Cytotoxic Withanolides from the Whole Herb of Physalis angulata L

Abstract

Physalis angulata L. is a medicinal plant of the Solanaceae family, which is used to produce a variety of steroids. The present study reports on the cytotoxic withanolides of this plant. The species of Physalis angulata L. was identified by DNA barcoding techniques. Two new withanolides (1-2), together with six known analogues (3-8), were isolated from the whole plant of Physalis angulata L. The structures of these new compounds were determined on the basis of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. The withanolides exhibited strong cytotoxic activities against A549, Hela and p388 cell lines. Furthermore, compounds 1 and 2 induced typical apoptotic cell death in A549 cell line according to the evaluation of the apoptosis-inducing activity by flow cytometric analysis.

Keywords: Physalis angulata L.; Solanaceae; cytotoxic activities; withanolides.

Figure 1

Structures of compounds 1–8 from P. angulata L.

Figure 2

Key HMBC, NOE and ¹H-¹H COSY correlations of 1 and 2.

Figure 3

Calculated and experimental ECD spectra for 1 and 2 in MeOH.

Figure 4

A549 cell apoptosis induced by 1 and 2. (A) Annexin V/FITC flow cytometry to detect the effect of different concentrations of 1 (5, 10, 20 μM) and 2 (10, 20, 40 μM) on apoptosis rate. n = 3, ** p < 0.01. (B) Apoptotic rates of A549 cells as induced by compounds 1 and 2, which were inspected by Annexin V-PI. Controls were normal A549 cells; A549 cells treated with various concentrations of compounds 1 and 2 for 24 h. Each experiment was repeated 3 times. Data are represented as mean ± SD, n = 3, **p < 0.01 vs. Control.