Sambucus nigra

Sambucus nigra (Black Elderberry)

1. Identity, Taxonomy, and Botanical Description

Botanical name: Sambucus nigra L. Common names include black elderberry, common elder, European elder, and European elderberry. Sambucus nigra L. is a species of the Adoxaceae family (formerly classified under Caprifoliaceae). The genus name Sambucus derives from the Latin word for a type of musical instrument, reflecting the historical use of hollow elder stems to make pipes and flutes.

Sambucus nigra is a perennial shrub belonging to the family Adoxaceae, widely distributed in the temperate regions of Europe, North Africa, and Western Asia. It is a medicinal shrub or small tree native to the western and southern parts of Europe and North Africa. The species has also been introduced into other parts of the world, including North America, South East Asia, and Australia.

It has pinnate leaves with five leaflets, short-stalked, elliptic, 4–12 cm long. Inflorescences are small, yellowish-white, with three small bracts, and may have a peduncle; calyx minute, five-lobed; corolla five-cleft gamopetalous; five yellow stamens; and a tricarpellate pistil of three stigmas. The fruits are small, round, blue-black to purple-black berries that ripen in late summer and autumn, borne in large drooping clusters.

Common Preparations and Dosage Forms

Elderberry preparations are used as components of dietary supplements in the form of syrups, drops, tablets, capsules, lozenges, aerosols, emulsions, or suspensions. Commercial preparations most commonly use ripe fruit (berry) extracts or flower extracts. A very popular supplement with antiviral properties is the Sambucol preparation, patented in Israel by Dr. Madeleine Mumcuoglu. In food applications, flowers are used to make cordials, teas, and flavoring agents, while berries are made into jams, wines, juices, and pies.

2. Traditional and Historical Use

Sambucus nigra is native to most of Europe, northwest Africa, and southwest Asia. The medicinal properties of this species were well-known even in ancient times. Hippocrates (460–370 BCE) recommended S. nigra for constipation, dropsy, and menstrual pain, while Pliny the Elder (23–79 CE), in his work Naturalis Historia, attributed diuretic properties to this plant.

Sambucus nigra, the elderberry, has long been used for its medicinal properties in treating numerous diseases. Based on this traditional knowledge, its different pharmacological activities have been the focus of active research. All parts of the tree have long been used in traditional medicine — the bark, the leaves, the flowers, and the fruit.

The plant has been used successfully for centuries for medicinal purposes and to prepare tea, wines, and liquors. Traditional folk medicine uses the infusion from dried flowers because of its diuretic effects, which include reducing fever, promoting perspiration, and moderating cough.

S. nigra was reported to possess several traditional medicinal properties including antidiabetic, purgative, diuretic, hemostatic, and diaphoretic properties.

Many Sambucus species have been used over centuries in Brazilian Traditional Medicine, Korean Traditional Medicines, Traditional Turkish Medicines, Iranian Traditional Medicines, and Traditional Chinese Medicines, as traditional sources of medicines in various forms including infusions, decoctions, crude extracts, and concoctions.

Across European traditions, especially in the Iberian Peninsula, the plant held an exceptional role. The bush or small tree is one of the plants most reported and used — for medicinal and other purposes — by informants in many Mediterranean areas. It is one of the most versatile of plants, being used for food, medicine, crafts, and games, as well as for ornamental purposes. Almost every part of the plant, including the bark, roots, leaves, flowers, and fruit, has some uses. A diachronic study of Sambucus nigra spanning over a millennium reflects various attitudes and uses within the context of a changing human society.

Elderberry has for a long time been used in folk medicine as a diaphoretic, antipyretic, and diuretic agent. In European folk medicine, the flowers were particularly prized for their febrifuge and diaphoretic properties, especially in the treatment of the early stages of colds and fevers. Sambucus nigra flowers (elderflower) have been widely used in traditional medicine for the relief of early symptoms of common cold.

3. Key Constituents and Active Compounds

Anthocyanins (Fruit)

Elderberry is a very rich source of anthocyanins in comparison to other fruits. The fruit of Sambucus nigra contains anthocyanins, especially cyanidin-3-glucoside and cyanidin-3-sambubioside. Two other (minor) anthocyanins are cyanidin-3,5-diglucoside and cyanidin-3-sambubioside-5-glucoside. In addition, trace quantities of cyanidin-3-rutinoside, pelargonidin-3-glucoside, and delphinidin-3-rutinoside were identified in the fruit of certain elderberry cultivars.

The polyphenol content of the fruit extract was found to be about 1.4 times higher than that of the flower extract, due to the high content of anthocyanins: 50,557.1 mg/100 g DW, of which there are 24,341.1 ± 1017.4 mg/100 g DW cyanidin-3-glucoside and 21,051.4 ± 951.5 mg/100 g DW cyanidin-3-O-sambubioside. The polyphenol content changes at different stages of fruit ripening, and each compound shows its own individual change pattern during this process. The content of anthocyanins generally increases as berries ripen. The content of polyphenols and anthocyanins is also dependent on the growing season.

Flavonoids and Phenolic Acids

The primary polyphenol constituents in the flower extract are flavonoids and phenolic acids, while anthocyanins are the main components in the fruit extract. Both flowers and leaves of black elder are a rich source of basic substances such as rutin, quercetin, protocatechuic acid, 3,5-dicaffeoylquinic acid, neochlorogenic acid, and tannins, as well as vitamin E.

Hydroxycinnamic acids and flavonol glycosides are the major phenolic constituents in elderflowers. The biological properties of elderflower have been related to its high content in polyphenolic compounds which are known for their antioxidant potential activity in both in vitro and in vivo studies: flavonoids, including quercetin, rutin, and kaempferol among others; hydroxycinnamic acids such as chlorogenic (CGA), caffeic (CA), and protocatechuic acids.

Among phenolic acids, chlorogenic acid, sinapic acid, and t-cinnamic acid are predominant, with average contents of 139.09, 72.84, and 51.29 mg/g extract, respectively. Rutin and quercetin, with average contents of 1105.39 and 306.6 mg/g extract, respectively, were the dominant flavonoids.

Cyanogenic Glycosides

All parts of the elderberry contain cyanogenic glycosides, the most abundant of which are sambunigrin and prunasin. Furthermore, elderberry contains m-hydroxy-substituted glycosides, such as zierin and holocalin. These compounds are potentially toxic and life-threatening, because they can be hydrolysed, resulting in the release of cyanide. However, they occur primarily in unripe berries and are degraded during heat treatment. The highest amounts of sambunigrin are present in elder leaves (27.68–209.61 µg/g FW), lower amounts were found in flowers (1.23–18.88 µg/g FW), whereas berries contain the lowest amounts (0.08–0.77 µg/g FW).

Terpenes and Other Constituents

Research on the extract of flowers and berries of elder has found numerous pentacyclic triterpenes, which are of great pharmacological relevance due to their "multi-target" properties, such as wound healing and anti-inflammatory, anti-bacterial, and antiviral effects. To date, about 425 secondary constituents have been isolated and identified across the Sambucus genus, including phenolic compounds, terpenoids, fatty acids, cyanogenic glycosides, phytosterols, lectins, and others.

Elderberry plant (Sambucus nigra) is a good source of protein, free and conjugated forms of amino acids, unsaturated fatty acids, fibre fractions, vitamins, antioxidants, and minerals. Analysis of elderberry showed that it contains high biological-activity components, primarily polyphenols — mostly anthocyanins, flavonols, phenolic acids, and proanthocyanidins — as well as terpenes and lectins.

4. Mechanisms of Action

Antiviral Mechanisms

The berries have demonstrated antiviral activity against certain viruses. Elderberries contain many active chemicals, including anthocyanins (primarily cyanidin-3-glucoside and cyanidin-3-sambubioside), which have been shown to boost immune function and exhibit anti-viral effects. Oral ingestion of elderberry results in detectable levels of these anthocyanins in blood plasma.

Anti-Inflammatory Mechanisms

Sambucus nigra's health benefits primarily stem from flavonoid-mediated modulation of NF-κB and PPARγ pathways, demonstrating dose-dependent antioxidant and anti-inflammatory activities. Furthermore, its anthocyanins demonstrate significant potential in natural food preservation and immune support.

Many medicinal plants rich in polyphenols have shown anti-inflammatory activity in pharmacological experiments, and polyphenols have shown an ability to suppress prostaglandin pathways. Flavones effectively reduce the synthesis of cyclooxygenase-2, whereas flavonoids can inhibit eicosanoids such as prostaglandins, decreasing inflammation and pain. Several studies have demonstrated black elder's anti-inflammatory effects via the decreased production of pro-inflammatory cytokines, including IL-6 and TNF-α, and reduced neutrophil activation.

Antioxidant Mechanisms

The biological properties of S. nigra are closely related to its chemical constituents. Anthocyanins, other polyphenolic compounds, and organic acids, known for their antioxidant potential activity, are the dominant classes of phytochemicals that characterize S. nigra. In vitro studies indicate the antioxidant properties of Sambucus nigra fruit extracts. These compounds can also increase the activity of enzymes in the small intestine, liver, and lungs, including peroxidase, S-transferase, glutathione reductase, and catalase.

Antimicrobial Mechanisms

Research showed that the content of phenolic acids and flavonoids in the extracts determined their antibacterial activity. Elderberry polyphenol extracts exhibited activity against selected bacterial strains within the concentration range of 0.5–0.05%. The most sensitive bacteria to the extracts were Micrococcus luteus, Proteus mirabilis, Pseudomonas fragii, and Escherichia coli. Of the compounds analyzed, apigenin, kaempferol, and ferulic, protocatechuic, and p-coumarin acids had the greatest influence on the high antibacterial activity of elderberry extracts.

Antidiabetic Mechanisms

Black elderberry (Sambucus nigra L.) flowers are rich in polyphenolic compounds, including chlorogenic acid and quercetin derivatives, which are known for their health benefits, particularly their antioxidant and antidiabetic properties. Results indicated that the Black Beauty, Obelisk, and Haschberg cultivars demonstrated significant inhibition of α-glucosidase, with a high inhibitory potential against α-amylase enzymes for the Obelisk cultivar. These in vitro enzyme-inhibition findings are preliminary and have not been confirmed in clinical trials.

5. Scientific Evidence by Area of Use

5.1 Upper Respiratory Tract Infections and Influenza

This is the best-studied therapeutic application of Sambucus nigra, and it represents the primary area for which clinical evidence exists.

A 2019 meta-analysis of four studies found that supplementation with black elderberry (Sambucus nigra) was significantly effective at reducing the total duration and severity of upper respiratory symptoms, compared with placebo.

Collectively, the evidence obtained from across five clinical studies involving 936 adults indicates that mono-herbal preparations of Sambucus nigra L. berry, 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.

Key individual trials include:

• A randomized trial used a standardized elderberry extract (Sambucol® syrup). Participants received either 15 ml of the elderberry syrup or placebo four times a day during five days. The effects of the treatment were monitored by a visual analogue scale. It was found that in the group treated with the elderberry syrup, symptoms ebbed on average four days earlier than in the placebo group.
• In one study, 32 people with flu-like symptoms took lozenges containing 175 mg of elderberry extract four times a day for 2 days. After 24 hours, they reported an improvement in symptoms, such as fever, headache, muscle aches, and nasal congestion.
• A double-blind, randomized control trial looked at whether elderberry extract could prevent people from experiencing cold-like symptoms after traveling on an airplane. People took lozenges containing 300 mg of elderberry extract and 150 mg of rice flour twice a day for 10 days before traveling.

A larger emergency department trial also tested elderberry. An evidence-based systematic review by the Natural Standard Research Collaboration concluded that there is good scientific evidence that elderberry extract supplementation can effectively relieve symptoms of influenza. Each 15-ml dose of the oral liquid used in this trial contained the fruit juice equivalent to 5.7 g of Sambucus nigra (black elderberry).

Evidence characterization: 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. The systematic review screened 1,187 records and included five randomized trials on elderberry for the treatment or prevention of viral respiratory illness. Overall, the evidence base is encouraging but is constrained by small sample sizes, short study durations, variable preparations, and mostly short-term assessments. The body of evidence is rated as preliminary to moderate in strength.

5.2 COVID-19

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, pre-clinical research exploring the potential effects of S. nigra berry on COVID-19 has been encouraged.

5.3 Anti-Inflammatory Activity

Fruit extract (SNFrE) revealed pronounced and dose-dependent in vivo anti-inflammatory activity assessed by the cotton pellet-induced granuloma test. Doses of 10, 20, and 50 mg/kg BW of SNFrE reduced the weight of induced granuloma in rats by 20.3%, 20.5%, and 28.4%, respectively. At the highest dose (50 mg/kg BW), SNFrE had significant (p < 0.01) anti-inflammatory activity comparable to that of diclofenac, the reference compound used (10 mg/kg BW).

Researchers did not find any clinical studies linking elderberry to clinical inflammatory outcomes in humans. However, three studies measured production of cytokines ex vivo after ingestion of elderberry. Anti-inflammatory evidence in humans therefore remains largely indirect and preliminary.

5.4 Antioxidant Activity

Results from cell culture experiments 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. Elderberry extracts prevented GSH depletion, ROS production, and DNA fragmentation in in vitro models. These findings are in vitro and have not been confirmed in large, controlled human trials.

5.5 Cardiovascular and Metabolic Health

Black elderberry can prevent oxidative stress and reduce blood pressure and prevent cardiovascular diseases and diabetes mellitus thanks to the polyphenols it contains. However, it is not correct to prove its beneficial effects on the prevention of chronic diseases and to make generalisations. Therefore, there is a need for more comprehensive evidence-based clinical studies and data.

Elderberry berries have been found to show multiple bioactivities, including antidiabetic, anti-infective, antineoplastic, anti-obesity, and antioxidant activities. These findings are largely from in vitro and animal studies. No large-scale, properly powered, randomized controlled trials in humans have yet confirmed elderberry's efficacy for cardiovascular disease or diabetes prevention.

5.6 Anticancer Properties

It has been shown that the alcoholic extract of elderberry flowers affects the proliferation of a breast cancer cell line (MCF7). The results indicate that incubation of MCF7 cells with different concentrations of this extract significantly affected the level of ERα and PR steroid receptors in these cells. A decrease in ERα and an increase in PR were observed by immunocytochemistry. This indicates the important role of the ingredients present in the S. nigra L. flower extract in chemoprevention and/or cancer therapy.

Scientific research indicates the high antioxidant potential of kaempferol from the group of flavonoids due to the capture of free radicals, mainly reactive oxygen species, which determines its anticancer properties. All such findings are in vitro only; no clinical trials in cancer patients have been conducted with elderberry as a primary intervention.

5.7 Antibacterial Activity

The antibacterial activity of elder flowers, berries, and leaves (aqueous or ethanol extracts of freeze-dried elder concentrates) was studied against 13 nosocomial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA), which is known as a clinically significant pathogen connected with infections of skin and soft tissue. These findings are in vitro only and have not been validated in clinical trials.

5.8 Neuroprotective Properties

A cell culture study assessed the antioxidant and protective potentials of Sambucus nigra flowers in the human neuroblastoma (SH-SY5Y) cell line using different in vitro approaches. The antioxidant capacity was first evaluated by the ORAC and DPPH methods. Cell viability and intracellular ROS formation were determined, together with the effect on the cell antioxidant defenses. Elderberry polyphenols and their potential molecular targets are associated with the modulation of key enzymes and the activation of metabolic pathways, with reported cardiovascular and neuroprotective activities. Evidence for neuroprotection remains exclusively preclinical.

6. Body Systems and Health Areas Associated with Sambucus nigra

• Immune system: Immunomodulatory and immunostimulatory effects observed in ex vivo cytokine studies and clinical trials for respiratory infections.
• Respiratory system: Best-documented clinical use; associated with reduced duration and severity of common cold and influenza.
• Cardiovascular system: Preclinical evidence for blood pressure modulation and antioxidant cardioprotection; no robust human trials.
• Metabolic/endocrine system: Inhibition of α-glucosidase and α-amylase in vitro; traditional use as antidiabetic agent; no confirmed human clinical trials.
• Gastrointestinal system: Historical use as a purgative and laxative (unprocessed bark and leaves); cellular antioxidant protection in intestinal cell lines.
• Skin: Traditional external use; flowers and fruits have been traditionally and officially employed in dermatology and cosmetology applications.
• Nervous system: Preliminary in vitro neuroprotective evidence; no human trials.

7. Dosage Forms and Dosages Reported in Clinical Studies

Most studies administer elderberry in lozenge, capsule, syrup, or juice forms, with doses ranging from 175 to 900 mg/day (15 to 177 mL in liquid forms) over periods of 48 hours to four weeks when used for treatment, and for up to 12 weeks when used as a preventative measure.

• Influenza treatment: 15 mL of syrup taken 4 times per day for 5 days has been used in clinical trials.
• Air travel respiratory health: Initially 600 mg/day starting 10 days before travel, followed by 900 mg/day starting the day before travel and continued for 4 or 5 days post-flight.
• Lozenge form: 175 mg of elderberry extract taken four times a day for 2 days has been used in clinical studies for flu-like symptoms.
• Emergency room influenza trial: 15 ml (1 tablespoon) of liquid extract; participants aged 5–12 took the medication 2 times per day (morning/night) for 5 days; participants aged 13 and above took the medication 4 times per day (morning/noon/afternoon/night) for 5 days.

Dosing information in general is based on limited evidence from clinical trials. The wide variation in doses across studies reflects differences in extraction method, standardization, and formulation. No universally accepted standardized dose has been established.

8. Safety Considerations and Drug Interactions

Cyanogenic Glycoside Toxicity

Elderberry also contains cyanogenic glycosides, which are potentially toxic. Polyphenols, known for their free radical scavenging (antioxidant) activity, are the most important group of bioactive compounds present in elderberry in relatively high concentration. Cyanogenic glycosides are potentially toxic and life-threatening because they can be hydrolysed, resulting in the release of cyanide. However, they occur primarily in unripe berries and are degraded during heat treatment.

While ripe berries have lower levels than other plant parts, improper processing or consuming large amounts of raw berries can cause nausea, vomiting, diarrhea, and, in severe cases, cyanide poisoning. The concentration of toxic compounds varies with plant part, ripeness, and growing conditions. Berries from higher altitudes may contain more cyanogenic glycosides.

The consumption of immature plants or high quantities of fruits may cause nausea, vomiting, and diarrhea. Thermal processing of raw material leads to the decay of sambunigrin, so the consumption of fruits subjected to heating processes does not cause symptoms of poisoning.

Safety of Processed Commercial Products

While elderberry is generally recognized as safe when properly prepared, clinical trials on long-term safety are limited. The evidence included in most reviews is derived from clinical studies involving adult participants and examining short-term use of commercial formulations of S. nigra berry for up to 16 days.

Adverse events, reported in two reviewed 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.

Drug Interactions

There are no clinical trials on the interaction of elderberry components with medicines. Only concerns associated with the use of elderberry together with antidiabetic drugs, morphine, phenobarbital, diuretics, and immunoactive drugs are considered.

Due to the immune-stimulating properties of Sambucus nigra, there is a theoretical concern that it could interfere with the efficacy of immunosuppressive medications used for organ transplant recipients (e.g., cyclosporine, tacrolimus) or for the treatment of autoimmune disease. These concerns are theoretical rather than established by direct clinical evidence.

Product Adulteration

Commercial elderberry products may be adulterated or mislabeled, so sourcing from reputable suppliers is important.

Bioavailability

The bioavailability of active constituents in elderberry extracts is considered to be poor. This is a significant limiting factor in translating in vitro findings to human clinical outcomes and may partially account for inconsistencies across clinical trials.

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