Cucurbitane Triterpenoids from Momordica charantia and Their Cytoprotective Activity in tert-Butyl Hydroperoxide-Induced Hepatotoxicity of HepG2 Cells

Abstract

NoteMomordica charantia L., a slender-stemmed tendril climber, belongs to the family Cucurbitaceae and is commonly known as bitter gourd or bitter melon. It is wildly cultivated as a vegetable crop in tropical and subtropical areas, including Asia, East Africa, and South America. Tissues of this plant have extensively been used as folk medicine for the treatment of diabetes and diseases of liver in Taiwan. The previous pharmacological studies have demonstrated that the extracts or constituents of tissues of M. charantia possess anti-diabetic and anti-inflammatory activities.1-3) The Cucurbitaceae plants have been recognized as rich sources of cucurbitane-type triterpenoids possessing anti-diabetic activity.3) More than seventy cucurbitane-type triterpenoids have been identified from the fruits, [3][4][5][6][7][8][9][10] seeds, 11,12) roots, 13) leaves and vines 14,15) of M. charantia. As part of our program aimed at the discovery of the cucurbitane-type triterpenes from M. charantia originated in Taiwan, we have reported the isolation and structure elucidation of 21 cucurbitane-type triterpenoids from the MeOH extract of the stems of this plant. [16][17][18] In our continuing investigation on the same extract, we further isolated two novel pentanorcucurbitane triterpenes, 22-hydroxy-23,24,25,26,27-pentanorcucurbit-5-en-3-one (1) and 3,7-dioxo-23,24,25,26,27-pentanorcucurbit-5-en-22-oic acid (2), as well as a novel trinorcucurbitane triterpene, 25,26,27-trinorcucurbit-5-ene-3,7,23-trione (3) (Fig. 1). In this paper, we describe the isolation and structure elucidation of compounds 1-3 and the cytoprotective activities of compounds 2 and 3 in tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity of HepG2 cells. Results and DiscussionCompound 1 The 13 C-NMR spectrum of 1 revealed 25 carbon signals, which were assigned by the distortionless enhancement by polarization transfer (DEPT) experiments as six aliphatic methyl, seven aliphatic methylene, four aliphatic methine, four aliphatic quaternary, one oxygenated methylene, one olefinic methine, one quaternary olefinic, and one isolated ketone carbonyl carbons. Its high resolution electron impact mass spectrum (HR-EI-MS) exhibited a molecular ion at m/z 372.3048, consistent with the molecular formula, C 25 H 40 O 2 , which indicated six degrees of unsaturation. Two degrees of unsaturation were attributable to a trisubstituted olefin and a ketone group, and the remaining four units of unsaturation were accounted for the tetracyclic skeleton. On the basis of the fact that the major tetracyclic triterpenoids presenting in the genus Momordica plants are cucurbitane-type triterpenes, compound 1 was tentatively proposed to be a 23,24,25,26,27-pentanorcucurbitacin derivative. By comparison of the 1 Hand 13 C-NMR data with those of the known compound, (23E)-25-hydroxycucurbita-5,23-diene-3,7-dione, 16) indicated that both compounds exhibited identical structure in rings A-D of the tetracyclic skeleton and the 13 C-NMR signals of C-23-C-27 of the side chain were absent in 1....

Bitter melon: a panacea for inflammation and cancer

“…(23 S * )-3 β -hydroxy-7 β , 23-dimethoxy-cucurbita- 5, 24-dien-19-al ( 8 ) and (23R * )-23- O -methylmomordicine IV ( 9 ) also show cytotoxic activity against HL60 cell line with IC 50 values being 6.2 ± 0.7 μmol·L −1 and 7.6 ± 0.5 μmol·L −1 , respectively [52] . 25, 26, 27-trinorcucurbit-5-ene-3, 7, 23-trione ( 10 ) and 3, 7-dioxo-23, 24, 25, 26, 27-penta-norcucurbit-5-en-22-oic acid ( 11 ) have cytoprotective effects in tert -butyl hydroperoxide ( t -BHP)-induced hepatotoxicity of HepG2 cells [54] . Harinantenaina et al .…”

“…have isolated and structurally characterized Charantoside I–VIII from the methanolic extract of the fruits of Japanese MC [51] . Momordicine I – VIII [54, 63, 77–79] are also found in MC.…”

Applications of Thermal Activation, Ball‐milling and Aqueous Medium in Stereoselective Michael Addition of Nitromethane to Enynones Catalyzed by Chiral Squaramides

“…Here we report a stereoselective addition of nitromethane to en-ynones that requires the reaction to be performed either in a biphasic water-dichloromethane medium, at elevated temperatures, or with ball-milling. [15] However, such Michael additions relied on iminium-ion catalysis and required as much as 15 mol% of intricate chiral bifunctional primary amine-thiourea catalysts. Further reaction of the adducts led to 1,5-diketones with three contiguous stereocenters after hydration/Michael cyclization sequences.…”

“…[14] This structural motif has also been found in compounds exhibiting interesting bioactivities. [15] However, such Michael additions relied on iminium-ion catalysis and required as much as 15 mol% of intricate chiral bifunctional primary amine-thiourea catalysts. [16a] This approach is further complicated by the limited stability of polyconjugated nitroalkenes.…”

New Norcucurbitane Triterpenoids from Momordica charantia var. abbreviata

“…So far, only six cucurbitane triterpenoids were identified from its fruit [11] and leaf [6], four of which were isolated from the MeOH extract of the fruits by us previously [11] including two 27-norcucurbitane triterpenoids. Several norcucurbitane triterpenoids have also been identified from the roots [12], vines and leaves [13,14], stems [15,16], fruits [17,18], and seeds [19] of Momordica charantia Linn. In a continuation of our interest in the isolation and structure elucidation of secondary metabolites from Taiwanese M. charantia var.…”