Of twelve reduced and acetylated derivatives of
shikonin, a chemical constituent of Shikon, the accelerating activity on
granuloma formation and the inhibitory activity on delayed-type
allergy were investigated in order to find a compound having more characteristic effect than
shikonin on wound healing in experimental animals. As a result, it was found that a reduced and pentaacetylated derivative of
shikonin,
MDS-004, has more excellent pharmacological activity.
MDS-004 (0.1-1 mg/pellet) accelerated dose-dependently felt-pellet-induced
granuloma formation when given topically together with felt-pellets in rats. It also produced strong inhibition against delayed-type
allergies (ear
edema) caused by
oxazolone and
dinitrofluorobenzene by topical application of up to 1 mg/ear to the ear skin of mice; its potency was far superior to that of
shikonin. Orally administered
MDS-004, unlike
shikonin, inhibited
carrageenan-induced hind paw
edema, and exhibited tendency to heal
acetic acid-induced
gastric ulcer in rats. However,
MDS-004, as well as commercial wound healing drugs tested and
shikonin, did not show any healing action in the incised and open
wound models in rats, if applied topically to the
wound as 5 and 10% powders. On the other hand,
MDS-004 did not produce irritative action on the ear skin at a topical dose of 1 mg/ear different from
shikonin, and any behavioral changes after
oral administration of 100 mg/kg in mice. These results suggest that a white
powder MDS-004, different from deep purple
shikonin, has accelerating action on
granuloma formation without irritative action and stronger inhibitory action on delayed-type
allergy by topical application than
shikonin.