Biomedical subjects

T De Bruyne

Publications and source records attributed to T De Bruyne.

25 records · Page 2Linked to original sources

PubMed1997

Isoquinoline derivatives isolated from the fruit of Annona muricata as 5-HTergic 5-HT1A receptor agonists in rats: unexploited antidepressive (lead) products.

The fruit and the leaves of Annona muricata (Annonaceae) are used in traditional medicine for their tranquillizing and sedative properties. Extracts of the plant have been shown to inhibit binding of [3H]rauwolscine to 5-HTergic 5-HT1A receptors in calf hippocampus, and three alkaloids, annonaine (1), nornuciferine (2) and asimilobine (3), isolated from the fruit have been shown to have IC50 values of 3 microM, 9 microM and 5 microM, respectively, although in ligand-binding studies it was not possible to determine whether interaction of these ligands with the receptor was agonistic or antagonistic. This paper presents the results of functional assays of the alkaloids. The inhibition of cAMP accumulation was tested in NIH-3T3 cells stably transfected with the 5-HT1A receptor from man. None of the alkaloids showed antagonistic properties towards the 5-HT1A receptors because in the antagonistic tests no influence on the forskolin-stimulated increase of cAMP level was detected. Full agonistic properties were measured for all three compounds; the inhibition constants (Ki) for 1, 2 and 3 were < 10 microM. Inhibition of the binding of the radioligand to the 5-HT1A receptor was observed in every ligand-binding assay performed with the alkaloids; the Ki values for 1, 2 and 3 were in the microM range. These results imply that the fruit of Annona muricata possesses anti-depressive effects, possibly induced by compounds 1, 2 and 3, and that in the past potent leads for the development of anti-depressive therapeutics have not been used.

Alkaloids↗

PubMed1997

Cirsimarin and cirsimaritin, flavonoids of Microtea debilis (Phytolaccaceae) with adenosine antagonistic properties in rats: leads for new therapeutics in acute renal failure.

In traditional medicine Microtea debilis is used against proteinuria. In ligand-binding studies extracts of Microtea debilis have been shown to inhibit the binding of [3H]1,3-dipropyl-8-cyclopentylxanthine ([3H]DPCPX) to adenosine-A1 receptors in rat forebrain membranes. Subsequently, cirsimarin, a flavonoid, was isolated as the active component and was shown to function as adenosine antagonist at the adenosine-A1 receptor in-vitro. In this study we have investigated the adenosine-A2 receptor activity of cirsimarin the in-vivo inhibition of the effects of adenosine by cirsimarin in rats, the absorption of cirsimarin and the inhibition of the binding of [3H]DPCPX to the adenosine-A1 receptor by urine samples obtained after oral administration of crude extract of Microtea debilis, cirsimarin or cirsimaritin to rats. Cirsimarin inhibited the binding of [3H]5'-N-ethylcarboxamidoadenosine ([3H]NECA) to adenosine-A2 receptors in rat striatum with an inhibition constant, Ki, of 6.5 +/- 0.3 microM. The decrease of heart rate and blood pressure induced by adenosine was significantly inhibited by cirsimarin. After oral administration of 8 and 80 mg kg-1 cirsimarin, the compound could not be detected in either plasma or urine, but the presence of cirsimaritin was established. By use of beta-glucuronidase, glucuronides of cirsimaritin were also detected in the urine. The concentrations of cirsimaritin in the plasma were 0.126 +/- 0.04, 0.138 +/- 0.015, and 0.120 +/- 0.022 microM, respectively, 2, 5 and 12 h after administration of 8 mg kg-1 cirsimarin. The concentrations of cirsimaritin in the urine at the same times after administration of the same dose were 2.05 +/- 1.86, 5.05 +/- 2.6 and 2.06 +/- 0.09 microM, respectively. The inhibition of the binding of [3H]DPCPX to the adenosine-A1 receptor by urine samples collected 2, 5 and 12 h after oral administration of 8 mg kg-1 cirsimarin or a crude extract of Microtea debilis containing approximately 8 mg kg-1 cirsimarin and 2.8 mg kg-1 cirsimaritin, or 6.8 mg kg-1 cirsimaritin, was not significantly different from that of urine samples collected from untreated rats, in contrast with urine samples collected 1 and 2 days after oral administration of 80 mg kg-1 cirsimarin. Approximately 3% of the cirsimarin was excreted in the urine as cirsimaritin. The results indicate that in the kidney and urinary tract the concentrations of cirsimaritin produced after ingestion of more than 8 mg kg-1 cirsimarin can be high enough to inhibit the interaction of adenosine with its receptors; this might explain the effectiveness of Microtea debilis preparations against proteinuria in traditional medicine.

Acute Kidney Injury↗

PubMed1996

Triterpenoid saponins from Maesa lanceolata.

Six new homologous triterpenoid saponins were isolated from the methanol extract of the leaves of Maesa lanceolata and characterized as 3 beta-O-[alpha-L-rhamnopyranosyl(1 --> 2)-beta-D-galactopyranosyl (1 --> 3)]-[beta-D-galactopyranosyl(1 --> 2)]-beta-D-glucuronopyranosides alpha-diol, 22 alpha-angeloyloxy-16 alpha-butanoyloxy-13 beta,28-oxydoolean-21 beta,28 alpha-diol, 16 alpha,22 alpha-diangeloyloxy-13 beta,28-oxydoolean-21 beta,-28 alpha-diol, 22 alpha-angeloyloxy-13 beta,28-oxydo-16 alpha-(2-methyl-butanoyloxy)-olean-21 beta,28 alpha-diol, 21 beta-acetoxy-22 alpha-angeloyloxy-13 beta,28-oxydo-16 alpha-propanoyloxyolean-28 alpha-ol, 21 beta-acetoxy-22 alpha-angeloyloxy-16 alpha-butanoyloxy-13 beta,28-oxydoolean-28 alpha-01. The structures were established on the basis of chemical and spectral evidence.

Carbohydrate Conformation↗

PubMed1996

Anti-complementary activity of Crataegus sinaica.

The 80% and 70% acetone extracts from fruits and leaves of Crataegus sinaica Boiss (Rosaceae) and the ethyl acetate-, butanol-, and water-fractions obtained from these initial extracts as well as the isolated compounds, quercetin (1) (1), hyperoside (quercetin 3-O-galactoside) (2) (2), rutin (quercetin 3-O-rutinoside) (3) (2), vitexin (4) (1), rhamnosylvitexin (5) (3), monoacetylrhamnosylvitexin (6) (3), epicatechin (7) (4), procyanidin B-5 (8) (4), proanthocyanidin A-2 (9) (5), procyanidin B-2 (10) (4), and procyanidin C-1 (11) (4), were tested for their influence on the classical (CP) and alternative (AP) pathways of complement-mediated hemolysis. All extracts and fractions showed a strong anti-complementary effect in a dose-dependent way which was more pronounced on the CP than on the AP. The results indicated that the pure proanthocyanidins were active on the CP. Procyanidin C-1 and proanthocyanidin A-2 were the most active on the CP and also showed activity on AP, whereas the flavonoids isolated were generally less active. However, rutin, showed a strong activity, quercetin and rhamnosylvitexin a moderate activity on the CP. This is the first report on the chemical constituents and complement-modulating activity of C. sinaica and on the occurrence of proanthocyanidin A-2 (9) in hawthorn.

Biflavonoids↗

PubMed1996

In vitro biological activities of alkaloids from Cryptolepis sanguinolenta.

In our biological screening of higher plants, an aqueous and an 80% EtOH extract from the root bark of Cryptolepis sanguinolenta showed potent antibacterial, anticomplementary, and moderate antiviral activities, but no antifungal effect could be detected. Bioassay-guided fractionation of the 80% EtOH extract led to the isolation of three alkaloids: quindoline (1), hydroxycryptolepine (2), cryptolepine.HCl (3), and the corresponding base cryptolepine (4). All compounds strongly inhibited the growth of Gram-positive bacteria (MIC < or = 100 micrograms/ml) and showed a moderate (MIC = 125 or 250 micrograms/ml), a weak (MIC = 500 micrograms/ml), or no activity (MIC > 500 micrograms/ml) against selected Gram-negative bacteria. They also possessed a bactericidal effect depending on the bacterial strain. Compounds 1, 2 and 3 displayed a dose-dependent inhibitory effect on the classical pathway of the complement system while compounds 2 and 3 activated the alternative pathway, except for compound 1. Compound 3 was found to possess an antiherpetic activity. Compounds 1 and 4 showed no antiviral effect, but were quite cytotoxic in the antiviral test system down to a concentration of 1 microgram/ml.

Alkaloids↗

PubMed1995

In vitro anticomplementary activity of constituents from Morinda morindoides.

In a screening program for complement classical pathway modulation, an 80% MeOH extract of the leaves of Morinda morindoides showed potent dose-dependent anticomplementary activity. Bioassay-guided chromatographic separation of the active constituents led to the isolation of ten flavonoids of which two were aglycones. The compounds were tested in vitro for their putative complement-inhibiting properties on the classical (CP) and the alternative (AP) pathways of the complement system. The results indicated that quercetin [1], quercetin 3-O-rhamnoside (quercitrin) [5], and quercetin 3-O-rutinoside (rutin) [7] showed similar anticomplementary activities (inhibition) on the CP of complement. A mixture of two kaempferol triglycosides isolated and denoted as M(015), also had a good inhibitory effect. The effects of these compounds were dose-dependent for this pathway. On the AP of complement, quercetin [1] and M(015) had, respectively, more pronounced inhibitory and activatory effects than the other tested flavonoids, but their effects were not dose-dependent for this pathway. The other isolated flavonoids showed weak effects or were inactive for both pathways.

Animals↗

PubMedDate not supplied

Structure-activity relationship of flavonoids with superoxide scavenging activity.

The superoxide scavenging activities of 12 flavonoids were measured. The superoxide anions were generated by a hypoxanthine-xanthine oxidase system and measured by the nitrite method. The results showed that the scavenging ability enhanced with an increasing number of hydroxyl groups in ring B. Substitution at C3 position with a hydroxyl group increased the activity. Compared to a methoxyl group or a glycoside in this position, a free hydroxyl group showed the highest activity. A saturated C2-C3 bond showed a higher activity than a unsaturated bond. The absence of a carbonyl group at C4 position increased the activity.

Flavonoids↗