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Inhibitory effects of wild Origanum elongatum extracts on Fusarium oxysporum mycelium growth and spores germination: Evidence from in-vitro, in-planta, and in-silico experiments

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Journal of Natural Pesticide Research 2024年 10卷

作者： Hari, Amal Lahlali, Rachid Ortaakarsu, Ahmet Buğra Taarji, Noamane Laasli, Salah-Eddine Karaaoui, Khawla Benjelloun, Meryem Ouchari, Wafae Sobeh, Mansour Echchgadda, Ghizlane Department of Plant Protection Ecole Nationale d'Agriculture de Meknes Meknes 50001 Morocco Laboratory of Functional Ecology and Environmental Engineering Faculty of Sciences and Technology Sidi Mohamed Ben Abdellah University Fez Morocco Department of Chemistry Faculty of Science Gazi University Ankara 06590 Turkey AgroBioSciences Program College of Agriculture and Environmental Sciences University Mohammed VI Polytechnic Ben-Guerir Morocco

Fusarium wilt, caused by Fusarium oxysporum, is one of the most devastating diseases to crops including potatoes. This fungus is widespread and dispersed via resistant spores. In this study, organic (methanol, hexane, and chloroform) and aqueous extracts of the aerial parts of wild Origanum elongatum were tested against mycelium and spores of F. oxysporum in both in-vitro (using the poisoned food technique) and in-planta assays. Further, the chemical composition of the extract was identified via HPLC-PdA-MS/MS. Then, molecular modeling was used to clarify the antifungal activity of identified biomolecules. The obtained results showed that organic and aqueous extracts showed significant antifungal and anti-sporulation activities with different effectiveness depending on the extract, concentration, and application test. In in-vitro assays of the aqueous extract, the highest antifungal activity was recorded at concentrations of 10 mg mL⁻¹, while the highest anti-sporulation activity (91.79 %) was observed at 50 mg mL⁻¹. In the organic extracts, methanol was the most effective against fungus with 100 % inhibition of mycelium at 5 mg mL ⁻¹ and the highest anti-sporulation effect (73.58 %) at 20 mg mL⁻¹. In in-planta assays, the methanolic extract at 20 mg mL⁻¹ achieved 0 % disease severity, while the aqueous extract at 50 mg mL⁻¹ reduced severity to 7 %, both significantly more effective than the untreated control. Therefore, methanol was the most effective and these biological properties are supported by a wide range of bioactive molecules, including 56 molecules compared to only 28 molecules in the aqueous extract. These include glycosides of apigenin and kaempferol and salvianolic acid b. However, more research is needed to clarify the inhibition action of the individual components and their synergetic actions in controlled and field conditions. © 2024 The Authors

关键词： Anti-fungal Anti-sporulation activities F. oxysporum Molecular modeling O. elongatum

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Advancing supercapacitors with NiMn-LdH@V2C MXene: A synergistic pathway to enhanced energy storage

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Journal of Energy Storage 2025年 129卷

作者： Saranraj, A. Abinaya, S. Lakshmi, U.S. Govindasamy, Mani Jose, Sujin P. Advanced Materials Laboratory School of Physics Madurai Kamaraj University Tamil Nadu Madurai 625021 India International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Research Center for Intelligent Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan

Layered double hydroxides (LdHs) exhibit limitations in supercapacitor applications due to poor conductivity, insufficient stability, and severe nanosheet aggregation. This study addresses these challenges by constructing a novel composite material. The design involves in-situ anchoring of highly dispersed Nickel-Manganese Layered double Hydroxide (NiMn-LdH) nanoparticles (∼10 nm) onto V2C MXene sheets via chemical bonding. The negatively charged MXene surface provides abundant nucleation sites for NiMn-LdH during crystallization, while surface functional groups further strengthen the material connection. This enhanced interface facilitates superior charge transfer and ion diffusion between MXene and NiMn-LdH. Compared to pristine materials, the NiMn-LdH@V2C MXene composite demonstrates a significantly higher specific capacitance (1393 F g⁻¹ at 1 A g⁻¹). Additionally, it exhibits excellent cycling stability (99 % coulombic efficiency after 10,000 cycles at 5 A g⁻¹) and good rate capability (80 % capacitance retention at 20 A g⁻¹). Furthermore, a symmetric supercapacitor (SSC) was fabricated with the NiMn-LdH@V2C MXene composite. The device also achieves a high energy density of 52 Wh kg⁻¹ and a power density of 799 W kg⁻¹. These results highlight the potential of NiMn-LdH@V2C MXene composite as a promising approach for designing next-generation supercapacitor electrodes with exceptional performance and durability.

关键词： Affordable And Clean Energy Electrochemical Energy storage Layered double Hydroxide Symmetric V2C MXene

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Emerging contaminants:A One Health perspective

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The Innovation 2024年第4期5卷 140-170,139页

作者： Fang Wang Leilei Xiang Kelvin Sze-Yin Leung Martin Elsner Ying Zhang Yuming Guo Bo Pan Hongwen Sun Taicheng An Guangguo Ying Bryan WBrooks deyi Hou damian EHelbling Jianqiang Sun Hao Qiu Timothy MVogel Wei Zhang Yanzheng Gao Myrna JSimpson Yi Luo Scott XChang Guanyong Su Bryan MWong Tzung-May Fu dong Zhu Karl JJobst Chengjun Ge Frederic Coulon Jean damascene Harindintwali Xiankui Zeng Haijun Wang Yuhao Fu Zhong Wei Rainer Lohmann Changer Chen Yang Song Concepcion Sanchez-Cid Yu Wang Ali El-Naggar Yiming Yao Yanran Huang Japhet Cheuk-Fung Law Chenggang Gu Huizhong Shen Yanpeng Gao Chao Qin Hao Li Tong Zhang Natàlia Corcoll Min Liu daniel SAlessi Hui Li Kristian KBrandt Yolanda Pico Cheng Gu Jianhua Guo Jianqiang Su philippe Corvini Mao Ye Teresa Rocha-Santos Huan He Yi Yang Meiping Tong Weina Zhang Fidèle Suanon Ferdi Brahushi Zhenyu Wang Syed AHashsham Marko Virta Qingbin Yuan Gaofei Jiang Louis A.Tremblay Qingwei Bu Jichun Wu Willie Peijnenburg Edward Topp Xinde Cao Xin Jiang Minghui Zheng Taolin Zhang Yongming Luo Lizhong Zhu Xiangdong Li damiàBarceló Jianmin Chen Baoshan Xing Wulf Amelung Zongwei Cai Ravi Naidu Qirong Shen Janusz Pawliszyn Yong-guan Zhu Andreas Schaeffer Matthias C.Rillig Fengchang Wu Gang Yu James M.Tiedje State Key Laboratory of Soil and Sustainable Agriculture Institute of Soil ScienceChinese Academy of SciencesNanjing 210008China University of Chinese Academy of Sciences Beijing 100049China Department of Chemistry Hong Kong Baptist UniversityHong KongChina HKBU Institute of Research and Continuing Education Shenzhen Virtual University ParkShenzhenChina Technical University of Munich TUM School of Natural SciencesInstitute of Hydrochemistry85748 GarchingGermany School of Resources&Environment Northeast Agricultural UniversityHarbin 150030China Climate Air Quality Research UnitSchool of Public Health and Preventive MedicineMonash UniversityMelbourneVICAustralia Faculty of Environmental Science&Engineering Kunming University of Science&TechnologyKunming 650500China Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria College of Environmental Science and EngineeringNankai UniversityTianjin 300350China Guangdong Key Laboratory of Environmental Catalysis and Health Risk Control School of Environmental Science and EngineeringInstitute of Environmental Health and Pollution ControlGuangdong University of TechnologyGuangzhou 510006China Ministry of Education Key Laboratory of Environmental Theoretical Chemistry South China Normal UniversityGuangzhouGuangdong 510006China Department of Environmental Science Baylor UniversityWacoTXUSA Center for Reservoir and Aquatic Systems Research(CRASR) Baylor UniversityWacoTXUSA School of Environment Tsinghua UniversityBeijing 100084China School of Civil and Environmental Engineering Cornell UniversityIthacaNY 14853USA Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province Zhejiang University of TechnologyHangzhou 310014China School of Environmental Science and Engineering Shanghai Jiao Tong UniversityShanghai 200240China Laboratoire d’Ecologie Microbienne Universite Claude Bernard Lyon 1UMR CNRS 5557UMR INRAE 1418VetAgro Sup69622 VilleurbanneFrance Department of Pla

Environmental pollution is escalating due to rapid global development that often prioritizes human needs over planetary *** global efforts to mitigate legacy pollutants,the continuous introduction of new substances remains a major threat to both people and the *** response,global initiatives are focusing on risk assessment and regulation of emerging contaminants,as demonstrated by the ongoing efforts to establish the UN’s Intergovernmental science-Policy Panel on Chemicals,Waste,and Pollution *** review identifies the sources and impacts of emerging contaminants on planetary health,emphasizing the importance of adopting a One Health *** for monitoring and addressing these pollutants are discussed,underscoring the need for robust and socially equitable environmental policies at both regional and international *** actions are needed to transition toward sustainable pollution management practices to safeguard our planet for future generations.

关键词： pollution planet contaminants

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development and application of the electrospun Microtube Array Membrane (MTAM) substrate as a potential drug encapsulation platform for continuous drug release platform for treatment of Elevated intraocular pressure (IOP) in glaucoma disease

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Polymer 2025年 333卷

作者： Jou-Chen Huang Ching-Yu Lee Chee Ho Chew Wan-Ting Huang Shun-Chieh Chang Chien-Chung Chen Department of Ophthalmology Taipei Medical University Hospital Taipei Taiwan Department of Ophthalmology School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Department of Orthopedics Taipei Medical University Hospital Taipei Taiwan Department of Orthopaedics School of Medicine College of Medicine Taipei Medical University Taipei Taiwan Graduate Institute of Biomedical Materials and Tissue Engineering Taipei Medical University Taipei 11052 Taiwan International PhD Program for Cell Therapy and Regeneration Medicine College of Medicine Taipei Medical University Taipei 110 Taiwan The PhD Program for Translational Medicine Taipei Medical University Taipei 11052 Taiwan International Ph.D. Program in Biomedical Engineering College of Biomedical Engineering Taipei Medical University Taipei 110 Taiwan Ph.D Program in Biotechnology Research and Development College of Pharmacy Taipei Medical University Taipei 110 Taiwan

Glaucoma is the leading cause of blindness which is characterized by the elevation of intraocular pressure (IOP) which results in optic nerve damage. Clinically, the current mainstay of treatment which involves the use of anti-glaucoma agents delivered in the form of topical eye drops have limitations such as short drug retention times, pulsatile delivery and localized adverse effects. In this work, we strive to demonstrate the development of a novel drug encapsulation device, known as Microtube Array Membrane (MTAM) as a potential substrate for encapsulation of clinically available anti-glaucoma agent that is based on the materials Polysulfone (PSF) and poly(lactic acid) (PLA) and poly(glycolic acid) (PLA-PLGA) copolymer. The resulting MTAM variants demonstrated tunable microstructures, mechanical properties and drug release; where pore sizes ranging from from 0.24 ± 0.02 μm to 17.62 ± 4.62 μm was successfully fabricated, and with loading efficiency of Brimonidine Tartrate up to 90 %. Sustained drug release was observed over 3 days under simulated tear physiological conditions, with the PLA-PLGA MTAM variants released the greatest amount of drug encapsulated within and sustained even in the presence of simulated tears turnover. Critically, the encapsulation of the drug within the respective MTAMs seemed to mitigate any toxicity effects that was largely reported in direct use of Brimonidine Tartrate. Potentially, with more research and development, the MTAM based drug encapsulation could effective be deployed as a novel drug release system in future localized and sustained drug delivery.

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Perioperative dexmedetomidine Infusion Improves Perioperative Care of Bariatric-Metabolic Surgery: A Single Center Experience with Meta-Analysis

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Obesity Surgery 2024年第2期34卷 416-428页

作者： Chang, Po-Chih Huang, Ivy Ya-Wei Liu, Sian-de Huang, Chih-Kun Lin, Tsun-En Jhou, Hong-Jie Chen, Po-Huang Chang, Ting-Wei School of Medicine College of Medicine National Sun Yat-Sen University 804 Kaohsiung Taiwan Division of Thoracic Surgery Department of Surgery Kaohsiung Medical University Hospital/Kaohsiung Medical University Kaohsiung City Taiwan Weight Management Cente Kaohsiung Medical University Hospital/Kaohsiung Medical University No. 100 Tzyou 1st Road Kaohsiung City 80756 Taiwan Ph. D. Program in Biomedical Engineering College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Department of Sports Medicine College of Medicine Kaohsiung Medical University Kaohsiung City Taiwan Department of Nursing Kaohsiung Medical University Hospital/ Kaohsiung Medical University Kaohsiung City Taiwan Department of Pharmacy New Taipei Municipal TuCheng Hospital (Built and Operated By Chang Gung Medical Foundation) New Taipei City 236 Taiwan Body Science and Metabolic Disorders International Medical Center China Medical University Hospital Taichung City Taiwan Specialist Nursing Office Department of Nursing Kaohsiung Medical University Hospital Kaohsiung Medical University Kaohsiung City Taiwan Department of Neurology Changhua Christian Hospital Changhua Taiwan Department of Internal Medicine Tri-Service General Hospital National Defense Medical Center Taipei City Taiwan

Purpose: This study aims to determine the effects of perioperative dexmedetomidine infusion (PdI) on Asian patients undergoing bariatric–metabolic surgery (BMS), focusing on the need for pain medications and management of postoperative nausea and vomiting (PONV), and to investigate the association with these variables, including patients’ characteristics and BMS data. Materials and Methods: A retrospective review of prospectively collected data was conducted in an Asian weight management center from August 2016 to October 2021. A total of 147 native patients with severe obesity were enrolled. All patients were informed of the full support of perioperative pain medications for BMS. The pain numeric rating scale scores, events of PONV, needs for pain medications, and the associated patients’ characteristics were analyzed. A p-value of < 0.05 was considered statistically significant. Furthermore, to verify the effects of perioperative usage of dexmedetomidine for BMS, a systematic review with meta-analysis of currently available randomized control trials was performed. Results: Among the 147 enrolled patients, 107 underwent laparoscopic sleeve gastrectomy and 40 underwent laparoscopic Roux-en-Y gastric bypass. PdI has been used as an adjunct multimodal analgesia for BMS in our institution since June 2017 (group d;n = 114). In comparison with those not administered with perioperative dexmedetomidine (group C;n = 33), lower pain numeric rating scale scores (2.52 ± 2.46 vs. 4.27 ± 2.95, p = 0.007) in the postanesthesia care unit, fewer PONV (32.46% vs. 51.52%;p = 0.046), and infrequent needs of additional pain medications (19.47% vs. 45.45%;p = 0.003) were observed in group d. Multivariable analysis demonstrated that type II diabetes mellitus was correlated with the decreased need of pain medications other than PdI (p = 0.035). Moreover, dexmedetomidine seemed to have a better analgesic effect for patients with longer surgical time based on our meta-analysis. Conclusion:

关键词： Analgesia Bariatric–Metabolic Surgery dexmedetomidine Pain Severe Obesity

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Highly efficient capture of E. coli using amidoximated polyacrylonitrile nanofiber membrane immobilized with reactive green 19 dye/polyhexamethylene biguanide: Antibacterial and cytotoxicity studies

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Separation and Purification technology 2024年 338卷

作者： Quang-Vinh Le Bing-Lan Liu Penjit Srinophakun Jeng-Ywan Shih Chi-Yun Wang Chen‑Yaw Chiu Shen-Long Tsai Kuei-Hsiang Chen Yu-Kaung Chang Department of Chemical Engineering National Taiwan University of Science and Technology Taipei City 10607 Taiwan Department of Applied Chemistry Chaoyang University of Technology Taichung 413310 Taiwan Department of Chemical Engineering Kasetsart University 50 Ngamwongwan Road Chatuchak Bangkok 10900 Thailand Department of Chemical Engineering Ming Chi University of Technology New Taipei City 243303 Taiwan International Ph.D. Program in Innovative Technology of Biomedical Engineering and Medical Devices Ming Chi University of Technology New Taipei City 243303 Taiwan Bone and Joint Research Centre Chang Gung Memorial Hospital Taoyuan City 333423 Taiwan Department of Chemical Engineering and Materials Science Yuan Ze University Zhongli Dist. Taoyuan City 320315 Taiwan

In this study, we synthesized an amidoximated polyacrylonitrile nanofiber membrane (P-Oxime). Subsequently, we grafted reactive green 19 (RG19) dye onto its surface, resulting in the formation of the P-Oxime-RG19 membrane. Further enhancement was achieved by physically attaching poly(hexamethylene biguanide) hydrochloride (phMB) to the P-Oxime-RG19 membrane, leading to the formation of the P-Oxime-RG19-phMB membrane. Extensive characterization of the nanofiber membranes was conducted, focusing on crucial physical and mechanical properties such as functional group content, morphology, and thermostability. The optimization of various modification conditions, including initial dye and phMB concentrations, duration, temperature, and nitrile group conversion to oxime concentrations, played a pivotal role in achieving superior antibacterial performance in P-Oxime-RG19-phMB nanofiber membranes. In-depth analyses involved the application of kinetic and equilibrium thermodynamic models to unravel the modification processes of RG19 dye and phMB in the nanofiber membranes. Under the carefully tuned optimal modification conditions, the P-Oxime-RG19-phMB nanofiber membrane exhibited remarkable antibacterial efficacy, achieving nearly 100% disinfection of E. coli . In addition to exploring its antimicrobial capabilities, we thoroughly examined the repeatability and biocompatibility of the nanofiber membranes. The results indicated not only the P-Oxime-RG19-phMB nanofiber membrane was a highly promising antibacterial material but also highlighted its potential for diverse applications, particularly in food and textile fabrication, owing to its exceptional performance and suitability.

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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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Magnetic-based photosensitizer to improve the efficiency of antimicrobial photodynamic therapy against mature dental caries-related biofilms

MedComm - Biomaterials and Applications

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MedComm - Biomaterials and Applications 2023年第4期2卷

作者： Balhaddad, Abdulrahman A. Mokeem, Lamia Alsahafi, Rashed Weir, Michael d. Xu, Hockin H. K. Melo, Mary Anne S. Department of Restorative Dental Sciences College of Dentistry Imam Abdulrahman Bin Faisal University Dammam Saudi Arabia Ph.D. Program in Dental Biomedical Sciences University of Maryland School of Dentistry Baltimore MD United States Department of Restorative Dental Sciences College of Dentistry Umm Al-Qura University Makkah Saudi Arabia Department of Advanced Oral Sciences and Therapeutics Biomaterials & Tissue Engineering Division University of Maryland School of Dentistry Baltimore MD United States Department of General Dentistry Division of Operative Dentistry University of Maryland School of Dentistry Baltimore MD United States

Antimicrobial photodynamic therapy (aPdT) shows promise in eliminating oral pathogens without inducing microbial resistance. Yet, it faces limited biofilm penetration by the photosensitizer, which hinders its efficacy against mature, thick biofilms. This study assesses the effectiveness of the MagTBO (magnetic nanoparticles and toluidine-blue ortho) nanoplatform against mature Streptococcus mutans biofilms associated with dental caries. The study employs constant-depth film fermenter (CdFF) models, known as “artificial mouth,” to replicate caries processes and allow biofilm growth over teeth. This method enables the evaluation of biofilm-induced mineral loss under cariogenic challenge over 5 and 10 days. The study shows that MagTBO improves aPdT's effectiveness against highly mature and complex biofilms over 5 and 10 days. However, the biofilm reduction unaffected the mineral content in the underlying dentin. This presents a promising approach for clinical aPdT protocols. However, it is crucial to acknowledge that these findings are based on in vitro studies and may necessitate further clinical confirmation. In summary, our data indicate that magnetic-based photosensitizers enhance the modulation of pathogenic oral biofilms by aPdT, offering potential advancements in clinical aPdT protocols. © 2023 The Authors. MedComm – Biomaterials and Applications published by John Wiley & Sons Australia, Ltd on behalf of Sichuan International Medical Exchange & Promotion Association (SCIMEA).

关键词： biofilms dental caries magnetic fields nanotechnology photochemotherapy

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Ohwia caudata extract relieves the IL-17A-induced inflammatory response of synoviocytes through modulation of SOCS3 and JAK2/STAT3 activation

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Environmental Toxicology 2023年第8期38卷 1914-1924页

作者： Lu, Cheng-You Kuo, Chia-Hua Kuo, Wei-Wen Hsieh, dennis Jine-Yuan Wang, Tso-Fu Shih, Cheng-Yen Lin, Pi-Yu Lin, Shinn-Zong Ho, Tsung-Jung Huang, Chih-Yang Department of Post-Baccalaureate Medicine College of Medicine National Chung Hsing University Taichung Taiwan Department of Sports Sciences University of Taipei Taipei Taiwan Department of Biological Science and Technology China Medical University Taichung Taiwan Ph.D. Program for Biotechnology Industry China Medical University Taichung Taiwan School of Medical Laboratory and Biotechnology Chung Shan Medical University Taichung Taiwan Clinical Laboratory Chung Shan Medical University Hospital Taichung Taiwan Department of Hematology and Oncology Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Tzu Chi University Hualien Taiwan Buddhist Tzu Chi Medical Foundation Hualien Taiwan Buddhist Compassion Relief Tzu Chi Foundation Hualien Taiwan Bioinnovation Center Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Neurosurgery Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Integration of Chinese Medicine and Modern Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Department of Chinese Medicine Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Cardiovascular and Mitochondrial Related Disease Research Center Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation Hualien Taiwan Graduate Institute of Biomedical Sciences China Medical University Taichung Taiwan Department of Biological Science and Technology Asia University Taichung Taiwan Center of General Education Buddhist Tzu Chi Medical Foundation Tzu Chi University of Science and Technology Hualien Taiwan

Fibroblast-like synoviocytes accumulation, proliferation and activation, and the subsequent inflammatory mediators production play a key role in the progression of rheumatoid arthritis (RA). It is well established that Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling triggers inflammation, and induces cytokine levels in RA. Ohwia caudata have long been used against many disorders. However, in RA, the effects of O. caudata have not been elucidated. In the current study, synoviocytes were used to evaluate the suppressive effects of O. caudate extract (OCE) on the pro-inflammatory cytokines production. In vitro, the underlying mechanisms by which OCE inhibits inflammatory response through regulation of suppressors of cytokine signaling 3 (SOCS3) and JAK2/STAT3 expression in IL-17A-treated HIG-82 synoviocytes were investigated. The results demonstrated that the proliferation of IL-17A-challenged cells were increased in comparison with non-stimulated control cells. The synoviocyte proliferation was decreased significantly of OCE concentrations in dose dependent manner. The p-JAK2, p-STAT3, interleukin (IL)-1β, and IL-6 were reduced in IL-17A-challenged cells treated with OCE. Furthermore, AZd1480 (a JAK2-specific inhibitor) or WP1066 (a STAT3-specific inhibitor) affected the inflammatory mediators production in IL-17A-challenged synoviocytes, and OCE failed to mitigate the IL-17A-induced inflammatory mediators and SOCS3, acting as a feedback inhibitor of the JAK/STAT3 pathway, in the presence of SOCS3 siRNA, indicating that the beneficial effects of OCE on the regulation of inflammatory response homeostasis were dependent on SOCS3 and the JAK2/STAT3 signaling pathway. Our study also showed that SOCS3 was markedly activated by OCE in RA fibroblast-like synoviocytes, thereby decreasing the JAK/STAT3 pathway, and the IL-1β, and IL-6 activation. Thus, O. caudate should be further investigated as a candidate anti-inflammatory and anti-a

关键词： Chemical activation

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Polymethoxyflavone from Citrus depressa as an inhibitor against various variants of SARS-CoV-2 spike protein

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Journal of Ethnopharmacology 2024年 320卷 117412页

作者： Liu, Ta-Wei Hsu, Su-Jung Hsieh, Yves S.Y. Liu, Hui-Kang Lee, Ching-Kuo School of Pharmacy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Graduate Institute of Pharmacognosy College of Pharmacy Taipei Medical University Taipei 11042 Taiwan Division of Glycoscience Department of Chemistry School of Engineering Sciences in Chemistry Biotechnology and Health KTH Royal Institute of Technology AlbaNova University Centre Stockholm SE106 91 Sweden National Research Institute of Chinese Medicine (NRICM) Ministry of Health and Welfare Taipei City Taiwan Ph. D. Program in the Clinical Drug Development of Herbal Medicine Taipei Medical University Taipei Taiwan

Ethnopharmacological relevance: In traditional Taiwanese medicine, Citrus depressa Hayata serves as the raw material of Chen-Pi which has been widely used to treat respiratory ailments. Scientific investigations have validated the attributes of C. depressa, elucidating its valuable properties, including antioxidative, anti-inflammatory, anticancer, neuroprotion, hepatoprotection, and hypolipidemic effects. Aim of the study: This study aims to isolate a universal inhibitor of the SARS-CoV-2 spike protein from C. depressa and confirm the mechanism by which these inhibitors disrupt the binding of the spike protein to hACE2. Materials and methods: The whole fruit of C. depressa was subjected to ethanol extraction, following by partitioning to obtain water, butanol, and ethyl acetate fractions. To identify the inhibitory components in citrus fruits, we performed both the SPR assay and the SARS-CoV-2 pseudo-virus assays. Subsequently, we employed a bioassay-guided approach to efficiently isolate and characterize the bioactive constituents that hindered the interaction between the SARS-CoV-2 spike protein and hACE2, using a combination of MPLC and Semi-preparative HPLC for compound isolation. ELISA based spike protein binding assay evaluate the inhibitory activities of the extract and potential constituents against multiple spike protein variants. To further shed light on the inhibitory mechanism, candidate inhibitors were validated through the SPR assay and molecular docking. Results: The crude extract and ethyl acetate layer derived from C. depressa showed significant inhibitory activity on SARS-CoV-2 Omicron BA.4/5, with IC₅₀ of 77.4 μg/mL and 100 μg/mL, respectively. Ten potential compounds from C. depressa have been identified with inhibitory activity against various SARS-CoV-2 spike proteins. 2′-hydroxy-4,4′,5′,6′-tetramethoxychalcone (Cd3) and 5-hydroxy-3′,4′,6,7,8-pentamethoxyflavone (Cd8) also showed good inhibitory activity to the spike protein, with K

关键词： ACE-2 Citrus depress Polymethoxyflavone SARS-CoV-2 Spike protein

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