into the modern medicine practice.
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Affiliation(s)
- Yulia Kirdeeva
- Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; (Y.K.); (O.F.); (A.D.)
| | - Olga Fedorova
- Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; (Y.K.); (O.F.); (A.D.)
| | - Alexandra Daks
- Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; (Y.K.); (O.F.); (A.D.)
| | - Nikolai Barlev
- Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; (Y.K.); (O.F.); (A.D.)
- Orekhovich Institute of Biomedical Chemistry, 119435 Moscow, Russia
| | - Oleg Shuvalov
- Institute of Cytology, Russian Academy of Sciences, 194064 St. Petersburg, Russia; (Y.K.); (O.F.); (A.D.)
- Orekhovich Institute of Biomedical Chemistry, 119435 Moscow, Russia
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18
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Inai M, Ueno Y, Sagara H, Ouchi H, Yoshimura F, Kan T. Total Synthesis of Isosilybin B. European J Org Chem 2022. [DOI: 10.1002/ejoc.202200653] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Makoto Inai
- University of Shizuoka School of Pharmaceutical Sciences 52-1 Yada, Suruga-ku 422-8526 Shizuoka JAPAN
| | - Yoshinori Ueno
- Shizuoka Kenritsu Daigaku Department School of Pharmaceutical Sciences JAPAN
| | - Hiroto Sagara
- Shizuoka Kenritsu Daigaku Department School of Pharmaceutical Sciences JAPAN
| | - Hitoshi Ouchi
- Shizuoka Kenritsu Daigaku Department School of Pharmaceutical Sciences JAPAN
| | - Fumihiko Yoshimura
- Shizuoka Kenritsu Daigaku Department School of Pharmaceutical Sciences JAPAN
| | - Toshiyuki Kan
- Shizuoka Kenritsu Daigaku Department School of Pharmaceutical Sciences JAPAN
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Křen V, Valentová K. Silybin and its congeners: from traditional medicine to molecular effects. Nat Prod Rep 2022; 39:1264-1281. [PMID: 35510639 DOI: 10.1039/d2np00013j] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Covering: 2015 up to 2022 (Feb)Silymarin, an extract of milk thistle (Silybum marianum) fruits, has been used in various medicinal applications since ancient times. A major component of silymarin is the flavonolignan silybin and its relatives isosilybin, silychristin, silydianin, 2,3-dehydrosilybin, and some others. Except for silydianin, they occur in nature as two stereomers. This review focuses on recent developments in chemistry, biosynthesis, modern advanced analytical methods, and transformations of flavonolignans specifically reflecting their chirality. Recently described chemotypes of S. marianum, but also the newest findings regarding the pharmacokinetics, hepatoprotective, antiviral, neuroprotective, and cardioprotective activity, modulation of endocrine functions, modulation of multidrug resistance, and safety of flavonolignans are discussed. A growing number of studies show that the respective diastereomers of flavonolignans have significantly different activities in anisotropic biological systems. Moreover, it is now clear that flavonolignans do not act as antioxidants in vivo, but as specific ligands of biological targets and therefore their chirality is crucial. Many controversies often arise, mainly due to the non-standard composition of this phytopreparation, the use of various undefined mixtures, the misattribution of silymarin vs. silybin, and also the failure to consider the chemistry of the respective components of silymarin.
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Affiliation(s)
- Vladimír Křen
- Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, Prague 4, CZ 14220, Czech Republic.
| | - Kateřina Valentová
- Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, Prague 4, CZ 14220, Czech Republic.
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20
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Mi XJ, Choi HS, Perumalsamy H, Shanmugam R, Thangavelu L, Balusamy SR, Kim YJ. Biosynthesis and cytotoxic effect of silymarin-functionalized selenium nanoparticles induced autophagy mediated cellular apoptosis via downregulation of PI3K/Akt/mTOR pathway in gastric cancer. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 99:154014. [PMID: 35247670 DOI: 10.1016/j.phymed.2022.154014] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/10/2021] [Revised: 02/08/2022] [Accepted: 02/25/2022] [Indexed: 06/14/2023]
Abstract
BACKGROUND Silymarin, a blend of flavonolignans isolated from plant Silybum marianum L., has long been used as an herbal medicine. Biogenic routes especially the plant-based synthesis of selenium nanoparticles (SeNPs) is safe, eco-friendly, nontoxic and being considered as one of the best strategies for treatment of cancer. PURPOSE Silymarin-mediated green synthesis of SeNPs and their possibility as an anticancer agent have not been reported to date. Therefore, our present study was aimed to synthesize and characterize the selenium mediated silymarin nanoparticles (Si-SeNPs) from silymarin and investigate their possibility as an anticancer agent. METHODS The physicochemical characteristics of Si-SeNPs were analyzed using various analytical techniques, such as HPLC, field emission-transmission electron microscope, energy-dispersive X-ray spectrometer, and thermogravimetric analysis. The underlying molecular mechanism were evaluated using AGS gastric cancer cells. RESULTS Compared with silymarin, the Si-SeNPs exhibited significantly increased cytotoxic effect of AGS cells without exhibiting toxicity on normal cells. Real time PCR and western blotting analysis indicated that Si-SeNPs induced expression of Bax/Bcl-2, cytochrome c, and cleavage of caspase proteins, which is associated with mitochondria-mediated apoptosis signaling in AGS cells. Moreover, agonist assay using PI3K activator indicated that Si-SeNPs-inhibited PI3K/AKT/mTOR pathways were significantly associated as an autophagy and apoptosis signaling in AGS cells. CONCLUSION Our study demonstrated the improved anticancer efficacy of Si-SeNPs- induced apoptosis and autophagy pathways, and therefore recommended Si-SeNPs as a novel anticancer agent after in vivo studies.
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Affiliation(s)
- Xiao-Jie Mi
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea
| | - Han Sol Choi
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea
| | - Haribalan Perumalsamy
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea; Research Institute for Convergence of Basic Science, Hanyang University, Seoul 04763, Republic of Korea
| | - Rajeshkumar Shanmugam
- Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha University, SIMATS, Chennai 600077, TN, India
| | - Lakshmi Thangavelu
- Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha University, SIMATS, Chennai 600077, TN, India
| | - Sri Renukadevi Balusamy
- Department of Food Science and Biotechnology, Sejong University, Gwangjin-gu, Seoul, 05006, Republic of Korea.
| | - Yeon-Ju Kim
- Graduate School of Biotechnology, and College of Life Science, Kyung Hee University, Yongin-si, 17104, Gyeonggi-do, Republic of Korea.
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Synthesis and antitumor activity of novel silibinin and 2,3-dehydrosilybin derivatives with carbamate groups. Med Chem Res 2022; 31:533-544. [PMID: 35194363 PMCID: PMC8853087 DOI: 10.1007/s00044-022-02854-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 01/20/2022] [Indexed: 11/03/2022]
Abstract
A novel series of silibinin and 2,3-dehydrosilybin derivatives bearing carbamate groups were designed, synthesized and their in vitro anticancer activities were screened against human cancer cell lines including MCF-7, NCI-H1299, HepG2 and HT29 by CCK-8 assay. The results showed that most of the compounds significantly suppressed the proliferation of tested cancer cells. Among them, compounds 2h, 3h and 3f demonstrated markedly higher antiproliferative activity on MCF-7 cells with IC50 values of 2.08, 5.54 and 6.84 µM, respectively. Compounds 3e, 3g and 2g displayed better cytotoxic activity against NCI-H1299 cells with IC50 values of 8.07, 8.45 and 9.09 µM, respectively. Compounds 3g, 3c and 3h exhibited a promising inhibitory effect against HepG2 cells with IC50 values of 8.88, 9.47 and 9.99 µM, respectively. Compounds 3e, 2e and 3c revealed effective biological potency on HT29 cells with IC50 values of 6.27, 9.13 and 9.32 µM, respectively. In addition, the outcomes of the docking studies between compounds 2f, 2h, 3e, 3g and Hsp90 receptor (PDB ID: 4AWO) suggest the possible mechanism of inhibition against MCF-7 cell lines.
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22
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Koltai T, Fliegel L. Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions. J Evid Based Integr Med 2022; 27:2515690X211068826. [PMID: 35018864 PMCID: PMC8814827 DOI: 10.1177/2515690x211068826] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 10/20/2021] [Accepted: 12/06/2021] [Indexed: 12/14/2022] Open
Abstract
The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture of 6 flavolignan isomers. The 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin is functionally the most active of these compounds. This group of flavonoids has been extensively studied and they have been used as hepato-protective substances for the mushroom Amanita phalloides intoxication and mainly chronic liver diseases such as alcoholic cirrhosis and nonalcoholic fatty liver. Hepatitis C progression is not, or slightly, modified by silymarin. Recently, it has also been proposed for SARS COVID-19 infection therapy. The biochemical and molecular mechanisms of action of these substances in cancer are subjects of ongoing research. Paradoxically, many of its identified actions such as antioxidant, promoter of ribosomal synthesis, and mitochondrial membrane stabilization, may seem protumoral at first sight, however, silymarin compounds have clear anticancer effects. Some of them are: decreasing migration through multiple targeting, decreasing hypoxia inducible factor-1α expression, inducing apoptosis in some malignant cells, and inhibiting promitotic signaling among others. Interestingly, the antitumoral activity of silymarin compounds is limited to malignant cells while the nonmalignant cells seem not to be affected. Furthermore, there is a long history of silymarin use in human diseases without toxicity after prolonged administration. The ample distribution and easy accessibility to milk thistle-the source of silymarin compounds, its over the counter availability, the fact that it is a weed, some controversial issues regarding bioavailability, and being a nutraceutical rather than a drug, has somehow led medical professionals to view its anticancer effects with skepticism. This is a fundamental reason why it never achieved bedside status in cancer treatment. However, in spite of all the antitumoral effects, silymarin actually has dual effects and in some cases such as pancreatic cancer it can promote stemness. This review deals with recent investigations to elucidate the molecular actions of this flavonoid in cancer, and to consider the possibility of repurposing it. Particular attention is dedicated to silymarin's dual role in cancer and to some controversies of its real effectiveness.
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Affiliation(s)
- Tomas Koltai
- Hospital del Centro Gallego de Buenos Aires, Buenos Aires, Argentina
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23
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Wu S, Chen G, Zhang Q, Wang G, Chen QH. 3- O-Carbamoyl-5,7,20- O-trimethylsilybins: Synthesis and Preliminary Antiproliferative Evaluation. Molecules 2021; 26:6421. [PMID: 34770829 PMCID: PMC8588252 DOI: 10.3390/molecules26216421] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Revised: 10/20/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022] Open
Abstract
To search for novel androgen receptor (AR) modulators for the potential treatment of castration-resistant prostate cancer (CRPC), naturally occurring silibinin was sought after as a lead compound because it possesses a moderate potency towards AR-positive prostate cancer cells and its chemical scaffold is dissimilar to all currently marketed AR antagonists. On the basis of the structure-activity relationships that we have explored, this study aims to incorporate carbamoyl groups to the alcoholic hydroxyl groups of silibinin to improve its capability in selectively suppressing AR-positive prostate cancer cell proliferation together with water solubility. To this end, a feasible approach was developed to regioselectively introduce a carbamoyl group to the secondary alcoholic hydroxyl group at C-3 without causing the undesired oxidation at C2-C3, providing an avenue for achieving 3-O-carbamoyl-5,7,20-O-trimethylsilybins. The application of the synthetic method can be extended to the synthesis of 3-O-carbamoyl-3',4',5,7-O-tetramethyltaxifolins. The antiproliferative potency of 5,7,20-O-trimethylsilybin and its nine 3-carbamoyl derivatives were assessed in an AR-positive LNCaP prostate cancer cell line and two AR-null prostate cancer cell lines (PC-3 and DU145). Our preliminary bioassay data imply that 5,7,20-O-trimethylsilybin and four 3-O-carbamoyl-5,7,20-O-trimethylsilybins emerge as very promising lead compounds due to the fact that they can selectively suppress AR-positive LNCaP cell proliferation. The IC50 values of these five 5,7,20-O-trimethylsilybins against the LNCaP cells fall into the range of 0.11-0.83 µM, which exhibit up to 660 times greater in vitro antiproliferative potency than silibinin. Our findings suggest that carbamoylated 5,7,20-O-trimethylsilybins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
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Affiliation(s)
- Sitong Wu
- Department of Chemistry and Biochemistry, California State University, Fresno, CA 93740, USA; (S.W.); (G.C.)
| | - Guanglin Chen
- Department of Chemistry and Biochemistry, California State University, Fresno, CA 93740, USA; (S.W.); (G.C.)
| | - Qiang Zhang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA; (Q.Z.); (G.W.)
| | - Guangdi Wang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA; (Q.Z.); (G.W.)
| | - Qiao-Hong Chen
- Department of Chemistry and Biochemistry, California State University, Fresno, CA 93740, USA; (S.W.); (G.C.)
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Raja HA, Oberlies NH, Stadler M. Occasional comment: Fungal identification to species-level can be challenging. PHYTOCHEMISTRY 2021; 190:112855. [PMID: 34273757 DOI: 10.1016/j.phytochem.2021.112855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/13/2023]
Affiliation(s)
- Huzefa A Raja
- Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, PO Box 26170, Greensboro, NC, 27402-6170, USA.
| | - Nicholas H Oberlies
- Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, PO Box 26170, Greensboro, NC, 27402-6170, USA.
| | - Marc Stadler
- Department of Microbial Drugs, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124, Braunschweig, Germany.
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Abstract
The natural diastereomeric mixture of silybins A and B is often used (and considered) as a single flavonolignan isolated from the fruit extract of milk thistle (Silybum marianum), silymarin. However, optically pure silybin diastereomers are required for the evaluation of their biological activity. The separation of silybin diastereomers by standard chromatographic methods is not trivial. Preparative chemoenzymatic resolution of silybin diastereomers has been published, but its optimization and scale-up are needed. Here we present a continuous flow reactor for the chemoenzymatic kinetic resolution of silybin diastereomers catalyzed by Candida antarctica lipase B (CALB) immobilized on acrylic resin beads (Novozym® 435). Temperature, flow rate, and starting material concentration were varied to determine optimal reaction conditions. The variables observed were conversion and diastereomeric ratio. Optimal conditions were chosen to allow kilogram-scale reactions and were determined to be −5 °C, 8 g/L silybin, and a flow rate of 16 mL/min. No significant carrier degradation was observed after approximately 30 cycles (30 days). Under optimal conditions and using a 1000 × 15 mm column, 20 g of silybin per day can be easily processed, yielding 6.7 and 5.6 g of silybin A and silybin B, respectively. Further scale-up depends only on the size of the reactor.
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Křen V. Chirality Matters: Biological Activity of Optically Pure Silybin and Its Congeners. Int J Mol Sci 2021; 22:ijms22157885. [PMID: 34360650 PMCID: PMC8346157 DOI: 10.3390/ijms22157885] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 07/19/2021] [Indexed: 12/31/2022] Open
Abstract
This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.
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Affiliation(s)
- Vladimír Křen
- Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Vídeňská 1083, 142 20 Prague, Czech Republic
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Tvrdý V, Pourová J, Jirkovský E, Křen V, Valentová K, Mladěnka P. Systematic review of pharmacokinetics and potential pharmacokinetic interactions of flavonolignans from silymarin. Med Res Rev 2021; 41:2195-2246. [PMID: 33587317 DOI: 10.1002/med.21791] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 01/06/2021] [Accepted: 01/29/2021] [Indexed: 12/15/2022]
Abstract
Silymarin is an extract from the seeds (fruits) of Silybum marianum that contains flavonolignans and flavonoids. Although it is frequently used as a hepatoprotective agent, its application remains somewhat debatable, in particular, due to the low oral bioavailability of flavonolignans. Moreover, there are claims of its potential interactions with concomitantly used drugs. This review aims at a systematic summary and critical assessment of known information on the pharmacokinetics of particular silymarin flavonolignans. There are two known major reasons for poor systemic oral bioavailability of flavonolignans: (1) rapid conjugation in intestinal cells or the liver and (2) efflux of parent flavonolignans or formed conjugates back to the lumen of the gastrointestinal tract by intestinal cells and rapid excretion by the liver into the bile. The metabolism of phase I appears to play a minor role, in contrast to extensive conjugation and indeed the unconjugated flavonolignans reach low plasma levels after common doses. Only about 1%-5% of the administered dose is eliminated by the kidneys. Many in vitro studies tested the inhibitory potential of silymarin and its components toward different enzymes and transporters involved in the absorption, metabolism, and excretion of xenobiotics. In most cases, effective concentrations are too high to be relevant under real biological conditions. Most human studies showed no silymarin-drug interactions explainable by these suggested interferences. More interactions were found in animal studies, likely due to the much higher doses administered.
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Affiliation(s)
- Václav Tvrdý
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic
| | - Jana Pourová
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic
| | - Eduard Jirkovský
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic
| | - Vladimír Křen
- Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
| | - Kateřina Valentová
- Laboratory of Biotransformation, Institute of Microbiology of the Czech Academy of Sciences, Prague, Czech Republic
| | - Přemysl Mladěnka
- Department of Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Králové, Charles University, Hradec Králové, Czech Republic
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28
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Tsiailanis AD, Tzakos AG, Mavromoustakos T. Advancing the Therapeutic Efficacy of Bioactive Molecules by Delivery Vehicle Platforms. Curr Med Chem 2021; 28:2697-2706. [PMID: 32503399 DOI: 10.2174/0929867327666200605154506] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2020] [Revised: 05/05/2020] [Accepted: 05/13/2020] [Indexed: 11/22/2022]
Abstract
Drugs have to overcome numerous barriers to reach their desired therapeutic targets. In several cases, drugs, especially the highly lipophilic molecules, suffer from low solubility and bioavailability and therefore their desired targeting is hampered. In addition, undesired metabolic products might be produced or off-targets could be recognized. Along these lines, nanopharmacology has provided new technological platforms, to overcome these boundaries. Specifically, numerous vehicle platforms such as cyclodextrins and calixarenes have been widely utilized to host lipophilic drugs such as antagonists of the angiotensin II AT1 receptor (AT1R), as well as quercetin and silibinin. The encapsulation of these drugs in supramolecules or other systems refines their solubility and metabolic stability, increases their selectivity and therefore decreases their effective dose and improves their therapeutic index. In this mini review we report on the formulations of silibinin and AT1R antagonist candesartan in a 2-HP-β-cyclodextrin host molecule, which displayed enhanced cytotoxicity and increased silibinin's and candesartan's stability, respectively. Moreover, we describe the encapsulation of quercetin in gold nanoparticles bearing a calixarene supramolecular host. Also, the encapsulation of temozolomide in a calixarene nanocapsule has been described. Finally, we report on the activity enhancement that has been achieved upon using these formulations as well as the analytical and computational methods we used to characterize these formulations and explore the molecular interactions between the host and quest molecules.
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Affiliation(s)
| | - Andreas G Tzakos
- Department of Chemistry, University of Ioannina, Ioannina 45110, Greece
| | - Thomas Mavromoustakos
- Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis Zografou 15771, Greece
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29
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Palit P, Mukhopadhyay A, Chattopadhyay D. Phyto-pharmacological perspective of Silymarin: A potential prophylactic or therapeutic agent for COVID-19, based on its promising immunomodulatory, anti-coagulant and anti-viral property. Phytother Res 2021; 35:4246-4257. [PMID: 33817867 PMCID: PMC8250558 DOI: 10.1002/ptr.7084] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2020] [Revised: 02/13/2021] [Accepted: 02/23/2021] [Indexed: 12/16/2022]
Abstract
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.
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Affiliation(s)
- Partha Palit
- Department of Pharmaceutical Sciences, Drug Discovery Research Laboratory, Assam University, Silchar, India
| | | | - Debprasad Chattopadhyay
- Division of Microbiology & Virology, ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, India.,Division of Virology, ICMR-National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata, West Bengal, India
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30
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Azadpour M, Farajollahi MM, Varzi AM, Hashemzadeh P, Mahmoudvand H, Barati M. Extraction, Chemical Composition, Antioxidant Property, and In-vitro Anticancer Activity of Silymarin from Silybum marianum on Kb and A549 Cell Lines. Curr Drug Discov Technol 2021; 18:511-517. [PMID: 32860361 DOI: 10.2174/1570163817666200827111127] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/23/2020] [Accepted: 07/30/2020] [Indexed: 11/22/2022]
Abstract
INTRODUCTION This study aimed to evaluate the antioxidant property of Silymarin (SM) extracted from the seed of Silybum marianum and its anticancer activity on KB and A549 cell lines following 24, 48, and 72 h of treatment. METHODS Ten grams of powdered S. marianum seeds were defatted using n-hexane for 6 hours and then extracted by methanol. The Silymarin extracted of extraction components. The extracted components of Silymarin were measured by spectrophotometric assay and HPLC analysis. 2, 2- diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phenol content, total flavonoid content, and total antioxidant capacity were measured to detect the antioxidant properties of SM. The anticancer activity of the SM on cell lines evaluated by MTT. RESULTS In HPLC analysis, more than 50% of the peaks were related to silybin A and B. SM was reduced DPPH (the stable free radical) with a 50% inhibitory concentration (IC50) of 6.56 μg/ ml in comparison with butylated hydroxyl toluene (BHT), which indicated an IC50 of ~3.9 μg/ ml. The cytotoxicity effect of SM on the cell lines was studied by MTT assay. The cytotoxicity effect of the extracted Silymarin on KB and A549 cell lines was observed up to 80 and 70% at 156 and 78 μg/ml, respectively. The IC50 value of the extracted SM on KB and A549 cell lines after 24 hours of treatment was seen at 555 and 511 μg/ml, respectively. CONCLUSION Due to the good antioxidant and anticancer properties of the isolated Silymarin, its use as an anticancer drug is suggested.
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Affiliation(s)
- Mojgan Azadpour
- Research Center of Pediatric Infectious Diseases, Hazrat-e-Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
| | - Mohammad Morad Farajollahi
- Faculty of Science, Department of Medical Biotechnology, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran
| | - Ali Mohammad Varzi
- Facutuly of Science, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Pejman Hashemzadeh
- Facutuly of Science, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Hossein Mahmoudvand
- Facutuly of Science, Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Mitra Barati
- Research Center of Pediatric Infectious Diseases, Hazrat-e-Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
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31
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Nasab EM, Athari SM, Ghafarzade S, Nasab ARM, Athari SS. Immunomodulatory effects of two silymarin isomers in a Balb/c mouse model of allergic asthma. Allergol Immunopathol (Madr) 2020; 48:646-653. [PMID: 32284261 DOI: 10.1016/j.aller.2020.01.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2019] [Revised: 12/31/2019] [Accepted: 01/02/2020] [Indexed: 11/25/2022]
Abstract
INTRODUCTION AND OBJECTIVES Allergic asthma is a complex chronic disease of the respiratory system presenting with cough, dyspnea, wheezing and airway obstruction. More than 300 million people of all age spectrums suffer from asthma worldwide. Immunological and inflammatory processes are main contributors to asthma. Cytokines produced by T helper 2 lymphocytes play main roles in asthma development and progression. Silymarin, a therapeutic agent with anti-oxidative properties, is a main component of Silybium marinum. We herein aimed to compare the anti-inflammatory and anti-allergic effects of two silymarin isomers, isosilybin A and silydianin, in the treatment of allergic asthma. MATERIALS AND METHODS After isolating and purifying isosilybin A and silydianin, Balb/c mouse model of allergic asthma was produced using ovalbumin injection. Seventy mice were categorized into five (1 normal and 4 asthmatic) groups (n = 14 per group). Mice in three of four asthmatic groups were treated with either isosilybin A, silydianin or budesonide. The 4th asthmatic group was used as positive control, with the non-asthmatic group serving as negative control. Airway hyperresponsiveness (AHR) and levels of IL-4, IL-5 and IL-13 in the BAL fluid were determined. Gene expressions of IL-4, IL-5, IL-13 and MUC5ac, as well as IgE serum level were also measured. Cellular composition of BAL fluid and lungs histopathology were finally investigated. RESULTS Isosilybin A and silydianin reduced eosinophilic infiltration of lungs, IL-4 and IL-5 levels in BAL fluid, IL-4 and IL-5 gene expressions, as well as AHR in Balb/c mouse model of asthma. However, no significant changes were observed in IL-13 level and mucus hyper-secretion. CONCLUSION According to our study, isosilybin A and silydianin can control main symptoms of asthma by modulating immune responses.
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32
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Kumar N, Jose J. Current developments in the nanomediated delivery of photoprotective phytochemicals. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:38446-38471. [PMID: 32761528 DOI: 10.1007/s11356-020-10100-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 07/10/2020] [Indexed: 06/11/2023]
Abstract
Natural products have been used to protect the skin from harmful UV radiation for decades. Due to the ecotoxicological implications of synthetic sunscreen exposure in aquatic ecosystems, there is a greater need to explore alternative sources of UV filters. Recent research has focused on discovering novel UV absorbing photoprotective molecules from nature. In response to the excessive damage caused by UVB rays, plants induce the production of high concentrations of phytoprotective secondary metabolites and anti-oxidative enzymes. Despite promising UV absorbing and photoprotective properties, plant secondary metabolites have been underutilized in topical delivery due to low solubility and high instability. Numerous phytochemicals have been effectively nanosized, incorporated in formulations, and studied for their sustained effects in photoprotection. The present review outlines recent developments in nanosizing and delivering photoprotective crude plant extract and phytochemicals from a phytochemical perspective. We searched for articles using keywords: "UV damage," "skin photoprotection," "photodamage," and "nano delivery" in varied combinations. We identified and reviewed literature from 43 original research articles exploring nanosized phytochemicals and crude plant extracts with photoprotective activity. Nanosized phytochemicals retained higher amounts of bioactive compounds in the skin and acted as depots for their sustained release. Novel approaches in nanosizing considerably improved the photostability, efficacy, and water resistance of plant secondary metabolites. We further discuss the need for broad-spectrum sunscreen products, potential challenges, and future growth in this area.
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Affiliation(s)
- Nimmy Kumar
- Department of Pharmacognosy, NITTE Gulabi Shetty Memorial Institute of Pharmaceutical Sciences, NITTE Deemed-to-be University, 575018, Mangalore, India
| | - Jobin Jose
- Department of Pharmaceutics, NITTE Gulabi Shetty Memorial Institute of Pharmaceutical Sciences, NITTE Deemed-to-be University, Mangalore, 575018, India.
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Mizuno M, Mori K, Tsuchiya K, Takaki T, Misawa T, Demizu Y, Shibanuma M, Fukuhara K. Design, Synthesis, and Biological Activity of Conformationally Restricted Analogues of Silibinin. ACS OMEGA 2020; 5:23164-23174. [PMID: 32954167 PMCID: PMC7495755 DOI: 10.1021/acsomega.0c02936] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 07/30/2020] [Indexed: 05/12/2023]
Abstract
Silibinin (Sib), one of the main components of milk thistle extract, has attracted considerable attention because of its various biological activities, which include antioxidant activity and potential effects in diabetes and Alzheimer's disease (AD). In a previous study, we synthesized catechin analogues by constraining the geometries of (+)-catechin and (-)-epicatechin. The constrained analogues exhibited enhanced bioactivities, with the only major difference between the two being their three-dimensional structures. The constrained geometry in (+)-catechin resulted in a high degree of planarity (PCat), while (-)-epicatechin failed to maintain planarity (PEC). The three-dimensional structure of Sib may be related to its ability to inhibit aggregation of amyloid beta (Aβ). We therefore introduced PCat and PEC into Sib to demonstrate how the constrained molecular geometry and differences in three-dimensional structures may enhance such activities. Introduction of PCat into Sib (SibC) resulted in effective inhibition of Aβ aggregation, α-glucosidase activity, and cell growth, suggesting that not only reduced flexibility but also the high degree of planarity may enhance the biological activity. SibC is expected to be a promising lead compound for the treatment of several diseases.
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Affiliation(s)
- Mirei Mizuno
- Division
of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Kazunori Mori
- Division
of Cancer Cell Biology, School of Pharmacy, Showa University, 1-5-8
Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Keisuke Tsuchiya
- Division
of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
- Division
of Organic Chemistry, National Institute
of Health Sciences, 3-25-26
Tonomachi, Kawasaki-ku, Kawasaki-City, Kanagawa 210-9501, Japan
| | - Takashi Takaki
- Division
of Electron Microscopy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Takashi Misawa
- Division
of Organic Chemistry, National Institute
of Health Sciences, 3-25-26
Tonomachi, Kawasaki-ku, Kawasaki-City, Kanagawa 210-9501, Japan
| | - Yosuke Demizu
- Division
of Organic Chemistry, National Institute
of Health Sciences, 3-25-26
Tonomachi, Kawasaki-ku, Kawasaki-City, Kanagawa 210-9501, Japan
| | - Motoko Shibanuma
- Division
of Cancer Cell Biology, School of Pharmacy, Showa University, 1-5-8
Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
| | - Kiyoshi Fukuhara
- Division
of Organic and Medicinal Chemistry, School of Pharmacy, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
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Aboelwafa HR, El-kott AF, Abd-Ella EM, Yousef HN. The Possible Neuroprotective Effect of Silymarin against Aluminum Chloride-Prompted Alzheimer's-Like Disease in Rats. Brain Sci 2020; 10:E628. [PMID: 32932753 PMCID: PMC7564174 DOI: 10.3390/brainsci10090628] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 08/23/2020] [Accepted: 09/08/2020] [Indexed: 12/25/2022] Open
Abstract
Alzheimer's disease (AD) is a worldwide rapidly growing neurodegenerative disease. Here, we elucidated the neuroprotective effects of silymarin (SM) on the hippocampal tissues of aluminum chloride (AlCl3)-induced Alzheimer-like disease in rats using biochemical, histological, and ultrastructural approaches. Forty rats were divided into control, SM, AlCl3, and AlCl3 + SM groups. Biochemically, AlCl3 administration resulted in marked elevation in levels of lipid peroxidation (LPO) and nitric oxide (NO) and decrease in levels of reduced glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). Moreover, AlCl3 significantly increased tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1β), and acetylcholinesterase (AChE) activities. Furthermore, myriad histological and ultrastructural alterations were recorded in the hippocampal tissues of AlCl3-treated rats represented as marked degenerative changes of pyramidal neurons, astrocytes, and oligodendrocytes. Additionally, some myelinated nerve fibers exhibited irregular arrangement of their myelin coats, while the others revealed focal degranulation of their myelin sheaths. Severe defects in the blood-brain barrier (BBB) were also recorded. However, co-administration of SM with AlCl3 reversed most of the biochemical, histological, and ultrastructural changes triggered by AlCl3 in rats. The results of the current study indicate that SM can potentially mend most of the previously evoked neuronal damage in the hippocampal tissues of AlCl3-kindled rats.
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Affiliation(s)
- Hanaa R. Aboelwafa
- Department of Biological and Geological Sciences, Faculty of Education, Ain Shams University, Cairo 11566, Egypt;
| | - Attalla F. El-kott
- Biology Department, Faculty of Science, King Khalid University, Abha 61421, Saudi Arabia;
- Zoology Department, College of Science, Damanhour University, Damanhour 22511, Egypt
| | - Eman M. Abd-Ella
- Zoology Department, College of Science, Fayoum University, Fayoum 63514, Egypt;
- Biology Department, College of Science and Art, Al-Baha University, Al-Mandaq 65581, Saudi Arabia
| | - Hany N. Yousef
- Department of Biological and Geological Sciences, Faculty of Education, Ain Shams University, Cairo 11566, Egypt;
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Stastnik O, Pavlata L, Mrkvicova E. The Milk Thistle Seed Cakes and Hempseed Cakes are Potential Feed for Poultry. Animals (Basel) 2020; 10:ani10081384. [PMID: 32785057 PMCID: PMC7459908 DOI: 10.3390/ani10081384] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2020] [Revised: 08/01/2020] [Accepted: 08/06/2020] [Indexed: 11/16/2022] Open
Abstract
The aims of this work were to summarize the nutritional value of the milk thistle seed cakes and hempseed cakes and describe the influence on selected performance parameters, metabolism and animal health from inclusion of these non-traditional feeds into diets. It seems more appropriate to apply the extract of the bioactive substances complex to the livestock diets than addition of expellers or other forms of plants processing. The seed expellers, etc. mostly worsened the chickens' performance parameters with higher doses in diets, while most of the work using the extract yields had positive results on animal performance.
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Shah M, Nawaz S, Jan H, Uddin N, Ali A, Anjum S, Giglioli-Guivarc'h N, Hano C, Abbasi BH. Synthesis of bio-mediated silver nanoparticles from Silybum marianum and their biological and clinical activities. MATERIALS SCIENCE & ENGINEERING. C, MATERIALS FOR BIOLOGICAL APPLICATIONS 2020; 112:110889. [PMID: 32409047 DOI: 10.1016/j.msec.2020.110889] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 03/11/2020] [Accepted: 03/20/2020] [Indexed: 01/31/2023]
Abstract
The purpose of current study was green synthesis of silver nanoparticles (AgNPs) from seeds and wild Silybum plants in comparison with their respective extracts followed by characterization and biological potency. The biologically synthesized AgNPs were subjected to characterization using techniques like XRD, FTIR, TEM, HPLC and SPE. Highly crystalline and stable NPs were obtained using Silybum wild plant (NP1) and seeds (NP3) with size range between 18.12 and 13.20 nm respectively. The synthesized NPs and their respective extracts revealed a vast range of biological applications showing antibacterial, antioxidant, anti-inflammatory, cytotoxic and anti-aging potencies. The highest antioxidant activity (478.23 ± 1.9 μM, 176.91 ± 1.3 μM, 83.5 ± 1.6% μgAAE/mg, 156.32 ± 0.6 μgAAE/mg) for ABTS, FRAP, FRSA, TRP respectively was shown by seed extract (NP4) followed by highest value of (117.35 ± 0.9 μgAAE/mg) for TAC by wild extract (NP2). The highest antifungal activity (13 mm ± 0.76) against Candida albicans was shown by NP3 while antibacterial activity of (6 mm against Klebsiella pneumonia) was shown by NP3 and NP4. The highest anti-inflammatory activity (38.56 ± 1.29 against COX1) was shown by NP2. Similarly, the high value of (48.89 ± 1.34 against Pentosidine-Like AGEs) was shown by NP4. Also, the high anti-diabetic activity (38.74 ± 1.09 against α-amylase) was shown by NP4. The extracts and the synthesized NPs have shown activity against hepato-cellular carcinoma (HepG2) human cells. The HPLC analysis revealed that the highest value of silymarin component (silybin B 2289 mg/g DW) was found for NP4. Silydianin is responsible for capping. Among the green synthesized AgNPs and the extracts used, the effect of NP4 was most promising for further use.
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Affiliation(s)
- Muzamil Shah
- Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Sabir Nawaz
- Department of Microbiology, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Hasnain Jan
- Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Noor Uddin
- Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Ashaq Ali
- Key State Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, 430072 Wuhan, China
| | - Sumaira Anjum
- Department of Biotechnology, Kinnaird College for Women, Lahore 54000, Pakistan
| | - Nathalie Giglioli-Guivarc'h
- EA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, 37000 Tours, France; COSM'ACTIFS, Bioactifs et Cosmétiques, CNRS GDR3711, 45067 Orléans CEDEX 2, France
| | - Christophe Hano
- COSM'ACTIFS, Bioactifs et Cosmétiques, CNRS GDR3711, 45067 Orléans CEDEX 2, France; Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), INRA USC1328, Université d'Orléans, 45067 Orléans CEDEX 2, France
| | - Bilal Haider Abbasi
- Department of Biotechnology, Quaid-i-Azam University, Islamabad 45320, Pakistan; EA2106 Biomolécules et Biotechnologies Végétales, Université de Tours, 37000 Tours, France; COSM'ACTIFS, Bioactifs et Cosmétiques, CNRS GDR3711, 45067 Orléans CEDEX 2, France; Laboratoire de Biologie des Ligneux et des Grandes Cultures (LBLGC), INRA USC1328, Université d'Orléans, 45067 Orléans CEDEX 2, France.
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Jiang Z, Sekhon A, Oka Y, Chen G, Alrubati N, Kaur J, Orozco A, Zhang Q, Wang G, Chen QH. 23- O-Substituted-2,3-Dehydrosilybins Selectively Suppress Androgen Receptor-Positive LNCaP Prostate Cancer Cell Proliferation. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20922326] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
As part of our ongoing project to search for natural product-based antiandrogens, nine derivatives of 2,3-dehydrosilybin have been synthesized for the evaluation of its antiproliferative activity in an androgen receptor-positive prostate cancer cell model. Specifically, 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin was synthesized through two approaches, and eight 23- O-substituted-3,5,7,20- O-tetramethyl-2,3-dehydrosilybins were achieved from 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin. The antiproliferative potency of 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and its eight derivatives were assessed in an androgen receptor (AR)-positive LNCaP prostate cancer cell line, as well as in two AR-negative (PC-3 and DU145) prostate cancer cell models as a comparison. Our WST cell proliferation assay data indicate 3,5,7,20- O-tetramethyl-2,3-dehydrosilybin and most of its 23- O-substituents can selectively inhibit AR-positive LNCaP prostate cancer cell proliferation. Our data suggest that 3,5,7,20- O-tetramethyl-2,3-dehydrosilibins could serve as a natural product-based scaffold for new antiandrogens for lethal castration-resistant prostate cancer.
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Affiliation(s)
- Ziran Jiang
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Arman Sekhon
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Yogeshwari Oka
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Guanglin Chen
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Nagat Alrubati
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Jasleen Kaur
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Alexia Orozco
- Department of Chemistry, California State University, Fresno, CA, USA
| | - Qiang Zhang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA, USA
| | - Guangdi Wang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA, USA
| | - Qiao-Hong Chen
- Department of Chemistry, California State University, Fresno, CA, USA
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Wojas O, Krzych-Fałta E, Samel-Kowalik P, Żalikowska-Gardocka M, Majsiak E, Mari A, Samoliński B. A case of allergy to Silybum marianum ( milk thistle) and Eragrostis tef ( teff). ALLERGY, ASTHMA, AND CLINICAL IMMUNOLOGY : OFFICIAL JOURNAL OF THE CANADIAN SOCIETY OF ALLERGY AND CLINICAL IMMUNOLOGY 2020; 16:23. [PMID: 32322285 PMCID: PMC7161110 DOI: 10.1186/s13223-020-00421-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Accepted: 03/26/2020] [Indexed: 11/14/2022]
Abstract
BACKGROUND This paper presents a peculiar first case of an allergy to Silybum marianum (milk thistle) and Eragrostis tef (teff). Both teff and milk thistle have been presented in the literature (both domestic and foreign) in a positive light, the former as a new part of gluten-free diet, and the latter as a treatment for a number of conditions, particularly those of the liver. CASE PRESENTATION A 29-year-old male presented at our clinic due to an episode of itching and burning in his mouth, swollen tongue, and difficulty swallowing following ingestion of teff flakes. He also reported sneezing, runny nose, watering and burning eyes, and wheezing following inhalation exposure to ground milk thistle. The patient's occupation is associated with exposure to these allergens. The patient underwent comprehensive allergy diagnostic assessments (including skin-prick testing, serum specific IgE levels, Faber test, spirometry, and acoustic rhinometry) and gastroenterological assessments. The diagnosis was established on skin tests with native allergens (milk thistle 16/35, teff flour 22/60, negative control 0/0, histamine 3/5) provided by the patient. There are no commercially available (standardized) tests for milk thistle or teff either in Poland or anywhere else in the world. CONCLUSIONS Milk thistle is available in the form of dry, finely-ground preparations (which are used as additives to bread, soups, and yoghurts) and extracts (which are used as ingredients in over-the-counter herbal remedies). Teff is a gluten-free cereal whose grains are rich in methionine, calcium, iron, folic acid, and antioxidants. This case report presents milk thistle and teff as potentially new allergens. A literature review revealed no similar allergy cases in Poland or elsewhere in the world.
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Affiliation(s)
- O. Wojas
- Deprtament of Environmental Hazard Prevention and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - E. Krzych-Fałta
- Deprtament of Environmental Hazard Prevention and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - P. Samel-Kowalik
- Deprtament of Environmental Hazard Prevention and Allergology, Medical University of Warsaw, Warsaw, Poland
| | - M. Żalikowska-Gardocka
- Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Warsaw, Poland
| | - E. Majsiak
- Polish-Ukrainian Foundation for the Development of Medicine, Lublin, Poland
| | - A. Mari
- Clinician and Scientist in Allergy and Immunology Centri Associati di Allergologia Molecolare (CAAM), Rome, Italy
| | - B. Samoliński
- Deprtament of Environmental Hazard Prevention and Allergology, Medical University of Warsaw, Warsaw, Poland
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AbouZid SF, Ahmed HS, Abd El Mageed AEMA, Moawad AS, Owis AI, Chen SN, Nachtergael A, McAlpine JB, Friesen JB, Pauli GF. Linear regression analysis of silychristin A, silybin A and silybin B contents in Silybum marianum. Nat Prod Res 2020; 34:305-310. [PMID: 30488719 DOI: 10.1080/14786419.2018.1527838] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Revised: 09/07/2018] [Accepted: 09/20/2018] [Indexed: 10/27/2022]
Abstract
Quantitative correlations between the contents of the flavonolignans silychristin A and silybins A/B provide biosynthetic clues that support a pathway in which one mesomeric form of a taxifolin radical is undergoing an oxidative coupling with a coniferyl alcohol radical. The flavonolignan content and patterns reported in the literature for 53 samples, representing populations of the Silybum marianum plant growing in different parts of the world, were subject to a meta-analysis. Linear regression analyses were carried out on these data sets, and a mathematical model was derived that predicts the content of silychristin A relative to the metabolomic pattern of its congeners. The validity of the model was verified by applying it to test samples. This approach could potentially become a tool to enhance the understanding of both the relative composition of the silymarin complex and the biosynthetic pathways that underlie its formation.
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Affiliation(s)
- Sameh F AbouZid
- Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Hayam S Ahmed
- Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | | | - Abeer S Moawad
- Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Asmaa I Owis
- Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt
| | - Shao-Nong Chen
- UIC/NIH Center for Botanical Dietary Supplements Research, Chicago, IL, USA
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - Amandine Nachtergael
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - James B McAlpine
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
| | - J Brent Friesen
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
- Physical Sciences Department, Rosary College of Arts and Sciences, Dominican University, River Forest, IL, USA
| | - Guido F Pauli
- UIC/NIH Center for Botanical Dietary Supplements Research, Chicago, IL, USA
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA
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Fasinu PS, Rapp GK. Herbal Interaction With Chemotherapeutic Drugs-A Focus on Clinically Significant Findings. Front Oncol 2019; 9:1356. [PMID: 31850232 PMCID: PMC6901834 DOI: 10.3389/fonc.2019.01356] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Accepted: 11/18/2019] [Indexed: 11/30/2022] Open
Abstract
One of the most consequential risks associated with the concomitant use of herbal products and chemotherapeutic agents is herb-drug interactions. The risk is higher in patients with chronic conditions taking multiple medications. Herb-drug interaction is particularly undesirable in cancer management because of the precipitous dose-effect relationship and toxicity of chemotherapeutic agents. The most common mechanism of herb-drug interaction is the herbal-mediated inhibition and/or induction of drug-metabolizing enzymes (DME) and/or transport proteins leading to the alteration in the pharmacokinetic disposition of the victim drug. Most mechanistic research has focused on laboratory-based studies, determining the effects of herbal products on DMEs and extrapolating findings to predict clinical relevance; however, not all DME/transporter protein inhibition/induction results in clinical herb-drug interaction. This study reviews relevant literature and identified six herbal products namely echinacea, garlic, ginseng, grapefruit juice, milk thistle, and St John's wort, which have shown interactions with chemotherapeutic agents in humans. This focus on clinically significant herb-drug interaction, should be of interest to the public including practitioners, researchers, and consumers of cancer chemotherapy.
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Affiliation(s)
- Pius S Fasinu
- Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC, United States
| | - Gloria K Rapp
- Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC, United States
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41
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Kalantari A, Salimi A, Kalantari H, Ebrahimi Broojeni J, Rashidi I, Raesi Vanani A, Bácskay I. The hepatoprotective effect of livergol microemulsion preparation (nanoparticle) against bromobenzene induced toxicity in mice. Toxicol Rep 2019; 6:444-448. [PMID: 31193476 PMCID: PMC6529715 DOI: 10.1016/j.toxrep.2019.05.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2018] [Revised: 04/20/2019] [Accepted: 05/08/2019] [Indexed: 12/17/2022] Open
Abstract
Livergol (LG), which is the extract of Silybum marianum and commonly known as milk thistle possess hepatoprotective effect. Orally administered LG significantly suppresses Bromobenzene (BB)-induced increases in serum activity of enzymes AST, ALT, ALP. Treatment with LG has improved hepatic damages due to BB severe degeneration and vacuolation of hepatocytes. Based on the results the efficacy of LG in MEs showed better drug solubility and permeability which lead to improve drug absorption among different biological membranes. The hepatoprotective effect of this formulation against BB toxicity has been conducted through the control release, high diffusion and absorption rates and improve and increase in oral bioavailability of active pharmaceutical agents. Livergol (LG), which is the extract of Silybum marianum and commonly known as milk thistle possess hepatoprotective effect and have got licensed for sale in Iran and other countries. LG was evaluated for its capacity to counteract the toxic effects of bromobenzene (BB) on mouse liver. The bioactive component of this plant is known to reinforce naturally occurring liver function through antioxidant activity, the stimulation of bile production and regeneration by the liver organ, resulting in enhanced protection against toxicants, hepatitis, and cirrhosis. The major bioactive components of this product are the flavonolignan ssilibinin, silidianin, silicristin, and isosilibinin. Mice were treated for 10 days with daily gavage of microemulsions (MEs), into which 0–400 mg/kg LG was dispersed. 0.36 ml/kg BB was injected intraperitoneally (ip) to each animal on day 10, followed by sacrifice on day 11, and histological evaluation of hematoxylin-eosin (HE)‐stained liver tissue samples, afterwards followed by evaluation liver enzymes level, aminotransferase (AST), alanine aminotransaminase (ALT) and alkaline phosphatase (ALP) activities. Significant suppression of BB-mediated damage to liver tissue, and increased in AST, ALT, and ALP level was observed to occur dose-responsively with LG administration, suggesting a use for LG as a chemoprotectant for persons chronically exposed to industrial solvents.
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Affiliation(s)
- Azin Kalantari
- Faculty of Pharmacy, Department of Pharmaceutical Technology, University of Debrecen Health Science Center, Debrecen, Hungary
| | - Anayatollah Salimi
- Nanotechnology Research Center, Department of Pharmaceutics, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Heibatullah Kalantari
- Nanotechnology Research Center, Department of Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Jalal Ebrahimi Broojeni
- Nanotechnology Research Center, Department of Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Iran Rashidi
- Nanotechnology Research Center, Department of Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Atefeh Raesi Vanani
- Nanotechnology Research Center, Department of Pharmacology and Toxicology, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ildikó Bácskay
- Faculty of Pharmacy, Department of Pharmaceutical Technology, University of Debrecen Health Science Center, Debrecen, Hungary
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Zhang T, Kawaguchi N, Yoshihara K, Hayama E, Furutani Y, Kawaguchi K, Tanaka T, Nakanishi T. Silibinin efficacy in a rat model of pulmonary arterial hypertension using monocrotaline and chronic hypoxia. Respir Res 2019; 20:79. [PMID: 31023308 PMCID: PMC6485095 DOI: 10.1186/s12931-019-1041-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Accepted: 04/02/2019] [Indexed: 01/07/2023] Open
Abstract
Background C-X-C chemokine receptor type 4 (CXCR4) may be involved in the development of pulmonary arterial hypertension (PAH). CXCR4 inhibitor AMD3100 was described to have a positive effect on the prevention of pulmonary arterial muscularization in PAH models. Silibinin is a traditional medicine that has an antagonistic effect on CXCR4. We investigated the effect of silibinin using rat models of PAH. Methods PAH was induced by a single subcutaneous injection of monocrotaline. The rats were maintained in a chronic hypoxic condition (10% O2) with or without silibinin. To evaluate the efficacy of silibinin on PAH, right ventricular systolic pressure (RVSP), Fulton index (weight ratio of right ventricle to the left ventricle and septum), percent medial wall thickness (% MT), and vascular occlusion score (VOS) were measured and calculated. Immunohistochemical analysis was performed targeting CXCR4 and c-Kit. Reverse transcription-quantitative polymerase chain reaction was performed for the stem cell markers CXCR4, stromal cell derived factor-1 (SDF-1), c-Kit, and stem cell factor (SCF), and the inflammatory markers monocyte chemoattractant protein 1 (MCP1), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNFα). Statistical analyses were performed using t-test and one-way analysis of variance with Bonferroni’s post hoc test. Results Silibinin treatment for 1 week reduced RVSP and Fulton index. Treatment for 2 weeks reduced RVSP, Fulton index, % MT, and VOS, as well as downregulating the expression of CXCR4, SDF-1, and TNFα in pulmonary arteries. In contrast, treatment for 3 weeks failed to ameliorate PAH. The time-course study demonstrated that RVSP, Fulton index, % MT, and VOS gradually increased over time, with a decrease in the expression of CXCR4 and TNFα occurring after 2 weeks of PAH development. After 3 weeks, SDF-1, c-Kit, and SCF began to decrease and, after 5 weeks, MCP1 and IL-6 gradually accumulated. Conclusions The CXCR4 inhibitor silibinin can ameliorate PAH, possibly through the suppression of the CXCR4/SDF-1 axis, until the point where PAH becomes a severe and irreversible condition. Silibinin results in reduced pulmonary arterial pressure and delays pulmonary arteriolar occlusion and pulmonary vascular remodeling. Electronic supplementary material The online version of this article (10.1186/s12931-019-1041-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Tingting Zhang
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.,Department of Structural Heart Disease, The First Affiliated Hospital of Xi'an Jiaotong University, 277 Yanta West Road, Xi'an, 710061, Shaanxi, China
| | - Nanako Kawaguchi
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
| | - Kenji Yoshihara
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Emiko Hayama
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Yoshiyuki Furutani
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Kayoko Kawaguchi
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Takeshi Tanaka
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan
| | - Toshio Nakanishi
- Department of Pediatric Cardiology and Adult Congenital Cardiology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku, Tokyo, 162-8666, Japan.
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Ameliorative effect of Silybin on bisphenol A induced oxidative stress, cell proliferation and steroid hormones oxidation in HepG2 cell cultures. Sci Rep 2019; 9:3228. [PMID: 30824780 PMCID: PMC6397216 DOI: 10.1038/s41598-019-40105-8] [Citation(s) in RCA: 33] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 02/01/2019] [Indexed: 01/28/2023] Open
Abstract
Bisphenol A (BPA) and silybin are considered xenoestrogens and could interfere with the action of endogenous hormones. It was demonstrated a higher level of BPA in plasma of nonalcoholic steatohepatitis (NASH) patients, compared to those with steatosis (NAFL). We investigated the effect of BPA and silybin, alone or in combination, on proliferation, oxidative stress and steroid metabolism in HepG2 grown in high glucose concentration medium (H-HepG2). Cell viability was assessed by adding 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT). TBARS were quantified by spectrophotometry. The effect of BPA, silybin and their combination on the expression of phosphorilized extracellular signal-regulated kinase (ERK), ERK and Caspase 3 was determined by Western blot analysis. The identifications of lipids and steroid hormones was performed by mass spectrometry. BPA elicited in H-HepG2 oxidative stress and steroid hormones oxidation leading to the formation of metabolite with estrogenic and genotoxic potentials. Silybin ameliorates the harmful BPA-induced effect decreasing glucose uptake and lipid peroxidation. Moreover silybin activates the synthesis of vitamin D3 metabolites and prevent the steroid hormones oxidation. BPA could be considered as an important risk factor in worsening and progression of NAFLD. At the same time silybin could be a valid support to counteract these effects in NASH patients.
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Involvement of CXCR4 in Normal and Abnormal Development. Cells 2019; 8:cells8020185. [PMID: 30791675 PMCID: PMC6406665 DOI: 10.3390/cells8020185] [Citation(s) in RCA: 102] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2018] [Revised: 01/30/2019] [Accepted: 02/13/2019] [Indexed: 02/06/2023] Open
Abstract
CXC motif chemokine receptor type 4 (CXCR4) is associated with normal and abnormal development, including oncogenesis. The ligand of CXCR4 is stromal cell-derived factor (SDF), also known as CXC motif ligand (CXCL) 12. Through the SDF-1/CXCR4 axis, both homing and migration of hematopoietic (stem) cells are regulated through niches in the bone marrow. Outside of the bone marrow, however, SDF-1 can recruit CXCR4-positive cells from the bone marrow. SDF/CXCR4 has been implicated in the maintenance and/or differentiation of stemness, and tissue-derived stem cells can be associated with SDF-1 and CXCR4 activity. CXCR4 plays a role in multiple pathways involved in carcinogenesis and other pathologies. Here, we summarize reports detailing the functions of CXCR4. We address the molecular signature of CXCR4 and how this molecule and cells expressing it are involved in either normal (maintaining stemness or inducing differentiation) or abnormal (developing cancer and other pathologies) events. As a constituent of stem cells, the SDF-1/CXCR4 axis influences downstream signal transduction and the cell microenvironment.
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45
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Sharifpanah F, Ali EH, Wartenberg M, Sauer H. The milk thistle (Silybum marianum) compound Silibinin stimulates leukopoiesis from mouse embryonic stem cells. Phytother Res 2019; 33:452-460. [PMID: 30548344 DOI: 10.1002/ptr.6241] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/10/2018] [Revised: 10/30/2018] [Accepted: 11/05/2018] [Indexed: 01/02/2023]
Abstract
The milk thistle compound Silibinin (i.e., a 1:1 mixture of Silybin A and Silybin B) stimulates vasculogenesis of mouse embryonic stem (ES) cells. Because vasculogenesis and leukopoiesis are interrelated, the effect of Silibinin on leukopoiesis of ES cells was investigated. Treatment of differentiating ES cells with hydrosoluble Silibinin-C-2',3-dihydrogen succinate dose-dependent increased the number of CD18+ , CD45+ , and CD68+ cells, indicating leukocyte/macrophage differentiation. Silibinin treatment activated phosphoinositide 3-kinase (PI3K), AKT (protein kinase B), signal transducer and activator of transcription 3 (STAT3), stimulated hypoxia-induced factor-1α (HIF-1α), and vascular endothelial growth factor receptor 2 (VEGFR2) expression and raised intracellular nitric oxide (NO). Western blot experiments showed that upon coincubation with either the PI3K inhibitor LY294002, the STAT3 inhibitor Stattic, the AKT antagonist AKT inhibitor VIII, or the NO inhibitor L-NAME, the Silibinin-induced expression of CD18, CD45, and CD68 was abolished. Moreover, the stimulation of HIF-1α and VEGFR2 expression was blunted upon STAT3 and PI3K/AKT inhibition. Treatment of differentiating ES cells with L-NAME abolished the stimulation of VEGFR2 and VE-cadherin expression achieved with Silibinin, indicating that NO is involved in vasculogenesis and leukocyte differentiation pathways. In summary, the data of the present study demonstrate that Silibinin stimulates leukocyte differentiation of ES cells, which is associated to vasculogenesis and regulated by PI3K/AKT-, STAT3-, and NO-mediated signaling.
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Affiliation(s)
- Fatemeh Sharifpanah
- Department of Physiology, Faculty of Medicine, Justus Liebig University Giessen, Giessen, Germany
| | - Enas Hussein Ali
- Department of Physiology, Faculty of Medicine, Justus Liebig University Giessen, Giessen, Germany
| | - Maria Wartenberg
- Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology and Intensive Medical Care, University Hospital Jena, Friedrich-Schiller-University Jena, Jena, Germany
| | - Heinrich Sauer
- Department of Physiology, Faculty of Medicine, Justus Liebig University Giessen, Giessen, Germany
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Mina PR, Kumar Y, Verma AK, Khan F, Tandon S, Pal A, Darokar MP. Silymarin, a polyphenolic flavonoid impede Plasmodium falciparum growth through interaction with heme. Nat Prod Res 2019; 34:2647-2651. [DOI: 10.1080/14786419.2018.1548449] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Affiliation(s)
- Pooja Rani Mina
- Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
| | - Yogesh Kumar
- Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
| | - Ajeet Kumar Verma
- Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
| | - Feroz Khan
- Metabolic & Structural Biology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
| | - Sudeep Tandon
- Chemical Processing Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, India
| | - Anirban Pal
- Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
| | - Mahendra Pandurang Darokar
- Molecular Bioprospection Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow, U.P., India
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Vue B, Zhang S, Vignau A, Chen G, Zhang X, Diaz W, Zhang Q, Zheng S, Wang G, Chen QH. O-Aminoalkyl- O-Trimethyl-2,3-Dehydrosilybins: Synthesis and In Vitro Effects Towards Prostate Cancer Cells. Molecules 2018; 23:molecules23123142. [PMID: 30501133 PMCID: PMC6320956 DOI: 10.3390/molecules23123142] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2018] [Revised: 11/26/2018] [Accepted: 11/29/2018] [Indexed: 01/08/2023] Open
Abstract
As part of our ongoing silybin project, this study aims to introduce a basic nitrogen-containing group to 7-OH of 3,5,20-O-trimethyl-2,3-dehydrosilybin or 3-OH of 5,7,20-O-trimethyl-2,3-dehydrosilybin via an appropriate linker for in vitro evaluation as potential anti-prostate cancer agents. The synthetic approaches to 7-O-substituted-3,5,20-O-trimethyl-2,3-dehydrosilybins through a five-step procedure and to 3-O-substituted-5,7,20-O-trimethyl-2,3- dehydrosilybins via a four-step transformation have been developed. Thirty-two nitrogen-containing derivatives of silybin have been achieved through these synthetic methods for the evaluation of their antiproliferative activities towards both androgen-sensitive (LNCaP) and androgen-insensitive prostate cancer cell lines (PC-3 and DU145) using the WST-1 cell proliferation assay. These derivatives exhibited greater in vitro antiproliferative potency than silibinin. Among them, 11, 29, 31, 37, and 40 were identified as five optimal derivatives with IC50 values in the range of 1.40⁻3.06 µM, representing a 17- to 52-fold improvement in potency compared to silibinin. All these five optimal derivatives can arrest the PC-3 cell cycle in the G₀/G₁ phase and promote PC-3 cell apoptosis. Derivatives 11, 37, and 40 are more effective than 29 and 31 in activating PC-3 cell apoptosis.
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Affiliation(s)
- Bao Vue
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - Sheng Zhang
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - Andre Vignau
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - Guanglin Chen
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - Xiaojie Zhang
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - William Diaz
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
| | - Qiang Zhang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
| | - Shilong Zheng
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
| | - Guangdi Wang
- Department of Chemistry and RCMI Cancer Research Center, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USA.
| | - Qiao-Hong Chen
- Department of Chemistry, California State University, Fresno, 2555 E. San Ramon Avenues, M/S SB70, Fresno, CA 93740, USA.
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Feldman NB, Gromovykh TI, Sedyakina NE, Krasnyuk II, Lutsenko SV. Cytotoxic and Antitumor Activity of Liposomal Silibinin. BIONANOSCIENCE 2018. [DOI: 10.1007/s12668-018-0556-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
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Rafizadeh A, Koohi-Dehkordi M, Sorkheh K. Molecular insights of genetic variation in milk thistle (Silybum marianum [L.] Gaertn.) populations collected from southwest Iran. Mol Biol Rep 2018; 45:601-609. [PMID: 29882084 DOI: 10.1007/s11033-018-4198-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2017] [Accepted: 05/24/2018] [Indexed: 10/14/2022]
Abstract
Milk thistle (Silybum marianum) is among the world's popular medicinal plants. Start Codon Targeted (SCoT) marker system was utilized to investigate the genetic variability of 80 S. marianum genotypes from eight populations in Iran. SCoT marker produced 255 amplicons and 84.03% polymorphism was generated. The SCoT marker system's polymorphism information content value was 0.43. The primers' resolving power values were between 4.18 and 7.84. The percentage of polymorphic bands was between 33.3 and 100%. The Nei's gene diversity (h) was 0.19-1.30 with an average 0.72. The Shannon's index (I) ranged from 0.29 to 1.38 with an average value of 0.83. The average gene flow (0.37) demonstrated a high genetic variation among the studied populations. The variation of 42% was displayed by the molecular variance analysis among the populations while a recorded variation of 58% was made within the populations. Current investigation suggested that SCoT marker system could effectively evaluate milk thistle genotypes genetic diversity.
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Affiliation(s)
- Azam Rafizadeh
- Department of Agricultural Science, Payame-Noor University, P. O. Box 19395-3697, Tehran, Iran
| | - Mehrana Koohi-Dehkordi
- Department of Agricultural Science, Payame-Noor University, P. O. Box 19395-3697, Tehran, Iran.
| | - Karim Sorkheh
- Department of Agronomy and Plant Breeding, Faculty of Agriculture, Shahid Chamran University of Ahvaz, P. O. Box 61355/144, Ahvaz, Iran
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Ruan HS, Zhang HF, Teng K. Optimization of Microwave-assisted Extraction of Silymarin from Silybum marianum Straws by Response Surface Methodology and Quantification by High-Performance Liquid Chromatograph Method. Pharmacogn Mag 2018; 14:22-26. [PMID: 29576697 PMCID: PMC5858236 DOI: 10.4103/pm.pm_556_16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2016] [Revised: 01/10/2017] [Indexed: 11/05/2022] Open
Abstract
Background: Silybum marianum, a member of the Aster family, is a well-known Chinese herb and the source of a popular antioxidant that is extensively used in Asia. The abundant S. marianum straws are still underutilized and wastefully discarded to pollute the environment. Objective: To solve the above problem and better utilize S. marianum straws, the objective of this study was to optimize the conditions for extraction of silymarin from S. marianum straws. Materials and Methods: A combination of microwave-assisted extraction and response surface methodology (RSM) was used for silymarin from S. marianum straws and yield assessment by high-performance liquid chromatography method. The RSM was based on a five-level, four-variable central composite design (CCD). Results: The results indicated that the optimal conditions to obtain highest yields of silymarin were microwave power of 146 W, extraction time of 117 s, liquid-to-solid ratio of 16:1 mL/g, and ethanol concentration of 43% (v/v). Validation tests indicated that under the optimized conditions, the actual yield of silymarin was 6.83 ± 0.57 mg/g with relative standard deviation of 0.92% (n = 5), which was in good agreement with the predicted yield. Conclusions: The exploitation of the natural plant resources present very important impact for the economic development. The knowledge obtained from this work should be useful to further exploit and apply this material. SUMMARY
Silymarin has been isolated from Silybum marianum straws by microwave-assisted extraction and response surface methodology The results obtained are helpful for the full utilization of S. marianum straws The microwave-assisted extraction is a very useful method for the extraction of important phytochemicals from plant materials. Abbreviations used: MAE: Microwave-assisted extraction, RSM: Response surface methodology, HPLC: High-performance liquid chromatography, CCD: Central composite design, ANOVA: Analysis of variance.
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Affiliation(s)
- Hong-Sheng Ruan
- College of China Medicine, Zhejiang Pharmaceutical College, Ningbo, PR China
| | - Hai-Feng Zhang
- College of Pharmacy and Food Science, Tonghua Normal University, Tonghua, PR China
| | - Kun Teng
- College of Pharmacy and Food Science, Tonghua Normal University, Tonghua, PR China
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