Metabolite profiling and bioactivity of Cicerbita alpina (L.) Wallr. (Asteraceae, Cichorieae)

Abstract

Cicerbita alpina (L.) Wallr. is a perennial herbaceous plant in the tribe Cichorieae (Lactuceae), Asteraceae family, distributed in the mountainous regions in Europe. In this study, we focused on the metabolite profiling and the bioactivity of C. alpina leaves and flowering heads methanol-aqueous extracts. The antioxidant activity of extracts, as well as inhibitory potential towards selected enzymes, involving in several human diseases, including metabolic syndrome (α-glucosidase, α-amylase, and lipase), Alzheimer's disease, (cholinesterases: AChE, BchE), hyperpigmentation (tyrosinase), and cytotoxicity were assessed. The workflow comprised ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS). UHPLC-HRMS analysis revealed more than 100 secondary metabolites, including acylquinic, acyltartaric acids, flavonoids, bitter sesquiterpene lactones (STLs), such as lactucin, dihydrolactucin, their derivatives, and coumarins. Leaves showed a stronger antioxidant activity compared to flowering heads, as well as lipase (4.75 ± 0.21 mg OE/g), AchE (1.98 ± 0.02 mg GALAE/g), BchE (0.74 ± 0.06 mg GALAE/g), and tyrosinase (49.87 ± 3.19 mg KAE/g) inhibitory potential. Flowering heads showed the highest activity against α-glucosidase (1.05 ± 0.17 mmol ACAE/g) and α-amylase (0.47 ± 0.03). The obtained results highlighted C. alpina as a rich source of acylquinic, acyltartaric acids, flavonoids, and STLs with significant bioactivity, and therefore the taxon could be considered as a potential candidate for the development of health-promoting applications.

Keywords: Cicerbita alpina; UHPLC-HRMS; antioxidant properties; cytotoxic activity; enzyme inhibitory activity; secondary metabolites.

Figure 1

Total ion chromatogram (TIC) in negative ion mode of C. alpina leaves extract (A); extracted ion chromatogram of peaks at m/z 473.072 (B); (−) ESI/MS-MS spectrum of dicaffeoyltartaric acid (cichoric acid) (47) (C).

Figure 2

(−) ESI/MS-MS spectrum of isoetin (85) (A); quercetin (92) (B); possible fragmentation and preliminary structure of isoetin (85) and quercetin (92) (C).

Figure 3

PLS-DA analysis on the bioactivities of C. alpina. (A) Scatter plot. (B) ROC curve. (C) VIP score plot. (D) Loading plot.

Figure 4

Cytotoxicity of C. alpina extracts towards THP-1 cells (by the student t-test, different letters indicate significant difference between plant parts in the same concentration (a and b), p ≤ 0.05.).