Cocktail recipes containing Psoralea corylifolia seeds (PCS) are used to empirically treat Parkinson disease. A PCS isolate Delta(3),2-hydroxybakuchiol (BU) can inhibit dopamine uptake in dopamine transporter (DAT) transfected Chinese hamster ovary (CHO) cells, and dopamine reuptake blockade may provide an alternative approach for ameliorating parkinsonism. Here, we assessed the potential dopaminergic neuroprotective, and antiparkinsonian-like activity of BU. BU sample size was increased by using a scale-up extraction paradigm. Pharmacologically, BU significantly protected SK-N-SH cells from 1-methyl-4-phenylpyridinium (MPP(+)) insult, produced striking inhibitory actions on dopamine/norepinephrine uptake and WIN35,428 binding in synaptosomes on in vivo administration, and significantly preventing poor performance on rotarod and dopaminergic loss in substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice. BU acts by protecting dopaminergic neurons from MPP(+) injury and preventing against MPTP-induced behavioral and histological lesions in the Parkinson's disease (PD) model, possibly by inhibiting monoamine transporters. These findings suggest that BU could be meaningful in PD treatment.

Safflower (Carthamus tinctorius L.), a member of the family Compositae, geologically distributes in all regions in China, and is utilized for producing herbal medicines for the treatment of inflammatory diseases, hyperlipemia, arteriosclerosis, gynecological disorders, and osteoporosis. 1) To date, it has been known to contain flavonoids, 2) cartharmin, safflower yellow A, quinochalone, safflomin, cartorimine, alkaloids, 3) lignans, fatty acids, 4) triterpene alcohols, 5) and serotonin derivatives.6-8) Additionally, several coumaroylspermidine analogs also were found in safflower, i.e., a principal analog N 1 ,N 5 ,N 10 -(E)-tri-p-coumaroylspermidine (EEE) and its three cis-trans isomers [N 1 ,N 5 9) indicating that that some other geometric isomers of tri-p-coumaroylspermidine could exist in the natural plant. In our previous preliminary screening, we discovered that safflower extracts (especially ethyl acetate extract (HE) and n-butyl alcohol fraction) had regulatory actions on the monoamine transports in transporter-transgenic Chinese hamster ovary (CHO) cells, that is, activations of dopamine (DA)/norepinephrine (NE) uptake and an inhibition of serotonin (5HT) uptake, 10) implying that there may be some constituent(s) acting as serotonin transporter (SERT) blocker(s). In this study, we thereby chose to isolate and characterize the structurally unknown, SERT-targeting compound(s) from the HE fraction by using an activity-directed extraction method and a series of NMR techniques. Finally, one of the active isolates was identified and elucidated as N 1 ,N 5 -(Z)-N 10 -(E)-tri-p-coumaroylspermidine (CX), a new tri-p-coumaroylspermidine as postulated previously by us. Results and DiscussionThe ethyl acetate extract of safflower (Carthamus tinctorius L.) was separated by column chromatography on silica gel and Sephadex LH-20 in combination with a concomitant bioactivity-tracing technique (detailed paradigm described in Supplemental) to afford a bioactive compound CX (designated as carthamide X by us) (Fig. 1). HPLC showed that the purity of CX sample was 95.6% (while the content of CX in HE was only 0.028%). Due to the sensitivity, validity, and feasibility, 10) our screening platform previously established by using isotope-ligand-detection methods is suggested suitable for tracing some structurally unknown/unstable compounds with a sparse content in natural plants when combined with phytochemical techniques, which could, however, be hard to be isolated by traditional phytochemical method alone.The We previously reported that safflower (Carthamus tinctorius L.) ethyl acetate extract (HE) possessed an inhibitory action on serotonin (5HT) uptake in Chinese hamster ovary (CHO) cells expressing 5HT transporter (SERT) (S6 cells). Here, HE was adopted to go through an activity-guided isolation, and then an ingredient with potent SERT inhibitory action was obtained, which was elucidated as N

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