Development of Potential Therapeutic Agents from Black Elderberries (the Fruits of Sambucus nigra L.)

Abstract

Elderberry (Sambucus nigra L.) is a widespread deciduous shrub, of which the fruits (elderberries) are used in the food industry to produce different types of dietary supplement products. These berries have been found to show multiple bioactivities, including antidiabetic, anti-infective, antineoplastic, anti-obesity, and antioxidant activities. An elderberry extract product, Sambucol^®, has also been used clinically for the treatment of viral respiratory infections. As the major components, phenolic compounds, such as simple phenolic acids, anthocyanins and other flavonoids, and tannins, show promising pharmacological effects that could account for the bioactivities observed for elderberries. Based on these components, salicylic acid and its acetate derivative, aspirin, have long been used for the treatment of different disorders. Dapagliflozin, an FDA-approved antidiabetic drug, has been developed based on the conclusions obtained from a structure-activity relationship study for a simple hydrolyzable tannin, β-pentagalloylglucoside (β-PGG). Thus, the present review focuses on the development of therapeutic agents from elderberries and their small-molecule secondary metabolites. It is hoped that this contribution will support future investigations on elderberries.

Keywords: Sambucol®; antioxidants; antitumor; antiviral; elderberries; phenolic constituents; therapeutic agents.

Figure 1

Structures of the major constituents identified from elderberries.

Figure 2

Structures of ursolic acid and oleanolic acid isolated from elderberries and a synthetic derivative of oleanolic acid, bardoxolone methyl (CDDO-Me), which has been evaluated in cancer clinical trial investigations.

Figure 3

Crystal structures of p-hydroxybenzoic acid, salicylic acid, chlorogenic acid, and quinic acid encapsulated by β-cyclodextrin (β-CD) and the structures of salicylic acid and aspirin. The crystal structure plots were drawn using ORTEP-3 for Windows version 2020.1 [53], based on data from the literature. The ORTEP diagram for quinic acid shows one of the two complexes of quinic acid and β-CD, for which water molelcules are omitted, and the disordered region of the β-CD molecule is presented. In the ORTEP plots, oxygen atoms are red, carbon atoms are blue, and the small white circles represent hydrogen atoms, which are drawn with an artificial radius.

Figure 4

Structures of the antidiabetic lead compounds, α-PGG and β-PGG, and of dapagliflozin, an FDA-approved antidiabetic drug.

Figure 5

Examples of biological properties reported for elderberries and their major bioactive secondary metabolites.