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Scientific World Journal 2025年第1期2025卷 9466270页

作者： Floriano, Juliana Ferreira Rodrigues, Daniel Ohara, Rie Almeida, Nara Lígia Martins Lara, Vanessa Soares Sartorelli, Patricia Graeff, Carlos Frederico de Oliveira Grecco, Simone dos Santos González, Alejandra Hortencia Miranda D’Alpino, Paulo Henrique Perlatti Imperial College London National Heart and Lung Institute imperial.ac.uk GBR London United Kingdom Botucatu Medical School São Paulo State University (UNESP) São Paulo unesp.br BRA Botucatu Brazil Bioengineering and Biomaterials Group School of Pharmaceutical Sciences São Paulo State University (UNESP) unesp.br BRA Araraquara São Paulo Brazil Biotechnology and Innovation in Health Program Universidade Anhanguera de São Paulo (UNIAN) São Paulo BRA Brazil Brazil Department of Health Management Fundação Nacional de Gestão de Saúde São Paulo Brazil Undergraduate Program Medical School Universidade Nove de Julho Bauru São Paulo Brazil Department of Surgery Stomatology Pathology and Radiology Bauru School of Dentistry University of São Paulo (USP) São Paulo usp.br BRA Bauru Brazil Department of Chemistry Institute of Environmental Chemical and Pharmaceutical Sciences Federal University of São Paulo São Paulo unifesp.br BRA Diadema Brazil Department of Physics School of Sciences POSMAT-Post-Graduate Program in Materials Science and Technology São Paulo State University (UNESP) São Paulo Bauru Brazil Department of Research and Development (RD) and Innovation Center Triplet Biotechnology Solutions Inc Bauru São Paulo Brazil Post-Graduate Program in Dentistry Uniderp Anhanguera University Mato Grosso do Sul Campo Grande Brazil Post-Graduate Program in Integrated Dental Sciences University of Cuiabá (UNIC) Mato Grosso do Sul Cuiabá Brazil Department of Physics School of Sciences São Paulo State University (UNESP) São Paulo unesp.br BRA Bauru Brazil

Chronic wounds have a significant impact on patients’ quality of life, necessitating the management of pain, infection, bleeding, and emotional challenges. Debridement, which involves the removal of nonviable tissue, is crucial for promoting wound healing. In addition to surgical methods, cost-effective alternatives such as local solutions and ointments with biological properties have been explored. The use of natural compounds with anti-inflammatory, antibacterial, and collagen-synthesizing abilities holds promise for wound healing. This in vitro and in vivo preclinical study aimed to assess the safety and effectiveness of a wound healing ointment containing bioactive ingredients derived from medicinal plants (extracts, essential oils, and vegetable oils). The chemical composition of the ointment was characterized using Fourier transform infrared (FTIR) spectroscopy to gain insights into its synergistic action. Preclinical tests were conducted following standardized protocols. FTIR analysis revealed similarities between the product’s spectrum and that of bioactive compounds. The in vitro tests demonstrated that all formulations of the ointment induced no cell death, DNA damage, or acute toxicity in cell cultures (p < 0.05). No lethal dose was observed, indicating the safety of the ointment at all concentrations. The ointment also stimulated a notably more organized, significantly higher collagen production compared to control groups (p < 0.05). In vivo preclinical analyses also demonstrated no adverse responses being effective in the healing process compared to the control group (silver sulfadiazine) in terms of wound contraction and ulcer re-epithelization (p < 0.05). Significantly higher means of wound contraction were observed in the groups treated with the bioactive-containing ointment when compared to both the positive control group (sulfadiazine) and the control untreated groups (p < 0.05). The regenerative ointment exhibited excellent biocompatibility and bi

关键词： biocompatibility chronic wounds natural compounds preclinical tests wound care

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Design, synthesis, and biological evaluation of indolin-2-one derivatives as novel cyclin-dependent protein kinase 8 (CDK8) inhibitors

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Biomedicine and Pharmacotherapy 2023年第1期159卷 114258-114258页

作者： Hsu, Jui-Yi Hsu, Kai-Cheng Sun, Ching Chou, Ching-Hsuan Lin, Tony Eight Sung, Tzu-Ying Tseng, Hui-Ju Yen, Shih-Chung Yang, Chia-Ron Huang, Wei-Jan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University and Academia Sinica Taipei Taiwan Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan TMU Research Center for Drug Discovery Taipei Medical University Taipei Taiwan TMU Research Center of Cancer Translational Medicine Taipei Medical University Taipei Taiwan Cancer Center Wan Fang Hospital Taipei Medical University Taipei Taiwan School of Pharmacy College of Medicine National Taiwan University Taipei Taiwan Biomedical Translation Research Center Academia Sinica Taipei Taiwan Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy University of Southern California Los Angeles CA United States Warshel Institute for Computational Biology The Chinese University of Hong Kong (Shenzhen) Guangdong Shenzhen China School of Pharmacy Taipei Medical University Taipei Taiwan

Cyclin-dependent protein kinase 8 (CDK8) plays important roles in regulating fibrotic growth factors and inflammatory signaling pathways. Long-term chronic inflammation of the lungs can lead to idiopathic pulmonary fibrosis (IPF). Abnormal alveolar epithelial regeneration leads to the release of various fibrotic growth factors and the activation of inflammatory cells. CDK8 regulates profibrotic cytokines broadly implicated in the pathogenesis of fibrosis. Therefore, inhibition of CDK8 is considered a promising strategy for treating IPF. Here, CDK8 inhibitors were designed and optimized using a fragment-based drug design strategy. Testing results revealed that 71% of the synthesized compounds inhibited CDK8 activity better than the original compound E966–0530. Of these compounds, compound 4k exhibited the strongest CDK8 enzyme-inhibiting activity (IC₅₀ =129 nM). Notably, it displayed a 13-fold increase in potency when compared to E966–0530. Experiments on toxicity and inhibition of epithelial-mesenchymal transition (EMT) protein expressions showed that compound 4k can inhibit EMT protein expressions, but with no significant cytotoxicity for alveolar epithelial cells. Compound 4k showed a potent inhibitory effect in cell migration assays. Furthermore, compound 4k significantly inhibited the phosphorylation of p-Smad3 and RNA Pol II, which are critical mediators in the fibrotic response signaling pathway. Compound 4k remarkably reduced TGF-β1-induced oxidative stress. The above results reveal optimized CDK8 inhibitors with potential use for IPF therapeutic treatment. © 2023 The Authors

关键词： Cyclin-dependent protein kinase 8 (CDK8) Idiopathic pulmonary fibrosis (IPF) Indolin-2-one Kinase inhibitor Lead optimization

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The biocompatibility and hemostatic efficacy of silk fibroin nanofibrils fabricated by Shear-Induced phase separation process

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Chemical Engineering Journal 2023年 474卷

作者： Lu, Po-Wen Wu, Yu-Tzu Chang, Liang-Yu Lu, Tzu-Wei Jaihao, Chonlachat Huang, Ching-Shuan Murphy Chuang, Mo-Fei Lin, Chunche Chen, Innie Brangule, Agnese Zarkov, Aleksej Kareiva, Aivaras Yang, Jen-Chang Graduate Institute of Biomedical Materials and Tissue Engineering College of Biomedical Engineering Taipei Medical University Taipei11052 Taiwan Division of Gastroenterology and Hepatology Department of Internal Medicine Shuang Ho Hospital Taipei Medical University Zhongzheng Rd. Taipei Zhonghe23561 Taiwan Graduate Institute of Nanomedicine and Medical Engineering College of Biomedical Engineering Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Dentistry Taipei Medical University Hospital Taipei11031 Taiwan Institute of Organic and Polymeric Materials National Taipei University of Technology Taipei106344 Taiwan Research and Development Center for Smart Textile Technology National Taipei University of Technology Taipei106344 Taiwan Innie Chen Department of Obstetrics and Gynecology University of Ottawa OttawaONK1H 7W9 Canada Department of Pharmaceutical Chemistry Riga Stradins University RīgaLV-1007 Latvia Institute of Chemistry Vilnius University Naugarduko 24 VilniusLT-03225 Lithuania International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei11031 Taiwan Research Center of Biomedical Device Taipei Medical University Taipei11031 Taiwan Research Center of Digital Oral Science and Technology Taipei Medical University Taipei11031 Taiwan

The objectives of this study were to investigate the biocompatibility and hemostatic efficacy of silk fibroin nanofibrils (SFNFs). Unlike a conventional dialysis/freeze-drying process, SFNFs were prepared using a novel shear-induced phase-separation method. The morphology, particle size distribution, protein secondary structures, and crystalline structures of the resulting SFNFs were respectively investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), laser diffraction (LD), Fourier-transform infrared (FTIR) spectroscopy, and x-ray diffraction (XRD) deconvolution analyses. Polar and non-polar extractants of SFNFs under a bath ratio of 0.2 g/mL were collected after individually soaking them into 0.9% normal saline and cottonseed oil. In vitro hemolysis ratios, biocompatibility, and sensitization tests were carried out. Then, the hemostatic efficacy was assayed using a rat liver punch biopsy model. Compared to dialyzed/freeze-dried SF, the harvested SFNFs revealed high surface area in morphology. The median particle size distribution, D50, was 294 μm for SFNFs. Shear-induced hydrogen bonding, crystallization, and phase separation tended to give the SFNFs a high crystalline index (CI) and degree of crystallinity (DC). The hemolysis ratio of SFNFs was 0.86 ± 0.40%, and it was classified as being non-hemolytic (0%∼2%). The test results of toxicity and skin sensitization were both negative. The hemostasis time for SFNFs (2.8 ± 0.6 min) was statistically less than that of oxidized cellulose (4.3 ± 0.9 min) (p © 2023 Elsevier B.V.

关键词： Biocompatibility

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Nanomolar resveratrol reduces early alterations of pancreatitis and pancreatic cancer in pancreatic acinar cells

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Phytomedicine Plus 2022年第3期2卷 100301-100301页

作者： Pereira, Thiago M.C. Carvalho, Glaucimeire R. Luaces-Regueira, María Bugallo-Casal, Ana Iglesias-Mejuto, Ana Nugteren, Lonneke Schmidt, Martina Viña, Dolores Vasquez, Elisardo C. Campos-Toimil, Manuel Physiology and Pharmacology of Chronic Diseases (FIFAEC) Center for Research in Molecular Medicine and Chronic Diseases (CiMUS) University of Santiago de Compostela 15782 Spain Pharmaceutical Sciences Graduate Program Vila Velha University ES Vila Velha Brazil Federal Institute of Education Science and Technology (IFES) ES Vila Velha Brazil Department of Molecular Pharmacology University of Groningen Groningen Netherlands Clinical Neuroscience Research Laboratory Health Research Institute of Santiago de Compostela (IDIS) Santiago de Compostela Spain

Resveratrol is a natural phytoalexin present in human diet with a potential beneficial effect in many diseases including chronic and acute pancreatitis, a potentially fatal disease with significant morbimortality accompanied with obscure pathogenesis and without effective treatments. Resveratrol has also been shown to be a promising anti-tumor molecule on the millimolar scale. In this study, the protective effects of nanomolar concentrations of resveratrol against early events common to pancreatic cancer and pancreatitis induced by supra-physiological concentrations of cholecystokinin (CCK, 100 nM) were evaluated. Resveratrol (200, 500 nM) reduced CCK-induced intracellular trypsin activation and cell injury in isolated rat pancreatic acinar cells (PAC). The damage induced by high CCK and the protective effect of resveratrol was also measured in pancreatic tissue explants by analyzing histological changes. Finally, the effect of resveratrol on the CCK-enhanced nuclear factor κB (NF-κB) expression was studied by Western blot experiments in the AR42J pancreatic acinar cell line. Our results show, for the first time, the ability of resveratrol to reduce premature intracellular activation of trypsin and necrosis in PAC. It is suggested that resveratrol counteracts CCK-induced pancreatic tissue breakdown by downregulation of NF-κB in the nuclear fraction. Since these effects occur at nanomolar concentrations that can be achieved by oral intake, our results suggest that dietary consumption of resveratrol could have a preventive effect and delay the evolution of pancreatitis and pancreatic cancer. © 2022

关键词： CCK: cholecystokinin DMEM: Dulbecco´s modified eagle medium NF-κB: nuclear factor κB PAC: pancreatic acinar cells Pancreatic acinar cells, Pancreatic cancer, Pancreatitis, PI: propidium iodide REAP: Rapid, efficient, and practical method Resveratrol

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Development of oral pharmaceutical formulation of standardized crude ethanolic extract of Atractylodes lancea(Thunb) DC.

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Journal of Chinese pharmaceutical sciences 2020年第4期29卷 280-293页

作者： Thananchanoke Rattanathada Tullayakorn Plengsuriyakarn Rathapon Asasujarit Anurak Cheoymang Juntra Karbwang Kesara Na-Bangchang Graduate Program in Bioclinical Science Chulabhorn International College of MedicineThammasat UniversityPhaholyothin RoadKhlong LuangPathum Thanil2120Thailand Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat UniversityPhaholyothin RoadKhlong LuangPathum Thani 12120Thailand Department of Pharmaceutical Sciences Faculty of PharmacyThammasat UniversityPathumthani 12120Thailand Department of Clinical Product Development Institute of Tropical MedicineNagasaki University1-12-4 SakamotoNagasaki852-8523Japan Drug Discovery and Development Center Office of Advanced Science and TechnologyThammasat UniversityPathumthani 12120Thailand

Cholangiocarcinoma(CCA), the adenocarcinoma of the biliary duct, is commonly reported in Asia with the highest incidence in northeastern Thailand. Chemotherapy of this type of cancer is limited due to the lack of effective chemotherapeutic drugs. A series of previous studies support further research and development of Atractylodes lancea(Thunb) DC.(AL) as a potential candidate for the treatment of CCA as a crude ethanolic extract. In the present study, we aimed to develop an oral pharmaceutical formulation(capsule) of the standardized AL crude ethanolic extract for further clinical development in patients with CCA. Major steps included macroscopic and microscopic authentication of the AL rhizomes, preparation of standardized AL extract, preparation of oral pharmaceutical formulation(capsule) of the standardized AL extract, quantitative and qualitative analysis of the marker compound(atractylodin) in the formulated AL extract, evaluation of contaminations of heavy metals, pesticides residues, and microorganisms in the ground AL rhizomes and the formulated(capsule) powder of AL, physicochemical and pharmaceutical properties of the formulated AL extract/capsule, and cytotoxicity evaluation of the formulated AL extract. Results of all evaluations confirmed satisfactory pharmaceutical properties of oral(capsule) formulation of the standardized AL extract.

关键词： Atractylodes lancea(Thunb)DC. Capsule formulation Atractylodin β-Eudesmol Cholangiocarcinoma

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SRT1720 as an SIRT1 Activator for Alleviating Paraquat-Induced Models of Parkinson's Disease

SSRN

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SSRN 2022年

作者： Chao, Chih-Chang Huang, Chuen-Lin Cheng, Jing-Jy Chiou, Chun-Tang Lee, I-Jung Yang, Ying-Chen Hsu, Ting-Huang Yei, Chan Lin, Pei-Yin Cheng, Jih-Jung Huang, Nai-Kuei Institute of Neuroscience National Chengchi University Taipei Taiwan Medical Research Center Cardinal Tien Hospital Hsintien New Taipei City Taiwan Graduate Institute of Physiology Department of Physiology and Biophysics National Defense Medical Center Taipei114 Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei112 Taiwan Institute of Biophotonics National Yang-Ming University Taipei112 Taiwan Herbal Medicine Department Yokohama University of Pharmacy Yokohama Japan Department of Biotechnology and Animal Science National Ilan University Ilan Taiwan School of Pharmaceutical Sciences National Yang-Ming Chiao Tung University Taipei Taiwan Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan

Epidemiological studies have linked herbicides and Parkinson’s disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720’s protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1a and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD. © 2022, The Authors. All rights reserved.

关键词： Mitochondria

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Personal health records - Potential one-stop approach in polypharmacy

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Computer Methods and programs in Biomedicine Update 2022年 2卷

作者： Chen, Ya-Lin Satria, Fauzi Budi Jamshed, Shazia Babar, Zaheer-Ud-Din Mukherjee, Nilesh Yang, Hsuan-Chia Li, Yu-Chuan Iqbal, Usman Graduate Institute of Biomedical Informatics College of Medical Science and Technology Taipei Medical University Taipei Taiwan PhD Program in Global Health & Health Security College of Public Health Taipei Medical University Taipei Taiwan Department of Pharmacy Practice Faculty of Pharmacy UniSZA Kuala Terengganu Malaysia Qualitative Research-Methodological Application in Health Sciences Research Group Kulliyyah of Pharmacy International Islamic University Malaysia Kuantan Malaysia Centre for Pharmaceutical Policy and Practice Research Department of Pharmacy University of Huddersfield Huddersfield United Kingdom Master of Science in Systems Biology Manipal School of Life Sciences Manipal Academy of Higher Education Manipal India International Center for Health Information Technology (ICHIT) Taipei Medical University Taipei Taiwan

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Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration (vol 613, pg 169, 2023)

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NATURE 2023年第7949期614卷 E45-E45页

作者： Moiseeva, Victoria Cisneros, Andres Sica, Valentina Deryagin, Oleg Lai, Yiwei Jung, Sascha Andres, Eva An, Juan Segales, Jessica Ortet, Laura Lukesova, Vera Volpe, Giacomo Benguria, Alberto Dopazo, Ana Benitah, Salvador Aznar Urano, Yasuteru del Sol, Antonio Esteban, Miguel A. A. Ohkawa, Yasuyuki Serrano, Antonio L. L. Perdiguero, Eusebio Munoz-Canoves, Pura Department of Medicine and Life Sciences Pompeu Fabra University Barcelona Spain CIBERNED Barcelona Spain Altos labs Inc San Diego CA USA ICREA Barcelona Spain Cardiovascular Regeneration Program CNIC Centro Nacional de Investigaciones Cardiovasculares Madrid Spain Laboratory of Integrative Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China Key Laboratory of Regenerative Biology Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China Guangdong Provincial Key Laboratory of Stem Cells and Regenerative Medicine Guangzhou Institutes of Biomedicine and Health Chinese Academy of Sciences Guangzhou China University of Science and Technology of China Hefei China Bioland Laboratory Guangzhou Regenerative Medicine and Health Guangdong Laboratory Guangzhou China CIC bioGUNE-BRTA (Basque Research and Technology Alliance) Bizkaia Technology Park Derio Spain Computational Biology Group Luxembourg Centre for Systems Biomedicine University of Luxembourg Esch-sur-Alzette Luxembourg IKERBASQUE Basque Foundation for Science Bilbao Spain Genomic Unit Centro Nacional de Investigaciones Cardiovasculares and CIBERCV Madrid Spain Institute for Research in Biomedicine and BIST Barcelona Spain Laboratory of Chemistry & Biology Graduate School of Pharmaceutical Sciences and School of Medicine The University of Tokyo Tokyo Japan Division of Transcriptomics. Medical Institute of Bioregulation Kyushu University Fukuoka Japan

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Synthesis and biological evaluation of C-4 substituted phenoxazine-bearing hydroxamic acids with potent class II histone deacetylase inhibitory activities

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Journal of enzyme inhibition and medicinal chemistry 2023年第1期38卷 2212326页

作者： Jung-Chun Chu Hui-Ju Tseng Sung-Bau Lee Kai-Cheng Hsu Ling-Wei Hsin Ru-Hao Liang Tony Eight Lin Nain-Chu Gao Liang-Chieh Chen Wan-Hsun Lu Andrew H-J Wang Wei-Jan Huang Ph.D. Program in Drug Discovery and Development Industry College of Pharmacy Taipei Medical University Taipei Taiwan. School of Pharmacy Taipei Medical University Taipei Taiwan. Department of Pharmacology and Pharmaceutical Sciences School of Pharmacy University of Southern California Los Angeles California United States. Graduate Institute of Cancer Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. Ph.D. Program for Cancer Molecular Biology and Drug Discovery College of Medical Science and Technology Taipei Medical University Taipei Taiwan. TMU Research Center for Drug Discovery Taipei Medical University Taipei Taiwan. School of Pharmacy College of Medicine National Taiwan University Taipei Taiwan. Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei Taiwan. The Ph.D. Program for Translational Medicine College of Medical Science and Technology Taipei Medical University Taipei Taiwan.

Class II histone deacetylases (HDACs) are considered as potential targets to treat Alzheimer's disease (AD). Previously, C-3 substituted phenothiazine-containing compounds with class II HDAC-inhibiting activities was found to promote neurite outgrowth. This study replaced phenothiazine moiety with phenoxazine that contains many C-3 and C-4 substituents. Some resulting compounds bearing the C-4 substituent on a phenoxazine ring displayed potent class II HDAC inhibitory activities. Structure-activity relationship (SAR) of these compounds that inhibited HDAC isoenzymes was disclosed. Molecular modelling analysis demonstrates that the potent activities of C-4 substituted compounds probably arise from π-π stacked interactions between these compounds and class IIa HDAC enzymes. One of these, compound exhibited the most potent class II HDAC inhibition (IC= 3-870 nM). Notably, it protected neuron cells from HO-induced neuron damage at sub-μM concentrations, but with no significant cytotoxicity. These findings show that compound is a lead compound for further development of anti-neurodegenerative agents.

关键词： Histone deacetylase (HDAC) neuron cells phenoxazine structure-activity relationship (SAR)

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Evaluating the antiviral efficacy and specificity of chlorogenic acid and related herbal extracts against SARS-CoV-2 variants via spike protein binding intervention

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Journal of Traditional and Complementary Medicine 2024年

作者： Hsieh, Wen-Yu Yu, Chu-Nien Chen, Chang-Chang Chiou, Chun-Tang Green, Brian D. Lee, Oscar K. Wu, Chia-Chune Doan, Ly Hien Huang, Chi-Ying F. Huang, Cheng Liu, Chien-Ju Chen, Yu-Hsin Cheng, Jing-Jy Pan, Heng-Chih Liu, Hui-Kang Biomedical Industry Ph.D. Program National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Clinical Medicine National Yang Ming Chiao Tung University Taipei 11221 Taiwan Division of Chinese Materia Medica Development National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei 11221 Taiwan Institute for Global Food Security School of Biological Sciences Queen's University Belfast Belfast BT7 1NN United Kingdom Department of Orthopedics China Medical University Hospital Taichung Taiwan Institute of Biopharmaceutical Sciences College of Pharmaceutical Sciences National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Biotechnology Vietnam Academy of Science and Technology Hanoi Viet Nam Program in Molecular Medicine College of Life Sciences National Yang Ming Chiao Tung University Taipei 11221 Taiwan Taiwan National Graduate Program in Molecular Medicine Academia Sinica National Yang Ming Chiao Tung University Taipei 11221 Taiwan Institute of Clinical Medicine College of Medicine National Yang Ming Chiao Tung Taipei 11221 Taiwan Department of Biotechnology and Laboratory Science in Medicine School of Biomedical Science and Engineering National Yang Ming Chiao Tung Taipei 11221 Taiwan Department of Biochemistry School of Medicine Kaohsiung Medical University Kaohsiung 80708 Taiwan Department of Earth and Life Sciences University of Taipei Taipei 11036 Taiwan Tea and Beverage Research Station Ministry of Agriculture Yangmei Township Taoyuan County 326011 Taiwan Taichung District Agricultural Research and Extension Station Ministry of Agriculture Chang-Hwa County 515008 Taiwan Division of Basic Chinese Medicine National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei 11221 Taiwan Department of Nephrology Chang Gung Memorial Hospital Keelung City 204201 Taiwan Ph.D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus infect the respiratory tract through surface proteins, causing similar symptoms. Since the onset of the COVID-19 pandemic, both viruses have posed significant ongoing global health threats. Like the influenza virus, SARS-CoV-2 evolves into variants that can reduce vaccine efficacy. Thus, herbal medicines are being explored as supplementary options to enhance protection against these infections. This study aimed to investigate the therapeutic potential of chlorogenic acid (3-CQA) and related extracts from green coffee beans and Echinacea purpurea against SARS-CoV-2 variants and H1N1 infection. The methods employed included an ELISA-based trimeric spike protein binding assay, viral infection assays, plaque assays, and molecular docking studies. Results showed that 3-CQA blocked spike protein/angiotensin converting enzyme 2 (ACE2) binding for most SARS-CoV-2 variants of concern, except the Delta variant. Extracts from Green coffee bean and E. purpurea effectively blocked all variants tested. Additionally, antibodies blocked spike protein binding up to Omicron BA.2. Molecular docking suggested that 3-CQA binding to Omicron BA.1, BA.2, and BA.4, though not to the Delta spike protein, may lead to steric hindrance, preventing receptor-binding domain interactions with ACE2. Finally, both 3-CQA and E. purpurea extract showed preventive effects against H1N1 viral infection, though with lower potency compared to SARS-CoV-2. In conclusion, 3-CQA has potential as a phytoconstituent marker for herbs with bioactive properties against SARS-CoV-2 and H1N1 viral infections. © 2024 Center for Food and Biomolecules, National Taiwan University

关键词： Chlorogenic acid COVID-19 Echinacea purpurea Green coffee bean H1N1 influenza virus SARS-CoV-2 variants Spike protein

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