The mechanism of honokiol-induced and magnolol-induced inhibition on muscle contraction and Ca2+ mobilization in rat uterus

The effects of honokiol and magnolol extracted from the Magnolia officinalis on muscular contractile responses and intracellular Ca2+ mobilization were investigated in the non-pregnant rat uterus. Honokiol and magnolol (1-100 mumol/l) were observed to inhibit spontaneous and uterotonic agonists (carbachol, PGF(2alpha), and oxytocin)-, high K+-, and Ca2+ channel activator (Bay K 8644)-induced uterine contractions in a concentration-dependent manner. The inhibition rate of honokiol on spontaneous contractions appeared to be slower than that of magnolol-induced response. The time periods that were required for honokiol and magnolol, at 100 mumol/l, to abolish 50% spontaneous contractions were approximately 6 min. Furthermore, honokiol and magnolol at 10 mumol/l also blocked the Ca2+-dependent oscillatory contractions. Consistently, the increases in intracellular Ca2+ concentrations ([Ca2+](i)) induced by PGF(2alpha) and high K+ were suppressed by both honokiol and magnolol at 10 mumol/l. After washout of these treatments, the rise in [Ca2+](i) induced by PGF(2alpha) and high K+ was still partially abolished. In conclusion, the inhibitory effects of honokiol and magnolol on uterine contraction may be mediated by blockade of external Ca2+ influx, leading to a decrease in [Ca2+](i). Honokiol and magnolol may be considered as putative Ca2+ channel blockers and be of potential value in the treatment of gynecological dysfunctions associated with uterine muscular spasm and dysmenorrhea.