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      Antiviral effect of phytochemicals from medicinal plants: Applications and drug delivery strategies

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          Abstract

          Viral infections affect three to five million patients annually. While commonly used antivirals often show limited efficacy and serious adverse effects, herbal extracts have been in use for medicinal purposes since ancient times and are known for their antiviral properties and more tolerable side effects. Thus, naturally based pharmacotherapy may be a proper alternative for treating viral diseases. With that in mind, various pharmaceutical formulations and delivery systems including micelles, nanoparticles, nanosuspensions, solid dispersions, microspheres and crystals, self-nanoemulsifying and self-microemulsifying drug delivery systems (SNEDDS and SMEDDS) have been developed and used for antiviral delivery of natural products. These diverse technologies offer effective and reliable delivery of medicinal phytochemicals. Given the challenges and possibilities of antiviral treatment, this review provides the verified data on the medicinal plants and related herbal substances with antiviral activity, as well as applied strategies for the delivery of these plant extracts and biologically active phytochemicals.

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          Antibacterial, antifungal, and antiviral activities of some flavonoids.

          Didem Orhan, Berrin Ozçelik, Selda Özgen … (2010)
          Antibacterial and antifungal activities of six plant-derived flavonoids representing two different structural groups were evaluated against standard strains of Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecalis, Bacillus subtilis and their drug-resistant isolates, as well as fungi (Candida albicans, C. krusei) using the microdilution broth method. Herpes simplex virus Type-1 and Parainfluenza-3 virus were employed for antiviral assessment of the flavonoids using Madin-Darby bovine kidney and Vero cell lines. Ampicillin, gentamycin, ofloxacin, levofloxacin, fluconazole, ketoconazole, acyclovir, and oseltamivir were used as the control agents. All tested compounds (32-128 microg/ml) showed strong antimicrobial and antifungal activities against isolated strains of P. aeruginosa, A. baumanni, S. aureus, and C. krusei. Rutin, 5,7-dimethoxyflavanone-4'-O-beta-D-glucopyranoside and 5,7,3'-trihydroxy-flavanone-4'-O-beta-D-glucopyranoside (0.2-0.05 microg/ml) were active against PI-3, while 5,7-dimethoxyflavanone-4'-O-[2''-O-(5'''-O-trans-cinnamoyl)-beta-D-apiofuranosyl]-beta-D-glucopyranoside (0.16-0.2 microg/ml) inhibited potently HSV-1. Copyright 2009 Elsevier GmbH. All rights reserved.
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            Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry

            Wenjiao Wu, Richan Li, Xianglian Li … (2015)
            Influenza A viruses (IAVs) cause seasonal pandemics and epidemics with high morbidity and mortality, which calls for effective anti-IAV agents. The glycoprotein hemagglutinin of influenza virus plays a crucial role in the initial stage of virus infection, making it a potential target for anti-influenza therapeutics development. Here we found that quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) with half maximal inhibitory concentration (IC50) of 7.756 ± 1.097, 6.225 ± 0.467, and 2.738 ± 1.931 μg/mL, respectively. Mechanism studies identified that quercetin showed interaction with the HA2 subunit. Moreover, quercetin could inhibit the entry of the H5N1 virus using the pseudovirus-based drug screening system. This study indicates that quercetin showing inhibitory activity in the early stage of influenza infection provides a future therapeutic option to develop effective, safe and affordable natural products for the treatment and prophylaxis of IAV infections.
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              Exosomes for the Enhanced Tissue Bioavailability and Efficacy of Curcumin.

              Farrukh Aqil, Radha Munagala, Jeyaprakash Jeyabalan … (2017)
              Exosomes are extracellular microvesicles with a particle size of 30-100 nm and carry a cargo of proteins, lipids, RNA, and DNA. Their properties of shuttling in-and-out of the cells suggest that these particles can be exploited as a nano drug carrier. In this manuscript, we show that curcumin can be delivered effectively using milk-derived exosomes. Curcumin when mixed with exosomes in the presence of 10% ethanol:acetonitrile (1:1) provided a drug load of 18-24%, and the formulation stored at - 80°C was stable for 6 months as determined by particle size analysis, drug load, and antiproliferative activity. The uptake of exosomes by cancer cells involved caveolae/clathrin-mediated endocytosis. Oral administration of exosomal curcumin (ExoCUR) in Sprague-Dawley rats demonstrated 3-5 times higher levels in various organs versus free agent. ExoCUR showed enhanced antiproliferative activity against multiple cancer cell lines including, breast, lung, and cervical cancer compared with the free curcumin. ExoCUR showed significantly higher anti-inflammatory activity measured as NF-κB activation in human lung and breast cancer cells. To determine in vivo antitumor activity, nude mice bearing the cervical CaSki tumor xenograft were treated with ExoCUR by oral gavage, curcumin diet, exosomes alone, and PBS as controls. While curcumin via dietary route failed to elicit any effect, exosomes had a modest (25-30%) tumor growth inhibition. However, ExoCUR showed significant inhibition (61%; p < 0.01) of the cervical tumor xenograft. No gross or systemic toxicity was observed in the rats administered with the exosomes or ExoCUR. These results suggest that exosomes can be developed as potential nano carriers for delivering curcumin which otherwise has encountered significant tissue bioavailability issues in the past.
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                Author and article information

                Contributors
                Shimon Ben-Shabat: sbs@bgu.ac.il
                Arik Dahan:
                ORCID: http://orcid.org/0000-0002-3498-3514
                arikd@bgu.ac.il
                Journal
                Journal ID (nlm-ta): Drug Deliv Transl Res
                Journal ID (iso-abbrev): Drug Deliv Transl Res
                Title: Drug Delivery and Translational Research
                Publisher: Springer US (New York )
                ISSN (Print): 2190-393X
                ISSN (Electronic): 2190-3948
                Publication date (Electronic): 1 December 2019
                Publication date (Print): 2020
                Volume: 10
                Issue: 2
                Pages: 354-367
                Affiliations
                [1 ]GRID grid.7489.2, ISNI 0000 0004 1937 0511, Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, , Ben-Gurion University of the Negev, ; 8410501 Beer-Sheva, Israel
                [2 ]Eastern R&D Center, Kiryat Arba, Israel
                Author information
                http://orcid.org/0000-0002-3498-3514
                Article
                Publisher ID: 691
                DOI: 10.1007/s13346-019-00691-6
                PMC ID: 7097340
                PubMed ID: 31788762
                SO-VID: 9caee0b8-6b83-46ec-a516-4fe25beecf8b
                Copyright © © Controlled Release Society 2019
                License:

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                Subject: Review Article
                Custom metadata
                issue-copyright-statement © Controlled Release Society 2020

                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: antiviral,phytomedicine,herbal extracts,flavonoid,solubility,oral drug delivery
                Data availability:
                ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine
                Keywords: antiviral, phytomedicine, herbal extracts, flavonoid, solubility, oral drug delivery

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