ISOLATION AND CHARACTERIZATION OF CHEMICAL CONSTITUENTS FROM CHRYSOPHYLLUM ALBIDUM G. DON-HOLL. STEM-BARK EXTRACTS AND THEIR ANTIOXIDANT AND ANTIBACTERIAL PROPERTIES.

BACKGROUND: The plant, Chrysophyllum albidum is indigenous to Nigeria and its stem-bark has wide application in traditional medicine for the treatment of infections and oxidative stress related diseases. The aim of the study was to isolate the chemical constituents responsible for the antioxidant and antibacterial activity from the stem-bark of the plant in order to justify some of its ethnomedicinal uses. MATERIALS AND METHODS: Crude extract of stem-bark of Chrysophyllum albidum obtained from 80% ethanol was successively partitioned with ethyl acetate (EtOAc) and n-butanol. The solvent fractions and isolated compounds were tested for antioxidant property using 2-2-diphenyl-1-picrylhydrazyl. Antibacterial activities were also assessed by means of agar-diffusion and broth micro dilution methods. EtOAc fraction was repeatedly fractionated on column chromatography to afford four compounds and their chemical structures were established using NMR (1D and 2D) and MS. RESULTS: Chromatographic fractionation of EtOAc fraction with the highest antioxidant and antimicrobial activities afforded stigmasterol (1),: epicatechin (2),: epigallocatechin (3): and procyanidin B5 (4).: Procyanidin B5 isolated for the first time from genus Chrysophyllum demonstrated the highest antioxidant activity with IC50 values of 8.8 µM and 11.20 µM in DPPH and nitric oxide assays respectively and equally demonstrated the highest inhibitory activity against Escherichia coli (MIC 156.25 µg/mL), Staphylococcus aureus (MIC 156.25 µg/mL), Pseudomonas aeruginosa (MIC 625 µg/mL) and Bacillus subtilis (MIC 156.25 µg/mL). CONCLUSION: The antibacterial and antioxidant activities of epicatechin, epigallocatechin and procyanidin B5 isolated from Chrysophyllum albidum stem-bark validate the folkloric uses.

Antioxidant activity and cytotoxicity study of the flavonol glycosides from Bauhinia galpinii.

The antioxidant activity of the crude extract and solvent fractions obtained from the leaves of Bauhinia galpinii was evaluated in terms of capacity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals. The crude extract and the more polar solvent fractions (ethyl acetate and butanol) showed considerable antioxidant activity. The antioxidant potential of the extracts, expressed as EC50, ranged between 28.85 +/- 1.28 microg mL(-1)and 118.16 +/- 6.41 microg mL(-1). L-Ascorbic acid was used as a standard (EC50 = 19.79 +/- 0.14 microM). Bioassay guided fractionation of the two active solvent fractions led to the isolation of three flavonoid glycosides, identified as: quercetin-3-O-galactopyranoside (1), myricetin-3-O-galactopyranoside (2), and 2''-O-rhamnosylvitexin (3). These compounds are reported for the first time from this species. The structures of the compounds were determined on the basis of spectral studies (1H NMR, 13C NMR and MS). Their antioxidant potential was evaluated using a DPPH spectrophotometric assay. Compound 2 had higher and 3 had lower antioxidant activity than L-ascorbic acid. No cytotoxic effects were displayed by compounds 1 and 3, but compound 2 was cytotoxic to Vero cells (LC50 = 74.68 microg mL(-1)) and bovine dermis cells (LC50 = 30.69 microg mL(-1)).

Clinical evaluation of Acalypha ointment in the treatment of superficial fungal skin diseases.

In an open non-comparative study to evaluate the efficacy and safety of Acalypha wilkesiana ointment in superficial fungal skin diseases, 32 Nigerian patients with clinical and mycological evidence of superficial mycoses were recruited. Twelve patients defaulted and were lost to follow up, while one patient withdrew because of intolerable excoriation at the site of the lesion. Of the 19 patients that completed the trial, clinical cure was achieved in 73.3% of the patients. The ointment was very efficacious in the treatment of Tinea pedis, Pityriasis versicolor and Candida intetrigo where the cure rate was 100% in each condition. It is recommended that Acalypha ointment can be used for the treatment of these superficial mycoses.

Antimicrobial constituents of the leaves of Acalypha wilkesiana and Aacalypha hispida.

An activity directed fractionation of a 50% aqueous ethanol extract of A. wilkesiana and A. hispida leaves resulted in the isolation of gallic acid, corilagin and geraniin as the compounds responsible for the observed antimicrobial activity. Quercetin 3-O-rutinoside and kaempferol 3-O-rutinoside were also isolated from the inactive fraction of A. hispida. The structures were established by permethylation, 2D - NMR ((1)H and (13)C) and MS data.

Antimicrobial spectrum of Alchornea cordifolia leaf extract.

The 50% aqueous ethanol extract of Alchornea cordifolia (Schum and Thonn) Muell. Arg. leaf was screened for activity against 74 microbial strains representing aerobic, facultative and anaerobic bacteria as well as fungi. The panel of test strains included organisms from culture collections as well as clinical and environmental isolates. A concentration of 5 mg/mL of extract inhibited 36.5% of the isolates and 95.9% were inhibited by a concentration of 20 mg/mL. Only three strains, all filamentous fungi, were not susceptible to 40 mg/mL of the extract, the highest concentration tested. The extract showed the best activity against gram-positive bacteria and yeasts with inhibitory concentrations against these organisms being under 5 mg/mL. The results demonstrate that the A. cordifolia extract has a very broad spectrum of activity and suggests that it may be useful in the treatment of various microbial infections.

Pharmacokinetics and bioavailability of drotaverine in humans.

The pharmacokinetics and bioavailability of drotaverine was studied in 10 healthy volunteers after administration of single 80 mg oral and intravenous doses of the HCl salt of the drug, in a crossover fashion. Plasma and urine samples were analyzed for the unchanged drug by HPLC. The pharmacokinetic parameters, such as elimination half-life, plasma clearance, renal clearance and apparent volume of distribution, were not influenced by the route of drug administration. The drug was mainly eliminated by non-renal routes since renal clearance accounted for only 0.31 +/- 0.13% of the total plasma clearance. The absolute bioavailability was variable and ranged from 24.5-91% with a mean of 58.2 +/- 18.2% (mean +/- SD). It is suggested that the high variation in the bioavailability of drotaverine HCl after oral administration may result in significant interindividual differences in therapeutic response.

Quantitative analysis of 1-naphthol in urine of neonates exposed to mothballs: the value in infants with unexplained anaemia.

In Nigeria, severe NNJ is common in babies exposed to mothballs and other icterogenic agents. High-performance liquid chromatographic (HPLC) method was employed for quantitative analysis of 1 and 2-naphtol in the urine of 50 neonates aged one to 19 days. Five of the 25 babies who had a history of exposure to mothballs, and none of the babies without a history of exposure had 1-naphtol in their urine. The value of 1-naphtol ranged between 0.75 and 11.69 micrograms/ml with mean of 5 +/- 5 micrograms/ml. The overall correlation coefficient (r) between bilirubin values and 1-naphtol was 0.1 while it was 1 in the three G-6-PD deficient infants. The procedure will be very useful in the evaluation of infants with unexplained NNJ, anaemia, acute haemolytic jaundice and haemoglobinuria if naphthalene poisoning is suspected.

Synthesis, stereochemistry, and analgesic activity of 4-mono- and 4,4-disubstituted 1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines.

The synthesis of 4-alkyl-, 4-aralkyl-, and 4-alkenyl-1,2,3,4,5,6-hexahydro-2,6-methano-3-benzazocines is described together with some 4,4-disubstituted and 8-hydroxy derivatives. Evidence of the stereochemistry of the 4-substituent was from 1H and 13C NMR. In the 4-methyl series the equatorial epimer 1b has a higher analgesic (hot-plate) potency than 1a, and 10a, 10c, and 10f are also good agonists. 5a afforded analgesic properties without an antagonist component. Surprisingly 10d, bearing an 8-OH function, was without analgesic activity, contrasting with the significant hot-plate activity exhibited by 1,2,3,4,5,6-hexahydro-3,5,6-trimethyl-2,6-methano-3-benzazocine. If the assumption is made that the more active enantiomorph in members of this series is configurationally related to (-)-morphine, then it may be that the enantiotopic edge in hexahydro-2,6-methano-3-benzazocines has a narrow steric requirement for analgesic responses.