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.

Anti-oxidative and anti-inflammatory activities of some isolated constituents from the stem bark of Allanblackia monticola Staner L.C (Guttiferae).

Stem bark of Allanblackia monticola has been used in association with others plant in the Cameroonian folk medicine for the treatment of various diseases such amoebic dysentery, diarrhoea, lung infections, and skin diseases. The methylene chloride fraction, its isolated compounds like alpha-mangostin, lupeol and acid betulinic were screened for antioxidant activity using free radical scavenging method. These isolated compounds were further tested for anti-inflammatory properties using carrageenan-induced model. Methylene chloride fraction, showed concentration-dependent radical scavenging activity, by inhibiting 1,1-diphenyl-1-picryl-hydrazyl radical (DPPH) with an IC(50) value of 14.60 microg/ml. alpha-Mangostin and betulinic acid (500 microg/ml), showed weak radical scavenging activity with a maximum inhibition reaching 38.07 microg/ml and 26.38 microg/ml, respectively. Betulinic acid, lupeol and alpha-mangostin (5 mg/kg and 9.37 mg/kg) showed anti-inflammatory activity with a maximum inhibition of 57.89%, 57.14% and 38.70%, respectively. Methylene chloride fraction of Allanblackia monticola and some derivatives, have antioxidant and anti-inflammatory activities.

Apoptotic effects on B-cell chronic lymphocytic leukemia (B-CLL) cells of heterocyclic compounds isolated from Guttiferaes.

A series of 10 heterocyclic compounds purified from Allanblackia were tested on two B cell lines, ESKOL and EHEB, and on cells from B-CLL patients. Several molecules inhibited the proliferation of both cell lines and promoted apoptosis of B-CLL cells through different mechanisms, some of them elicited a dissipation of the mitochondrial transmembrane potential, other triggered caspase-3 activation and cleavage of the inducible nitric oxide synthase. Blood mononuclear cells and B-lymphocytes from healthy donors appeared less sensitive than B-CLL cells. These results indicate that these molecules may be of interest in the development of new therapies for B-CLL.

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.

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.

Vasodilator effect of the extracts and some coumarins from the stem bark of Mammea africana (Guttiferae).

CH(2)Cl(2) fraction obtained from the stem bark of Mammea africana inhibited noradrenaline (NA) or KCl-induced contraction in isolated guinea pig and rat aorta. The vasorelaxant potency of the CH(2)Cl(2) fraction of Mammea africana was diminished by a pre-treatment with Nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, which was however not affected by indomethacin pre-treatment. These findings indicated that the vasorelaxant effect of Mammea africana may be partially endothelium dependent, mediated by nitric oxide and that vasoactive prostanoids might not be contributing to the vasorelaxation effect. Three bioactive compounds were isolated from this CH(2)Cl(2) fraction and identified as 4-n-propylcoumarins (1) (mammea B/BB), 4-phenylcoumarins (2) (mammea A/AA or mammeisin) and (B/BA) (3) and might involved in the vasorelaxant effect of the extract. The mechanisms of the vasorelaxant effect might therefore be multiple, including endothelium dependence and the mechanisms, which interfere with the liberation of Ca(2+) into the muscle cell.

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

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, alpha-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 (IC(50)) recorded varied from 0.7 to 83.5 mug/ml. The cytotoxicities of the compounds and crude extract, against cultures of human melanoma cells (A375), were then investigated, and cytotoxicity/antimalarial IC(50) 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.

Secondary metabolites from Senecio burtonii (Compositae).

A cacalolide derivative named 4alpha-[2'-hydroxymethylacryloxy]-1beta-hydroxy-14-(5-->6) abeo eremophilan-12,8-olide and a shikimic acid derivative named (3'E)-(1alpha)-3-hydroxymethyl-4beta,5alpha-dimethoxycyclohex-2-enyloctadec-3'-enoate along with three known compounds, octacosan-1-ol, 3beta-hydroxyolean-12-en-28-oic acid and 3beta-acetoxyolean-12-en-28-oic acid were isolated from Senecio burtonii. Their structures and relative configurations were established on the basis of spectroscopic analysis.

Cytotoxic and antimicrobial coumarins from Mammea africana.

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.

Scaphopetalone and scaphopetalumate, a lignan and a triterpene ester from Scaphopetalum thonneri.

From the methanol extract of the stem bark of Scaphopetalum thonneri, two new compounds, including one lignan, named scaphopetalone, one new ester of ferulic acid, named scaphopetalumate were isolated together with three known compounds including: two coumarins (scopoletin and scopolin), and one pentacyclic triterpene (oleanolic acid). The structure of the new compounds were elucidated by means of spectroscopic analyses.