From Ethnopharmacological Field Study to Phytochemistry and Preclinical Research: The Example of Ghanaian Medicinal Plants for Improved Wound Healing

After prolonged exposure to ascorbate, collagen synthesis in cultured human skin fibroblasts increased approximately 8-fold with no significant change in synthesis of noncollagen protein. This effect of ascorbate appears to be unrelated to its cofactor function in collagen hydroxylation. The collagenous protein secreted in the absence of added ascorbate was normal in hydroxylysine but was mildly deficient in hydroxyproline. In parallel experiments, lysine hydroxylase (peptidyllysine, 2-oxoglutarate:oxygen 5-oxidoreductase, EC 1.14.11.4) activity increased 3-fold in response to ascorbate administration whereas proline hydroxylase (prolyl-glycyl-peptide, 2-oxoglutarate:oxygen oxidoreductase, EC 1.14.11.2) activity decreased considerably. These results suggest that collage polypeptide synthesis, posttranslational hydroxylations, and activities of the two hydroxylases are independently regulated by ascorbate.

Wounds represent a major health burden and drain on healthcare resources in the world including Ghana and Africa. The majority of the people of Ghana and Africa still patronize traditional medicine for their health needs including various forms of wounds. The aim of this study is the identification of medicinal plants, type of wounds, dosage forms and collection methods used traditionally in treating wounds in the Bosomtwi-Atwima-Kwanwoma district, Ghana. In vitro screening of selected extracts from these plants on cell physiology of human dermal fibroblasts and keratinocytes was to be performed. Validated questionnaires were administered to 78 traditional healers in 54 communities of the district. Interviews and structured conversations were used to administer the questionnaires. Selected herbal material dominantly used by the healers was collected, identified and aqueous and ethanolic extracts were investigated in vitro on influence on cell physiology of keratinocytes and dermal fibroblasts (MTT-, BrdU-, LDH-assay). Antioxidant activities of ethanolic extracts were determined by free radical scavenging activity. Antiadhesive activity against Helicobacter pylori on human stomach cells was investigated for extracts reported to be used for stomach ulcer treatment. The ethnopharmacological survey revealed 104 plants species belonging to 47 families. The detailed use of these plants is documented. Aqueous extracts of Phyllanthus muellerianus, Pycnanthus angolensis and Combretum smeathmanni influenced the mitochondrial activity and proliferation of dermal fibroblasts and keratinocytes significantly. Ethanolic extracts of selected plants exhibited strong antioxidant activities comparable to alpha-tocopherol. For Spathodea campanulata, Hoslundia opposita and Pycnanthus angolensis, which were reported by the healers to be used also for wound healing in case of stomach ulcers, strong antiadhesive activity against Helicobacter pylori was demonstrated, while the extracts did not exhibit any direct cytotoxicity against the bacterium. Traditional use of many wound-healing plants from Ghana can be well rationalized by the in vitro investigation of aqueous extracts. E.g. extracts of Phyllanthus muellerianus, Pycnanthus angolensis and Combretum smeathmanni exhibited significant influence on the cell viability and proliferation of keratinocytes and dermal fibroblasts.

Phyllanthus urinaria Linnea (Euphorbiaceae) is a widely used traditional medicinal plant by oriental countries and has been reported to possess various biological activities. Previously, the acetone extract from Phyllanthus urinaria was found to inhibit herpes simplex virus (HSV) infection. In this study, geraniin and 1,3,4,6-tetra-O-galloyl-beta-D-glucose (1346TOGDG), both of which were isolated from the acetone extract of Phyllanthus urinaria, were examined for their activity against HSV-1 and HSV-2 in vitro. Results showed that geraniin actively suppressed HSV-2 infection, whereas 1346TOGDG effectively inhibited HSV-1 infection. The 50% inhibitory concentration (IC(50)) was 18.4+/-2.0 microM for geraniin against HSV-2 infection, and 19.2+/-4.0 microM for 1346TOGDG against HSV-1. No toxic effect towards the host cell was observed at the antiviral concentrations. In conclusion, geraniin and 1346TOGDG were found to inhibit HSV-1 and HSV-2 multiplication at different magnitudes of potency.