ABSTRACT
CONTEXT: Cussonia arborea Hochst. ex A. Rich (Araliaceae) is a folk medicine used to treat various diseases. However, there is no report of the root phytochemistry. OBJECTIVE: This study isolates and identifies the immunomodulatory compounds from root-bark of C. arborea. MATERIALS AND METHODS: The methanol extract (18 g) was subjected to repeated column chromatography resulting in isolation of five compounds (1-5). Structure determination was achieved by analysis of their 1 D and 2 D NMR, and mass spectroscopy. The compounds (100-1.0 µg/mL) were examined immunomodulatory for effect on production of reactive oxygen species (ROS) from whole blood phagocytes and on proliferation of T-cells. The compounds cytotoxicity (100-1.0 µg/mL) was evaluated on NIH-3T3 normal fibroblast cells. RESULTS: Three pentacyclic triterpenoids [3, 23-dihydroxy-12-oleanen-28-oic acid (1), 3ß-hydroxylolean-12-en-28-oic (2) and 23-hydoxy-oxo-urs-12-en-28-oic acid (5)], two phytosterols: [stigmasterol (3)] and [3-O-ß-d-glucopyranosyl stigmasterol (4)] were all isolated from the methanol soluble extract. All the tested compounds (1-4) were found to be nontoxic on NIH-3T3 cells. Compound 1 and 2 moderately inhibited the production of ROS (IC50 = 24.4 ± 4.3 and 37.5 ± 0.1 µg/mL, respectively) whereas compound 2 exhibited the highest inhibitory effect (IC50 = 12.6 ± 0.4 µg/mL) on proliferation of phytoheamagglutinin (PHA) activated T-cells. CONCLUSIONS: The isolated compounds (1-5) are reported for the first time from this species. In addition, compound 2 with suppressive potential on production of intracellular ROS and proliferation of T-cells could be of immense value in control of autoimmune diseases as well as in immune compromised patients.
Subject(s)
Araliaceae/chemistry , Immunologic Factors/pharmacology , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Animals , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Humans , Immunologic Factors/administration & dosage , Immunologic Factors/isolation & purification , Inhibitory Concentration 50 , Magnetic Resonance Spectroscopy , Mass Spectrometry , Medicine, Traditional/methods , Mice , NIH 3T3 Cells , Plant Bark , Plant Extracts/administration & dosage , T-Lymphocytes/drug effects , T-Lymphocytes/metabolismABSTRACT
BACKGROUND: There is a lack of information on CYP2D6, a major metabolizing enzyme, in Africa ethnic nationalities. The objective was to determine CYP2D6 phenotype in Yoruba Nigerians using dextromethorphan (DEX). METHOD: A total of 89 healthy volunteers received 30 mg of DEX orally followed by blood and urine sample collection at 3-hour and over 8 h post-dose, respectively. DEX and dextrorphan (DOR) concentrations were determined using High Performance Liquid Chromatography (HPLC). The metabolic ratio (MR, DEX/DOR) were plotted for the phenotype determination. RESULTS: The log MR that separated poor (PMs) from normal metabolizers (NMs) was 0.28 and 0.75 for urine and plasma, respectively. Two subjects (2.3%) identified as PMs had a mean MR of 17 and 3.2 in plasma and urine, significantly higher than that of NMs (p < .0001). A positive correlation between urine and plasma MR was noted. CONCLUSION: The prevalence of PMs in the Yoruba Nigerians was similar to that reported among blacks.
