Studies on the Active Principle of Mangolia Bark. Centrally Acting Muscle Relaxant Activity of Mangolol and Hönokiol

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Abstract
The centrally acting muscle relaxant effect was compared along the fractions of the ether extract of M. officinales bark and its purified constituents, magnolol and honokiol. Male albino mice were used for the muscle relaxation test. Mephenesin, methocarbamol and chlorpromazine were used as reference drugs. The median effective dose and 95% confidence limits were determined for the muscle relaxation test. Young chicks, 4 to 13 days of age, were used for making a spinal reflex preparation. Magnolol 100 mg/kg, produced prominent muscle relaxation for 2 h. The dose of 250 mg/kg induced loss of the righting reflex in some of the mice, and muscle relaxation lasted over 3 h. The minimum effective dose of magnolol was 90 mg/kg while the sedative symptoms were observed with much lower doses. Honokiol at a dose of 250 mg/kg showed a muscle relaxing effect for 3 h and 500 mg/kg produced loss of the righting reflex. The muscle relaxing effect of both compounds disappeared gradually and fully recovered 24 h after injection. Ether extract 1g/kg induced loss of the righting reflex 30 min after injection for nearly 60 min. The duration of clinging was markedly shortened for more than 4 h. The effects of the alkaline soluble fraction obtained from the ether extract on the general behavior of mice and on muscle tone were similar to those of the ether extract. Morphenesin produced rapid and short-acting muscle relaxation. The dose of 150 mg/kg induced muscle relaxation within 5 min after the injection and the effect disappeared within 30 min. Methocarbamol at a dose less than 400 mg/kg produced an effect on muscle tone similar to mephenesin. Chlorpromazine at a dose of less than 15 mg/kg showed long-lasting muscle relaxation, while duration of clinging to the net was never shortened to zero. Magnolol (75 mg/kg, i.p.) completely inhibited the extensor reflex in the 40 min after the injection. The onset of the action was gradual and the duration was long (over 2 h). The time course of the action was similar to that of the muscle tone experiment in mice. This inhibition was antagonized by a large dose of strychnine (400 .mu.g/kg, i.p.), indicating that the inhibition was not exerted by a curare-like activity. Honokiol showed almost the same effect as magnolol on the spinal reflex, but a higher dose (150 mg/kg, i.p.) was required to exert the same degree of inhibition as magnolol. Complete inhibition of the reflex was also obtained with mephenesin (50 mg/kg, i.p.), but the onset and the duration of action were much shorter (about 30 min) than those of magnolol. Magnolol and honokiol have a distinct and long-lasting muscle relaxant activity.