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Planta Med 2003; 69(8): 725-732
DOI: 10.1055/s-2003-42791
Original Paper
Biochemistry, Physiology, in vitro-Cultures
© Georg Thieme Verlag Stuttgart · New York

Gene Expression Changes in the Human Fibroblast Induced by Centella asiatica Triterpenoids

Christopher D. Coldren1, 2, 3, 7 , Puziah Hashim1, 4, 5 , Johari Mohd. Ali1, 2, 6 , Se-Kyung Oh1, 4 , Anthony J. Sinskey1, 2 , ChoKyun Rha1, 4
  • 1Malaysia-MIT Biotechnology Partnership Program,
  • 2Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
  • 3BioMicro Center, Massachusetts Institute of Technology, Cambridge, MA, USA
  • 4Biomaterials Science and Engineering Laboratory, Massachusetts Institute of Technology, Cambridge, MA, USA
  • 5Bioprocess and Chemical Technology Center, Standard and Industrial Research Institute of Malaysia, Shah Alam, Malaysia
  • 6University of Malaya, 50603 Kuala Lumpur, Malaysia
  • 7Current address: Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, CO, USA
This research is funded by the Malaysia-MIT Biotechnology Partnership Program (MMBPP), Natural Product Discovery sub program, phase I. C.D.C. acknowledges the support of an N.I.H. Genome Sciences training grant.
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Publikationsverlauf

Received: November 26, 2002

Accepted: April 18, 2003

Publikationsdatum:
06. Oktober 2003 (online)

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Abstract

The molecular pathways underlying the diverse biological activity of the triterpeniod compounds isolated from the tropical medicinal plant Centella asiatica were studied with gene microarrays and real-time reverse transcription polymerase chain reaction (real-time RT-PCR) to quantify the expression of 1053 human genes in human fibroblasts. Fibroblast cells grown in culture were used as a model system to evaluate the stimulation of wound healing by titrated extract from Centella asiatica (TECA) as well as by the four principal triterpenoid components of Centella. TECA treatment effects the expression of genes involved in angiogenesis and the remodeling of extracellular matrix, as well as diverse growth factor genes. The extent of expression change of TNFAIP6, an extracellular hyaluronan binding protein, was found to be largely dose-dependent, to respond most strongly to the free acids asiatic acid and madecassic acid, and to increase in expression over 48 hours of treatment. These results show that Centella triterpenes evoke a gene-expression response consistent with their prevailing medical uses in the treatment of connective tissue disorders such as wound healing and microangiopathy. The identification of genes modulated by these compounds provides the basis for a molecular understanding of Centella’s bioactivity, and opportunities for the quantitative correlation of this activity with clinical effectiveness at a molecular level.

Abbreviations

TNFAIP6:tumor necrosis factor alpha, induced protein 6

ECM:extracellular matrix

AA: asiatic acid

MA:madecassic acid

AS: asiaticoside

MS:madecassoside

TECA:titrated extract of Centella asiatica

MTT:3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium

GAPDH:glyceraldehyde-3-phosphate dehydrogenase

Key words

Centella asiatica - Apiaceae - asiatic acid - madecassic acid - wound healing - gene expression

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Dr. ChoKyun Rha

Biomaterials Science and Engineering Laboratory, 56-265

Massachusetts Institute of Technology

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eMail: ckrha@mit.edu