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.

Norcucurbitane triterpenoids from the fruits of Momordica charantia var. abbreviata.

Two new 27-norcucurbitane triterpenoids, 27-nor-3beta-hydroxy-7beta-methoxycucurbita-5,23(E)-dien-25-one (1) and 27-nor-3beta-hydroxy-5beta,19-epoxycucurbita-6,23(E)-dien-25-one (2), together with two known cucurbitane triterpenes, 23(E)-7beta-methoxycucurbita-5,23,25-trien-3beta-ol (3) and 5beta,19-epoxy-25-methoxycucurbita-6,23(E)-dien-3beta-ol (4), were isolated from the fruits of Momordica charantia var. abbreviata. Their structures were determined by analysis of spectroscopic data and comparison with the data of known analogues.

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.

EMCD, a hypoglycemic triterpene isolated from Momordica charantia wild variant, attenuates TNF-α-induced inflammation in FL83B cells in an AMP-activated protein kinase-independent manner.

Insulin resistance is a causative factor for type 2 diabetes, whereas the development of insulin resistance is closely related to chronic inflammation induced by factors such as tumor necrosis factor-α (TNF-α). Momordica charantia, also known as bitter melon, has been used as an herbal medicine and reported to ameliorate inflammation and hyperglycemia. Previously, a triterpene 5ß,19-epoxy-25-methoxy-cucurbita-6,23-diene-3ß,19-diol (EMCD), purified from M. charantia L. wild variant WB24, was found to activate AMP-activated protein kinase (AMPK) and have a hypoglycaemic effect in TNF-α-treated FL83B cells. AMPK has been a target for developing anti-diabetic medicine and suggested to play a role in anti-inflammation. The current study aims to investigate if EMCD might repress TNF-α-induced inflammation via AMPK. TNF-α-induced inflammation in FL83B cells was characterized using Western blotting and reverse transcriptase-polymerase chain reaction. Consequently, the expression of inflammatory markers including inducible nitric oxide synthase (iNOS), the p65 subunit of nuclear factor-κB (NF-κB), protein-tyrosine phosphatase-1B, TNF-α and interleukin-1ß were significantly elevated by TNF-α in the cell, and EMCD obviously suppressed the TNF-α-induced expression of these markers. When the effect of EMCD was tested simultaneously with epigallocatechin-3-gallate (EGCG), a catechin from green tea reported to be anti-inflammatory, EMCD showed a more obvious anti-inflammatory activity than EGCG did. Investigation of the underlying mechanism suggested that EMCD inhibited the activation of the IκB kinase (IKK) complex and the NF-κB pathway, and the effect was likely independent of AMPK. Collectively, the multiple functions of EMCD suggest it to be a potential agent in treating diabetic complications and other inflammation-related disorders.

Cucurbitane-type triterpenoids from the fruit pulp of Momordica charantia.

Three new cucurbitane-type triterpenoids, 5beta,19-epoxy-23(R)-methoxycucurbita-6,24-dien-3beta-ol (1), 5beta,19-epoxy-23(S)-methoxycucurbita-6,24-dien-3beta-ol (2), and 3beta-hydroxy-23(R)-methoxycucurbita-6,24-dien-5beta,19-olide (3), were isolated from the fruit pulp of Momordica charantia. Their structures were established on the basis of extensive NMR (1H, 13C, COSY, HMQC, HMBC, and NOESY) and EI-MS studies. Compound 1 exhibited cytotoxic activity against the SK-Hep 1 cell line.

A cell-based screening identifies compounds from the stem of Momordica charantia that overcome insulin resistance and activate AMP-activated protein kinase.

Treatment of insulin resistance is a critical strategy in the prevention and management of type 2 diabetes. The crude extracts from all parts of Momordica charantia L. have been reported by many studies for the effective treatment of diabetes and related complications. However, the exact ingredients responsible for the hypoglycemic effect and the underlying mechanism of their actions have not been well characterized because of the lack of a proper assay and screening system. A new cell-based, nonradioactive, and nonfluorescent screening method was demonstrated in this study to screen for natural products from the stem of M. charantia, aiming to identify hypoglycemic components that can overcome cellular insulin resistance. The results suggest triterpenoids being potential hypoglycemic components of the plant and the mechanism underlying their action involving AMP-activated protein kinase.

Cucurbitane-type triterpenoids from Momordica charantia.

Five new cucurbitane-type triterpenes, (23E)-25-methoxycucurbit-23-ene-3beta,7beta-diol (1), (23E)-cucurbita-5,23,25-triene-3beta,7beta-diol (2), (23E)-25-hydroxycucurbita-5,23-diene-3,7-dione (3), (23E)-cucurbita-5,23,25-triene-3,7-dione (4), and (23E)-5beta,19-epoxycucurbita-6,23-diene-3beta,25-diol (5), together with one known triterpene, (23E)-5beta,19-epoxy-25-methoxycucurbita-6,23-dien-3beta-ol (6), have been isolated from the methanol extract of the stems of Momordica charantia. The structures of the new compounds were elucidated by spectroscopic methods.