Showing papers on "Oleanolic acid published in 1999"
Journal Article•
TL;DR: The results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.
Abstract: The new synthetic oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a potent, multifunctional molecule. It induces monocytic differentiation of human myeloid leukemia cells and adipogenic differentiation of mouse 3T3-L1 fibroblasts and enhances the neuronal differentiation of rat PC12 pheochromocytoma cells caused by nerve growth factor. CDDO inhibits proliferation of many human tumor cell lines, including those derived from estrogen receptor-positive and -negative breast carcinomas, myeloid leukemias, and several carcinomas bearing a Smad4 mutation. Furthermore, it suppresses the abilities of various inflammatory cytokines, such as IFN-gamma, interleukin-1, and tumor necrosis factor-alpha, to induce de novo formation of the enzymes inducible nitric oxide synthase (iNos) and inducible cyclooxygenase (COX-2) in mouse peritoneal macrophages, rat brain microglia, and human colon fibroblasts. CDDO will also protect rat brain hippocampal neurons from cell death induced by beta-amyloid. The above activities have been found at concentrations ranging from 10(-6) to 10(-9) M in cell culture, and these results suggest that CDDO needs further study in vivo, for either chemoprevention or chemotherapy of malignancy as well as for neuroprotection.
329 citations
TL;DR: The lupane‐type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitida Müll‐Arg, believed to be the first compound to be isolated from U. nitida for in vivo activity.
Abstract: The lupane-type triterpene betulinic acid was isolated from an ethanol extract of the root bark of the Tanzanian tree Uapaca nitida Mull-Arg. (Euphorbiaceae). The in vitro antiplasmodial IC50 values of betulinic acid against chloroquine resistant (K1) and sensitive (T9-96) Plasmodium falciparum were found to be 19.6 micrograms/mL and 25.9 micrograms/mL, respectively. The in vitro activities of several related triterpenes were also evaluated. Betulin was found to be inactive at 500 micrograms/mL for both K1 and T9-96. Ursolic acid exhibited IC50 values of 36.5 micrograms/mL and 28 micrograms/mL, and oleanolic acid exhibited IC50 values of 88.8 micrograms/mL and 70.6 micrograms/mL against K1 and T9-96, respectively. When betulinic acid was tested for in vivo activity in a murine malaria model (P. berghei) the top dosage employed of 250 mg/kg/day was ineffective at reducing parasitaemia and exhibited some toxicity. Betulinic acid has not previously been evaluated for in vivo activity. This is believed to be the first compound to be isolated from U. nitida.
157 citations
TL;DR: The results show that the protective effects of oleanolic acid against the carbon tetrachloride-induced hepatotoxicity may, at least in part, be due to its ability to block bioactivation ofcarbon tetrACHloride mainly by the inhibition of expression and activities of P450 2E1.
152 citations
TL;DR: From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR, flavan-3-ol polymers, consisting of epicatechin as their extender flavan units, were also found to be potent inhibitory principles against HIV-1 protease.
Abstract: From CH2Cl2 and MeOH extracts of the stems of Cynomorium songaricum RUPR. (Cynomoriaceae), ursolic acid and its hydrogen malonate were isolated as inhibitors of human immunodeficiency virus type 1 (HIV-1) protease, with 50% inhibitory concentrations (IC50) of 8 and 6 microM, respectively. Amongst various synthesized dicarboxylic acid hemiesters of related triterpenes, inhibitory activity tended to increase in the order of oxalyl, malonyl, succinyl and glutaryl hemiesters, for triterpenes such as ursolic acid, oleanolic acid and betulinic acid. The most potent inhibition was observed for the glutaryl hemiesters, with an IC50 of 4 microM. From the water extract of the stems of C. songaricum, flavan-3-ol polymers, consisting of epicatechin as their extender flavan units, were also found to be potent inhibitory principles against HIV-1 protease.
106 citations
Patent•
19 May 1999
TL;DR: The saponin mixtures and compounds have properties related to the regulation of apoptosis and cytotoxicity of cells and exhibit potent anti-tumor effects against a variety of tumor cells as mentioned in this paper.
Abstract: The invention provides novel saponin mixtures and compounds which are isolated from the species Acacia victoriae and methods for their use. These compounds may contain a triterpene moiety, such as acacic or oleanolic acid, to which oligosaccharides and monoterpenoid moieties are attached. The mixtures and compounds have properties related to the regulation of apoptosis and cytotoxicity of cells and exhibit potent anti-tumor effects against a variety of tumor cells.
99 citations
TL;DR: The results showed that after IP 250 and 500 mg/kg betulinic acid, the serum concentrations reached peaks at 0.15 and 0.23 h, respectively, which indicates that the agent exhibits potential anti‐tumour activity and functions in this regard via apoptosis.
Abstract: Betulinic acid is a naturally occurring pentacyclic triterpenoid. Betulinic acid has recently been selected by the National Cancer Institute for addition into the RAID (Rapid Access to Intervention in Development) programme. The agent exhibits potential anti-tumour activity and functions in this regard via apoptosis. The objective of the present study was to determine the pharmacokinetics of betulinic acid in CD-1 mice. Serum samples were obtained at designed times after a single 250 or 500 mg/kg intraperitoneal (IP) dose of betulinic acid. Tissue samples (skin, heart, liver, spleen, kidney, lung, brain, colon, caecum, ovary, uterus, thymus, lymph node, bladder, perirenal fat, mammary gland and small intestine) were collected after betulinic acid administration (500 mg/kg). Betulinic acid was extracted with methylene chloride and quantitatively analysed by HPLC/MS. Oleanolic acid and madecassic acid were used as internal standards. Pharmacokinetic parameters were calculated using the WinNonlin pharmacokinetic software package. A two-compartment, first-order model was selected for pharmacokinetic modelling. The results showed that after IP 250 and 500 mg/kg betulinic acid, the serum concentrations reached peaks at 0.15 and 0.23 h, respectively. The 250 and 500 mg/kg above betulinic acid IP doses were found to have elimination half-lives of 11.5 and 11.8 h and total clearances of 13.6 and 13.5 L/kg/h, respectively. The pharmacokinetic parameters observed for IP betulinic acid 500 mg/kg in the skin of mice were as follows: k(a) (h(-1)) 0.257, k(10) (h(-1)) 0.234, t(1/2(alpha)) (h) 2.63, t(1/2(beta)) (h) 20.2, V (L/kg) 0.61, AUC (microg/h/mL) 3504, T(max) (h) 3.90 and C(max) (microg/mL) 300.9. The distribution of betulinic acid in tissues at 24 h post-IP administration in a descending order was as follows: perirenal fat, ovary, spleen, mammary gland, uterus, bladder, lymph node, liver, small intestine, caecum, lung, thymus, colon, kidney, skin, heart and brain.
75 citations
TL;DR: Seven previously reported triterpene saponins based upon oleanolic acid or hederagenin, along with two known lignans, (+)-pinoresinol and beta-peltatin, were isolated from a saponin fraction prepared from the MeOH extract of the roots of Pulsatilla chinensis.
Abstract: Two new triterpene saponins (8 and 9) and seven previously reported triterpene saponins (1−7) based upon oleanolic acid or hederagenin, along with two known lignans, (+)-pinoresinol (10) and β-peltatin (11), were isolated from a saponin fraction prepared from the MeOH extract of the roots of Pulsatilla chinensis. The structures of the new saponins were determined by spectroscopic analysis, including 2D NMR spectroscopic techniques, and the results of hydrolytic cleavage. The isolated compounds and some derivatives were evaluated for their cytotoxic activity against HL-60 human leukemia cells.
75 citations
TL;DR: A new natural product, 4-epifriedelin, and 12 known terpenoids have been isolated from the leaves of Syzygium formosanum, reported for the first time.
Abstract: A new natural product, 4-epifriedelin (1), and 12 known terpenoids have been isolated from the leaves of Syzygium formosanum. The known compounds include caryophyllene oxide, friedelin, canophyllal, glutinol, alpha-terpineol, phytol, betulinic acid, uvaol, lupeol, betulin, ursolic acid, and oleanolic acid. All of these compounds are reported for the first time from S. formosanum.
48 citations
TL;DR: Two triterpenoid compounds, ursolic acid and uvaol, were isolated from Crataegus pinnatifida Bunge leaves and the inhibition appears to be selective for chitin synthase II, whereas Uvaol has no inhibitory activity up to 280 micrograms/ml.
Abstract: Two triterpenoid compounds, ursolic acid and uvaol, were isolated from Crataegus pinnatifida Bunge leaves. Ursolic acid inhibits chitin synthase II from S. cerevisiae with an IC50 value of 0.84 microgram/ml and the inhibition appears to be selective for chitin synthase II, whereas uvaol has no inhibitory activity up to 280 micrograms/ml. Oleanolic acid, alpha-hederin hydrate, and betulic acid inhibited the chitin synthase II activity under the same conditions with an IC50 of 5.6, 64.3, and 98.7 micrograms/ml, respectively.
45 citations
TL;DR: A number of semisynthetic analogs of oleanolic acid have been synthesized and tested for their complement inhibitory, cytotoxic and apoptotic activities and compounds 10 and 17 exhibited complement inhibitories potency superior to o Leanolic acid.
44 citations
TL;DR: Seven new β-amyrin derived oleanane-type triterpene coumaroyl esters were isolated from the twigs and leaves of Casuarina equisetifolia together with two known triterpenoids, erythrodiol and oleanolic acid, and a number of benzoic acid derivatives.
TL;DR: The results suggest that sympathetic nervous system, but not capsaicin-sensitive sensory nerves, be involved in the enhancements of GIT by 3, 4, and 6, and that the 3-O-glycoside moiety seems to be essential to show the GIT accelerating activity, and the 28- oleanolic acid moiety reduce the activity.
TL;DR: The protective effects of oleanolic acid-type saponins and their derivatives on in vitro immunological liver injury of primary cultured rat hepatocytes were studied and could represent a balance between hepatoprotective action and hepatotoxicity.
Abstract: The protective effects of oleanolic acid-type saponins and their derivatives on in vitro immunological liver injury of primary cultured rat hepatocytes were studied. A known antihepatotoxic saponin (chikusetsusaponin IVa, 1) showed hepatoprotective activity in this model. Although a rhamnosyl derivative (2) of 1 similarly showed hepatoprotective activity, its prosapogenin (5) did not show any hepatoprotective activity. On the contrary, 5 exhibited cytotoxicity toward liver cells. In the absence of antiserum, monodesmosyl saponins showed hepatotoxicity, while the bisdesmosyl saponins except for 1, did not show such hepatotoxicity. In order to clarify the effects of the sugar residues at C-3 and C-28 responsible for hepatoprotective and hepatotoxic actions, oleanolic acid 3-O-glucuronide (2a) and oleanolic acid 28-O-glucoside (2b) were prepared and tested. 2b showed neither hepatoprotective action nor hepatotoxicity. In contrast, 2a was effective at 90 microM on hepatoprotection, although it showed strong hepatotoxicity. Oleanolic acid (2c) itself showed both hepatoprotective action and weak hepatotoxicity. Therefore, the hepatoprotective activity of these types of saponins could represent a balance between hepatoprotective action and hepatotoxicity.
Journal Article•
TL;DR: Results suggest that OA-beta CD is a potential anti-caries agent and shows the highest caries score in rats in the infected control groups.
Abstract: Earlier work in vitro showed that oleanolic acid (OA) was a potential inhibitor of insoluble glucan (ISG) synthesis from mutans streptococci (MS). In this study, two oleanolic acid-cyclodextrin inclusion compounds (OA-CDs), oleanolic acid-G1-beta-cyclodextrin (OA-G1-beta CD) and oleanolic acid-beta-cyclodextrin (OA-beta CD), were assayed for their effects on ISG synthesis from Streptococcus mutans MT8148R, and on the growth of oral bacteria. OA-beta CD inhibited ISG synthesis by 55.3 and 37.4% at 62.5 and 15.6 micrograms/ml of OA, respectively. Both OA-CDs inhibited the growth of MS, S. sanguis, and S. salivarius at 4 to 8 micrograms/ml of OA. The anticariogenic effect of the OA-beta CD was examined in a rat-caries model. Rats in the infected control groups showed the highest caries score. The infected treatment group B (0.5% OA in diet) showed lower scores than the control group. These results suggest that OA-beta CD is a potential anti-caries agent.
TL;DR: Five new triterpenoid saponins, nipponosides A-E (1, 3-6), were isolated from Acanthopanax nipponicus leaves, along with a known saponin, kalop anaxsaponin G (2), based on chemical and spectral methods.
Abstract: Five new triterpenoid saponins, nipponosides A−E (1, 3−6), were isolated from Acanthopanax nipponicus leaves, along with a known saponin, kalopanaxsaponin G (2). Nipponosides A−E were characterized as the 28-O-α-l-rhamnopyranosyl(1→4)-β-d-glucopyranosyl(1→6)-β-d-glucopyranosyl ester of 3-oxohederagenin, oleanolic acid 3-O-β-d-glucopyranoside, gypsogenin 3-O-β-d-glucopyranoside, 3β,23,29-trihydroxyolean-12-en-28-oic acid, and 3β,20α,23-trihydroxy-30-nor-olean-12-en-28-oic acid, respectively. The structures of these new compounds were based on chemical and spectral methods.
TL;DR: Seventeen triterpenes isolated from cacti and the 10 derivatives were examined for the inhibition of tumor promoter-induced effects in vitro, such as stimulation of 32Pi-incorporation into phospholipids of cultured cells.
TL;DR: Results indicate that both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for gastric emptying in non-nutrient meal- or nutrient meal-loaded mice, and the 28-ester glucoside moiety and 2'-O-beta-D-glucopyranosid moiety reduce the activity.
TL;DR: Seven known oleanolic acid glycosides were isolated from the MeOH extract ofTiarella polyphylla and tested for the anticomplement activity and hemolytic activity.
Abstract: Seven known oleanolic acid glycosides (1–7) were isolated from the MeOH extract ofTiarella polyphylla. The structures were identified to be 3-O-(β-D-glucopyranosyl) oleanolic acid (1), 3-O-[β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl] oleanolic acid (2), 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl] oleanolic acid (3), 3-O-[β-D-glucopyranosyl-(1→3)-β-D-glucopyranosyl] oleanolic acid 28-O-β-D-glucopyranosyl ester (4), 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl] lleanolic acid 28-O-β-D-glucopyranosyl ester (5), 3-O-[a-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranosyl] oleanolic acid (6), and 3-O-[α-L-rhamnopyranosyl-(1→3)-β-D-glucuronopyranosyl] oleanolic acid 28-O-β-D-glucopyranosyl ester (7) on the basis of physicochemical and spectral data. These triterpene glycosides were tested for the anticomplement activity and hemolytic activity. Bisdesmosidic saponins,4, 5, and7, showed anticomplement activity; in contrast, monodesmosidic saponins,1–3, and6, showed direct hemolytic activity. Methyl esterified monodesmosidic saponins showed anticomplement activity at a low concentration and hemolytic activity at a high concentration.
Patent•
22 Dec 1999
TL;DR: Olive oil is fortified with oleanolic acid by including olive leaves in the malaxation mash of conventional olive oil pressing in an amount of 5-50 wt % as mentioned in this paper.
Abstract: Olive oil is fortified with oleanolic acid by including olive leaves in the malaxation mash of conventional olive oil pressing in an amount of 5-50 wt %, based on the weight of the malaxation mash The invention comprises vegetable oils fortified with a concentrate of oleanolic acid and, optionally, oleuropein Food products fortified with oleanolic acid containing oils or concentrates according to the invention are also part of the invention
TL;DR: Phytochemical reinvestigation of ISODON ORESBIUS afforded neoangustifolin, characterized as a separated component for the first time, established as butyl rosmarinate by a combination of 1D- and 2D-NMR techniques.
Abstract: Phytochemical reinvestigation of Isodon oresbius afforded, in addition to oleanolic acid, ursolic acid, sodoponin, astragalin, and quercetin-3-O-glucoside, three known (oresbiusin A, rosmarinic acid and methyl rosmarinate) and a new rosmarinic acid derivative as well as an ent-kaurene diterpenoid, neoangustifolin, characterized as a separated component for the first time. By a combination of 1D- and 2D-NMR techniques the structure of the new compound was established as butyl rosmarinate. The in vitro antifungal assay showed that neoangustifolin was active against Candida albicans with the MIC being 50 mu g/ml.
TL;DR: In this paper, two triterpenes were obtained from the aerial part of Salvia mellifera and their structures identified on the basis of spectroscopic data and chemical correlations as 11α-hydroxy-urs-12-en-3-one and 11β-hydroxyl-3oxo-urs -12en-28-oic acid.
Abstract: Two new triterpenes have been obtained from the aerial part of Salvia mellifera and their structures identified on the basis of spectroscopic data and chemical correlations as 11α-hydroxy-urs-12-en-3-one and 11β-hydroxy-3-oxo-urs-12-en-28-oic acid. the known triterpenes ursolic acid, oleanolic acid, ursa-9(11),12-dien-3-one, ursa-9(11),12-dien-3β-ol, β-amirine and the sterol β-sitosterol were also isolated from the same source.
TL;DR: Synthetic way for 13 C-labeled oleanolic acid 1 and myricerone 2 has been developed, starting from the parent 1 and 2. The procedure involves ring opening and closure of the A rings of these oleanane triterpenes as discussed by the authors.
Journal Article•
TL;DR: In this article, the structure of nine compounds including coumarin n-amyrin, p-AMRIN, a-Amyrin acetate, pamyrIN acetate and oleanolic acid were reported from the genus Cuscuta.
Abstract: Nine compounds including coumarin n-amyrin, p-amyrin, a-amyrin acetate, p-amyrin acetate, oleanolic acetate, oleanolic acid, stigmasterol and lupeol arereported forthe firsttime fromthegenus Cuscuta. Their structures have been established with the help of spectral data.
Journal Article•
TL;DR: The roots of Anemone tomentosa (Maxim.) Pei have been used as traditional medicine for the treatment of dysentery, infantile malnutrition, carbuncles, etc and Ethyl acetate extract of the roots displaied stronger antifeedant activity against Leucania separata Walker.
Abstract: The roots of Anemone tomentosa (Maxim.) Pei (Ranunculaceae) have been used as traditional medicine for the treatment of dysentery, infantile malnutrition, carbuncles, etc. Ethyl acetate extract of the roots displaied stronger antifeedant activity against Leucania separata Walker. Eleven compounds were isolated by silica gel column chromatography from the extract and their structures were identified as 4,5-dimethoxyl-7-methyl-coumarin (1), 4-methoxyl-5-methyl-6,7-methylenedioxy-coumarin (2), 4, 7-dimethoxyl-5-methy-coumarin (3), oleanolic acid (4), oleanonic acid (5), 3-O-beta-D-xylopyranosyl oleanolic acid (6), beta-sitosterol (7), stigmasterol (8), daucosterol (9), 3-O-beta-D-glucopyranosyl stigmasterol (10) and ergosterol peroxide (11) respectively on the basis of spectral evidence. Compounds 1 and 2 are new natural products.
Journal Article•
TL;DR: The method is good for determining oleanolic acid and ursolic acid in Chinese medicines and had good linearity in the range of 0.0025-0.4000 mg/ml.
Abstract: OBJECTIVE To develop a GC method to determine the oleanolic acid and ursolic acid in Spica Prunellae. METHOD Before GC analysis, the sample was derivatized with CH2N2 solution. The GC conditions were as follows: comumn-10% SE-30(2m x 3mm) and column temperature -270 degrees C. RESULT The two constituents were well separated and had good linearity in the range of 0.0025-0.4000 mg/ml. The average recoveries and RSD of oleanolic acid were 93.53% and 3.5%, 94.18% and 3.0% respectively. CONCLUSION The method is good for determining oleanolic acid and ursolic acid in Chinese medicines.
TL;DR: The first partial synthesis of monodesmosidic oleanolic acid trisaccharides was described in this article, where the influence of the linkage and the configurations of the carbohydrate units on the haemolytic activity of these saponins was investigated.
Abstract: The first partial synthesis of monodesmosidic oleanolic acid trisaccharides is described. Their haemolytic index is lower compared to the corresponding disaccharide. The influence of the linkage and the configurations of the carbohydrate units on the haemolytic activity of these saponins was investigated.
Journal Article•
TL;DR: Five compounds were isolated from the methanolic extract of the aerial parts of Onychium lucidum for the first time and their structures were elucidated on the basis of detailed spectroscopic analysis, in particular, two-dimensional NMR.
Abstract: Ten compounds were isolated from the methanolic extract of the aerial parts of Onychium lucidum These compounds were identified as luteoloside(1), 3,7-dimethylquercetin(2), contigoside B(3), onychin(4), lucidol(1β-methoxy-2β,3α,4β,5α,6β-pentahydroxycyclohexane)(5), onychiol B(6),β-sitosterol(7), daucosterol(8), oleanolic acid(9) and sucrose(10). Compound 5 is a new constituent, while 1, 2 and 9 were isolated from the genus Onychium for the first time. Their structures were elucidated on the basis of detailed spectroscopic analysis, in particular, two-dimensional NMR( 1H- 1H COSY; 1H- 1H NOE; 1H- 13 C COSY, COLOC)data.
Patent•
19 Jan 1999
TL;DR: Oleanolic acid 3-O-monodesmoside has excellent antiallergic action and anti-inflammatory action and is useful for treating prurigo, dermal pruritus, eczema, dermatitis, urticaria, allergic rhinitis, allergic conjuctivitis, immediate asthma, etc, as an anti-pruritus agent collectively having the actions as mentioned in this paper.
Abstract: PROBLEM TO BE SOLVED: To obtain an anti-pruritus agent inducting slight side effect by making the agent contain oleanolic acid 3-O-monodesmoside as an active component SOLUTION: This medical agent contains oleanolic acid 3-O-monodesmoside introduced from momordin Ic derived from Jifushi (dried fruit of Chenopodium scoparia L), momordin I derived from Mokubekkon (dried root of Momordica cochinchinensis Spreng), and chikusetsu saponin V derived from Panax ginseng, Panax japonicum, etc, as an active component The agent is further added with known additives, as necessary, mixed and prepared to a peroral or a parenteral agent by usual methods An administration dose of the active component is daily about 01-1 mg/kg of oleanolic acid 3-O-monodesmoside The oleanolic acid 3-O-monodesmoside also has excellent antiallergic action and anti-inflammatory action and is useful for treating prurigo, dermal pruritus, eczema, dermatitis, urticaria, allergic rhinitis, allergic conjuctivitis, immediate asthma, etc, as an anti-pruritus agent collectively having the actions
Patent•
19 May 1999
TL;DR: In this paper, the saponin mixtures and compounds isolated from Acacia victoriae species, and methods of use thereof are described, which have properties associated with the regulation of cell apoptosis and cytotoxicity and exhibit potent anti-tumor effects against various tumor cells.
Abstract: The present invention provides novel saponin mixtures and compounds isolated from Acacia victoriae species, and methods of use thereof. These compounds may contain triterpene residues such as acacinic acid or oleanolic acid, to which oligosaccharide and monoterpenoid residues are bound. These mixtures and compounds have properties associated with the regulation of cell apoptosis and cytotoxicity and exhibit potent anti-tumor effects against various tumor cells.