| Diabetes mellitus has long been a clinical problem for hundreds of years. More than 194 million people in the world now suffer from the disorder. About 15% of all diabetic patients would develop unhealing foot ulcers which compile significant proportion of nontraumatic lower-extremity amputations. Basing on the clinical experience of Prof. Xi Jiu Yi in Shanghai, literature review and an innovative interpretation of traditional Chinese medicine, two formulae (F1 & F2) derived from a well known herbal formula: the "Pills of Six Drugs with Rehmannia" were created for clinical trials. With the early successful limb salvage rate of over 80% observed in a clinical series studied at the Prince of Wales Hospital, Hong Kong, multi-directional studies on the two formulae were carried out. The aim was to find out the clinical efficacy of Formulae 1 & 2, and their component herbs, and the biological mechanism of action. A series of in-vitro, ex-vivo and in-vivo experimental models were completed for the latter purposes.;Granulation formation is an important issue essential for ulcer healing. Therefore a CRL-7522 fibroblast cell line and primary fibrobass from eight diabetic foot ulcer patients (ex-vivo) were used to detect the granulation enhancing activities of the Formulae 1 & 2 and component herbs. The two formulae and some of their component herbs viz, Radix Astragali (HQ), Radix Rehmanniae (SD) and Rhizoma Atractylodis Macrocephalae (BZ) showed significant enhancement effects on the cell viability and apparently facilitated granulation formation. Hence the Formulae 1 & 2, and the three component herbs were selected for further studies. The other nine component herbs of the formulae were found to have no significant enhancing effects on cell viability. With an established diabetic rat model (n0 STZ and n5 STZ), a piece of full-thickness skin was removed from the foot of the rat to develop a diabetic rat foot ulcer model. The ulcer area was measured by a specially designed area measuring programme, namely the Image Analytical Programme. The ulcer areas and their percentage reductions over time were recorded and analysed using statistical multilevel models with adjustments for weight, blood glucose level and the presence of extra ulcers. Results revealed that the ulcer area was significantly reduced by the Formulae 1 & 2, and one of their component herbs, Radix Rehmanniae (SD).;Basing on the traditional TCM interpretation, experience of recent research studies and our experimental findings, a few component herbs in Formulae 1 & 2 would be tentatively selected for a new formula. They were Radix Rehmanniae, Radix Astragali, Rhizoma Atractylodis Macrocephalae, Rhizoma Alismatis, Cortex Moutan and Rhizoma Smilacis Chinensis. Whether the new formula could give better efficacy would need to be tested in new clinical trials and experimental models. (Abstract shortened by UMI.). |
