Plant Extracts and Phytochemicals from the Asteraceae Family with Antiviral Properties

Abstract

Asteraceae (Compositae), commonly known as the sunflower family, is one of the largest plant families in the world and includes several species with pharmacological properties. In the search for new antiviral candidates, an in vitro screening against dengue virus (DENV) was performed on a series of dichloromethane and methanolic extracts prepared from six Asteraceae species, including Acmella bellidioides, Campuloclinium macrocephalum, Grindelia pulchella, Grindelia chiloensis, Helenium radiatum, and Viguiera tuberosa, along with pure phytochemicals isolated from Asteraceae: mikanolide (1), eupatoriopicrin (2), eupahakonenin B (3), minimolide (4), estafietin (5), 2-oxo-8-deoxyligustrin (6), santhemoidin C (7), euparin (8), jaceidin (9), nepetin (10), jaceosidin (11), eryodictiol (12), eupatorin (13), and 5-demethylsinensetin (14). Results showed that the dichloromethane extracts of C. macrocephalum and H. radiatum and the methanolic extracts prepared from C. macrocephalum and G. pulchella were highly active and selective against DENV-2, affording EC₅₀ values of 0.11, 0.15, 1.80, and 3.85 µg/mL, respectively, and SIs of 171.0, 18.8, >17.36, and 64.9, respectively. From the pool of phytochemicals tested, compounds 6, 7, and 8 stand out as the most active (EC₅₀ = 3.7, 3.1, and 6.8 µM, respectively; SI = 5.9, 6.7, and >73.4, respectively). These results demonstrate that Asteraceae species and their chemical constituents represent valuable sources of new antiviral molecules.

Keywords: Asteraceae; antiviral; dengue; flavonoids; phenolic compounds; plant extract; sesquiterpene lactones; terpenoids.

Figure 1

Sesquiterpene lactones isolated from species belonging to the Asteraceae family: Mikanolide (1); eupatoriopicrin (2); eupahakonenin B (3); minimolide (4); estafietin (5); 2-oxo-8-deoxy-ligustrin (6); santhemoidin C (7).

Figure 2

Phenolic compounds isolated from species belonging to the Asteraceae family: Euparin (8); jaceidin (9); nepetin (10); jaceosidin (11); eryodictiol (12); eupatorin (13); 5-demethylsinensetin (14).

Figure 3

Antiviral activity of dichloromethane (A) and methanolic extracts (B) and against DENV-2 in Vero cells. Cells were infected with DENV-2 (m.o.i. 0.1 PFU/cell) and, after 1 h adsorption at 37 °C, were treated with medium containing different dilutions of the dichloromethane extracts or vehicle. After 48h of infection, viral yield was determined via plaque assay. Extracts that were considered inactive were not included. Results are expressed as the mean values ± standard deviation (SD).

Figure 4

Antiviral activity of pure compounds against DENV-2 in Vero cells. Cells were infected with DENV-2 (m.o.i. 0.1 PFU/cell) and, after 1 h adsorption at 37 °C, were treated with medium containing different dilutions of the pure compounds or vehicle (dimethyl sulfoxide). After 48 h of infection, viral yield was determined via plaque assay. Results are expressed as the mean values ± standard deviation (SD).

Figure 5

HPLC analysis of (A) MGPU and (B) MCM. (Chromatographic system: stationary phase: C-18; mobile phase: 15–85% MEOH in 35 min; detector: PDA, 210 nm).

Figure 6

HPLC analysis of (A) DHR and (B) DCM. (Chromatographic system: stationary phase: C-18; mobile phase: 15–85% MEOH in 35 min; detector: PDA, 210 nm).