Annona muricata L., known as graviola, is an evergreen plant of the tropical regions and is a rich source of natural products. Graviola has various biological activities, and it is best known for its anticancer activity. This study aimed to investigate the effects of crude graviola extract in vitro on breast cancer cells; in particular, we aimed to identify an agent against triple negative breast cancer (TNBC). We used the TNBC MDA-MB-231 cell line as the experimental model and the ER(+) non-TNBC MCF-7 breast cancer cell line as the control. We identified annonaceous acetogenins, including annonacin isomers, characteristic to this plant by using liquid chromatography tandem mass spectrometry (LC/MS/MS). We observed a significant decrease in the cell viability in both cell lines within 48 h, whereas impaired cell motility and invasiveness were observed only in the MDA-MB-231 cell line. While the MCF-7 cells showed an ER-dependent mechanism of apoptosis, the apoptosis of MDA-MB-231 cells was governed by an intrinsic apoptotic pathway triggered by graviola leaf extract (GLE).

Supporting information 1D and 2D NMR spectra of 1a/1b, 2a/2b and 3a/3b are available online at http://www.thieme-connect.de/products. AbStr Ac tCis-trans isomers of N 1 ,N 5 ,N 9 ,N 14 -tetra-p-coumaroyl thermospermines and N 1 ,N 5 ,N 10 ,N 14 -tetra-p-coumaroyl spermines were found in Matricaria chamomilla, German chamomile using countercurrent chromatography with methylene chloride-methanol-water (1:1:1, v/v/v). Their structures were elucidated based on spectroscopic and spectrometric data (1D and 2D NMR, and HRESIMS). The antagonistic activity against the neurokinin-1 receptor was examined by a calcium assay, measuring the cytosolic fluorescence triggered by substance P binding to the receptor. The compounds 1a/1b, 2a/2b, and 3a/3b potently suppressed the calcium flux compared to the known antagonist L-703,606 oxalate, indicating that the compounds competitively inhibited the binding of substance P. They also suppressed substance P-induced proliferation in MDA-MB-453, the HER2-amplified breast cancer cell line. It is suggested that tetracoumaroyl thermospermines and tetracoumaroyl spermines are promising antagonists, exerting positive effects on substance P/neurokinin-1 receptor-related diseases.

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Senna leaf is widely consumed as tea to treat constipation or to aid in weight loss. Sennoside A, A1 , and B are dirheinanthrone glucosides that are abundant and the bioactive constituents in the plant. They are isomers that refer to the (R*R*), (S*S*), and (R*S*) forms of protons on C-10 and C-10' centers and it is difficult to refine them individually due to their structural similarities. The new separation method using counter-current chromatography successfully purified sennoside A, A1 , and B from senna leaf (Cassia acutifolia) while reversed-phase medium-pressure liquid chromatography yielded sennoside A only. n-Butanol/isopropanol/water (5:1:6, v/v/v) was selected as the solvent system for counter-current chromatography operation, and the partition coefficients were carefully determined by adding different concentrations of formic acid. High-resolution mass spectrometry and NMR spectroscopy were performed to verify the chemical properties of the compounds.