Abstract
Shikonin is the main active principle in the root of Lithospermum erythrorhizon , widely used in traditional Chinese medicine for its anti-inflammatory and wound
healing properties. Recent research highlights shikoninʼs antitumor properties and
capacity to prevent acute ulcerative colitis. The aim of the present study was to
evaluate the ability of shikonin to prevent, in vivo , the early phases of colorectal cancer development, with special focus on its cytotoxic
mechanism in vitro . We employed the azoxymethane/dextran sulfate sodium model of colitis in Balb/C mice.
Body weight and drinking were monitored throughout the experiment, and length of colon
and lesions of the colon were recorded on termination of the experiment in all of
the experimental groups. Colons underwent histological evaluation and biochemical
analyses [myeloperoxidase activity assay, measurement of interleukin-6, evaluation
of proinflammatory enzymes (cyclooxygenase-2 and inducible nitric oxide synthase),
and nuclear factor-κ B activation by Western blot]. Caco-2 cells were used to evaluate, in vitro , the effect of shikonin on proliferation, cytotoxicity, cell cycle, and apoptosis.
Our results reveal that shikonin significantly protected the intestinal tissue of
our animals by preventing the shortening of the colorectum and ulcer formation in
a dose-dependent manner. Shikonin attenuated the expression of cyclooxygenase-2 and
inducible nitric oxide synthase, and myeloperoxidase activity, and inhibited the production
of interleukin-6 and activation of nuclear factor-κ B. It induced Bcl-2 and inhibited caspase 3. In conclusion, shikonin acts as a chemopreventive
agent in the azoxymethane/dextran sulfate sodium model through inhibition of the proinflammatory
milieu generated during the disease, an important risk factor in cancer development.
Key words
Lithospermum erythrorhizon
- Boraginaceae - inflammatory bowel disease - shikonin - ulcerative colitis -
in vivo
