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
