Planta Medica International Open 2017; 4(S 01): S1-S202
DOI: 10.1055/s-0037-1608052
Poster Session
Georg Thieme Verlag KG Stuttgart · New York

Cryptotanshinone from Salvia miltiorrhiza Bunge lowers the Cytokeratin 1/10 expression in primary human Keratinocytes in vitro

S Esch
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
A Hensel
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
S Brandt
1   University of Münster, Institute of Pharmaceutical Biology and Phytochemistry, Münster, Germany
,
S König
2   University of Münster, Interdisciplinary Centre for Clinical Research, Core Unit Proteomics, Münster, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
24 October 2017 (online)

 

Salvia miltiorrhiza Bunge (danshen) is commonly used in TCM to treat vascular and coronary heart diseases and is also applied in psoriasis therapy. Cryptotanshinone, one out of four characteristic tanshinones found in danshen, shows an activity versus hypertrophic scars [1]. This inspired subsequent research on potential effects of S. miltiorrhiza extract and cryptotanshinone on the differentiation process of primary human keratinocytes (NHEK).

A quantified EtOH 50% extract from S. miltiorrhiza roots (50 µg/mL) reduced cytokeratin 10 (KRT10) expression in NHEK over seven days nearly to the limit of detection (Western blot analysis), whereas involucrin (IVL) expression remained unchanged. This dramatic changes in keratinocyte differentiation by the extract could be assigned to the presence of cryptotanshinone, which suppresses the KRT1/10 expression at 1µM nearly completely. This was also proven by gene expression analysis by qPCR: The gene expression for CK1/10 after 60h under the influence of cryptotanshinone (1µM) was reduced to > 90%.

At higher concentrations crytotanshinone influenced cell vitality negatively (MTT vitality assay IC50= 14.4µM, BrdU proliferation assay IC50= 8.2µM).

To determine possible target structures in the differentiation signaling pathway, Drug Affinity Responsive Target Stability (DARTS) was used. By comparing the protein stability of HaCaT total cell lysate versus thermolysin with and without cryptotanshinone preincubation and consecutive protein sequencing, heat shock protein 90 was identified as a potential major molecular target for cryptotanshinone. An inhibition of this chaperon is known to result in reduced KRT1/10 expression [2]. From these data the use of cryptotanshinone and S. miltiorrhiza extract for skin diseases seems to be rationalized.

[1] Qi Ye et al. Evidence-Based Complementary and Alternative Medicine

[2] Sadanori Miyoshi et al. FEBS openbio