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1
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Groß C, Seifert R. Critical analysis of Echinacea preparations marketed in Germany. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:5743-5756. [PMID: 39607548 PMCID: PMC11985562 DOI: 10.1007/s00210-024-03634-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/17/2024] [Accepted: 11/14/2024] [Indexed: 11/29/2024]
Abstract
Colds are the most common cause of incapacity to work in 2023 and therefore have a significant impact on the German economy. Echinacea preparations are considered a non-specific immune stimulant that is used as a phytotherapeutic agent for the treatment and prevention of colds. In the 2021 ZEIT ranking of the best-selling pharmacy-only medicines in Germany, four Echinacea preparations were among the top ten, and they experienced a new hype during the SARS-CoV-2 pandemic. In this study, 22 Echinacea monopreparations, which are approved as herbal medicinal products, were analyzed based on their package inserts. The preparations used in clinical studies were compared with the preparations available on the market with regard to the criteria of plant species used, plant part used, preparation (extract or pressed juice), drug-extract ratio, single dose administered, standardization of the preparations, prior performance of an ingredient analysis, galenics, dosage, duration of administration, and daily dose administered. The analysis revealed that the preparations available on the market are very heterogeneous. The composition can vary considerably in terms of ingredients. For customers, these products appear homogeneous in terms of their presentation on the market. The legal framework conditions promote this situation. The clinical studies are also unable to adequately reflect the market situation. New studies based on market reality, with an analysis of ingredients in the preparations used, a standardized study design, and the inclusion of hematological and biochemical parameters in the evaluation should improve this situation. Days of incapacity for work as an outcome parameter could be well suited.
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Affiliation(s)
- Carina Groß
- Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany
| | - Roland Seifert
- Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
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Arumugam H, Wong KH, Low ZY, Lal S, Choo WS. Plant extracts as a source of antiviral agents against influenza A virus. J Appl Microbiol 2025; 136:lxaf056. [PMID: 40058769 DOI: 10.1093/jambio/lxaf056] [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: 06/13/2024] [Revised: 12/20/2024] [Accepted: 03/07/2025] [Indexed: 03/26/2025]
Abstract
The influenza virus, especially influenza A (IAV), has remained a constant global health threat due to its high morbidity rate and ability to undergo antigenic shifts and drifts, causing pandemics and epidemics. Due to the rapid evolution of IAV, novel therapeutics are urgently required to combat these viruses effectively, as they develop resistance against current therapeutics. Natural products have been the subject of debate for alternative IAV therapy, where the abundance of bioactive compounds offers numerous potentials for novel anti-IAV drug discovery. Therefore, this review discusses the antiviral effects of natural plant extracts against IAV. Examples are Silybum marianum, Scutellaria baicalensis, Angelica dahurica, Peganum harmala, Sambucus nigra, Echinacea purpurea, Panax ginseng, and Camellia sinensis. Most studies found that Si. marianum inhibits viral ribonucleic acid (RNA) synthesis. In contrast, Sc. baicalensis, A. dahurica, Sa. nigra, C. sinensis, and E. purpurea were effective in preventing the entry or binding of IAV into host cells. On the other hand, Sc. baicalensis and Pa. ginseng exert their anti-IAV effect via immunomodulation. Peganum harmala, on the contrary, exhibits a direct virucidal effect against IAV. These studies have shown promising results from using natural products against IAV, which may aid in formulating combinatorial compounds as anti-IAV therapy.
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Affiliation(s)
- Hanushree Arumugam
- School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
| | - Ka Heng Wong
- School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
| | - Zheng Yao Low
- School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
| | - Sunil Lal
- School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
| | - Wee Sim Choo
- School of Science, Monash University Malaysia, 47500 Bandar Sunway, Selangor DE, Malaysia
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Puchalski K, Gerstel JA, Jimoh A, Shokoohinia Y, Langland J. Effects of Echinacea purpurea and Alkylamides on Respiratory Virus Replication and IL-8 Expression In Vitro. Molecules 2025; 30:386. [PMID: 39860258 PMCID: PMC11767596 DOI: 10.3390/molecules30020386] [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: 11/13/2024] [Revised: 01/04/2025] [Accepted: 01/10/2025] [Indexed: 01/27/2025] Open
Abstract
Echinacea purpurea is a perennial medicinal herb with important immunomodulatory and anti-inflammatory properties, especially purported for the alleviation of cold and flu symptoms. Different classes of secondary metabolites of the plant, such as alkylamides, caffeic acid derivatives, polysaccharides, flavonoids, and glycoproteins, are believed to be biologically and pharmacologically active. Although previous research suggests that the alkylamides present in Echinacea may be responsible for reducing the symptoms associated with the common cold or flu through their immunomodulatory activity, the roles of specific alkylamides and their targets (i.e., immune and/or antiviral) have not been well-elucidated or established. This study tested the antiviral and cytokine regulatory activity of various specific alkylamides that are present predominantly in Echinacea root extracts and found that one specific alkylamide, Dodeca-2E,4E-Dienoic acid isobutylamide, had potent antiviral activity against rhinovirus (the causative agent of most common colds) and influenza virus, as well as potent inhibition of IL-8 cytokine production. IL-8 is responsible for many of the symptoms associated with the common cold and is upregulated in other common respiratory infections. The broad activity and low cytotoxicity of this specific alkylamide support its potential use for treating rhinovirus and influenza virus infections.
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Affiliation(s)
| | | | | | | | - Jeffrey Langland
- Ric Scalzo Institute for Botanical Research, Sonoran University of Health Sciences, Tempe, AZ 85282, USA; (K.P.); (J.A.G.); (A.J.); (Y.S.)
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4
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Licata A, Seidita A, Como S, de Carlo G, Cammilleri M, Bonica R, Soresi M, Veronese N, Chianetta R, Citarrella R, Giannitrapani L, Barbagallo M. Herbal and Dietary Supplements as Adjunctive Treatment for Mild SARS-CoV-2 Infection in Italy. Nutrients 2025; 17:230. [PMID: 39861359 PMCID: PMC11767322 DOI: 10.3390/nu17020230] [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: 11/25/2024] [Revised: 01/02/2025] [Accepted: 01/03/2025] [Indexed: 01/27/2025] Open
Abstract
During the COVID-19 pandemic, several observational studies proved a certain efficacy of nutraceuticals, herbal products, and other dietary supplements as adjuvant therapies used alongside antiviral drugs. Although their use has not been widespread in Italy, according to preliminary evidence, many supplements with demonstrated immunomodulatory effects, such as vitamins C and D, herbal medicines and essential oils, might relieve the respiratory symptoms of COVID-19, since SARS-CoV-2 can activate inflammasome-mediated inflammatory signaling pathways. Other observational studies have shown that herbal treatments, such as Echinacea purpurea and ginseng, help alleviate respiratory symptoms and reduce serum levels of inflammatory cytokines, which are typically overexpressed in both adult and pediatric SARS-CoV-2 patients. Further, vitamins C and D can attenuate the immune response thanks to their cytokine suppression ability and to their known antimicrobial activity and potential to modulate T helper cell response. The strong immune response triggered by SARS-CoV-2 infection is responsible for the severity of the disease. Preliminary data have also shown that L-arginine, an endothelial-derived relaxing factor, is able to modulate endothelial damage, which appears to be one of the main targets of this systemic disease. Finally, some essential oils and their isolated compounds, such as eucalyptol, may be helpful in reducing many of the respiratory symptoms of COVID-19, although others, such as menthol, are not recommended, since it can lead to an undervaluation of the clinical status of a patient. In this narrative review, despite the lack of strong evidence in this field, we aimed to give an overview of the current available literature (mainly observational and cross-sectional studies) regarding herbal products and dietary supplements and their use in the treatment of mild disease from SARS-CoV-2 infection. Obviously, dietary supplements and herbal products do not constitute a standardized treatment for COVID-19 disease, but they could represent an adjunctive and useful treatment when used together with antivirals.
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Affiliation(s)
- Anna Licata
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Aurelio Seidita
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90146 Palermo, Italy; (A.S.)
- Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90146 Palermo, Italy
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy
| | - Silvia Como
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Gabriele de Carlo
- Unit of Internal Medicine, “V. Cervello” Hospital, Ospedali Riuniti “Villa Sofia-Cervello”, 90146 Palermo, Italy; (A.S.)
| | - Marcella Cammilleri
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Roberta Bonica
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Maurizio Soresi
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Nicola Veronese
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Roberta Chianetta
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Roberto Citarrella
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
| | - Lydia Giannitrapani
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
- Institute for Biomedical Research and Innovation (IRIB), National Research Council (CNR), 90146 Palermo, Italy
| | - Mario Barbagallo
- Unit of Internal Medicine, AOU Policlinico “P. Giaccone”, Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90134 Palermo, Italy; (S.C.); (M.C.); (N.V.)
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Kota S, Nelapati AK, Govada VR. Plant resources for immunonutrients and immunomodulators to combat infectious respiratory viral diseases: a review. 3 Biotech 2024; 14:302. [PMID: 39554986 PMCID: PMC11568085 DOI: 10.1007/s13205-024-04143-y] [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: 06/05/2024] [Accepted: 10/26/2024] [Indexed: 11/19/2024] Open
Abstract
Boosting the immune system has become a crucial aspect in the global battle against the COVID-19 pandemic and other similar infections to protect oneself against symptoms, especially in the prevention of viral infections of the lower respiratory tract. The importance of conducting more studies to create successful herbal formulations as infection prevention measures is emphasized in this review, which looks at the function of immune-boosting nutrients, medicinal plants, and herbal treatments. We reviewed and analyzed 207 studies published from 1946 to the present using reputable databases like Google Scholar, PubMed, and NCBI. The review examined 115 plant species in total and identified 12 key nutrients, including vitamins A, D, C, omega-3 fatty acids, iron, and zinc, while noting that four plant families, Rosaceae, Asteraceae, Amaryllidaceae, and Acanthaceae, show potential against respiratory infections like influenza, RSV, and SARS-CoV. To lower the risk of infection, it is recommended to consume nutritious meals that have immune-modulating qualities. Information on the bioactive components of medicinal herbs, spices, and plants that have been effective in treating respiratory viral infections and related conditions is compiled in this review, which highlights phytoactive substances with antibacterial and antiviral activity as effective modulators to lower the risk of infections. Furthermore, it is highlighted that ancient knowledge systems, like Ayurveda and Naturopathy, should be integrated to help develop new herbal formulations. To improve immunity and lessen vulnerability to serious respiratory infections, the results highlight the need for including immune-modulating foods and plant-based medicines into everyday routines.
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Affiliation(s)
- Sobha Kota
- Department of Chemical Engineering, RVR & JC College of Engineering, Guntur, Andhra Pradesh 522 019 India
| | - Anand Kumar Nelapati
- Department of Biotechnology, Vignan’s Foundation for Science, Technology and Research, Vadlamudi, Guntur, Andhra Pradesh 522 213 India
| | - Vayunandana Rao Govada
- Department of Chemical Engineering, RVR & JC College of Engineering, Guntur, Andhra Pradesh 522 019 India
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Hsieh WY, Yu CN, Chen CC, Chiou CT, Green BD, Lee OK, Wu CC, Doan LH, Huang CYF, Huang C, Liu CJ, Chen YH, Cheng JJ, Pan HC, Liu HK. Evaluating the antiviral efficacy and specificity of chlorogenic acid and related herbal extracts against SARS-CoV-2 variants via spike protein binding intervention. J Tradit Complement Med 2024. [DOI: 10.1016/j.jtcme.2024.11.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2025] Open
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Ahmadi F. Phytochemistry, Mechanisms, and Preclinical Studies of Echinacea Extracts in Modulating Immune Responses to Bacterial and Viral Infections: A Comprehensive Review. Antibiotics (Basel) 2024; 13:947. [PMID: 39452214 PMCID: PMC11504277 DOI: 10.3390/antibiotics13100947] [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: 09/11/2024] [Revised: 10/05/2024] [Accepted: 10/05/2024] [Indexed: 10/26/2024] Open
Abstract
BACKGROUND Echinacea species, particularly Echinacea purpurea, Echinacea angustifolia, and Echinacea pallida, are renowned for their immunomodulatory, antibacterial, and antiviral properties. OBJECTIVES This review explores the mechanisms by which echinacea herbal extracts modulate immune responses, focusing on their effects on both innate and adaptive immunity in bacterial and viral infections. RESULTS Key bioactive compounds, such as alkamides, caffeic acid derivatives, flavonoids, and polysaccharides, contribute to these effects. These compounds enhance immune cell activity, including macrophages and natural killer cells, stimulating cytokine production and phagocytosis. The antibacterial activity of echinacea against respiratory pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Legionella pneumophila) and skin pathogens (Staphylococcus aureus, Propionibacterium acnes) is reviewed, as well as its antiviral efficacy against viruses like herpes simplex, influenza, and rhinovirus. Echinacea's potential as a complementary treatment alongside conventional antibiotics and antivirals is discussed, particularly in the context of antibiotic resistance and emerging viral threats. CONCLUSIONS Challenges associated with variability in phytochemical content and the need for standardized extraction processes are also addressed. This review provides a comprehensive overview of echinacea's therapeutic potential and outlines future directions for research, including clinical trials and dosage optimization.
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Affiliation(s)
- Fatemeh Ahmadi
- UWA School of Agriculture and Environment, The University of Western Australia, Perth 6009, Australia;
- Tasmanian Institute of Agriculture, University of Tasmania, Hobart 7001, Australia
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Lee SK, Lee DR, Min DE, Park SH, Kim DG, Kim EJ, Choi BK, Kwon KB. Ethanolic Extract from Echinacea purpurea (L.) Moench Inhibits Influenza A/B and Respiratory Syncytial Virus Infection in vitro: Preventive Agent for Viral Respiratory Infections. Prev Nutr Food Sci 2024; 29:332-344. [PMID: 39371516 PMCID: PMC11450288 DOI: 10.3746/pnf.2024.29.3.332] [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: 04/05/2024] [Revised: 05/10/2024] [Accepted: 06/04/2024] [Indexed: 10/08/2024] Open
Abstract
Among the most frequent causes of respiratory infections in humans are influenza A virus H1N1 (H1N1), influenza B virus (IVB), and respiratory syncytial virus (RSV). Echinacea is a perennial wildflower belonging to the Asteraceae family. Echinacea purpurea (L.) Moench is a species belonging to the Echinacea genus. Its characteristic compound, chicoric acid (CA), is known for its physiological activities, including antiviral effects and immune enhancement. Activities of E. purpurea 60% ethanol extract (EPE) and CA in inhibiting infections caused by H1N1, IVB, and RSV subtype A (RSV-A) were evaluated through plaque inhibition tests, quantification of viral gene expression, and analysis of transmission electron microscopy (TEM) images. Additionally, inhibitory activities of EPE and CA for hemagglutination and neuraminidase (NA) of H1N1 and IVB were determined. In the plaque reduction assays, both EPE and CA reduced infectivity against H1N1, IVB, and RSV-A. Furthermore, quantitative real-time polymerase chain reaction analysis revealed that EPE and CA reduced gene expression levels for H1N1, IVB, and RSV-A, whereas TEM image analysis confirmed their inhibitory effects on host cell infection by these viruses. Hemagglutination assays exhibited the ability of EPE and CA to hinder H1N1 and IVB attachment to host cell receptors. Furthermore, EPE and CA displayed inhibition activity against the NA of H1N1 and IVB. These findings suggest that EPE and CA can suppress the infection and propagation of H1N1, IVB, and RSV-A, demonstrating their potential as preventive and therapeutic agents for viral respiratory infections or as ingredients for health functional foods.
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Affiliation(s)
- Sung-Kwon Lee
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | - Dong-Ryung Lee
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | - Da-Eun Min
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | | | - Deok-Geun Kim
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | - Eun-Ji Kim
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | - Bong-Keun Choi
- Research Institute, NUON Co., Ltd., Gyeonggi 13201, Korea
| | - Kang-Beom Kwon
- Department of Physiology, College of Korean Medicine, Wonkwang University, Jeonbuk 54538, Korea
- Ilwonbio Co., Ltd., Jeonbuk 54538, Korea
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Chen BK, Chan CH, Tsao A, Wang CK. Improvement of Echinacea purpurea and Ganoderma lucidum Extracts with Cell Model on Influenza A/B Infection. Molecules 2024; 29:3609. [PMID: 39125012 PMCID: PMC11314549 DOI: 10.3390/molecules29153609] [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: 06/27/2024] [Revised: 07/25/2024] [Accepted: 07/25/2024] [Indexed: 08/12/2024] Open
Abstract
Since 2019, COVID-19 has been raging around the world. Respiratory viral infectious diseases such as influenza and respiratory syncytial virus (RSV) infection are also prevalent, with influenza having the ability to cause seasonal pandemics. While vaccines and antiviral drugs are available to prevent and treat disease, herbal extracts would be another option. This study investigated the inhibitory effects of extracts of Echinacea purpurea (EP) and Ganoderma lucidum (G. lucidum) and the advanced G. lucidum drink (AG) on influenza A/B viruses. To determine whether EP and G. lucidum extracts enhance cell immunity and thus prevent virus infection or act to directly suppress viruses, cell survival and hemagglutination (HA) assays were used in this study. Cells were treated with samples at different concentrations (each sample concentration was tested from the highest non-cytotoxic concentration) and incubated with influenza A/B for 24 h, with the results showing that both G. lucidum and EP extracts and mixtures exhibited the ability to enhance cell survival against viruses. In the HA assay, AG and EP extract showed good inhibitory effect on influenza A/B viruses. All of the samples demonstrated an improvement of the mitochondrial membrane potential and improved resistance to influenza A/B virus infection. EP and G. lucidum extracts at noncytotoxic concentrations increased cell viability, but only AG and EP extract directly decreased influenza virus titers. In conclusion, results indicate the ability of EP and G. lucidum extract to prevent viruses from entering cells by improving cell viability and mitochondrial dysfunction and EP extract showed direct inhibition on viruses and prevented viral infection at post-infection strategy.
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Affiliation(s)
- Bo-Kai Chen
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan;
| | - Chi-Ho Chan
- Department of Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan;
- Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
| | - Arthur Tsao
- SFG Health Lab, Standard Foods Group, Taoyuan 337402, Taiwan;
| | - Chin-Kun Wang
- Department of Nutrition, Chung Shan Medical University, 110, Section 1, Jianguo North Road, Taichung 40201, Taiwan;
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Gancitano G, Mucci N, Stange R, Ogal M, Vimalanathan S, Sreya M, Booker A, Hadj-Cherif B, Albrich WC, Woelkart-Ardjomand K, Kreft S, Vanden Berghe W, Hoexter G, Schapowal A, Johnston SL. Echinacea Reduces Antibiotics by Preventing Respiratory Infections: A Meta-Analysis (ERA-PRIMA). Antibiotics (Basel) 2024; 13:364. [PMID: 38667040 PMCID: PMC11047471 DOI: 10.3390/antibiotics13040364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2024] [Revised: 03/19/2024] [Accepted: 03/31/2024] [Indexed: 04/29/2024] Open
Abstract
Respiratory tract infections (RTIs) are the leading cause of antibiotic prescriptions, primarily due to the risk for secondary bacterial infections. In this study, we examined whether Echinacea could reduce the need for antibiotics by preventing RTIs and their complications, and subsequently investigated its safety profile. A comprehensive search of EMBASE, PubMed, Google Scholar, Cochrane DARE and clinicaltrials.gov identified 30 clinical trials (39 comparisons) studying Echinacea for the prevention or treatment of RTIs in 5652 subjects. Echinacea significantly reduced the monthly RTI occurrence, risk ratio (RR) 0.68 (95% CI 0.61-0.77) and number of patients with ≥1 RTI, RR = 0.75 [95% CI 0.69-0.81] corresponding to an odds ratio 0.53 [95% CI 0.42-0.67]. Echinacea reduced the risk of recurrent infections (RR = 0.60; 95% CI 0.46-0.80), RTI complications (RR = 0.44; 95% CI 0.36-0.54) and the need for antibiotic therapy (RR = 0.60; 95% CI 0.39-0.93), with total antibiotic therapy days reduced by 70% (IRR = 0.29; 95% CI 0.11-0.74). Alcoholic extracts from freshly harvested Echinacea purpurea were the strongest, with an 80% reduction of antibiotic treatment days, IRR 0.21 [95% CI 0.15-0.28]. An equal number of adverse events occurred with Echinacea and control treatment. Echinacea can safely prevent RTIs and associated complications, thereby decreasing the demand for antibiotics. Relevant differences exist between Echinacea preparations.
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Affiliation(s)
- Giuseppe Gancitano
- 1st Carabinieri Paratrooper Regiment “Tuscania”, Italian Ministry of Defence, 57127 Livorno, Italy
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
| | - Nicola Mucci
- Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy;
| | - Rainer Stange
- Institute of Social Medicine, Epidemiology and Health Economics, Charité-Universitätsmedizin Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, 10117 Berlin, Germany;
| | - Mercedes Ogal
- Pediatric Clinic Brunnen, 6440 Brunnen, Switzerland;
| | - Selvarani Vimalanathan
- Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (S.V.); (M.S.)
| | - Mahfuza Sreya
- Pathology & Laboratory Medicine, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada; (S.V.); (M.S.)
| | - Anthony Booker
- Research Group for Optimal Health, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London W1B 2HW, UK; (A.B.); (B.H.-C.)
- Research Group ‘Pharmacognosy and Phytotherapy’, UCL School of Pharmacy, London WC1N 1AX, UK
| | - Bushra Hadj-Cherif
- Research Group for Optimal Health, School of Life Sciences, College of Liberal Arts and Sciences, University of Westminster, London W1B 2HW, UK; (A.B.); (B.H.-C.)
| | - Werner C. Albrich
- Division of Infectious Disease, Infection Prevention and Travel Medicine, Cantonal Hospital, 9000 St. Gallen, Switzerland;
| | - Karin Woelkart-Ardjomand
- Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria;
| | - Samo Kreft
- Faculty of Pharmacy, University of Ljubljana, 1000 Ljubliana, Slovenia;
| | - Wim Vanden Berghe
- Department of Biomedical Sciences, University of Antwerp, 2000 Antwerp, Belgium;
| | - Godehard Hoexter
- Statistical Consulting Godehard Hoexter, 79100 Freiburg, Germany;
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Li TJ, Lin TW, Lu TY, Tseng CK, Lin CK, Chu HT, Li IC, Chen CC. Phellinus linteus mycelia extract in COVID-19 prevention and identification of its key metabolic compounds profiling using UPLC-QTOF-MS/MS spectrometry. Fitoterapia 2023; 171:105695. [PMID: 37797793 DOI: 10.1016/j.fitote.2023.105695] [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: 05/02/2023] [Revised: 09/27/2023] [Accepted: 10/02/2023] [Indexed: 10/07/2023]
Abstract
For centuries, food, herbal medicines, and natural products have been valuable resources for discovering novel antiviral drugs, uncovering new structure-activity relationships, and developing effective strategies to prevent/treat viral infections. One such resource is Phellinus linteus, a mushroom used in folk medicine in Taiwan, Japan, Korea, and China. In this rich historical context, the key metabolites of Phellinus linteus mycelia ethanolic extract (GKPL) impacting the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at multiple stages have yet to be explored. Thus, this study systematically identifies and assesses the inhibitory effect of GKPL on the SARS-CoV-2 virus. Initially, the concentrations and contact times of GKPL against SARS-CoV-2 pseudovirus were assessed in HepG2 cells. Subsequently, utilizing the Ultra Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry method, potential biomarkers in the fungal extract were discerned. Metabolomic analysis identified 18 compounds in GKPL, with hispidin and hypholomine B present in the highest amounts. These compounds were isolated using chromatographic techniques and further identified through 1D NMR spectroscopic and mass spectrometry analysis. Hispidin and hypholomine B were found to inhibit the infection of SARS-CoV-2 pseudovirus by reducing angiotensin-converting enzyme 2 gene expression in HepG2, thereby decreasing viral entry. Moreover, hispidin and hypholomine B effectively block the spike receptor-binding domain, while hypholomine B, for the first time, showed significant inhibition of 3CL protease. This suggests that GKPL, enriched with hispidin and hypholomine B, has the potential to be used as an active ingredient against SARS-CoV-2.
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Affiliation(s)
- Tsung-Ju Li
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan
| | - Ting-Wei Lin
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan
| | - Ting-Yu Lu
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan
| | | | | | - Hsin-Tung Chu
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan
| | - I-Chen Li
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan.
| | - Chin-Chu Chen
- Biotech Research Institute, Grape King Bio Ltd., Taoyuan City 325, Taiwan; Department of Food Science, Nutrition, and Nutraceutical Biotechnology, Shih Chien University, Taipei City 104, Taiwan; Institute of Food Science and Technology, National Taiwan University, Taipei City 106, Taiwan; Department of Bioscience Technology, Chung Yuan Christian University, Taoyuan City 320, Taiwan.
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12
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Dosoky NS, Kirpotina LN, Schepetkin IA, Khlebnikov AI, Lisonbee BL, Black JL, Woolf H, Thurgood TL, Graf BL, Satyal P, Quinn MT. Volatile Composition, Antimicrobial Activity, and In Vitro Innate Immunomodulatory Activity of Echinacea purpurea (L.) Moench Essential Oils. Molecules 2023; 28:7330. [PMID: 37959750 PMCID: PMC10647913 DOI: 10.3390/molecules28217330] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2023] [Revised: 10/20/2023] [Accepted: 10/26/2023] [Indexed: 11/15/2023] Open
Abstract
Echinacea purpurea (L.) Moench is a medicinal plant commonly used for the treatment of upper respiratory tract infections, the common cold, sore throat, migraine, colic, stomach cramps, and toothaches and the promotion of wound healing. Based on the known pharmacological properties of essential oils (EOs), we hypothesized that E. purpurea EOs may contribute to these medicinal properties. In this work, EOs from the flowers of E. purpurea were steam-distilled and analyzed by gas chromatography-mass spectrometry (GC-MS), GC with flame-ionization detection (GC-FID), and chiral GC-MS. The EOs were also evaluated for in vitro antimicrobial and innate immunomodulatory activity. About 87 compounds were identified in five samples of the steam-distilled E. purpurea EO. The major components of the E. purpurea EO were germacrene D (42.0 ± 4.61%), α-phellandrene (10.09 ± 1.59%), β-caryophyllene (5.75 ± 1.72%), γ-curcumene (5.03 ± 1.96%), α-pinene (4.44 ± 1.78%), δ-cadinene (3.31 ± 0.61%), and β-pinene (2.43 ± 0.98%). Eleven chiral compounds were identified in the E. purpurea EO, including α-pinene, sabinene, β-pinene, α-phellandrene, limonene, β-phellandrene, α-copaene, β-elemene, β-caryophyllene, germacrene D, and δ-cadinene. Analysis of E. purpurea EO antimicrobial activity showed that they inhibited the growth of several bacterial species, although the EO did not seem to be effective for Staphylococcus aureus. The E. purpurea EO and its major components induced intracellular calcium mobilization in human neutrophils. Additionally, pretreatment of human neutrophils with the E. purpurea EO or (+)-δ-cadinene suppressed agonist-induced neutrophil calcium mobilization and chemotaxis. Moreover, pharmacophore mapping studies predicted two potential MAPK targets for (+)-δ-cadinene. Our results are consistent with previous reports on the innate immunomodulatory activities of β-caryophyllene, α-phellandrene, and germacrene D. Thus, this study identified δ-cadinene as a novel neutrophil agonist and suggests that δ-cadinene may contribute to the reported immunomodulatory activity of E. purpurea.
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Affiliation(s)
- Noura S. Dosoky
- Essential Oil Science, dōTERRA International, 1248 W 700 S, Pleasant Grove, UT 84062, USA;
| | - Liliya N. Kirpotina
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (L.N.K.); (I.A.S.)
| | - Igor A. Schepetkin
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (L.N.K.); (I.A.S.)
| | | | - Brent L. Lisonbee
- Innova Bio, Utah Valley University, 800 W University Pkwy, Orem, UT 84058, USA; (B.L.L.); (J.L.B.); (T.L.T.)
| | - Jeffrey L. Black
- Innova Bio, Utah Valley University, 800 W University Pkwy, Orem, UT 84058, USA; (B.L.L.); (J.L.B.); (T.L.T.)
| | - Hillary Woolf
- Research and Development, dōTERRA International, 389 S 1300 W, Pleasant Grove, UT 84062, USA; (H.W.); (B.L.G.)
| | - Trever L. Thurgood
- Innova Bio, Utah Valley University, 800 W University Pkwy, Orem, UT 84058, USA; (B.L.L.); (J.L.B.); (T.L.T.)
| | - Brittany L. Graf
- Research and Development, dōTERRA International, 389 S 1300 W, Pleasant Grove, UT 84062, USA; (H.W.); (B.L.G.)
| | - Prabodh Satyal
- Essential Oil Science, dōTERRA International, 1248 W 700 S, Pleasant Grove, UT 84062, USA;
| | - Mark T. Quinn
- Department of Microbiology and Cell Biology, Montana State University, Bozeman, MT 59717, USA; (L.N.K.); (I.A.S.)
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Veldman LBM, Belt-Van Zoen E, Baars EW. Mechanistic Evidence of Andrographis paniculata (Burm. f.) Wall. ex Nees, Pelargonium sidoides DC., Echinacea Species and a Combination of Hedera helix L., Primula veris L./ Primula elatior L. and Thymus vulgaris L./ Thymus zygis L. in the Treatment of Acute, Uncomplicated Respiratory Tract Infections: A Systematic Literature Review and Expert Interviews. Pharmaceuticals (Basel) 2023; 16:1206. [PMID: 37765014 PMCID: PMC10537612 DOI: 10.3390/ph16091206] [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: 05/31/2023] [Revised: 08/17/2023] [Accepted: 08/18/2023] [Indexed: 09/29/2023] Open
Abstract
Reducing inappropriate antibiotic (AB) use by using effective non-antibiotic treatments is one strategy to prevent and reduce antimicrobial resistance (AMR). Andrographis paniculata (Burm. f.) Wall. ex Nees, Pelargonium sidoides DC., Echinacea species and a combination of ivy (Hedera helix L.), primrose (Primula veris L./Primula elatior L.) and thyme (Thymus vulgaris L./Thymus zygis L.) have promising clinical effects in uncomplicated, acute upper respiratory tract infections (URTI) treatment. However, mechanistic evidence of these herbal treatments is lacking. The objective of this Pstudy is to provide an overview of mechanistic evidence for these effects. Thirty-eight databases were searched. Included studies were mechanistic studies (in vitro, animal, and human studies and reviews) on these herbs; published before June 2021. Non-mechanistic studies or studies on combinations of herbs other than ivy/primrose/thyme were excluded. Furthermore, three experts in traditional, complementary and integrative healthcare (TCIH) research and pharmacognosy were interviewed to collect additional expert knowledge. The results show that A. paniculata acts through immunomodulation and antiviral activity, possibly supplemented by antibacterial and antipyretic effects. P. sidoides acts through antiviral, indirect antibacterial, immunomodulatory and expectorant effects. Echinacea species likely act through immunomodulation. The combination of ivy/primrose/thyme combines secretolytic and spasmolytic effects from ivy with antibacterial effects from thyme. Studies on primrose were lacking. This mechanistic evidence supports the difference-making evidence from clinical studies, contributes to evidence-based recommendations for their use in URTI treatment, and guides future mechanistic studies on URTI treatments.
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Affiliation(s)
- Liesbeth B. M. Veldman
- Faculty of Healthcare, University of Applied Sciences Leiden, 2333 Leiden, The Netherlands
| | - Eefje Belt-Van Zoen
- Faculty of Healthcare, University of Applied Sciences Leiden, 2333 Leiden, The Netherlands
| | - Erik W. Baars
- Faculty of Healthcare, University of Applied Sciences Leiden, 2333 Leiden, The Netherlands
- Louis Bolk Institute, 3981 Bunnik, The Netherlands
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Sumer J, Keckeis K, Scanferla G, Frischknecht M, Notter J, Steffen A, Kohler P, Schmid P, Roth B, Wissel K, Vernazza P, Klein P, Schoop R, Albrich WC. Novel Echinacea formulations for the treatment of acute respiratory tract infections in adults-A randomized blinded controlled trial. Front Med (Lausanne) 2023; 10:948787. [PMID: 37138742 PMCID: PMC10150997 DOI: 10.3389/fmed.2023.948787] [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: 05/20/2022] [Accepted: 03/16/2023] [Indexed: 05/05/2023] Open
Abstract
Background Echinacea purpurea has clinical antiviral activity against respiratory viruses and modulates immune functions. In this study, we compared higher doses of new Echinacea formulations with conventional formulations at lower, preventive doses for therapy of respiratory tract infections (RTIs). Methods In this randomized, blinded, controlled trial, healthy adults (n = 409) were randomized between November 2018 and January 2019 to one of four Echinacea formulations, which were taken in case of an RTI for up to 10 days. New formulations A (lozenges) and B (spray) delivered an increased dose of 16,800 mg/d Echinacea extract during days 1-3 and 2,240-3,360 mg/d afterward; as controls, conventional formulations C (tablets) and D (drops) delivered a lower daily dose of 2,400 mg, usually taken for prevention. The primary endpoint was time to clinical remission of first RTI episodes based on the Kaplan-Meier analysis of patient-reported, investigator-confirmed, respiratory symptoms assessed for up to 10 days. In a sensitivity analysis, the mean time to remission beyond day 10 was calculated by extrapolating the treatment effects observed on days 7 to 10. Results A total of 246 participants (median age 32 years, 78% female participants) were treated for at least one RTI. Recovery by day 10 (complete absence of symptoms) was achieved in 56 and 44% of patients with the new and conventional formulations, respectively, showing a median time to recovery of 10 and 11 days, respectively (p = 0.10 in intention-to-treat analysis, p = 0.07 in per-protocol analysis). In the extrapolated sensitivity analysis, new formulations resulted in a significantly shorter mean time to remission (9.6 vs. 11.0 days, p < 0.001). Among those with an identified respiratory virus, viral clearance until day 10 based on real-time PCR from nasopharyngeal swabs was more frequent with new formulations (70 vs. 53%, p = 0.046). Tolerability and safety (adverse events: 12 vs. 6%, p = 0.19) were good and similar between formulations. There was one severe adverse event with a potential hypersensitivity reaction in a recipient of the novel spray formulation. Conclusion In adults with acute RTI, new Echinacea formulations with higher doses resulted in faster viral clearance than conventional formulations in prophylactic dosages. The trend for faster clinical recovery was not significant by day 10 but became so upon extrapolation. A dose increase during acute respiratory symptoms might improve the clinical benefits of orally administered Echinacea formulations. Trial registration The study was registered in the Swiss National Clinical Trials Portal (SNCTP000003069) and on ClinicalTrials.gov (NTC03812900; URL https://clinicaltrials.gov/ct2/show/NCT03812900?cond=echinacea&draw=3&rank=14).
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Affiliation(s)
- Johannes Sumer
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Karin Keckeis
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Giulia Scanferla
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Manuel Frischknecht
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Julia Notter
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Ana Steffen
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Philipp Kohler
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Patrick Schmid
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Bianca Roth
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital of Lucerne, Luzern, Switzerland
| | | | - Pietro Vernazza
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
| | - Peter Klein
- d.s.h. Statistical Services GmbH, Rohrbach, Germany
| | | | - Werner C. Albrich
- Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland
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15
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Weishaupt R, Buchkov A, Kolev E, Klein P, Schoop R. Reduction of Viral Load in Patients with Acute Sore Throats: Results from an Observational Clinical Trial with Echinacea/Salvia Lozenges. Complement Med Res 2023; 30:299-306. [PMID: 36889292 PMCID: PMC10664317 DOI: 10.1159/000530017] [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: 07/19/2022] [Accepted: 02/27/2023] [Indexed: 03/10/2023]
Abstract
BACKGROUND Acute tonsillopharyngitis or sore throat is an initial sign of viral respiratory tract infection (RTI) and an optimal indicator for early antiviral and anti-inflammatory intervention. Both of these actions have been attributed to Echinacea purpurea and Salvia officinalis. METHODS 74 patients (age 13-69 years) with acute sore throat symptoms (<48 h) were treated with five Echinacea/Salvia lozenges per day (4,000 mg Echinacea purpurea extract [Echinaforce®] and 1,893 mg Salvia officinalis extract [A. Vogel AG, Switzerland] daily) for 4 days. Symptom intensities were recorded in a diary and oropharyngeal swab samples collected for virus detection and quantification via RT-qPCR. RESULTS The treatment was exceptionally well tolerated, no complicated RTI developed, and no antibiotic treatment was required. A single lozenge reduced throat pain by 48% (p < 0.001) and tonsillopharyngitis symptoms by 34% (p < 0.001). Eighteen patients tested virus positive at inclusion. Viral loads in these patients was reduced by 62% (p < 0.03) after intake of a single lozenge and by 96% (p < 0.02) after 4 days of treatment compared to pre-treatment. CONCLUSIONS Echinacea/Salvia lozenges represent a valuable and safe option for the early treatment of acute sore throats capable to alleviate symptoms and contribute to reducing viral loads in the throat. Hintergrund Akute Tonsillopharyngitis oder Halsschmerzen/entzündungen sind ein erstes Anzeichen einer viralen Atemwegsinfektion (vAWI) und ein optimaler Indikator für eine frühzeitige antivirale und entzündungshemmende Intervention. Beide Wirkungen werden Echinacea purpurea und Salvia officinalis zugeschrieben. Methoden 74 Patienten (Alter 13–69 Jahre) mit akuten Halsschmerzen/entzündungen (<48 h) wurden mit fünf Echinacea/Salvia-Lutschtabletten pro Tag (Tagesdosis: 4'000 mg Echinacea purpurea-Extrakt [Echinaforce®] und 1'893 mg Salvia officinalis Extrakt [A. Vogel AG, Schweiz]) behandelt für 4 Tage. Die Symptomintensität wurde in einem Tagebuch aufgezeichnet und Rachenabstrichproben wurden zum Virusnachweis und zur Quantifizierung mittels RT-qPCR entnommen. Resultate Die Behandlung wurde außergewöhnlich gut vertragen, es entwickelte sich keine komplizierten AWI und es waren keine Antibiotikabehandlungen erforderlich. Eine einzelne Lutschtablette reduzierte die akuten Halsschmerzen um 48% ( p < 0,001) und die allgemeinen Tonsillopharyngitis Symptome um 34% ( p < 0,001). Achtzehn Patienten wurden bei der Aufnahme viruspositiv getestet. Die Viruslast wurde bei diesen Patienten nach Einnahme einer einzigen Lutschtablette um 62% ( p < 0,03), und nach 4-tägiger Behandlung um 96% ( p < 0,02) reduziert im Vergleich zu vor der Behandlung. Schlussfolgerungen Echinacea/Salvia-Lutschtabletten stellen eine sichere Option für die frühzeitige Behandlung akuter Halsschmerzen/entzündungen dar, die Symptome lindern, und zur Verringerung der Viruslast im Hals beitragen können.
Affiliation(s)
| | - Alexandar Buchkov
- Convex CRC, Diagnostics and Consultation Center Convex, Sofia, Bulgaria
| | - Emil Kolev
- Convex CRC, Diagnostics and Consultation Center Convex, Sofia, Bulgaria
| | - Peter Klein
- d.s.h. Statistical Services GmbH, Rohrbach, Germany
| | - Roland Schoop
- Medical Department, A. Vogel AG, Roggwil, Switzerland
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16
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Dutta AK, Gazi MS, Uddin SJ. A systemic review on medicinal plants and their bioactive constituents against avian influenza and further confirmation through in-silico analysis. Heliyon 2023; 9:e14386. [PMID: 36925514 PMCID: PMC10011005 DOI: 10.1016/j.heliyon.2023.e14386] [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: 08/06/2022] [Revised: 02/26/2023] [Accepted: 03/03/2023] [Indexed: 03/11/2023] Open
Abstract
Background Avian influenza or more commonly known as bird flu is a widespread infectious disease in poultry. This review aims to accumulate information of different natural plant sources that can aid in combating this disease. Influenza virus (IV) is known for its ability to mutate and infect different species (including humans) and cause fatal consequences. Methods Total 33 plants and 4 natural compounds were identified and documented. Molecular docking was performed against the target viral protein neuraminidase (NA), with some plant based natural compounds and compared their results with standard drugs Oseltamivir and Zanamivir to obtain novel drug targets for influenza in chickens. Results It was seen that most extracts exhibit their action by interacting with viral hemagglutinin or neuraminidase and inhibit viral entry or release from the host cell. Some plants also interacted with the viral RNA replication or by reducing proinflammatory cytokines. Ethanol was mostly used for extraction. Among all the plants Theobroma cacao, Capparis Sinaica Veil, Androgarphis paniculate, Thallasodendron cillatum, Sinularia candidula, Larcifomes officinalis, Lenzites betulina, Datronia molis, Trametes gibbose exhibited their activity with least concentration (below 10 μg/ml). The dockings results showed that some natural compounds (5,7- dimethoxyflavone, Aloe emodin, Anthocyanins, Quercetin, Hemanthamine, Lyocrine, Terpenoid EA showed satisfactory binding affinity and binding specificity with viral neuraminidase compared to the synthetic drugs. Conclusion This review clusters up to date information of effective herbal plants to bolster future influenza treatment research in chickens. The in-silico analysis also suggests some potential targets for future drug development but these require more clinical analysis.
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Affiliation(s)
- Ashit Kumar Dutta
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Md Shamim Gazi
- Biotechnology and Genetic Engineering Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
| | - Shaikh Jamal Uddin
- Pharmacy Discipline, Life Science School, Khulna University, Khulna 9208, Bangladesh
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Dhara AK, Nayak AK. Introduction to antiviral therapy. VIRAL INFECTIONS AND ANTIVIRAL THERAPIES 2023:3-22. [DOI: 10.1016/b978-0-323-91814-5.00025-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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18
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Bajrai LH, El-Kafrawy SA, Hassan AM, Tolah AM, Alnahas RS, Sohrab SS, Rehan M, Azhar EI. In vitro screening of anti-viral and virucidal effects against SARS-CoV-2 by Hypericum perforatum and Echinacea. Sci Rep 2022; 12:21723. [PMID: 36522420 PMCID: PMC9754313 DOI: 10.1038/s41598-022-26157-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2022] [Accepted: 12/12/2022] [Indexed: 12/23/2022] Open
Abstract
Hypericum perforatum and Echinacea are reported to have antiviral activities against several viral infections. In this study, H. perforatum (St. John's Wort) and Echinacea were tested in vitro using Vero E6 cells for their anti-viral effects against the newly identified Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) through its infectious cycle from 0 to 48 h post infection. The hypericin of H. perforatum and the different parts (roots, seeds, aerial) of two types of Echinacea species (Echinacea purpurea and Echinacea angustifolia) were tested for their anti-viral activities to measure the inhibition of viral load using quantitative real-time polymerase chain reaction (qRT-PCR) on cell culture assay. Interestingly, the H. perforatum-Echinacea mixture (1:1 ratio) of H. perforatum and Echinacea was tested as well on SARS-CoV-2 and showed crucial anti-viral activity competing H. perforatum then Echinacea effects as anti-viral treatment. Therefore, the results H. perforatum and Echinacea species, applied in this study showed significant anti-viral and virucidal effects in the following order of potency: H. perforatum, H. perforatum-Echinacea mixture, and Echinacea on SARS-CoV-2 infectious cycle. Additionally, molecular simulation analysis of the compounds with essential proteins (Mpro and RdRp) of the SARS-CoV-2 revealed the most potent bioactive compounds such as Echinacin, Echinacoside, Cyanin, Cyanidin 3-(6''-alonylglucoside, Quercetin-3-O-glucuronide, Proanthocyanidins, Rutin, Kaempferol-3-O-rutinoside, and Quercetin-3-O-xyloside. Thus, based on the outcome of this study, it is demanding the setup of clinical trial with specific therapeutic protocol.
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Affiliation(s)
- Leena Hussein Bajrai
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
- Biochemistry Department, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
| | - Sherif Ali El-Kafrawy
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmed Mohamed Hassan
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ahmed Majdi Tolah
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Rabig, Saudi Arabia
| | - Rabie Saleh Alnahas
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Sayed Sartaj Sohrab
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Mohd Rehan
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
- King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Esam Ibraheem Azhar
- Special Infectious Agents Unit-BSL3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
- Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
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Eliopoulos AG, Angelis A, Liakakou A, Skaltsounis LA. In Vitro Anti-Influenza Virus Activity of Non-Polar Primula veris subsp. veris Extract. Pharmaceuticals (Basel) 2022; 15:ph15121513. [PMID: 36558964 PMCID: PMC9787935 DOI: 10.3390/ph15121513] [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: 10/31/2022] [Revised: 11/21/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
Medicinal plants have long been recognized as a tremendous source of candidate compounds for the development of pharmaceuticals, including anti-viral agents. Herein, we report the identification of anti-influenza virus activity in non-polar Primula veris L. subsp. veris extracts. We show that P. veris subsp. veris flower extracts, obtained using supercritical fluid or ultrasound-based extraction, possess virucidal/virus inactivation properties and confer prophylactic and therapeutic effects against influenza virus-induced cytolysis in vitro. By GC-MS and UPLC-HRMS analysis of non-polar P. veris subsp. veris extracts we identified terpenes, flavones, tocopherols, and other classes of phytochemicals with known or putative anti-influenza properties. In silico prediction of cellular functions and molecular pathways affected by these phytochemicals suggests putative effects on signal transduction, inflammasome, and cell death pathways that are relevant to influenza virus pathogenesis. Combining P. veris subsp. veris with extracts of medicinal plants with proven anti-influenza activity such as Echinacea purpurea (L.) Moench and Cistus creticus L. subsp. creticus achieves an impressive protective effect against infection by influenza virus H1N1 in vitro and reduced progeny virus production by infected cells. Collectively, these findings uncover a previously uncharted biological property of non-polar P. veris flower extracts that warrants further studies to assess clinical efficacy.
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Affiliation(s)
- Aristides G. Eliopoulos
- Department of Biology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece
- Center of Basic Research, Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece
- Correspondence: (A.G.E.); (L.A.S.)
| | - Apostolis Angelis
- Department of Pharmacy, Division of Pharmacognosy and Natural Products Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
| | - Anastasia Liakakou
- Department of Pharmacy, Division of Pharmacognosy and Natural Products Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
| | - Leandros A. Skaltsounis
- Department of Pharmacy, Division of Pharmacognosy and Natural Products Chemistry, National and Kapodistrian University of Athens, 15771 Athens, Greece
- Correspondence: (A.G.E.); (L.A.S.)
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Vimalanathan S, Shehata M, Sadasivam K, Delbue S, Dolci M, Pariani E, D’Alessandro S, Pleschka S. Broad Antiviral Effects of Echinacea purpurea against SARS-CoV-2 Variants of Concern and Potential Mechanism of Action. Microorganisms 2022; 10:2145. [PMID: 36363737 PMCID: PMC9694187 DOI: 10.3390/microorganisms10112145] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2022] [Revised: 10/14/2022] [Accepted: 10/24/2022] [Indexed: 09/19/2023] Open
Abstract
SARS-CoV-2 variants of concern (VOCs) represent an alarming threat as they show altered biological behavior and may escape vaccination effectiveness. Broad-spectrum antivirals could play an important role to control infections. The activity of Echinacea purpurea (Echinaforce® extract, EF) against (i) VOCs B1.1.7 (alpha), B.1.351.1 (beta), P.1 (gamma), B1.617.2 (delta), AV.1 (Scottish), B1.525 (eta), and B.1.1.529.BA1 (omicron); (ii) SARS-CoV-2 spike (S) protein-pseudotyped viral particles and reference strain OC43 as well as (iii) wild type SARS-CoV-2 (Hu-1) was analyzed. Molecular dynamics (MD) were applied to study the interaction of Echinacea's phytochemical markers with known pharmacological viral and host cell targets. EF extract broadly inhibited the propagation of all investigated SARS-CoV-2 VOCs as well as the entry of SARS-CoV-2 pseudoparticles at EC50's ranging from 3.62 to 12.03 µg/mL. The preventive addition of 25 µg/mL EF to epithelial cells significantly reduced sequential infection with SARS-CoV-2 (Hu-1) and OC43. MD analyses showed constant binding affinities to VOC-typical S protein variants for alkylamides, caftaric acid, and feruloyl-tartaric acid in EF extract and interactions with serine protease TMPRSS-2. EF extract demonstrated stable virucidal activity across seven tested VOCs, likely due to the constant affinity of the contained phytochemical substances to all spike variants. A possible interaction of EF with TMPRSS-2 partially would explain the cell protective benefits of the extract by the inhibition of membrane fusion and cell entry. EF may therefore offer a supportive addition to vaccination endeavors in the control of existing and future SARS-CoV-2 virus mutations.
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Affiliation(s)
- Selvarani Vimalanathan
- Pathology & Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 2B5, Canada
| | - Mahmoud Shehata
- Institute of Medical Virology, Justus Liebig University Giessen, 35392 Giessen, Germany
- Center of Scientific Excellence for Influenza Viruses, National Research Centre, Giza 12622, Egypt
| | - Kannan Sadasivam
- Centre for High Computing, Central Leather Research Institute, Adyar, Chennai 600020, India
| | - Serena Delbue
- Laboratory of Molecular Virology, Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy
| | - Maria Dolci
- Laboratory of Molecular Virology, Department of Biomedical, Surgical and Dental Sciences, University of Milano, 20133 Milano, Italy
| | - Elena Pariani
- Department of Biomedical Sciences for Health, University of Milano, 20133 Milano, Italy
| | - Sarah D’Alessandro
- Department of Pharmacological and Biomedical Sciences, University of Milano, 20133 Milano, Italy
| | - Stephan Pleschka
- Institute of Medical Virology, Justus Liebig University Giessen, 35392 Giessen, Germany
- German Center for Infection Research, Partner Site Giessen-Marburg-Langen, 35392 Giessen, Germany
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Khan MAS, Parveen R, Hoque SA, Ahmed MF, Rouf ASS, Rahman SR. Implementing in vitro and in silico approaches to evaluate anti-influenza virus activity of different Bangladeshi plant extracts. ADVANCES IN TRADITIONAL MEDICINE 2022. [DOI: 10.1007/s13596-022-00669-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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22
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de Oliveira JR, Antunes BS, do Nascimento GO, Kawall JCDS, Oliveira JVB, Silva KGDS, Costa MADT, Oliveira CR. Antiviral activity of medicinal plant-derived products against SARS-CoV-2. Exp Biol Med (Maywood) 2022; 247:1797-1809. [PMID: 35894129 PMCID: PMC9679310 DOI: 10.1177/15353702221108915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
This review presents information from several studies that have demonstrated the antiviral activity of extracts (Andrographis paniculata, Artemisia annua, Artemisia afra, Cannabis sativa, Curcuma longa, Echinacea purpurea, Olea europaea, Piper nigrum, and Punica granatum) and phytocompounds derived from medicinal plants (artemisinins, glycyrrhizin, and phenolic compounds) against SARS-CoV-2. A brief background of the plant products studied, the methodology used to evaluate the antiviral activity, the main findings from the research, and the possible mechanisms of action are presented. These plant products have been shown to impede the adsorption of SARS-CoV-2 to the host cell, and prevent multiplication of the virus post its entry into the host cell. In addition to antiviral activity, the plant products have also been demonstrated to exert an immunomodulatory effect by controlling the excessive release of cytokines, which is commonly associated with SARS-CoV-2 infections.
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Affiliation(s)
- Jonatas Rafael de Oliveira
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Beatriz Sales Antunes
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Gabriela Oliveira do Nascimento
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Jaqueline Cadorini de Souza Kawall
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - João Victor Bianco Oliveira
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Kevin Gustavo dos Santos Silva
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Mariana Aparecida de Toledo Costa
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
| | - Carlos Rocha Oliveira
- School of Medicine, Anhembi Morumbi University (UAM), Avenida Deputado Benedito Matarazzo, 6707 - Jardim Aquarius, São José dos Campos 12242-010, SP, Brazil
- Post-graduation Program in Biomedical Engineering, Federal University of Sao Paulo (UNIFESP), Rua Talim, 330 - Vila Nair, São José dos Campos 12231-280, SP, Brazil
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Pilarska G, Twarużek M, Ałtyn I. The Presence of Molds and Their Secondary Metabolites in Purple Coneflower-Based Dietary Supplements (Echinacea purpurea (L.) Moench). Toxins (Basel) 2022; 14:toxins14090607. [PMID: 36136545 PMCID: PMC9502472 DOI: 10.3390/toxins14090607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 08/16/2022] [Accepted: 08/25/2022] [Indexed: 11/16/2022] Open
Abstract
Purple coneflower (Echinacea purpurea (L.) Moench) is a plant in the family Asteraceae, mainly grown in North America. Echinacea purpurea has been used in conventional medicine. The plant has immuno-stimulating and antibacterial properties, but neither mold contamination nor a mycotoxin presence have been evaluated. Our goal is to determine the degree to which molds and mycotoxins contaminate dietary supplements based on purple coneflower distributed on the Polish market. We analyzed 21 samples divided into four groups: sachets (n = 5), dry raw material (n = 3), capsules (n = 9), and tablets (n = 4). The mycological analysis of dietary supplements shows that the average number of molds is 1012 cfu/g, and the most common molds are Aspergillus spp., Phoma spp. and Eurotium spp. The mycotoxins most common in the samples are ZEN (18/21), DON (5/21) and T-2 toxin (3/21).
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Affiliation(s)
- Gabriela Pilarska
- Department of Physiology and Toxicology, Faculty of Biological Sciences, Kazimierz Wielki University, 85-064 Bydgoszcz, Poland
| | - Magdalena Twarużek
- Department of Physiology and Toxicology, Faculty of Biological Sciences, Kazimierz Wielki University, 85-064 Bydgoszcz, Poland
| | - Iwona Ałtyn
- Department of Physiology and Toxicology, Faculty of Biological Sciences, Kazimierz Wielki University, 85-064 Bydgoszcz, Poland
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Al-Harrasi A, Behl T, Upadhyay T, Chigurupati S, Bhatt S, Sehgal A, Bhatia S, Singh S, Sharma N, Vijayabalan S, Palanimuthu VR, Das S, Kaur R, Aleya L, Bungau S. Targeting natural products against SARS-CoV-2. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2022; 29:42404-42432. [PMID: 35362883 PMCID: PMC8972763 DOI: 10.1007/s11356-022-19770-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 03/13/2022] [Indexed: 06/01/2023]
Abstract
The human coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus; the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2). Natural products, secondary metabolites show positive leads with antiviral and immunotherapy treatments using genomic studies in silico docking. In addition, it includes the action of a mechanism targeting the SARS-CoV-2. In this literature, we aimed to evaluate the antiviral movement of the NT-VRL-1 unique terpene definition to Human coronavirus (HCoV-229E). The effects of 19 hydrolysable tannins on the SARS-CoV-2 were therefore theoretically reviewed and analyzed utilising the molecular operating surroundings for their C-Like protease 3CLpro catalytic dyad residues Angiotensin converting enzyme-2 (MOE 09). Pedunculagin, tercatan, and castalin were detected as interacting strongly with SARS-receptor Cov-2's binding site and catalytic dyad (Cys145 and His41). SARS-CoV-2 methods of subunit S1 (ACE2) inhibit the interaction of the receiver with the s-protein once a drug molecule is coupled to the s-protein and prevent it from infecting the target cells in alkaloids. Our review strongly demonstrates the evidence that natural compounds and their derivatives can be used against the human coronavirus and serves as an area of research for future perspective.
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Affiliation(s)
- Ahmed Al-Harrasi
- Natural & Medical Sciences Research Center, University of Nizwa, Birkat Al Mawz, Oman
| | - Tapan Behl
- Chitkara College of Pharmacy, Chitkara University, Punjab, India.
| | - Tanuj Upadhyay
- Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India
| | - Sridevi Chigurupati
- Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Buraidah, Kingdom of Saudi Arabia
| | - Shvetank Bhatt
- Amity Institute of Pharmacy, Amity University, Gwalior, Madhya Pradesh, India
| | - Aayush Sehgal
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Saurabh Bhatia
- Natural & Medical Sciences Research Center, University of Nizwa, Birkat Al Mawz, Oman
- School of Health Science, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India
| | - Sukhbir Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Neelam Sharma
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Shantini Vijayabalan
- Faculty of Health and Medical Sciences, School of Pharmacy, Taylor's University, Subang Jaya, Kuala Lumpur, Malaysia
| | - Vasanth Raj Palanimuthu
- Department of Pharmaceutical Biotechnology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamilnadu, India
| | - Suprava Das
- Department of Pharmacology, Faculty of Medicine, AIMST University, Semeling, Bedong, Kedah, Malaysia
| | - Rajwinder Kaur
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Lotfi Aleya
- Chrono-Environment Laboratory, UMR CNRS 6249, Bourgogne Franche-Comté University, Besançon, France
| | - Simona Bungau
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, Romania
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Kiriacos CJ, Khedr MR, Tadros M, Youness RA. Prospective Medicinal Plants and Their Phytochemicals Shielding Autoimmune and Cancer Patients Against the SARS-CoV-2 Pandemic: A Special Focus on Matcha. Front Oncol 2022; 12:837408. [PMID: 35664773 PMCID: PMC9157490 DOI: 10.3389/fonc.2022.837408] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 03/21/2022] [Indexed: 12/12/2022] Open
Abstract
Background Being "positive" has been one of the most frustrating words anyone could hear since the end of 2019. This word had been overused globally due to the high infectious nature of SARS-CoV-2. All citizens are at risk of being infected with SARS-CoV-2, but a red warning sign has been directed towards cancer and immune-compromised patients in particular. These groups of patients are not only more prone to catch the virus but also more predisposed to its deadly consequences, something that urged the research community to seek other effective and safe solutions that could be used as a protective measurement for cancer and autoimmune patients during the pandemic. Aim The authors aimed to turn the spotlight on specific herbal remedies that showed potential anticancer activity, immuno-modulatory roles, and promising anti-SARS-CoV-2 actions. Methodology To attain the purpose of the review, the research was conducted at the States National Library of Medicine (PubMed). To search databases, the descriptors used were as follows: "COVID-19"/"SARS-CoV-2", "Herbal Drugs", "Autoimmune diseases", "Rheumatoid Arthritis", "Asthma", "Multiple Sclerosis", "Systemic Lupus Erythematosus" "Nutraceuticals", "Matcha", "EGCG", "Quercetin", "Cancer", and key molecular pathways. Results This manuscript reviewed most of the herbal drugs that showed a triple action concerning anticancer, immunomodulation, and anti-SARS-CoV-2 activities. Special attention was directed towards "matcha" as a novel potential protective and therapeutic agent for cancer and immunocompromised patients during the SARS-CoV-2 pandemic. Conclusion This review sheds light on the pivotal role of "matcha" as a tri-acting herbal tea having a potent antitumorigenic effect, immunomodulatory role, and proven anti-SARS-CoV-2 activity, thus providing a powerful shield for high-risk patients such as cancer and autoimmune patients during the pandemic.
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Affiliation(s)
- Caroline Joseph Kiriacos
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Monika Rafik Khedr
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Miray Tadros
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Rana A. Youness
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
- Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, Egypt
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26
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Burlou-Nagy C, Bănică F, Jurca T, Vicaș LG, Marian E, Muresan ME, Bácskay I, Kiss R, Fehér P, Pallag A. Echinacea purpurea (L.) Moench: Biological and Pharmacological Properties. A Review. PLANTS (BASEL, SWITZERLAND) 2022; 11:plants11091244. [PMID: 35567246 PMCID: PMC9102300 DOI: 10.3390/plants11091244] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Revised: 04/27/2022] [Accepted: 05/02/2022] [Indexed: 05/25/2023]
Abstract
Echinacea purpurea (L.) Moench (EP)is a perennial herbaceous flowering plant, commonly known as purple coneflower and it belongs to the Asteraceae family. The Echinacea genus is originally from North America, in the United States, and its species are widely distributed throughout. There are nine different species of Echinacea, but only three of them are used as medicinal plants with wide therapeutic uses: Echinacea purpurea (L.) Moench, Echinacea pallida (Nutt.) Nutt. and Echinacea angustifolia DC. Several significant groups of bioactive compounds with pharmacological activities have been isolated from Echinacea species. Numerous beneficial effects have been demonstrated about these compounds. The immunomodulatory effect was initially demonstrated, but over time other effects have also been highlighted. The present review gives a comprehensive summary of the chemical constituents, bioactive compounds, biological effects and therapeutical uses of purple coneflower. Research shows that such a well-known and recognized species needs to be further studied to obtain efficient products with a guarantee of the safety.
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Affiliation(s)
- Cristina Burlou-Nagy
- Doctoral School of Pharmaceutical Sciences, University of Oradea, 410087 Oradea, Romania;
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
| | - Florin Bănică
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
| | - Tünde Jurca
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
| | - Laura Grațiela Vicaș
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
| | - Eleonora Marian
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
| | - Mariana Eugenia Muresan
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410068 Oradea, Romania;
| | - Ildikó Bácskay
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary; (I.B.); (P.F.)
| | - Rita Kiss
- Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary;
| | - Pálma Fehér
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Debrecen, H-4032 Debrecen, Hungary; (I.B.); (P.F.)
| | - Annamaria Pallag
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania; (F.B.); (T.J.); (L.G.V.); (E.M.)
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27
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Kolev E, Mircheva L, Edwards MR, Johnston SL, Kalinov K, Stange R, Gancitano G, Berghe WV, Kreft S. Echinacea Purpurea For the Long-Term Prevention of Viral Respiratory Tract Infections During Covid-19 Pandemic: A Randomized, Open, Controlled, Exploratory Clinical Study. Front Pharmacol 2022; 13:856410. [PMID: 35559249 PMCID: PMC9087554 DOI: 10.3389/fphar.2022.856410] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 03/21/2022] [Indexed: 11/13/2022] Open
Abstract
SARS-CoV-2 vaccination is effective in preventing severe Covid-19, but efficacy in reducing viral load and transmission wanes over time. In addition, the emergence of novel SARS-CoV-2 variants increases the threat of uncontrolled dissemination and additional antiviral therapies are urgently needed for effective containment. In previous in vitro studies Echinacea purpurea demonstrated strong antiviral activity against enveloped viruses, including SARS-CoV-2. In this study, we examined the potential of Echinacea purpurea in preventing and treating respiratory tract infections (RTIs) and in particular, SARS-CoV-2 infections. 120 healthy volunteers (m,f, 18-75 years) were randomly assigned to Echinacea prevention or control group without any intervention. After a run-in week, participants went through 3 prevention cycles of 2, 2 and 1 month with daily 2,400 mg Echinacea purpurea extract (Echinaforce®, EF). The prevention cycles were interrupted by breaks of 1 week. Acute respiratory symptoms were treated with 4,000 mg EF for up to 10 days, and their severity assessed via a diary. Naso/oropharyngeal swabs and venous blood samples were routinely collected every month and during acute illnesses for detection and identification of respiratory viruses, including SARS-CoV-2 via RT-qPCR and serology. Summarized over all phases of prevention, 21 and 29 samples tested positive for any virus in the EF and control group, of which 5 and 14 samples tested SARS-CoV-2 positive (RR = 0.37, Chi-square test, p = 0.03). Overall, 10 and 14 symptomatic episodes occurred, of which 5 and 8 were Covid-19 (RR = 0.70, Chi-square test, p > 0.05). EF treatment when applied during acute episodes significantly reduced the overall virus load by at least 2.12 log10 or approx. 99% (t-test, p < 0.05), the time to virus clearance by 8.0 days for all viruses (Wilcoxon test, p = 0.02) and by 4.8 days for SARS-CoV-2 (p > 0.05) in comparison to control. Finally, EF treatment significantly reduced fever days (1 day vs 11 days, Chi-square test, p = 0.003) but not the overall symptom severity. There were fewer Covid-19 related hospitalizations in the EF treatment group (N = 0 vs N = 2). EF exhibited antiviral effects and reduced the risk of viral RTIs, including SARS-CoV-2. By substantially reducing virus loads in infected subjects, EF offers a supportive addition to existing mandated treatments like vaccinations. Future confirmatory studies are warranted.
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Affiliation(s)
- Emil Kolev
- Clinical Research Center DCC Convex Ltd., Sofia, Bulgaria
| | | | - Michael R. Edwards
- Virtus Respiratory Research Limited, London Bioscience Innovation Centre, London, United Kingdom
- National Heart Lung Institute, Imperial College London St Marys Campus, London, United Kingdom
| | - Sebastian L. Johnston
- Virtus Respiratory Research Limited, London Bioscience Innovation Centre, London, United Kingdom
- National Heart Lung Institute, Imperial College London St Marys Campus, London, United Kingdom
| | | | - Rainer Stange
- Charité—Universitätsmedizin Berlin, Immanuel Hospital Berlin, Berlin, Germany
| | - Giuseppe Gancitano
- 1st “Tuscania” Paratrooper Regiment Carabinieri, Italian Ministry of Defence, Livorno, Italy
| | - Wim Vanden Berghe
- Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES) and Integrated Personalized and Precision Oncology Network (IPPON), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium
| | - Samo Kreft
- Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia
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Tráj P, Herrmann EM, Sebők C, Vörösházi J, Mackei M, Gálfi P, Kemény Á, Neogrády Z, Mátis G. Protective effects of chicoric acid on polyinosinic-polycytidylic acid exposed chicken hepatic cell culture mimicking viral damage and inflammation. Vet Immunol Immunopathol 2022; 250:110427. [DOI: 10.1016/j.vetimm.2022.110427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Revised: 04/08/2022] [Accepted: 04/12/2022] [Indexed: 10/18/2022]
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Rathinasabapathy T, Sakthivel LP, Komarnytsky S. Plant-Based Support of Respiratory Health during Viral Outbreaks. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:2064-2076. [PMID: 35147032 DOI: 10.1021/acs.jafc.1c06227] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
Respiratory viruses are linked to major epidemic events that have plagued humans through recorded history and possibly much earlier, ranging from common colds, influenza, and coronavirus infections to measles. However, difficulty in developing effective pharmaceutical solutions to treat infected individuals has hindered efforts to manage and minimize respiratory viral outbreaks and the associated mortality. Here we highlight a series of botanical interventions with different and often overlapping putative mechanisms of action to support the respiratory system, for which the bioactive pharmacophore was suggested and the initial structure-activity relationships have been explored (Bupleurum spp., Glycyrrhiza spp., Andrographis spp.), have been proposed with uncertainty (Echinacea spp., Zingiber spp., Verbascum spp., Marrubium spp.), or remained to be elucidated (Sambucus spp., Urtica spp.). Investigating these metabolites and their botanical sources holds potential to uncover new mediators of the respiratory health outcomes as well as molecular targets for future break-through therapeutic interventions targeting respiratory viral outbreaks.
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Affiliation(s)
- Thirumurugan Rathinasabapathy
- Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, North Carolina 28081, United States
- Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, North Carolina 27695, United States
| | - Lakshmana Prabu Sakthivel
- Department of Pharmaceutical Technology, College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu 620024, India
| | - Slavko Komarnytsky
- Plants for Human Health Institute, North Carolina State University, North Carolina Research Campus, 600 Laureate Way, Kannapolis, North Carolina 28081, United States
- Department of Food, Bioprocessing, and Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, North Carolina 27695, United States
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30
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Kaur N, Sharma P, Aditya A, Shanavas A. Taking leads out of nature, can nano deliver us from COVID-like pandemics? Biomed Phys Eng Express 2022; 8. [PMID: 35078168 DOI: 10.1088/2057-1976/ac4ec8] [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: 10/19/2021] [Accepted: 01/25/2022] [Indexed: 11/11/2022]
Abstract
The COVID-19 crisis has alerted the research community to re-purpose scientific tools that can effectively manage emergency pandemic situations. Researchers were never so desperate to discover a 'magic bullet' that has significant clinical benefits with minimal or no side effects. At the beginning of the pandemic, due to restricted access to traditional laboratory techniques, many research groups delved into computational screening of thousands of lead molecules that could inhibit SARS-CoV-2 at one or more stages of its infectious cycle. Several in silico studies on natural derivatives point out their potency against SARS-CoV-2 proteins. However, theoretical predictions and existing knowledge on related molecules reflect their poor oral bioavailability due to biotransformation in the gut and liver. Nanotechnology has evolved into a key field for precise and controlled delivery of various drugs that lack aqueous solubility, have low oral bioavailability and possess pronounced toxicity in their native form. In this review, we discuss various nanoformulations of natural products with favorable ADME properties, and also briefly explore nano-drug delivery to lungs, the primary site of SARS-CoV-2 infection. Natural products are also envisioned to augment nanotechnology-based 1) personnel protective equipment for ex vivo viral inactivation and 2) wearable sensors that perform rapid and non-invasive analysis of volatile organic compounds in exhaled breath of the infected person after therapeutic food consumption.
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Affiliation(s)
- Navneet Kaur
- Institute of Nano Science and Technology, Sector 81, Knowledge city, Mohali, 140306, INDIA
| | - Priyanka Sharma
- Institute of Nano Science and Technology, Sector 81, Knowledge city, Mohali, 140306, INDIA
| | - Adrija Aditya
- Institute of Nano Science and Technology, Sector 81, Knowledge city, Mohali, 140306, INDIA
| | - Asifkhan Shanavas
- Institute of Nano Science and Technology, Sector 81, Knowledge city, Mohali, 140306, INDIA
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Nicolussi S, Ardjomand-Woelkart K, Stange R, Gancitano G, Klein P, Ogal M. Echinacea as a Potential Force against Coronavirus Infections? A Mini-Review of Randomized Controlled Trials in Adults and Children. Microorganisms 2022; 10:211. [PMID: 35208665 PMCID: PMC8879308 DOI: 10.3390/microorganisms10020211] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Revised: 01/07/2022] [Accepted: 01/14/2022] [Indexed: 01/03/2023] Open
Abstract
Echinacea purpurea has been shown to broadly inhibit coronaviruses and SARS-CoV-2 in vitro. This review discusses the available clinical evidence from randomized, blinded and controlled human studies. Two RCTs capturing incidence of viral respiratory tract infections during Echinacea preventative treatment were identified including coronavirus infections. Incidence and/or viral loads were measured by RT-PCR and symptom severity was recorded. In a first study, Jawad et al. collected nasopharyngeal swabs from adults (N = 755) over 4 months of continuous prevention. Overall, 24 and 47 enveloped virus infections occurred, including 21 and 33 coronavirus detections (229E; HKU1; OC43) with Echinaforce® extract (2400 mg daily) and placebo, respectively (p = 0.0114). In a separate study, Ogal et al. administered the same extract (1200 mg) or control for 4 months to children (4-12 years) (N = 203). Echinacea reduced the incidence of enveloped virus infections from 47 to 29 (p = 0.0038) whereas 11 and 13 coronavirus detections (229E, OC43, NL63) were counted (p > 0.05). Respiratory symptoms during coronavirus infections were significantly lower with area-under-curve AUC = 75.8 (+/-50.24) versus 27.1 (+/-21.27) score points (p = 0.0036). Importantly, viral loads in nasal secretions were significantly reduced by 98.5% in the Echinacea group, with Ct-values 31.1 [95% CI 26.3; 35.9] versus 25.0 [95% CI 20.5; 29.5] in the control group (p = 0.0479). Results from clinical studies confirm the antiviral activity found for Echinacea in vitro, embracing enveloped respiratory pathogens and therefore coronaviruses as well. Substantiating results from a new, completed study seem to extrapolate these effects to the prevention of SARS-CoV-2 infections. As hypothesized, the established broad antiviral activity of Echinacea extract appears to be inclusive for SARS-CoV-2.
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Affiliation(s)
| | - Karin Ardjomand-Woelkart
- Department of Pharmacognosy, Institute of Pharmaceutical Sciences, University of Graz, 8010 Graz, Austria;
| | - Rainer Stange
- Institute of Social Medicine, Epidemiology and Health Economics, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität and Humboldt-Universität zu Berlin, 10117 Berlin, Germany;
| | - Giuseppe Gancitano
- 1st “Tuscania” Paratrooper Regiment Carabinieri, Italian Ministry of Defence, 57127 Livorno, Italy;
| | - Peter Klein
- d.s.h. Statistical Services GmbH, 85296 Rohrbach, Germany;
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Efficacy of the commercial plant products acting against influenza-a review. FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES 2021; 7:238. [PMID: 34926706 PMCID: PMC8669228 DOI: 10.1186/s43094-021-00385-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2021] [Accepted: 11/29/2021] [Indexed: 11/10/2022] Open
Abstract
Background Influenza infection always poses a threat to human and animal health. Vaccines and antiviral drugs are recommended to deal with the situation. The drawback of these remedial agents made the scientist change their focus on an alternative therapy. The anti-influenza effects of plants have been extensively studied, and many pharmaceutical companies have prepared their products on this basis.
Main body The present review documents the successfully launched anti-influenza commercial products. In specific, it exposes the scientifically validated and evidence-based supporting inhibitory action of influenza and its strains. Conclusion This review highlighted the efficacy of the commercial products which effectively combat influenza. It provides a complementary strategy to deal with the worst-case scenario of flu. Meanwhile, to face the emerging strains, brand new products are in great necessity besides prevailing and available drugs.
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Caliskan UK, Karakus MM. Evaluation of botanicals as potential COVID-19 symptoms terminator. World J Gastroenterol 2021; 27:6551-6571. [PMID: 34754152 PMCID: PMC8554406 DOI: 10.3748/wjg.v27.i39.6551] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/01/2021] [Accepted: 09/16/2021] [Indexed: 02/06/2023] Open
Abstract
Information about the coronavirus disease 2019 (COVID-19) pandemic is still evolving since its appearance in December 2019 and has affected the whole world. Particularly, a search for an effective and safe treatment for COVID-19 continues. Botanical mixtures contain secondary metabolites (such as flavonoids, phenolics, alkaloids, essential oils etc.) with many therapeutic effects. In this study, the use of herbal treatments against COVID-19 was evaluated. Medical synthetic drugs focus mainly on respiratory symptoms, however herbal therapy with plant extracts may be useful to relieve overall symptoms of COVID-19 due to the variety of bioactive ingredients. Since COVID-19 is a virus that affects the respiratory tract, the antiviral effects of botanicals/plants against respiratory viruses have been examined through clinical studies. Data about COVID-19 patients revealed that the virus not only affects the respiratory system but different organs including the gastrointestinal (GI) system. As GI symptoms seriously affect quality of life, herbal options that might eliminate these problems were also evaluated. Finally, computer modeling studies of plants and their active compounds on COVID-19 were included. In summary, herbal therapies were identified as potential options for both antiviral effects and control of COVID-19 symptoms. Further data will be needed to enlighten all aspects of COVID-19 pathogenesis, before determining the effects of plants on severe acute respiratory syndrome coronavirus 2.
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Affiliation(s)
- Ufuk Koca Caliskan
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
| | - Methiye Mancak Karakus
- Department of Pharmacognosy and Pharmaceutical Botany, Gazi University, Ankara 06500, Turkey
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Ayrle H, Mevissen M, Bruckmaier RM, Wellnitz O, Kaske M, Bieber A, Vögtlin A, Fricker R, Walkenhorst M. Effects of an oral hydro-ethanolic purple coneflower extract on performance, clinical health and immune parameters in calves. Res Vet Sci 2021; 138:148-160. [PMID: 34144282 DOI: 10.1016/j.rvsc.2021.05.022] [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] [Received: 04/10/2020] [Revised: 04/13/2021] [Accepted: 05/25/2021] [Indexed: 11/28/2022]
Abstract
The objective of this randomized, placebo-controlled, double-blinded field trial was to investigate the effects of oral administration of purple coneflower (Echinacea purpurea L. (EP)) on performance, health and immune parameters in calves. Calves (n = 27) were enrolled to three groups (9 calves per group): 0.5 g EP/calf per day (ECL), 5 g EP/calf per day (ECH) or placebo. Calves were vaccinated with Bluetongue-Virus (BTV) serotype 4 vaccine to investigate EPs effects on seroconversion. Clinical and performance parameters, inter alia body weight, health and milk intake were recorded for 57 days. Blood samples were analyzed for BTV antibodies and IgG by ELISA, white and red blood cell counts by flow cytometry and mRNA abundance of various inflammatory markers in leukocytes (IL-1β, IL-8, tumor necrosis factor α (TNFα), cyclooxygenase 2 (Cox-2) and prostaglandin E synthase) was studied. The findings demonstrated no differences between groups regarding performance parameters. In all groups, calves suffered from diarrhea for a minimum of 2 days, but EP reduced the number of diarrhea days by 44% in ECL and increased the body temperature. Interestingly, ECL resulted in an increased number of respiratory disease days during the follow-up period. EP did not change blood cell and IgG counts, whereas eosinophil granulocytes were reduced in ECL. Decreased levels of hemoglobin and hematocrit were found in ECH. Prostaglandin E synthase levels in leukocytes were higher in ECL and ECH, whereas no differences were obtained for IL-1β, IL-8, TNFα and Cox-2. Due to the unexpected occurrence of BTV seropositive calves before the first vaccination, 13 calves were excluded from the evaluation on seroconversion and no statistical analyses could be performed regarding antibody production. BTV-4 antibodies were not produced in 4 placebo-calves, whereas 4 of 5 and 1 of 6 ECL- and ECH-calves produced antibodies. Further investigations are needed to draw final conclusions on mode of action and efficacy of EP in calves.
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Affiliation(s)
- Hannah Ayrle
- Department of Livestock Sciences, Research Institute of Organic Agriculture (FiBL), Ackerstrasse 113, Frick 5070, Switzerland; Division Veterinary Pharmacology & Toxicology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, Bern 3012, Switzerland.
| | - Meike Mevissen
- Division Veterinary Pharmacology & Toxicology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Länggassstrasse 124, Bern 3012, Switzerland.
| | - Rupert M Bruckmaier
- Veterinary Physiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, Bern 3012, Switzerland.
| | - Olga Wellnitz
- Veterinary Physiology, Department of Clinical Research and Veterinary Public Health, Vetsuisse Faculty, University of Bern, Bremgartenstrasse 109a, Bern 3012, Switzerland.
| | - Martin Kaske
- Swiss Calf Health Service, Department of Farm Animals, Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 260, Zurich 8057, Switzerland.
| | - Anna Bieber
- Department of Livestock Sciences, Research Institute of Organic Agriculture (FiBL), Ackerstrasse 113, Frick 5070, Switzerland.
| | - Andrea Vögtlin
- Institute of Virology and Immunology, Bern & Mittelhäusern, Switzerland and Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, Bern 3012, Switzerland.
| | - Raffael Fricker
- Institute of Virology and Immunology, Bern & Mittelhäusern, Switzerland and Department of Infectious Diseases and Pathobiology, Vetsuisse Faculty, University of Bern, Länggassstrasse 122, Bern 3012, Switzerland.
| | - Michael Walkenhorst
- Department of Livestock Sciences, Research Institute of Organic Agriculture (FiBL), Ackerstrasse 113, Frick 5070, Switzerland.
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Kontarov NA, Dolgova EI, Pogarskaya IV, Kontarova EO, Yuminova NV. Kinetics of Influenza A/BANGKOK/1/1979(Н3N2) Virus Thermal Inactivation in the Presence of Polyallylamine. MOSCOW UNIVERSITY BIOLOGICAL SCIENCES BULLETIN 2021; 76:34-38. [PMID: 34024957 PMCID: PMC8129961 DOI: 10.3103/s0096392521010028] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/18/2020] [Revised: 01/21/2021] [Accepted: 02/02/2021] [Indexed: 11/30/2022]
Abstract
Polyelectrolytes currently play an increasingly important role in antivirus therapy. Antiviral activity towards influenza virus, measles virus, herpes simplex virus type 1, and cytomegalovirus was demonstrated for the 6000 Da polyelectrolyte polyallylamine. A nontoxic polyallylamine concentration of 30 µM at which the compound retains its antiviral effect towards measles and influenza viruses but lacks any toxic effect on human cells was previously determined. It is well known, at the same time, that simultaneous virus exposure to physical environmental factors and chemical substances causes a more significant decrease in virus infectivity. Temperature is among these physical factors since thermal exposure causes virus inactivation. Analysis of virus thermal inactivation parameters is of high practical importance when it comes to the development of vaccines against influenza virus and to the study of how virus particles infectivity decreases on various surfaces. In this view, the study of kinetic and thermodynamical characteristics of influenza virus thermal inactivation in the presence of the antiviral preparation polyallylanime is of particular interest. The paper reports that thermal inactivation of influenza virus in the temperature range of 38-60°C in the presence of polyallylamine follows the first-order reaction kinetics. Thermodynamic parameters of influenza virus thermal inactivation evidence that influenza virus surface proteins are involved in the inactivation process as a result of their interaction with polyallylamine. The obtained results show that polyallylamine may be used to accelerate thermal inactivation of the influenza virus.
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Affiliation(s)
- N. A. Kontarov
- Sechenov First Moscow State Medical University (Sechenov University), Ministry of Healthcare of the Russian Federation, 119991 Moscow, Russia
- Mechnikov Research Institute of Vaccines and Sera, 115088 Moscow, Russia
| | - E. I. Dolgova
- Mechnikov Research Institute of Vaccines and Sera, 115088 Moscow, Russia
| | - I. V. Pogarskaya
- Mechnikov Research Institute of Vaccines and Sera, 115088 Moscow, Russia
| | - E. O. Kontarova
- Federal Research and Clinical Center, Federal Medical and Biological Agency, 115682 Moscow, Russia
| | - N. V. Yuminova
- Mechnikov Research Institute of Vaccines and Sera, 115088 Moscow, Russia
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Declerck K, Novo CP, Grielens L, Van Camp G, Suter A, Vanden Berghe W. Echinacea purpurea (L.) Moench treatment of monocytes promotes tonic interferon signaling, increased innate immunity gene expression and DNA repeat hypermethylated silencing of endogenous retroviral sequences. BMC Complement Med Ther 2021; 21:141. [PMID: 33980308 PMCID: PMC8114977 DOI: 10.1186/s12906-021-03310-5] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Accepted: 04/27/2021] [Indexed: 12/12/2022] Open
Abstract
Background Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections. Methods Transcriptome, epigenome and kinome profiling allowed a systems biology level characterisation of genomewide immunomodulatory effects of a standardized Echinacea purpurea (L.) Moench extract in THP1 monocytes. Results Gene expression and DNA methylation analysis revealed that Echinaforce® treatment triggers antiviral innate immunity pathways, involving tonic IFN signaling, activation of pattern recognition receptors, chemotaxis and immunometabolism. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi) genomic protective response against viral infections. Conclusions Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity through tonic IFN regulation of pattern recognition and chemokine gene expression and DNA repeat hypermethylated silencing of HERVs in monocytes. These results suggest that immunomodulation by Echinaforce® treatment holds promise to reduce symptoms and duration of infection episodes of common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2, with strongly impaired interferon (IFN) response and weak innate antiviral defense. Supplementary Information The online version contains supplementary material available at 10.1186/s12906-021-03310-5.
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Affiliation(s)
- Ken Declerck
- Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium
| | - Claudina Perez Novo
- Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium
| | - Lisa Grielens
- Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium
| | - Guy Van Camp
- Center of Medical Genetics, Department of Biomedical Sciences, University of Antwerp (UA) and University Hospital Antwerp (UZA), Antwerp, Belgium
| | | | - Wim Vanden Berghe
- Laboratory of Protein Chemistry, Proteomics and Epigenetic Signaling (PPES), Department of Biomedical Sciences, University of Antwerp (UA), Antwerp, Belgium.
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Optimization of callus cultures at Echinacea purpurea L. for the amount of caffeic acid derivatives. ELECTRON J BIOTECHN 2021. [DOI: 10.1016/j.ejbt.2021.02.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Ogal M, Johnston SL, Klein P, Schoop R. Echinacea reduces antibiotic usage in children through respiratory tract infection prevention: a randomized, blinded, controlled clinical trial. Eur J Med Res 2021; 26:33. [PMID: 33832544 PMCID: PMC8028575 DOI: 10.1186/s40001-021-00499-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Accepted: 03/12/2021] [Indexed: 12/17/2022] Open
Abstract
Background In children, up to 30% of viral respiratory tract infections (RTIs) develop into bacterial complications associated with pneumonia, sinusitis or otitis media to trigger a tremendous need for antibiotics. This study investigated the efficacy of Echinacea for the prevention of viral RTIs, for the prevention of secondary bacterial complications and for reducing rates of antibiotic prescriptions in children. Methods Echinaforce® Junior tablets [400 mg freshly harvested Echinacea purpurea alcoholic extract] or vitamin C [50 mg] as control were given three times daily for prevention to children 4–12 years. Two × 2 months of prevention were separated by a 1-week treatment break. Parents assessed respiratory symptoms in children via e-diaries and collected nasopharyngeal secretions for screening of respiratory pathogens (Allplex® RT-PCR). Results Overall, 429 cold days occurred in NITT = 103 children with Echinacea in comparison to 602 days in NITT = 98 children with vitamin C (p < 0.001, Chi-square test). Echinacea prevented 32.5% of RTI episodes resulting in an odds ratio of OR = 0.52 [95% CI 0.30–0.91, p = 0.021]. Six children (5.8%) with Echinacea and 15 children (15.3%) with vitamin C required 6 and 24 courses of antibiotic treatment, respectively (reduction of 76.3%, p < 0.001). A total of 45 and 216 days of antibiotic therapy were reported in the two groups, respectively (reduction of 80.2% (p < 0.001). Eleven and 30 events of RTI complications (e.g., otitis media, sinusitis or pneumonia) occurred with Echinacea and vitamin C, respectively (p = 0.0030). Echinacea significantly prevented influenza (3 vs. 20 detections, p = 0.012) and enveloped virus infections (29 vs. 47 detections, p = 0.0038). Finally, 76 adverse events occurred with Echinacea and 105 events with vitamin C (p = 0.016), only three events were reported possibly related with Echinacea. Conclusions Our results support the use of Echinacea for the prevention of RTIs and reduction of associated antibiotic usage in children. Trial registration clinicaltrials.gov, NCT02971384, 23th Nov 2016. Supplementary Information The online version contains supplementary material available at 10.1186/s40001-021-00499-6.
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Affiliation(s)
| | | | - Peter Klein
- d.s.h. Statistical Services GmbH, Rohrbach, Germany
| | - Roland Schoop
- A Vogel AG, Grünaustrasse 4, 9325, Roggwil, TG, Switzerland.
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Fasogbon BM, Ademuyiwa OH, Bamidele OP, Wahab IE, Ola-Adedoyin AT, Alakija O. Positive Therapeutic Role of Selected Foods and Plant on Ailments with a Trend Towards COVID-19: A Review. Prev Nutr Food Sci 2021; 26:1-11. [PMID: 33859954 PMCID: PMC8027051 DOI: 10.3746/pnf.2021.26.1.1] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2020] [Revised: 11/19/2020] [Accepted: 12/17/2020] [Indexed: 12/14/2022] Open
Abstract
Each day since December 2019, increasing numbers of cases of the novel coronavirus 2019 (COVID-19) infection are being detected as it spreads throughout all continents of the world except Antarctica. The virus is transmitted through contact with an infected environment or person, and the symptoms include fever, cough, and difficulty breathing. The healthcare systems of many countries are overwhelmed due to limited therapeutic options and the absence of an approved vaccine. Due to its poor healthcare systems, Africa may be the worst hit continent if other therapeutic alternatives are not explored. This review explores the source and origin of the COVID-19 infection, and alternative therapeutic options derived from available and cheap medicinal foods and plants that have been shown to alleviate similar infections. The results demonstrate the inhibitory activities of selected food crops and plants against human viruses similar to the novel COVID-19.
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Affiliation(s)
| | | | | | | | | | - Oluwabukunmi Alakija
- Department of Food Science and Technology, Obafemi Awolowo University, Ile-Ife 220282, Nigeria
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Natural Products from Medicinal Plants with Anti-Human Coronavirus Activities. Molecules 2021; 26:molecules26061754. [PMID: 33800977 PMCID: PMC8003969 DOI: 10.3390/molecules26061754] [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: 02/23/2021] [Revised: 03/16/2021] [Accepted: 03/18/2021] [Indexed: 01/08/2023] Open
Abstract
Since the emergence of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) first reported in Wuhan, China in December 2019, COVID-19 has spread to all the continents at an unprecedented pace. This pandemic has caused not only hundreds of thousands of mortalities but also a huge economic setback throughout the world. Therefore, the scientific communities around the world have focused on finding antiviral therapeutic agents to either fight or halt the spread of SARS-CoV-2. Since certain medicinal plants and herbal formulae have proved to be effective in treatment of similar viral infections such as those caused by SARS and Ebola, scientists have paid more attention to natural products for effective treatment of this devastating pandemic. This review summarizes studies and ethnobotanical information on plants and their constituents used for treatment of infections caused by viruses related to the coronavirus family. Herein, we provide a critical analysis of previous reports and how to exploit published data for the discovery of novel therapeutic leads to fight against COVID-19.
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Nagoor Meeran M, Javed H, Sharma C, Goyal SN, Kumar S, Jha NK, Ojha S. Can Echinacea be a potential candidate to target immunity, inflammation, and infection - The trinity of coronavirus disease 2019. Heliyon 2021; 7:e05990. [PMID: 33585706 PMCID: PMC7870107 DOI: 10.1016/j.heliyon.2021.e05990] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2020] [Revised: 12/18/2020] [Accepted: 01/11/2021] [Indexed: 02/06/2023] Open
Abstract
Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing public health emergency. The pathogenesis and complications advanced with infection mainly involve immune-inflammatory cascade. Therefore, the therapeutic strategy relies on immune modulation, reducing infectivity and inflammation. Given the interplay of infection and immune-inflammatory axis, the natural products received attention for preventive and therapeutic usage in COVID-19 due to their potent antiviral and anti-immunomodulatory activities. Recently, Echinacea preparations, particularly E. purpurea, have been suggested to be an important antiviral agent to be useful in COVID-19 by modulating virus entry, internalization and replication. In principle, the immune response and the resultant inflammatory process are important for the elimination of the infection, but may have a significant impact on SARS-CoV-2 pathogenesis and may play a role in the clinical spectrum of COVID-19. Considering the pharmacological effects, therapeutic potential, and molecular mechanisms of Echinacea, we hypothesize that it could be a reasonably possible candidate for targeting infection, immunity, and inflammation in COVID-19 with recent recognition of cannabinoid-2 (CB2) receptors and peroxisome proliferator-activated receptor gamma (PPARγ) mediated mechanisms of bioactive components that make them notable immunomodulatory, anti-inflammatory and antiviral agent. The plausible reason for our hypothesis is that the presence of numerous bioactive agents in different parts of plants that may synergistically exert polypharmacological actions in regulating immune-inflammatory axis in COVID-19. Our proposition is to scientifically contemplate the therapeutic perspective and prospect of Echinacea on infection, immunity, and inflammation with a potential in COVID-19 to limit the severity and progression of the disease. Based on the clinical usage for respiratory infections, and relative safety in humans, further studies for the evidence-based approach to COVID-19 are needed. We do hope that Echinacea could be a candidate agent for immunomodulation in the prevention and treatment of COVID-19.
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Affiliation(s)
- M.F. Nagoor Meeran
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box - 17666, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Hayate Javed
- Department of Anatomy, College of Medicine and Health Sciences, PO Box - 17666, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Charu Sharma
- Department of Internal Medicine, College of Medicine and Health Sciences, PO Box - 17666, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Sameer N. Goyal
- Shri Vile Parle Kelvani Mandal's Institute of Pharmacy, Dhule 424001, Maharashtra, India
| | - Sanjay Kumar
- Division of Hematology/Nephrology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
- Department of Life Sciences, School of Basic Science and Research, Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201310, India
| | - Niraj Kumar Jha
- Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Knowledge Park III, Greater Noida, Uttar Pradesh 201310, India
| | - Shreesh Ojha
- Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, PO Box - 17666, United Arab Emirates University, Al Ain, United Arab Emirates
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Brendler T, Al‐Harrasi A, Bauer R, Gafner S, Hardy ML, Heinrich M, Hosseinzadeh H, Izzo AA, Michaelis M, Nassiri‐Asl M, Panossian A, Wasser SP, Williamson EM. Botanical drugs and supplements affecting the immune response in the time of
COVID
‐19: Implications for research and clinical practice. Phytother Res 2020; 35:3013-3031. [DOI: 10.1002/ptr.7008] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 12/16/2020] [Accepted: 12/16/2020] [Indexed: 12/14/2022]
Affiliation(s)
- Thomas Brendler
- Department of Botany and Plant Biotechnology University of Johannesburg Johannesburg South Africa
- Plantaphile Collingswood New Jersey USA
| | - Ahmed Al‐Harrasi
- Natural and Medical Sciences Research Centre University of Nizwa Nizwa Oman
| | - Rudolf Bauer
- Institute of Pharmaceutical Sciences, Department of Pharmacognosy University of Graz Graz Austria
| | | | - Mary L. Hardy
- Association of Integrative and Holistic Medicine San Diego California USA
| | - Michael Heinrich
- Research Group ‘Pharmacognosy and Phytotherapy’, UCL School of Pharmacy University of London London UK
- Graduate Institute of Integrated Medicine, College of Chinese Medicine China Medical University Taichung Taiwan
| | - Hossein Hosseinzadeh
- Pharmaceutical Research Center, Pharmaceutical Technology Institute Mashhad University of Medical Sciences Mashhad Iran
- Department of Pharmacodynamics and Toxicology, School of Pharmacy Mashhad University of Medical Sciences Mashhad Iran
| | - Angelo A. Izzo
- Department of Pharmacy, School of Medicine University of Naples Federico II Naples Italy
| | - Martin Michaelis
- Industrial Biotechnology Centre and School of Biosciences University of Kent Canterbury UK
| | - Marjan Nassiri‐Asl
- Department of Pharmacology, School of Medicine Shahid Beheshti University of Medical Sciences Tehran Iran
- Neurobiology Research Center Shahid Beheshti University of Medical Sciences Tehran Iran
| | | | - Solomon P. Wasser
- Institute of Evolution and Department of Evolutionary and Environmental Biology University of Haifa Haifa Israel
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Weishaupt R, Bächler A, Feldhaus S, Lang G, Klein P, Schoop R. Safety and Dose-Dependent Effects of Echinacea for the Treatment of Acute Cold Episodes in Children: A Multicenter, Randomized, Open-Label Clinical Trial. CHILDREN (BASEL, SWITZERLAND) 2020; 7:E292. [PMID: 33333722 PMCID: PMC7765151 DOI: 10.3390/children7120292] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 11/16/2022]
Abstract
Background: Due to the frequency and severity of cold symptoms in children, and the risk of associated complications, effective treatments are urgently needed. Here we evaluated the safety profile and treatment benefits of Echinacea in children with acute cold and flu symptoms. Methods: A total of 79 children (4-12 years) were randomized to a treatment regimen of three or five times daily Echinaforce Junior tablets (total of 1200 or 2000 mg Echinacea extract, EFJ) for the prospective treatment of upcoming cold and flu episodes at first signs. Parents recorded respiratory symptoms daily during episodes in their child and physicians and parents subjectively rated tolerability. Results: EFJ was used to treat 130 cold episodes in 68 children and was very well tolerated by more than 96% positive physician's ratings. EFJ-treated cold episodes lasted 7.5 days on average, with nine out of 10 episodes being fully resolved after 10 days. Five EFJ tablets daily reduced the average episode duration by up to 1.7 days (p < 0.02) in comparison to three EFJ tablets daily regimen. Effective symptom resolution finally contributed to a low antibiotic prescription rate in this study of 4.6%. Conclusions: EFJ tablets present a valuable option for the treatment of acute cold episodes in children showing a wide safety margin and increased therapeutic benefits at five tablets daily.
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Affiliation(s)
| | - Arnold Bächler
- Pediatric Practice, Notkerstrasse 14, 9000 St. Gallen, Switzerland;
| | - Simon Feldhaus
- Paramed Ambulatory, Paramed AG, Haldenstrasse 1, 6340 Baar, Switzerland;
| | - Günter Lang
- General Practice, Burgstrasse 112, 4125 Riehen, Switzerland;
| | - Peter Klein
- d.s.h. Statistical Services GmbH, Turmbergweg 5, 85296 Rohrbach, Germany;
| | - Roland Schoop
- A. Vogel AG, Grünaustrasse 4, 9325 Roggwil, Switzerland;
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Lai Y, Zhang Q, Long H, Han T, Li G, Zhan S, Li Y, Li Z, Jiang Y, Liu X. Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation. Front Pharmacol 2020; 11:607027. [PMID: 33362562 PMCID: PMC7759152 DOI: 10.3389/fphar.2020.607027] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 11/09/2020] [Indexed: 12/25/2022] Open
Abstract
Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear. Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology. Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology. Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05). Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.
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Affiliation(s)
- Yanni Lai
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Qiong Zhang
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Haishan Long
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Tiantian Han
- The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Geng Li
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Shaofeng Zhan
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yiwei Li
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Zonghui Li
- Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yong Jiang
- Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine, Shenzhen, China
| | - Xiaohong Liu
- The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China
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Zitterl-Eglseer K, Marschik T. Antiviral Medicinal Plants of Veterinary Importance: A Literature Review. PLANTA MEDICA 2020; 86:1058-1072. [PMID: 32777833 DOI: 10.1055/a-1224-6115] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families-Herpesviridae, Orthomyxoviridae, Paramyxoviridae, Parvoviridae, Poxviridae, Nimaviridae, Coronaviridae, Reoviridae, and Rhabdoviridae-that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.
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Affiliation(s)
- Karin Zitterl-Eglseer
- Institute of Animal Nutrition and Functional Plant Compounds, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
| | - Tatiana Marschik
- Unit of Veterinary Public Health and Epidemiology, Department for Farm Animals and Veterinary Public Health, University of Veterinary Medicine, Vienna, Austria
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Silveira D, Prieto-Garcia JM, Boylan F, Estrada O, Fonseca-Bazzo YM, Jamal CM, Magalhães PO, Pereira EO, Tomczyk M, Heinrich M. COVID-19: Is There Evidence for the Use of Herbal Medicines as Adjuvant Symptomatic Therapy? Front Pharmacol 2020; 11:581840. [PMID: 33071794 PMCID: PMC7542597 DOI: 10.3389/fphar.2020.581840] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/28/2020] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Current recommendations for the self-management of SARS-Cov-2 disease (COVID-19) include self-isolation, rest, hydration, and the use of NSAID in case of high fever only. It is expected that many patients will add other symptomatic/adjuvant treatments, such as herbal medicines. AIMS To provide a benefits/risks assessment of selected herbal medicines traditionally indicated for "respiratory diseases" within the current frame of the COVID-19 pandemic as an adjuvant treatment. METHOD The plant selection was primarily based on species listed by the WHO and EMA, but some other herbal remedies were considered due to their widespread use in respiratory conditions. Preclinical and clinical data on their efficacy and safety were collected from authoritative sources. The target population were adults with early and mild flu symptoms without underlying conditions. These were evaluated according to a modified PrOACT-URL method with paracetamol, ibuprofen, and codeine as reference drugs. The benefits/risks balance of the treatments was classified as positive, promising, negative, and unknown. RESULTS A total of 39 herbal medicines were identified as very likely to appeal to the COVID-19 patient. According to our method, the benefits/risks assessment of the herbal medicines was found to be positive in 5 cases (Althaea officinalis, Commiphora molmol, Glycyrrhiza glabra, Hedera helix, and Sambucus nigra), promising in 12 cases (Allium sativum, Andrographis paniculata, Echinacea angustifolia, Echinacea purpurea, Eucalyptus globulus essential oil, Justicia pectoralis, Magnolia officinalis, Mikania glomerata, Pelargonium sidoides, Pimpinella anisum, Salix sp, Zingiber officinale), and unknown for the rest. On the same grounds, only ibuprofen resulted promising, but we could not find compelling evidence to endorse the use of paracetamol and/or codeine. CONCLUSIONS Our work suggests that several herbal medicines have safety margins superior to those of reference drugs and enough levels of evidence to start a clinical discussion about their potential use as adjuvants in the treatment of early/mild common flu in otherwise healthy adults within the context of COVID-19. While these herbal medicines will not cure or prevent the flu, they may both improve general patient well-being and offer them an opportunity to personalize the therapeutic approaches.
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Affiliation(s)
- Dâmaris Silveira
- Department of Pharmacy, Faculty of Health Sciences, University of Brasilia, Brasilia, Brazil
| | - Jose Maria Prieto-Garcia
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, United Kingdom
| | - Fabio Boylan
- School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland
| | - Omar Estrada
- Biophysics and Biochemistry Center, Venezuelan Institute of Scientific Research, Caracas, Venezuela
| | | | | | | | - Edson Oliveira Pereira
- Department of Pharmacy, Faculty of Health Sciences, University of Brasilia, Brasilia, Brazil
| | - Michal Tomczyk
- Faculty of Pharmacy, Medical University of Bialystok, Bialystok, Poland
| | - Michael Heinrich
- Pharmacognosy and Phytotherapy, School of Pharmacy, University College of London, London, United Kingdom
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Signer J, Jonsdottir HR, Albrich WC, Strasser M, Züst R, Ryter S, Ackermann-Gäumann R, Lenz N, Siegrist D, Suter A, Schoop R, Engler OB. In vitro virucidal activity of Echinaforce®, an Echinacea purpurea preparation, against coronaviruses, including common cold coronavirus 229E and SARS-CoV-2. Virol J 2020; 17:136. [PMID: 32907596 PMCID: PMC7479405 DOI: 10.1186/s12985-020-01401-2] [Citation(s) in RCA: 46] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2020] [Accepted: 08/16/2020] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Coronaviruses (CoVs) were long thought to only cause mild respiratory and gastrointestinal symptoms in humans but outbreaks of Middle East Respiratory Syndrome (MERS)-CoV, Severe Acute Respiratory Syndrome (SARS)-CoV-1, and the recently identified SARS-CoV-2 have cemented their zoonotic potential and their capacity to cause serious morbidity and mortality, with case fatality rates ranging from 4 to 35%. Currently, no specific prophylaxis or treatment is available for CoV infections. Therefore we investigated the virucidal and antiviral potential of Echinacea purpurea (Echinaforce®) against human coronavirus (HCoV) 229E, highly pathogenic MERS- and SARS-CoVs, as well as the newly identified SARS-CoV-2, in vitro. METHODS To evaluate the antiviral potential of the extract, we pre-treated virus particles and cells and evaluated remaining infectivity by limited dilution. Furthermore, we exposed cells to the extract after infection to further evaluate its potential as a prophylaxis and treatment against coronaviruses. We also determined the protective effect of Echinaforce® in re-constituted nasal epithelium. RESULTS In the current study, we found that HCoV-229E was irreversibly inactivated when exposed to Echinaforce® at 3.2 μg/ml IC50. Pre-treatment of cell lines, however, did not inhibit infection with HCoV-229E and post-infection treatment had only a marginal effect on virus propagation at 50 μg/ml. However, we did observe a protective effect in an organotypic respiratory cell culture system by exposing pre-treated respiratory epithelium to droplets of HCoV-229E, imitating a natural infection. The observed virucidal activity of Echinaforce® was not restricted to common cold coronaviruses, as both SARS-CoV-1 and MERS-CoVs were inactivated at comparable concentrations. Finally, the causative agent of COVID-19, SARS-CoV-2 was also inactivated upon treatment with 50μg/ml Echinaforce®. CONCLUSIONS These results show that Echinaforce® is virucidal against HCoV-229E, upon direct contact and in an organotypic cell culture model. Furthermore, MERS-CoV and both SARS-CoV-1 and SARS-CoV-2 were inactivated at similar concentrations of the extract. Therefore we hypothesize that Echinacea purpurea preparations, such as Echinaforce®, could be effective as prophylactic treatment for all CoVs due to their structural similarities.
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Affiliation(s)
| | | | - Werner C Albrich
- Division of Infectious Diseases and Hospital Epidemiology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - Marc Strasser
- SPIEZ LABORATORY, Austrasse, 3700, Spiez, Switzerland
| | - Roland Züst
- SPIEZ LABORATORY, Austrasse, 3700, Spiez, Switzerland
| | - Sarah Ryter
- SPIEZ LABORATORY, Austrasse, 3700, Spiez, Switzerland
| | | | - Nicole Lenz
- SPIEZ LABORATORY, Austrasse, 3700, Spiez, Switzerland
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Shahrajabian MH, Sun W, Cheng Q. Traditional Herbal Medicine for the Prevention and Treatment of Cold and Flu in the Autumn of 2020, Overlapped With COVID-19. Nat Prod Commun 2020. [DOI: 10.1177/1934578x20951431] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
Many herbs and plants included in several traditional systems have promising bioactive compounds for modern drug therapy. The second round of COVID-19 cases will be accompanied by the spread of seasonal influenza in the fall. The combination of the influenza season and the second wave of COVID-19 may lead to more confusion and put more pressure on public health systems. A literature survey was accomplished using multiple databases including PubMed, Science Direct, ISI web of knowledge, and Google Scholar. The most important antiviral herbs for cold and flu are Thymus vulgaris, honeysuckle flowers, Andrographis, yarrow, peppermint leaf and oil, and Calendula. The most important expectorant herbs for flu and cold are tulsi, snake root, licorice root, clove, slippery elm root, marshmallow osha root, and sage leaf. Immunostimulant herbs for these 2 diseases are Echinacea root, Eucalyptus, garlic, ginseng, marshmallow, slippery elm, Isatisroot, Usnea lichen, myrrh resin, and ginger root. In this mini-review, we mention the key role of some of the most important herbal plants and prescriptions against influenza and cold on the basis of traditional Asian medicine.
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Affiliation(s)
| | - Wenli Sun
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
| | - Qi Cheng
- Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, China
- College of Life Sciences, Hebei Agricultural University, Baoding, Hebei, China; Global Alliance of HeBAU-CLS&HeQiS for BioAl-Manufacturing, Baoding, Hebei, China
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AbouAitah K, Swiderska-Sroda A, Kandeil A, Salman AMM, Wojnarowicz J, Ali MA, Opalinska A, Gierlotka S, Ciach T, Lojkowski W. Virucidal Action Against Avian Influenza H5N1 Virus and Immunomodulatory Effects of Nanoformulations Consisting of Mesoporous Silica Nanoparticles Loaded with Natural Prodrugs. Int J Nanomedicine 2020; 15:5181-5202. [PMID: 32801685 PMCID: PMC7398888 DOI: 10.2147/ijn.s247692] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 06/02/2020] [Indexed: 12/12/2022] Open
Abstract
Background Combating infectious diseases caused by influenza virus is a major challenge due to its resistance to available drugs and vaccines, side effects, and cost of treatment. Nanomedicines are being developed to allow targeted delivery of drugs to attack specific cells or viruses. Materials and Methods In this study, mesoporous silica nanoparticles (MSNs) functionalized with amino groups and loaded with natural prodrugs of shikimic acid (SH), quercetin (QR) or both were explored as a novel antiviral nanoformulations targeting the highly pathogenic avian influenza H5N1 virus. Also, the immunomodulatory effects were investigated in vitro tests and anti-inflammatory activity was determined in vivo using the acute carrageenan-induced paw edema rat model. Results Prodrugs alone or the MSNs displayed weaker antiviral effects as evidenced by virus titers and plaque formation compared to nanoformulations. The MSNs-NH2-SH and MSNs-NH2-SH-QR2 nanoformulations displayed a strong virucidal by inactivating the H5N1 virus. They induced also strong immunomodulatory effects: they inhibited cytokines (TNF-α, IL-1β) and nitric oxide production by approximately 50% for MSNs-NH2-SH-QR2 (containing both SH and QR). Remarkable anti-inflammatory effects were observed during in vivo tests in an acute carrageenan-induced rat model. Conclusion Our preliminary findings show the potential of nanotechnology for the application of natural prodrug substances to produce a novel safe, effective, and affordable antiviral drug.
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Affiliation(s)
- Khaled AbouAitah
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland.,Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), P.C.12622, Dokki, Giza, Egypt
| | - Anna Swiderska-Sroda
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
| | - Ahmed Kandeil
- Center of Scientific Excellence for Influenza Viruses, Water Pollution Research Department, Environmental Research Division, National Research Centre (NRC) P.C.12622, Dokki, Giza, Egypt
| | - Asmaa M M Salman
- Medicinal and Pharmaceutical Chemistry Department, Pharmaceutical and Drug Industries Research Division, National Research Centre (NRC), P.C. 12622, Dokki, Giza, Egypt
| | - Jacek Wojnarowicz
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
| | - Mohamed A Ali
- Center of Scientific Excellence for Influenza Viruses, Water Pollution Research Department, Environmental Research Division, National Research Centre (NRC) P.C.12622, Dokki, Giza, Egypt
| | - Agnieszka Opalinska
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
| | - Stanislaw Gierlotka
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
| | - Tomasz Ciach
- Biomedical Engineering Laboratory, Faculty of Chemical and Process Engineering, Warsaw University of Technology, Warsaw, Poland
| | - Witold Lojkowski
- Laboratory of Nanostructures and Nanomedicine, Institute of High Pressure Physics, Polish Academy of Sciences, Warsaw, Poland
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Hensel A, Bauer R, Heinrich M, Spiegler V, Kayser O, Hempel G, Kraft K. Challenges at the Time of COVID-19: Opportunities and Innovations in Antivirals from Nature. PLANTA MEDICA 2020; 86:659-664. [PMID: 32434254 PMCID: PMC7356065 DOI: 10.1055/a-1177-4396] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/20/2020] [Revised: 05/05/2020] [Accepted: 05/13/2020] [Indexed: 05/03/2023]
Abstract
As viral infections are an increasing threat to human societies, the need for new therapeutic strategies is becoming even more obvious. As no vaccine is available for COVID-19, the development of directly acting antiviral agents and preventive strategies have to be considered. Nature provides a huge reservoir of anti-infectious compounds, from which we can deduce innovative ideas, therapies, and products. Anti-adhesive natural products interact with the receptor-mediated recognition and early interaction of viruses with the host cells, leading to a reduced internalisation of the virus and reduced infections (e.g., procyanidin-B-2-di-O-gallate against influenza and herpes virus). Lignans like podophyllotoxin and bicyclol show strong antiviral activities against different viruses, and essential oils can directly interact with viral membranes and reduce the host's inflammatory responses (e.g., 1,8-cineol). Echinacea extracts stimulate the immune system, and bioavailable alkamides are key players by interacting with immunomodulating cannabinoid receptors. COVID-19 and SARS-CoV-2 infections have, in part, successfully been treated in China by preparations from traditional Chinese medicine and, while it is too early to draw conclusions, some promising data are available. There is huge potential, but intensified research is needed to develop evidence-based medicines with a clearly defined chemical profile. Intensified research and development, and therefore funding, are needed for exploiting nature's reservoir against viral infections. Combined action for basic research, chemistry, pharmacognosy, virology, and clinical studies, but also supply chain, sustainable sourcing, and economic aspects have to be considered. This review calls for intensified innovative science on natural products for the patients and for a healthier world!
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Affiliation(s)
- Andreas Hensel
- Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
| | - Rudolf Bauer
- Institute of Pharmaceutical Sciences, University of Graz, Graz, Austria
| | - Michael Heinrich
- Pharmacognosy and Phytotherapy, UCL School of Pharmacy, London, UK
| | - Verena Spiegler
- Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, Germany
| | - Oliver Kayser
- Technical Biochemistry, TU Dortmund University, Dortmund, Germany
| | - Georg Hempel
- Institute of Pharmaceutical and Medical Chemistry, Clinical Pharmacy, University of Münster, Münster, Germany
| | - Karin Kraft
- University Medicine Rostock, Chair of Complementary Medicine, Rostock, Germany
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