Ellagitannins from Phyllanthus muellerianus: geraniin stimulates keratinocytes differentiation and collagen synthesis of skin dermal fibroblasts – new concept for improved wound-healing
Leaves from Phyllanthus muellerianus (Kuntze) Exell. are traditionally used for wound healing in western Africa. Aqueous extracts of dried leaves recently have been shown to stimulate proliferation of human keratinocytes and dermal fibroblasts . Within bioassay-guided fractionation the ellagitannins geraniin, corilagin, furosin, the flavonoids quercetin-3-O-β-D-glucoside (isoquercitrin), kaempferol-3-O-β-glucoside (astragalin), quercetin-3-O-rutinoside (rutin), as well as gallic acid, methyl gallate, caffeic acid, chlorogenic acid, 3,5-dicaffeoylquinic acid and caffeoylmalic acid (phaselic acid) have been identified in P. muellerianus for the first time. Geraniin was shown to be the dominant component of an aqueous extract (5.5%, m/m, related to the dried leaves). Geraniin and furosin increased the cellular energy status of human skin cells (normal human dermal fibroblasts, NHDF, HaCaT keratinocytes), triggering the cells towards higher proliferation rates, with fibroblasts being more sensitive than keratinocytes. Highest stimulation of NHDF by geraniin was found at 5µM, and of keratinocytes at 50 to 100µM. Furosin stimulated NHDF at about 50µM, keratinocytes at about 150 to 200µM. Toxicity of geraniin, as measured by LDH release, was observed at 20µM for NHDF and 150µM for keratinocytes. Toxicity of furosin – less than that of geraniin – was observed at >400µM. Furosin and geraniin stimulated the biosynthesis of collagen from NHDF at 50µM and 5–10µM respectively. Geraniin at 105µM significantly stimulated the differentiation in NHEK while furosin had a minor influence on the expression of involucrin and cytokeratins K1 and K10.
References: 1. Agyare et al., (2009). J. Ethnopharmacol. 125:393–403.