Biomedical subjects

Dirk Vanden Berghe

Publications and source records attributed to Dirk Vanden Berghe.

16 recordsLinked to original sources

PubMed2006

A novel isoflavonoid from Millettia puguensis.

From the roots of Millettia puguensis (Leguminosae), a novel isoflavonoid (5), 2'-methoxy-4',5'-methylenedioxy-7,8-[2-(1-methylethenyl)furo]isoflavone, and four known compounds, i. e., lupeol (1), (-)-maackiain (2), 6,7-dimethoxy-3',4'-methylenedioxyisoflavone (3) and 7,2'-dimethoxy-4',5'-methylenedioxyisoflavone (4) were isolated and identified by 1H-, 13C-NMR and mass spectroscopy. All compounds were evaluated for their antiprotozoal and cytotoxic activities, but only a moderate antileishmanial activity was observed for compound 3 (IC50 = 32 microM against Leishmania infantum), and a moderate cytotoxicity for compound 2 (IC50 = 43 microM on MRC-5 cells).

Animals↗

PubMed2006

Anti-infective potential of natural products: how to develop a stronger in vitro 'proof-of-concept'.

Natural products, either as pure compounds or as standardized plant extracts, provide unlimited opportunities for new drug leads because of the unmatched availability of chemical diversity. To secure this, a number of pivotal quality standards need to be set at the level of extract processing and primary evaluation in pharmacological screening models. This review provides a number of recommendations that will help to define a more sound 'proof-of-concept' for antibacterial, antifungal, antiviral and antiparasitic potential in natural products. An integrated panel of pathogens is proposed for antimicrobial profiling, using accessible standard in vitro experimental procedures, endpoint parameters and efficacy criteria. Primary requirements include: (1) use of reference strains or fully characterized clinical isolates, (2) in vitro models on the whole organism and if possible cell-based, (3) evaluation of selectivity by parallel cytotoxicity testing and/or integrated profiling against unrelated micro-organisms, (4) adequately broad dose range, enabling dose-response curves, (5) stringent endpoint criteria with IC(50)-values generally below 100microug/ml for extracts and below 25microM for pure compounds, (6) proper preparation, storage and in-test processing of extracts, (7) inclusion of appropriate controls in each in vitro test replicate (blanks, infected and reference controls) and (8) follow-up of in vitro activity ('hit'-status) in matching animal models ('lead'-status).

Anti-Infective Agents↗

PubMed2006

Effect of different flavonoids on collagen synthesis in human fibroblasts.

In this study, we discovered that flavonoids belonging to the subclasses: (flavanone, flavone, and flavonol) display differential effects on the synthesis of collagen in human dermal fibroblasts. At 80 microg/ml flavonoids quercetin-3,3',4', 5,7-pentahydroxyflavone, 3-methyl quercetin, and 7-hydroxyflavone significantly decreased the total protein concentration which was a direct consequence of their cytotoxic effect, while naringenin exhibited no effect on total collagen and total protein concentration. Quercetin-3,3'4',7-tetramethyl ether, 4'-hydroxyflavanone, flavanone, and fisetin significantly decreased collagen concentration while morin, rutin, and chrysin increased collagen concentration without changing the overall protein concentration. The initial screening performed in this study enables the identification of compounds that exert significant effects on fibroblast function and show potential as starting material for pharmaceutical preparations targeted against various disorders centered around disturbed collagen metabolism.

Collagen↗

PubMed2006

Antiparasitic activity of some xanthones and biflavonoids from the root bark of Garcinia livingstonei.

A new biflavanoid, ent-naringeninyl-(I-3alpha,II-8)-4'-O-methylnaringenin (6), along with five known xanthones and two known biflavonoids, was isolated from the root bark of Garcinia livingstonei collected in Tanzania. The absolute configuration of 6 was established by CD spectroscopy. This compound showed moderate activity against P. falciparum (IC(50) 6.7 microM). Antitrypanosomal activity (IC(50) 0.87 microM) was observed for 1,4,5-trihydroxy-3-(3-methylbut-2-enyl)-9H-xanthen-9-one (3). The dimeric xanthone garcilivin A (4) showed a higher and nonselective antiparasitic activity and cytotoxicity (IC(50) 2.0 microM against MRC-5 cells) than its diastereoisomer garcilivin C (5) (IC(50) 52.3 microM).

Animals↗

PubMed2005

Method development and validation for monitoring in vivo oxidative stress: evaluation of lipid peroxidation and fat-soluble vitamin status by HPLC in rat plasma.

Monitoring in vivo oxidative stress implicates the evaluation of damage and defence parameters by well-established, validated methods. We report two optimized and validated HPLC methods for measurement of malondialdehyde (MDA) and fat-soluble vitamins in rat plasma. For the MDA method, optimization experiments of the thiobarbituric acid test resulted in the addition of 1% butylhydroxytoluene to the reaction mixture and in a heating time reduction to 40 min, ensuring inhibition of further lipid peroxidation during the test. Validation experiments showed good linearity, precision and recovery. The use of HPLC with coulometric array detection technology permits simultaneous and sensitive analysis of different fat-soluble vitamins and related compounds (tocopherols, retinoids, carotenoids and coenzyme Q10), which are identified by both retention time and electrochemical characteristics. Furthermore, this method is extended to the analysis of coenzyme Q9, the predominant homologue in rats. Validation experiments with rat plasma gave good results.

Animals↗

PubMed2004

Diterpenes from the brown algae Dictyota dichotoma and Dictyota linearis.

Nineteen secondary metabolites of the brown alga Dictyota dichotoma (Huds.) Lam. and fifteen metabolites of the brown alga D. linearis (Ag.) Grev. were isolated and their chemical structures were elucidated on the basis of their NMR and mass spectral data. The diterpenes isopachydictyolal (1) from D. dichotoma and 4alpha-acetyldictyodial (2) from D. linearis are new natural products. The antiviral activity of metabolites isolated in adequate amounts was evaluated in laboratory assays against Herpes simplex virus I (HSV I) and Poliomyelitis Virus I, using Vero cells as hosts.

Animals↗

PubMed2004

Plant substances as anti-HIV agents selected according to their putative mechanism of action.

Despite the continuous advances made in antiretroviral combination therapy, AIDS has become the leading cause of death in Africa and the fourth worldwide. Today, many research groups are exploring the biodiversity of the plant kingdom to find new and better anti-HIV drugs with novel mechanisms of action. In this review, plant substances showing a promising anti-HIV activity are discussed according to the viral targets with which they interact. Most of these compounds, however, interfere with early steps in the HIV replication, such as the virus entry steps and the viral enzymes reverse transcriptase and integrase, whereas until now almost no plant compounds have been found to interact with the many other viral targets. Since some plant substances are known to modulate several cellular factors, such as NF-kappa B and TNF-alpha, which are also involved in the replication of HIV, their role as potential anti-HIV products is also discussed. In conclusion, several plant-derived antiviral agents are good candidates to be further studied for their potential in the systemic therapy and/or prophylaxis of HIV infections, most probably in combination with other anti-HIV drugs.

Acquired Immunodeficiency Syndrome↗

PubMed2004

An ex-vivo angiogenesis assay as a screening method for natural compounds and herbal drug preparations.

Angiogenesis is a fundamental component of complex biological processes, including oncogenesis. The aim of this work was to optimise and validate an ex-vivo angiogenesis assay as a quantitative (PC image) biological method for testing promising natural compounds and herbal drug preparations for their pro-/anti-angiogenic activity. The bioassay is based on the principle of wound healing and quantifies the effect of angiogenic agents on neovessel outgrowth of human placental vessels embedded in a three-dimensional fibrin matrix. The assay was validated by using known, well characterised pro- and anti-angiogenic effectors (basic fibroblast growth factor and carboxyamidotriazole, respectively), and an angiogenesis inhibitor of plant origin (green tea leaves extract) was used as a reference product to demonstrate the applicability of the assay for plant extracts. Other standardised plant extracts prepared from olive tree leaves and horse chestnut seeds were tested for their angiogenic potential, but showed only slight inhibitory or no activity, respectively. The results presented here indicate that this human ex-vivo angiogenic assay is "ready to use" for screening of herbal drug preparations and pure compounds.

Aesculus↗

PubMed2004

In vitro and in vivo activities of a triterpenoid saponin extract (PX-6518) from the plant Maesa balansae against visceral leishmania species.

The in vitro and in vivo activities of a mixture of six oleane triterpene saponins, recovered from the methanolic extract of the leaves of the Vietnamese plant Maesa balansae (PX-6518), were evaluated against drug-sensitive visceral Leishmania strains. The in vitro 50% inhibitory concentration (IC(50)) against intracellular Leishmania infantum amastigotes was 0.04 micro g/ml. The cytotoxic concentrations causing 50% cell death (CC(50)s) were about 1 micro g/ml in murine macrophage host cells and >32 micro g/ml in human fibroblasts (MRC-5 cell line). Evaluation in the Leishmania donovani BALB/c mouse model indicated that a single subcutaneous administration of 0.4 mg/kg at 1 day after infection reduced liver amastigote burdens by about 95% in all treated animals. If treatment was delayed until 14 days after infection, a dose of 1.6 mg/kg of body weight was required to maintain the same level of activity. Single 250-mg/kg doses of sodium stibogluconate (Pentostam) 1 and 14 days after infection produced comparable efficacies. A single dose of PX-6518 at 2.5 mg/kg administered 5 days before infection was still 100% effective in preventing liver infection, suggesting a particularly long residual action. Spleen and bone marrow could not be cleared by PX-6518 nor sodium stibogluconate. PX-6518 did not show activity after oral dosing at up to 200 mg/kg for 5 days. This study concludes that triterpenoid saponins from M. balansae show promising in vitro and in vivo antileishmanial potential and can be considered as new lead structures in the search for novel antileishmanial drugs.

Animals↗

PubMed2004

Comparative activities of the triterpene saponin maesabalide III and liposomal amphotericin B (AmBisome) against Leishmania donovani in hamsters.

Maesabalide III (MB-III), an oleane triterpene saponin isolated from the Vietnamese plant Maesa balansae, is a new antileishmanial lead compound whose activity against Leishmania donovani (MHOM/ET/67/L82) in groups of five golden hamsters was evaluated after administration of a single subcutaneous dose on either day 1 (prophylactic treatment) or day 28 (curative treatment) after infection. Liposomal amphotericin B (AmBisome), administered intravenously at 5 mg/kg of body weight, was used as the reference drug. Amastigote burdens in liver, spleen, and bone marrow were determined either 7 days (early effects) or 56 days (late effects) after treatment. Prophylactic administration of MB-III at 0.2 mg/kg reduced liver amastigote burdens by 99.8 and 83% within 7 and 56 days after treatment, respectively. In the latter group, however, all animals became ill and some died. Both MB-III at 0.8 mg/kg and liposomal amphotericin B were 100% effective against liver stages, but clearance from the spleen and bone marrow was not achieved. Curative administration of MB-III at 0.2 and 0.4 mg/kg was not protective, as no survivors were left at the termination of the experiment on day 84. Despite the high level of reduction of the liver amastigote burden after treatment with MB-III at 0.8 mg/kg (94.2%) or liposomal amphotericin B (99.4%), clinical protection could not be obtained in either group, with two deaths occurring and the residual liver burdens persisting. It is concluded that administration of a single dose of MB-III at 0.8 mg/kg has efficacy potential comparable to that of a single dose of liposomal amphotericin B at 5 mg/kg and is therefore considered a promising new antileishmanial lead compound. However, multiple-dose pharmacological, toxicological, and pharmacokinetic studies are still needed before it can become a valid drug candidate for development.

Amphotericin B↗

PubMed2003

Phytoestrogens: recent developments.

Phytoestrogens are polyphenolic non-steroidal plant compounds with estrogen-like biological activity. Based on their chemical structure, phytoestrogens can be classified into four main groups, i. e., isoflavonoids, flavonoids, stilbenes, and lignans. For each group, the chemistry, dietary sources and biotransformation of the most interesting compounds will be discussed. Since phytoestrogens are structurally very similar to the estrogen 17beta-estradiol, they may exhibit selective estrogen receptor modulating activities. Therefore, special attention will be given to the hormonal effects of various isoflavonoids, including genistein, daidzein, coumestrol and equol, several prenylated flavonoids, especially 8-prenylnaringenin, and the stilbene resveratrol. Furthermore, their non-hormonal effects will be discussed briefly. Finally, the latest developments on the potential protective properties of phytoestrogens and phytoestrogen-containing foods against hormone-dependent breast and prostate cancers and cardiovascular diseases, and as estrogen replacement therapy for postmenopausal women will be discussed.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Anticomplement and antioxidant activities of new acetylated flavonoid glycosides from Centaurium spicatum.

In addition to the three acetylated flavonol glycosides, quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-beta-galactopyranoside, quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-3-acetyl-beta-galactopyranoside, and quercetin 3- O-[(2,3,4- triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-4-acetyl-beta-galactopyranoside, which have recently been isolated from Centaurium spicatum (L.) Fritsch (Gentianaceae), a new pentaacetylated flavonoid glycoside was isolated from the same plant. Structure elucidation, especially the localization of the acetyl groups, and complete (1)H- and (13)C-NMR assignments, was carried out using one- and two-dimensional NMR methods, including (1)H- and (13)C-NMR, DEPT-135 and DEPT-90, and gradient-assisted experiments such as DQF-COSY, TOCSY, HSQC and HMBC. The structure of the new flavonoid glycoside was established as quercetin 3- O-[(2,3,4-triacetyl-alpha-rhamnopyranosyl)-(1-->6)]-3,4-diacetyl-beta-galactopyranoside. The anticomplement and antioxidant activities of these compounds were evaluated. The triacetylated flavonoid glycoside showed the highest activity in the two assays.

Antioxidants↗

PubMed2002

Antiviral activity of simalikalactone D, a quassinoid from Quassia africana.

After removing lipophilic material, the ground root bark of Quassia africana Baill. (Simaroubaceae) was extracted with ethanol 95 %. Partitioning between chloroform, ethyl acetate and water yielded three crude extracts. Pronounced activities were shown by the chloroform and ethyl acetate crude extracts against Herpes simplex, Semliki forest, Coxsackie and Vesicular stomatitis viruses. By repeated column chromatography and preparative thin layer chromatography on silica gel, two quassinoids, i. e., quassin and simalikalactone D were isolated. Structures of the pure compounds were established primarily using NMR spectroscopy. Mass spectral information confirmed the assigned structures. Simalikalactone D was responsible, at least in part, for the high antiviral activity observed for the chloroform crude extract. Quassin showed no activity. For quassinoids the ester group at C-15 and the epoxymethano bridge between C-8 and C-13 appeared to be important structural features in order to exhibit a pronounced antiviral activity.

Antineoplastic Agents, Phytogenic↗

PubMed2002

Antiviral and antioxidant activity of flavonoids and proanthocyanidins from Crataegus sinaica.

The antiviral and antioxidant activity of some fractions and of a series of flavonoids and proanthocyanidins obtained from Crataegus sinaica (Rosaceae) was evaluated. The O-glycosidic flavonoids and the oligomeric proanthocyanidins exhibited significant inhibitory activity against herpes simplex virus type 1 (HSV-1), which was shown to be due to an extracellular mechanism for procyanidin C-1. Procyanidin C-1 also had the highest antioxidant activity in both the microsomal lipid peroxidation and the hydroxyl radical scavenging assay. In addition to the previously reported phenolic compounds, the pentacyclic triterpenoid ursolic acid (1) and a tetrameric (2) and pentameric procyanidin (3) are reported for the first time.

Animals↗

PubMed2002

In vitro antioxidant profile of phenolic acid derivatives.

Several caffeic acid esters isolated from propolis exhibit interesting antioxidant properties, but their in vivo use is compromised by hydrolysis of the ester bond in the gastrointestinal tract. Therefore, a series of caffeic acid amides were synthesized and their in vitro antioxidant profile was determined. A series of hydroxybenzoic acids, hydroxycinnamic acids, and the synthesized caffeic acid amides were tested for both their 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging and microsomal lipid peroxidation-inhibiting activity. Some of the highly active antioxidants were further tested by means of electron paramagnetic resonance for their hydroxyl radical scavenging activity. Since a promising antioxidant compound should show a lipid peroxidation-inhibiting activity at micromolar level and a low cytotoxicity, the cytotoxicity of the phenolic compounds was also studied. In all the assays used, the caffeic acid anilides and the caffeic acid dopamine amide showed an interesting antioxidant activity.

Antioxidants↗

PubMedDate not supplied

Characterisation of new oligoglycosidic compounds in two Chinese medicinal herbs.

A series of caffeic acid derivatives (3,5-dicaffeoyl-quinic acid, 3,4-dicaffeoyl-quinic acid, and 4,5-dicaffeoyl-quinic acid), and the new compound beta,3,4-trihydroxyphenethyl-O-[beta-apiofuranosyl-(1-->4)-alpha- rhamnopyranosyl-(1-->3)]-(4-O-caffeoyl)-beta-glucopyranoside (wedelosin), as well as three known flavonoid glycosides (quercetin 3-O-beta-glucoside, kaempferol 3-O-beta-apiosyl-(1-2)-beta-glucoside, and astragalin or kaempferol 3-O-beta-glucoside) were isolated from the Chinese medicinal herb Wedelia chinensis. Wedelosin showed an inhibitory activity on both the classical and the alternative activation pathway of the complement system. Another Chinese medicinal herb, Kyllinga brevifolia, yielded two known flavonoid glycosides [kaempferol 3-O-beta-apiosyl-(1-2)-beta-glucoside and isorhamnetin 3-O-beta-apiosyl-(1-2)-beta-glucoside], and a new quercetin triglycoside [quercetin 3-O-beta-apiofuranosyl-(1-->2)-beta-glucopyranoside 7-O-alpha-rhamnopyranoside]. The latter compound showed a moderate anti-viral activity.

Antiviral Agents↗