Configuration of the vitamin E analogue garcinoic acid extracted from Garcinia Kola seeds

Vitamin E derivatives bearing a carboxylic group have recently gained great attention because of their antitumoral properties. Garcinoic acid (trans-13'-carboxy-delta-tocotrienol) is a vitamin E analog extracted from Garcinia Kola seeds in which the carboxylic group is at the end of the aliphatic side chain and reported to be a racemate based on the optical rotation measurements. However, CD determination of a sample of the acid analyzed by us gave a positive peak at 208 nm, indicating that it is not a racemate. To assess the enantiomeric composition of garcinoic acid, it was thus transformed to alpha-tocopherol and analyzed by chiral HPLC on column OD-H. On the basis of the elution order of alpha-tocopherol stereoisomers, the garcinoic acid sample resulted to be enantiopure with R configuration at carbon 2 of the chroman ring. Moreover, in a preliminary test, the acid and some of its derivatives showed a marked antiproliferative effect on glioma C6 cancer cells.     

Evaluation of metabolic,antioxidant and anti-inflammatory effects of Garcinia kola on diabetic rats

Garcinia kola (G. kola), is a plant characterized by its hypoglycemic properties. We recently reported our findings on the extracts of G. kola, in which we found that it prevented the loss of inflammation-sensible neuronal populations in streptozotocin (STZ)-induced rat models of type 1 diabetes mellitus (T1DM).In the present study we assessed the effect of G. kola bioactive compounds extracted successively with water, hexane, methylene chloride, ethyl acetate, and butanol. through analyzing biochemical markers of oxidative stress, inflammation, and metabolic function in STZ-induced diabetic animals.Animals made diabetic by a single injection with STZ (60 mg/kg, i.p.), were treated daily with either vehicle solution, insulin, or G. kola extracts and its fractions from the first to the 6th-week post-injection. Biochemical markers; glucose, insulin, C-peptide, neuron-specific enolase (NSE), creatinine kinase, glutathione peroxidase, malondialdehyde (MDA), resistin, soluble E-selectin (SE-Selectin), and C-reactive proteins (CRP) levels in the sera were determined in the study groups. A marked increase in blood glucose (209.26% of baseline value), and a decrease in body weight (−12.37%) were observed in diabetic control animals but not in animals treated with either insulin or G. kola extracts and its fractions. The sub-fraction F5, G. kola ethyl acetate had the highest bioactive activities, with a maintenance of blood sugar, malondialdehyde, C-peptide, E-selectin, C-reactive protein (CRP) and neuron-specific enolase (NSE) to levels and responses comparable to healthy non-diabetic vehicle group and the positive control diabetic insulin-treated group.Our findings suggest that G. kola may have a strong therapeutic potential against T1DM and its microvascular complications.     

Gas chromatography-mass spectrometry characterisation of the anti-Listeria components of Garcinia kola seeds

Adsorption chromatography was used to separate the bioactive constituents of the crude n-hexane extract of Garcinia kola seeds. The silica gel 60 column fractions were eluted using the solvent combination of benzene:ethanol:ammonium hydroxide (BEA) in the ratio combination of 36:4:0.4 v/v. The fractions were tested for anti-Listeria activities by determining their MIC₅₀, MIC₉₀ or MIC against 4 Listeria isolates. The fractions were labelled BEA1 to BEA5 and 3 out of the 5 fractions eluted were active against the test Listeria species with MIC’s ranging from MIC 0.157 mg/mL to MIC₅₀ 0.625 mg/mL. The most active fractions, BEA2 and BEA3, were subjected to gas chromatography coupled to mass spectrometry (GC-MS) to identify their composition. Fraction BEA2 constituted of 18 compounds mostly sterols and the BEA3 fraction contained 27 compounds with the most abundant compounds being fatty acids derivatives. The BEA2 fraction’s interactions with antibiotics proved to be 100% synergistic with ciprofloxacin and ampicillin whilst it exhibited 50% additivity and 50% synergism with penicillin G. However, all the interactions of the BEA2 fraction with each of the conventional antibiotics used were synergistic against the human listeriosis causative bacteria Listeria monocytogenes.     

Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia

R.U.B. EBANA, B.E. MADUNAGU, E.D. EKPE AND I.N. OTUNG. 1991. The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, pydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa , β-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed.     

Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia.

The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, hydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, beta-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed.     

Anti-ulcerogenic and proton pump (H+, K+ ATPase) inhibitory activity of Kolaviron from Garcinia kola Heckel in rodents

Anti-ulcer potential and proton pump inhibitory activity of kolaviron (KV) isolated from Garcinia kola Heckel has been evaluated using different ulcer models. Cold-restraint (CRU), aspirin (ASP), alcohol (AL), pyloric ligation (PL) induced gastric ulcer models were used to assess anti-ulcerogenic activity of KV in rats. Effects of KV on gastric juice for free and total acidity, peptic activity and mucin secretion were also evaluated. The H+, K+-ATPase activity was assayed in gastric microsomes, spectrophotometrically. Results of this study showed that KV (200 mg/kg) reduced the incidence of ulcers in CRU (69.0%), PL (67.6%), ASP (68.6%) and AL (51.5%). Reductions were also observed in free acidity (32.6%), total acidity (56.2%) and peptic activity (35.4%) with increase in mucin secretion by 40.1%. KV inhibited the H+,K+-ATPase activity with IC50 of 43.8 microg/ml compared with omeprazole with IC50 of 32.3 microg/ml. KV showed both cytoprotective and anti-secretory potentials against peptic ulcer models, and a proton pump inhibitory activity. KV may emerge as a potent anti-ulcer compound.     

Antifungal garcinia acid esters from the fruits of Garcinia atroviridis

Two new garcinia acid derivatives, 2-(butoxycarbonylmethyl)-3-butoxycarbonyl-2-hydroxy-3-propanolide and 1',1"-dibutyl methyl hydroxycitrate, were isolated from the fruits of Garcinia atroviridis guided by TLC bioautography against the fungus Cladosporium herbarum. The structures of these compounds were established by spectral analysis. The former compound represents a unique beta-lactone structure and the latter compound is most likely an artefact of garcinia acid (= hydroxycitric acid). Both compounds showed selective antifungal activity comparable to that of cycloheximide (MID: 0.5 microg/spot) only against C herbarum at the MIDs of 0.4 and 0.8 microg/spot but were inactive against bacteria (Bacillus subtilis, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli), other fungi (Alternaria sp., Fusarium moniliforme and Aspergillus ochraceous) including the yeast Candida albicans.     

Xanthones and benzophenones from Garcinia griffithii and Garcinia mangostana

A new polyisoprenylated benzophenone, guttiferone I, together with the known compounds cambogin, 1,7-dihydroxyxanthone, 1,3,6,7-tetrahydroxyxanthone and 1,3,5,6-tetrahydroxyxanthone were isolated from the stem bark of Garcinia griffithii. The acetone extract of the heartwood of Garcinia mangostana contained one new diprenylated xanthone (mangoxanthone) and a new benzophenone (3',6-dihydroxy-2,4,4'-trimethoxybenzophenone) as well as the known xanthones dulxanthone D, 1,3,7-trihydroxy-2-methoxyxanthone, 1,3,5-trihydroxy-13,13-dimethyl-2H-pyran[7,6-b]xanthen-9-one. Their structures were established on the basis of spectroscopic studies and chemical correlation.     

Fatty acid synthase inhibitors of phenolic constituents isolated from Garcinia mangostana

Natural inhibitors of fatty acid synthase (FAS) are emerging as potential therapeutic agents to treat cancer and obesity. The bioassay-guided chemical investigation of the hulls of Garcinia mangostana led to the isolation of 13 phenolic compounds (1–13) mainly including xanthone and benzophenone, in which compounds 7, 8, 9, 10, and 11 were isolated from this plant for the first time and compound 9 was a new natural product. These isolates possess strong inhibitory activity of FAS with the IC₅₀ values ranging from 1.24 to 91.07 μM. The study indicates that two types of natural products, xanthones and benzophenones, could be considered as promising FAS inhibitors.     

Histological alterations by a diet containing seeds of Garcinia kola: effect on liver, kidney, and intestine in the rat

Histological examination of liver, kidney, and duodenum of rats fed a diet containing 10% (w/w) dry powdered seeds of Garcinia kola for 6 weeks revealed cellular changes that were not observed in pair-fed control animals. The main cellular changes observed in the rats fed on Garcinia kola diet included vacuolation of duodenal villous epithelial cells, numerous intracytoplasmic vacuoles in hepatocytes, and mild hydropic degeneration in cells of the renal proximal tubular epithelium. These changes are probably due to the flavonoids contained in G. kola seeds.     

Xanthones from three Garcinia species

From the stem bark of three previously uninvestigated Garcinia species a number of xanthones have been isolated including three that appear to be novel. The novel compounds are characterized as isocowanin (8-geranyl-4-(3,3-dimethylallyl)-7-methoxy-1,3,6-trihydroxyxanthone), isocowanol (8-geranyl-4-(3-hydroxymethyl-3-methylallyl)-7-methoxy-1,3,6-trihydroxyxanthone) and nervosaxanthone (4,8-di(3,3-dimethylallyl)-2-(1,1-dimethylallyl)-1,3,5,6-tetrahydroxyxanthone). The chemotaxonomic significance of oxygenation patterns in these xanthones is briefly discussed.     

Evaluating antioxidative activities of amino acid substitutions on mastoparan-B

Mastoparan-B is a peptide toxin isolated from the venom of Vespa basalis, the most dangerous hornet found in Taiwan. This study is aimed to evaluate the antioxidative activities of several amino acid substitutions on MP-B, and examined the influences of mast cell degranulation and hemolytic activities in parallel with antioxidative activities. The correlations between the biological function and amino acid sequence were assessed. Our study shows original MP-B is a valuable antioxidant at low concentration in competing with nitric-oxide for oxygen molecules and possesses good antioxidative enzyme activities resembled to superoxidase dismutase and glutathione peroxidase. And there are no predominant rates of mast cell degranulation and hemolytic effects in such condition. With proper substitutions, the reducing power, DPPH scavenging activity and glutathione reductase-like enzyme activity of MP-B can increase clearly. The results demonstrate that MP-B analogs are very potential to be applicable antioxidants for other antioxidative usages.     

Molecular design of anti-MRSA agents based on the anacardic acid scaffold

A series of anacardic acid analogues possessing different side chains viz. phenolic, branched, and alicyclic were synthesized and their antibacterial activity tested against methicillin-resistant Staphylococcus aureus (MRSA). The maximum activity against this bacterium occurred with the branched side-chain analogue, 6-(4',8'-dimethylnonyl)salicylic acid, and the alicyclic side-chain analogue, 6-cyclododecylmethyl salicylic acid, with the minimum inhibitory concentration (MIC) of 0.39 microg/mL, respectively. This activity was superior to that of the most potent antibacterial anacardic acid isolated from the cashew Anacardium occidentale (Anacardiaceae), apple and nut, that is, the 6-[8'(Z),11'(Z),14'-pentadecatrienyl]salicylic acid.     

Anti-ageing effects of protocatechuic acid from Alpinia on spleen and liver antioxidative system of senescent mice

The effects of Alpinia protocatechuic acid (PCA) on spleen and liver antioxidant system in aged rats have been studied. Alpinia PCA, a phenolic compound, was first isolated from the dried fruits of Alpinia Oxyphylla Miq. in our laboratory. Young and aged rats were injected intraperitoneally with Alpinia PCA at single doses of 5 mg kg(-1) (low dose) or 10 mg kg(-1) (high dose) per day for 7 days. The activities of endogenous antioxidants and the content of lipid peroxide in spleen and liver were assayed. Compared with young group, aged rats had significantly lower splenic weights, lower activities of glutathione peroxidase (GSH-PX) and catalase (CAT), higher level of malondialdehyde (MDA) in spleen and liver. The results proved that Alpinia PCA significantly elevated the splenic weights, increased the activities of GSH-PX and CAT and decreased the MDA level of aged rats. All these suggested that Alpinia PCA was a potential anti-ageing agent, and its effects on spleen and liver were achieved at least partly by promoting endogenous antioxidant enzymatic activities and normalizing age-associated alterations. It may be therapeutically useful to minimize age-associated disorders where oxidative damage is the major cause.     

Xanthones from the heartwood of Garcinia mangostana

Twelve xanthones were isolated from the hexane extract of the heartwood of Garcinia mangostana from Myanmar. Their structures were determined using 1D and 2D NMR techniques     

Xanthones from the bark of Garcinia merguensis

The bark of Garcinia merguensis yielded 10 xanthones, merguenone, 1,5-dihydroxy-6'-methyl-6'-(4-methyl-3-pentenyl)-pyrano(2',3':3,2)-xanthone, subelliptenone H, 8-deoxygartanin, rheediaxanthone A, morusignin G, 6-deoxyjacareubin, 1,3,5-trihydroxy-4,8-di(3-methylbut-2-enyl)-xanthone, rheediachromenoxanthone and 6-deoxyisojacareubin. The structure of merguenone was determined using spectroscopic techniques, mainly 1D and 2D NMR spectroscopy.     

Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii

The antimalarial activity of 22 xanthones against chloroquino-resistant strains of Plasmodium falciparum was evaluated. Natural caloxanthone C (1), demethylcalabaxanthone (2), calothwaitesixanthone (3), calozeyloxanthone (4), dombakinaxanthone (5), macluraxanthone (6), and 6-deoxy-gamma-mangostin (7) were isolated from Calophyllum caledonicum. 1,6-dihydroxyxanthone (8), pancixanthone A (9), isocudraniaxanthone B (10), isocudraniaxanthone A (11), 2-deprenylrheediaxanthone B (12) and 1,4,5-trihydroxyxanthone (13) were isolated from Garcinia vieillardii. Moreover, synthetic compounds (14-22) are analogues or intermediates of xanthones purified from Calophyllum caledonicum (Oger J.M., Morel C., Helesbeux J.J., Litaudon M., Seraphin D., Dartiguelongue C., Larcher G., Richomme P., Duval O. 2003. First 2-Hydroxy-3-Methylbut-3-Enyl substituted xanthones isolated from Plants: structure elucidation, synthesis and antifungal activity. Natural Product Research 17(3), 195-199; Helesbeux J.J., Duval O., Dartiguelongue C., Seraphin D., Oger J.M., Richomme P., 2004. Synthesis of 2-hydroxy-3-methylbut-3-enyl substituted coumarins and xanthones as natural products. Application of the Schenck ene reaction of singlet oxygen with ortho-prenylphenol precursors. Tetrahedron 60(10), 2293-2300). The relationship between antimalarial activity and molecular structure of xanthones has also been explored. The most potent xanthones (2), (3) and (7) (IC50 = c.a. 1.0 microg/mL) are 1,3,7 trioxygenated and prenylated on the positions 2 and 8.     

Phenolic compounds from the flowers of Garcinia dulcis

Dulcisxanthones C-F and dulcinone together with 22 known compounds were isolated from the flowers of Garcinia dulcis. Their structures were determined by spectroscopic methods. The abilities of some of these compounds to act as radical scavengers and antibacterial agents were investigated.