Select Global Immune-Boosting Plants Used in Folklore Medicine

There are numerous foods and herbal plants that boost the immune system. They stimulate the activity of cells responsible for fighting infections. In fact, over centuries, people have relied on herbs and other plants for treating medical conditions and boosting immunity. Considering the worldwide coronavirus pandemic, natural immune boosters are being sought after in the current war against this viral infection. Most likely, immune-boosting plants help human health by tackling viruses, bacteria, and abnormal cells in the form of prevention, to support and strengthen the body's natural immune system. In this chapter, we review several terrestrial species and plants from various sources including China, India, Europe, and Africa, which have long folklore use, and we provide information on the chemistry and biological activity where available. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022.

Elderberry Extracts: Characterization of the Polyphenolic Chemical Composition, Quality Consistency, Safety, Adulteration, and Attenuation of Oxidative Stress- and Inflammation-Induced Health Disorders.

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.

Plant lectins as versatile tools to fight coronavirus outbreaks.

The S protein forming the homotrimeric spikes of pathogenic beta-coronaviruses, such as MERS-CoV, SARS-CoV and SARS-CoV-2, is a highly glycosylated protein containing mainly N-glycans of the complex and high-mannose type, as well as O-glycans. Similarly, the host cell receptors DPP4 for MERS-CoV and ACE2 for SARS-CoV and SARS-CoV-2, also represent N- and O-glycosylated proteins. All these glycoproteins share common glycosylation patterns, suggesting that plant lectins with different carbohydrate-binding specificities could be used as carbohydrate-binding agents for the spikes and their receptors, to combat COVID19 pandemics. The binding of plant lectins to the spikes and their receptors could mask the non-glycosylated receptor binding domain of the virus and the corresponding region of the receptor, thus preventing a proper interaction of the spike proteins with their receptors. In this review, we analyze (1) the ability of plant lectins to interact with the N- and O-glycans present on the spike proteins and their receptors, (2) the in vitro and in vivo anti-COVID19 activity already reported for plant lectins and, (3) the possible ways for delivery of lectins to block the spikes and/or their receptors.

The Pros and Cons of Using Elderberry (Sambucus nigra) for Prevention and Treatment of COVID-19.

Background: The novel severe acute respiratory syndrome coronavirus 2 emerged in 2019. Health-care systems around the world are looking for alternative prevention and treatment remedies. Herbal supplements are popular among consumers as a complementary method to prevent and treat illnesses. One of them is Sambucus nigra. Methods: We searched for related articles in Scopus, Web of Science, PubMed, Google Scholar, and the Directory of Open Access Journals using the following keywords: elderberry, S. nigra, and COVID-19. Results: Elderberry has antiviral properties due to its ability to modulate inflammatory cytokines. The current evidence suggests elderberry is appropriate for the prevention and initial treatment of viral disease. Concerns have been raised that elderberry may overstimulate the immune system, increasing the risk of a cytokine storm. There is not yet enough evidence to support this claim. Conclusions: For COVID-19 patients, further research is required since elderberry may provoke a cytokine storm if administered therapeutically.

Attitudes and approaches towards COVID-19 management among the public and pharmacists in Northern Cyprus

Purpose: To study the attitudes and approaches towards COVID-19 management among the public and pharmacists in Northern Cyprus. Method: Questionnaire were administered face-to-face and online to volunteer pharmacists and other members of the public, after receiving approval from the Near East University Ethics Boards. Responses to the questionnaire were evaluated statistically.

Inhibition of Human Respiratory Influenza A Virus and Human Betacoronavirus-1 by the Blend of Double-Standardized Extracts of Aronia melanocarpa (Michx.) Elliot and Sambucus nigra L.

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 ß-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.

Antiviral activity of plant juices and green tea against SARS-CoV-2 and influenza virus.

Respiratory viruses pose a significant threat to global health. They initially infect the naso- and oropharyngeal regions, where they amplify, cause symptoms, and may also be transmitted to new hosts. Preventing initial infection or reducing viral loads upon infection might soothe symptoms, prevent dissemination into the lower airways, or transmission to the next individual. Several natural products have well-described direct antiviral activity or may ameliorate symptoms of respiratory infections. We thus analyzed the potential of plant-derived products to inactivate respiratory viral pathogens and determined the antiviral activity of black chokeberry (Aronia melanocarpae [Michx.] Elliott), elderberry (Sambucus nigra L.), and pomegranate (Punica granatum L.) juice, as well as green tea (Camellia sinensis [L.] Kuntze) on the infectivity of the surrogate-modified vaccinia virus Ankara, and the respiratory viruses severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza A virus (IAV), and adenovirus Type 5. Black chokeberry and pomegranate juice, and green tea reduced SARS-CoV-2 and IAV titers by ≥80% or ≥99%. This suggests that oral rinsing with these products may reduce viral loads in the oral cavity which might prevent viral transmission.

Primary care experience on Stimunex® gocce in children with recurrent respiratory infections: a real-world study during the COVID-19 pandemic era.

BACKGROUND: Respiratory infections (RI) significantly burden society, mainly when there are recurrent respiratory infections (RRI). Thus, there is a need to prevent RI in clinical practice. In this regard, the modulation of the immune system and resolution of the inflammatory cascade could represent an ideal way to prevent RI. Stimunex® gocce, a multicomponent food supplement, contains Sambucus nigra extract, ß-glucan, Zinc, and Vitamin D3. This study investigated its ability to prevent RRI in children using a real-world setting: the pediatric primary care. MATERIALS AND METHODS: Two hundred and ninety-eight children with RRI were enrolled in the current study. The food supplement was randomly prescribed to 160 children with RRI daily for 4 months (Active group); the remaining 138 children with RRI were treated only with standard therapy for RI (Control group). The number and duration of RI, parental perception of symptom severity and treatment efficacy, use of medications, and school and working absence were evaluated. RESULTS: Children treated with Stimunex® gocce had significantly less RI than the Control group, both concerning upper and lower RI (p˂0.001 and 0.003, respectively) during the follow-up period. Moreover, children in the Active group experienced shorter RI duration during the treatment and follow-up phases (p˂0.001 for both). In addition, parents of treated children perceived less severe symptoms and better treatment efficacy during the first and follow-up phases (p˂0.001 for all). The food supplement was well tolerated and there was no adverse event. CONCLUSIONS: The current real-world study demonstrated that Stimunex® gocce supplementation in children with RRI might safely prevent RI episodes and reduce RI duration. These outcomes should be highlighted as obtained during the COVID-19 pandemic era, characterized by a dramatic reduction of RI.

A cross-sectional survey of herbal remedy taking to prevent COVID-19 in Turkey. (COVID-19 dedicated issue.)

The Coronavirus disease 2019 (Covid-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has led to unprecedented challenges for human life. During this pandemic, Turkish people have used various herbal remedies for both the prevention of Covid-19 and the alleviate of its symptoms. The present study aimed to investigate the herbal remedies used to prevent Covid-19 in Turkey and to determine whether the usage of herbal remedies was associated with sociodemographic properties. A cross-sectional study using an online questionnaire was conducted between November and December 2020. A total of 871 individuals (15 years of age or older) who lived in various provinces of Turkey participated in this study. Analysis was made in SPSS version 26.0 software using the descriptive statistics and appropriate tests of statistical significance for the comparisons. About 54.4% (n=474) of the participants reported that they have used herbal remedies during the pandemic period. We identified a total of 45 plant species, the most frequently cited were ginger (Zingiber officinale Roscoe), linden (Tilia spp.), elderberry (Sambucus nigra L.), sage (Salvia spp.), and rosehip (Rosa canina L.), respectively. It has been found that the usage of herbal remedies was associated with several demographic variables. A considerable proportion of the participants reported the use of herbal remedies in order to prevent disease. This paper demonstrated the potential herbal remedies that can be used against Covid-19. Further research should be carried out to evaluate the efficacy of these medicinal plants and should control the flow of misleading information.

Potential immunomodulatory and antiviral food effect in the context of COVID-19 pandemic

Background: Up to date drug-based treatments for COVID-19 have not been approved. The most effective way to face this public health problem is prevention with adequate nutrition, hygiene, and protection measures. Food has historically been used by people to improve their nutrition and complement the treatment or prevention of diseases. The various bioactive compounds of some foods are known, which in experimental studies demonstrated their antiviral and immunomodulatory action.

Medicinal plants preferences for the treatment of COVID-19 symptoms in Central and Eastern Anatolia

Aim of study: This study aimed to determine the medicinal plant use preferences of herbalists' customers against the COVID-19 symptoms during pandemic period. Area of study: The study was carried out in nine provinces located in the Central and Eastern Anatolia Region of Turkey and the herbalists selling medicinal plants. Material and methods: Data on 35 plants from 373 customers and 49 herbalists were collected between April 2020 and December 2020. Relative Frequency of Citation (RFC) and Fidelity Level (FL) quantitative indices were used to measure the use, cultural significance, and specificity of plants. Main results: The highest RFC was found for Thymus spp. (0.59). It was followed by Ceratonia siliqua L. (0.56), Zingiber officinale Roscoe (0.56), and Mentha pulegium L. (0.50), respectively. The plants in the study area with a high FL were Zingiber officinale (84.83%) for cough, Thymus spp. (80.95%) for fever, Mentha pulegium (76.47%) for nausea-vomiting. Sambucus nigra L., Echinacea angustifolia DC., and Thymus spp. were the plants whose sales/demand increased the most during the pandemic period. Highlights: It was understood that there was a significant increase in the sales of species such as Sambucus nigra, Echinacea angustifolia, and Thymus spp., during the pandemic period. This situation showed that there was a consensus among the public that these plants were effective against COVID-19 symptoms.

An Exploratory Review of Potential Adjunct Therapies for the Treatment of Coronavirus Infections.

OBJECTIVE: The purpose of this exploratory review was to examine vitamin D, zinc, vitamin A, elderberry (Sambucus nigra), garlic (Allium sativum), licorice (Glycyrrhiza glabra), stinging nettle (Urtica dioica), N-acetylcysteine, quercetin, and selenium as potential adjunct therapies for the treatment of coronavirus infections. METHODS: A search of PubMed was performed for articles published from 2005 to 2021. Keywords searched were "zinc," "vitamin A," "vitamin D," "Sambucus nigra," "Allium sativum," "Glycyrrhiza glabra," "Urtica dioica," "N-acetylcysteine," "quercetin," "selenium," and "coronavirus." RESULTS: There were 47 articles selected for this review. Findings included that vitamin D, zinc, vitamin A, S. nigra, A. sativum, G. glabra, U. dioica, N-acetylcysteine, quercetin, and selenium have been shown to produce antiinflammatory, immunostimulatory, or antiviral effects that may enhance the actions of standard therapeutics for the treatment of coronavirus infections. Specific to effects against COVID-19, we found research articles related to the effects of only vitamin D, zinc, G. glabra, quercetin, and selenium. CONCLUSION: We identified nonpharmaceutical supplements (vitamin D, zinc, vitamin A, S. nigra, A. sativum, G. glabra, and U. dioica) which may have potential to provide support for those with coronavirus infections. However, rigorous clinical studies need to be performed before any clinical recommendations can be made.

Wild Sambucus nigra L. from north-east edge of the species range: A valuable germplasm with inhibitory capacity against SARS-CoV2 S-protein RBD and hACE2 binding in vitro.

Berries and flowers of Sambucus nigra L. tree are well known for their ability to mitigate symptoms of upper respiratory disorders related to reported antiviral properties. Industrial application and commercial cultivation of S. nigra is largely limited to a few widely grown cultivars. Restricted genetic diversity of cultivated S. nigra can be disadvantageous if new industrial applications are discovered. In this study wild S. nigra populations located on the north-east edge of the species natural range were explored by assessing genetic origin, berry and flower anti-oxidative potential, and berry rutin content. Best performing wild S. nigra extracts were selected for an assessment of previously unreported biological activity- inhibitory capacity against SARS-CoV2 S1 protein receptor binding domain (RBD) binding to recombinant human angiotensin -converting enzyme 2 (ACE2) receptor in vitro based on competitive enzyme linked immunosorbent assay (ELISA). Inter-simple sequence repeat (ISSR) marker-based genetic characterization suggested that explored wild S. nigra populations result from wild gene pool expanding northwards with admixture of historically introduced cultivated S. nigra. Average values of total phenolic content, anti-radical activity, and total flavonoids content of wild S. nigra populations did not exceed those of cv. 'Haschberg'. Concentration-dependent inhibition of ACE2-SARS-CoV2 S-protein RBD binding was demonstrated in vitro for elderberry fruits and flowers extracts (IC50 of 1.66 mg DW ml-1 and 0.532 mg DW ml-1, respectively). Wild elderberry fruit extract exhibited higher inhibitory capacity than the extract from berries of cv 'Haschberg'. This study validates the requirement for S. nigra wild germplasm bioprospecting and opens up directions for further research of new anti-SARS-CoV2 industrial applications of S. nigra.

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.