Isolation and Identification of Cucurbitane-Type Triterpenoids with Partial Agonist/Antagonist Potential for Estrogen Receptors from Momordica charantia

Abstract

This study aims at investigating the estrogenic activity and active cucurbitane-type triterpenoid compounds of bitter gourd (Momordica charantia, MC) using a transactivation assay for estrogen receptors (ER) α and β. The lyophilized fruits of MC were exhaustively extracted with ethyl acetate (EA) and 95% ethanol (EtOH), sequentially. The nonsaponifiable fraction (NS) of the EA extract as well as the acid hydrolyzed EtOH extract (AH) was fractionated and isolated by repeated column chromatography and further purified by preparative HPLC or RP-HPLC. One known compound, 5β,19-epoxycucurbita-6,24-diene-3β,23ξ-diol (6), was isolated from the NS, and five new compounds (1-5) were isolated from AH and identified as cucurbita-6,22(E),24-trien-3β-ol-19,5β-olide (1), 5β,19-epoxycucurbita-6,22(E),24-triene-3β,19-diol (2), 3β-hydroxycucurbita-5(10),6,22(E),24-tetraen-19-al (3), 19-dimethoxycucurbita-5(10),6,22(E),24-tetraen-3β-ol (4), and 19-nor-cucurbita-5(10),6,8,22(E),24-pentaen-3β-ol (5). In the noncytotoxic concentration range, compounds 1, 2, 5 and 6 showed weak agonistic activity via ER α and β. Compounds 1, 2, 3 and 6 significantly antagonized the transactvation of 17β-estradiol (E(2)) via both ER α and β. In conclusion, this study demonstrates, for the first time as far as we know, the partial agonist/antagonist activity via ER of four new and one known cucurbitane-type triterpenoids from MC. Further studies are worthy to explore the selective estrogen receptor modulator (SERM) activity of MC.

Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) extract and its bioactive components suppress Propionibacterium acnes-induced inflammation

“…Chemical investigations by GC-MS and NMR indicated the presence of many biologically active constituents, including phytol and lutein, in the nonsaponifiable (NS) fraction of EA extract from wild bitter melon fruits (Hsu et al, 2011). In our previous study (Hsu et al, 2011), NS fraction was fractionated and separated by silica gel chromatography that was sequentially eluted with 0%, 2%, 5%, 10%, 20%, 30%, 50% and 100% EA in hexane.…”

“…The combined solutions were evaporated to yield the EA extracts. The saponifiable (S) and nonsaponifiable (NS) fractions of WBM EA extract were prepared using previous procedure (Hsu et al, 2011) with some modification. Briefly, the EA extract was saponified by dissolving in 10-fold (w/ v) of a mixture of tetrahydrofuran (THF) and 10 N NaOH in equal volume and incubated at 60°C overnight.…”

“…In our previous study (Hsu et al, 2011), NS fraction was fractionated and separated by silica gel chromatography that was sequentially eluted with 0%, 2%, 5%, 10%, 20%, 30%, 50% and 100% EA in hexane. The isolated active compound from fraction 14 was identified as lutein by NMR and mass spectrometry (Fig.…”

“…abbreviata Seringe) is a wild variety of Momordica charantia and is consumed as both a vegetable and as folk medicine in Taiwan. Bitter melon is known to contain numerous components such as alkaloids, steroidal glucosides, phenolics (Krawinkel & Keding, 2006), lysophosphatidylcholines (Kobori et al, 2008), conjugated linolenic acid isomers (Chuang et al, 2006), and cucurbitane-type triterpenoids (Chang et al, 2011;Hsu, Hsieh, Kuo, & Huang, 2011). 1-R-linolenoyl-LPC and 1-linoleoyl-LPC has been shown to negatively regulate TNF-a production in endotoxin lipopolysaccharide (LPS)-activated RAW264.7 macrophages (Kobori et al, 2008).…”

Cucurbitane Triterpenoids from the Fruit Pulp of Momordica charantia and Their Cytotoxic Activity

“…Tissues of this plant have been used not only as a vegetable, but also as a folk medicine for the treatment of diabetes and bitter stomachic in Asian. Several pharmacological investigations have showed that the extracts or compounds of tissues of M. charantia possess cytotoxic, anti-diabetic, and anti-inflammatory activities [1][2][3][4] More than seventy cucurbitane-type triterpenes have been isolated from the fruits, [3][4][5][6][7][8][9][10][11][12][13][14] seeds, 15,16 root, 17 leaves and vines [18][19][20] of M. charantia. In the course of our research for bioactive secondary metabolites from Taiwanese M. charantia, we had reported the isolation and structure elucidation of twenty-five cucurbitanetype triterpenoids from the MeOH extract of the stems of this plant.…”