Chemistry and bioactivity studies of African medicinal plants Ximenia caffra, Hibiscus sabdariffa and Combretum micranthum
Creators: name: Zhen, Jing
Publisher: name: No Publisher Supplied
Year: 2016

description: Africa has been and continues to be an important source of medicinal plants yet only a relative few have been extensively studied. Three different traditional African medicinal plants Ximenia caffra, Hibiscus sabdariffa and Combretum micranthum, were selected for phytochemical investigations and potential pharmacological activities. For Ximenia caffra, more than ten polyphenol compounds were identified in the leaf sample using LC/UV/MS profiling, including gallic acid, catechin, quercetin, kaempferol and their derivatives. The antioxidant capacities of leaf extract were determined by Folin-Ciocalteu assay as 261.87 ± 7.11 mg GAE/g and ABTS free radical scavenging assay as 1.46 ± 0.01 mmol TE/g. The anti-proliferative effect of Ximenia caffra leaf extract was measured by MTS assay with IC50 value of 239.0 ± 44.5 µg/ml. Cell-based assays show that the leaf extract inhibits the mRNA expression of pro-inflammatory genes (iL-6, iNOS, and TNF- α) by using RT-qPCR, indicating its anti-inflammatory effects. Further studies suggest that the underlying therapeutic mechanism may involve the suppression of NF-κB, a shared pathway between cell death and inflammation. For Hibiscus sabdariffa, which is originally native to Africa, the phytochemical profile of leaves from 25 different populations from worldwide accessions were determined by LC/MS and compared with each other. Ten polyphenols including neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, quercetin, kaempferol and their glycosides were identified together with 5-(hydroxymethyl)furfural, some of which were quantified with commercially available standards. The leaves have shown anti-oxidant activities as measured by Folin-Ciocalteu assay and ABTS free radical scavenging assay. Leaves extracts reduced LPS-induced NO production in RAW 264.7 cell in a dose-dependent manner indicating the extract’s potential anti-inflammatory activity. The compound 5- HMF was identified in dried samples and later investigated as a biomarker of the freshness of the leaf samples. For plant Combretum micranthum, in prior phytochemical investigations, our lab identified a group of new skeleton compounds named kinkéloids. As a continuation of this project, two total synthetic methods for these novel compounds kinkéloids A group and B were developed, which were then applied for regioisomers determination, scale-up synthesis and potential analogues synthesis. The key and final step was achieved by Mannich reaction, through which the piperidine moiety coupled to the flavan moiety. One method goes through the synthesis of intermediate compound eriodictyol followed by further de-oxygenation using NaBH3CN, while the second scheme involves the formation of o-quinone methide and the inverse electron-demand Diels-Alder reaction. The identities of synthesized kinkéloids were further confirmed through the comparison with the ones in the plant leaves extract using LC/MS. The enantiomers of each previous identified flavan molecules in the leaf samples were successfully separated on AD-RH column. A series of novel kinkéloids analogues were synthesized with different flavonoid aglycones and the attached nitrogen-containing moieties. The synthesized analogues were screened for the inhibitory activity of α- glucosidase, in which compound 23 has the lowest IC50 of 4.1 μM. Kinetic analysis indicates synthesized compounds 15 and 23 inhibit enzyme in a non-competitive model with Ki value of 37.8 ± 0.8 and 13.2 ± 0.6 μM. Further docking study suggests that the preferred binding pocket is close to the catalytic center, correlating to the experimental results very well. Structure activity relationship study indicates that 4’-hyroxyl group and the 4-position carbonyl group are important for the inhibitory activity. Addition of extra hydrogen bonding and hydrophobic groups on ring A may increase the inhibitory activity.