Cytotoxic and Anti-Inflammatory Triterpenoids in the Vines and Leaves of Momordica charantia.

The vines and leaves of Momordica charantia L. are used as herbal medicines to treat inflammation-related disorders. However, their safety profile remains uncharacterized, and the constituents in their extracts that exert anti-inflammatory and adverse effects remain unclear. This study isolated the characteristic cucurbitane-type triterpenoid species in the vines and leaves of M. charantia L. and analyzed their cytotoxicity, anti-inflammatory effects, and underlying mechanisms. Four structurally related triterpenoids-momordicines I, II, IV, and (23E) 3ß,7ß,25-trihydroxycucurbita-5,23-dien-19-al (TCD)-were isolated from the triterpenoid-rich fractions of extracts from the vines and leaves of M. charantia. Momordicine I was cytotoxic on normal cells, momordicine II exerted milder cytotoxicity, and momordicine IV and TCD had no obvious adverse effects on cell growth. TCD had anti-inflammatory activity both in vivo and in vitro. In lipopolysaccharide-stimulated RAW 264.7 cells, TCD inhibited the inhibitor kappa B kinase/nuclear factor-κB pathway and enhanced the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and glutamate-cysteine ligase modifier subunit through the extracellular signal-regulated kinase1/2 and p38. Thus, the vines and leaves of M. charantia should be used with caution. An extraction protocol that can enrich TCD but remove momordicine I would likely enhance the safety of the extract.

Bitter Melon Extract Yields Multiple Effects on Intestinal Epithelial Cells and Likely Contributes to Anti-diabetic Functions.

The intestines have been recognized as important tissues for metabolic regulation, including glycemic control, but their vital role in promoting the anti-diabetic effects of bitter melon, the fruit of Momordica charantia L, has seldom been characterized, nor acknowledged. Evidence suggests that bitter melon constituents can have substantial interactions with the intestinal epithelial cells before circulating to other tissues. We therefore characterized the effects of bitter melon extract (BME) on intestinal epithelial cells. BME was found to contain substantial amounts of carbohydrates, proteins, and triterpenoids. TNF-α induced insulin resistance in an enterocyte cell line of IEC-18 cells, and BME promoted glucose utilization of the insulin-resistant cells. Further analysis suggested that the increased glucose consumption was a result of the combined effects of insulin sensitizing and insulin substitution functions of BME. The functions of insulin substitution were likely generated due to the activation of AMP-activated protein kinase. Meanwhile, BME acted as a glucagon-like peptide 1 (GLP-1) secretagogue on enteroendocrine cells, which may be mediated by the activation of bitter-taste receptors. Therefore, BME possesses insulin sensitizing, insulin substitution, and GLP-1 secretagogue functions upon intestinal cells. These effects of BME on intestinal cells likely play a significant part in the anti-diabetic action of bitter melon.

New bioactive chromanes from Litchi chinensis.

Seven new δ-tocotrienols, designated litchtocotrienols A-G (1-7), together with one glorious macrocyclic analogue, macrolitchtocotrienol A (8), and one new meroditerpene chromane, cyclolitchtocotrienol A (9), were isolated from the leaves of Litchi chinensis. Their structures were mainly determined by extensive spectroscopic analysis, and their biological activities were evaluated by cytotoxicity against human gastric adenocarcinoma cell lines (AGS, ATCC CRL-1739) and hepatoma carcinoma cell line (HepG2 2.2.1.5). The structure-activity relationship of the isolated compounds was also discussed.

Anti-Inflammatory Effects and Mechanisms of Fatsia polycarpa Hayata and Its Constituents.

Fatsia polycarpa, a plant endemic to Taiwan, is an herbal medicine known for treating several inflammation-related diseases, but its biological function needs scientific support. Thus, the anti-inflammatory effects and mechanisms of the methanolic crude extract (MCE) of F. polycarpa and its feature constituents, that is, brassicasterol (a phytosterol), triterpenoids 3 α -hydroxyolean-11,13(18)-dien-28-oic acid (HODA), 3 α -hydroxyolean-11-en-28,13 ß -olide (HOEO), fatsicarpain D, and fatsicarpain F, were investigated. MCE and HOEO, but not brassicasterol, dose-dependently inhibited lipopolysaccharide- (LPS-)induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in RAW 264.7 macrophage line, whereas HODA, fatsicarpain D and fatsicarpain F were toxic to RAW cells. Additionally, MCE and HOEO suppressed LPS-induced production of nitric oxide, prostaglandin E2, and interleukin-1 ß and interfered with LPS-promoted activation of the inhibitor kappa B kinase (IKK)/nuclear factor- κ B (NF- κ B) pathway, and that of the mitogen-activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In animal tests, MCE and HOEO effectively ameliorated 12-O-tetradecanoylphorobol-13 acetate- (TPA-)induced ear edema of mice. Thus, MCE of F. polycarpa exhibited an obvious anti-inflammatory activity in vivo and in vitro that likely involved the inhibition of the IKK/NF- κ B pathway and the MAPKs, which may be attributed by triterpenoids such as HOEO.

Two new sesquiterpene lactones from Ixeris chinensis.

Phytochemical investigation of Ixeris chinensis NAKAI (Asteraceae) has resulted in the isolation of a new guaianolide-type sesquiterpene lactone, ixerochinolide (1) as well as the related glucoside, ixerochinoside (2). In addition, the known guaianolides, 8beta-hydroxy-3-oxo-guaia-4(15),10(14),11(13)-trien-1alpha,5alpha,6beta,7alphaH-12,6-olide (8beta-hydroxydehydrozaluzanin), 8beta,15-dihydroxy-2-oxo-guaia-1(10),3,11(13)-trien-5alpha,6beta,7alphaH-12,6-olide (lactucin), 3beta,8alpha,10alpha-trihydroxy-guaia-4(15),11(13)-dien-1alpha,5alpha,6beta,7alphaH-12,6-olide (10alpha-hydroxy-10,14-dihydro-desacylcynaropicrin) and 3beta-D-glucopyranosyloxy-8beta-(p-hydroxyphenylacetyloxy)-guaia-4(15),10(14),11(13)-trien-1alpha,5alpha,6beta,7alphaH-12,6-olide (8-epicrepioside) were identified. The structures were determined on the basis of spectral analyses, especially 1- and 2D NMR. Compound 1 exhibited significant cytotoxicity against human PC-3 tumor cells.