Chemical constituents of theAnnona glabrafruit and their cytotoxic activity

Abstract

Context: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. Annona glabra Linn (Annonaceae) is used in traditional medicine as an anticancer drug. Phytochemical investigation of this plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids. In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria. Objective: Isolation, structure determination, and cytotoxic activity evaluation of compounds from the methanol extract from A. glabra fruits. Materials and methods: Using chromatographic methods to isolate compounds from the A. glabra methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds which showed significant cytotoxic activity were chosen for further study apoptosis characteristics. (5), 3,4-dihydroxybenzoic acid (6), blumenol A (7), cucumegastigmane I (8), and icariside B 1 (9), were isolated from the fruits of A. glabra. Icariside D 2 (3) was found to show significant cytotoxic activity on the HL-60 cell line with the IC 50 value of 9.0 ± 1.0 mM and did not show cytotoxic activity on the Hel-299 normal cell line. The further test indicated that compound 3 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells. Discussion and conclusion: The results suggested that the constituents from A. glabra may contain effective compounds which can be used as anticancer agents.

Natural Products and Acute Myeloid Leukemia: A Review Highlighting Mechanisms of Action

“…increased the level of c-caspase-3, -9, Bax, while decreasing the level of Bcl-2 [64]. Elevated expression level of c-caspase-3, Bax and suppressed expression of Bcl-2, c-myc, p-AKT were demonstrated following the treatment of icariside D 2 [65]. Also, icariside II treatment promoted c-caspase-3 activity, c-PARP, PTP and SHP-1 expression in U937 cells.…”

Discovery of Dihydrophaseic Acid Glucosides from the Florets of Carthamus tinctorius

“…Thus, the absolute configuration of 1 was determined as 2 E ,4 E ,1’ R ,3’ S ,5’ R ,8’ S, and the structure of 1 was elucidated as (2 E ,4 E )-dihydrophaseic acid methyl ester-3- O - β -D-glucopyranoside. To the best of our knowledge, recently, free acid and glucoside ester of compound 1 were reported from Annona glabra fruit [ 19 ].…”

Metabolic engineering Escherichia coli for efficient production of icariside D2

“…Recently, more attentions have been paid on the pharmacological studies of icariside D2. It has been reported that icariside D2 had synergistic inhibitive effect on angiotensin-converting enzyme [4] and remarkable anticancer activity to kill leukemia cells in vitro [5], demonstrating the therapeutic and nutraceutical potential of icariside D2 in the health care industry.…”

“…Although icariside D2 has been identified from several plants such as Epimedium [1], Apium graveolens [4], Annona glabra [5], Ficus microcarpa [6], Tinospora sinensis [7], and Rhodiola crenulata [8], extraction of icariside D2 suffers low yields for the low content and limited plant resources. Chemical synthesis for glycoside products has always been frustrated by the diversity of stereochemistries and regiochemistries, and generally requires multiple protection and deprotection steps to achieve regio-selectivity in glycosylation [9].…”