Structure-related inhibitory activity of oleanolic acid glycosides on gastric emptying in mice

We examined the effects of various oleanolic acid oligoglycosides obtained from traditional herbs on gastric emptying in non-nutrient meal- or nutrient meal-loaded mice. Test samples were given orally to fasted mice 0.5 h before loading of test meals. Oleanolic acid 3-O-monodesmosides [oleanolic acid 3-O-glucuronide (3, 12.5-50 mg/kg), momordin Ic (4, 25 and 50 mg/kg), momordin I (6, 12.5-50 mg/kg), and 28-O-deglucosyl-chikusetsusaponins IV (8, 12.5-50 mg/kg) and V (10, 50 mg/kg)] were found to show inhibitory effects on gastric emptying in 1.5% CMC-Na test meal-loaded mice. 4, 6, and 8 also inhibited gastric emptying in mice given 40% glucose test meal, milk test meal, and 60% ethanol test meal. 3 inhibited gastric emptying in mice given milk test meal or 60% ethanol test meal, but lacked significant inhibition in 40% glucose test meal-loaded mice. 10 (50 mg/kg) also slightly inhibited gastric emptying in milk test meal-loaded mice, but lacked the significant inhibition in mice given 40% glucose or 60% ethanol test meal. Whereas oleanolic acid 3,28-0-bisdesmosides [momordin IIc (5), chikusetsusaponins IV (7) and V (9)], oleanolic acid 28-O-monodesmoside [compound O (2)], and their common aglycon [oleanolic acid (1)] showed no such effects at dose of 50 mg/kg. 28-O-Deglucosyl-chikusetsusaponin V (10) showed a little inhibition in these experiments. These results indicate that both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 28-ester glucoside moiety and 2'-O-beta-D-glucopyranoside moiety reduce the activity.     

Effects of escins Ia, Ib, IIa, and IIb from horse chestnuts on gastrointestinal transit and ileus in mice.

The effects of saponin fraction and its principal constituents escins Ia (1), Ib (2), IIa (3), and IIb (4) from horse chestnuts on gastrointestinal transit (GIT) and ileus were investigated in mice. Ileus was induced by acetic acid peritoneal irritation or by laparotomy with manipulation. One hour after the oral administration, the saponin fraction (12.5-100 mg/kg) and 14 (12.5-50 mg/ kg, except for 3 at 12.5 mg/kg) dose-dependently accelerated GIT. The optimal effects of the saponin fraction (25 mg/kg) occurred 5-240 min (applied intervals between the fraction and the charcoal meal) after the oral administration. The fraction (12.5-100 mg/ kg) and 1-4 (12.5-50 mg/kg, except for 1 and 2 at 12.5 mg/kg) dose-dependently prevented the inhibition of GIT induced by the acetic acid peritoneal irritation. They (12.5-100mg/kg) also dose-dependently prevented the inhibition of GIT induced by the laparotomy with manipulation. Desacylescins I (5) and II (6) (50 mg/kg) showed no such effects. These results demonstrated that the saponin fraction and 1-4 accelerated GIT and prevented the experimental ileus, and indicate that the 21, 22-acyl groups are essential for the accelerative effects of 1-4. The accelerations of GIT by 1-4 were completely abolished by the pretreatment with streptozotocin (100 mg/kg, iv), but not by the pretreatment with capsaicin (75 mg/kg in total, sc) or atropine (10 mg/kg, sc). These results imply that the sympathetic nervous system may be, but neither capsaicin-sensitive sensory nerves nor the cholinergic mechanism, involved in the accelerations of GIT by escins 1-4.     

Roles of capsaicin-sensitive sensory nerves, endogenous nitric oxide, sulfhydryls, and prostaglandins in gastroprotection by momordin Ic, an oleanolic acid oligoglycoside, on ethanol-induced gastric mucosal lesions in rats.

The roles of capsaicin-sensitive sensory nerves (CPSN), endogenous nitric oxide (NO), sulfhydryls (SHs), prostaglandins (PGs) in the gastroprotection by momordin Ic, an oleanolic acid oligoglycoside isolated from the fruit of Kochia scoparia (L.) SCHRAD., on ethanol-induced gastric mucosal lesions were investigated in rats. Momordin Ic (10 mg/kg, p.o.) potentially inhibited ethanol-induced gastric mucosal lesions. The effect of momordin Ic was markedly attenuated by the pretreatment with capsaicin (125 mg/kg in total, s.c., an ablater of CPSN), N(G)-nitro-L-arginine methyl ester (L-NAME, 70 mg/kg, i.p., an inhibitor of NO synthase), N-ethylmaleimide (NEM, 10 mg/kg, s.c., a blocker of SHs), or indomethacin (10 mg/kg, s.c., an inhibitor of PGs biosynthesis). The attenuation of L-NAME was abolished by L-arginine (300 mg/kg, i.v., a substrate of NO synthase), but not by D-arginine (300 mg/kg, i.v., the enatiomer of L-arginine). The effect of the combination of capsaicin with indomethacin, NEM, or L-NAME was not more potent than that of capsaicin alone. The combination of indomethacin and NEM, indomethacin and L-NAME, or indomethacin and NEM and L-NAME increased the attenuation of each alone. These results suggest that CPSN play an important role in the gastroprotection by momordin Ic on ethanol-induced gastric mucosal lesions, and endogenous PGs, NO, and SHs interactively participate, in rats.     

Possible involvement of 5-HT and 5-HT2 receptors in acceleration of gastrointestinal transit by escin Ib in mice

We have reported previously that escin Ib accelerated gastrointestinal transit (GIT) in mice, and that its effect may be mediated by the release of endogenous prostaglandins (PGs) and nitric oxide (NO). In this study, the possible involvement of 5-HT and 5-HT receptors in the GIT acceleration of escin Ib was investigated in mice. The acceleration of GIT by escin Ib (25 or 50 mg/kg, p.o.) was attenuated by pretreatment with ritanserin (0.5-5 mg/kg, s.c., a 5-HT(2A/2C/2B) receptor antagonist), but not with MDL 72222 (1 and 5 mg/kg, s.c.) and metoclopramide (10 mg/kg, s.c.) (5-HT3 receptor antagonists) or tropisetron (1 and 10 mg/kg, s.c., a 5-HT(3/4) receptor antagonist). Furthermore, pretreatment with ketanserin (0.05-5 mg/kg, s.c.), haloperidol (1-5 mg/kg, s.c.) and spiperone (0.5-5 mg/kg, s.c.) (5-HT2A receptor antagonists), as well as a bolus of dl-p-chlorophenylalanine methyl ester (PCPA, 1000 mg/kg, p.o., 1, 6 or 24 h before administration of the sample) (an inhibitor of 5-HT synthesizing enzyme tryptophan hydroxylase) and reserpine (5 mg/kg, p.o.) (a 5-HT depletor), but not 6-hydroxydopamine (80 mg/kg, i.p., a dopamine depletor) or repeated PCPA (300 mg/kg x2, p.o., 72 and 48 h before administration of the sample), also attenuated the effects of escin Ib. It is postulated that escin Ib accelerates GIT, at least in part, by stimulating the synthesis of 5-HT to act through 5-HT2, possibly 5-HT2A receptors, which in turn causes the release of NO and PGs.     

Glycosides from Roots of Cyathula officinalis Kuan

Abstract: To search for new and bioactive compounds from traditional Chinese medicines, a new glycoside, 3-O-[α- L -rhamnopyranosyl-(1→3)-( n -butyl-β- D -glucopyranosiduronate)]-28-O-β- D -glucopyranosyloleanolic acid ( 1 ), was isolated from the roots of Cyathula officinalis Kuan, along with 3-O-(methyl-β- D -glucopyranosiduronate)-28-O-β- D -glucopyranosyl oleanolic acid ( 2 ), 3-O-β- D -glucopyranosyl oleanolic acid ( 3 ), 3-O-β- D -glucuronopyranosyl oleanolic acid ( 4 ), 3-O-[β- L -rhamnopyranosyl-(1→3)-(β- D -glucuronopyranosyl)] oleanolic acid ( 5 ), 3-O-(β- D -glucuronopyranosyl)-28-O-β- D -glucopyranosyl oleanolic acid ( 6 ), 28-O-β- D -glucuronopyranosyl-(1→4)-β- D -glucopyranosyl hederagenin ( 7 ), 3-O-[β- L -rhamnopyranosyl-(1→3)-β- D -glucuronopyranosyl]-28-O-β- D -glucopyranosyl oleanolic acid ( 8 ), and 3-O-[β- D -glucopyranosyl-(1→2)-α- L -rhamnopyranosyl-(1→3)-β- D -glucuronopyranosyl]-28-O-β- D -glucopyranosyl oleanolic acid ( 9 ). The structures of these compounds were determined based on spectral and chemical evidence. The 50 per cent growth-inhibiting (GI₅₀) of compounds 1 and 5 against MDA-MB-231 (a human breast cancer cell line) was 3.44 × 10^-4 and 4.66 × 10^-4 mol/L, respectively.
(Managing editor: Wei WANG)     

Roles of endogenous prostaglandins and nitric oxide in inhibitions of gastric emptying and accelerations of gastrointestinal transit by escins Ia, Ib, IIa, and IIb in mice

We reported previously that escins Ia, Ib, IIa, and IIb, isolated from horse chestnuts, inhibited the 30-min gastric emptying (GE) in mice. In this study, the effects of escins Ia-IIb on gastrointestinal transit (GIT), and the roles of endogenous prostaglandins (PGs) and nitric oxide (NO) in the effects of escins Ia--IIb on GE and GIT were investigated in fasted mice. Escins Ia-IIb (12.5-50 mg/kg, p.o.) dose-dependently accelerated GIT. Both GE inhibitions and GIT accelerations by escins Ia-IIb (25 mg/kg) were markedly attenuated by pretreatment with indomethacin (10 mg/kg, s.c., an inhibitor of PGs synthesis). Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p., an inhibitor of constitutive and inducible NO synthase) attenuated the effects of escins Ia-IIb on GIT, but not on GE. The effect of L-NAME was reversed by L-arginine (600 mg/kg, i.p., a substrate of NO synthase), but not by D-arginine (900 mg/kg, i.p., the enantiomer of L-arginine). The GIT accelerations of escins Ia-IIb were not attenuated by pretreatment with D-NAME (10 mg/kg, i.p., the enantiomer of L-NAME) or dexamethasone (5 mg/kg, i.p., an inhibitor of inducible form of NO synthase). The results suggest that endogenous PGs play an important role in both GE inhibitions and GIT accelerations, and constitutive NO is involved in the GIT accelerations, by escins Ia--IIb in mice.     

Synthesis, anti-inflammatory, analgesic and antioxidant activities of some tetrasubstituted thiophenes

Sets of tetrasubstituted thiophene esters 4a-4g, 5a-5f and 6a-6e were synthesized by reaction of 1-(alpha-Carbomethoxy-beta-aminothiocrotonoyl)-aryl/aroyl amines (3) with 3-(bromoacetyl)coumarin, 1,4-dibromodiacetyl and chloroacetone respectively. The compound 3 were synthesized by nucleophilic addition of aryl/aroylisothiocyanate and enamine (2). The synthesized targeted compounds (4a-4g, 5a-5f and 6a-6e) were evaluated for their in vivo anti-inflammatory activity in carrageenin-induced rat hind paw oedema model at three graded doses employed at 10, 20 and 40 mg/kg body weight using mefanamic acid, ibuprofen and in vivo analgesic activity in acetic acid induced writhing response model at 10 mg/kg dose using ibuprofen as standard drug. The compounds 4a-4f, 5c, 5f, 6c and 6e were evaluated for their in vitro antioxidant nitric oxide radical scavenging assay at the concentrations of 5, 10, 15, 20, 25, 30 and 35 microg/mL using ascorbic acid as standard drug. Among all the targeted compounds 4c showed maximum anti-inflammatory activity of 71% protection at 10 mg/kg and 77% protection at 20 mg/kg to inflamed paw and analgesic activity of 56% inhibition and also maximum in vitro nitric oxide radical scavenging activity having IC(50) value 31.59 microg/mL.     

Carnosic acid, a new class of lipid absorption inhibitor from sage

The methanolic extract from the leaves of Salvia officinalis L. (sage) showed significant inhibitory effect on serum triglyceride elevation in olive oil-loaded mice (500 and 1000 mg/kg, p.o.) and inhibitory activity (IC(50): 94 microg/mL) against pancreatic lipase, which is participated in digestion of lipids. Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction. Among these compounds, carnosic acid and carnosol substantially inhibited pancreatic lipase activity with IC(50) values of 12 microg/mL (36 microM) and 4.4 microg/mL (13 microM), respectively. Carnosic acid significantly inhibited triglyceride elevation in olive oil-loaded mice at doses of 5-20 mg/kg (p.o.). However, other constituents (carnosol, royleanonic acid, oleanolic acid) did not show any effects at a dose of 200 mg/kg (p.o.). Furthermore, carnosic acid (20 mg/kg/day, p.o.) reduced the gain of body weight and the accumulation of epididymal fat weight in high fat diet-fed mice after 14 days.     

Further saponins from Meryta lanceolata

Five new oleanane-type saponins along with 11 known ones were isolated from the leaves and stems of Meryta lanceolata. The new saponins were characterised by spectroscopic analysis including FAMS, 1 and 2D NMR experiments and the results of hydrolysis as 3-O-[beta-d-glucopyranosyl-(1-->2)-beta-d-glucuronopyranosyl] hederagenin 28-O-[alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranosyl] ester, 3-O-[beta-d-glucopyranosyl-(1-->2)-beta-d-glucuronopyranosyl] oleanolic acid 28-O-[alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranosyl]ester, 3-O-[beta-d-glucopyranosyl-(1-->2)-beta-d-glucuronopyranosyl] oleanolic acid 28-O-[alpha-l-rhamnopyranosyl-(1-->4)-beta-d-6-O-acetyl glucopyranosyl-(1-->6)-beta-d-glucopyranosyl]ester, 3-O-[beta-d-glucopyranosyl-(1-->3)-beta-d-glucopyranosyl-(1-->3)-alpha-l-arabinopyranosyl] oleanolic acid 28-O-[alpha-l-rhamnopyranosyl-(1-->4)-beta-d-glucopyranosyl-(1-->6)-beta-d-glucopyranosyl] ester and 3-O-[beta-d-glucopyranosyl-(1-->2)-beta-d-glucuronopyranosyl] hederagenin, respectively.     

Effects of a newly synthesized leukotriene antagonist, NZ-107, on immediate-type hypersensitivity reaction in rats and guinea-pigs.

The effects of 4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone (NZ-107) on immediate type hypersensitivity reactions in rats and guinea-pigs were studied. 1. When NZ-107, at a dose of 50 mg/kg (i.p.) or 100 mg/kg (orally), was administered to rats, 48-h homologous passive cutaneous anaphylaxis (PCA) reaction and histamine-, leukotriene C4 (LTC4)- and leukotriene D4 (LTD4)-induced skin reactions were suppressed by the agent. 2. NZ-107 (10(-6) g/ml) inhibited both LTC4- and LTD4-induced contractions of isolated rat stomach smooth muscle. 3. NZ-107 inhibited antigen-induced histamine release from rat peritoneal mast cells by 26% at a concentration of 10(-4) g/ml. 4. NZ-107, at doses of 25 and 50 mg/kg (orally), significantly inhibited guinea-pig 3-h heterologous PCA reaction. 5. NZ-107 inhibited antigen-induced histamine release from guinea-pig lung tissue by 17% and 48% at concentrations of 5 x 10(-5) and 10(-4) g/ml, respectively. 6. NZ-107, at doses of 25 and 50 mg/kg (i.p.), inhibited antigen-induced bronchoconstriction and eosinophil accumulation in the bronchoalveolar lavage fluid (BALF) of guinea-pigs. These results suggest that NZ-107 has anti-allergic action including inhibition of eosinophil accumulation in an antigen-challenged airway lesion in rats and guinea-pigs. The anti-allergic action of this agent is thought to be due to its action as a histamine and LT antagonist and its consequent inhibition of antigen-induced histamine release.     

Triterpenoid saponins from Schefflera arboricola

Nine triterpenoid saponins were isolated from the leaves and stems of Schefflera arboricola. The saponins were characterised, on the basis of chemical and spectral evidence, as 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid, 3-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucuronopyranosyl] echinocystic acid, 3-O-[beta-D-apiofuranosyl-(1-->4)-beta-D-glucuronopyranosyl] oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-ramnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid, 3-O-alpha-L-rhamnopyranosyl-(1-->4)-[beta-D-galactopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid and 3-O-beta-D-apiofuranosyl-(1-->4)-[alpha-L-arabinopyranosyl-(1-->2)-] beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester.     

四川溲疏的化学成分研究(英文)

运用多种色谱技术从四川溲疏(Deutzia setchuenensis Franch)全草的95%乙醇提取物中首次分离到9个化合物。通过波谱方法和与已知品对照的手段将它们鉴定为:β-谷甾醇(1)、白桦酯醇(2)、hydrangetin(3)、齐墩果酸(4)、肉桂酸(5)、齐墩果酸-3-O-β-D-吡喃葡萄糖醛酸苷(6)、β-胡萝卜苷(7)、齐墩果酸-3-O-(β-D-吡喃葡萄糖醛酸-6-正丁酯)(8)和齐墩果酸-3-O-β-D-吡喃葡萄糖醛酸-28-O-β-D-吡喃葡萄糖苷(9)。     

古蔺雪胆中的新三萜皂苷

从采自四川汉源县的古蔺雪胆(Hemsleya penxianensis var.gulinensiks)中分到9个三萜皂苷化合物,通过化学反应和光谱方法鉴定了它们的结构。其中7个为已知化合物,分别为齐墩果酸-28-O-β-D-比喃葡萄糖苷(1),3-O-β-D-吡喃葡萄糖醛基齐墩果酸苷(3),3-O-β-D-吡喃葡萄糖醛基—齐墩果酸—28-O-α-L-吡喃阿拉伯糖苷(4),3-O-β-D-吡喃葡萄糖醛基—齐墩果酸—28-O-β-D-吡喃葡萄糖苷(5),3-O-α-L-阿拉伯糖基—(1→3)—β—D-吡喃葡萄糖醛基—齐墩果酸—28—O—β—D—吡喃葡萄糖苷(6),3—O—(6′—丁酯)—β-D-吡喃葡萄糖醛基—齐墩果酸—28-O-α-L-阿拉伯糖苷(7),3-O-(6′-丁酯)—β—D吡喃葡萄糖醛基—齐墩果酸—28-O-β-D-吡喃葡萄糖苷(8)。两个新化合物,即雪胆皂苷A(2)和雪胆皂苷B(9)。     

Triterpene saponins and iridoid glucosides from galium rivale

Three new glycosides of the oleanene-type triterpenes, rivalosides C-E (1-3), along with three known triterpene saponins, momordin IIb (4) and rivalosides A-B (5-6), and five known iridoid glucosides: monotropein, scandoside, deacetylasperulosidic acid, geniposidic acid and asperulosidic acid, were isolated from aerial parts of Galium rivale. The structures of the new compounds were elucidated by spectral methods and chemical means as 2alpha-acetoxy-3alpha, 19alpha-dihydroxy-olean-12-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1--> 6)-beta-D-glucopyranoside, 2alpha,3alpha, 19alpha-trihydroxy-olean- 12-en-28-oic acid 28-O-beta-D-glucopyranosyl-(1 --> 6)-beta-D-glucopyranoside and 3-O-beta-D-glucuronopyranosyl-24-hydroxy-olean-12-en-28-oic acid 28-O-beta-D-glucopyranoside, for rivalosides C-E, respectively. The taxonomic significance of the rivalosides in G. rivale was discussed.     

Prostaglandin biosynthesis in rabbit kidney medulla: Inhibition vs. by aspirin, indomethacin and meclofenamic acid

The non-steroidal anti-inflammatory drugs aspirin, indomethacin and meclofenamic acid were compared for their potency and duration of inhibition of prostaglandin biosynthesis in rabbit kidney medulla. Indomethacin and meclofenamic acid showed equal potency of inhibition (IC₅₀ 0.88 μM and 0.85 μM respectively) while aspirin was a much weaker inhibitor (IC₅₀ 120 μM). , indomethacin was the most powerful inhibitor (ID₅₀ 0.034 mg/kg) followed by meclofenamic acid (0.45 mg/kg) and aspirin (2.35 mg/kg).Studies on the duration of inhibition by these compounds showed the effect of indomethacin and meclofenamic acid to be completely reversed within 4–6 hours. In contrast, return of kidney prostaglandin biosynthetic activity following aspirin inhibition is very slow and significant inhibition is still present 48 hours after a single aspirin injection. The inhibitory effect of aspirin could be blocked by pretreatment with indomethacin, indicating that both drugs interact with related sites on the cyclo-oxygenase enzyme. The irreversible inhibition of the cyclo-oxygenase by aspirin as demonstrated in studies of other investigators suggests that the return of kidney prostaglandin synthetase activity after aspirin inhibition represents synthesis of new cyclo-oxygenase protein.     

Triterpenoid saponins from Meryta lanceolata

Four new oleanane-type saponins and a known one were isolated from the leaves and stems of Meryta lanceolata. The new saponins were characterised by spectroscopic means and chemical hydrolysis as 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester, 3-O-[beta-D- glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-[beta-D-glucopyranosyl-(1-->2)]-alpha-L-arabinopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-6-O-acetyl glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester, 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl]oleanolic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester and 3-O-[beta-D-glucopyranosyl-(1-->2)-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranosyl]echinocystic acid 28-O-[alpha-L-rhamnopyranosyl-(1-->4)-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranosyl] ester. The NMR assignments were made by means of HOHAHA, 1H-1H COSY, HMQC, HMBC and NOE difference studies.     

Oleanane saponins from Gymnema sylvestre

Six oleanane-type saponins, along with two known triterpene saponins, were isolated from the leaves of Gymnema sylvestre. The structures of the oleanane triterpene glycosides were characterized as longispinogenin 3-O-beta-D-glucuronopyranoside, 21 beta-benzoylsitakisogenin 3-O-beta-D-glucuronopyranoside, 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester, oleanolic acid 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl(1-->6)-beta-D- glucopyranoside, 3-O-beta-D-xylopyranosyl(1-->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl ester and 3-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl oleanolic acid 28-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ester on the basis of hydrolysis and spectral evidence, including 1D- and 2D-NMR (TOCSY, ROESY, HMQC and HMBC) and FABMS analyses.     

Prostaglandin biosynthesis in rabbit kidney medulla: inhibition in-vitro vs. in-vivo by aspirin, indomethacin and meclofenamic acid.

The non-steroidal anti-inflammatory drugs aspirin, indomethacin and meclofenamic acid were compared for their potency and duration of inhibition of prostaglandin biosynthesis in rabbit kidney medulla. Indomethacin and meclofenamic acid showed equal potency of inhibition in-vitro (IC50 0.88 micron and 0.85 micron respectively) while aspiring was a much weaker inhibitor (IC50 120 micron). In-vivo, indomethacin was the most powerful inhibitor (ID50 0.034 mg/kg) followed by meclofenamic acid (0.45 mg/kg) and aspirin (2.35 mg/kg). Studies on the duration of in-vivo inhibition by these compounds showed the effect of indomethacin and meclofenamic acid to be completely reversed within 4-6 hours. In contrast, return of kidney prostaglandin biosynthetic activity following aspirin inhibition is very slow and significant inhibition is still present 48 hours after a single aspiring injection. The inhibitory effect of aspirin in-vivo could be blocked by pretreatment with indomethacin, indicating that both drugs interact with related sites on the cyclo-oxygenase enzyme. The irreversible inhibition of the cyclo-oxygenase by aspirin as demonstrated in studies of other investigators suggests that the return of kidney prostaglandin synthetase activity after aspirin inhibition represents synthesis of new cyclo-oxygenase protein.     

Synthesis of oleanolic acid saponins mimicking components of Chinese folk medicine Di Wu

3,28-Di-O-rhamnosylated oleanolic acid saponins, mimicking components of Chinese folk medicine Di Wu, have been designed and synthesized. One-pot glycosylation and ‘inverse procedure’ technologies have been applied thus significantly simplifying the preparation of desired saponins. The cytotoxic activity of compounds 3-O-[α-l-rhamnopyranosyl-(1→2)-β-d-xylopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl-(1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (3), 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl- (1→4)-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl] ester (4), 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[α-l-rhamnopyranosyl] ester (5), and 3-O-[α-l-rhamnopyranosyl]oleanolic acid 28-O-[6-O-(α-l-rhamnopyranosyl)hexyl] ester (6) was preliminarily evaluated against HL-60 human promyelocytic leukemia cells. The natural saponin 3 and designed saponin 4 exhibited comparable moderate cytotoxic activity under our testing conditions.     

Anti-inflammatory and anti-arthritic effects of new synthetic 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione

We previously reported that 3-(4-hydroxyphenyl)-4-(4-thiomethoxyphenyl)-1H-pyrrole-2,5-dione (1, HMP) has a strong inhibitory effect on prostaglandin E(2) (PGE(2)) production. In this study, the anti-inflammatory and anti-arthritic effects of HMP were evaluated on LPS-induced RAW 264.7 macrophages and rats with carrageenan-induced paw edema and adjuvant-induced arthritis (AIA). The attenuation of PGE(2) production by HMP was found to be caused by the inhibition of cyclooxygenase-2 (COX-2) activity, but not COX-1 activity. However, HMP did not affect COX-2 at the protein or mRNA levels, whereas it suppressed the releases and expressions of inflammatory cytokines, such as, interleukin-1β (IL-1β) and IL-6 in LPS-induced macrophages. Furthermore, HMP suppressed LPS-induced nitric oxide (NO) production by down regulating the protein and mRNA expressions of inducible nitric oxide synthase (iNOS). In rats with carrageenan-injected acute inflammation, oral administration of HMP (25 or 50mg/kg, po) reduced paw swelling, and PGE(2) release and myeloperoxidase (MPO) activity in tissue. Furthermore, HMP (25 or 50mg/kg, po) significantly reduced paw swelling, arthritic indices and plasma PGE(2) concentrations in rat with AIA. These results show that HMP reduces swelling in a model acute inflammation and inhibits arthritic responses in a model of chronic inflammation via the inhibition of PGE(2) production. These results suggest that HMP is a potential therapeutic agent for the treatment of arthritis and associated disorders.