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(Alternative Medicine Review, March 2005)
Use and Potential Benefit
The Commission E approved the internal use of elder flower for colds. The British Herbal Compendium lists its uses for common cold, feverish conditions, and as a diuretic (Bradley, 1992). The German Standard License for elder flower tea calls it a diaphoretic medicine for the treatment of feverish common colds or catarrhal complaints (Braun et al., 1997).
Prophylaxis and treatment of Influenza. Some laboratory studies suggest that elder may reduce mucus production and possess anti-inflammatory and antiviral effects. Proven to kill H5N1 in-vitro. The flowers and berries (blue/black only) contain flavonoids, which have been found pre-clinically to possess a variety of biochemical and pharmacological actions, including antioxidant and immunologic properties.
Active Constituents
The fruit of Sambucus nigra (elderberries) contains several constituents responsible for pharmacological activity. Among these are the flavonoids quercetin and rutin, anthocyanins identified as cyanidin-3-glucoside and cyanidin-3-sambubioside, (3) the hemagglutinin protein Sambucus nigra agglutinin III (SNA-III), (4) cyanogenic glycosides including sambunigrin, (5,6) viburnic acid, and vitamins A and C. (2)
Pharmacokinetics
Due to limited research, the pharmacokinetics of many constituents of Sambucus nigra are not completely understood. Available research has focused on the absorption and urinary excretion of the anthocyanin constituents.
Historically, researchers were uncertain whether anthocyanins were absorbed unless they were first hydrolyzed in the gastrointestinal tract. Recently, however, several small pharmacokinetic studies of elderberry extract in healthy volunteers demonstrated elderberry anthocyanins are indeed absorbed and excreted in an intact form.
Within four hours of consuming 12 g elderberry extract containing 720 mg total anthocyanins, the two major anthocyanins in elderberry extract were identified in the urine of four elderly women. (3)
A second similar study involving 16 healthy volunteers confirmed the presence of the same two anthocyanins in the urine of study subjects after oral administration of elderberry extract. (7)
In another study involving six healthy volunteers, a single oral dose of 30 mL elderberry extract (147.3 mg total anthocyanins) resulted in a rapid urinary excretion rate of intact anthocyanins with only 0.37 percent of the original dose being present in the urine at seven hours post-ingestion. (8)
One study investigated the absorption of elderberry anthocyanins in a single male subject given 25 g elderberry extract (1.5 g total anthocyanins); high-performance liquid chromatography (HPLC) analysis detected two anthocyanin peaks in plasma collected 30 minutes post-dose. (9)
Another study detected anthocyanins from elderberry in glycoside form in both plasma and urine four hours after dosing. (10)
Mechanisms of Action Antiviral
While there are several mechanisms responsible for the beneficial effects of Sambucus nigra and extracts of its berries, perhaps the most important and best studied are the antiviral effects. Mumcuoglu, an Israeli virologist, was the first to discover elderberry constituents neutralize the activity of the hemagglutinin spikes found on the surface of several viruses. When these hemagglutinin spikes are deactivated the viruses can no longer pierce cell walls or enter the cell and replicate. (11)
Based on these findings, Sambucol[R], a syrup containing 38-percent standardized extract of black elderberry, was developed. Numerous studies using the Sambucol preparation have shown it to neutralize and reduce the infectivity of influenza viruses A and B, (12,13) HIV strains and clinical isolates, (14) and Herpes simplex virus type 1 (HSV-1) strains and clinical isolates. (15) It probably does so in the same manner as with influenza viruses, via neutralization of the virus resulting in reduced infectivity.
Immune Modulation via Cytokine Production
Elderberry extracts also have immune-modulating activity in healthy individuals as well as in those with viral infections or other diseases characterized by immunosuppression. Production of certain cytokines leads to activation of phagocytes and facilitates their movement to inflamed tissues. (16) Two studies using blood-derived monocytes from healthy donors demonstrated the ability of several Sambucol extracts to significantly increase cytokine production.
Cytokines tested were tumor necrosis factor-alpha (TNF-[alpha]), and interleukins (IL)-1[beta], -6, and -8. (17) A second similar study also measured monocyte production of IL-10 when exposed to various Sambucol preparations and confirmed the results of the first study. A 1.3- to 6.2-fold increase in cytokine production was observed compared to control. A 2.3-fold increase in IL-10 was also observed. (18)
Antioxidant
Elderberries contain several anthocyanin flavonoids known to possess significant antioxidant properties. Research has demonstrated low-level concentrations (4 mcg/mL) of elderberry anthocyanins can efficiently regenerate alpha-tocopherol from alpha-tocopheroxyl radicals in models of copper-mediated LDL oxidation. (19) Since it has been observed that anthocyanin glycosides are indeed absorbed in humans, (3,7-10) it is likely that supplementing with elderberry extracts containing anthocyanins provides significant antioxidant benefit.
It has been established that endothelial cell dysfunction results in changes in the redox status of cells. (20) Based on this premise and previous research on elderberry's antioxidant potential, Youdin et al demonstrated elderberry anthocyanin incorporation into endothelial cells confers increased protection against oxidative stress.
Human aortic endothelial cells incorporated elderberry anthocyanins into both the membrane and cytosol, affording significantly enhanced resistance to damage from reactive oxygen species. The most pronounced affect was seen with protection against [H.sub.2][O.sub.2]-induced loss in cell viability.
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