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Randomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B Virus Infections
Abstract
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.
... Regarding respiratory tract diseases caused by the influenza virus, the incidence of infection was lower in the group that gargled with tea catechin extract than in the control group [129]. For this same virus, a randomized study using elderberry extract showed that the treatment was safe and effective on both virus types, A and B [130]. ...
... In our previous interventional study, the S. ebulus fruits were found to improve lipid profile in healthy volunteers [39]. Some studies show that supplementation with Sambucus nigra was found to substantially reduce upper respiratory symptoms in case of viral infections, such as the common cold and influenza [40][41][42]. S. ebulus fruit extract has been found to be effective in treating paederus dermatitis in humans, exerting anti-inflammatory, wound healing, and analgesic effects [43]. ...
Sambucus ebulus (SE) fruits are used for immune stimulation and amelioration of gastrointestinal inflammatory conditions. Currently, there is no scientific evidence of their effects on various aspects of the immune response mechanisms in humans. The purpose of this study was to evaluate the immunomodulatory potential of SE fruit infusion intake in healthy humans. Anthocyanin content was determined with UPLC-ESI-MS/MS. Fifty-three volunteers enrolled in a 4-week SE infusion intake intervention. Blood count, serum total protein, Interleukin 1 beta (IL-1β), Interleukin 6 (IL-6), Tumor Necrosis Factor Alpha (TNFα), High-sensitivity C-reactive protein (hs-CRP), C3, and C4 levels were measured on automatic analyzers, and Interleukin 8 (IL-8) was measured manually with an ELISA kit. Cyanidin-3-O-galactoside (48.15 mg/g DW), followed by cyaniding-3-sambubioside (43.41 ± 1.07 mg/g DW), were the most abundant anthocyanins in SE samples. A significant decrease in total protein (2.82%), IL-6 (20.15%), TNFα (5.38%), IL-8 (5.50%), C3 (4.16%), and C4 (14.29%) was established in the whole group. Total protein, IL-8, TNFα, and C4 decreased in women (3.11%, 4.76%, 5.09%, and 11.11%), and IL-6 decreased (40.61%) in men. Hb (1.20%) and hematocrit (1.55%) levels decreased in the whole group and in the women group (1.61% and 2.20%). SE fruits exert immune-modulatory activity as revealed by decreased pro-inflammatory status and complement activity markers in healthy volunteers after a 4-week intervention.
... 2. Zakay-Rones et al. (2004) conducted another RCT on 60 patients and found that influenza symptoms were relived on average four days earlier, and rescue medication was significantly less in those receiving elderberry extract compared with placebo. Patients received 15 ml elderberry (Sambucol) or placebo four times a day for five days. ...
... 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.
... An ethanolic Sambucus Formosana Nakai (also known as Sambucus javanica) extract, a species of elderberry rich in phenolic acid components, exhibited antiviral activity against human coronavirus HCoV-NL63 in vitro [37]. 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.
... Also, elderberries are known to boost immunity and have been used for treatment of viral infections, such as influenza A and B, and other respiratory infections. The plant is rich in dietary fibers, polyphenols, and vitamins C and A [159][160][161]. ...
This chapter highlights the traditional use of Mediterranean edible plants, frequently
used as herbs and spices in Mediterranean cuisine, and medicinal plants, used
as natural therapeutics among the people in the Mediterranean region. The high
phytonutrient content and diversity of these edible and nonedible wild plants in the
Mediterranean are emphasized and their folk use is reviewed. The herbs, spices, and
medicinal plants are vital constituents of the Mediterranean dietary pattern and lifestyle,
known as the Mediterranean diet (MD). They significantly contribute to high
antioxidant and anti-inflammatory character of the diet and its health and well-being
benefits.
... Vijayan et al., 2004;Koch et al., 2007;Zakay-Rones et al., 2004;Krawitz et al., 2011;Shulong et al., 2008;Singh et al., 2013;Yang et al., 2006;Yadav et al., 2021). At different regional levels, medicinal plants' natural constituents are used to treat ailments, with or without processing. ...
... Several studies showed the major potent immune-modulating components of the EB extract are anthocyanins, phenolic acids, and flavonoids [40,56]. Although the immune-stimulating role of these secondary metabolites is well established in the literature, immunological studies relating to fish immune cells are limited to our knowledge [14,37,[57][58][59]. In addition, most of the experiments performed to understand the role of the nutraceuticals were performed in the in vivo condition, which does not provide specific information regarding the capabilities of the nutraceuticals at the cellular level. ...
The study of nutraceuticals and their connection to immunity is an expanding field of research. The use of nutraceuticals to alleviate stress and enhance immunity in adverse aquaculture environments have been examined to a certain extent. To elucidate the understanding, we focused on the immunological effect of membrane-separated 13% anthocyanin standardized elderberry (EB) extract with maltodextrin excipient, widely used first-line nutraceuticals to augment the immunity, in aquaculture fish, Nile tilapia. To evaluate the potential of EB-extract, we assessed their capability to enhance lymphocyte proliferation and interleukin-2 production in an in-vitro condition using spleen and thymus lymphocytes. The experiments on spleen and thymus T-cells demonstrated significantly higher T-cell proliferation by EB-extract when lectin mitogen Con A was present as a stimulator. Likewise, our spleen B-cell proliferation result reveals a significant effect of EB-extracts, along with B-cell stimulator non-lectin mitogen LPS. Further, the quantification of IL-2 indicates elevated IL-2 levels when spleen T-cells were cultured with EB-extracts and with Con A present as a stimulator. These suggest that 13% anthocyanin standardized EB-extracts can aggrandize fish cells’ cellular and humoral immune responses. With further research, elderberry extracts could be used to supplement commercial feed in aquaculture to reduce stress and stimulate the immune response.
Kara mürver, latince ismiyle Sambucus nigra, uzun yıllardır kullanılan Adoxaceae familyasına ait bir bitkidir. Ortak isimleri arasında kara mürver, siyah yaşlı, Avrupa yaşlısı, Avrupa mürveri ve Avrupa kara mürveri de vardır. Hipokrat tarafından doğanın en şifalı bitkisi olarak görüldüğü de bilinmektedir. Meyveleri koyu mor-siyah renktedir. 100 gramı ortalama 73 kalori içerir ve vitamin-mineral açısından oldukça zengin bir yapıya sahiptir. Kara mürver, yapısında birçok faydalı bileşik bulundurmaktadır. Bunlar arasında en önemli olanlar flavonoidler, fenolik asitler ve antosiyaninlerdir. En baskın olanı ise antioksidan özelliği olduğu bilinen antosiyaninlerdir. Bunların yanında kara mürver, içerdiği siyanojenik glikozitlerden kaynaklı olarak zehirlenmeye sebep olabilmektedir. Bunu önleyebilmek için mutlaka ısıl işleme maruz bırakıldıktan sonra tüketilmesi gerekmektedir. Kara mürverin diüretik, laksatif, diyaforetik, antioksidan, antiviral, immünomodülatör, antiinflamatuar, antimikrobiyal, antikonvülsan, antidepresan ve antikarsinojenik gibi çeşitli etkilere sahip olduğu bilinmektedir. Aynı zamanda diyabet, hipertansiyon, obezite, hiperlipidemi, metabolik işlev bozuklukları, üriner parametreler üzerinde de kullanılabilmektedir. Hem sağlıklı hem de hasta organizmalarda vücudun savunma mekanizmalarını düzenlemeye destek olarak bağışıklık sistemini güçlendirdiği bilinmektedir. Henüz çalışmalar yetersiz olsa da COVID-19 için de kullanılabileceği düşünülmektedir. Bu derlemede kara mürverin antioksidan, antiviral, antibakteriyel, antiinflamatuar, antikanser etkileri ve bağışıklık sistemiyle ilişkisinden bahsedilmiştir.
Elderberry is highly reputed for its health-improving effects. Multiple pieces of evidence indicate that the consumption of berries is linked to enhancing human health and preventing or delaying the onset of chronic medical conditions. Compared with other fruit, elderberry is a very rich source of anthocyanins (approximately 80% of the polyphenol content). These polyphenols are the principals that essentially contribute to the high antioxidant and anti-inflammatory capacities and the health benefits of elderberry fruit extract. These health effects include attenuation of cardiovascular, neurodegenerative, and inflammatory disorders, as well as anti-diabetic, anticancer, antiviral, and immuno-stimulatory effects. Sales of elderberry supplements skyrocketed to $320 million over the year 2020, according to an American Botanical Council (ABC) report, which is attributable to the purported immune-enhancing effects of elderberry. In the current review, the chemical composition of the polyphenolic content of the European elderberry (Sambucus nigra) and the American elderberry(Sambucus canadensis), as well as the analytical techniques employed to analyze, characterize, and ascertain the chemical consistency will be addressed. Further, the factors that influence the consistency of the polyphenolic chemical composition, and hence, the consistency of the health benefits of elderberry extracts will be presented. Additionally, adulteration and safety as factors contributing to consistency will be covered. The role of elderberry in enhancing human health alone with the pharmacological basis, the cellular pathways, and the molecular mechanisms underlying the observed health benefits of elderberry fruit extracts will be also reviewed
Rapid diagnostic methods are important in managing respiratory tract infections and in identifying epidemics at an early stage. In viral infections, diagnosis may be obtained in 1 to 5 hours by the detection of viral antigens or nucleic acids directly in the clinical specimen. During the past year, excellent reports have been published on the use of such methods for diagnosis of the influenza, parainfluenza, respiratory syncytial, rhino-, and adenoviruses. Polymerase chain reaction and sensitive immunoassays can also be used to detect other agents not normally present in the airways, ie, Mycoplasma, Chlamydia, Legionella, and Pneumocystis organisms and Mycobacterium tuberculosis. In the management of bacterial pneumonia, however, gram stain of sputum with an assessment of sputum quality and bacterial numbers is still very useful because the mere presence of the commonly causative bacteria does not imply a causative diagnosis. Detection of soluble pneumococcal polysaccharide antigen may give supplementary information, especially in patients treated with antibiotics and in those unable to produce a representative sputum specimen. Broncho-scopically obtained material is preferred when possible, both for bacterial culture and for a rapid diagnostic test.
(C) Lippincott-Raven Publishers.
Spray-dried elderberry juice, containing high amounts of anthocyanin glucosides, was investigated for its antioxidant and prooxidant potentials and mechanisms. A strong, concentration-dependent prolongation of the lag phase of copper-induced oxidation of human low-density lipoprotein (LDL) was found, but the maximum oxidation rate was unchanged. Peroxyl-radical-driven LDL oxidation showed both prolongation of lag time and reduction of maximum oxidation rate. In the case of copper-mediated oxidation, the anthocyanins were able to reduce α-tocopheroxyl radical to α-tocopherol. Clear prooxidant activity in copper-mediated oxidation was observed, depending on the time of addition of extract: whenever the extract was present from the beginning or added within the first 10 min, the antioxidant effect prevailed. Addition at later times led to a considerable reduction of lag phase and increase of maximum oxidation rate. No such effect was found in peroxyl-radical-mediated LDL oxidation; on the contrary, the extract was even able to reduce the propagation rate considerably. Keywords: Antioxidants; anthocyanins; lipid peroxidation; low-density lipoprotein; Sambucus nigra
The SHS-174 preparation, a lyophilized infusion from flowers of Sambucus nigra L., aerial parts of Hypericum perforatum L., and roots of Saponaria officinalis (100 g; 70 g; 40 g) exhibited an antiviral effect. It inhibited the reproduction of different strains of influenza virus types A and B, both in vitro and in vivo, and herpes simplex virus type 1, in vitro. The preparation contains flavonoids, triterpene saponins, phenolic acids, tannins and polysaccharides which could be responsible for its antiviral properties.
The in vitro activity against herpes simplex virus type 1 of the major flavonoids identified in propolis was investigated. Flavonols were found to be more active than flavones, the order of importance being galangin, kaempferol, and quercetin. The efficacy against HSV-1 of binary flavone-flavonol combinations has been also investigated. The synergy demonstrated by all combinations could explain why propolis is more active than its individual compounds.
We developed a direct enzyme immunoassay [EIA; Enzygnost Influenza A(Ag) and Enzygnost Influenza B(Ag)] for the direct detection of influenza A and B virus antigens in nasopharyngeal secretion specimens (NPS). The test is performed without sonification of specimens, and results are obtained within 4 h. A direct comparison between direct EIA and quantitation of virus shedding for influenza A and B virus antigen detection was carried out. A total of 210 NPS and 98 nasopharyngeal wash specimens (NPW) were investigated. We isolated influenza A viruses from 79 (37.6%) of 210 NPS; of these 79 cell-culture-positive NPS, 70 (88.6%) were also positive by direct EIA. Of 29 (13.8%) NPS from which influenza B virus was isolated, 24 (82.8%) NPS were positive by direct EIA. Virus shedding was determined quantitatively in 48 NPS from patients with influenza A and in 24 NPS from patients with influenza B. Only a crude correlation between optical density values and virus concentrations was observed. Detection of influenza virus antigens in NPS by direct EIA showed sensitivities of 89.7% for influenza A virus and 87.9% for influenza B virus and specificities of 99.3% for influenza A virus and 100% for influenza B virus. With direct EIA, all NPW were negative for influenza A virus, although virus was isolated from 21 (21.4%) NPW. Of 15 NPW from which influenza B virus was isolated, 7 showed positive results in direct EIA. In addition, direct EIA is suitable for detecting influenza A and B viruses in cell cultures before the appearance of any cytopathic effects and can be used as a cell culture confirmation test.
Flavonoids (103 species) were tested for inhibitory activity against influenza virus sialidase using sodium p-nitrophenyl-N-acetyl-alpha-D-neuraminate as substrate. 5,7,4'-Trihydroxy-8-methoxyflavone from the root of Scutellaria baicalensis showed the most potent activity (IC50, 55 microM), and this flavone appeared to be a non-competitive inhibitor of the enzyme. Whereas, negligible or weak inhibitory activities were observed for mouse liver sialidase, beta-galactosidase and alpha-mannosidase as tested. This flavone also inhibited the infection by influenza virus A/PR/8/34 of Madin-Darby canine kidney cells, and replication of the virus in the allantoic sack of embryonated egg. These results suggest that flavone, which has potent influenza virus sialidase inhibitory activity, may have anti-influenza virus activity.
Of a variety of flavanoids, the flavans were generally more effective than flavones and flavanones in selective inhibition of HIV-1, HIV-2 or SIV infection. Studies of their effects on the binding of sCD4 and antibody to gp120 indicated that the effective compounds interact irreversibly with gp120 to inactive virus infectivity and block infection.
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.