Metabolites of orally administered Magnolia officinalis extract in rats and man and its antidepressant-like effects in mice

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Abstract
As a part of our search for the active metabolite from the bark of Magnolia officinalis (Magnoliaceae), the aqueous extract was orally administered to rats, and metabolites in the urine were analysed by a high-performance liquid chromatograph equipped with a photodiode array detector. When the extract was given to rats, five metabolites (sinapic acid-4-O-sulfate (1), sinapic acid-4-O-β-glucuronide (2), sinapic acid (3), 3-[2′,6-dihydroxy-5′-(2-propenyl)[1,1′-biphenyl]-3-yl]-(E)-2-propenoic acid (4), and an unchanged form, magnolol (5)) were detected in the urine. It was revealed that metabolites 1–3 and 4 were respectively derived from syringin and magnolol contained in the extract. In a human urine sample, metabolites 3–5 and dihydroxydihydromagnolol (6) were detected. These structures were identified by a combination of spectral methods and/or by comparison with authentic compounds obtained by synthesis. Among these free form metabolites (3–6), acute treatments with magnolol and dihydroxydihydromagnolol (50–100 mg kg−1, i.p.) attenuated the forced swim-induced experimental depression in mice. The results indicated that magnolol and dihydroxydihydromagnolol were the antidepressant constituents of Magnolia officinalis.