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|Title: ||Ellagitannins from Phyllanthus muellerianus (Kuntze) Exell.: Geraniin and furosin stimulate cellular activity, differentiation and collagen synthesis of human skin keratinocytes and dermal fibroblasts|
|Authors: ||Agyare, Christian|
|Keywords: ||Phyllanthus muellerianus (Kuntze) Exell.|
|Issue Date: ||2011|
|Citation: ||Phytomedicine, 18 (2011); 617–624|
|Abstract: ||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
(1), corilagin (2), furosin (3), the flavonoids quercetin-3-O- -d-glucoside (isoquercitrin), kaempferol-3-
O- -d-glucoside (astragalin), quercetin-3-O-d-rutinoside (rutin), 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
Suitable analytical methods for quality control of geraniin in P. muellerianus extract (methanol/water,
70/30) have been developed and validated based on ICH guidelines (ICH-compliant protocol).
Geraniin and furosin increased the cellular energy status of human skin cells (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 5 M, and of keratinocytes
at 50–100 M. Furosin stimulated NHDF at about 50 M, keratinocytes at about 150–200 M.
Necrotic cytotoxicity of geraniin, as measured by LDH release, was observed at 20 M for NHDF and
150 M for keratinocytes. Toxicity of furosin – less than that of geraniin – was observed at >400 M.
Furosin and geraniin stimulated the biosynthesis of collagen from NHDF at 50 Mand 5–10 Mrespectively.
Geraniin at 105 Msignificantly stimulated the differentiation in NHEK while furosin had a minor
influence on the expression of involucrin and cytokeratins K1 and K10. The study proves clearly that
hydrophilic extracts from P. muellerianus and especially the lead compound geraniin exhibit stimulating
activity on dermal fibroblasts and keratinocytes, leading to increased cell proliferation, barrier formation
and formation of extracellular matrix proteins. From these findings the traditional clinical use of such
extracts for wound healing seems to be justified.|
|Description: ||An article published by Phytomedicine, 18 (2011); 617–624|
|Appears in Collections:||College of Health Sciences|
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