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Huang X, Yang J, Ho CT, Ke Q, Kou X. Functional flavor agents: enhancing health benefits and consumer preferences. Crit Rev Food Sci Nutr 2025:1-29. [PMID: 40338670 DOI: 10.1080/10408398.2025.2494297] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/10/2025]
Abstract
Increasing health consciousness among consumers has significantly driven the demand for functional foods; however, market acceptance largely hinges on flavor profiles. Functional flavor agents, which simultaneously enhance taste and provide health benefits, meet the dual consumer demand for flavor and nutrition. This review classifies functional flavor agents into five categories based on their sensory characteristics. Their health benefits are explored with a focus on their potential roles in disease prevention and treatment, including improved energy metabolism, cardiovascular support, anti-tumor effects, modulation of gut microbiota, and enhancement of immune function. Emerging trends in the food industry are highlighted, underscoring the significant influence of these agents on product innovation. However, the integration of functional flavor agents into food products presents challenges, particularly in optimizing interactions to maximize both sensory appeal and health benefits. Innovative approaches are required to navigate the complex interplay between flavor agents and food components, enhancing flavor stability and sensory quality. Ultimately, the strategic application of functional flavor agents in food production holds promise for fostering a health-oriented market that aligns with consumer expectations for taste and nutrition.
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Affiliation(s)
- Xin Huang
- Collaborative Innovation Center of Fragrance Flavour and Cosmetics, School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, China
| | - Jiaqi Yang
- Collaborative Innovation Center of Fragrance Flavour and Cosmetics, School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, China
| | - Chi-Tang Ho
- Department of Food Science, Rutgers University, New Brunswick, NJ, USA
| | - Qinfei Ke
- Collaborative Innovation Center of Fragrance Flavour and Cosmetics, School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, China
| | - Xingran Kou
- Collaborative Innovation Center of Fragrance Flavour and Cosmetics, School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai, China
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2
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Li J, Ma J, Cao R, Zhang Q, Li M, Wang W, Wang Y, Li W, Zhu Y, Leng L. A skin organoid-based infection platform identifies an inhibitor specific for HFMD. Nat Commun 2025; 16:2513. [PMID: 40082449 PMCID: PMC11906866 DOI: 10.1038/s41467-025-57610-2] [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: 06/24/2024] [Accepted: 02/27/2025] [Indexed: 03/16/2025] Open
Abstract
The EV-A71 poses a serious threat to the health and lives of children. The EV-A71 can be transmitted by direct and indirect skin contact. Therefore, there is an urgent need to create novel skin models using human-derived cells to study the biology and pathogenesis of the virus and facilitate drug screening. Here, we use human induced pluripotent stem cells-derived skin organoids (hiPSC-SOs) as a model for EV-A71 infection and find that multiple cell types within the skin organoids, including epidermal cells, hair follicle cells, fibroblasts, and nerve cells, express EV-A71 receptors and are susceptible to EV-A71 infection. We elucidate the specific response of different cell types to EV-A71 and reveal that EV-A71 infection can degrade extracellular collagen and affect fibroblasts. We find that EV-A71 can mediate epidermal cell damage through autophagy and Integrin/Hippo-YAP/TAZ signaling pathways, thereby promoting hyperproliferation of progenitor cells. Based on this finding, we identify an autophagy-associated protein as a drug target of EV-A71 and discover an EV-A71 replication inhibitor. Altogether, these data suggest that hiPSC-SOs can be used as an infectious disease model to study skin infectious diseases, providing a valuable resource for drug screening to identify candidate virus therapeutics.
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Affiliation(s)
- Jun Li
- Stem cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Department of Dermatology, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, China
| | - Jie Ma
- State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China
| | - Ruiyuan Cao
- National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China
| | - Qiyu Zhang
- Stem cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Department of Dermatology, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, China
| | - Mansheng Li
- State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China
| | - Wenwen Wang
- Stem cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- Department of Dermatology, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, 100730, China
| | - Yujie Wang
- Stem cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Wei Li
- National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China
| | - Yunping Zhu
- State Key Laboratory of Medical Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing, 102206, China
| | - Ling Leng
- Stem cell and Regenerative Medicine Lab, Institute of Clinical Medicine, State Key Laboratory of Complex, Severe, and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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Shen P, Zhang L, Jiang X, Yu B, Zhang J. Targeting HMGB1 and Its Interaction with Receptors: Challenges and Future Directions. J Med Chem 2024; 67:21671-21694. [PMID: 39648929 DOI: 10.1021/acs.jmedchem.4c01912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/10/2024]
Abstract
High mobility group box 1 (HMGB1) is a nonhistone chromatin protein predominantly located in the nucleus. However, under pathological conditions, HMGB1 can translocate from the nucleus to the cytoplasm and subsequently be released into the extracellular space through both active secretion and passive release mechanisms. The distinct cellular locations of HMGB1 facilitate its interaction with various endogenous and exogenous factors, allowing it to perform diverse functions across a range of diseases. This Perspective provides a comprehensive overview of the structure, release mechanisms, and multifaceted roles of HMGB1 in disease contexts. Furthermore, it introduces the development of both small molecule and macromolecule inhibitors targeting HMGB1 and its interaction with receptors. A detailed analysis of the predicted pockets is also presented, aiming to establish a foundation for the future design and development of HMGB1 inhibitors.
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Affiliation(s)
- Pingping Shen
- Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Libang Zhang
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, PR China
| | - Xuewa Jiang
- Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China
| | - Boyang Yu
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, P. R. China
| | - Jian Zhang
- Department of Resources Science of Traditional Chinese Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 210009, P. R. China
- Jiangsu Key Laboratory of TCM Evaluation and Translational Research, China Pharmaceutical University, Nanjing 211198, P. R. China
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4
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Giangrandi I, Dinu M, Napoletano A, Maggini V, Lombardi N, Crescioli G, Gallo E, Mascherini V, Antonelli M, Donelli D, Vannacci A, Firenzuoli F, Sofi F. Licorice and liver function in patients with primary liver disease: A systematic review and meta-analysis of RCTs. Phytother Res 2024; 38:4614-4627. [PMID: 39079711 DOI: 10.1002/ptr.8288] [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: 09/22/2023] [Revised: 05/24/2024] [Accepted: 06/23/2024] [Indexed: 10/25/2024]
Abstract
Licorice (Glycyrrhiza spp.) has been a cornerstone of traditional Chinese and Japanese medicine. This systematic review and meta-analysis aimed to evaluate the efficacy of licorice formulations, alone or in combination with other herbs, on liver function enzymes in patients with primary liver disease. We systematically searched MEDLINE, Embase, Scopus, Web of Science, and Cochrane Library up to April 2024. Randomized controlled trials (RCTs) comparing the effects of Glycyrrhiza spp. preparations versus placebo or standard of care controls were included. Standard Cochrane methods were used to extract data and appraise eligible studies. A total of 15 RCTs, involving 1367 participants, were included in the analysis. The studies varied widely in geographical location, duration, and licorice preparations used. Licorice significantly reduced alanine aminotransferase (ALT) by 15.63 U/L (95% CI: -25.08, -6.18; p = 0.001) and aspartate aminotransferase (AST) by 7.37 U/L (95% CI: -13.13, -1.61; p = 0.01) compared to control groups. Subgroup analyses revealed that purified glycyrrhizic acid compounds were particularly effective, showing greater reductions in ALT and AST without significant heterogeneity. Although licorice treatment did not significantly impact gamma-glutamyl transferase and total bilirubin (TBIL) levels overall, specific licorice-herb preparations did show a notable reduction in TBIL. The safety profile of licorice was consistent with known side effects, predominantly mild and related to its mineralocorticoid effects. Despite heterogeneity and potential language bias, the findings suggest that licorice can enhance liver function. Further studies should standardize licorice preparations and explore its role in multifaceted herbal formulations to better understand its hepatoprotective mechanisms.
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Affiliation(s)
- Ilaria Giangrandi
- Unit of Clinical Nutrition, Careggi University Hospital, Florence, Italy
| | - Monica Dinu
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Antonia Napoletano
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
| | - Valentina Maggini
- Research and Innovation Center for Phytotherapy and Integrated Medicine - Referring Center for Phytotherapy, Tuscany Region, Careggi University Hospital, Florence, Italy
| | - Niccolò Lombardi
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
- Integrative Medicine Unit, Tuscan Regional Centre of Pharmacovigilance, Florence, Italy
| | - Giada Crescioli
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
- Integrative Medicine Unit, Tuscan Regional Centre of Pharmacovigilance, Florence, Italy
| | - Eugenia Gallo
- Research and Innovation Center for Phytotherapy and Integrated Medicine - Referring Center for Phytotherapy, Tuscany Region, Careggi University Hospital, Florence, Italy
| | - Vittorio Mascherini
- Research and Innovation Center for Phytotherapy and Integrated Medicine - Referring Center for Phytotherapy, Tuscany Region, Careggi University Hospital, Florence, Italy
| | - Michele Antonelli
- Deparment of Public Health, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, Italy
| | - Davide Donelli
- Division of Cardiology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
| | - Alfredo Vannacci
- Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
- Integrative Medicine Unit, Tuscan Regional Centre of Pharmacovigilance, Florence, Italy
| | - Fabio Firenzuoli
- Research and Innovation Center for Phytotherapy and Integrated Medicine - Referring Center for Phytotherapy, Tuscany Region, Careggi University Hospital, Florence, Italy
| | - Francesco Sofi
- Unit of Clinical Nutrition, Careggi University Hospital, Florence, Italy
- Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy
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Cristani M, Citarella A, Carnamucio F, Micale N. Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer. Biomolecules 2024; 14:1031. [PMID: 39199418 PMCID: PMC11352298 DOI: 10.3390/biom14081031] [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: 07/30/2024] [Revised: 08/16/2024] [Accepted: 08/18/2024] [Indexed: 09/01/2024] Open
Abstract
Oxidative stress is a key factor in the pathological processes that trigger various chronic liver diseases, and significantly contributes to the development of hepatocarcinogenesis. Natural antioxidants reduce oxidative stress by neutralizing free radicals and play a crucial role in the treatment of free-radical-induced liver diseases. However, their efficacy is often limited by poor bioavailability and metabolic stability. To address these limitations, recent advances have focused on developing nano-drug delivery systems that protect them from degradation and enhance their therapeutic potential. Among the several critical benefits, they showed to be able to improve bioavailability and targeted delivery, thereby reducing off-target effects by specifically directing the antioxidant to the liver tumor site. Moreover, these nanosystems led to sustained release, prolonging the therapeutic effect over time. Some of them also exhibited synergistic effects when combined with other therapeutic agents, allowing for improved overall efficacy. This review aims to discuss recent scientific advances in nano-formulations containing natural antioxidant molecules, highlighting their potential as promising therapeutic approaches for the treatment of liver cancer. The novelty of this review lies in its comprehensive focus on the latest developments in nano-formulations of natural antioxidants for the treatment of liver cancer.
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Affiliation(s)
- Mariateresa Cristani
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, Italy;
| | - Andrea Citarella
- Department of Chemistry, University of Milan, Via Golgi 19, I-20133 Milano, Italy;
| | - Federica Carnamucio
- Center of Pharmaceutical Engineering and Sciences, Department of Pharmaceutics, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Nicola Micale
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres 31, I-98166 Messina, Italy;
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Halder J, Dubey D, Kanti Rajwar T, Mishra A, Satpathy B, Sahoo D, Prasad Yadav N, Kumar Rai V, Pradhan D, Manoharadas S, Kar B, Ghosh G, Rath G. Local delivery of methotrexate/glycyrrhizin-loaded hyaluronic acid nanofiber for the management of oral cancer. Int J Pharm 2024; 660:124311. [PMID: 38848798 DOI: 10.1016/j.ijpharm.2024.124311] [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: 02/19/2024] [Revised: 05/29/2024] [Accepted: 06/04/2024] [Indexed: 06/09/2024]
Abstract
The challenges in treating oral cancer include the limited effectiveness and systemic side effects of conventional chemotherapy and radiation therapy. Hyaluronic acid (HA) based Glycyrrhizin (GL) and Methotrexate (MT) loaded localized delivery systems, specifically nanofiber (NF) based platforms, were developed to address these challenges. The electrospinning method was used for the successful fabrication of a homogenous NF membrane and characterized for morphology, drug entrapment efficiency, tensile strength, and ex-vivo mucoadhesive study. Also, it was evaluated for in-vitro drug release profile, ex-vivo drug permeability, in-vitro anti-inflammatory, apoptosis assay by MTT and flow, and against specific cell lines in order to determine their potential for therapeutic use. Superior tensile breaking force (50 g), mucoadhesive strength of 153 gm/cm2, drug permeability, and releasing properties of designed NF, making them perfect requirements for oral cavity delivery. The anticancer potential of MT in the MTT assay and flow cytometry analysis was significantly increased in oral epidermal carcinoma cell (KB cell) for drug-loaded NF with 63.97 ± 1.99 % apoptosis, at 24 h. With these incorporated, GL with MT in NF had an anti-inflammatory potential, also demonstrated in-vitro and in-vivo. In the Ehrlich Ascites Carcinoma (EAC) induced mice model, the optimal formulation's shows better potential for tumor regression when comparing the developed NF formulation to the drugs. Experimental results show that by lowering mucositis-related inflammation and enhancing the effectiveness of oral cancer treatment, a developed nanofiber-based local drug delivery system offers a feasible strategy for managing oral cancer.
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Affiliation(s)
- Jitu Halder
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Debasmita Dubey
- Institute of Medical Sciences and Sum Hospital, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Tushar Kanti Rajwar
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Ajit Mishra
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Bibhanwita Satpathy
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Debasish Sahoo
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, U.P., India
| | - Narayan Prasad Yadav
- Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants, P.O. CIMAP, Lucknow 226015, U.P., India
| | - Vineet Kumar Rai
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Deepak Pradhan
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Salim Manoharadas
- Department of Botany and Microbiology, College of Science, King Saud University, P.O. Box. 2454, 11451 Riyadh, Saudi Arabia
| | - Biswakanth Kar
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Goutam Ghosh
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India
| | - Goutam Rath
- School of Pharmaceutical Sciences, Siksha O Anusandhan (Deemed to be University), Bhubaneswar, Odisha, India.
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Gu W, Zeng Q, Wang X, Jasem H, Ma L. Acute Lung Injury and the NLRP3 Inflammasome. J Inflamm Res 2024; 17:3801-3813. [PMID: 38887753 PMCID: PMC11182363 DOI: 10.2147/jir.s464838] [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: 02/20/2024] [Accepted: 05/22/2024] [Indexed: 06/20/2024] Open
Abstract
Acute lung injury (ALI) manifests through harm to the capillary endothelium and alveolar epithelial cells, arising from a multitude of factors, leading to scattered interstitial alterations, pulmonary edema, and subsequent acute hypoxic respiratory insufficiency. Acute lung injury (ALI), along with its more serious counterpart, acute respiratory distress syndrome (ARDS), carry a fatality rate that hovers around 30-40%. Its principal pathological characteristic lies in the unchecked inflammatory reaction. Currently, the main strategies for treating ALI are alleviation of inflammation and prevention of respiratory failure. Concerning the etiology of ALI, NLRP3 Inflammasome is essential to the body's innate immune response. The composition of this inflammasome complex includes NLRP3, the pyroptosis mediator ASC, and pro-caspase-1. Recent research has reported that the inflammatory response centered on NLRP3 inflammasomes plays a key part in inflammation in ALI, and may hence be a prospective candidate for therapeutic intervention. In the review, we present an overview of the ailment characteristics of acute lung injury along with the constitution and operation of the NLRP3 inflammasome within this framework. We also explore therapeutic strategies targeting the NLRP3 inflammasome to combat acute lung injury.
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Affiliation(s)
- Wanjun Gu
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Qi Zeng
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Xin Wang
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Huthaifa Jasem
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
| | - Ling Ma
- Department of Anesthesiology, Shengjing Hospital of China Medical University, Shenyang, People’s Republic of China
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Rijo P, Abuamara TMM, Ali Lashin LS, Kamar SA, Isca VMS, Mohammed TS, Abdrabo MSM, Amin MA, Abd El Maksoud AI, Hassan A. Glycyrrhizic Acid Nanoparticles Subside the Activity of Methicillin-Resistant Staphylococcus aureus by Suppressing PBP2a. Pharmaceuticals (Basel) 2024; 17:589. [PMID: 38794159 PMCID: PMC11123903 DOI: 10.3390/ph17050589] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2024] [Revised: 04/18/2024] [Accepted: 04/24/2024] [Indexed: 05/26/2024] Open
Abstract
Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA) are classified as high-risk infections that can lead to death, particularly among older individuals. Nowadays, plant nanoparticles such as glycyrrhizic acid are recognized as efficient bactericides against a wide range of bacterial strains. Recently, scientists have shown interest in plant extract nanoparticles, derived from natural sources, which can be synthesized into nanomaterials. Interestingly, glycyrrhizic acid is rich in antioxidants as well as antibacterial agents, and it exhibits no adverse effects on normal cells. In this study, glycyrrhizic acid nanoparticles (GA-NPs) were synthesized using the hydrothermal method and characterized through physicochemical techniques such as UV-visible spectrometry, DLS, zeta potential, and TEM. The antimicrobial activity of GA-NPs was investigated through various methods, including MIC assays, anti-biofilm activity assays, ATPase activity assays, and kill-time assays. The expression levels of mecA, mecR1, blaR1, and blaZ genes were measured by quantitative RT-qPCR. Additionally, the presence of the penicillin-binding protein 2a (PBP2a) protein of S. aureus and MRSA was evaluated by a Western blot assay. The results emphasized the fabrication of GA nanoparticles in spherical shapes with a diameter in the range of 40-50 nm. The data show that GA nanoparticles exhibit great bactericidal effectiveness against S. aureus and MRSA. The treatment with GA-NPs remarkably reduces the expression levels of the mecA, mecR1, blaR1, and blaZ genes. PBP2a expression in MRSA was significantly reduced after treatment with GA-NPs. Overall, this study demonstrates that glycyrrhizic acid nanoparticles have potent antibacterial activity, particularly against MRSA. This research elucidates the inhibition mechanism of glycyrrhizic acid, which involves the suppressing of PBP2a expression. This work emphasizes the importance of utilizing plant nanoparticles as effective antimicrobial agents against a broad spectrum of bacteria.
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Affiliation(s)
- Patricia Rijo
- CBIOS—Lusófona University’s Research Center for Biosciences and Health Technologies, 1749-024 Lisbon, Portugal;
- Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal
| | - Tamer M. M. Abuamara
- Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan; (T.M.M.A.); (L.S.A.L.); (S.A.K.)
- Department of Histology, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Lashin Saad Ali Lashin
- Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan; (T.M.M.A.); (L.S.A.L.); (S.A.K.)
- Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt
| | - Sherif A. Kamar
- Department of Basic Medical Science, Faculty of Dentistry, Al-Ahliyya Amman University, Amman 19111, Jordan; (T.M.M.A.); (L.S.A.L.); (S.A.K.)
- Department of Anatomy and Embryology, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt
| | - Vera M. S. Isca
- CBIOS—Lusófona University’s Research Center for Biosciences and Health Technologies, 1749-024 Lisbon, Portugal;
| | - Tahseen S. Mohammed
- Department of Public Health and Community Medicine, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt; (T.S.M.); (M.S.M.A.)
| | - Mohamed S. M. Abdrabo
- Department of Public Health and Community Medicine, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt; (T.S.M.); (M.S.M.A.)
| | - Mohamed A. Amin
- Department of Basic Medical Science, Faculty of Dentistry, Zarqa University, Zarqa 13110, Jordan;
- Department of Microbiology and Immunology, Faculty of Medicine, Al-Azhar University, Cairo 11884, Egypt
| | - Ahmed I. Abd El Maksoud
- College of Biotechnology, Misr University of Science and Technology, Giza 12573, Egypt;
- Department of Industrial Biotechnology, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat 32897, Egypt
| | - Amr Hassan
- Department of Bioinformatics, Genetic Engineering and Biotechnology Research Institute (GEBRI), University of Sadat City, Sadat 32897, Egypt
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Islam MR, Rauf A, Alash S, Fakir MNH, Thufa GK, Sowa MS, Mukherjee D, Kumar H, Hussain MS, Aljohani ASM, Imran M, Al Abdulmonem W, Thiruvengadam R, Thiruvengadam M. A comprehensive review of phytoconstituents in liver cancer prevention and treatment: targeting insights into molecular signaling pathways. Med Oncol 2024; 41:134. [PMID: 38703282 DOI: 10.1007/s12032-024-02333-5] [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: 12/08/2023] [Accepted: 02/13/2024] [Indexed: 05/06/2024]
Abstract
Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.
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Affiliation(s)
- Md Rezaul Islam
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Abdur Rauf
- Department of Chemistry, University of Swabi, Anbar, 23561, Khyber Pakhtunkhwa, Pakistan.
| | - Shopnil Alash
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Md Naeem Hossain Fakir
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Gazi Kaifeara Thufa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Mahbuba Sharmin Sowa
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Daffodil Smart City, Birulia, Savar, Dhaka, 1216, Bangladesh
| | - Dattatreya Mukherjee
- Raiganj Government Medical College and Hospital, Pranabananda Sarani, Raiganj, 733134, West Bengal, India
| | - Harendra Kumar
- Dow University of Health Sciences, Mission Rd, New Labour Colony Nanakwara, Karachi, 74200, Sindh, Pakistan
| | - Md Sadique Hussain
- School of Pharmacy, Suresh Gyan Vihar University, Mahal Road, Jagatpura, Jaipur, 302017, Rajasthan, India
| | - Abdullah S M Aljohani
- Department of Medical Biosciences, College of Veterinary Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Muhammad Imran
- Chemistry Department, Faculty of Science, King Khalid University, P.O. Box 9004, 61413, Abha, Saudi Arabia
| | - Waleed Al Abdulmonem
- Department of Pathology, College of Medicine, Qassim University, Buraydah, Saudi Arabia
| | - Rekha Thiruvengadam
- Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical & Technical Sciences (SIMATS), Saveetha University, Chennai, 600077, Tamil Nadu, India.
| | - Muthu Thiruvengadam
- Department of Crop Science, College of Sanghuh Life Science, Konkuk University, Seoul, 05029, South Korea
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10
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Chung MC, Su LJ, Chen CL, Wu LC. AI-assisted literature exploration of innovative Chinese medicine formulas. Front Pharmacol 2024; 15:1347882. [PMID: 38584602 PMCID: PMC10995307 DOI: 10.3389/fphar.2024.1347882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 02/21/2024] [Indexed: 04/09/2024] Open
Abstract
Objective: Our study provides an innovative approach to exploring herbal formulas that contribute to the promotion of sustainability and biodiversity conservation. We employ data mining, integrating keyword extraction, association rules, and LSTM-based generative models to analyze classical Traditional Chinese Medicine (TCM) texts. We systematically decode classical Chinese medical literature, conduct statistical analyses, and link these historical texts with modern pharmacogenomic references to explore potential alternatives. Methods: We present a novel iterative keyword extraction approach for discerning diverse herbs in historical TCM texts from the Pu-Ji Fang copies. Utilizing association rules, we uncover previously unexplored herb pairs. To bridge classical TCM herbal pairs with modern genetic relationships, we conduct gene-herb searches in PubMed and statistically validate this genetic literature as supporting evidence. We have expanded on the present work by developing a generative language model for suggesting innovative TCM formulations based on textual herb combinations. Results: We collected associations with 7,664 PubMed cross-search entries for gene-herb and 934 for Shenqifuzheng Injection as a positive control. We analyzed 16,384 keyword combinations from Pu-Ji Fang's 426 volumes, employing statistical methods to probe gene-herb associations, focusing on examining differences among the target genes and Pu-Ji Fang herbs. Conclusion: Analyzing Pu-Ji Fang reveals a historical focus on flavor over medicinal aspects in TCM. We extend our work on developing a generative model from classical textual keywords to rapidly produces novel herbal compositions or TCM formulations. This integrated approach enhances our comprehension of TCM by merging ancient text analysis, modern genetic research, and generative modeling.
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Affiliation(s)
- Meng-Chi Chung
- Department of Biomedical Science and Engineering, National Central University (NCU), Jhong-Li City, Taiwan
| | - Li-Jen Su
- Department of Biomedical Science and Engineering, National Central University (NCU), Jhong-Li City, Taiwan
- Education and Research Center for Technology Assisted Substance Abuse Prevention and Management, National Central University (NCU), Taoyuan, Taiwan
- Core Facilities for High Throughput Experimental Analysis, Department of Biomedical Sciences and Engineering, National Central University (NCU), Taoyuan, Taiwan
- IIHMED Reproductive Center, Taipei, Taiwan
- Tian Medicine Phamaceutical Company Ltd., Taipei, Taiwan
| | - Chien-Lin Chen
- IIHMED Reproductive Center, Taipei, Taiwan
- School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan
- Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan
| | - Li-Ching Wu
- Department of Biomedical Science and Engineering, National Central University (NCU), Jhong-Li City, Taiwan
- Education and Research Center for Technology Assisted Substance Abuse Prevention and Management, National Central University (NCU), Taoyuan, Taiwan
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11
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Zhou XQ, Li YP, Dang SS. Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy. World J Hepatol 2024; 16:164-176. [PMID: 38495282 PMCID: PMC10941735 DOI: 10.4254/wjh.v16.i2.164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 01/10/2024] [Accepted: 01/18/2024] [Indexed: 02/27/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and poses a major challenge to global health due to its high morbidity and mortality. Conventional chemotherapy is usually targeted to patients with intermediate to advanced stages, but it is often ineffective and suffers from problems such as multidrug resistance, rapid drug clearance, nonspecific targeting, high side effects, and low drug accumulation in tumor cells. In response to these limitations, recent advances in nanoparticle-mediated targeted drug delivery technologies have emerged as breakthrough approaches for the treatment of HCC. This review focuses on recent advances in nanoparticle-based targeted drug delivery systems, with special attention to various receptors overexpressed on HCC cells. These receptors are key to enhancing the specificity and efficacy of nanoparticle delivery and represent a new paradigm for actively targeting and combating HCC. We comprehensively summarize the current understanding of these receptors, their role in nanoparticle targeting, and the impact of such targeted therapies on HCC. By gaining a deeper understanding of the receptor-mediated mechanisms of these innovative therapies, more effective and precise treatment of HCC can be achieved.
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Affiliation(s)
- Xia-Qing Zhou
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Ya-Ping Li
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China
| | - Shuang-Suo Dang
- Department of Infectious Diseases, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi Province, China.
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12
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Zhang R, Asikaer A, Chen Q, Wang F, Lan J, Liu Y, Hu L, Zhao H, Duan H. Network pharmacology and in vitro experimental verification unveil glycyrrhizin from glycyrrhiza glabra alleviates acute pancreatitis via modulation of MAPK and STAT3 signaling pathways. BMC Complement Med Ther 2024; 24:58. [PMID: 38280993 PMCID: PMC10821312 DOI: 10.1186/s12906-024-04372-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 01/23/2024] [Indexed: 01/29/2024] Open
Abstract
Acute pancreatitis (AP) is a severe gastrointestinal inflammatory disease with increasing mortality and morbidity. Glycyrrhiza glabra, commonly known as Liquorice, is a widely used plant containing bioactive compounds like Glycyrrhizin, which possesses diverse medicinal properties such as anti-inflammatory, antioxidant, antiviral, and anticancer activities. The objective of this study is to investigate the active components, relevant targets, and underlying mechanisms of the traditional Chinese medicine Glycyrrhiza glabra in the treatment of AP. Utilizing various computational biology methods, we explored the potential targets and molecular mechanisms through Glycyrrhizin supplementation. Computational results indicated that Glycyrrhizin shows promising pharmacological potential, particularly with mitogen-activated protein kinase 3 (MAPK3) protein (degree: 70), forming stable complexes with Glycyrrhizin through ionic and hydrogen bonding interactions, with a binding free energy (ΔGbind) of -33.01 ± 0.08 kcal/mol. Through in vitro experiments, we validated that Glycyrrhizin improves primary pancreatic acinar cell injury by inhibiting the MAPK/STAT3/AKT signaling pathway. Overall, MAPK3 emerges as a reliable target for Glycyrrhizin's therapeutic effects in AP treatment. This study provides novel insights into the active components and potential targets and molecular mechanisms of natural products.
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Affiliation(s)
- Rui Zhang
- Department of pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Aiminuer Asikaer
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 405400, PR China
| | - Qi Chen
- Department of pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Fang Wang
- College of Stomotology, Zunyi Medical University, Zunyi, 563000, China
| | - Junjie Lan
- Department of pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Yang Liu
- Department of Hepatobiliary Surgery II, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Linfang Hu
- Department of pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Huaye Zhao
- Department of pharmacy, Guizhou Provincial People's Hospital, Guiyang, 550002, China
| | - Hongtao Duan
- School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing, 405400, PR China.
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13
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Nawaz A, Manzoor A, Ahmed S, Ahmed N, Abbas W, Mir MA, Bilal M, Sheikh A, Ahmad S, Jeelani I, Nakagawa T. Therapeutic approaches for chronic hepatitis C: a concise review. Front Pharmacol 2024; 14:1334160. [PMID: 38283838 PMCID: PMC10811011 DOI: 10.3389/fphar.2023.1334160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2023] [Accepted: 12/18/2023] [Indexed: 01/30/2024] Open
Abstract
Hepatitis C virus (HCV) infection is a significant global health concern, prompting the need for effective treatment strategies. This in-depth review critically assesses the landscape of HCV treatment, drawing parallels between traditional interferon/ribavirin therapy historically pivotal in HCV management and herbal approaches rooted in traditional and complementary medicine. Advancements in therapeutic development and enhanced clinical outcomes axis on a comprehensive understanding of the diverse HCV genome, its natural variations, pathogenesis, and the impact of dietary, social, environmental, and economic factors. A thorough analysis was conducted through reputable sources such as Science Direct, PubMed, Scopus, Web of Science, books, and dissertations. This review primarily focuses on the intricate nature of HCV genomes and explores the potential of botanical drugs in both preventing and treating HCV infections.
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Affiliation(s)
- Allah Nawaz
- Joslin Diabetes Center, Harvard Medical School, Harvard University, Boston, MA, United States
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Azhar Manzoor
- Department of Surgery, Bahawal Victoria Hospital, Bahawalpur, Pakistan
| | - Saeed Ahmed
- Department of Medicine, and Surgery, Rawalpindi Medical University, Rawalpindi, Punjab, Pakistan
| | - Naveed Ahmed
- Department of Pharmacy, University of Poonch Rawalakot, Rawalakot, Azad Jammu and Kashmir (AJ&K), Pakistan
| | - Waseem Abbas
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Mushtaq Ahmad Mir
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
| | - Muhammad Bilal
- First Department of Internal Medicine, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Alisha Sheikh
- Jammu Institute of Ayurveda and Research, University of Jammu, Jammu, India
| | - Saleem Ahmad
- Cardiovascular Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, LA, United States
| | - Ishtiaq Jeelani
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
| | - Takashi Nakagawa
- Department of Molecular and Medical Pharmacology, Faculty of Medicine, University of Toyama, Toyama, Japan
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14
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Zhang Y, Li H, Liu X, Wang Q, Zhao D, Su M, Jia Z, Shen S. Integrating Metabolomics and Network Pharmacology to Decipher the Hepatoprotective Effect Mechanisms of Magnesium Isoglycyrrhizinate Injection. Curr Issues Mol Biol 2023; 46:279-298. [PMID: 38248321 PMCID: PMC10813909 DOI: 10.3390/cimb46010019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2023] [Revised: 12/15/2023] [Accepted: 12/28/2023] [Indexed: 01/23/2024] Open
Abstract
This study aimed to explore the liver protective effects of a fourth-generation glycyrrhizic acid product (magnesium isoglycyrrhizinate injection, MII) in the treatment of mice with drug-induced liver injury-specifically, to determine its effects on plasma metabolites. Moreover, the possible mechanism of its intervention in lipid metabolism and amino acid metabolism through the liver protective effect was preliminarily explored, combined with network pharmacology. The liver injury model of mice was established using acetaminophen (APAP). The protective effect of MII on the mice model was evaluated using pathological tissue sections and biochemical indices such as alanine transaminase (ALT), aspartate aminotransferase (AST), and superoxide dismutase (SOD). Metabolomics analysis of plasma was performed using the UHPLC-QTOF/MS technique to screen for potential biomarkers and enriched metabolic pathways. The potential targets and pathways of MII were predicted by network pharmacology, and the mechanism was verified by Western blot analysis. MII significantly improved the pathological liver changes in mice with liver injury. The content of ALT and AST was decreased, and the activity of SOD was increased significantly (p < 0.05, 0.01). A total of 29 potential biomarkers were identified in the metabolomics analysis, mainly involving seven pathways, such as lipid metabolism and amino acid metabolism. A total of 44 intersection targets of MII in the treatment of liver injury were obtained by network pharmacology, involving lipid metabolism and other related pathways. Western blot analysis results showed that MII could significantly reduce the expression of JAK2 and STAT3. MII can effectively ameliorate liver injury in modeled mice through related pathways such as lipid metabolism and amino acid metabolism. This study could provide not only a scientific basis for the elucidation of the mechanism of action of MII in exerting a hepatoprotective effect, but also a reference for its rational clinical application.
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Affiliation(s)
- Yihua Zhang
- Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China; (Y.Z.); (H.L.); (M.S.)
- NDMA Key Laboratory for Quality Control and Evaluation of Generic Drug, Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050200, China; (X.L.); (Q.W.); (D.Z.)
| | - Hui Li
- Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China; (Y.Z.); (H.L.); (M.S.)
- NDMA Key Laboratory for Quality Control and Evaluation of Generic Drug, Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050200, China; (X.L.); (Q.W.); (D.Z.)
| | - Xueli Liu
- NDMA Key Laboratory for Quality Control and Evaluation of Generic Drug, Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050200, China; (X.L.); (Q.W.); (D.Z.)
| | - Qiang Wang
- NDMA Key Laboratory for Quality Control and Evaluation of Generic Drug, Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050200, China; (X.L.); (Q.W.); (D.Z.)
| | - Dong Zhao
- NDMA Key Laboratory for Quality Control and Evaluation of Generic Drug, Hebei Institute for Drug and Medical Device Control, Shijiazhuang 050200, China; (X.L.); (Q.W.); (D.Z.)
| | - Ming Su
- Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China; (Y.Z.); (H.L.); (M.S.)
| | - Zhixin Jia
- National Institutes for Food and Drug Control, Beijing 102629, China;
| | - Shigang Shen
- Key Laboratory of Analytical Science and Technology of Hebei Province, College of Chemistry and Materials Science, Hebei University, Baoding 071002, China; (Y.Z.); (H.L.); (M.S.)
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15
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Halder J, Mahanty R, Rajwar TK, Rai VK, Kar B, Ghosh G, Rath G. Nanofibers of Glycyrrhizin/Hydroxypropyl-β-Cyclodextrin Inclusion Complex: Enhanced Solubility Profile and Anti-inflammatory Effect of Glycyrrhizin. AAPS PharmSciTech 2023; 24:196. [PMID: 37783948 DOI: 10.1208/s12249-023-02662-0] [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: 06/21/2023] [Accepted: 09/19/2023] [Indexed: 10/04/2023] Open
Abstract
Despite having a wide range of therapeutic advantages, glycyrrhizin (GL) has few commercial applications due to its poor aqueous solubility. In this study, we combined the benefits of hydroxypropyl β-cyclodextrin (HP-βCD) supramolecular inclusion complexes and electrospun nanofibers to improve the solubility and therapeutic potential of GL. A molecular inclusion complex containing GL and HP-βCD was prepared by lyophilization at a 1:2 molar ratio. GL and hydroxypropyl β-cyclodextrin inclusion complexes were also incorporated into hyaluronic acid (HA) nanofibers. Prepared NF was analyzed for physical, chemical, thermal, and pharmaceutical properties. Additionally, a rat model of carrageenan-induced hind paw edema and macrophage cell lines was used to evaluate the anti-inflammatory activity of GL-HP-βCD NF. The DSC and XRD analyses clearly showed the amorphous state of GL in nanofibers. In comparison to pure GL, GL-HP-βCD NF displayed improved release (46.6 ± 2.16% in 5 min) and dissolution profiles (water dissolvability ≤ 6 s). Phase solubility results showed a four-fold increase in GL solubility in GL-HP-βCD NF. In vitro experiments on cell lines showed that inflammatory markers like IL-1β, TNF-α, and IL-6 were significantly lower in GL-HP-βCD NF compared to pure GL (p < 0.01 and p < 0.05). According to in vivo results, the prepared nanofiber exhibits a better anti-inflammatory effect than pure GL (63.4% inhibition vs 53.7% inhibition). The findings presented here suggested that GL-HP-βCD NF could serve as a useful strategy for improving the therapeutic effects of GL.
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Affiliation(s)
- Jitu Halder
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Ritu Mahanty
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Tushar Kanti Rajwar
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Vineet Kumar Rai
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Biswakanth Kar
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Goutam Ghosh
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India
| | - Goutam Rath
- School of Pharmaceutical Sciences, Siksha 'O' Anusandhan (Deemed to Be University), Bhubaneswar, Odisha, India.
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16
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Zhang Y, Sheng Z, Xiao J, Li Y, Huang J, Jia J, Zeng X, Li L. Advances in the roles of glycyrrhizic acid in cancer therapy. Front Pharmacol 2023; 14:1265172. [PMID: 37649893 PMCID: PMC10463042 DOI: 10.3389/fphar.2023.1265172] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 08/07/2023] [Indexed: 09/01/2023] Open
Abstract
Since the first 70 years of reporting cancer chemotherapy, malignant tumors have been the second most common cause of death in children and adults. Currently, the commonly used anti-cancer methods include surgery, chemotherapy, radiotherapy, and immunotherapy. Although these treatment methods could alleviate cancer, they lead to different forms of side effects and have no particularly significant effect on prolonging the patients' life span. Glycyrrhizic acid (GL), a native Chinese herbal extract, has a wide range of pharmacological effects, such as anti-cancer, anti-inflammatory, antioxidant, and immune regulation. In this review, the anti-cancer effects and mechanisms of GL are summarized in various cancers. The inhibition of GL on chemotherapy-induced side effects, including hepatotoxicity, nephrotoxicity, genotoxicity, neurotoxicity and pulmonary toxicity, is highlighted. Therefore, GL may be a promising and ideal drug for cancer therapy.
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Affiliation(s)
- Yuqian Zhang
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Zixuan Sheng
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jing Xiao
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Yang Li
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jie Huang
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
| | - Jinjing Jia
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Physiology, Jiaxing University Medical College, Jiaxing, China
| | - Xiansi Zeng
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Biochemistry and Molecular Biology, Jiaxing University Medical College, Jiaxing, China
| | - Li Li
- Research Center of Neuroscience, Jiaxing University Medical College, Jiaxing, China
- Department of Physiology, Jiaxing University Medical College, Jiaxing, China
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17
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Greco LA, Reay WR, Dayas CV, Cairns MJ. Exploring opportunities for drug repurposing and precision medicine in cannabis use disorder using genetics. Addict Biol 2023; 28:e13313. [PMID: 37500481 PMCID: PMC10909568 DOI: 10.1111/adb.13313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2023] [Revised: 05/09/2023] [Accepted: 06/16/2023] [Indexed: 07/29/2023]
Abstract
Cannabis use disorder (CUD) remains a significant public health issue globally, affecting up to one in five adults who use cannabis. Despite extensive research into the molecular underpinnings of the condition, there are no effective pharmacological treatment options available. Therefore, we sought to further explore genetic analyses to prioritise opportunities to repurpose existing drugs for CUD. Specifically, we aimed to identify druggable genes associated with the disorder, integrate transcriptomic/proteomic data and estimate genetic relationships with clinically actionable biochemical traits. Aggregating variants to genes based on genomic position, prioritised the phosphodiesterase gene PDE4B as an interesting target for drug repurposing in CUD. Credible causal PDE4B variants revealed by probabilistic finemapping in and around this locus demonstrated an association with inflammatory and other substance use phenotypes. Gene and protein expression data integrated with the GWAS data revealed a novel CUD associated gene, NPTX1, in whole blood and supported a role for hyaluronidase, a key enzyme in the extracellular matrix in the brain and other tissues. Finally, genetic correlation with biochemical traits revealed a genetic overlap between CUD and immune-related markers such as lymphocyte count, as well as serum triglycerides.
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Affiliation(s)
- Laura A. Greco
- School of Biomedical Sciences and PharmacyThe University of NewcastleCallaghanNew South WalesAustralia
- Precision Medicine Research ProgramHunter Medical Research InstituteNew LambtonNew South WalesAustralia
| | - William R. Reay
- School of Biomedical Sciences and PharmacyThe University of NewcastleCallaghanNew South WalesAustralia
- Precision Medicine Research ProgramHunter Medical Research InstituteNew LambtonNew South WalesAustralia
| | - Christopher V. Dayas
- School of Biomedical Sciences and PharmacyThe University of NewcastleCallaghanNew South WalesAustralia
| | - Murray J. Cairns
- School of Biomedical Sciences and PharmacyThe University of NewcastleCallaghanNew South WalesAustralia
- Precision Medicine Research ProgramHunter Medical Research InstituteNew LambtonNew South WalesAustralia
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18
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Yang Y, Fu X, Xia B, Zhou L, Zhang H, Li C, Ye X, Liu T. Glycyrrhizic acid glycosides reduces extensive tripterygium glycosides-induced lipid deposition in hepatocytes. Heliyon 2023; 9:e17891. [PMID: 37483744 PMCID: PMC10362073 DOI: 10.1016/j.heliyon.2023.e17891] [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: 02/01/2023] [Revised: 06/25/2023] [Accepted: 06/30/2023] [Indexed: 07/25/2023] Open
Abstract
Aim Tripterygium glycosides (TG) extracted from the plant Tripterygium wilfordii Hook F has been used to treat chronic kidney diseases for many years. However, hepatotoxicity limits its clinical application. Glycyrrhizic acid glycosides (GA) can reduce TG hepatotoxicity, however, further investigation into the underlying molecular mechanisms by which GA attenuates TG-induced hepatotoxicity is required. Methods Sprague‒Dawley rats were randomly divided into the control group, the TG groups (TG189 mg/kg group, TG472.5 mg/kg group), and the TG + GA groups (TG189 mg/kg + GA20.25 mg/kg group, TG472.5 mg/kg + GA20.25 mg/kg group). After 21 consecutive days of intragastric administration, structural and molecular changes in hepatocytes were detected. Results After 21 days of TG treatment, the serum level of the total bilirubin, triglyceride, total cholesterol, and low-density lipoprotein cholesterol increased in the TG189 mg/kg and TG472.5 mg/kg groups when compared to the control group. High-density lipoprotein cholesterol levels were reduced in both TG groups. The ultrastructure of hepatocytes and the structural integrity of the liver were compromised. In addition, the relevant molecular level of the peroxisome proliferators-activated receptor α (PPARα) and acyl-CoA synthetase long-chain family members (ACSLs) pathway was modulated. With the addition of 20.25 mg/kg GA, the serum biochemical indexes and liver tissue structure ultrastructure of hepatocytes were improved, and the PPARα-ACSLs pathway was corrected. Conclusion The combined application of GA and TG improved abnormal lipid metabolism, repaired liver structure, reduced lipid deposition in hepatocytes, and reduced TG-induced hepatotoxicity.
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Bafandeh S, Khodadadi E, Ganbarov K, Asgharzadeh M, Köse Ş, Samadi Kafil H. Natural Products as a Potential Source of Promising Therapeutics for COVID-19 and Viral Diseases. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2023; 2023:5525165. [PMID: 37096202 PMCID: PMC10122587 DOI: 10.1155/2023/5525165] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 03/19/2023] [Accepted: 03/24/2023] [Indexed: 04/26/2023]
Abstract
Background A global pandemic has recently been observed due to the new coronavirus disease, caused by SARS-CoV-2. Since there are currently no antiviral medicines to combat the highly contagious and lethal COVID-19 infection, identifying natural sources that can either be viricidal or boost the immune system and aid in the fight against the disease can be an essential therapeutic support. Methods This review was conducted based on published papers related to the herbal therapy of COVID-19 by search on databases including PubMed and Scopus with herbal, COVID-19, SARS-CoV-2, and therapy keywords. Results To combat this condition, people may benefit from the therapeutic properties of medicinal plants, such as increasing their immune system or providing an antiviral impact. As a result, SARS-CoV-2 infection death rates can be reduced. Various traditional medicinal plants and their bioactive components, such as COVID-19, are summarized in this article to assist in gathering and debating techniques for combating microbial diseases in general and boosting our immune system in particular. Conclusion The immune system benefits from natural products and many of these play a role in activating antibody creation, maturation of immune cells, and stimulation of innate and adaptive immune responses. The lack of particular antivirals for SARS-CoV-2 means that apitherapy might be a viable option for reducing the hazards associated with COVID-19 in the absence of specific antivirals.
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Affiliation(s)
- Soheila Bafandeh
- Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ehsaneh Khodadadi
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
| | - Khudaverdi Ganbarov
- Research Laboratory of Microbiology and Virology, Baku State University, Baku, Azerbaijan
| | - Mohammad Asgharzadeh
- Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Şükran Köse
- Department of Infectious Diseases and Clinical Microbiology, Dokuz Eylül Üniversitesi, Izmir, Turkey
| | - Hossein Samadi Kafil
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
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Helou M, Nasr J, El Osta N, Jabbour E, Husni R. Liver manifestations in COVID-19 patients: A review article. World J Clin Cases 2023; 11:2189-2200. [PMID: 37122526 PMCID: PMC10131011 DOI: 10.12998/wjcc.v11.i10.2189] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 02/09/2023] [Accepted: 03/10/2023] [Indexed: 03/30/2023] Open
Abstract
The coronavirus disease 2019 (COVID-19) initially presented as a disease that affected the lungs. Then, studies revealed that it intricately affected disparate organs in the human body, with the liver being one of the most affected organs. This review aimed to assess the association between COVID-19 and liver function, shedding light on its clinical implication. However, its exact pathophysiology remains unclear, involving many factors, such as active viral replication in the liver cells, direct cytotoxic effects of the virus on the liver or adverse reactions to viral antigens. Liver symptoms are mild-to-moderate transaminase elevation. In some patients, with underlying liver disease, more serious outcomes are observed. Thus, liver function should be meticulously considered in patients with COVID-19.
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Affiliation(s)
- Mariana Helou
- Division of Emergency Medicine, Department of Internal Medicine, Lebanese American University Medical Center, Lebanese American University School of Medicine, Beirut 1102-2801, Lebanon
| | - Janane Nasr
- Division of Infectious Diseases, Department of Internal Medicine, Lebanese American University, School of Medicine, Beirut 1102-2801, Lebanon
| | - Nour El Osta
- Division of Emergency, Department of Internal Medicine, Lebanese American University, School of Medicine, Beirut 1102-2801, Lebanon
| | - Elsy Jabbour
- Division of Emergency, Department of Internal Medicine, Lebanese American University, School of Medicine, Beirut 1102-2801, Lebanon
| | - Rola Husni
- Division of Infectious Diseases, Department of Internal Medicine, Lebanese American University, School of Medicine, Beirut 1102-2801, Lebanon
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21
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Li C, Han P, Mao H, Lv C, Huang K, Jin M. Glycyrrhizic Acid-Based Carbonized Dots Boost Antiviral Activity against Influenza A Virus via Multisite Inhibition Mechanisms. ACS APPLIED MATERIALS & INTERFACES 2023; 15:10441-10451. [PMID: 36789721 DOI: 10.1021/acsami.2c21319] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Influenza A virus (IVA) has been continuously causing pandemics in several animal hosts and has become a worldwide public health threat. Currently, antiviral drugs have become associated with a lot of side effects and limited activity against emerging drug-resistant influenza viruses. Therefore, the development of novel antiviral drugs is of great importance. In this study, we synthesized a kind of carbon dots (CDs) with high dispersibility from glycyrrhizic acid (GA) using a simple dry heating method. Compared with glycyrrhizic acid alone, GA-CDs exhibit superior solubility and significantly improve the antiviral property against IVA. Investigation of the mechanism revealed that GA-CDs act against IVA mainly by inhibiting viral internalization, replication of the viral genome, neuraminidase activity, and host inflammatory responses. More importantly, in a mouse model, GA-CDs can significantly alleviate the clinical symptoms and decrease mortality and lung viral titers. In vitro and in vivo experiments demonstrate that GA-CDs possess extraordinary therapeutic effects; therefore, we propose that GA-CDs may be a promising alternative therapy for IVA infection.
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Affiliation(s)
- Chengfei Li
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P. R. China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P. R. China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan 430070, P. R. China
| | - Pengfei Han
- College of Science, Huazhong Agricultural University, Wuhan 430070, P. R. China
| | - Haiying Mao
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P. R. China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P. R. China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan 430070, P. R. China
| | - Changjie Lv
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P. R. China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P. R. China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan 430070, P. R. China
| | - Kun Huang
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P. R. China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P. R. China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan 430070, P. R. China
| | - Meilin Jin
- State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, P. R. China
- College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, P. R. China
- Key Laboratory of Development of Veterinary Diagnostic Products, Ministry of Agriculture, Wuhan 430070, P. R. China
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22
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Wang H, Yu T, An N, Sun Y, Xu P, Han P, Zhao Y, Wang L, Ni X, Li Y, Li G, Liu Y, Peng J, Hou M, Hou Y. Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia. Haematologica 2023; 108:843-858. [PMID: 36263841 PMCID: PMC9973480 DOI: 10.3324/haematol.2022.281557] [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: 06/08/2022] [Indexed: 11/09/2022] Open
Abstract
Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 (HMGB1) protein associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18β-glycyrrhetinic acid (18β-GA), could be used for its anti-inflammatory and immune-modulatory effects, although its ability to correct immune balance in ITP is unclear. In this study, we showed that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18β-GA stimulated the production of regulatory T cells (Treg), restored the balance of CD4+ T-cell subsets and enhanced the suppressive function of Treg through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18β-GA in Treg of ITP patients. Furthermore, we found that 18β-GA alleviated thrombocytopenia in mice with ITP. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Treg increased significantly, while the level of plasma HMGB1 and serum antiplatelet antibodies decreased significantly in ITP mice along 18β-GA treatment. In addition, 18β-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicate that 18β-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.
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Affiliation(s)
- Haoyi Wang
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Tianshu Yu
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Ning An
- Laboratory of Cancer Signaling, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) Stem Cells, University of Liège, CHU, Sart-Tilman, Liège, 4000 Belgium
| | - Yunqi Sun
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Pengcheng Xu
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Panpan Han
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Yajing Zhao
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Lingjun Wang
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Xiaofei Ni
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Yubin Li
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Guosheng Li
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Yanfeng Liu
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Jun Peng
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012
| | - Ming Hou
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan.
| | - Yu Hou
- Department of Hematology, Qilu Hospital of Shandong University, Shandong University, Jinan, Shandong, 250012, China; Shandong Provincial Key Laboratory of Immunohematology, Qilu Hospital of Shandong University, Jinan.
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Abstract
INTRODUCTION Since the end of 2019, a new disease outbreak has been spreading worldwide, after starting from Wuhan, China. The viral pathogen responsible for the disease was named as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), and for the illness the acronym COVID-19 was coined (COronaVIrus Disease 2019). Viral pathogenesis, epidemiology, and clinics are still somewhat obscure, when occurring during childhood the most. The aim of this study was to evaluate the features of liver involvement and damage in course of COVID-19. EVIDENCE ACQUISITION An insight into what is known as to COVID-19 and hepatic damage in adulthood as well as pediatric age was given. All the most relevant papers up to 15/10/2020 were identified and discussed. An extensive search strategy was carried out to identify all paper published from December 1st, 2019, to September 5, 2020, combining the key words "coronavirus," "coronavirus infection," "SARS-CoV-2," "COVID-19," "liver," "liver injury," "hepatic injury," "children," "pediatric" in key electronic bibliographic databases (PubMed, Google Scholar), following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. EVIDENCE SYNTHESIS Establishing whether liver damage is due to a direct viral action or host immune system inflammatory reaction or consequence of the administered drugs or secondary to another organ failure (for example the heart) is difficult. What is sure is the fact that liver function should be checked at the time of admission to hospital and during hospitalization. CONCLUSIONS In conclusion, liver involvement during COVID-19 is likely due to a multifactorial origin. An aberrant immune system reaction to SARS-CoV-2 is probably the most important underlying trigger, though more extended studies are needed for a definitive confirmation. The markers of liver injury should be carefully in each patient admitted for COVID-19: in fact, in case of altered hepatic markers, a specific therapy to protect liver is needed.
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Affiliation(s)
- Simone Mameli
- Graduate School in Pediatrics, University of Cagliari, Cagliari, Italy
| | - Maria A Marcialis
- Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy
| | - Pier P Bassareo
- Mater Misericordiae University Hospital and Our Lady's Children's Hospital Crumlin, University College of Dublin, Dublin, Ireland -
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, University of Cagliari, Cagliari, Italy
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García-Salazar G, Urbán-Morlán Z, Mendoza-Elvira S, Quintanar-Guerrero D, Mendoza S. Broad Antiviral Spectrum of Glycyrrhizic Acid for Human and Veterinary Medicine: Reality or Fiction? Intervirology 2022; 66:41-53. [PMID: 36455522 PMCID: PMC10015762 DOI: 10.1159/000528198] [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: 07/11/2022] [Accepted: 11/14/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND Emerging virus infections provoke health problems in people and animals, which generate social and economic issues worldwide. This has spurred the search for new pharmacological strategies to confront them. SUMMARY The purpose of this review is to draw the reader's attention to pharmacological evaluations of glycyrrhizic acid (GA) and its analogs on the broad range of viruses known in human and veterinary medicine. GA is the main water-soluble constituent extracted from the roots of plants from the genus Glycyrrhiza, commonly known as licorice root. It has long been used due to its broad spectrum of bioactivities, including anti-inflammatory, antiulcer, and antitumor properties. It has also been proposed as an antiviral agent. Medicines derived from GA are currently being used to combat acute and chronic hepatitis and herpes viruses. KEY MESSAGES This review suggests that GA could be a new broad-spectrum antiviral due to its ability to inhibit DNA or RNA viruses both in vitro and in vivo. GA could be a potential drug for preventing and/or treating various viral diseases.
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Affiliation(s)
- Gilberto García-Salazar
- Departamento de Investigación y Posgrado en Alimentos, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, Mexico,
| | - Zaida Urbán-Morlán
- Facultad de Química, Centro de Información de Medicamentos, Universidad Autónoma de Yucatán, Mérida, Mexico
| | - Susana Mendoza-Elvira
- Laboratorio de Microbiología y Virología de las Enfermedades Respiratorias del Cerdo, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - David Quintanar-Guerrero
- Laboratorio de Investigación y Posgrado en Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Sandra Mendoza
- Departamento de Investigación y Posgrado en Alimentos, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro, Mexico
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25
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Mohammed GF, Al-Dhubaibi MS, Bahaj SS, Elneam AIA. Systemic immunotherapy for the treatment of warts: A literature review. J Cosmet Dermatol 2022; 21:5532-5536. [PMID: 36017650 DOI: 10.1111/jocd.15330] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Revised: 08/12/2022] [Accepted: 08/23/2022] [Indexed: 12/27/2022]
Abstract
BACKGROUND Immunotherapy has emerged as a critical therapeutic tool for the treatment of warts. Immunotherapy for warts is currently restricted to recalcitrant lesions. A small number of regimens appear to be extremely effective. Furthermore, there is a scarcity of evidence-based research. OBJECTIVE Furthermore, in the majority of cases, their safety and effectiveness have not been evaluated in double-blind, controlled clinical trials, making the reproducibility of many of the listed treatments difficult to analyze and a possible placebo effect difficult to rule out. METHODS Analyzing and discussing different types of systemic immunotherapy. The different types of immunotherapy for warts are mentioned in this report. RESULTS Systemic immunotherapeutic modalities commonly used in the treatment Echinacea, propolis, oral retinoids, glycyrrhizinic acid, levamisole, cimetidine, and zinc sulfate have all been reported as effective treatment modalities for different types of warts. CONCLUSION Immunotherapy has emerged as one of the most important therapeutic modalities for warts. Such treatment is required not only for recalcitrant or multiple lesions, but also in the majority of treated cases.
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Affiliation(s)
- Ghada Farouk Mohammed
- Department of Dermatology, Venereology and Sexology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | | | - Saleh Salem Bahaj
- Department of Microbiology and Immunology, Faculty of Medicine and Health Sciences, Sana'a University, Sana'a, Yemen
| | - Ahmed Ibrahim Abd Elneam
- Department of Clinical Biochemistry, Department of Basic Medical Sciences, College of Medicine, Shaqra University, Dawadmi, Saudi Arabia.,Molecular Genetics and Enzymology Department, Human Genetics and Genome Research Institute, National Research Center, Cairo, Egypt
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26
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Zhou X, Li X, Yi K, Liang C, Geng S, Zhu J, Xie C, Zhong C. Magnesium isoglycyrrhizinate ameliorates lipopolysaccharide-induced liver injury by upregulating autophagy and inhibiting inflammation via IL-22 expression. Bioorg Chem 2022; 128:106034. [DOI: 10.1016/j.bioorg.2022.106034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/01/2022] [Accepted: 07/14/2022] [Indexed: 12/15/2022]
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Joshi C, Chaudhari A, Joshi C, Joshi M, Bagatharia S. Repurposing of the herbal formulations: molecular docking and molecular dynamics simulation studies to validate the efficacy of phytocompounds against SARS-CoV-2 proteins. J Biomol Struct Dyn 2022; 40:8405-8419. [PMID: 33988079 PMCID: PMC8127611 DOI: 10.1080/07391102.2021.1922095] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2020] [Accepted: 03/26/2021] [Indexed: 12/15/2022]
Abstract
Herbal formulations mentioned in traditional medicinal texts were investigated for in silico effect against SARS-COV-2 proteins involved in various functions of a virus such as attachment, entry, replication, transcription, etc. To repurpose and validate polyherbal formulations, molecular docking was performed to study the interactions of more than 150 compounds from various formulations against the SARS-CoV-2 proteins. Molecular dynamics (MD) simulation was performed to evaluate the interaction of top scored ligands with the various receptor proteins. The docking results showed that Liquiritic acid, Liquorice acid, Terchebulin, Glabrolide, Casuarinin, Corilagin, Chebulagic acid, Neochebulinic acid, Daturataturin A, and Taraxerol were effective against SARS-COV-2 proteins with higher binding affinities with different proteins. Results of MD simulations validated the stability of ligands from potent formulations with various receptors of SARS-CoV-2. Binding free energy analysis suggested the favourable interactions of phytocompounds with the recpetors. Besides, in silico comparison of the various formulations determined that Pathyadi kwath, Sanjeevani vati, Yashtimadhu, Tribhuvan Keeratiras, and Septillin were more effective than Samshamni vati, AYUSH-64, and Trikatu. Polyherbal formulations having anti-COVID-19 potential can be used for the treatment with adequate monitoring. New formulations may also be developed for systematic trials based on ranking from these studies.Communicated by Ramaswamy H. Sarma.
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Affiliation(s)
- Chinmayi Joshi
- Gujarat Biotechnology Research Centre, Gandhinagar, Gujarat, India
| | - Armi Chaudhari
- Gujarat Biotechnology Research Centre, Gandhinagar, Gujarat, India
| | - Chaitanya Joshi
- Gujarat Biotechnology Research Centre, Gandhinagar, Gujarat, India
| | - Madhvi Joshi
- Gujarat Biotechnology Research Centre, Gandhinagar, Gujarat, India
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28
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Cetin Aluc C, Gok B, Kecel-Gunduz S, Budama-Kilinc Y. Glycyrrhizic acid Poly(D,L-lactide-co-glycolide) nanoparticles: anti-aging cosmeceutical formulation for topical applications. PeerJ 2022. [DOI: 10.7717/peerj.14139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Glycyrrhizic acid (GA) is one of the components of licorice roots (Glycyrrhiza glabra L.). GA is a triterpenoid saponin can be used as a medicinal plant with its antiallergic, antiviral, anti-inflammatory, anti-ulcer, hepatoprotective, anticancer, anti-oxidation activities and several other therapeutic properties. The aim of this study is to develop an anti-aging formulation for topical application containing GA. In this context, GA-loaded Poly (D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) were prepared using the double emulsion method, and were characterized by various spectroscopic methods. The efficacy of GA-PLGA NPs was evaluated with in vitro and in silico methods. The encapsulation efficiency and loading capacity were calculated. The in vitro release study was conducted, and the GA release profile was determined. The genotoxic activity of GA and GA-PLGA NPs was evaluated by the Ames test using TA98 and TA100 mutant strains of Salmonella typhimurium. The cytotoxic potential of GA-PLGA NPs was evaluated on the HaCaT cell line using the MTT assay. According to the genotoxicity and cytotoxicity results, it was found that the GA-PLGA NP formulation did not exhibit genotoxic and cytotoxic effects. Moreover, the efficacy of GA in preventing UVB-induced photo-aging in HaCaT cells and the clarification of the molecular mechanism of GA binding to MMPs were revealed by molecular docking analysis. In addition, through molecular dynamics (MD) analysis, the binding interaction of GA with MMPs in a dynamic system, and protein-ligand stability were predicted as a result of 50 ns MD simulation studies considering various analysis parameters. Finally, it was evaluated that GA-PLGA nanoformulation might be used as an alternative anti-aging skin care product candidate via topical application.
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Affiliation(s)
- Cigdem Cetin Aluc
- Graduate School of Natural and Applied Science, Yildiz Technical University, Istanbul, Türkiye
- Abdi Ibrahim Pharmaceuticals, Abdi Ibrahim Production Facilities, Istanbul, Türkiye
| | - Bahar Gok
- Graduate School of Natural and Applied Science, Yildiz Technical University, Istanbul, Türkiye
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Okovityi SV, Raikhelson KL, Prikhodko VA. Combined hepatoprotective pharmacotherapy for liver disease. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2022:5-20. [DOI: 10.31146/1682-8658-ecg-203-7-5-20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
Abstract
Fixed-dose drug products as well as non-fixed hepatoprotective drug combinations are commonly used in modern clinical practice. Combined and concurrent drug use makes it possible to augment the pharmacological effects of individual agents, or extend the range of their potential indications. The drugs most commonly considered for combination therapy include essential phospholipids, glycyrrhizinic acid, ursodeoxycholic acid, silibinin, and S-adenosylmethionine. This paper discusses the rationale for combined use of liver-targeting drugs from a pathogenetic viewpoint, and provides a review of the evidence from clinical trials on combined pharmacotherapy for liver disease.
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Affiliation(s)
- Sergey V. Okovityi
- Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, Saint Petersburg State University; Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, Saint Petersburg State University
| | - Karina L. Raikhelson
- Scientific, Clinical and Educational Center of Gastroenterology and Hepatology, Saint Petersburg State University
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30
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Fujii S, Shoyama Y, Nomura S, Uto T. Development of Highly Sensitive Chemiluminescence Enzyme Immunostaining Assay to Determine Glycyrrhizin Content Using Anti-glycyrrhizin Monoclonal Antibody. Chem Pharm Bull (Tokyo) 2022; 70:694-698. [PMID: 36184451 DOI: 10.1248/cpb.c22-00405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Licorice, the root of Glycyrrhiza spp., is used in a large number of herbal medicines, such as traditional Chinese medicines, Japanese Kampo medicines, and therapeutic drugs. Since glycyrrhizin (GL) is among the main components in licorice and exhibits numerous beneficial pharmacological activities, the content of GL directly affects biological activity. The quality control based on GL content is an important factor in ensuring biological activity; however, the content of GL in licorice varies depending on plant cultivation environment, genetic factors, and species type. Previously, we prepared an anti-GL monoclonal antibody (anti-GL mAb) and employed it in various immunochemical assays for quality control of licorice and licorice-based products. In this study, we employed the anti-GL mAb in chemiluminescence enzyme immunostaining (CLEIS) to develop a very simple, rapid, specific, and sensitive quality control assay for licorice products, with a limit of detection of 3.9 ng. Furthermore, the CLEIS assay enabled semiquantitative analysis of GL in Kampo medicines. Our results showed that multiple samples can be simultaneously analyzed using CLEIS, and it is a useful tool for determining GL content, as well as ensuring chemical quality control of licorice-containing products and herbal medicines.
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Affiliation(s)
- Shunsuke Fujii
- Department of Health and Nutrition, Faculty of Health Management, Nagasaki International University
| | - Yukihiro Shoyama
- Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University
| | - Shuichi Nomura
- Department of Health and Nutrition, Faculty of Health Management, Nagasaki International University
| | - Takuhiro Uto
- Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Nagasaki International University
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31
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Plakoglobin and High-Mobility Group Box 1 Mediate Intestinal Epithelial Cell Apoptosis Induced by Clostridioides difficile TcdB. mBio 2022; 13:e0184922. [PMID: 36043787 DOI: 10.1128/mbio.01849-22] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Clostridioides difficile infection (CDI) is the leading cause of antibiotic-associated intestinal disease, resulting in severe diarrhea and fatal pseudomembranous colitis. TcdB, one of the essential virulence factors secreted by this bacterium, induces host cell apoptosis through a poorly understood mechanism. Here, we performed an RNA interference (RNAi) screen customized to Caco-2 cells, a cell line model of the intestinal epithelium, to discover host factors involved in TcdB-induced apoptosis. We identified plakoglobin, also known as junction plakoglobin (JUP) or γ-catenin, a member of the catenin family, as a novel host factor and a previously known cell death-related chromatin factor, high-mobility group box 1 (HMGB1). Disruption of those host factors by RNAi and CRISPR resulted in resistance of cells to TcdB-mediated and mitochondrion-dependent apoptosis. JUP was redistributed from adherens junctions to the mitochondria and colocalized with the antiapoptotic factor Bcl-XL. JUP proteins could permeabilize the mitochondrial membrane, resulting in the release of cytochrome c. Our results reveal a novel role of JUP in targeting the mitochondria to promote the mitochondrial apoptotic pathway. Treatment with glycyrrhizin, an HMGB1 inhibitor, resulted in significantly increased resistance to TcdB-induced epithelial damage in cultured cells and a mouse ligated colon loop model. These findings demonstrate the critical roles of JUP and HMGB1 in TcdB-induced epithelial cell apoptosis. IMPORTANCE Clostridioides difficile infection (CDI) is the leading cause of hospital-acquired diarrhea. Toxins, especially TcdB, cause epithelial cell apoptosis, but the underlying cell death mechanism is less clear. Through an apoptosis-focused RNAi screen using a bacterium-made small interfering (siRNA) library customized to a human colonic epithelial cell model, we found a novel host factor, plakoglobin (γ-catenin), as a key factor required for cell apoptosis induced by TcdB. Plakoglobin targets and permeabilizes mitochondria after stimulation by TcdB, demonstrating a hitherto underappreciated role of this catenin family member in the apoptosis of intestinal epithelial cells. We also found a previously known cell death-related chromatin factor, HMGB1, and explored the inhibition of HMGB1 for CDI therapy in vivo.
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Xie CQ, Fan FX, Li PT, Cai C, Li XZ, Song JH, Xu JG, Xu QL. [Effects and mechanism of diammonium glycyrrhizinate on liver injury in severely scalded rats]. ZHONGHUA SHAO SHANG YU CHUANG MIAN XIU FU ZA ZHI 2022; 38:735-743. [PMID: 36058696 DOI: 10.3760/cma.j.cn501225-20220120-00011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Objective: To investigate the effects and mechanism of diammonium glycyrrhizinate (DG) on liver injury in severely scalded rats. Methods: The experimental research method was used. Fifty-four female Sprague-Dawley rats aged 7-9 weeks were divided into sham injury group with simulated injury on the back, and simple scald group and scald+DG group with scald of 30% total body surface area on the back, with 18 rats in each group. Rats in sham injury group were not specially treated after injury, and rats in simple scald group and scald+DG group were rehydrated for antishock. Besides, rats in scald+DG group were injected intraperitoneally with 50 mg/kg DG at post injury hour (PIH) 1, 25, and 49. Rats in the three groups were collected, the serum content of liver function injury related indexes including aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), total protein, and albumin was measured by automatic biochemical assay analyzer, and serum content of ornithine carbamoyl transferase (OCT) was measured by enzyme-linked immunosorbent assay method at PIH 24, 48, and 72; hepatic histopathological changes at PIH 72 were observed by hematoxylin-eosin staining; the mRNA expressions of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), glucose regulated protein 78 (GRP78), activating transcription factor 4 (ATF4), and protein kinase R-like endoplasmic reticulum kinase (PERK) in liver tissue were detected by real-time fluorescent quantitative reverse transcription polymerase chain reaction at PIH 24, 48, and 72. The protein expressions of Bcl-2, Bax, GRP78, PERK, and ATF4 in liver tissue were detected by Western blotting at PIH 72 in sham injury group and PIH 24, 48, and 72 in simple scald group and scald+DG group. The number of samples was 6 in each group at each time point. Data were statistically analyzed with analysis of variance for factorial design, one-way analysis of variance, and Bonferroni test. Results: Compared with that in sham injury group, the serum content of AST, ALT, and LDH was significantly increased (P<0.01), and the serum content of total protein and albumin was significantly decreased (P<0.05 or P<0.01) of rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the serum AST content of rats in scald+DG group at PIH 24 was decreased significantly (P<0.05); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 48 was decreased significantly (P<0.01), and the serum total protein content was increased significantly (P<0.01); the serum AST, ALT, and LDH content of rats in scald+DG group at PIH 72 was decreased significantly (P<0.01), and the serum total protein and albumin content was increased significantly (P<0.01). At PIH 24, 48, and 72, the serum OCT content of rats in simple scald group was (48.5±3.9), (40.8±2.4), and (38.7±2.0) U/L, which was significantly higher than (15.1±2.5), (15.7±2.6), and (16.4±3.7) U/L in sham injury group (P<0.01), and (39.0±4.5), (31.8±2.0), and (22.1±2.6) U/L in scald+DG group (P<0.05 or P<0.01). At PIH 72, the cells in liver tissue of rats in sham injury group had normal morphology and regular arrangement, with no obvious inflammatory cell infiltration; the cells in liver tissue of rats in simple scald group had disordered arrangement, diffuse steatosis, and moderate inflammatory cell infiltration; the cells in liver tissue of rats in scald+DG group arranged regularly, with scattered steatosis and a small amount of inflammatory cell infiltration. Compared with those in sham injury group, the Bcl-2 mRNA (P<0.05 or P<0.01) and protein expressions of liver tissue were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bax were significantly increased in rats in simple scald group at PIH 24, 48, and 72. Compared with those in simple scald group, the mRNA (P<0.05) and protein expressions of Bax in liver tissue of rats in scald+DG group were decreased significantly at PIH 48; the mRNA (P<0.01) and protein expressions of Bax in liver tissue of rats in scald+DG group were significantly decreased, and the mRNA (P<0.01) and protein expressions of Bcl-2 were significantly increased at PIH 72. Compared with those in sham injury group, the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK in liver tissue were significantly increased in rats in simple scald group at all post-injury time points. Compared with those in simple scald group, the mRNA (P<0.01) and protein expressions of ATF4 in liver tissue of rats in scald+DG group at PIH 48 were significantly decreased, and the mRNA (P<0.05 or P<0.01) and protein expressions of ATF4, GRP78, and PERK were significantly decreased in liver tissue of rats in scald+DG group at PIH 72. Conclusions: DG can effectively reduce the degree of liver injury in rats after severe scald, and the mechanism may involve alleviating endoplasmic reticulum stress and mitigating mitochondrial damage.
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Affiliation(s)
- C Q Xie
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - F X Fan
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - P T Li
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - C Cai
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - X Z Li
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - J H Song
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
| | - J G Xu
- Department of Immunology, School of Basic Medical Sciences of Anhui Medical University, Hefei 230032, China
| | - Q L Xu
- Department of Burns, the First Affiliated Hospital of Anhui Medical University, Hefei 230022, China
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Du T, Kaneko K, Sakai Y, Tsunoi M, Yoshitake T, Kotera A, Matsushima Y, Miura T, Kajimoto T. A Facile α-Glucuronidation Using Methyl 1,2,3,4-Tetra-<i>O</i>-acetyl-D-glucuronate as Glycosyl Donor. Chem Pharm Bull (Tokyo) 2022; 70:589-593. [DOI: 10.1248/cpb.c22-00123] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Tianqi Du
- College of Pharmaceutical Sciences, Ritsumeikan University
| | - Kimiyoshi Kaneko
- Research Organization of Science and Technology, Ritsumeikan University
| | - Yuki Sakai
- College of Pharmaceutical Sciences, Ritsumeikan University
| | - Masato Tsunoi
- College of Pharmaceutical Sciences, Ritsumeikan University
| | | | - Aki Kotera
- College of Pharmaceutical Sciences, Ritsumeikan University
| | | | - Tsuyoshi Miura
- School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Gao L, Wang N, Jiang Y, Hu J, Ma B, Wu T. Glycyrrhizic Acid Inhibits Core Fucosylation Modification Modulated EMT and Attenuates Bleomycin-Induced Pulmonary Fibrosis. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE : ECAM 2022; 2022:5943322. [PMID: 35845568 PMCID: PMC9279030 DOI: 10.1155/2022/5943322] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 05/24/2022] [Accepted: 05/27/2022] [Indexed: 11/17/2022]
Abstract
Idiopathic pulmonary fibrosis (IPF) is a fatal and incurable chronic interstitial lung disease with an unknown etiology. Recent evidence suggests that epithelial-mesenchymal transition (EMT) is one of the possible factors in the pathogenesis of pulmonary fibrosis. Glycyrrhizic acid (GA) is a natural active ingredient extracted from the root of the traditional Chinese herb licorice, which has been shown in previous studies to have the effect of alleviating lung injury. In this study, our objective was to investigate whether GA could ameliorate pulmonary fibrosis by altering EMT, as well as the therapeutic potential of changing core fucosylation (CF) to target EMT-related pathways. First, we verified that GA partially reverses EMT in a rat model of bleomycin-induced lung interstitial fibrosis, alleviating pulmonary fibrosis, and implying that GA has antifibrotic potential. Next, we discovered that GA attenuated lung interstitial fibrosis by reducing CF modifications to some extent. Interestingly, we found that GA therapy reduced the expression of phosphorylated Smad2/3 (p-Smad2/3) and β-catenin in the EMT pathway and that GA inhibited the modification of TGF-βR and WNT receptor proteins by CF, suggesting that GA may interfere with the EMT process by modulating TGF-βR, WNT core fucosylation modifications to attenuate pulmonary fibrosis. In conclusion, these findings indicate that GA could be a potential therapeutic agent for IPF, and further support the idea that targeting CF alterations could be a novel technique for the treatment of diseases involving EMT.
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Affiliation(s)
- Lili Gao
- Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Nan Wang
- Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Yu Jiang
- Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Jinying Hu
- Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
| | - Baojie Ma
- Department of Anesthesia, Dalian Women and Children's Medical Group, Dalian 116000, China
| | - Taihua Wu
- Department of Respiratory Medicine, The First Affiliated Hospital of Dalian Medical University, Dalian 116011, China
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Wang KL, Yu YC, Chen HY, Chiang YF, Ali M, Shieh TM, Hsia SM. Recent Advances in Glycyrrhiza glabra (Licorice)-Containing Herbs Alleviating Radiotherapy- and Chemotherapy-Induced Adverse Reactions in Cancer Treatment. Metabolites 2022; 12:metabo12060535. [PMID: 35736467 PMCID: PMC9227067 DOI: 10.3390/metabo12060535] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2022] [Revised: 05/31/2022] [Accepted: 06/02/2022] [Indexed: 11/16/2022] Open
Abstract
Cancers represent a significant cause of morbidity and mortality worldwide. They also impose a large economic burden on patients, their families, and health insurance systems. Notably, cancers and the adverse reactions to their therapeutic options, chemotherapy and radiotherapy, dramatically affect the quality of life of afflicted patients. Therefore, developing approaches to manage chemotherapy- and radiotherapy-induced adverse reactions gained greater attention in recent years. Glycyrrhiza glabra (licorice), a perennial plant that is one of the most frequently used herbs in traditional Chinese medicine, has been heavily investigated in relation to cancer therapy. Licorice/licorice-related regimes, used in combination with chemotherapy, may improve the adverse effects of chemotherapy. However, there is little awareness of licorice-containing herbs alleviating reactions to radiotherapy and chemotherapy, or to other induced adverse reactions in cancer treatment. We aimed to provide a descriptive review, and to emphasize the possibility that licorice-related medicines could be used as an adjuvant regimen with chemotherapy to improve quality of life (QoL) and to reduce side effects, thus, improving compliance with chemotherapy. The experimental method involved searching different databases, including PubMed, the Cochrane Library, and Wang Fang database, as of May 2022, to identify any relevant studies. Despite a lack of high-quality and large-scale randomized controlled trials, we still discovered the potential benefits of licorice-containing herbs from published clinical studies. These studies find that licorice-containing herbs, and their active ingredients, reduce the adverse reactions caused by chemotherapy and radiotherapy, and improve the QoL of patients. This comprehensive review will serve as a cornerstone to encourage more scientists to evaluate and develop effective Traditional Chinese medicine prescriptions to improve the side effects of chemotherapy and radiation therapy.
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Affiliation(s)
- Kai-Lee Wang
- Department of Nursing, Ching Kuo Institute of Management and Health, Keelung 20301, Taiwan;
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Ying-Chun Yu
- Sex Hormonal Research Center, Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 40403, Taiwan;
- Graduate Institute of Biomedical Sciences, Center for Tumor Biology, School of Medicine, China Medical University, Taichung 40403, Taiwan
| | - Hsin-Yuan Chen
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Yi-Fen Chiang
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
| | - Mohamed Ali
- Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo 11566, Egypt;
| | - Tzong-Ming Shieh
- School of Dentistry, China Medical University, Taichung 40403, Taiwan;
| | - Shih-Min Hsia
- School of Nutrition and Health Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan; (H.-Y.C.); (Y.-F.C.)
- Graduate Institute of Metabolism and Obesity Sciences, College of Nutrition, Taipei Medical University, Taipei 11031, Taiwan
- School of Food and Safety, Taipei Medical University, Taipei 11031, Taiwan
- Nutrition Research Center, Taipei Medical University Hospital, Taipei 11031, Taiwan
- Correspondence:
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Weaver AJ, Borgogna TR, O’Shea-Stone G, Peters TR, Copié V, Voyich J, Teintze M. 18β-Glycyrrhetinic Acid Induces Metabolic Changes and Reduces Staphylococcus aureus Bacterial Cell-to-Cell Interactions. Antibiotics (Basel) 2022; 11:antibiotics11060781. [PMID: 35740189 PMCID: PMC9220049 DOI: 10.3390/antibiotics11060781] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Revised: 06/02/2022] [Accepted: 06/07/2022] [Indexed: 12/04/2022] Open
Abstract
The rise in bacterial resistance to common antibiotics has raised an increased need for alternative treatment strategies. The natural antibacterial product, 18β-glycyrrhetinic acid (GRA) has shown efficacy against community-associated methicillin-resistant Staphylococcus aureus (MRSA), although its interactions against planktonic and biofilm modes of growth remain poorly understood. This investigation utilized biochemical and metabolic approaches to further elucidate the effects of GRA on MRSA. Prolonged exposure of planktonic MRSA cell cultures to GRA resulted in increased production of staphyloxanthin, a pigment known to exhibit antioxidant and membrane-stabilizing functions. Then, 1D 1H NMR analyses of intracellular metabolite extracts from MRSA treated with GRA revealed significant changes in intracellular polar metabolite profiles, including increased levels of succinate and citrate, and significant reductions in several amino acids, including branch chain amino acids. These changes reflect the MRSA response to GRA exposure, including potentially altering its membrane composition, which consumes branched chain amino acids and leads to significant energy expenditure. Although GRA itself had no significant effect of biofilm viability, it seems to be an effective biofilm disruptor. This may be related to interference with cell–cell aggregation, as treatment of planktonic MRSA cultures with GRA leads to a significant reduction in micro-aggregation. The dispersive nature of GRA on MRSA biofilms may prove valuable for treatment of such infections and could be used to increase susceptibility to complementary antibiotic therapeutics.
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Affiliation(s)
- Alan J. Weaver
- Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; (A.J.W.J.); (G.O.-S.); (T.R.P.)
| | - Timothy R. Borgogna
- Department of Microbiology & Cell Biology, Montana State University, Bozeman, MT 59717, USA;
| | - Galen O’Shea-Stone
- Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; (A.J.W.J.); (G.O.-S.); (T.R.P.)
| | - Tami R. Peters
- Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; (A.J.W.J.); (G.O.-S.); (T.R.P.)
| | - Valérie Copié
- Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; (A.J.W.J.); (G.O.-S.); (T.R.P.)
- Correspondence: (V.C.); (J.V.); (M.T.); Tel.: +406-994-7244 (V.C.); +406-994-7184 (J.V.); +406-994-6515 (M.T.)
| | - Jovanka Voyich
- Department of Microbiology & Cell Biology, Montana State University, Bozeman, MT 59717, USA;
- Correspondence: (V.C.); (J.V.); (M.T.); Tel.: +406-994-7244 (V.C.); +406-994-7184 (J.V.); +406-994-6515 (M.T.)
| | - Martin Teintze
- Department of Chemistry & Biochemistry, Montana State University, Bozeman, MT 59717, USA; (A.J.W.J.); (G.O.-S.); (T.R.P.)
- Correspondence: (V.C.); (J.V.); (M.T.); Tel.: +406-994-7244 (V.C.); +406-994-7184 (J.V.); +406-994-6515 (M.T.)
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Shen C, Shen B, Zhu J, Yuan H, Hu J. Topical delivery of pluronic F127/TPGS mixed micelles-based hydrogel loaded with glycyrrhizic acid for atopic dermatitis treatment. Drug Dev Ind Pharm 2022; 47:1975-1985. [PMID: 35579672 DOI: 10.1080/03639045.2022.2077957] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
OBJECTIVE The purpose of this study was to develop pluronic F127/D-a-tocopheryl polyethylene glycol 1000 succinate mixed micelles-based hydrogel (MMs-gel) for topical delivery of GL to improve its skin permeability and atopic dermatitis (AD) treatment. SIGNIFICANCE GL loaded MMs-gel (GL-MMs-gel) could be potentially used as a promising nanocarrier for the treatment of AD. METHODS GL-MMs were prepared by thin film hydration method and then loaded into carbopol gel. The formulation of GL-MMs-gel was optimized by full factorial design and systematically characterized for drug content, pH, spreadability, in vitro drug release and percutaneous permeation, etc. The therapeutic effect of GL-MMs-gel was also investigated in AD-like skin lesion model in BALB/c mice and compared with GL solution-based gel (GL-sol-gel). RESULTS Spherical GL-MMs with particle size of ∼30 nm were successfully incorporated into carbopol gel to form GL-MMs-gel with drug content of (98.80 ± 1.30) %, pH of 6.0 ± 0.08, and spreadability of (7.1 ± 0.2) cm. In vitro drug release profile of GL-MMs-gel exhibited a sustained-release behavior. The permeation flux for GL-MMs-gel (5.15 ± 0.33 µg/cm2/h) was significantly higher than that of GL-sol-gel (3.08 ± 0.34 µg/cm2/h) and GL-MMs-gel increased the accumulative amounts of GL in rats' skin 8.41 times than GL-sol-gel. The GL-MMs-gel was more effective than GL-sol-gel in suppressions of various AD symptoms including skin lesions, edema, high IgE levels, epidermal hyperplasia, and mast cell infiltration. CONCLUSION All results revealed that MMs-gel could be a promising carrier for topical delivery of GL for the treatment of AD.
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Affiliation(s)
- Chengying Shen
- Department of Pharmacy, Jiangxi Provincial People's Hospital, Nanchang 330006, China.,Department of Pharmacy, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, China
| | - Baode Shen
- Key Lab of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Chinese Medicine, Nanchang 330004, China
| | - Junjun Zhu
- Department of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, China
| | - Hailong Yuan
- Department of Pharmacy, Air Force Medical Center, PLA, Beijing 100142, China
| | - Jianxin Hu
- Department of Pharmacy, Jiangxi Provincial People's Hospital, Nanchang 330006, China.,Department of Pharmacy, The First Affiliated Hospital of Nanchang Medical College, Nanchang 330006, China
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Hu F, Luo R, Duan S, Guo Q, Wang L, Jiang G, Fan C, Zou M, Wang T, Wang Y, Sun Y, Peng X. Evaluation of Glycyrrhizic Acid Therapeutic Effect and Safety in Mycoplasma gallisepticum (HS Strain)-Infected Arbor Acres Broilers. Animals (Basel) 2022; 12:1285. [PMID: 35625131 PMCID: PMC9137610 DOI: 10.3390/ani12101285] [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: 03/25/2022] [Revised: 05/12/2022] [Accepted: 05/16/2022] [Indexed: 12/04/2022] Open
Abstract
This study was conducted to evaluate the therapeutic effects and safety of GA in MG-infected broilers. Our results showed that the minimum inhibitory concentration of GA was 31.25 μg/mL. Moreover, GA inhibited the expression of MG adhesion protein (pMGA1.2) in the broilers' lungs. GA treatment clearly decreased the morbidity of CRD and mortality in the MG-infected broilers. Compared with the model group, GA treatment significantly decreased gross air sac lesion scores and increased average weight gain and feed conversion rate in the MG-infected broilers. Histopathological examination showed GA treatment attenuated MG-induced trachea, immune organ and liver damage in the broilers. Moreover, GA treatment alone did not induce abnormal morphological changes in these organs in the healthy broilers. Compared with the model group, serum biochemical results showed GA treatment significantly decreased the content of total protein, albumin, globulin, alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, uric acid, total cholesterol, and increased the content of albumin/globulin, alkaline phosphatase, apolipoprotein B and apolipoprotein A-I. In conclusion, GA displayed a significant therapeutic efficacy regarding MG infection and had no adverse effects on the broilers (100 mg/kg/d).
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Affiliation(s)
| | | | | | | | | | | | | | | | | | | | | | - Xiuli Peng
- Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction, Ministry of Education, College of Animal Science and Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; (F.H.); (R.L.); (S.D.); (Q.G.); (L.W.); (G.J.); (C.F.); (M.Z.); (T.W.); (Y.W.); (Y.S.)
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39
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Li L, Chen A, Liu B, Pan H, Yu Y, Liu Y. Preparation and pharmacokinetics of glycyrrhetinic acid and cell transmembrane peptides modified with liposomes for liver targeted-delivery. Biomed Mater 2022; 17. [PMID: 35483344 DOI: 10.1088/1748-605x/ac6b73] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 04/28/2022] [Indexed: 12/16/2022]
Abstract
The article presents a hepatocellular carcinoma cell surface-specific ligand glycyrrhetinic acid (GA) and cell-penetrating peptide (TAT) with good cell membrane penetration to modify the anti-tumor drug pingyangmycin (PYM) liver delivery system, which achieve targeted delivery of drugs and improve anti-tumor efficiency. In this study, we synthesized the pingyangmycin liposome modified by glycyrrhetinic acid and cell penetrating peptide(GA-TAT-PYM-L) and evaluated the anti-tumor effect of GA-TAT-PYM-Lin vitro. Using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylte-trazolium bromidecell proliferation method, GA-TAT-PYM-L had a stronger inhibitory effect on HepG2 cells than the free drug PYM at the same concentration. Acridine orange-ethidium bromide staining assays showed that GA-TAT-PYM-L had stronger apoptosis promotion effects on HepG2 cells in comparison to PYM. Pharmacokinetic studies indicated that, compared with PYM, GA-TAT-PYM-L enhanced mean residence time (MRT0-∞) and area under curve (AUC0-∞) by about 2.79-fold and 2.45-fold. TheT1/2was prolonged to 140.23 ± 14.13 min. Tissue distribution results showed that the PYM concentrations in livers from the GA-TAT-PYM-L group were always higher than other tissues at each monitoring period after 5 min, indicating that GA-TAT-PYM-L can achieve liver targeting.
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Affiliation(s)
- Li Li
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China.,Liaoning Key Laboratory of New Drug Research & Development, Shenyang 110036, People's Republic of China
| | - Anqi Chen
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China
| | - Bingmi Liu
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China.,Liaoning Pharmaceutical Engineering Research Center for Natural Medicine, Shenyang 110036, People's Republic of China
| | - Hao Pan
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China.,Liaoning Key Laboratory of New Drug Research & Development, Shenyang 110036, People's Republic of China
| | - Yanjie Yu
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China
| | - Yu Liu
- School of Pharmacy, Liaoning University, Shenyang 110036, People's Republic of China.,Liaoning University, Judicial Expertise Center, Shenyang 110036, People's Republic of China
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40
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Smirnova I, Petrova A, Lobov A, Minnibaeva E, Phoung TTT, Van LT, Khine MM, Esaulkova I, Slita A, Zarubaev V, Kazakova O. Azepanodipterocarpol is potential candidate for inhibits influenza H1N1 type among other lupane, oleanane, and dammarane A-ring amino-triterpenoids. J Antibiot (Tokyo) 2022; 75:258-267. [PMID: 35246615 PMCID: PMC8894567 DOI: 10.1038/s41429-022-00514-w] [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: 11/02/2021] [Revised: 01/28/2022] [Accepted: 01/30/2022] [Indexed: 11/26/2022]
Abstract
A series of lupane-, oleanane- and dammarane-based triterpenoids with 3β-amino, A-ring azepano- and 3,4-seco-fragments has been synthesized and evaluated for antiviral activity against influenza A(H1N1) virus. It was found that azepanodipterocarpol 8 and 3β-amino-28-oxoallobetulin 11 showed antiviral activity with IC50 1.1 and 2.6 μg ml-1, and selectivity index of 19 and 10, respectively.
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Affiliation(s)
- Irina Smirnova
- Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 pr. Oktyabrya, 450054, Ufa, Russian Federation.
| | - Anastasiya Petrova
- Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 pr. Oktyabrya, 450054, Ufa, Russian Federation
| | - Alexander Lobov
- Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 pr. Oktyabrya, 450054, Ufa, Russian Federation
| | - El'za Minnibaeva
- Department of Technical Chemistry and Materials Science, Bashkir State University, Faculty of Engineering, 32 Zaki Validi, 450076, Ufa, Russian Federation
| | - Thao Tran Thi Phoung
- Institute of Chemistry - Vietnamese Academy of Science and Technology 18, Hoang Quoc Viet street 18 Cau Giay district, Hanoi, Vietnam
| | - Loc Tran Van
- Institute of Chemistry - Vietnamese Academy of Science and Technology 18, Hoang Quoc Viet street 18 Cau Giay district, Hanoi, Vietnam
| | - Myint Myint Khine
- Department of Chemistry, University of Yangon, University Avenue Road, Kamayut Township, 11041, Yangon, Myanmar
| | - Iana Esaulkova
- Department of virology, St. Petersburg Pasteur Institute of Epidemiology and Microbiology, Experimental virology laboratory, 14 Mira St., St. Petersburg, 197001, Russian Federation
| | - Alexander Slita
- Department of virology, St. Petersburg Pasteur Institute of Epidemiology and Microbiology, Experimental virology laboratory, 14 Mira St., St. Petersburg, 197001, Russian Federation
| | - Vladimir Zarubaev
- Department of virology, St. Petersburg Pasteur Institute of Epidemiology and Microbiology, Experimental virology laboratory, 14 Mira St., St. Petersburg, 197001, Russian Federation
| | - Oxana Kazakova
- Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, 71 pr. Oktyabrya, 450054, Ufa, Russian Federation
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Qin J, Song J, Liang Y, Jiao A, Yang B. In-silico analysis identifies the anti-liver injury targets of diammonium glycyrrhizinate: validated in perfluorooctanoic acid-lesioned mouse model. Chem Biodivers 2022; 19:e202100938. [PMID: 35362201 DOI: 10.1002/cbdv.202100938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Accepted: 03/31/2022] [Indexed: 11/05/2022]
Abstract
Liver injury refers to a pathological condition that causes dysfunction to hepatic parenchymal cells. And diammonium glycyrrhizinate (DG) is clinically prescribed for hepatoprotection. To date, detailed information regarding DG against liver injury in molecular mechanisms remains unrevealed totally. In the present study, we applied network pharmacology and molecular docking to decipher substantial genes, biological functions of DG for treating liver injury. Furthermore, preclinical experiments using perfluorooctanoic acid (PFOA)-induced liver injury in mice were used to validate the bioinformatic findings. Our results showed that the target network of DG and liver injury predominantly shared 90 genes. Eleven core genes of DG treating liver injury including ALB, TP53, TNF, CASP3, PTGS2, JUN, TLR4, IL10, STAT3, NOS3, FOS. The gene ontology and KEGG enrichment further highlighted their importance in regulation of cell proliferation, regulation of transcription, inflammatory response, regulation of NF-kappaB import into nucleus, regulation of apoptotic process, T cell receptor signaling pathway, and Toll-like receptor signaling pathway. Moreover, DG treatment was found to rescue the PFOA-induced liver injury through the modulation of identified genes including TNF, CASP3, PTGS2, and ALB. Current integrated data from bioinformatics method and experimental validation uncovered that DG exerts potent actions to treat liver injury through regulating core targets associated with inflammation and immunomodulation.
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Affiliation(s)
- Jingru Qin
- Guangxi Medical University, College of Pharmacy, Shuangyong Road No.22, Nanning, CHINA
| | - Jianhua Song
- guangxi medical university, TCM, Zhongshan Road No 1, Guigang, CHINA
| | - Yujia Liang
- Guangxi Medical University, TCM, Shuangyong Road No.22, Nanning, CHINA
| | - Aijun Jiao
- Guangxi Medical University, TCM, Shuangyong Road No.22, Nanning, CHINA
| | - Bin Yang
- Guangxi Medical University, College of Pharmacy, Shuangyong Road No.22, 541004, Nanning, CHINA
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Dai W, Wang K, Zhen X, Huang Z, Liu L. Magnesium isoglycyrrhizinate attenuates acute alcohol-induced hepatic steatosis in a zebrafish model by regulating lipid metabolism and ER stress. Nutr Metab (Lond) 2022; 19:23. [PMID: 35331265 PMCID: PMC8944020 DOI: 10.1186/s12986-022-00655-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2021] [Accepted: 03/01/2022] [Indexed: 12/15/2022] Open
Abstract
Background Alcoholism is a well-known risk factor for liver injury and is one of the major causes of hepatic steatosis worldwide. Although many drugs have been reported to have protective effects against acute alcohol-induced hepatotoxicity, there is limited available treatment for alcoholic liver disease (ALD), indicating an urgent need for effective therapeutic options. Herein, we first reported the protective effects of magnesium isoglycyrrhizinate (MgIG) on acute alcohol-induced hepatic steatosis and its related mechanisms in a zebrafish model. Methods Alcohol was administered directly to embryo medium at 5 days post-fertilization (dpf) for up to 32 h. MgIG was given to the larvae 2 h before the administration of alcohol and then cotreated with alcohol starting at 5 dpf. Oil red O staining was used to determine the incidence of steatosis, and pathological features of the liver were assessed by hematoxylin–eosin staining. Biological indexes, total cholesterol (TC) and triacylglycerol (TG) were detected in the livers of zebrafish larvae. Morphological changes in the livers of zebrafish larvae were observed using liver-specific EGFP transgenic zebrafish (Tg(lfabp10a:eGFP)). The expression levels of critical molecules related to endoplasmic reticulum (ER) stress and lipid metabolism were detected by qRT–PCR, whole-mount in situ hybridization and western blotting. Results Alcohol-treated larvae developed hepatomegaly and steatosis after 32 h of exposure. We found that MgIG improved hepatomegaly and reduced the incidence of steatosis in a dose-dependent manner by oil red O staining and diminished deposits of alcohol-induced fat droplets by histologic analysis. Moreover, MgIG significantly decreased the levels of TC and TG in the livers of zebrafish larvae. Furthermore, the expression levels of critical genes involved in ER stress (atf6, irela, bip, chop) and the key enzymes regulating lipid metabolism (acc1, fasn, hmgcs1 and hmgcra) were significantly higher in the alcohol-treated group than in the control group. However, in the MgIG plus alcohol-treated group, the expression of these genes was markedly decreased compared with that in the alcohol-treated group. Whole-mount in situ hybridization and western blotting also showed that MgIG had an effect on the expression levels of critical genes and proteins involved in lipid metabolism and ER stress. Our results revealed that MgIG could markedly regulate these genes and protect the liver from ER stress and lipid metabolism disorders. Conclusions Our study is the first to demonstrate that MgIG could protect the liver from acute alcohol stimulation by ameliorating the disorder of lipid metabolism and regulating ER stress in zebrafish larvae. Supplementary Information The online version contains supplementary material available at 10.1186/s12986-022-00655-7.
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Affiliation(s)
- Wencong Dai
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Kunyuan Wang
- Department of Gastroenterology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, Guangdong, China
| | - Xinchun Zhen
- Department of Infectious Diseases, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, 519000, Guangdong, China
| | - Zhibin Huang
- Division of Cell, Developmental and Integrative Biology, School of Medicine, South China University of Technology, Guangzhou, 510006, Guangdong, China
| | - Li Liu
- State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
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Zheng X, Wang L, You L, Liu Y, Cohen M, Tian S, Li W, Li X. Dietary licorice enhances in vivo cadmium detoxification and modulates gut microbial metabolism in mice. IMETA 2022; 1:e7. [PMID: 38867726 PMCID: PMC10989944 DOI: 10.1002/imt2.7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2021] [Revised: 12/27/2021] [Accepted: 01/11/2022] [Indexed: 06/14/2024]
Abstract
Mass cadmium (Cd) poisoning is a serious health problem in many parts of the world. We propose that dietary intervention can be a practical solution to this problem. This study aimed to identify effective dietary products from traditional Chinese herbs that can detoxify Cd. Five candidate herbal foods with detoxifying potential were selected and subjected to mouse toxicological tests. The chemical composition and dose-response effects of licorice on mouse hepatocytes were determined. Licorice was selected for further tests to examine its effects on growth, tissue Cd accumulation, and gut and liver fitness of mice. The expression of hepatic metallothionein (Mt) genes was quantified in vitro in hepatocytes and in vivo in liver tissues of mice. The results showed that licorice dietary intervention was effective in reducing blood Cd by >50% within 1 month. Cd was also substantially reduced in the heart and lung tissues, but increased 2.1-fold in the liver. The liver of Cd poisoned mice improved with licorice intervention. Licorice treatment significantly induced Cd accumulation and expression of the Mt1 gene in hepatic cells both in vitro and in vivo. Licorice intake substantially altered gut microbial structure and enriched Parabacteroides distasonis. Omics results showed that licorice improved gut metabolism, particularly the metabolic pathways for glycyrrhizin, bile acids, and amino acids. Dietary licorice effectively reduced mouse blood Cd and had a profound impact on liver and gut fitness. We conclude that herbal licorice can be used as a dietary intervention for mass Cd poisoning.
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Affiliation(s)
- Xin Zheng
- Hebei Key Laboratory of Soil Ecology, Centre for Agricultural Resources Research, Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangChina
| | - Likun Wang
- Hebei Key Laboratory of Soil Ecology, Centre for Agricultural Resources Research, Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangChina
| | - Linhao You
- Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life ScienceHebei Normal UniversityShijiazhuangChina
| | - Yong‐Xin Liu
- Institute of Genetics and Developmental Biology, State Key Laboratory of Plant GenomicsChinese Academy of SciencesBeijingChina
| | - Michael Cohen
- Department of BiologySonoma State UniversityRohnert ParkCaliforniaUSA
| | - Siyu Tian
- Laboratory of Molecular Iron Metabolism, The Key Laboratory of Animal Physiology, Biochemistry and Molecular Biology of Hebei Province, College of Life ScienceHebei Normal UniversityShijiazhuangChina
| | - Wenjun Li
- Hebei Key Laboratory of Soil Ecology, Centre for Agricultural Resources Research, Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangChina
- University of Chinese Academy of SciencesBeijingChina
| | - Xiaofang Li
- Hebei Key Laboratory of Soil Ecology, Centre for Agricultural Resources Research, Institute of Genetics and Developmental BiologyChinese Academy of SciencesShijiazhuangChina
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Huang W, Lin Y, Kuo H, Sheu M, Feng Y, Feng I, Sun C, Hsieh P, Lim P, Chen C. Benefits of stronger
Neo‐Minophagen
C in acute hepatitis after transarterial chemoembolization therapy for hepatomas. ADVANCES IN DIGESTIVE MEDICINE 2022. [DOI: 10.1002/aid2.13305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Wen‐Chieh Huang
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Yu‐Min Lin
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Hsing‐Tao Kuo
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Ming‐Jen Sheu
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Yin‐Hsun Feng
- Division of Hematology and Oncology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - I‐Che Feng
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Chi‐Shu Sun
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Ping‐Hsin Hsieh
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Poh‐Poo Lim
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
| | - Chi‐Hsing Chen
- Division of Gastroenterology and Hepatology Department of Internal Medicine, Chi Mei Medical Center Tainan Taiwan
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Morita A, Omoya Y, Ito R, Ishibashi Y, Hiramoto K, Ohnishi S, Yoshikawa N, Kawanishi S. Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling. Biochem Biophys Rep 2021; 28:101181. [PMID: 34934826 PMCID: PMC8654616 DOI: 10.1016/j.bbrep.2021.101181] [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: 10/17/2021] [Revised: 11/29/2021] [Accepted: 11/30/2021] [Indexed: 11/30/2022] Open
Abstract
The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear. We investigated the effects of glycyrrhizin (GL) and its derivatives on liver differentiation using human iPS cells by using a flow cytometric analysis. GL promoted hepatic differentiation at the hepatoblast formation stage. The GL derivatives, 3-O-mono-glucuronyl 18β-glycyrrhetinic acid (Mono) and 3-O-[glucosyl (1 → 2)-glucuronyl] 18β-glycyrrhetinic acid increased AFP+ cell counts and albumin+ cell counts. Glucuronate conjugation seemed to be a requirement for hepatic differentiation. Mono exhibited the most significant hepatic differentiation effect. We evaluated the effects of (±)-2-(2,4-dichlorophenoxy) propionic acid (DP), a T1R3 antagonist, and sucralose, a T1R3 agonist, on hepatic differentiation, and found that DP suppressed Mono-induced hepatic differentiation, while sucralose promoted hepatic differentiation. Thus, GL promoted hepatic differentiation via T1R3 signaling. In addition, Mono increased β-catenin+ cell count and decreased Hes5+ cell count suggesting the involvement of Wnt and Notch signaling in GL-induced hepatic differentiation. In conclusion, GL exerted a hepatic differentiation effect via sweet receptor (T1R3), canonical Wnt, and Notch signaling.
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Key Words
- AFP, α-fetoprotein
- Api, 3-O-[apiosyl (1 → 2)-glucuronyl] βGA
- CBX, carbenoxolone, 3-O-hemisuccinyl βGA
- CK-19, cytokeratin 19
- DMSO, dimethyl sulfoxide
- DP, (±)-2-(2,4-dichlorophenoxy) propionic acid
- GL, glycyrrhizin
- Glc, 3-O-[glucosyl (1 → 2)-glucuronyl] βGA
- Glycyrrhizin
- HMGB1, high-mobility group box1
- HNF-4α, hepatocyte nuclear factor 4α
- Hepatic differentiation
- Hes, hairy and enhancer of split
- LSG, licorice saponin G
- LSH, licorice saponin H
- Liver regeneration
- Mono, 3-O-mono-glucuronyl βGA
- Sweet receptor
- T1R3
- αGA, 18α-glycyrrhetinic acid
- βGA, 18β-glycyrrhetinic acid
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Affiliation(s)
- Akihiro Morita
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Yuta Omoya
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Rie Ito
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Yuya Ishibashi
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Keiichi Hiramoto
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Shiho Ohnishi
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
| | - Nobuji Yoshikawa
- Matsusaka R&D Center, Cokey Co., Ltd., Matsusaka, Mie, 515-0041, Japan
| | - Shosuke Kawanishi
- Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, 513-8670, Japan
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Kumar B, Misra A, Singh SP, Dhar YV, Rawat P, Chattopadhyay D, Barik SK, Srivastava S. In-silico efficacy of potential phytomolecules from Ayurvedic herbs as an adjuvant therapy in management of COVID-19. J Food Drug Anal 2021; 29:559-580. [PMID: 35649148 PMCID: PMC9931022 DOI: 10.38212/2224-6614.3380] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Revised: 05/17/2021] [Accepted: 08/26/2021] [Indexed: 11/18/2022] Open
Abstract
The recent COVID-19 outbreak caused by SARS-CoV-2 virus has sparked a new spectrum of investigations, research and studies in multifarious directions. Efforts are being made around the world for discovery of effective vaccines/drugs against COVID-19. In this context, Ayurveda, an alternative traditional system of medicine in India may work as an adjuvant therapy in compromised patients. We selected 40 herbal leads on the basis of their traditional applications. The phytomolecules from these leads were further screened through in-silico molecular docking against two main targets of SARS-CoV-2 i.e. the spike protein (S; structural protein) and the main protease (MPRO; non-structural protein). Out of the selected 40, 12 phytomolecules were able to block or stabilize the major functional sites of the main protease and spike protein. Among these, Ginsenoside, Glycyrrhizic acid, Hespiridin and Tribulosin exhibited high binding energy with both main protease and spike protein. Etoposide showed good binding energy only with Spike protein and Teniposide had high binding energy only with main protease. The above phytocompounds showed promising binding efficiency with target proteins indicating their possible applications against SARS-CoV-2. However, these findings need to be validated through in vitro and in vivo experiments with above mentioned potential molecules as candidate drugs for the management of COVID-19. In addition, there is an opportunity for the development of formulations through different permutations and combinations of these phytomolecules to harness their synergistic potential.
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Affiliation(s)
- Bhanu Kumar
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | - Ankita Misra
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | - Satyendra Pratap Singh
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | - Yogeshwar Vikram Dhar
- Bioinformatics Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | - Poonam Rawat
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | | | - Saroj Kanta Barik
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
| | - Sharad Srivastava
- Pharmacognosy Division, CSIR-National Botanical Research Institute, Lucknow, U.P. 226001,
India
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Li L, Liu H, Tao W, Wen S, Fu X, Yu S. Pharmacological Inhibition of HMGB1 Prevents Muscle Wasting. Front Pharmacol 2021; 12:731386. [PMID: 34867338 PMCID: PMC8637759 DOI: 10.3389/fphar.2021.731386] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2021] [Accepted: 10/18/2021] [Indexed: 12/19/2022] Open
Abstract
Background: Cachexia is a multifactorial disorder characterized by weight loss and muscle wasting, making up for about 20% of cancer-related death. However, there are no effective drugs to combat cachexia at present. Methods: In this study, the effect of CT26 exosomes on C2C12 myotubes was observed. We compared serum HMGB1 level in cachexia and non-cachexia colon cancer patients. We further explored HMGB1 expression level in CT26 exosome. We added recombinant HMGB1 to C2C12 myotubes to observe the effects of HMGB1 on C2C12 myotubes and detected the expression level of the muscle atrophy-related proteins. Then, we used the HMGB1 inhibitor glycyrrhizin to reverse the effects of HMGB1 on C2C12 myotubes. Finally, HMGB1 inhibitor glycyrrhizin was utilized to relieve cachexia in CT26 cachexia mouse model. Results: Exosomes containing HMGB1 led to muscle atrophy with significantly decreased myotube diameter and increased expression of muscle atrophy-related proteins Atrogin1 and MuRF1. Further, we detected that HMGB1 induced the muscle atrophy mainly via TLR4/NF-κB pathway. Administration of the HMGB1 inhibitor glycyrrhizin could relieve muscle wasting in vitro and attenuate the progression of cachexia in vivo. Conclusion: These findings demonstrate the cachectic role of HMGB1, whether it is soluble form of HMGB1 or secreted from tumor cells as part of exosomes. HMGB1 inhibitor glycyrrhizin might be a promising drug in colon cancer cachexia.
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Affiliation(s)
- Lu Li
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Huiquan Liu
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Weili Tao
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Su Wen
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaofen Fu
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shiying Yu
- Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Roemer HC, Kunz L, Botzenhardt S. The influence of excessive consumption of liquorice on phenprocoumon (Marcumar®): a case report. J Int Med Res 2021; 49:3000605211049649. [PMID: 34826377 PMCID: PMC8646198 DOI: 10.1177/03000605211049649] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Here, the case of a 92-year-old female patient, who was diagnosed with atrial fibrillation and treated with phenprocoumon (Marcumar®), is reported. Pre-existing comorbidities were arterial hypertension, coronary heart disease, diabetes mellitus type 2, mild senile dementia and renal insufficiency. Despite treatment with phenprocoumon (Marcumar®), the patient experienced an ischaemic stroke. Her measured international normalized ratio (INR)-values during the months before the stroke were within the therapeutic range of 2–3, then suddenly decreased to 1.25. A retrospective inquiry failed to identify any significant changes in behaviour or therapy adherence, other than the consumption of 1.5 kg (3.3 lb) of hard-boiled candy liquorice in the days leading up to the stroke. The sudden decrease in INR-values may be explained by the influence of liquorice and its compounds on the pharmacokinetics of phenprocoumon (Marcumar®). In this context, the most important factors are the susceptibility of vitamin K antagonists to nutrition or metabolic irregularities, the influence of liquorice on the function of isoenzymes of the cytochrome P450 family that may lead to reduced bioavailability of phenprocoumon, and the influence of liquorice on peroxisome proliferator-activated receptor alpha transactivation.
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Affiliation(s)
- Hermann Casper Roemer
- Institute for General Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Luisa Kunz
- Institute for General Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
| | - Suzan Botzenhardt
- Institute for General Medicine, University Hospital Essen, University Duisburg-Essen, Essen, Germany
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49
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Abraham J, Florentine S. Licorice ( Glycyrrhiza glabra) Extracts-Suitable Pharmacological Interventions for COVID-19? A Review. PLANTS (BASEL, SWITZERLAND) 2021; 10:2600. [PMID: 34961070 PMCID: PMC8708549 DOI: 10.3390/plants10122600] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 11/12/2021] [Accepted: 11/23/2021] [Indexed: 06/06/2023]
Abstract
Even though vaccination has started against COVID-19, people should continue maintaining personal and social caution as it takes months or years to get everyone vaccinated, and we are not sure how long the vaccine remains efficacious. In order to contribute to the mitigation of COVID-19 symptoms, the pharmaceutical industry aims to develop antiviral drugs to inhibit the SARS-CoV-2 replication and produce anti-inflammatory medications that will inhibit the acute respiratory distress syndrome (ARDS), which is the primary cause of mortality among the COVID-19 patients. In reference to these tasks, this article considers the properties of a medicinal plant named licorice (Glycyrrhiza glabra), whose phytochemicals have shown both antiviral and anti-inflammatory tendencies through previous studies. All the literature was selected through extensive search in various databases such as google scholar, Scopus, the Web of Science, and PubMed. In addition to the antiviral and anti-inflammatory properties, one of the licorice components has an autophagy-enhancing mechanism that studies have suggested to be necessary for COVID-19 treatment. Based on reviewing relevant professional and historical literature regarding the medicinal properties of licorice, it is suggested that it may be worthwhile to conduct in vitro and in vivo studies, including clinical trials with glycyrrhizic and glycyrrhetinic acids together with other flavonoids found in licorice, as there is the potentiality to provide natural interventions against COVID-19 symptoms.
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Affiliation(s)
- Joji Abraham
- School of Engineering, Information Technology, and Physical Sciences, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3353, Australia
| | - Singarayer Florentine
- Centre for Environmental Management, School of Science, Psychology, and Sport, Mt Helen Campus, Federation University Australia, Ballarat, VIC 3353, Australia;
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50
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Fatima A, Malick TS, Khan I, Ishaque A, Salim A. Effect of glycyrrhizic acid and 18β-glycyrrhetinic acid on the differentiation of human umbilical cord-mesenchymal stem cells into hepatocytes. World J Stem Cells 2021; 13:1580-1594. [PMID: 34786159 PMCID: PMC8567450 DOI: 10.4252/wjsc.v13.i10.1580] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2021] [Revised: 05/25/2021] [Accepted: 09/19/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND End-stage liver disease is a global health complication with high prevalence and limited treatment options. Cell-based therapies using mesenchymal stem cells (MSCs) emerged as an alternative approach to support hepatic regeneration. In vitro preconditioning strategies have been employed to strengthen the regenerative and differentiation potential of MSCs towards hepatic lineage. Chemical compounds of the triterpene class; glycyrrhizic acid (GA) and 18β-glycyrrhetinic acid (GT) possess diverse therapeutic properties including hepato-protection and anti-fibrosis characteristics. They are capable of modulating several signaling pathways that are crucial in hepatic regeneration. Preconditioning with hepato-protective triterpenes may stimulate MSC fate transition towards hepatocytes. AIM To explore the effect of GA and GT on hepatic differentiation of human umbilical cord-MSCs (hUC-MSCs). METHODS hUC-MSCs were isolated and characterized phenotypically by flow cytometry and immunocytochemistry for the expression of MSC-associated surface molecules. Isolated cells were treated with GA, GT, and their combination for 24 h and then analyzed at three time points; day 7, 14, and 21. qRT-PCR was performed for the expression of hepatic genes. Expression of hepatic proteins was analyzed by immunocytochemistry at day 21. Periodic acid Schiff staining was performed to determine the functional ability of treated cells. RESULTS The fusiform-shaped morphology of MSCs in the treatment groups in comparison with the untreated control, eventually progressed towards the polygonal morphology of hepatocytes with the passage of time. The temporal transcriptional profile of preconditioned MSCs displayed significant expression of hepatic genes with increasing time of differentiation. Preconditioned cells showed positive expression of hepatocyte-specific proteins. The results were further corroborated by positive periodic acid Schiff staining, indicating the presence of glycogen in their cytoplasm. Moreover, bi-nucleated cells, which is the typical feature of hepatocytes, were also seen in the preconditioned cells. CONCLUSION Preconditioning with glycyrrhizic acid, 18β-glycyrrhetinic acid and their combination, successfully differentiates hUC-MSCs into hepatic-like cells. These MSCs may serve as a better therapeutic option for degenerative liver diseases in future.
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Affiliation(s)
- Abiha Fatima
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Tuba Shakil Malick
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Irfan Khan
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Aisha Ishaque
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan
| | - Asmat Salim
- Stem Cell Laboratory, Dr. Panjwani Center for Molecular Medicine and Drug Research, ICCBS, University of Karachi, Karachi 75270, Sindh, Pakistan.
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