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               From herbal teas to antiviral agents: Exploring the pharmaceutical prospects

               of Epilobium species


                                                                  3
                                                                                             1
               Olha  Mykhailenko,*    ,1,2,3   Thomas  Stegemann,   Victoriya  Georgiyants,   Kateryna
                         4

                                                                                                2,8
                                                    5
               Uminska, Banaz Jalil,  Y u -Li Chen,  Tsong-Long Hwang,    5,6,7  Michael Heinrich,  Michal
                                      2

               Korinek  #,6,9

               1  Department of Pharmaceutical Chemistry, National University of Pharmacy, Kharkiv, Ukraine
               2  Pharmacognosy and Phytotherapy Group, UCL School of Pharmacy, London, UK
               3  Department of Pharmaceutical Biology, Kiel University, Kiel, Germany
               4  Zhytomyr Basic Pharmaceutical Professional College, Zhytomyr, Ukraine
               5  Graduate Institute of Health Industry Technology and Research Center for Chinese Herbal
                 Medicine, College of Human Ecology, Chang Gung University of Science and Technology,
                 Taoyuan 33302, Taiwan
               6   Graduate  Institute  of  Natural  Products,  College  of  Medicine,  Chang  Gung  University,
                 Taoyuan 33302, Taiwan
               7  Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan 33305, Taiwan
               8  Department of Pharmaceutical Sciences and Chinese Medicine Resources, Chinese Medicine
                 Research Center, College of Chinese Medicine, China Medical University, Taichung, Taiwan
               9  Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University,
                 Kaohsiung 80708, Taiwan
               * E-mail: o.mykhailenko@nuph.edu.ua

               Abstract
                  Epilobium species (Onagraceae) have been traditionally used in European traditional herbal
               medicine  for  their  anti-inflammatory  and  urological  properties.  The  plants  represent  a
               promising source for pharmaceutical development. However, their phytochemical variability,
               quality control, and sustainable supply remain poorly understood. In addition, the plant has not
               been sufficiently tested as an antiviral agent, although daily consumption as a tea could be
               beneficial in the treatment of infectious diseases. Therefore, our comprehensive study included
               several steps, namely (1) assessing the optimal phenological stage of harvesting E. hirsutum
               and E. angustifolium under different growing conditions, (2) metabolomic profiling of more
               than ten Epilobium species from European countries, (3) assessing the quality of commercial
               willowherb teas available throughout Europe market, (4) investigating the antiviral potential of
               Epilobium  species-based  extracts.  The  study  found  that  environmental  factors  (shade  and
               humidity) significantly increased the levels of key metabolites (chlorogenic acid, isoquercitrin,
               hyperoside, oenothein B). QTOF-LC/MS metabolite profiling revealed high inter- and intra-
               species diversity, as well as new chemotypes and potential new marker compounds. Variability
               was also found among commercial tea samples, which may explain the different therapeutic
               uses of willowherb teas. Finally, E. hirsutum extract was shown to block the COVID-19 virus
               by preventing its attachment to cells. Water extracts were more effective than ethanolic extracts,
               with  oenothein  B  being  the  most  effective.  Willowherb  extracts  significantly  reduced
               inflammation in immune cells and acted as potent antioxidants. These results highlight the
               importance of integrating phenological, geographical, and metabolomic aspects to ensure the
               authenticity, safety, and efficacy of herbal medicines derived from Epilobium species.

               Keywords:  Epilobium  species;  Metabolomics;  Quality  control;  Pharmacological  assay;
                           Coronavirus
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