During the epidemics of the mediaeval period, doctors in Byzantium and Italy developed
the “Alipta muscata” as a preventive medicine against epidemics. When treating the
“black death” doctors constantly used it for self-medication. The main ingredient
of “Alipta muscata” was the oleoresin labdanum of Cistus creticus L. [1]. While the “black death” is mostly interpreted as Yersinia pestis, there is also an alternative interpretation as a viral haemorrhagic fever [2]. We
tested several extracts and fractions of labdanum on their activity against the dengue
virus (DENV-2 strain 00st-22A) in in vitro cultures on Vero cells (96-well-plates, 5 days). This haemorrhagic fever affects
up to 500 million patients annually with no chemotherapeutic agent available and causes
20.000 deaths. Preliminary experiments with a labdanum full extract did not yield
measureable results due to cytotoxic effects against Vero cells. In all following
experiments, cell viability was constantly checked using the MTT-test. Fractionation
of the dichloromethane raw-extract by liquid-liquid-extraction and column-chromatography
on silica-gel (gradient elution with Hexane, EtOAc, CHCl3, MeOH) succeeded in separating the anti-viral activity of labdanum from its cytotoxic
effect. In the most active fraction GS5 at 30 µg/ml, the dengue virus proliferation
was 100% suppressed and cell viability over 90%. Structural elucidation of major constituents
of GS5 is currently ongoing. Claims concerning the antiviral activity of above ground
parts of C. creticus have been made previously, but these generally ascribe this activity to hot water
soluble polyphenols and propose an unspecific tanning effect of the viral surface
proteins as the mechanism of action [3]. We describe an antiviral activity of a dichloromethane
extract of labdanum against a virulent haemorrhagic fever like dengue for the first
time.
[1] Husemann T. Archiv der Pharmacie. 1889;27:1075 – 1132
[2] Duncan CJ, Scott S. Postgrad Med J. 2005;81:315 – 20
[3] Ehrhardt C et al. Antiviral Res. 2007;76:38 – 47
