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Anti-Influenza Virus Effects of Elderberry Juice and Its Fractions
Abstract
Elderberry (Sambucus nigra L.) has traditionally been used for treating influenza and colds. We evaluated the antiviral effect of concentrated juice of elderberry (CJ-E) on the human influenza A virus (IFV). CJ-E had a relatively strong effect on IFV-infected mice, although its anti-IFV activity was weak in a cell culture system. The in vivo anti-IFV activities of the fractions were determined after separating CJ-E by ultrafiltration and anion-exchange chromatography. Oral administration of the high-molecular-weight fractions of CJ-E to IFV-infected mice suppressed viral replication in the bronchoalveolar lavage fluids (BALFs), and increased the level of the IFV-specific neutralizing antibody in the serum, as well as the level of secretory IgA in BALFs and feces. Fr. II from high-molecular-weight fraction HM, which contained acidic polysaccharides, showed relatively strong defense against IFV infection. We conclude that CJ-E had a beneficial effect by the stimulating immune response and preventing viral infection.
... In folk medicine, elderberry is used in the treatment of many diseases and ailments thanks to its antioxidant, anticarcinogenic, immune stimulating, antiallergic, antiviral, antibacterial [12,18,28], antidepressant and hypoglycemic properties, as well as the ability to reduce body fat and blood lipid concentrations [12]. Elderberry flowers can be used both for prevention and therapy of a wide array of diseases due to immunomodulatory [42,43], antiinflammatory [44][45][46], antioxidant [28,[47][48][49][50], antimicrobial [12,51,52] and antiviral [41,53,54] activities. In vitro experiments demonstrated the ability of elderberry extract or its constituents to suppress proliferation and viability of various cancer cell lines [25,33,[55][56][57][58] and to prevent angiogenesis in tumor [55,59]. ...
... It is widely accepted that elderberries' curative capacity is due to the presence of high amounts of polyphenolic compounds, primarily flavonols, phenolic acids and anthocyanins. The presence of polyphenols, which assure the defense of plants against pathogenic microorganisms, can also explain the ability of black elderberry to suppress the activity of viruses [41,53,54] and bacteria in the body [12,51,52] and in food items [19]. ...
... The protective effect of elderberry flavonoids and pectins against the influenza virus is probably mediated by stimulating the immune system of the host through enhancing the production of inflammatory cytokines such as interleukins IL-6, IL-8 and tumor necrosis factor (TNF) [54,68,83] and the subsequent stimulation of macrophages [84]. Therefore, elderberry antioxidants could protect the target tissues via reduction of oxidative stress and the downregulation of regulators of inflammatory processes. ...
The present review summarizes the current knowledge concerning provenance, properties, physiological and therapeutic actions of elderberry and the bioactive molecules present in the plant, with emphasis on their action on female reproduction. Elderberry or black elder (Sambucus nigra L.) attracts attention due to its easy cultivation and high availability of bioactive compounds. Most of the available data concerning black elder’s therapeutic action are focused on its effects such as activation of immune processes and anti-inflammatory processes (cytokine production, etc.) and regulation of hormones and their receptors in cancer cells. The effects of elderberry on reproduction have been poorly investigated so far. Nevertheless, conducted studies so far demonstrate the stimulatory influence of black elder extract and its constituents, such as rutin, anthocyanins and agglutinins, on the viability and steroidogenesis of healthy ovarian cells as well as their ability to promote apoptosis and reduce the viability and proliferation of ovarian cancer cells. Furthermore, the action of black elder extract and its constituent biomolecules, such as anthocyanins and lectins, on embryogenesis and the embryonal estradiol-estradiol receptor system have also been reported. The available information, despite limitations, suggest the applicability of black elder constituents for improvement of reproductive processes in animal biotechnology, animal production and assisted reproduction, as well as for prevention and treatment of reproductive disorders (including cancer) in veterinary and human medicine.
... The high polyphenol content-especially anthocyanins-is a main contributor to the antioxidant activity of elderberry fruits, jams, and syrups [29,30]. Elderberry wine also showed high antioxidant activity, dependent on the quantities of sugar and water used in its production and the degree of fineness of the fruit [31]. ...
... A study based on Direct Binding Assay and DART TOF-MS analysis identified and characterized two anti-influenza flavonoids in an elderberry fruit extract (5,7-dihydroxy-4oxo-2-(3,4,5-trihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate and 5,7,3 ,4 -tetra-O-methylquercetin) as the main determinant of antiviral activities [42]. These compounds directly bind to the Influenza A virus subtype H1N1 particles, preventing them from entering host cells and effectively reducing infection in vitro [30,42]. In addition, the antiviral effects of elderberry extracts include also inhibiting viral proliferation and hemagglutination, as well as stimulating the immune system by increasing the production of cytokines by monocytes [41,43,44]. ...
Sambucus is a cosmopolitan plant genus that has been used for centuries for its medicinal properties and nutritional value. Sambucus nigra, the most studied species, contains a wide range of bioactive compounds that have been linked to various health benefits. Moreover, the fruit of the elderberry is a rich source of phytochemicals and is used to make a variety of food products. In this review, after an introduction of the species, we outline the main points for its cultivation and production. We then illustrate the major phytochemical components and related beneficial properties, such as antioxidant, antimicrobial, and pharmaceutical activities. We also provide insights into genetic variability, functional diversity, and some evolutionary relationships that were evaluated with DNA-based techniques. We discuss that despite its long history of use and potential benefits, Sambucus nigra has received relatively little attention in terms of horticulture, breeding, and molecular genetics, while studies on its biochemical composition and health benefits are well developed. Further research is also needed to better understand the pre-harvest and post-harvest factors that influence plant growth and production, as well as to explore new applications and industrial uses of this underutilized species.
... In fact, fruit berries have a special thought in human diet over the last decades in international health and wellbeing market thanks to their antioxidant, anticancer and anti-aging effects [28]. Several works were published reporting the potential health benefits of berries, namely anti-proliferative [29] and anti-inflammatory [30] activities, immune response [31] and prevention of viral infections and coronary vascular diseases [32]. The highlights from various studies on human health effects by consuming different berries are resumed in Table 2. ...
... In addition, elderberry has been reported to stimulate the immune system by enhancing the production of cytokines by monocytes [30]. Kinoshita et al. [31] investigated the effects of concentrated elderberry (Sambucus nigra L.) juice (CJ-E) and its fractions on IFV (influenza A virus) replication and the specific defense functions involved in the human IFV infection. The results showed that CJ-E had a beneficial effect by stimulating immune response and preventing viral infection. ...
Berries are widely consumed in different forms (fruits, juice, jams, dried and candied berries), and contain high amounts of phenolic compounds providing several health benefits. Although its consumption continues to grow, most of these fruits are fragile and perishable due to their high moisture content. In this context, the scientific communities are interested in preserving these fruits and extending their shelf life while maintaining their benefits. In addition, the development of functional foods is given special attention by the food industry since the natural ingredients extracted or the whole fruit can be incorporated into different foods and improve their quality. This review goal is to discuss the most abundant bioactive compounds in various berries and their potential health benefits, as well as the different physical technologies its preservation, with a focus on ionizing radiation technology to extend berries’ shelf life and increase its bioactivity for potential enrichment in functional foods.
... In other studies, Krawitz et al. [42] tested standardized elderberry liquid extract against influenza A and B with 30% and 25% foci size reductions, respectively. Kinoshita et al. [43] showed weak anti-influenza activity of elderberry juice in vitro when the extract was administrated to cells during and after infection with influenza A virus, A/NWS/33. However, they observed prevention of the viral infection after oral administration of the high-molecular-weight fraction of concentrated elderberry juice to infected mice [43]. ...
... Kinoshita et al. [43] showed weak anti-influenza activity of elderberry juice in vitro when the extract was administrated to cells during and after infection with influenza A virus, A/NWS/33. However, they observed prevention of the viral infection after oral administration of the high-molecular-weight fraction of concentrated elderberry juice to infected mice [43]. In contrast, our results indicated that the EAM showed lower antiviral activity against A/H1N1 with higher toxicity; hence, we concluded that the EAM-ESN blend probably owes its toxicity to the EAM component. ...
Viral and bacterial diseases are among the greatest concerns of humankind since ancient times. Despite tremendous pharmacological progress, there is still a need to search for new drugs that could treat or support the healing processes. A rich source of bioactive compounds with antiviral potency include plants such as black chokeberry and elderberry. The aim of this study was to assess the in vitro antiviral ability of an originally designed double-standardized blend of extracts from Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L. (EAM-ESN) or separated extracts of A. melanocarpa (EAM) or S. nigra (ESN) against four human respiratory tract viruses: influenza A virus (A/H1N1), betacoronavirus-1 (HCoV-OC43) belonging to the same β-coronaviruses as the current pandemic SARS-CoV-2, human herpesvirus type 1 (HHV-1), and human adenovirus type 5 (HAdV-5). Antiviral assays (AVAs) were used to evaluate the antiviral activity of the plant extracts in a cell-present environment with extracts tested before, simultaneously, or after viral infection. The virus replication was assessed using the CPE scale or luminescent assay. The EAM-ESN blend strongly inhibited A/H1N1 replication as well as HCoV-OC43, while having a limited effect against HHV-1 and HAdV-5. This activity likely depends mostly on the presence of the extract of S. nigra. However, the EAM-ESN blend possesses more effective inhibitory activity toward virus replication than its constituent extracts. A post-infection mechanism of action of the EAM-ESN make this blend the most relevant for potential drugs and supportive treatments; thus, the EAM-ESN blend might be considered as a natural remedy in mild, seasonal respiratory viral infections.
... Two scenarios could be responsible for these reported effects: (i) direct antiviral properties, or (ii) immune-enhancing properties of components present in elderberries. Indeed, some studies reported a direct antiviral mechanism, thereby inhibiting viral replication, while others showed that the elderberry extract exhibits strong immunomodulatory properties [5,8,[13][14][15][16]. ...
... Based on these data, we hypothesize that polysaccharides, as well as anthocyanins, may contribute to the potent immune-modulatory properties of the elderberry extracts. In addition, Kinoshita et al. reported murine data showing that the oral uptake of elderberry juice induced a dose-dependent stimulatory effect, leading to increased titers of virus-neutralizing antibodies in bronchoalveolar lavage fluids as well as in the serum of the treated mice [15]. Since DCs are also important for the activation of B cells and thus for the production of antibodies [20], it is conceivable to speculate that the here reported elderberry extract (EC15), and its fractions, that is, CPS, BOUND and UNBOUND, could also enhance antibody production against, for example, different viruses, in vivo. ...
European black elderberry (Sambucus nigra L.) is a popular way to treat common colds or influenza infections. Mechanistically, this might be due to a direct antiviral effect or a stimulatory effect on the immune system of the host. Here, we evaluated the modulatory effects of black elderberry derived water extract (EC15) and its polysaccharide enriched fractions (CPS, BOUND, and UNBOUND) in comparison to a conventional alcoholic extract (EE25), regarding the phenotypical and functional properties of dendritic cells (DCs), which are essential cells to induce potent T cell responses. Interestingly, the water extract and its polysaccharide fractions potently induced DC maturation, while the ethanol extract did not. Moreover, the capacity to stimulate T cells by these matured DCs, as assessed using MLR assays, was statistically higher when induced by the water extracted fractions, compared to immature DCs. On the other hand, the ethanol extract EE25 did not induce T cell stimulation. Finally, the cytokine expression profiles of these DC—T cell cocultures were assessed and correlated well with increased T cell stimulation. Also, the expression of inflammatory cytokines, such as IL-6, TNF-α, and IFN-γ was highly increased in the presence of the elderberry water extract EC15, and the polysaccharide enriched CPS, BOUND, and UNBOUND fractions, but not by EE25. Thus, from these data, we conclude that the polysaccharides present in water-derived elderberry fractions induce potent immune-modulatory effects, which represents the basis for a strong immune-mediated response to viruses including influenza.
... 60 Additionally, concentrated juice of elderberry fruit and its fraction could interact with the replication of the virus at the stage of attachment and penetration of the virus to host cells in MDCK cells infected with H1N1 influenza virus. 61 Besides, a standardized commercial extract of elderberry exerted antiinfluenza activity in chicken embryos infected with H9N2 avian influenza virus in vitro at a dose of 95 mg/mL. 62 In A549 human epithelial cells infected with H9N2 influenza virus, low doses (5, 10, and 20 μg/mL) of elderberry fruit extract had no inhibitory effects on the replication of the virus, but high doses (40 and 80 μg/mL) could significantly reduce the virus titer and synthesis of viral protein, which suggested that the treatment of elderberry fruit extract could influence the entry of viruses or restrain the release of virus particles and the treatment time and dosage had an obvious influence on the effect of the elderberry fruit extract. ...
... 65 Oral supplementation of concentrated juice of elderberry fruit in the BALB/c mice model infected with H1N1 influenza virus exerted anti-influenza activity in a dose-dependent manner through stimulating the immune response, reducing the replication of the virus in bronchoalveolar lavage fluids (BALFs), and increasing the level of influenza virus-specific neutralizing antibodies and immunoglobulin A (IgA), and the high-molecular-weight fractions containing acidic polysaccharides might be its main anti-influenza component. 61 A standardized commercial extract of elderberry (0.4 mL/kg of bw) was also reported to decrease the load of the virus in broiler chickens infected with H9N2 avian influenza virus. 66 Several clinical trials also investigated the anti-influenza activity of elderberry, and most studies support its antiinfluenza activity. ...
... Studies have also indicated that the effectiveness of elderberries against infection may also be due to immune stimulation [39,62,74]. ...
... Other studies have proved that elderberry extract may affect the immune system by enhancing the production of cytokines by monocytes [74]. Torabian et al. [75], in their recent research, indicated that the immunomodulatory property of elderberry extracts manifested by increased expression of IL-6, IL-8, and TNF35. ...
In the current context, when more and more unknown pathogens appear, healthy eating and supplementing it with natural products play an increasingly important role in maintaining the health of the body. The European black elder (Sambucus nigra), found in abundance in the spontaneous flora, can provide us, as a raw material, elderberries, which have been known for thousands of years as having nutritional and healing properties. The phytotherapeutic principles found in elderberry fruits give them antiviral, antibacterial and antidiabetic properties, antitumor potential, antioxidant, antidepressant and immune boosting properties, as well as a certain impacts on obesity and metabolic dysfunctions. Polyphenols and lectins give elderberry fruits the ability to inhibit coronaviruses, which is a topic of great interest in our times. This article summarizes the existing data regarding the chemical composition, active principles and biopharmaceutical properties of elderberries, as well as their use.
... Although not the most traditional of berries, elderberries (Sambucus nigra L.) have also been used for years in the belief of their health benefits, especially against influenza and the common cold. Studies on mice showed that consumption of elderberries had negative effects on influenza A virus activity, which has been attributed to their high level of flavonoids [130]. The study states the total polyphenol and anthocyanin contents to be 42 mg/g and 6.6 mg/g, respectively. ...
... In vivo (rats) ↓ the ACE activity [110] Purple concord grape (Vitis labrusca) Immune system In vivo (humans) ↑ of γδ-T cells and ↓ of inflammatory cytokine release [120] Chokeberry Immune system In vivo (mice) ↑ phagocytic cell and T cell activities [121] Elderberry Immune system In vivo (mice) ↓ influenza A virus activity [130] Elderberry extract Immune system In vitro ↓ TNF-α and IFN-γ secretion [178] Calafat berry extract Cancer ...
Along with the increased knowledge about the positive health effects of food bioactives, the eating habits of many individuals have changed to obtain higher nutritional benefits from foods. Fruits are among the most preferred food materials in this regard. In particular, berry fruits are important sources in the diet in terms of their high nutritional content including vitamins, minerals, and phenolic compounds. Berry fruits have remedial effects on several diseases and these health-promoting impacts are associated with their phenolic compounds which may vary depending on the type and variety of the fruit coupled with other factors including climate, agricultural conditions, etc. Most of the berries have outstanding beneficial roles in many body systems of humans such as gastrointestinal, cardiovascular, immune, and nervous systems. Furthermore, they are effective on some metabolic disorders and several types of cancer. In this review, the health-promoting effects of bioactive compounds in berry fruits are presented and the most recent in vivo, in vitro, and clinical studies are discussed from a food science and nutrition point of view.
... The concentrated juice of elderberry stimulated the immune response and prevented viral infection in human influenza A virus (IFV)-infected mice. 45 The berries of Sambucus nigra L. are traditionally used to treat respiratory illnesses, such as colds and influenza. The fractions obtained from 50% ethanol and water extracts showed potent dose-dependent complement fixating activity and macrophage stimulating activity. ...
... Compounds 36 and 37 showed antiviral activities against the H3N2 influenza virus with IC 50 values of 33.3 and 33.3 μM, respectively, and the coxsackievirus B3.53 Three glycosidic bisindole alkaloids, isatindigobisindoloside B(38), isatindigobisindoloside E (39), and isatindigobisindoloside F (40), were isolated from an aqueous extract of the Isatis indigotica root. Compounds 38-40 showed antiviral activities against both the H3N2 influenza virus and coxsackievirus B3.54 Five indole alkaloids, oxoglyantrypine (41), norquinadoline A (42), deoxynortryptoquivaline(43), deoxytryptoquivaline(44), and tryptoquivaline(45), ...
Viral infectious diseases are serious threats to human health in both developing and developed countries. Although there is the continued development of new drugs from synthetic sources as antiviral agents, medicinal plants continue to provide the basic raw materials for some of the most important antiviral drugs. Alkaloids are a class of pharmacologically active plant compounds that are usually alkaline in nature. In this review, we tried to summarize recent progress in herb-based antiviral research, the advantages of using active plant compounds as antiviral agents, and the inflammatory responses initiated by alkaloids, based on the literature from 2009 to 2019, for the treatment of conditions, including influenza, human immunodeficiency virus, herpes simplex virus, hepatitis, and coxsackievirus infections. Articles are retrieved from PubMed, Google Scholar, and Web of Science using relevant keywords. In particular, the alkaloids from medicinal plants responsible for the molecular mechanisms of anti-inflammatory actions are identified and discussed. This review can provide a theoretical basis and approaches for using various alkaloids as antiviral treatments. More research is needed to develop alkaloidal compounds as antiviral therapeutic agents and potential regulators of the anti-inflammatory response.
... A reduction of LPS-induced proinflammatory cytokines (IL-1 , IL-6, TNF-) and β α COX-2 gene expression was reported in a murine macrophage model where the SN extract (1 mg/mL) had been exposed to a simulated gastrointestinal digestion process prior to the bioassay (Olejnik et al., 2015). Elderberry juice concentrate (10 mg/day) increases influenza A-specific neutralizing antibodies in bronchioalveolar lavage fluid of female BALB/c mice (Kinoshita, Hayashi, Katayama, Hayashi, & Obata, 2012). ...
... Sambucol-treated influenza A H9N2 virus-inoculated embryonic chicken eggs (95 mg/mL) resulted in a neutralizing index of >7.7, considered an effective antiviral treatment (Karimi, Mohammadi, & Dadras, 2014). Antiviral effects of elderberry juice concentrate were reported in four publications; concentrations between 150-1000 µg/mL showed impact on influenza A H1N1 (Kinoshita et al., 2012;Roschek Jr, Fink, McMichael, Li, & Alberte, 2009), HIV , and IBV viruses(C. Chen et al., 2013). ...
In times of health crisis, including the current COVID-19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday selfcare and health care, and since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well-being. Newly emerging viral infections, specifically COVID-19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, and specifically regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and anti-inflammatory effect include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate-yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.
... The flavonoids, quercetin-3-rutinoside (rutin), isorhamnetin-3-rutinoside (narcissin) and kaempferol-3-rutinoside (nicotiflorin) were found to be major constituents (Mikulic-Petkovsek et al. 2015). According to previously obtained data, acidic polysaccharides and polyphenols from elderflowers have potential health promoting effects, including antiviral, antiinflammatory and immune-stimulating effects (Ho 2017;Sidor and Gramza-Michałowska 2015;Kinoshita et al. 2012). However, there is not sufficient data about which specific compounds are responsible for the pharmacological activity of Sambucus nigra. ...
Pharmacopoeias are important resources for the quality control of medicinal plants and their products. Considering that approximately 80% of the world population to different extents relies on medicinal plants for the prevention and treatment of medical ailments the safety and suitability of medicinal plants is extremely important. Unfortunately, for many medicinal plants the active component or group of components responsible for their pharmacological activity are unknown. In such cases, the standardization of the medicinal plant material is performed using reference compounds that are either contained in the plant, but are known to not mediate the plants biological activity or are not contained in the plant at all, but find use as auxiliary reagents, for example, to help identify the necessary chromatographic zones/peaks. Additionally, many medicinal plants do not have qualitative or quantitative analysis procedures in place or use methods with low selectivity (spectrophotometry, colour reactions). In these cases, it is impossible to confidently and adequately standardize the medicinal plant material. Two other issues that complicate medicinal plant standardization include the variability of its chemical composition depending on multiple biotic and abiotic factors and the lack of sufficient data on the chemical composition of some plants. In this review, we analyzed medicinal plants common to the Eurasian Economic Union (EAEU), European, United State and Japanese Pharmacopoeias. We have analysed and systematized literature data devoted to the relation between the chemical composition and pharmacological activity of the plants presented in this review. Based on the analysed data, we have suggested more rational and adequate methods for the quality assessment and quantitative standardization of medicinal plants.
... Эксперименты in vitro и in vivo продемонстрировали способность экстракта бузины ингибировать развитие вирусов гриппа А и В [40,41]. Более того, после некоторых экспериментов, проведенных in vivo, было установлено, что бузина стимулирует иммунный ответ и эффективно подавляет репликацию вируса [42]. ...
Anthocyanins and polyphenols are the main biologically active substances in elderberry. Extraction methods exert a significant effect on the extraction effectiveness, bioavailability and preservation of biologically active compounds. The aim of this work was a review of the published results of scientific studies of elderberry and products of its processing, their effect on the body, as well as examination of methods for extraction and encapsulation of biologically active substances of elderberry. The review includes papers in English and Russian. A search for foreign literature in English on this theme was carried out in the bibliographic databases Google Scholar, Scopus, Web of Science, Elsevier, ResearchGate. To select scientific papers in Russian, a search was done in the scientific electronic library eLIBRARY.RU by keywords. The review of the scientific publications shows that the results of numerous studies confirm the high antioxidant activity of elderberry (Sambucus nigra L.), as well as wild elderberry (Sambucus ebulus), growing on the territory of the Belarus Republic and in other countries of Europe, Asia, North Africa and North America. This plant is applied in the traditional medicine and is used in the food industry as raw materials for creation of prophylactic and functional products due to the presence in the chemical composition of elderberry (Sambucus nigra L.) of bioactive flavonoids such as quercetin, kempherol and rutin, and other phenolic compounds. Bioactive compounds of elderberry possess several unique biological and pharmacological properties including the antioxidant, anti-tumor, anti-depressive, anti-diabetic, antiviral and antibacterial activities. To extract bioactive substances from elderberry, traditional extraction methods are used, such as maceration and Soxhlet extraction, as well as modern promising “green” technologies (for example, supercritical fluids, pulsed electric field, emulsion liquid extraction, microwave-assisted and ultrasound-assisted extraction). To preserve and protect biologically active substances in elderberry, encapsulation methods that are most effective are employed. The materials of this paper can be used in future studies on optimization of extraction processes to increase the nutritional value and antioxidant activity of new functional foods, food additives and products of pharmaceutical industry.
... Therefore, these findings not only supported the hypothesis of an antiviral utility of Ginkgo biloba [90][91][92] but also offered intriguing and important insights into the screening procedures that can be used in studies of anti-influenza virus activity [88]. Elderberry (Sambucus nigra) is one of the traditional natural treatments for respiratory problems [93,94] that was also recently investigated in in vitro and clinical studies [95,96]. Elderberry supplements have gained interest as a means of treating or preventing illness during the COVID-19 pandemic, but there was also concern that preparations from this plant might overstimulate the immune system and increase the risk of cytokine storms. ...
A complex network of processes inside the human immune system provides resistance against a wide range of pathologies. These defenses form an innate and adaptive immunity, in which certain immune components work together to counteract infections. In addition to inherited variables, the susceptibility to diseases may be influenced by factors such as lifestyle choices and aging, as well as environmental determinants. It has been shown that certain dietary chemical components regulate signal transduction and cell morphologies which, in turn, have consequences on pathophysiology. The consumption of some functional foods may increase immune cell activity, defending us against a number of diseases, including those caused by viruses. Here, we investigate a range of functional foods, often marketed as immune system boosters, in an attempt to find indications of their potential protective role against diseases caused by viruses, such as the influenza viruses (A and B), herpes simplex virus (HSV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in some cases mediated by gut microbiota. We also discuss the molecular mechanisms that govern the protective effects of some functional foods and their molecular constituents. The main message of this review is that discovering foods that are able to strengthen the immune system can be a winning weapon against viral diseases. In addition, understanding how the dietary components function can aid in the development of novel strategies for maintaining human bodily health and keeping our immune systems strong.
... Moreover, human clinical trials have shown that black elderberry extracts reduce symptom severity as well as the duration of viral infections, especially IAV and the Influenza B virus (IBV) [36,[38][39][40]. A juice concentrate of black elderberry suppressed viral replication in the bronchoalveolar lavage fluids of mice infected with human IAV [41]. ...
Coronavirus disease-19 (COVID-19) is still affecting the lives of people round the globe and remains a major public health threat. The emergence of new variants more efficiently transmitted, more virulent and more capable of escaping naturally acquired and vaccine-induced immunity creates a long-term negative outlook for the management of the pandemic. The development of effective and viable prevention and treatment options to reduce viral transmission is of the utmost importance. The fruits of the European black elderberry and extracts thereof have been traditionally used to treat viral infections such as coughs, cold and flu. Specifically, its efficacy against the Influenza A virus has been shown in vitro as well as in human clinical trials. In the current project, we investigated the antiviral activity of a black elderberry extract, mainly containing anthocyanins and phenolic compounds, against SARS-CoV-2 and its variants of concern and explored the possible mode of action by performing time of addition experiments. The results revealed that the extract displayed a strong anti-SARS-CoV-2 activity against the Wuhan type as well as the variants of concern Alpha, Beta, Gamma, Delta and Omicron with a comparable antiviral activity. Based on cytotoxicity data, a 2-log theoretical therapeutic window was established. The data accumulated so far suggest that the viral replication cycle is inhibited at later stages, inasmuch as the replication process was affected after virus entry. Therefore, it would be legitimate to assume that black elderberry extract might have the potential to be an effective treatment option for SARS-CoV-2 infections.
... Both in vitro and in vivo experiments demonstrated the ability of elderberry extract to inhibit the development of influenza A and B viruses [101][102][103]. Moreover, following some experiments carried out in vivo, it was demonstrated that elderberries stimulated the immune response and effectively suppressed viral replication [104]. ...
Elderberries are appreciated for their antioxidant properties. Sambucus nigra L. is an extremely abundant plant in the wild flora of Romania, but it is underutilized. Elderberry is used in modern and traditional medicine due to the complex chemical composition of the fruit. The content of phenolic compounds is high (516–8974 mg/100 g DW), of which the most abundant are anthocyanins. Phenolic compounds are known for their beneficial effects on the body. Numerous studies have demonstrated the antioxidant capacity, antibacterial, antiviral, antidiabetic, and anticancer properties of the fruit. It is considered that most of the therapeutic properties of elderberries can be correlated with the antioxidant activity they have. S. nigra fruits are also used in the food industry. Some studies have shown that the therapeutic properties of elderberries can also be found in the products obtained from them. Therefore, this review aimed to describe the chemical composition of elderberries and products obtained from them, the positive effects on the body, and the methods by which the bioactive compounds can be extracted from the fruits and analyzed. This manuscript is useful for extraction optimization and characterization in order to valorize new functional foods, food supplements, and also in new pharmaceutical products.
... Currently, extracts of the berries are used primarily as antiviral agents for colds, influenza and Herpes virus infection. Also, several clinical trials have shown that symptoms of influenza like sneezing and fever were quickly treated with elderberry including products which are both commercially produced or home recipes [2][3][4][5]. The effects of the plant and/or parts of plants come from its main natural components, which are flavonoids, catechins and proanthocyanidins. ...
Amaç: Bu kesitsel çalışmanın amacı Mürver içerikli ürünlerin Azerbaycan (AZ), Gürcistan (GEO), Özbekistan (UZB) ülkelerindeki algısı ve tüketimindeki değişimi belirlemek ve ölçmektir. Gereç ve Yöntem: Anket temelli, kesitsel, çoklu ülkede, dijital ortamda; eczane ve gıda takviyesi ürünleri kategorisi bulunan eczanelerin, sağlık ürünleri mağazalarının tüketicileri ile, 2021 yılının Nisan ve Ağustos ayları arasında gerçekleştirilmiştir. Sonuç ve Tartışma: Ankete katılanların büyük kısmı 31-50 yaş aralığında olup ve %85’lik kısmını kadınlar oluşturmaktaydı. 3 ülkenin ortalama verilerine göre ürünlerin nihai kullanıcıları çocuklar (%51) ve yaşlı aile üyeleridir (%39). Mürver içeren ürünler pandemi süresinde yüksek miktarda tüketilmelerine ragmen, pahalı ürünler olarak sınıflandırılmıştır. Pandemi döneminde, immun sistemi güçlendirmek bireysel sağlıkta önceliklenmiş ve daha önceki dönemlere göre önleyici yaklaşımlar daha önemli hale gelmiştir. Bu çalışma Azerbaycan, Gürcistan ve Özbekistan’da gerçekleştirilmiş, dijital anket temelli, kesitsel ilk çalışmadır.
... 161 It was discovered that elderberry juice has a considerable antiviral effect against influenza virus infection in humans when tested on the human IAV using concentrated elderberry juice. 162 Besides, some studies have shown that the elderberry's flavonoid components inhibit neuraminidase; 163 and bind to the envelope of influenza. 164 Furthermore, it was proved that elderberry syrup is effective against IAV infections. ...
Due to the absence of successful therapy, vaccines for protection are continuously being developed. Since vaccines must be thoroughly tested, viral respiratory tract infections (VRTIs), mainly coronaviruses, have seriously affected human health worldwide in recent years. In this review, we presented the relevant data which originated from trusted publishers regarding the practical benefits of functional foods (FFs) and their dietary sources, in addition to natural plant products, in viral respiratory and COVID-19 prevention and immune-boosting activities. As a result, FFs were confirmed to be functionally active ingredients for preventing COVID-19 and VRTIs. Furthermore, the antiviral activity and immunological effects of FFs against VRTIs and COVID-19 and their potential main mechanisms of action are also being reviewed. Therefore, to prevent COVID-19 and VRTIs, it is critical to identify controlling the activities and immune-enhancing functional food constituents as early as possible. We further aimed to summarize functional food constituents as a dietary supplement that aids in immune system boosting and may effectively reduce VRTIs and COVID-19 and promote therapeutic efficacy.
... As a result, it was suggested that the anthocyanidin components contained in blackcurrant might regulate viral uptake into cells and virus secretion from infected cells. Elderberry (Sambucus nigra L.) has also displayed antiviral effect against human influenza A virus in a mouse model (Kinoshita et al., 2012). In influenza A virus-infected mice, treatment with the elderberry fraction suppressed viral replication in bronchoalveolar lavage. ...
Viruses are known to cause a variety of diseases, ranging from mild respiratory diseases, such as the common cold, to fatal illnesses. Although the development of vaccines and targeted drugs have significantly improved the mortality rate and disease severity against a number of viral infections, there are still many viruses without proper treatment/prevention options and newly emerging viruses can pose serious health threats. For instance, the coronavirus disease 2019 (COVID-19) pandemic is producing significant healthcare and socio-economic burden worldwide, which may jeopardize the lives and livelihoods for years to come. Studies have identified functional foods with antiviral activity. Certain foods may target the viral life cycle or modulate the host immune system to enhance defense against viral infections. In this review, we will discuss some of the food products reported to display protective effects against viruses including the influenza virus, human immunodeficiency virus, and severe acute respiratory syndrome coronavirus 2.
... HA contributed to the ability of the virus to cause hemagglutination in human hosts (103,104), whose sambucol was found in vitro to avoid a four-fold increase to 16 times after influenza ( 105). Studies have also shown the effectiveness of S. nigra against infections that may be due to immune stimulation (106,107,108). The literature has shown a very high antiviral potential of the S. nigra plant. ...
As the number of viral infections and in particular resistant viral strains increasing, existing remedies need to be improved and brought into line with the discovery of new antiviral agents to fight persistent viral infections. It is generally believed that the gene pool of medicinal plants is valuable and endowed with precious compounds to treat metabolic and infectious disorders. The purpose of this review is to gather the facts and investigate into the therapeutic potential of medicinal plants, herbs and spices in the administration of various viral diseases. COVID-19 infections are treated with available antiviral therapy with unsatisfactory clinical results. Persistent viral infections that are resistant to the available antivirals are terrifying threats and a serious health problem like influenza infection. SARS CoV 2 remains a major threat to animal and human health, which urgently requires effective antivirals. Due to the increasing frequency of viral infections and particularly resistant viral strains, the available therapeutic facilities must be improved, compensated by the discovery of new antiviral agents to fight against refractory viral infections. The treatment of herbal remedies as readily available alternatives for their compatibility with the body and fewer side effects compared to synthetic chemical treatments has become popular worldwide. Introduction:
... Ruta graveolens L. é uma planta eficaz no tratamento da asma ( AKRAM et al., 2018;KINOSHITA et al., 2012;KRAWITZ et al., 2011;ZAKAY-RONES et al., 1995, 2004), influenza B (KRAWITZ et al., 2011ZAKAY-RONES et al., 1995, 2004 e redução substancial da duração e gravidade dos sintomas respiratórios (HAWKINS et al., 2019;ZAKAY-RONES et al., 1995). O pré-tratamento do vírus HSV-1 (cepas sensíveis e resistentes a aciclovir) (SCHNITZLER; KOCH; REICHLING, 2007) e HSV-2 (KOCH, C et al., 2008) com o óleo essencial derivado do gengibre causou uma redução significativa da infecciosidade, indicando que o efeito virucida do gengibre é principalmente exercido antes da adsorção do HSV nas células hospedeiras (KOCH, C et al., 2008;SCHNITZLER;KOCH;REICHLING, 2007). ...
As Leishmanioses são doenças infecto parasitárias causadas por protozoários do gênero Leishmania e transmitidas naturalmente por insetos fêmeas de diferentes espécies da família Phlebotominae. A Leishmaniose visceral (LV) é prevalente em 98 países, onde mais de um bilhão de pessoas vivem em áreas endêmicas, com risco de transmissão, com indícios e potenciais de franca propagação. Ademais, está entre as Doenças Tropicais Negligenciadas e ocupou o 3o lugar no ranking de mortalidade por tais doenças no Brasil entre os anos de 2000 a 2011. Foram confirmados 2.529 casos de LV humana em 2019. Analisando a viabilidade de tratamentos eficazes e com baixa toxicidade, tornam-se necessárias novas abordagens farmacológicas que visem reduzir o impacto da doença e da toxicidade terapêutica para auxiliar o profissional no direcionamento da conduta terapêutica mais segura. Nesse sentido, ganham espaço a utilização de arsenais terapêuticos baseados em extratos vegetais com potencial leishmanicida. Esse tipo de abordagem é considerada menos invasiva ao trazer benefícios ao paciente acometido, impactando positivamente no seu prognóstico. Assim, a busca por tratamento que apresente toxicidade reduzida é alvo de pesquisa em todo território nacional. Há o interesse em se estudar produtos naturais disponíveis nos biomas brasileiros, os quais aumentam as chances de encontrar substâncias que sejam úteis no desenvolvimento de novos fármacos. Desse modo, o objetivo deste capítulo é contextualizar a LV, os tipos de biomas do Brasil, e descrever uma breve abordagem sobre os avanços em terapêutica natural para seu tratamento.
... Ruta graveolens L. é uma planta eficaz no tratamento da asma ( AKRAM et al., 2018;KINOSHITA et al., 2012;KRAWITZ et al., 2011;ZAKAY-RONES et al., 1995, 2004), influenza B (KRAWITZ et al., 2011ZAKAY-RONES et al., 1995, 2004 e redução substancial da duração e gravidade dos sintomas respiratórios (HAWKINS et al., 2019;ZAKAY-RONES et al., 1995). O pré-tratamento do vírus HSV-1 (cepas sensíveis e resistentes a aciclovir) (SCHNITZLER; KOCH; REICHLING, 2007) e HSV-2 (KOCH, C et al., 2008) com o óleo essencial derivado do gengibre causou uma redução significativa da infecciosidade, indicando que o efeito virucida do gengibre é principalmente exercido antes da adsorção do HSV nas células hospedeiras (KOCH, C et al., 2008;SCHNITZLER;KOCH;REICHLING, 2007). ...
... In vitro, sambucol has been shown to prevent influenza fourfold to sixfold depending on the strain [40]. S. nigra efficiency against infection has also been discovered through research because of immune system activation [41][42][43]. Peptic polysaccharides, polyphenolic chemicals, and flavonoids found in S. nigra may have a role in viral suppression as well. The fruit extract from S. nigra has been shown to be effective in treating a variety of viral illnesses [44]. ...
Viruses have a high ability to resist drugs and adapt to all conditions. This has encouraged the scientific community to develop new therapeutic agents by using antioxidant compounds that are naturally present in foods and medicinal plants. Cellular harm caused by free radicals (Reactive Oxygen Spescies ROS) leads to many From the diseases such as diabetes, virus inflammation, impregnability diseases, and digestive diseases. ROS are created during Metabolism of complex chemical compounds. Some plants are characterized by their antioxidant and antiviral activity which increases their ability to fight viruses, therefore plants with antioxidant capacity protect cells by stopping the oxidation chain reaction, and also can contribute significantly to offsetting oxidative stress caused by viral disease. Essential oils extracted from plants may serve as potential alternative sources for treating diseases caused by certain viruses. This study aims to show the potential effect of natural antioxidants found in some foods, herbs and their essential oils in treating some viral diseases, as well as how they work in boosting immunity and inhibition of free radicals
... I, Fr. II, including acidic polysaccharides, may be responsible for the anti-influenza activity [74]. ...
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.
... Elderberries (Sambucus nigra L.): Elderberries are plants belonging to family Adoxaceae whose active ingredients are used to manufacture different products, such as elixirs and pills which have been used to treat viral infections like common cold and flu like symptoms. An animal study in mice revealed that concentrated elderberry juice suppressed the replication cycle of influenza virus by the stimulation of immune system responses (Kinoshita et al, 2012). Elderberry supplements were found to substantially reduce upper respiratory tract symptoms caused by viral infections (Hawkins et al., 2019). ...
Plants are a fascinating group of plants that have been
dominating the earth for 400 million years. During evolution, they
have undergone series of evolutionary changes to suit themselves
with the surrounding environment. These evolutionary changes
not only included morphological changes to suit varied climatic
conditions but also armed with intricate physiological changes to
synchronize with the former and fortify better adaptability. These
physiological changes of the plant later proved to be of immense help
to the humans who evolved much later somewhere between 6 million
to 2 million years ago. The physiological and biochemical evolution
of the plants with the synchronous origin of various taxa resulted
in the formation of numerous biochemical pathways producing a
large number of secondary metabolites whose one primary aim is to
protect the plants from herbivores and insect which in the due course
of evolution became an integral part of the food chain. However, the
secondary metabolites also proved to be of immense use to humans
since antiquity who unknowingly since prehistoric times used
plants for their food and medicine. It is only in the past hundred
years or so, people became aware of the chemical constituent of the
plants and started exploring their various beneficial properties. The
agricultural activities also coevolved with human civilization and
with the increase in population, higher yield along with protection
of crops from pathogen attack became a necessity. This lead to the
formulation of fertilizers which consequently paved the way for
biofertilizers with a fewer side effects on humans and animals but
with a more green approach towards fertility enhancement. With
the advent of industrialization the menace of pollution cropped up
and presently this pollution is encroaching soil water and air. This
is having a deleterious effect on the ecosystem concerning human
and animal health and also agricultural productivity. Thus keeping
this in mind the scientific community was determined to remediate
the polluted sites with the help of biological agents in which the
plants and microbes played an important role. This provided major
protection to agriculture from contamination thereby sustaining
productivity. Thus, an attempt is made to highlight the progress
and advances in the field of agriculture and plant science. Thus A
handbook of Agricultural and Plant Sciences is an attempt to compile
information related to the field of agriculture and plant science.
The main purpose of the book is to provide relevant information
to the readers on aspects largely cantered on plants. The book is
divided into three sections namely agriculture and sustainable
development, plants and microbes as nutraceutical agents, and
medicinal potential of plants. Selected chapters in relevance to
the sections have been accommodated to provide an overview. The
first section deals with various aspects through which crops can
be fortified through bio fertilization and also decontamination of
polluted lands. The world population is presently stressing upon
consumption of foods from natural sources as consumption of fast
food with artificial agents is leading to the onset of several diseases.
This has led to a group of foods that confers nutrition as well as
a medicinal benefit at the same time. They are presently termed
and considered nutraceuticals. The second section of the book deals
with the nutraceutical potential of plants and microbes which
are symbiotically associated with plants. The third section is also
related to the second one concerning the medicinal importance. This
section encompasses the medicinal importance of plants. Plants as
antiviral agents have been accommodated because of the current
pandemic situation. The section also contains a chapter on the ant
diabetic potential of plants and also the medicinal importance of
gymnosperms and bioactive potentials of bryophytes which adds
up to the variation in chapters focusing on the medicinal aspect.
The book is also accompanied by several tables within each chapter
which gives a clear and systematic description of the theme that is
discussed upon. The book is an academic venture and would benefit
the scientific community and readers who are interested in the field
of plant sciences.
... Elderberries contain different active ingredients and phytochemicals, including (pro)anthocyanins (Stuppner et al., 2020), flavonoids and (poly)phenolic acids (EMA, Committee on Herbal Medicinal Products, 2014;Ferreira et al., 2020), all of which are supposed to make their contributions to described antimicrobial and antiviral effects as well as immunomodulation, as shown in different preclinical studies (Barak et al., 2001(Barak et al., , 2002Frank et al., 2020;Kinoshita et al., 2012;Roschek et al., 2009;Torabian et al., 2019). As such, it could be shown that elderberry and in particular cyanidin 3-glucoside, its primary anthocyanin compound, reduce the infectivity of the influenza virus at different infection stages (Torabian et al., 2019) and elderberry extract reduces infectivity by binding to H1N1 virions, thereby blocking the ability to infect host cells (Roschek et al., 2009). ...
Infections of the respiratory system, including common cold and influenza, are affecting people worldwide and are more or less prone to spread depending on the season and viral load of the host. For reducing symptoms and duration of illness, treatment options to standard prescribed drugs are in demand. Natural products could provide immune-supporting treatment alternatives. Elderberry extracts have been used in traditional medicine for the treatment of respiratory infections for decades and numerous studies describe the beneficial effects of elderberries on the immune system and respiratory infectious disease. We investigated the immunomodulative and antiviral effects of a high-quality, anthocyanin-enriched elderberry fruit extract (eldosamb®). Results reveal that elderberry extract reduced the secretion of pro-inflammatory cytokines TNF-α and IFN-γ, leading to a shift towards the Th2-Helper cell response and showing antiviral efficacy against the MVA virus. Thus, with its anti-inflammatory and antiviral bioactivity the proprietary elderberry extract suggests its use as an immunomodulatory health product.
... Elderberries (Sambucus nigra L.): Elderberries are plants belonging to family Adoxaceae whose active ingredients are used to manufacture different products, such as elixirs and pills which have been used to treat viral infections like common cold and flu like symptoms. An animal study in mice revealed that concentrated elderberry juice suppressed the replication cycle of influenza virus by the stimulation of immune system responses (Kinoshita et al, 2012). Elderberry supplements were found to substantially reduce upper respiratory tract symptoms caused by viral infections (Hawkins et al., 2019). ...
A Curtain Raiser on Natural Supplements Being Targeted Choice of Surveillance As
Potential Anti-Viral Drugs : Neutraceutical Supplementations Vis-à-Vis Immune
Boosters
... The control mice were orally administered with vehicle (distilled water) alone. Because influenza virus (IFV) infection causes a reduction in body weight [29,30], mice belonging to each treatment group were weighed daily for day 14, beginning on the day of IFV inoculation (designated day 0). After euthanizing the animals via cervical dislocation by a skilled person to avoid causing pain, lung and bronchoalveolar lavage fluid (BALF) samples were collected from each group on days 3 and 14, and blood and fecal samples were collected on day 14 (Fig 1). ...
We evaluated whether the water dispersibility of lactic acid bacteria ( Enterococcus faecalis KH2) affects their efficacy. When cultured lactic acid bacteria are washed, heat-killed, and powdered, adhesion occurs between results in aggregation (non-treated lactic acid bacteria, n-LAB). However, dispersed lactic acid bacteria (d-LAB) with a lower number of aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. Mice were administered n-LAB or d-LAB Peyer’s patches in the small intestine were observed. Following n-LAB administration, a high amount of aggregated bacteria drifting in the intestinal mucosa was observed; meanwhile, d-LAB reached the Peyer’s patches and was absorbed into them. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in the influenza yield of bronchoalveolar lavage fluids on day 3 post-infection and neutralizing antibody titers of sera and influenza virus-specific immunoglobulin A in the feces on day 14 post-infection. Therefore, the physical properties of lactic acid bacteria affect their efficacy; controlling their water dispersibility can improve their effectiveness.
... Previous studies showed that elderberry exhibited inhibitory bacterial activity and effectively suppressed viral replication, acting against pathogens that cause infections of the upper respiratory tract. (Kong 2009;Kinoshita et al. 2012;Álvarez et al. 2018). Studies have also shown that both elderberry and elderflower extracts exerted diverse biological activities in different biological system, such as antioxidant, anti-inflammatory, antidiabetic and diuretic effects (Ulbricht et al. 2014;Sidor and Gramza-Michalowska 2014). ...
Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines could be an option in the treatment of rhinosinusitis due to their anti-inflammatory and anti-oxidative properties. The study aims to investigate the effect of intranasal Sambucus nigra L. subsp. nigra (SN) extract against inflammation, oxidative stress, and tissue remodeling in nasal and sinus mucosa, but also in serum, lungs, and brain, in Wistar rat model of subacute sinonasal inflammation induced by local administration of lipopolysaccharides (LPS), from Escherichia Coli. The cytokines (TNF-α, IL-1β, IL-6) and oxidative stress (malondialdehyde) in nasal mucosa, blood, lungs, and brain were analyzed. In addition, a histopathological examination was performed, and NF-kB, MMP2, MMP9, TIMP1 expressions were also evaluated in nasal mucosa. Both doses of LPS increased the production of cytokines in all the investigated tissues, especially in the nasal mucosa and blood (p < 0.01 and p < 0.05), and stimulated their secretion in the lungs, and partially in the brain. Malondialdehyde increased in all the investigated tissues (p < 0.01 and p < 0.05). In parallel, upregulation of NF-kB and MMP2 expressions with downregulation of TIMP1, particularly at high dose of LPS, was observed. SN extract reduced the local inflammatory response, maintained low levels of IL-6, TNF-α, and IL-1β. In lungs, SN reduced all cytokines levels while in the brain, the protective effect was noticed only on IL-6. Additionally, SN diminished lipid peroxidation and downregulated NF-kB in animals exposed to a low dose of LPS, with increased TIMP1 expression, while in animals treated with a high dose of LPS, SN increased NF-kB, MMP2, and MMP9 levels. In conclusion, SN extract diminished the inflammatory response, reduced generation of reactive oxygen species (ROS) and, influenced MMPs expressions, suggesting the benficial effect of SN extract on tissue remodeling in subacute rhinosinusitis and on systemic inflammatory response.
... Sambucus nigra L. or commonly called elderberry has been extensively used herb to treat influenza and colds. The research by Kinoshita and colleagues (2012) assessed antiviral activity of concentrated elderberry juice (CJ-E) on human influenza A virus, and results showed that CJ-E exerted relatively strong effect on mice infected with influenza virus [304]. However, its antiviral activity against influenza virus in vitro was not very remarkable. ...
To date, the leading causes of mortality and morbidity worldwide include viral infections , such as Ebola, influenza virus, acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and recently COVID-19 disease, caused by the SARS-CoV-2 virus. Currently, we can count on a narrow range of antiviral drugs, especially older generation ones like ribavirin and interferon which are effective against viruses in vitro but can often be ineffective in patients. In addition to these, we have antiviral agents for the treatment of herpes virus, influenza virus, HIV and hepatitis virus. Recently, drugs used in the past especially against ebolavirus, such as remdesivir and favipiravir, have been considered for the treatment of COVID-19 disease. However, even if these drugs represent important tools against viral diseases, they are certainly not sufficient to defend us from the multitude of viruses present in the environment. This represents a huge problem, especially considering the unprecedented global threat due to the advancement of COVID-19, which represents a potential risk to the health and life of millions of people. The demand, therefore, for new and effective antiviral drugs is very high. This review fo-cuses on three fundamental points: (1) presents the main threats to human health, reviewing the most widespread viral diseases in the world, thus describing the scenario caused by the disease in question each time and evaluating the specific therapeutic remedies currently available. (2) It comprehensively describes main phytochemical classes, in particular from plant foods, with proven antiviral activities, the viruses potentially treated with the described phytochemicals. (3) Consideration of the various applications of drug delivery systems in order to improve the bioa-vailability of these compounds or extracts. A PRISMA flow diagram was used for the inclusion of the works. Taking into consideration the recent dramatic events caused by COVID-19 pandemic, the cry of alarm that denounces critical need for new antiviral drugs is extremely strong. For these Citation: Behl, T.; Rocchetti, G.; Chadha, S.; Zengin, G.; Bungau, S.; Kumar, A.; Mehta, V.; Uddin, M.S.; Khullar, G.; Setia, D.; et al. Phyto-chemicals from Plant Foods as Po
... This is of course a critical issue, in that while a constant immune surveillance and proper macrophage outburst represent vital elements of defense system, when this is overwhelmend by an acute viral infection, such as in the herewith applied model, the exaggerated chemockine attraction of those cellular population triggers a vicious, selfmaintaining circle with deleterious outcome [32]. In such events, as shown very recently in the current pandemia it is well documented how overexpression of IL-6 and TNF-α are associated to eightened morbidity [33,34]. On the other the administration of GPK/B2O drastically reduced but not abolished the macrophage counting in BAL. ...
There is constant quest to prevent and counterfight annual influenza viral epidemics, given the limitations and drawbacks of antivirals chemicals so far. The aim of the present study was to test on an experimental viral model a phytocompound containing herbal ingredients endowed by, albeit scattered, reports of antiviral properties (GPK/B20, Viraxil, Named, Italy). Two influenza models were employed, i.e. H1N1 and H3N2. In vitro test showed that GSK/B20, especially at medium and high dose (50µl/mL to 100µl/mL) significantly reduced the infection of Madin-Darby-Canine-Kidney monolayers cells and progression of cytopathogenic effect over the observation period. More interestingly, when this compound was test 1h after infection on mice, especially at high dose (60g/kg/day), it appeared to significantly blunt the immune/inflammatory cells recruitment and the inflammatory cytokine cascade (at lung tissue level and bronco-alveolar lavage level), curbing also the related gene expression. This was associated to a reduced lung oedema, which is the correlate of respiratory distress in humans, viral load and scanning electron microscopy findings. In the meantime, more detailed experimental studies are warranted to unveil the range of mechanisms of actions that these natural ingredients are likely to be endowed with. Although these data have to be taken with caution having being obtained in an experimental-controlled setting, they suggest a potential safe application in the clinical practice, as recently corroborated for one of the herbal used.
... Mürverin konsantre suyunun insan influenza A virüsü üzerindeki antiviral etkisinin değerlendirildiği in vivo bir çalışmada, influenza A ile infekte farelere oral yoldan verilmesinin, bronkoalveolar lavaj sıvılarında (BALF'lar) viral replikasyonu baskıladığı ve serumdaki influenza A'ya özgü nötralize edici antikorun seviyesini arttırdığı ek olarak BALF'larda ve dışkıda salgı IgA seviyesini yükselttiği görülmüştür. Böylece mürver ekstresinin, bağışıklık cevabını uyararak ve viral infeksiyonu önleyerek antiviral etki gösterdiği bulunmuştur.59 Bupleurum spp. ...
In the COVID-19 pandemic, there are many publications or statements about the use of herbal products based on a scientific basis or not. In this review, the use of herbal products in COVID- 19 treatment by scanning PubMed, Google Scholar, Scopus, Cochrane, Clinical Trials and WHO web- sites, the pharmacological activities of plants, especially antiviral activity, and the effectiveness of isolated plant-derived compounds and extracts from the plants and their demonstrating molecular mod- eling studies, from preclinical to clinical studies have been discussed in a wide range. However, the fact that most of the studies are at the preclinical level and the studies that are specialized for COVID-19 and have reached the level of evidence for effective and safe use are insufficient. Besides, the complex struc- ture of herbal products and the fact that the infection has not yet been fully defined indicates that care should be taken in plant use. Therefore, many more studies and especially clinical studies are required for herbal products used in the COVID-19 treatment.
Keywords: COVID-19; phytoterapy; traditional medicine
... The control mice were administered orally with vehicle (distilled water) alone. Because influenza virus (IFV) infection causes a reduction in body weight [26,27], mice of each treatment group were weighed daily for 14 d, beginning on the day of IFV inoculation (designated day 0). Lung samples and bronchoalveolar lavage fluid (BALF) were collected from each group on days 3 and 14, and blood and fecal samples were collected on day 14 (Fig. 1). ...
We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.
... In this regard, elderberry (the whole fruit of Sambucus nigra L. containing multiple bioactive compounds) extract, which has been traditionally used to address cold and flu symptoms [11], has been shown in two recent meta-analyses to reduce overall symptom duration and severity when it is supplemented at the onset of upper respiratory infections in children and adults [12,13]. Moreover, preclinical studies have shown that the acidic polysaccharide-rich fraction contained in elderberry extract presented antimicrobial and antiviral effects, specifically against influenza viruses [14]. On the other hand, reishi (Ganoderma lucidum), the oldest known mushroom in ancient Chinese medicine [15], has been largely used to promote health and treat a large number of ailments [16]. ...
Elderly people are particularly vulnerable to respiratory tract infections, so natural strategies to ameliorate the duration and severity of these infections are of great interest in this population. The objective of this study is to evaluate the efficacy of the consumption of a combination of elderberry and reishi extracts on the incidence, severity, and duration of respiratory tract infections in a group of healthy elderly volunteers. A randomized, double-blind, placebo-controlled pilot study was performed during the winter season. A group of 60 nursing home residents ≥65 years of age was randomly assigned to receive a combination of 1.5 g of elderberry +0.5 g of reishi or a placebo daily for 14 weeks. Data about the health conditions of the volunteers were evaluated and recorded by a medical doctor every 2 weeks. The incidence of respiratory infections was similar in both groups. However, volunteers in the extract group presented a significantly lower duration of common cold events (2.5 vs. 4.8 days, p = 0.033).and a significantly lower probability of having a high severity influenza-like illness event (p = 0.039). Moreover, the incidence of sleep disturbances was significantly lower in the extract group (p = 0.049). Therefore, the administration of a combination of elderberry and reishi extracts to the elderly population during the winter season might be used as a natural strategy to reduce the duration and severity of respiratory tract infections.
... The active constituents inhibit the biosynthesis of the inflammatory cytokines IL-1a, IL-1b, and tumor necrosis factor-a in human peripheral mononuclear cells in vitro (Yesilada et al., 1997;Torabian et al., 2019). Several in vitro and in vivo experiments have shown the antiviral effects of extracts from elderberries, against Influenza virus (Serkedjieva et al., 1990;Zakay-Rones et al., 1995;Krawitz et al., 2011;Kinoshita et al., 2012;Porter and Bode, 2017). ...
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.
Dziki bez czarny (Sambucus nigra L.) jest jedną z najczęściej użytkowanych roślin zielarskich na świecie. W medycynie ludowej surowce czarnego bzu stosowane były przede wszystkim jako środki napotne, przeciwgorączkowe i moczopędne. Współcześnie udowodniono również działanie przeciwbakteryjne, przeciwwirusowe, przeciwdepresyjne, przeciwnowotworowe i hipoglikemizujące oraz obniżające stężenie tłuszczu i lipidów ekstraktów z bzu czarnego. Skład chemiczny kwiatów i owoców bzu czarnego jest zmienny i podlega różnym czynnikom zmienności (genetyczne, ontogenetyczne, środowiskowe, pozbiorcze). Kwiaty bzu czarnego zawierają flawonoidy, kwasy fenolowe, olejek eteryczny, kwasy organiczne, cukry i związki mineralne, podczas gdy w owocach dominują antocyjany. Bogaty skład chemiczny surowców bzu czarnego oraz ich silna aktywność biologiczna stwarzają duże możliwości zastosowania w produkcji farmaceutycznej, spożywczej i kosmetycznej.
While recent years have witnessed ever-growing evidence on the prebiotic attributes of anthocyanins for treatment of microbiota-associated diseases, the complex interplay between anthocyanin uptake, the gut microbiota, and the intestinal mucosal immune system remains poorly understood. Here, we investigate the effects of bilberry anthocyanins on the gut microbiota composition and metabolism, and the intestinal mucosal immune system of mice. We observed an increased proportion of IgA-producing plasma cells in the mesenteric lymph nodes (MLNs) and an enhanced secretion of secretory immunoglobulin A (sIgA) and antimicrobial peptides in the small intestine. Small intestine transcriptome analysis further suggested that anthocyanins influenced IgA production. We found that oral administration of anthocyanins altered the gut microbiota through maintaining the anaerobic intestinal environment, promoting the secretion of sIgA and antimicrobial peptides, and downregulating cell motility and mobile genetic elements of commensal bacteria. These observations suggest that the oral administration of anthocyanins helps in maintaining intestinal homeostasis and thus it may find applications in immunotherapy and related fields.
Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo studies met the inclusion criteria of this review. The inferences from scientific literature review, focusing on potential therapeutic consequences of medicinal plants on experimental models of HIV, HSV, influenza, hepatitis, and coxsackievirus have ascertained the curative antiviral potential of plants. Fifty-four medicinal plants belonging to 36 different families having antiviral potential were documented. Out of 54 plants, 27 individually belong to particular plant families. On the basis of the work of several independent research groups, the therapeutic potential of medicinal plants against listed common viral diseases in the region has been proclaimed. In this context, the herbal formulations as alternative medicine may contribute to the eradication of complicated viral infection significantly. The current review consolidates the data of the various medicinal plants, those are Sambucus nigra, Caesalpinia pulcherrima, and Hypericum connatum, holding promising specific antiviral activities scientifically proven through studies on experimental animal models. Consequently, the original research addressing the development of novel nutraceuticals based on listed medicinal plants is highly recommended for the management of viral disorders.
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.
COVID-19, the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 and has infected over 230 million people worldwide as of October 1, 2021. Common initial signs and symptoms include cough, fever, fatigue, headache, muscle aches and pain, and diarrhea [2]. Some individuals with COVID-19 become severely ill, usually starting about 1 week after symptom onset; severe COVID-19 often involves progressive respiratory failure and may also result in life-threatening pneumonia, multiorgan failure, and death. In addition, thousands of individuals-possibly 10% to 75%-who have had COVID-19 report symptoms of “long COVID” (including fatigue, muscle weakness, sleep difficulties, and cognitive dysfunction) for several months after the acute stage of illness has passed.
Currently, data are insufficient to support recommendations for or against the use of any vitamin, mineral, herb or other botanical, fatty acid, or other dietary supplement ingredient to prevent or treat COVID-19. And by law, dietary supplements are not allowed to be marketed as a treatment, prevention, or cure for any disease; only drugs can legally make such claims. Nevertheless, sales of dietary supplements marketed for immune health increased after the emergence of COVID-19 because many people hoped that these products might provide some protection from SARS-CoV-2 infection and, for those who develop COVID-19, help reduce disease severity.
The immune system defends the body against pathogens that cause disease and is comprised of innate responses, which are the first line of defense, and adaptive responses, which become engaged later.
Berries are acknowledged as a rich source of major dietary antioxidants and the fact that berry phenolics exhibit antioxidant property is widely accepted. Berries are abundant in Vitamin C and polyphenols such as anthocyanins, flavonoids, and phenolic acids. Polyphenols are found to have several therapeutic effects such as anti-inflammatory, antioxidant and antimicrobial properties. Increasing studies are being focused on natural products and their components for alternative therapeutics against viral infections. Especially berries such as Elderberry, blueberry, raspberry, and cranberry have proven to be effective against viral infections. Of note, the decoction of Honeysuckle (Lonicera japonica) has been shown to treat viral epidemic diseases. Owing to the rich source of various antiviral constituents, berries could be an alternative source for managing viral infections. In this review, we provide insights into how berry derived components inhibit viral infection and their clinical usefulness in viral disease management.
Idiopathic pulmonary fibrosis (IPF) is a group of lung disease that mainly affects the interstitium and ultimately results in the inflammation and damaging to the lung tissues [1]. The tissues present around the air sacs are called interstitium. Because of the thickening and scarring, lung tissues become damaged, and make it difficult to work. The scarring gets worse by the time which makes it difficult to breathe and keep the optimum levels of oxygen in the bloodstream. This affects the functioning of the vital organs as they are slowly depriving off oxygen. This disease is characterised by destruction of alveoli along with abnormal accumulation of fibroblasts giving the lungs a “honeycomb” like structure. Generally, this disease is more common in men over 50 years of age and two-thirds are diagnosed after 60 years of age [2]. Approximately 50,000 new cases of IPF are diagnosed each year and the symptoms came first into notice between the age of 50 and 70 years. Earlier the symptoms begin with the shortening of breathe but by the time this condition gets worse by eating or talking. At present, in the USA more than 80,000 adults are suffering from this disease and more than 30,000 cases are diagnosed every year [3]. Here the term “idiopathic” is used because the exact cause of scarring of tissues cannot be figured out (Fig. 15.1).
All over the world, different types of influenza viruses are responsible for seasonal pandemics annually. The influenza virus is responsible for 0.3–0.5 million deaths every year. Influenza A, B, and C are the three main types of influenza virus. Influenza A virus is the most infectious one among different types as it has the ability to change genetic shift and transfer from animal to human. Various synthetic drugs are prescribed for the treatment of influenza. But these drugs have their own drawbacks like the production of resistance and side effects. Hence remedies for influenza A can be obtained from nature. Different studies are carried over different plant extracts in the discovery of effective anti-influenza treatments. Various phytochemicals are being screened for effective and safe anti-influenza treatment. This chapter includes an overview of different plants and phytochemicals screened for anti-influenza A activity.
Tuberculosis is a highly contagious infectious disease triggered by Mycobacterium tuberculosis, which is widely spread by aerosol. The major site of infection is usually the lungs however the disease can attack any extra-pulmonary site as well, which is further diagnosis by necrotizing granulomatous inflammation. World Health Organization reported almost 8.9–10 million people are suffering from tuberculosis in 2019, including 56% men and 32% women, and 12% children. Multidrug-resistant tuberculosis (MDR-TB) is a medical condition in which Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin. In-vitro studies suggest that several bioactive compounds and their synthetic derivatives obtained from plants, fungi, and marine organism possesses antimycobacterial affinity. Phenolic compounds such as dihydrocubebin, hinokinin, ethoxycubebin possess the antimycobacterial activity. Mycobacterial cell envelope antagonists have been shown to obstruct the synthesis of mycolic acids, arabinogalactan, and peptidoglycan, essential components of the mycobacterial cell wall. The paramount antituberculous drugs hamper the development of mycolic acids or the aid mechanism which links them to the cell membrane. Medicines targeting RNA synthesis encompass those that restrict the assembly of bacterial DNA-dependent RNA polymerases, that are indispensable enzymes for RNA synthesis. Various molecular pathways for the target to cure tuberculosis entail the targets of M. tuberculosis cell wall synthesis, energy metabolism, folate metabolism, DNA replication, and RNA synthesis. Interestingly, in preserving the health of patients diagnosed with tuberculosis, medicinal plants have tremendous advantages with limited side effects as compare to the standard drugs.
More pregnant and nursing mothers are using herbal remedies than health care providers realize. Lack of familiarity with herbalism in addition to the sparsity of high-quality research for many complementary and alternative medicines are barriers for the western practitioner to engage a patient about herbal therapies. This review provides historical information and available evidence for Traditional Chinese and Western herbal medicines commonly sought by pregnant and nursing mothers. We will review herbs commonly used for: nausea and vomiting, constipation, gestational diabetes, threatened miscarriage, immune system support, parturition preparation, postpartum depression, postpartum bleeding and pain, wound healing, and lactation support.
In times of health crisis, including the current COVID‐19 pandemic, the potential benefit of botanical drugs and supplements emerges as a focus of attention, although controversial efficacy claims are rightly a concern. Phytotherapy has an established role in everyday self‐care and health care, but, since botanical preparations contain many chemical constituents rather than single compounds, challenges arise in demonstrating efficacy and safety. However, there is ample traditional, empirical, and clinical evidence that botanicals can offer some protection and alleviation of disease symptoms as well as promoting general well‐being. Newly emerging viral infections, specifically COVID‐19, represent a unique challenge in their novelty and absence of established antiviral treatment or immunization. We discuss here the roles and limitations of phytotherapy in helping to prevent and address viral infections, especially regarding their effects on immune response. Botanicals with a documented immunomodulatory, immunostimulatory, and antiinflammatory effects include adaptogens, Boswellia spp., Curcuma longa, Echinacea spp., Glycyrrhiza spp., medicinal fungi, Pelargonium sidoides, salicylate‐yielding herbs, and Sambucus spp. We further provide a clinical perspective on applications and safety of these herbs in prevention, onset, progression, and convalescence from respiratory viral infections.
Nanotechnology can be used as a sustainable solution to countless challenges affecting mankind. The utilization of nanoparticles has been documented in such diverse fields as medicine, agriculture, industry, energy generation, and pharmacy. Usually, the synthesis of these nanoparticles through physical and chemical techniques has several disadvantages, including impairment of human health and environmental hazards. Therefore, there is a need to search for novel and sustainable techniques for the synthesis of nanoparticles. The utilization of natural substances from biological sources could be a sustainable solution through the green synthesis of nanoparticles, especially from plant sources. This might be linked to an array of countless phytochemicals that are responsible for various biological activities. The green syntheses have several benefits: they are efficient, cost‐effective, sustainable, easy to prepare, ecofriendly, and demonstrate high antimicrobial activity against multidrug‐resistant pathogenic microorganisms. This chapter gives an insight into the biological activities of biogenic nanoparticles synthesized using phytochemicals obtained from important medicinal plants. These biological activities include the antibacterial, antifungal, neuroprotective, hepatoprotective, antiulcer, anticancer, and cardioprotective effects of nanoparticles. Moreover, detailed information on some biological activities during in vitro and in vivo trials is provided. The modes of action through which these nanoparticles exhibit their actions are also discussed.
American elderberry (Sambucus nigra subsp. canadensis) is a common fruiting shrub native to much of Eastern North America. While the fruit and flowers have been used for eons as food and medicine by both early and contemporary North Americans, its use is seeing a resurgence. This has resulted in a renewed interest in horticultural development and cultivation of elderberry, with numerous new products developed especially in the form of dietary supplements. Recent scientific research continues to underscore the health-benefitting attributes of both elderberry fruit and flowers, and is further fueling the development of a significant elderberry value chain from production, to processing, marketing, and consumption.
Bacterial RNA has recently emerged as an immune-stimulating factor during viral infection. The immune response in an organism is directly related to the progression of virus infections. Lactic acid bacteria in particular have anticancer, bioprotective, and antiallergic effects by modulating immunity. Here, we aimed to demonstrate the effect of bacterial RNA on in vitro production of IL-12, a proinflammatory cytokine, and on in vivo activity against influenza A virus (IFV) infection. Oral administration of heat-killed Enterococcus faecalis KH2 (KH2) or Lactobacillus plantarum SNK12 (SNK) in IFV-infected mice suppressed viral replication and stimulated production of virus-specific antibodies. However, ribonuclease-treated KH2 or SNK abrogated the effect, reducing IL-12 production in vitro and anti-IFV effects in vivo. Taken together, KH2 or SNK showed antiviral effects in vivo when administered orally, and the RNAs of KH2 and SNK play a part in these effects, despite the phylogenetic differences between the bacteria.
The common cold is the leading cause of doctor visits in the United States and annually results in 189 million lost school days. In the course of one year the U.S. population contracts approximately 1 billion colds. Influenza infection is still a leading cause of morbidity and mortality, accounting for 20-25 million doctor visits and 36,000 deaths per year in the United States. Conventional therapies for colds and flu focus primarily on temporary symptom relief and include over-the-counter antipyretics, anti-inflammatories, and decongestants. Treatment for influenza also includes prescription antiviral agents and vaccines for prevention. This article reviews the common cold and influenza viruses, presents the conventional treatment options, and highlights select botanicals (Echinacea spp., Sambucus nigra, larch arabinogalactan, Astragalus membranaceous, Baptisia tinctoria, Allium sativa, Panax quinquefolium, Eleutherococcus senticosus, Andrographis paniculata, olive leaf extract, and Isatis tinctoria) and nutritional considerations (vitamins A and C, zinc, high lactoferrin whey protein, N-acetylcysteine, and DHEA) that may help in the prevention and treatment of these conditions.
Black elderberries (Sambucus nigra L.) are well known as supportive agents against common cold and influenza. It is further known that bacterial super-infection during an influenza virus (IV) infection can lead to severe pneumonia. We have analyzed a standardized elderberry extract (Rubini, BerryPharma AG) for its antimicrobial and antiviral activity using the microtitre broth micro-dilution assay against three Gram-positive bacteria and one Gram-negative bacteria responsible for infections of the upper respiratory tract, as well as cell culture experiments for two different strains of influenza virus.
The antimicrobial activity of the elderberry extract was determined by bacterial growth experiments in liquid cultures using the extract at concentrations of 5%, 10%, 15% and 20%. The inhibitory effects were determined by plating the bacteria on agar plates. In addition, the inhibitory potential of the extract on the propagation of human pathogenic H5N1-type influenza A virus isolated from a patient and an influenza B virus strain was investigated using MTT and focus assays.
For the first time, it was shown that a standardized elderberry liquid extract possesses antimicrobial activity against both Gram-positive bacteria of Streptococcus pyogenes and group C and G Streptococci, and the Gram-negative bacterium Branhamella catarrhalis in liquid cultures. The liquid extract also displays an inhibitory effect on the propagation of human pathogenic influenza viruses.
Rubini elderberry liquid extract is active against human pathogenic bacteria as well as influenza viruses. The activities shown suggest that additional and alternative approaches to combat infections might be provided by this natural product.
Growing evidence supports a cardio-protective role for anthocyanins; however, there is limited evidence on their efficacy and safety following the consumption of relatively high but dietarily achievable doses in humans. We conducted a parallel-designed, randomized, placebo-controlled study to examine the effect of chronic consumption of anthocyanins on biomarkers of cardiovascular disease (CVD) risk and liver and kidney function in 52 healthy postmenopausal women (n = 26 in treatment and placebo groups). Volunteers (BMI, 24.7 +/- 3.6 kg/m(2); age, 58.2 +/- 5.6 y) consumed 500 mg/d anthocyanins as cyanidin glycosides (from elderberry) or placebo for 12 wk (2 capsules twice/d). At the beginning (wk 0) and end of the 12-wk intervention, levels of anthocyanins and biomarkers of CVD (inflammatory biomarkers, platelet reactivity, lipids, and glucose) and liver and kidney function (total bilirubin, albumin, urea, creatinine, alkaline phosphatase, alanine aminotransferase, and gamma-glutyl transferase) were assessed in fasted blood. Anthropometric, blood pressure, and pulse measurements were also taken. In addition, postprandial plasma anthocyanins were measured (t = 1, 2, 3 h) following a 500-mg oral bolus dose. After 12 wk of chronic exposure to anthocyanins, there was no significant change in biomarkers of CVD risk and liver and kidney function remained within clinically acceptable ranges. We observed no plasma accumulation of anthocyanins; however, postprandial metabolism increased (P = 0.02). In conclusion, these data suggest that chronic consumption of 500 mg/d of elderberry extract for 12 wk is apparently safe, but ineffective in altering biomarkers of CVD risk in healthy postmenopausal women.
A ionization technique in mass spectrometry called Direct Analysis in Real Time Mass Spectrometry (DART TOF-MS) coupled with a Direct Binding Assay was used to identify and characterize anti-viral components of an elderberry fruit (Sambucus nigra L.) extract without either derivatization or separation by standard chromatographic techniques. The elderberry extract inhibited Human Influenza A (H1N1) infection in vitro with an IC(50) value of 252+/-34 microg/mL. The Direct Binding Assay established that flavonoids from the elderberry extract bind to H1N1 virions and, when bound, block the ability of the viruses to infect host cells. Two compounds were identified, 5,7,3',4'-tetra-O-methylquercetin (1) and 5,7-dihydroxy-4-oxo-2-(3,4,5-trihydroxyphenyl)chroman-3-yl-3,4,5-trihydroxycyclohexanecarboxylate (2), as H1N1-bound chemical species. Compound 1 and dihydromyricetin (3), the corresponding 3-hydroxyflavonone of 2, were synthesized and shown to inhibit H1N1 infection in vitro by binding to H1N1 virions, blocking host cell entry and/or recognition. Compound 1 gave an IC(50) of 0.13 microg/mL (0.36 microM) for H1N1 infection inhibition, while dihydromyricetin (3) achieved an IC(50) of 2.8 microg/mL (8.7 microM). The H1N1 inhibition activities of the elderberry flavonoids compare favorably to the known anti-influenza activities of Oseltamivir (Tamiflu; 0.32 microM) and Amantadine (27 microM).
Sambucus nigra L. products - Sambucol - are based on a standardized black elderberry extract. They are natural remedies with antiviral properties, especially against different strains of influenza virus. Sambucol was shown to be effective in vitro against 10 strains of influenza virus. In a double-blind, placebo-controlled, randomized study, Sambucol reduced the duration of flu symptoms to 3-4 days. Convalescent phase serum showed a higher antibody level to influenza virus in the Sambucol group, than in the control group. The present study aimed to assess the effect of Sambucol products on the healthy immune system - namely, its effect on cytokine production. The production of inflammatory cytokines was tested using blood - derived monocytes from 12 healthy human donors. Adherent monocytes were separated from PBL and incubated with different Sambucol preparations i.e., Sambucol Elderberry Extract, Sambucol Black Elderberry Syrup, Sambucol Immune System and Sambucol for Kids. Production of inflammatory cytokines (IL-1 beta, TNF-alpha, IL-6, IL-8) was significantly increased, mostly by the Sambucol Black Elderberry Extract (2-45 fold), as compared to LPS, a known monocyte activator (3.6-10.7 fold). The most striking increase was noted in TNF-alpha production (44.9 fold). We conclude from this study that, in addition to its antiviral properties, Sambucol Elderberry Extract and its formulations activate the healthy immune system by increasing inflammatory cytokine production. Sambucol might therefore be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases. Sambucol could also have an immunoprotective or immunostimulatory effect when administered to cancer or AIDS patients, in conjunction with chemotherapeutic or other treatments. In view of the increasing popularity of botanical supplements, such studies and investigations in vitro, in vivo and in clinical trials need to be developed.
Some herbal remedies are sold as food additives and are believed to have immune-enhancing properties.
To study the effect of five herbal remedies--Sambucol Black Elderberry Extract, Sambucol Active Defense Formula and Sambucol for Kids (with known antiviral properties), Protec and Chizukit N (containing propolis and Echinacea, claimed to be immune enhancers)--on the production of cytokines, one of the main components of the immune system.
The production of four inflammatory cytokines (interleukin-1 beta, tumor necrosis factor alpha, and IL-6 and IL-8) and one anti-inflammatory cytokine (IL-10) was tested using blood-derived monocytes from 12 healthy donors.
The Sambucol preparations increased the production of five cytokines (1.3-6.2 fold) compared to the control. Protec induced only a moderate production of IL-8 (1.6 fold) and IL-10 (2.3 fold) while Chizukit N caused only a moderate increase in IL-10 production (1.4 fold). Both Protec and Chizukit N caused moderate decreases in IL-1 beta, TNF alpha and IL-6 production. Lipopolysaccharide, a known activator of monocytes, induced the highest levels of cytokine production (3.6-10.7 fold).
The three Sambucol formulations activate the healthy immune system by increasing inflammatory and anti-inflammatory cytokines production, while the effect of Protec and Chizukit N is much less. Sambucol could therefore have immunostimulatory properties when administered to patients suffering from influenza (as shown before), or immunodepressed cancer or AIDS patients who are receiving chemotherapy or other treatments.
Elderberry has been used in folk medicine for centuries to treat influenza, colds and sinusitis, and has been reported to have antiviral activity against influenza and herpes simplex. We investigated the efficacy and safety of oral elderberry syrup for treating influenza A and B infections. Sixty patients (aged 18-54 years) suffering from influenza-like symptoms for 48 h or less were enrolled in this randomized, double-blind, placebo-controlled study during the influenza season of 1999-2000 in Norway. Patients received 15 ml of elderberry or placebo syrup four times a day for 5 days, and recorded their symptoms using a visual analogue scale. Symptoms were relieved on average 4 days earlier and use of rescue medication was significantly less in those receiving elderberry extract compared with placebo. Elderberry extract seems to offer an efficient, safe and cost-effective treatment for influenza. These findings need to be confirmed in a larger study.
Polyphenolic compound catechins ((-)-epigallocatechin gallate (EGCG), (-)-epicatechin gallate (ECG) and (-)-epigallocatechin (EGC)) from green tea were evaluated for their ability to inhibit influenza virus replication in cell culture and for potentially direct virucidal effect. Among the test compounds, the EGCG and ECG were found to be potent inhibitors of influenza virus replication in MDCK cell culture and this effect was observed in all influenza virus subtypes tested, including A/H1N1, A/H3N2 and B virus. The 50% effective inhibition concentration (EC50) of EGCG, ECG, and EGC for influenza A virus were 22-28, 22-40 and 309-318 microM, respectively. EGCG and ECG exhibited hemagglutination inhibition activity, EGCG being more effective. However, the sensitivity in hemagglutination inhibition was widely different among three different subtypes of influenza viruses tested. Quantitative RT-PCR analysis revealed that, at high concentration, EGCG and ECG also suppressed viral RNA synthesis in MDCK cells whereas EGC failed to show similar effect. Similarly, EGCG and ECG inhibited the neuraminidase activity more effectively than the EGC. The results show that the 3-galloyl group of catechin skeleton plays an important role on the observed antiviral activity, whereas the 5'-OH at the trihydroxy benzyl moiety at 2-position plays a minor role. The results, along with the HA type-specific effect, suggest that the antiviral effect of catechins on influenza virus is mediated not only by specific interaction with HA, but altering the physical properties of viral membrane.
Influenza virus with resistance to antiviral drugs emerges with increased frequency in immunocompromised patients and can
limit the benefit of M2 and neuraminidase (NA) inhibitors. We document 3 cases of influenza in severely immunocompromised
patients from whom virus variants with molecular markers of resistance to anti-influenza drugs were recovered. Virus variants
recovered from 2 patients had mutations in the M2, NA (with a previously recognized Glu119Val NA substitution), and hemagglutinin
genes. We describe a novel Asp198Asn NA mutation in an influenza B virus and its decreased susceptibility to both oseltamivir
and zanamivir
Several parameters of the vanillin assay were examined to determine which must be most closely controlled to ensure accuracy and reproducibility. A 20-min extraction in methanol was found to be adequate. When corrected for background color, the modified vanillin assay was found to give nearly identical values with those obtained with the regular vanillin assay, except with group II sorghum. The reactions of tannin and catechin, the usual standard, with vanillin were found to differ markedly in reaction kinetics. Assays of purified tannin showed that use of catechin equivalents overestimates tannin content The assay was found to be extremely temperature dependent. Revised procedures for the vanillin assay are presented which give excellent reproducibility.
Rochelle salt, normally present in the dinitrosalicylic acid reagent for reducing sugar, interferes with the protective action of the sulfite, but is essential to color stability. The difficulty may be resolved either by eliminating Rochelle salt from the reagent and adding it to the mixture of reducing sugar and reagent after the color is developed, or by adding known amounts of glucose to the samples of reducing sugar to compensate for the losses sustained in the presence of the Rochelle salt. The optimal composition of a modified dinitrosalicylic acid reagent is given.
The levels of total polyphenols and o-diphenols were determined in virgin oils and in chloroform/methanol-extracted oils.
The solventextracted oils were richer in polyphenols than the virgin oils. High polyphenol content was associated with a high
resistance to oxidation of the oils. A linear relationship was found between polyphenol content and the oxidative stability
of the virgin oils during storage at 60 C. After removal of the polyphenols, the oxidative stability of the oils decreased
considerably and seemed to depend on polyunsaturated fatty acid concentration.
Simple sugars, oligosaccharides, polysaccharides, and their derivatives, including the methyl ethers with free or potentially free reducing groups, give an orange-yellow color when treated with phenol and concentrated sulfuric acid. The reaction is sensitive and the color is stable. By use of this phenol-sulfuric acid reaction, a method has been developed to determine submicro amounts of sugars and related substances. In conjunction with paper partition chromatography the method is useful for the determination of the composition of polysaccharides and their methyl derivatives.
Lactic acid bacteria (LAB) are known to have effects on immune function. From 203 strains of LAB isolated from fermented foods, we selected a beneficial strain, Lactobacillus plantarum strain YU (LpYU), which has high interleukin (IL)-12-inducing activity in mouse peritoneal macrophages. This activity of LpYU was partially mediated by Toll-like receptor (TLR) 2, but not TLR4 or TLR9. Oral administration of LpYU to ovalbumin (OVA)-immunized mice caused suppression of serum OVA-specific immunoglobulin E (IgE) levels, enhancing interferon (IFN)-γ production from spleen cells in response to OVA. Furthermore, LpYU enhanced natural killer cell activity in spleen cells and the production of IgA from Peyer's patch cells. Because activation of Th1 immune responses and IgA production induce antiviral effects, we evaluated the inhibitory effects of LpYU against the influenza A virus (A/NWS/33, H1N1) (IFV). Oral administration of LpYU suppressed viral proliferation in the lungs and in bronchoalveolar lavage fluids (BALFs). Both levels of IFV-specific secretory IgA in BALF and feces and titers of IFV-specific neutralizing antibody in BALFs and sera were increased. These results indicate that LpYU has a protective effect against IFV replication. We conclude that this strain has a beneficial effect in activating Th1 immune responses and preventing viral infection.
The reduced immunogenicity of the H5 hemagglutinin (HA), compared to seasonal HA serotypes, has stimulated searches for effective adjuvants to improve H5 vaccine efficacy. This study examined the immunogenicity and protective efficacy in ferrets immunized with a split-virion H5N1 vaccine combined with Advax™, a novel delta inulin-based polysaccharide adjuvant technology that has previously demonstrated ability to augment humoral and cellular immunity to co-administered antigens.
Ferrets were vaccinated twice 21 days apart with 7.5 μg or 22.5 μg of a split-virion preparation of A/Vietnam/1203/2004 with or without adjuvant. An additional group received just one immunization with 22.5 μg HA plus adjuvant. Serum antibodies were measured by hemagglutination inhibition and microneutralization assays. Vaccinated animals were challenged intranasally 21 days after the last immunization with 10(6) EID(50) of the homologous strain. Morbidity was assessed by observed behavior, weight loss, temperature, cytopenias, histopathology, and viral load.
No serum neutralization antibody was detected after two immunizations with unadjuvanted vaccine. Two immunizations with high or low dose adjuvanted vaccine stimulated high neutralizing antibody titers. Survival was 100% in all groups receiving adjuvanted-vaccine including the single dose group, compared to 67% survival with unadjuvanted vaccine, and 0% survival in saline or adjuvant-alone controls. Minimal morbidity was seen in all animals receiving adjuvanted vaccine, and was limited to rhinorrhea and mild thrombocytopenia, without fever, weight loss, or reduced activity. H5N1 virus was cleared from the nasal wash by day 4 post-challenge only in animals receiving adjuvanted vaccine which also prevented viral invasion of the brain in most animals.
In this initial study, Advax™ adjuvant formulations improved the protective efficacy of a split-virion H5N1 vaccine as measured by significantly enhanced immunogenicity, survival, and reduced morbidity.
Sambucus nigra (elder) has been documented as a traditional treatment of diabetes. In the present study, an aqueous extract of elder (AEE, 1 g/L) significantly increased 2-deoxy-glucose transport, glucose oxidation and glycogenesis of mouse abdominal muscle in the absence of added insulin (2 x 2 factorial design). in acute 20-min tests, 0.25-1 g/L AEE evoked a stepwise stimulation of insulin secretion from clonal pancreatic beta-cells. The insulin releasing effect of AEE (0.5 g/L) was significantly potentiated by 16.7 mmol/L of glucose and significantly reduced by 0.5 mmol/L of diazoxide. AEE did not further enhance insulin secretion in cells stimulated by 10 mmol/L of L-alanine, 1 mmol/L of 3-isobutyl-1-methylxanthine or a depolarizing concentration of KCl (25 mmol/L). Prior exposure of clonal pancreatic beta-cells to AEE did not alter subsequent stimulation of insulin secretion induced by 10 mmol/L of L-alanine, thereby precluding a detrimental effect on cell viability. The insulinotropic action of AEE was partially dependent upon use of heat during extract preparation. Activity of AEE was heat-stable, acetone-insoluble and unaltered by prolonged exposure to acid/alkali (0.1 mol/L of HCl and NaOH). However, activity was significantly decreased 41% by dialysis to remove components with molecular mass <2000 Da. Sequential extraction with solvents revealed activity in both methanol and water fractions, indicating a cumulative effect of more than one extract constituent. Known constituents of elder, including lectin, rutin and the lipophilic triterpenoid (lupeol) and sterol (beta-sitosterol), did not stimulate insulin secretion. The results demonstrate the presence of insulin-releasing and insulin-like activity in the traditional antidiabetic plant, Sambucus nigra.
Arctiin and its aglucone, arctigenin from the fruits of Arctium lappa L. showed potent in vitro antiviral activities against influenza A virus (A/NWS/33, H1N1) (IFV). Based on the data from time-of-addition experiments and on release tests of progeny viruses, arctigenin was assumed to interfere with early event(s) of viral replication after viral penetration into cells, and to suppress the release of progeny viruses from the host cells. Arctiin was orally effective against either IFV-inoculated normal or 5-fluorouracil (5-FU)-treated mice, being less effective as compared with oseltamivir. Noticeably, arctiin produced a larger amount of virus-specific antibody than those of control and oseltamivir in sera collected from 5-FU-treated mice. Furthermore, oral treatment of 5-FU-treated mice with arctiin did not induce any resistant viruses, although the same treatment with oseltamivir induced resistant viruses at a 50% frequency. When the combination of arctiin and oseltamivir was administered to normal mice infected with IFV, the virus yields in both bronchoalveolar lavage fluids and lungs were significantly reduced relative to those in the mice treated with arctiin or oseltamivir alone. Thus, monotherapy of arctiin or combined therapy of arctiin with oseltamivir would be another treatment option for influenza.
The berries of European elder are used in traditional German medicine for various complaints. Due to insufficient research data, elderberry fruit was not monographed by the German Commission E at the end of the last century. A comprehensive review of the literature was conducted to summarize the pharmacological and clinical effects of elderberry fruit. Several databases and other sources were searched to identify in vitro and animal studies, and clinical trials investigating elderberry fruit preparations. For the latter, the level of evidence was evaluated as described previously. Elderberry fruit preparations may provide antioxidant, antiviral and antiproliferative effects in vitro. One animal experiment and one clinical trial were able to back the antioxidative impact in terms of a weak antilipidemic effect. Antibacterial and antiinflammatory effects seem possible, but need further support. In rats, an aqueous elderberry fruit extract produced central depression and analgesia and an ethanol fruit extract improved acetic acid-induced colitis. Several in vitro studies together with two exploratory studies in humans and one open study in chimpanzees indicate that the aqueous elderberry extract Sambucol may be useful for the treatment of viral influenza infections. These promising effects of elderberry fruit preparations from experimental and clinical studies should be backed by more rigorous studies before these preparations are recommended in the prevention of diseases and in treatment schedules.
A standardized elderberry extract, Sambucol (SAM), reduced hemagglutination and inhibited replication of human influenza viruses type A/Shangdong 9/93 (H3N2), A/Beijing 32/92 (H3N2), A/Texas 36/91 (H1N1), A/Singapore 6/86 (H1N1), type B/Panama 45/90, B/Yamagata 16/88, B/Ann Arbor 1/86, and of animal strains from Northern European swine and turkeys, A/Sw/Ger 2/81, A/Tur/Ger 3/91, and A/Sw/Ger 8533/91 in Madin-Darby canine kidney cells. A placebo-controlled, double blind study was carried out on a group of individuals living in an agricultural community (kibbutz) during an outbreak of influenza B/Panama in 1993. Fever, feeling of improvement, and complete cure were recorded during 6 days. Sera obtained in the acute and convalescent phases were tested for the presence of antibodies to influenza A, B, respiratory syncytial, and adenoviruses. Convalescent phase serologies showed higher mean and mean geometric hemagglutination inhibition (HI) titers to influenza B in the group treated with SAM than in the control group. A significant improvement of the symptoms, including fever, was seen in 93.3% of the cases in the SAM-treated group within 2 days, whereas in the control group 91.7% of the patients showed an improvement within 6 days (p < 0.001). A complete cure was achieved within 2 to 3 days in nearly 90% of the SAM-treated group and within at least 6 days in the placebo group (p < 0.001). No satisfactory medication to cure influenza type A and B is available. Considering the efficacy of the extract in vitro on all strains of influenza virus tested, the clinical results, its low cost, and absence of side-effects, this preparation could offer a possibility for safe treatment for influenza A and B.
Oseltamivir is an effective inhibitor of influenza virus neuraminidase. Although viruses resistant to oseltamivir emerge less frequently than those resistant to amantadine or rimantadine, information on oseltamivir-resistant viruses arising during clinical use of the drug in children is limited. Our aim was to investigate oseltamivir resistance in a group of children treated for influenza.
We analysed influenza A viruses (H3N2) collected from 50 children before and during treatment with oseltamivir. We sequenced the genes for neuraminidase and haemagglutinin and studied the mutant neuraminidases for their sensitivity to oseltamivir carboxylate.
We found neuraminidase mutations in viruses from nine patients (18%), six of whom had mutations at position 292 (Arg292Lys) and two at position 119 (Glu119Val), which are known to confer resistance to neuraminidase inhibitors. We also identified another mutation (Asn294Ser) in one patient. Sensitivity testing to oseltamivir carboxylate revealed that the neuraminidases of viruses that have an Arg292Lys, Glu119Val, or Asn294Ser mutation were about 10(4)-10(5)-fold, 500-fold, or 300-fold more resistant than their pretreatment neuraminidases, respectively. Oseltamivir-resistant viruses were first detected at day 4 of treatment and on each successive day of the study. More than 10(3) infectious units per mL of virus were detected in some of the patients who did not shed drug-resistant viruses, even after 5 days of treatment.
Oseltamivir-resistant mutants in children being treated for influenza with oseltamivir arise more frequently than previously reported. Furthermore, children can be a source of viral transmission, even after 5 days of treatment with oseltamivir.
Anthocyanins and proanthocyanidins were characterized by HPLC-ESI-MS/MS coupled with a diode array and/or fluorescent detector in seven cultivars of Ribes nigrum (black currant) and Ribes rubrum (red currant, Red Lake), six cultivars of Ribes grossularia (gooseberries), Aronia melanocarpa(chokeberry), and Sambucus nigra (elderberry). Thirty-one different anthocyanins were detected in these berries, but not every anthocyanin was observed in each berry. A number of minor anthocyanins were identified from these berries for the first time. The concentrations of individual anthocyanins in all of the berries were quantified using relevant anthocyanidin 3-glucoside standards. Among the berries studied in this paper and in berries in general, chokeberry has the highest total anthocyanin concentrations [1480 mg/100 g of fresh weight (FW)], whereas the lowest total anthocyanin concentration in the berries studied was found in the gooseberry cv. Careless, which contained only 0.07 mg/100 g of FW. Two cultivars of gooseberries (Marigold and Leveller) did not contain any anthocyanins. Total proanthocyanidin concentrations in the berries studied ranged from 23 to 664 mg/100 g of FW in elderberry and chokeberry, respectively. Procyanidin or prodelphinidin polymers were the predominant components (>65% w/w) in most of the berries. The lipophilic and hydrophilic antioxidant capacities were measured by the oxygen radical absorbance capacity (ORAC(FL)) procedure. The total antioxidant capacity varied from 21 micromol of TE/g of FW in Careless gooseberry to 161 micromol of TE/g of FW in chokeberry. Total phenolics in the berries in general paralleled hydrophilic antioxidant capacity.
Foods and beverages rich in phenolic compounds, especially flavonoids, have often been associated with decreased risk of developing several diseases. However, it remains unclear whether this protective effect is attributable to the phenols or to other agents in the diet. Alleged health-promoting effects of flavonoids are usually attributed to their powerful antioxidant activities, but evidence for in vivo antioxidant effects of flavonoids is confusing and equivocal. This may be because maximal plasma concentrations, even after extensive flavonoid intake, may be low (insufficient to exert significant systemic antioxidant effects) and because flavonoid metabolites tend to have decreased antioxidant activity. Reports of substantial increases in plasma total antioxidant activity after flavonoid intake must be interpreted with caution; findings may be attributable to changes in urate concentrations. However, phenols might exert direct effects within the gastrointestinal tract, because of the high concentrations present. These effects could include binding of prooxidant iron, scavenging of reactive nitrogen, chlorine, and oxygen species, and perhaps inhibition of cyclooxygenases and lipoxygenases. Our measurements of flavonoids and other phenols in human fecal water are consistent with this concept. We argue that tocopherols and tocotrienols may also exert direct beneficial effects in the gastrointestinal tract and that their return to the gastrointestinal tract by the liver through the bile may be physiologically advantageous.
Anthocyanins (ACNs) are water-soluble plant pigments that have important functions in plant physiology as well as possible health effects. Over 100 common foods were screened for ACNs, and 24 of them were found to contain ACNs. Concentrations of total ACNs varied considerably from 0.7 to 1480 mg/100 g of fresh weight in gooseberry ('Careless' variety) and chokeberry, respectively. Not only does the concentration vary, but the specific anthocyanins present in foods are also quite different. Only six common aglycones, delphinidin, cyanidin, petunidin, pelargonidin, peonidin, and malvidin, were found in all of these foods. However, their sugar moieties and acylation patterns varied from food to food. Results from this study will add to the available data for the USDA Nutrient Database of flavonoids. On the basis of the concentration data and updated food intake data from NHANES 2001-2002, the daily intake of ACNs is estimated to be 12.5 mg/day/person in the United States. Of the different aglycones, cyanidin, delphinidin, and malvidin were estimated to contribute 45, 21, and 15%, respectively, of the total ACN intake. Nonacylated contributed 77% compared to 23% from acylated ACNs.
Influenza, a respiratory disease caused by influenza viruses, is still a worldwide threat with a high potential to cause a pandemic. Beside vaccination, only two classes of drugs are available for antiviral treatment against the pathogen. Here we show that CYSTUS052, a plant extract from a special variety of Cistus incanus that is rich in polymeric polyphenols, exhibits antiviral activity against a highly pathogenic avian influenza A virus (H7N7) in cell culture and in a mouse infection model. In vitro and in vivo treatment was performed with an aerosol formulation, because the bioavailability of high molecular weight polyphenols is poor. In MDCK cells, a 90% reduction of plaque numbers on cells pre-incubated with the plant extract was achieved. For in vivo experiments we used a novel monitoring system for influenza A virus-infected mice that allows measurement of body temperature and gross motor-activity of the animals. Mice treated with CYSTUS052 did not develop disease, showed neither differences in their body temperature nor differences in their gross motor-activity and exhibited no histological alterations of the bronchiolus epithelial cells.
An acidic polysaccharide (APS) was isolated from the extract of Cordyceps militaris grown on germinated soybeans. Analyses of sugar composition indicated that APS consisted of d-galactose, L-arabinose, D-xylose, L-rhamnose, and D-galacturonic acid. On the basis of the result of methylation analysis, APS was considered to be mainly composed of Araf-(1-->, -->5)-Araf-(1-->, -->4)-Galp-(1--> and -->4)-GalAp-(1--> residues. When the polysaccharide was intranasally administered, it decreased virus titers in the bronchoalveolar lavage fluid and the lung of mice infected with influenza A virus and increased survival rate. Furthermore, APS increased TNF-alpha and IFN-gamma levels in mice when compared with those of untreated mice. APS enhanced nitric oxide (NO) production and induced iNOS mRNA and protein expressions in RAW 264.7 murine macrophage cells. The induction of mRNA expression of cytokines including IL-1beta, IL-6, IL-10, and TNF-alpha was also observed. These results demonstrated that APS might have beneficial therapeutic effects on influenza A virus infection at least in part by modulation of the immune function of macrophages.
Neuraminidase inhibitors (NAIs) have been used since 2005 in France.
Influenza viruses isolated in hospital and community cases in winter 2005-2006 were evaluated for their sensitivity to NAIs.
Isolates were tested in duplicate with a fluorescence-based neuraminidase assay. The IC50 for oseltamivir or zanamivir was calculated for each strain. Mean IC50 (+/-S.D.) are expressed in nM. Viruses with IC50 superior or very superior to the upper limit (mean IC50+2.5 S.D.) were considered as outliers or resistant viruses, respectively. HA and NA genes for outliers, resistant strains and for a few sensitive strains were sequenced.
Out of 225 B isolates, one was found resistant to both oseltamivir and zanamivir with a D197Y mutation in NA and eight isolates were outliers for oseltamivir and/or zanamivir. Out of 151 A (H1N1) isolates, one was found resistant to oseltamivir but sensitive to zanamivir with a H275Y mutation in NA, two isolates were resistant to zanamivir and three isolates were outliers for oseltamivir and/or zanamivir. New mutations were detected in outliers compared to sensitive viruses.
Resistant influenza strains to NAIs are circulating at a stable and low level of 1% since the introduction of NAIs in clinical practice.
Fucoidan, a sulfated polysaccharide isolated from an edible brown alga Undaria pinnatifida, was previously shown to be a potent inhibitor of the in vitro replication of herpes simplex virus type 1 (HSV-1). HSV-1 is a member of herpes viruses that cause infections ranging from trivial mucosal ulcers to life-threatening disorders in immunocompromised hosts. In the in vivo conditions, the replication of HSV-1 is controlled under the immunoresponse coordinated by both the innate and adaptive immune systems. In the present study, the effects of the fucoidan were examined on in vivo viral replication and the host's immune defense system. Oral administration of the fucoidan protected mice from infection with HSV-1 as judged from the survival rate and lesion scores. Phagocytic activity of macrophages and B cell blastogenesis in vitro were significantly stimulated by the fucoidan, while no significant change in the release of NO(2)(-) by macrophages was observed. In in vivo studies, oral administration of the fucoidan produced the augmentation of NK activity in HSV-1-infected mice immunosuppressed by 5-fluorouracil treatment. CTL activity in HSV-1-infected mice was also enhanced by oral administration of the fucoidan. The production of neutralizing antibodies in the mice inoculated with HSV-1 was significantly promoted during the oral administration of the fucoidan for 3 weeks. These results suggested that oral intake of the fucoidan might take the protective effects through direct inhibition of viral replication and stimulation of both innate and adaptive immune defense functions.
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