Drug Designing: Open Access
Open Access
ISSN: 2169-0138
+44 1223 790975
ISSN: 2169-0138
+44 1223 790975
Jin-Ho Chung, J H Kwon and K Y Kim
Posters-Accepted Abstracts: Drug Des
Dysregulated tonic tension and calcium sensitization in blood vessels has been frequently observed in many cardiovascular
diseases. Despite a huge therapeutic potential, little is known about natural products targeting tonic tension and calcium
sensitization. Here we found that emodin, an anthraquinone derivative in herbal medicines, can dissipate tonic tension by
inhibiting protein kinase C δ-mediated calcium sensitization. Emodin was identified as an active ingredient of Polygonum
multiflorum extract for the inhibition of phenylephrine (PE)-induced vasoconstriction in rat isolated thoracic aorta. Emodin
also inhibited vasoconstriction induced by serotonin and endothelin-1. Of note, emodin generally suppressed vasoconstrictions
mediated by voltage-operated, store-operated calcium channels and intracellular calcium store. However, emodin did not
affect agonist-induced calcium increases in primary smooth muscle cells. In contrast, post-treatment of emodin following PE
stimulation significantly and potently dissipated tonic tension in rat aortic ring. Western blot analysis revealed that emodin
attenuated PE-increased phospho-MLC (pMLC) along with phosphorylation of MYPT and CPI-17. This was mediated by the
selective inhibition of PKCδ while PKCα was not involved. Taken together, we demonstrated that emodin dissipates tonic
tension through the blockade of PKCδ and CPI-17 mediated MLC-phosphatase inhibition. This new mode of action for antihypertensive
agents and a structural insight for PKCδ inhibition given by emodin may provide a new insight for the development
of modulators of tonic tension and hypertensive diseases.