||Momordin Ic has hypoglycemic, anticancer, anti-allergic, anti-pruritogenic, hepatoprotective, antinociceptive and anti-inflammatory effects. It accelerates gastrointestinal transit partially by stimulating synthesis of 5-HT to act through 5-HT(2), possibly 5-HT(2C) and/or 5-HT(2B) receptors, which, in turn, increases synthesis of prostaglandins. Momordin Ic induces apoptosis through oxidative stress-regulated mitochondrial dysfunction involving the MAPK and PI3K-mediated iNOS and HO-1 pathways.
|Eur J Pharmacol. 2000 Mar 24;392(1-2):71-7. |
|Acceleration of gastrointestinal transit by momordin Ic in mice: possible involvement of 5-hydroxytryptamine, 5-HT(2) receptors and prostaglandins.[Pubmed: 10748274]|
METHODS AND RESULTS:
Possible involvement of 5-hydroxytryptamine (5-HT), 5-HT receptors and prostaglandins in the acceleration of gastrointestinal transit by Momordin Ic was investigated in mice. Accelerative effect of Momordin Ic (25 mg/kg, p.o.) on gastrointestinal transit was attenuated by pretreatment with a bolus of DL-p-chlorophenylalanine methyl ester (an inhibitor of 5-HT synthesizing enzyme), but not repeated pretreatment with DL-p-chlorophenylalanine methyl ester. Furthermore, cyproheptadine (a nonselective 5-HT(2) receptor antagonist), ritanserin (a 5-HT(2A/2B/2C) receptor antagonist) and clozapine (a 5-HT(2A/2C) receptor antagonist) also attenuated the effect of Momordin Ic, but methiothepin (a 5-HT(1) receptor antagonist), MDL 72222 (3-tropanyl-3,5-dichlorobenzoate) and metoclopramide (5-HT(3) receptor antagonists), tropisetron (a 5-HT(3/4) receptor antagonist), ketanserin and haloperidol (5-HT(2A) receptor antagonists) did not. These results suggested a possible involvement of endogenous 5-HT and 5-HT(2B/2C) over 5-HT(2A) receptors. Attenuation by pretreatment with indomethacin (an inhibitor of prostaglandins synthesis) suggested involvement of prostaglandins.
It is postulated that Momordin Ic accelerates gastrointestinal transit partially by stimulating synthesis of 5-HT to act through 5-HT(2), possibly 5-HT(2C) and/or 5-HT(2B) receptors, which, in turn, increases synthesis of prostaglandins.
|J Pharmacol Exp Ther. 1999 May;289(2):729-34. |
|Inhibition of gastric emptying by triterpene saponin, momordin Ic, in mice: roles of blood glucose, capsaicin-sensitive sensory nerves, and central nervous system.[Pubmed: 10215646]|
|The roles of capsaicin-sensitive sensory nerves and the central nervous system in the inhibitory effect of Momordin Ic, a principal saponin constituent in various Chinese and Japanese herbal medicines, such as the fruit of Kochia scoparia (L.) SCHRAD., on gastric emptying were investigated in nonnutrient meal- or nutrient meal-loaded mice. |
METHODS AND RESULTS:
Momordin Ic (12.5-50 mg/kg) significantly inhibited gastric emptying in 1.5% carboxymethyl cellulose sodium salt test meal-loaded mice by 8.4%-60.6%, 40% glucose test meal-loaded mice by 42.8% (50 mg/kg), milk test meal-loaded mice by 36.4% (50 mg/kg), and 60% ethanol test meal-loaded mice by 37.2% (50 mg/kg). The inhibitory effect on the gastric emptying in 1.5% carboxymethyl cellulose sodium salt test meal-loaded mice was potentiated by glucose (2 g/kg, i.v. or 5 g/kg, i.p.), but markedly attenuated by pretreatment with alloxan (50 mg/kg, i.v.) and streptozotocin (100 mg/kg, i.v.), in which the activity of sympathetic nervous system was decreased, or by insulin (1 or 3 U/kg, s.c.). The effect of insulin (1 U/kg) was markedly reduced by glucose (2 g/kg, i.v.), which can directly nourish the brain, but not by fructose (2 g/kg, i.v.), which cannot be used by the brain. The effect of Momordin Ic was also attenuated by pretreatment with capsaicin (75 mg/kg in total, s.c.).
These results suggest that the inhibition of gastric emptying by Momordin Ic is relative to serum glucose and, at least in part, mediated by capsaicin-sensitive sensory nerves and the central nervous system.
|Chem Pharm Bull (Tokyo). 1998 Sep;46(9):1399-403. |
|Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity.[Pubmed: 9775435]|
METHODS AND RESULTS:
We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and Momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and Momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro.
These results indicate that oleanolic acid 3-O-glucuronide and Momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.
|Arch Pharm Res. 2002 Jun;25(3):336-42. |
|Anti-rheumatoid arthritis effect of the Kochia scoparia fruits and activity comparison of momordin lc, its prosapogenin and sapogenin.[Pubmed: 12135107]|
METHODS AND RESULTS:
MeOH extract of Kochia scoparia was fractionated into CHCl3-, EtOAc- and BuOH extracts and the last fraction were hydrolyzed by 3%-NaOH (MeOH-H2O) to compare the bioactivities on antinociceptive and anti-inflammatory effects. Silica gel column chromatography of BuOH fraction afforded a large amount of 3-O-beta-D-xylopyranosyl (1-->3)-beta-D-glucuronopyranosyl oleanolic acid (Momordin Ic, 4) and that of acid hydrolysate of BuOH fraction gave 3-O-beta-D-glucuronopyranosyl oleanolic acid (momordin lb, 3), its 6'-O-methyl ester (2) and oleanolic acid (1). Silica gel column chromatography of alkaline hydrolysate afforded a large amount of 4. MeOH extract and both EtOAc- and BuOH fractions were active in the rheumatoidal rat induced Freund's complete adjuvant reagent (FCA) whereas CHCl3 fraction was inactive. Compound 1 and 4 showed significant activities in the same assay but oleanolic acid 3-O-glucuronopyranoside (3) showed no activity. These fashions were also observed in carrageenan-induced edema of the rat and in the antinociceptive activity tests undertaken in hot plate- and writhing methods.
These results suggest that momordin lc and its aglycone, oleanolic acid, could be active principles for rheumatoid arthritis.