Elderberry Sambucus - NutraHacker Journal Club

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Black elderberry (Sambucus nigra) supplementation effectively treats upper respiratory symptoms: A meta-analysis of randomized, controlled clinical trials

Upper respiratory symptoms are often treated with over the counter drugs, antibiotics, and antiviral medications. Due to concerns about safety and efficacy, there is a demand for an alternative solution. Black elderberry (Sambucus nigra) has been used to treat cold and flu symptoms, but there are no large-scale studies or meta-analyses. This meta-analysis quantifies the effects of elderberry supplementation and evaluates moderators including vaccination status and the underlying pathology. This analysis included a total of 180 participants and evaluates moderators such as vaccination status and cause of the upper respiratory symptoms. Supplementation with elderberry was found to substantially reduce upper respiratory symptoms. The quantitative synthesis of the effects yielded a large mean effect size. These findings present an alternative to antibiotic misuse for upper respiratory symptoms due to viral infections, and a potentially safer alternative to prescription drugs for routine cases of the common cold and influenza.

Elderberry for prevention and treatment of viral respiratory illnesses: a systematic review

Background: Elderberry has traditionally been used to prevent and treat respiratory problems. During the COVID-19 pandemic, there has been interest in elderberry supplements to treat or prevent illness, but also concern that elderberry might overstimulate the immune system and increase the risk of 'cytokine storm'. We aimed to determine benefits and harms of elderberry for the prevention and treatment of viral respiratory infections, and to assess the relationship between elderberry supplements and negative health impacts associated with overproduction of pro-inflammatory cytokines. Methods: We conducted a systematic review and searched six databases, four research registers, and two preprint sites for studies. Two reviewers independently assessed studies for inclusion, extracted data from studies, assessed risk of bias using Cochrane tools, and evaluated certainty of estimates using GRADE. Outcomes included new illnesses and the severity and duration of illness. Results: We screened 1187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. We did not find any studies linking elderberry to clinical inflammatory outcomes. However, we found three studies measuring production of cytokines ex vivo after ingestion of elderberry. Elderberry may not reduce the risk of developing the common cold; it may reduce the duration and severity of colds, but the evidence is uncertain. Elderberry may reduce the duration of influenza but the evidence is uncertain. Compared to oseltamivir, an elderberry-containing product may be associated with a lower risk of influenza complications and adverse events. We did not find evidence on elderberry and clinical outcomes related to inflammation. However, we found evidence that elderberry has some effect on inflammatory markers, although this effect may decline with ongoing supplementation. One small study compared elderberry to diclofenac (a nonsteroidal anti-inflammatory drug) and provided some evidence that elderberry is as effective or less effective than diclofenac in cytokine reduction over time. Conclusions: Elderberry may be a safe option for treating viral respiratory illness, and there is no evidence that it overstimulates the immune system. However, the evidence on both benefits and harms is uncertain and information from recent and ongoing studies is necessary to make firm conclusions.

Efficacy of Functional Foods, Beverages, and Supplements Claiming to Alleviate Air Travel Symptoms: Systematic Review and Meta-Analysis

Airline passengers experience a range of symptoms when travelling on long flights. This review evaluated the efficacy of functional foods, beverages, and supplements claiming to address the effects of air travel for healthy adults. Products were identified in a scoping review of electronic databases, search engines, and grey literature (March to August 2019). A systematic review of the efficacy of product ingredients was conducted using five electronic databases from inception to February 2021. Articles were screened, data extracted, and assessed for risk of bias by two researchers independently. Meta-analysis was performed. Of the 3842 studies identified, 23 met selection criteria: melatonin (n = 10), Pycnogenol (n = 4), various macronutrients (n = 2), caffeine (n = 2), Centella asiatica (n = 1), elderberry (n = 1), Echinacea (n = 1), fluid (n = 1), and Pinokinase (n = 1). Meta-analysis (random effects model) indicated melatonin reduced self-reported jetlag following eastbound (n = 5) and westbound (n = 4) flights: standard mean difference -0.76 (95% CI = -1.06 to -0.45, I2 0%, p < 0.00001) and -0.66 (95% CI = -1.07 to -0.26, I2 45%, p = 0.001), respectively. Pycnogenol also reduced edema scores (n = 3), standard mean -4.09 (95% CI = -6.44 to -1.74), I2 98%, p = 0.0006). Overall, 12 of 183 ingredients contained in 199 products had evidence to support claims.

Elderberry diet ameliorates motor function and prevents oxidative stress-induced cell death in rat models of Huntington disease

Huntington's disease (HD) is an inherited neurodegenerative disorder which begins in the striatum and then spreads to other neural areas. Known as a progressive movement cognitive disorder, HD has no efficient therapy. Although the exact mechanism of HD is still unknown, several different etiological processes such as oxidative stress have been shown to play critical roles. Also, the current evidence indicates a strong correlation between immune activation and neural damage induced by neuroinflammatory and apoptotic agents in neurodegenerative disorders. Thus, natural products like Elderberry (EB) could be considered as a novel and potential therapeutic candidate for the treatment of this disease. In this study EB was added to the daily ration of ordinary rats for two months in order to ameliorate inflammatory and oxidative responses in rats injected with 3-nitropropionic acid (3-NP) in an experimental model of HD. Using Rotarod and electromyography setups, we showed that EB diet significantly recovered motor failure and muscle incoordination in 3-NP injected rats compared to the control group. Also, the molecular findings implied that EB diet led to a significant drop in 3-NP induced growth in caspase-3 and TNF-α concentration. The treatment also improved striatal antioxidative capacity by a significant reduction in ROS and a remarkable rise in GSH, which might be correlated with motor recovery in the tests. In sum, the findings demonstrate the advantages of EB treatment in the HD rat model with a score of beneficial anti-oxidative and anti-inflammatory effects.

The amelioration of nicotine-induced reproductive impairment in male mouse by Sambucus ebulus L. fruit extract

Nicotine as a toxic agent in cigarette smoke impairs the reproductive system. Sambucus ebulus extract (SEE) is shown to have some beneficial effects such as antioxidant properties. The aim of this study was to evaluate the effects of SEE on the hormones of the pituitary-gonadal axis, lipid peroxidation index, antioxidant enzymes, spermatogenesis, and epididymal sperm parameters in male mice treated with nicotine. Adult male mice were divided into five groups; A: normal saline, B: 1 mg/kg nicotine, C: 1 mg/kg nicotine and 10 mg/kg SEE, D: 1 mg/kg nicotine and 50 mg/kg SEE, D: 1 mg/kg nicotine and 100 mg/kg SEE. Treatments lasted for 35 days. The spermicidal activity of SEE was tested in vitro. Sperm count, motility and morphology were assessed for fertility. Serum testosterone, prolactin and luteinizing hormone (LH) were measured, using ELISA. Serum malondialdehyde (MDA), catalase (CAT), and superoxide dismutase (SOD) activity were measured, using colorimetric assays. Spermatogenesis was evaluated by Johnsen's score and morphometry in histological slides. SEE at different doses did not have any spermicidal activity. Sperm parameters were reduced in the nicotine-treated group, compared with controls (P<0.01). Nicotine reduced testosterone and LH levels (P<0.01) and increased prolactin (P<0.01). A hike in MDA and a reduction in SOD activity without change on CAT, were observed in the nicotine group. Nicotine caused hypospermatogenesis. SEE improved most of the above-mentioned parameters, especially in the doses of 50 and 100 mg/kg. Beneficial effects of SEE in the doses of 50 and 100 mg/kg on male reproduction impairment, induced by nicotine might be partly attributed to the reduction of oxidative stress and changes in the hormones of the pituitary-gonadal axis.

The effects of Sambucus nigra berry on acute respiratory viral infections: A rapid review of clinical studies

Brief overview: Collectively the evidence obtained from across five clinical studies involving 936 adults indicate that mono-herbal preparations of Sambucus nigra L. berry (S.nigra), when taken within 48 hours of the onset of acute respiratory viral infection, may reduce the duration and severity of common cold and influenza symptoms in adults. There is currently no evidence to support the use of S.nigra berry for the treatment or prevention of COVID-19. Given the body of evidence from preclinical studies demonstrating the antiviral effects of S.nigra berry, alongside the results from clinical studies involving influenza viral infections included in this review, pre-clinical research exploring the potential effects of S.nigra berry on COVID-19 are encouraged. Verdict: The evidence included in this review is mostly derived from clinical studies involving adult participants and examining short-term use of commercial formulations of S.nigra berry for up to 16 days. Findings from included studies suggest that mono-herbal preparations of S.nigra berry (in extract or lozenge formulation) may reduce influenza-type symptoms, including fever, headache, nasal congestion and nasal mucous discharge in adults, when taken within the first 48 hours of symptom onset. Within 2-4 days of S.nigra treatment, most adult participants experienced significant symptom reduction, by an average of 50%. Evidence regarding the effectiveness of S.nigra berry on the symptom of cough, and need for/use of medicines (including antibiotics) to treat acute respiratory infections, is currently unclear and inconsistent. Adverse events were rare with no serious events reported. Adverse events, reported in two studies, were more common in comparators than in treatments. There is currently no reliable or sufficient scientific evidence to support the use of S.nigra in pregnant or lactating women.

Polysaccharides from European Black Elderberry Extract Enhance Dendritic Cell Mediated T Cell Immune Responses

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.

Select Dietary Supplement Ingredients for Preserving and Protecting the Immune System in Healthy Individuals: A Systematic Review

Immune health products represent approximately 10% of all US dietary supplement sales. Claims made on products to support or boost the immune system are attractive to the otherwise healthy consumer who may or may not be experiencing certain life stressors. The purpose of this systematic review is to critically evaluate the purported benefits and/or potential harms of select dietary supplement ingredients frequently listed on the labels of products having immune health or related market claims. With a focus on resilience, research questions were related to whether dietary supplement ingredients are efficacious in preserving and protecting immune health in healthy individuals; and when faced with a stressor, whether taking a supplement prophylactically can assist in maintaining health and resisting or bouncing back more quickly. Thirty-nine randomized controlled studies involving populations including children, adults and seniors exposed to stressors, such as air travel, intense exercise, academic stress, and/or exposure to winter weather, met eligibility criteria. The studies included eight of the 27 supplement ingredients identified through a market-driven scoping review. Those ingredients used in single ingredient products were echinacea, elderberry, garlic, vitamin A, vitamin C, vitamin D, vitamin E, and zinc. Whereas some studies may point to evidence for benefit, specific gaps preclude the authors from making firm statements with regard to the overall evidence-base for these products and ingredients and in answering the research questions. As we move toward a vision of health promotion and resilience rather than a sole focus on disease prevention and treatment, further work in this area of dietary supplements is of utmost importance.

Elderberry ( Sambucus nigra L.) extracts promote anti-inflammatory and cellular antioxidant activity

Despite the high value of Portuguese elderberries, recognized for decades by European markets, only a few studies address their beneficial effects at cellular level. Aiming to explore the anti-inflammatory and the cellular antioxidant potential characterized extracts from the three main Portuguese elderberry cultivars (Sabugueiro, Sabugueira, Bastardeira) were used. Lipopolysaccharide-stimulated RAW 264.7 cells pre-exposed to elderberry extracts exhibited dose-dependent inhibition of nitric oxide release, evidencing anti-inflammatory activity. Concerning cellular antioxidant protection, HepG2 and Caco-2 cells pre-exposure to elderberry extracts (50 µg/mL) prevented up-to 90 % of tert-butyl hydroperoxide (t-BOOH)-induced toxicity. In Caco-2 cells, elderberry extracts prevented glutathione depletion, reactive oxygen species production, abnormal morphological changes and DNA fragmentation, in response to t-BOOH oxidative insult. Results demonstrated that elderberries have high potential in reducing cellular oxidative stress as well as in preventing inflammatory processes. Thus, elderberries have high potential as health promoters, acting as functional foods or as sources of nutraceuticals.

An elderberry-supplemented diet improves spermatogenesis in mice with busulfan-induced azoospermia

Context: Approximately 40-50% of all infertility cases are due to male infertility, and one of the most important causes of infertility is azoospermia. Aims: This study aimed to evaluate the potential effect of elderberry on the spermatogenesis process in the azoospermia mice model. Method: Thirty adult male mice were randomised into three groups: control; busulfan (45mg/kg); and busulfan+elderberry (2%), 6mL orally per animal. Sperm samples were collected from the tail of the epididymis, and testis specimens were also collected and then subjected to sperm parameters analysis, histopathological evaluation, reactive oxygen species (ROS), and glutathione (GSH) measurement to determine the mRNA expression and hormonal assay. Conclusions: It can be concluded that the elderberry diet may be considered a complementary treatment to improve the spermatogenesis process in busulfan-induced azoospermic mice. Implications: Considering some limitations, the elderberry diet can be an alternate option for improving testicular damage following chemotherapy.

A Plausible Association Between the Use of Elderberry and Autoimmune Hepatitis

Hepatic injury due to dietary and herbal supplements can often share similar clinical characteristics with autoimmune hepatitis (AIH). Sambucus species, commonly known as elderberry, have been used in traditional medicine for centuries to prevent and treat respiratory problems. Although there are no clear reports on the association of elderberry with AIH or drug-induced hepatitis, there have been concerns about negative health manifestations linked to elderberry and the overproduction of inflammatory cytokines. In this article, we discuss a case of a patient who developed autoimmune hepatitis while on long-term elderberry-containing supplements and a probable association between the two.

Elderberry ( Sambucus nigra L.): Bioactive Compounds, Health Functions, and Applications

Elderberry (Sambucus nigra L.) is rich in many bioactive compounds and exhibits diverse health functions, of which an understanding can be helpful for its better utilization in the food industry. This review mainly summarizes recent studies about the bioactive compounds and health functions of elderberry, highlighting the potential mechanism of action. In addition, the applications of elderberry in foods are also discussed. Elderberry contains diversely bioactive ingredients, such as (poly)phenolic compounds and terpenoid compounds. Recent studies report that some food processing methods can affect the content of bioactive compounds in elderberry. Additionally, elderberry exhibits various health functions in vitro and in vivo, including antioxidant, anti-inflammatory, anticancer, anti-influenza, antimicrobial, antidiabetic, cardiovascular protective, and neuroprotective activities, and their potential molecular mechanisms are associated with regulating some key signaling pathways and molecular targets. Up to now, there have been limited clinical trials supporting the health benefits of elderberry. Overall, elderberry is a promising dietary source of bioactive ingredients and has the potential to be developed into functional foods or nutraceuticals for preventing and treating certain chronic diseases.

Elderberries as a potential supplement to improve vascular function in a SARS-CoV-2 environment

Coronavirus disease 2019 (COVID-19) pandemic has been triggered by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Although recent studies demonstrate that SARS-CoV-2 possibly does not directly infect endothelial cells (EC), the endothelium may be affected as a secondary response due to the damage of neighboring cells, circulating pro-inflammatory cytokines, and/or other mechanisms. Long-term COVID-19 symptoms specifically nonrespiratory symptoms are due to the persistence of endothelial dysfunction (ED). Based on the literature, anthocyanins a major subgroup of flavonoid polyphenols found in berries, have been well researched for their vascular protective properties as well as the prevention of cardiovascular disease (CVD)-related deaths. Elderberries have been previously used as a natural remedy for treating influenza, cold, and consequently cardiovascular health due to a high content of cyanidin-3-glucoside (C3G) a major anthocyanin found in the human diet. The literature reported many studies demonstrating that EE has both antiviral and vascular protective properties that should be further investigated as a nutritional component used against the (in)direct effect of SARS-CoV-2 in vascular function. PRACTICAL APPLICATIONS: While previous work among the literature looks promising and builds a suggestion for investigating elderberry extract (EE) against COVID-19, further in vitro and in vivo research is required to fully evaluate EE mechanisms of action and its use as a supplement to aid current therapies.

Elderberry Diet Restores Spermatogenesis in the Transient Scrotal Hyperthermia-Induced Mice

Over the past years, several studies have also reported the adverse effects of hyperthermia on normal testicular tissues in several species including mice, rats, and humans. These deleterious impacts include temporarily drop in relative weight of testis along with a temporary partial or complete infertility. Sambucus nigra, also known as elderberry or sweet elder, is a source of bioactive compounds that has drawn growing attention for its potential beneficial effects in preventing and treating several diseases. This experimental research divided 30 mice into the following three groups: (1) control, (2) hyperthermia, and (3) hyperthermia receiving elderberry diet for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, immunohistochemistry against TNF-α and caspase-3 and serum testosterone, FSH and LH levels. Our outputs indicated that elderberry diet could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid, and Leydig cells together with an increasing level of the serum testosterone compared to the scrotal hyperthermia induced mice. In addition, it was found that the expression of TNF-α and caspase-3 significantly decreased in the treatment groups by elderberry diet compared to the scrotal hyperthermia-induced mice. In conclusion, it could be concluded that elderberry diet may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice.

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