Antiviral Potential and Chemical Composition of Wild Baccharis crispa Spreng. Populations (Asteraceae) from Córdoba, Argentina: Perspective on Population Variability

Abstract

Medicinal plants have been explored worldwide as potential alternatives for the prevention and treatment of different diseases, including viral infections. Baccharis crispa Spreng. (Asteraceae) is a native medicinal species widely used in South America. Given the influence of genetic and environmental factors on secondary metabolites biosynthesis and accumulation, this study aimed to evaluate the in vitro antiviral activity of four wild populations of B. crispa from Córdoba, Argentina, and assess the variability in their bioactivity and chemical composition. The cytotoxicity of chloroform, ethanol, and aqueous extracts from aerial parts was evaluated by the neutral red uptake method. Antiviral and virucidal activity against herpes simplex virus type 1 (HSV-1) and chikungunya virus (CHIKV) were assessed via plaque-forming unit (PFU) reduction assay. Phytochemical analyses of the extracts were conducted using HPLC-ESI- MS/MS. The Puesto Pedernera population showed the strongest antiviral activity, with inhibition rates of 82% for CHIKV and 79% against HSV-1, as well as potent virucidal effects, reducing PFU formation by up to 5 logarithms for both viruses. Remarkably, ethanol extract exhibited the least toxicity and strongest inhibitory activity. Villa del Parque population was inactive. We identified 38 secondary metabolites, predominantly phenolic acids (12) and flavonoids (18), in varying proportions. Delphinidin and delphinidin-3-glucoside are described for the first time in the species. Differences in phytochemical profiles were observed among extract types and populations. Key phenolic compounds showed moderate positive correlations with the evaluated bioactivities, emphasizing the complexity of phytochemical properties and interactions. These results highlight the therapeutic potential of B. crispa extracts against viral infections and underscore the importance of considering the geographical source of plant material in bioactivity evaluations.

Keywords: bioactivities; chikungunya virus; herpes simplex virus; natural products; population variability.

Figure 1

Effect of extracts from four wild populations of Baccharis crispa against HSV-1 and CHIKV. Viral inactivation of aqueous (Aqu) and organic extracts (CHCl₃ and EtOH) from four wild populations of B. crispa against HSV-1 and CHIKV. Data represent virus yield (log PFU/mL) compared to viral control (infected and untreated cells), expressed as $\overline{x}$ ± SD (n = 3) of three independent experiments. The dashed line represents the cut-off point for the virucidal activity; extracts below it are positive. * Significant difference between wild populations for the CHCl₃ extracts p ≤ 0.05 (ANOVA DGC test). ** Significant difference between wild populations for the EtOH extracts p ≤ 0.05 (ANOVA DGC test). *** Significant difference between wild populations for the Aqu extracts p ≤ 0.05 (ANOVA DGC test). CHIKV: chikungunya virus; HSV-1: herpes simplex virus type 1; CHCl₃: chloroform extract; EtOH: ethanol extract; Aqu: aqueous extract; VP: Villa del Parque population; TC: Tala Cañada population; SG: San Geronimo population; PP: Puesto Pedernera population.

Figure 2

Comparative phenolic profiles of four wild populations of B. crispa. Proportion of total (%) of the 38 phenolic compounds found in the wild populations of B. crispa (PP, VP, TC, SG). The compounds include phenolic acids, flavonoids, lignan, hydroxycoumarin, and other polyphenols. PP: Puesto Pedernera population (black); VP: Villa del Parque population (red); TC: Tala Cañada population (orange); SG: San Geronimo population (purple).

Figure 3

Multivariate analysis for phytochemical profiles and bioactivities of aqueous and organic extracts from four wild populations of Baccharis crispa. (A) Principal component analysis (PCA) biplot the distribution and abundance of the phenolic compounds. (B) Partial least squares discriminant analysis (PLS-DA) illustrating distinct groups between extract types (aqueous, chloroform, ethanol). (C) Hierarchical clustering analysis (HCA) displaying the relative abundance of phenolic compounds across different extract types and wild populations, with hierarchical clustering indicating the similarity between samples. The color scale on the right represents normalized values, ranging from −1 (blue, lower concentrations) to +3 (red, higher concentrations).

Figure 4

Correlogram showing the Pearson correlation between phenolic compound concentrations of each extract and bioactivities of Baccharis crispa. The color gradient represents correlation values, ranging from −1 (red, strong negative correlation) to +1 (blue, strong positive correlation), as shown by the scale on the right. The size and direction of the pie slices within the circles indicate the magnitude of the correlations.