Anatole Guy Blaise Azebaze

Cytotoxic and antimicrobial coumarins from Mammea africana

Abstract Six coumarin derivatives [three 4-phenylcoumarins (Mammea A/AA, Mammea A/BA and MAB 3), two 4-n-propylcoumarins (Mammea B/BB and Mammea B/BA) and one 4-n-pentylcoumarin (Mammea C/OB)], 1,5-dihydroxyxanthone and 1-methoxy-5-hydroxyxanthone have been isolated from the stem bark of Mammea africana Sabine collected in Cameroon. Although known, the structures of the coumarin derivatives were confirmed by spectral analysis, including two-dimensional nuclear magnetic resonance. All the coumarin compounds showed noteworthy cytotoxicity against the human 9-KB cell line. Both of the 4-n-propylcoumarins were also found to exhibit significant activity against Staphylococcus aureus.

Anti-hypertensive effects of the methanol/methylene chloride stem bark extract of Mammea africana in L-NAME-induced hypertensive rats

AIM OF THE STUDY The methanol/methylene chloride (CH(3)OH/CH(2)Cl(2)) extract from the stem bark of Mammea africana was showed to possess vasodilating effect in the presence and the absence of N(omega)-nitro-l-arginine methyl ester (l-NAME). The present study was designed to evaluate the effects of the methanol/methylene chloride from the stem bark of Mammea africana. MATERIALS AND METHODS The extract (200 mg/(kg day)) was administered orally in rats treated concurrently with l-NAME (40 mg/(kg day)). l-Arginine (100 mg/(kg day)) and captopril (20 mg/(kg day))were used as positive controls. Bodyweight, systolic arterial blood pressure and heart rate were measured weekly throughout the experiment period (28 days). At the end of treatment, animals were killed and the cardiac mass index evaluated. The aorta was used to evaluate the endothelium-dependant relaxation to carbachol. The aorta contraction induced by noradrenalin was also examined and expressed as a percentage of that induced by KCl. RESULTS The extract neither affected the body weight nor the heart rate. The extract as captopril completely prevented the development of arterial hypertension. Both the substances failed to restore the endothelium-dependent vascular relaxation and increased the vascular contraction to norepinephrine in relation to KCl contraction. They also significantly reduced the left ventricular hypertrophy induced by l-NAME. CONCLUSION These findings are in agreement with the traditional use of Mammea africana in the treatment of arterial hypertension and indicate that it may have a beneficial effect in patients with NO deficiency but will be unable to improve their endothelium-dependent vasorelaxation.

Hypoglycaemic effects of Mammea africana (Guttiferae) in diabetic rats.

AIM OF THE STUDY The stem bark of Mammea africana Sabine (Guttiferae) is used in African rain forest to treat various diseases, including diabetes mellitus. We investigated whether Mammea africana extract induced hypoglycaemic activity in rats. MATERIALS AND METHODS We tested the effects of acute (5h) and sub-acute (21 days) oral administrations of the CH(2)Cl(2)-MeOH stem bark extract of Mammea africana (19-300 mg/kg body weight) on blood glucose levels of normal and streptozotocin (STZ)-induced type 1 diabetic rats. The effects were compared with those of glibenclamide. RESULTS Acute administration reduced blood glucose in the diabetic rats only (33.87%, P<0.01). Sub-acute treatment for 21 days also reduced blood glucose level in diabetic rats (73.29%, P<0.01). A reduction or stabilization in total serum protein, triglyceride, cholesterol and alanine amino transferase levels was also observed. No effect was observed on body weight loss but food and water intakes were significantly reduced (P<0.01) in diabetic rats. The maximal anti-diabetic effect was obtained with the dose of 75 mg/kg and was more important than that of glibenclamide. CONCLUSION It can be concluded that extracts of Mammea africana exhibited a significant anti-hyperglycaemic activity and improved the metabolic alterations in STZ-diabetic rats. These results provide a rationale for the use of Mammea africana to treat diabetes mellitus and hypercholesterolemia.

Xanthones from the seeds of Allanblackia monticola and their apoptotic and antiproliferative activities.

Phytochemical investigations of the seeds of ALLANBLACKIA MONTICOLA have led to the isolation and characterization of one new xanthone derivative, named allanxanthone E ( 1), together with seven known compounds, including five xanthones, 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2-enyl)xanthone ( 2), alpha-mangostin ( 3) , garciniafuran ( 4) , allanxanthone C ( 5), and 1,6-dihydroxy-2,4-diprenylxanthone ( 6), and two pentacyclic triterpenes, friedelin and lupeol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and heteronuclear correlation evidence. Some of these compounds were evaluated for their apoptotic and antiproliferative activities against human leukemic B lymphocytes, such as the hairy cell leukemia-derived ESKOL cell line and cells from B-CLL (B-cell chronic lymphocytic leukemia) patients.

Antimicrobial and antileishmanial xanthones from the stem bark of Allanblackia gabonensis (Guttiferae)

The phytochemical study of stem bark of Allanblackia gabonensis has resulted in the isolation and characterisation of one new xanthone derivative, named allanxanthone D, together with 10 known compounds, including 6 xanthones derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and 1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6-deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one flavanol, epicathechin, two phytosterols, beta-sitosterol and campesterol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and hetero-nuclear evidence. These compounds were evaluated for their activity against Leishmania amazonensis in vitro and antimicrobial activities against a range of Gram negative and Gram positive bacteria.

Pentacyclic triterpenoids and ceramide mediate the vasorelaxant activity of Vitex cienkowskii via involvement of NO/cGMP pathway in isolated rat aortic rings.

ETHNOPHARMACOLOGICAL RELEVANCE Vitex cienkowskii Kotschy & Peyritsch is a deciduous tree, prescribed by Cameroonian traditional healers as one of the most popular plant widely used in many disorders including cardiovascular diseases. The preliminary pharmacological studies carried out on Vitex cienkowskii showed its vasorelaxant activities on guinea-pig aortic rings. AIM OF THE STUDY The present work evaluated the vasorelaxant activity of extract and isolated compounds from Vitex cienkowskii. MATERIALS AND METHODS Rat aortic rings were used to evaluate the in vitro vascular effect of the extract. The antioxidant activity was determined by measuring the reduction of the free radical 1,1-diphenyl-1-picryl-hydrazyl (DPPH). RESULTS Vitex cienkowskii induced significant relaxation in a concentration- and endothelium-dependent manner (EC(50)=12.12 μg/ml, CH(2)Cl(2)-MeOH, 1:1) and did not produce a vasorelaxant effect on contraction evoked by KCl (60 mM). In order to determine its mode of action, Vitex cienkowskii-induced relaxant effect was evaluated in the presence of indomethacin (10 μM), L-NAME (100 μM), ODQ (1 μM) and SQ22356 (100 μM). Relaxation was significantly blocked by L-NAME and ODQ. These results indicate that Vitex cienkowskii-mediated relaxation is endothelium dependent, probably due to NO release, and the consequent activation of vascular smooth muscle soluble guanylate cyclase (sGC), a signal transduction enzyme that forms the second messenger cGMP. Bio-guided study of Vitex cienkowskii allowed the isolation of the known pentacyclic triterpenoids and a ceramide. It is the first report of salvin A, maslinic acid and a ceramide from Vitex cienkowskii. The activity induced by these compounds indicated that they may be partly responsible for the vasorelaxant effect of the plant extract. A dose of 40 mg/kg of CH(2)Cl(2)-MeOH (1:1) extract administered intravenously induced a decrease of mean arterial pressure but did not affect the heart rate. Moreover the plant extracts were found to be highly active in the DPPH radical scavenging assay. CONCLUSION Vitex cienkowskii extract possesses antioxidant property, vasorelaxing, and hypotensive effect linked to the endothelium related factors, where nitric oxide is involved.

ANTIMICROBIAL AND ANTILEISHMANIAL XANTHONES FROM THE STEM BARK OF Allanblackia gabonensis

The phytochemical study of the stem bark of Allanblackia gabonensis has resulted in the isolation and characterization of one new xanthone derivative, named allanxanthone D, together with ten known compounds, including six xanthone derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and 1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6-deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one flavanol, epicathechin, two phytosterols, β-sitosterol, and campesterol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and heteronuclear evidence. These compounds were evaluated for their activity against Leishmania amazonensis in vitro and antimicrobial activities against a range of Gram-negative and Gram-positive bacteria.

Antimalarial and vasorelaxant constituents of the leaves of Allanblackia monticola (Guttiferae)

Abstract Phytochemical investigation of the leaves of Allanblackia monticola led to the isolation and characterisation of five prenylated xanthones [1,6-dihydroxy-3,7-dimethoxy-2-(3-methylbut-2-enyl)xanthone 1, α-mangostin 2, tovophyllin A 3, allanxanthone C 4 and 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2-enyl)xanthone 5], two biflavonoid derivatives (amentoflavone 6 and podocarpusflavone A 7) and one pentacyclic triterpene (friedelan-3-one 8). The structures of these compounds were established on the basis of homo- and hetero-nuclear, one- and two-dimensional, nuclear magnetic resonance. Compounds 2–8 and a crude methanolic extract of A. monticola leaves were each tested for antimalarial activity in vitro, using the chloroquine-sensitive F32 and chloroquine-resistant FcM29 strains of Plasmodium falciparum; the median inhibitory concentrations (IC50) recorded varied from 0.7 to 83.5 μg/ml. The cytotoxicities of the compounds and crude extract, against cultures of human melanoma cells (A375), were then investigated, and cytotoxicity/antimalarial IC50 ratios of 0.6–16.75 were recorded. In tests involving aortic rings from guinea pigs, a crude extract of the leaves of A. monticola was found to induce concentration-dependent vasorelaxation, causing up to 82% and 42% inhibition of noradrenaline- and KCl-induced contractions, respectively. The corresponding values for compounds 2 and 6 when tested against noradrenaline-induced contractions were approximately 18% and 35%, respectively.

Antioxidant, antitumor and antimicrobial activities of the crude extract and compounds of the root bark of Allanblackia floribunda

Context: Allanblackia floribunda Oliver (Guttiferae) is an African medicinal plant used traditionally to treat a variety of ailments. Objective:  We investigated the antitumor, radical scavenging, antimycobacterial, antibacterial and antifungal activities of the root bark extract of A. floribunda and three isolated phenolics, namely 1,7-dihydroxyxanthone (1), morelloflavone (2) and 7′-O-glucoside of morelloflavone (3). Materials and methods: The 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging assay was used for antioxidant tests, while crown gall tumor assay was used for assay of antitumor activity. The p-iodonitrotetrazolium chloride (INT) colorimetry and Microplate Alamar Blue Assay (MABA) were used for antimicrobial investigations. Results: Moderate tumor reducing activity was observed with the extract, while better activities were recorded with compounds 2 and 3. The antimycobacterial and antitumor activities of the extract are being reported for the first time. The DPPH radical scavenging test showed that all the studied samples were able to scavenge more than 50% of the free radical, with compound 3 showing the best inhibitory activity (IC50 of 49.08 µg/mL). Compounds 1 to 3 prevented the growth of Mycobacterium smegmatis and both extract and compound 2 were active on M. tuberculosis. The lowest MIC value for the extract (9.76 μg/mL) was recorded against Enterobacter aerogenes while the corresponding value for the compounds (4.88 µg/mL) was obtained with compound 2 on Trichophyton rubrum. Discussion and conclusion: The overall results of the present work provide baseline information for the potential use of the root bark extract of A. floribunda as an antimicrobial, antitumor and antioxidant phytomedicine.

Anticoccidial constituents from the stem bark of Turraeanthus africanus

In order to study some biological active products, phytochemical investigation of the stem bark of Turraeanthus africanus have led to the isolation of a novel compound 1, a new benzoic acid derivative, named turraeanthin C, and two known compounds sesamin (2) and stigmasterol. The structures of these compounds were established by spectral analysis, including two-dimensional nuclear magnetic resonance. The extract and the isolated compounds 1 and 2 showed noteworthy activity against Toxoplasma gondii intracellular parasite in mammals.