Antidepressant polyprenylated acylphloroglucinols from Hypericum ascyron.

Phytochemical investigation on the 90% EtOH extract of the air-dried aerial parts of Hypericum ascyron resulted in the isolation of three new polycyclic polyprenylated derivatives ascyronines A-C (1-3). Structural elucidation of all the compounds was performed by spectral methods such as 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the polycyclic polyprenylated acylphloroglucinols were evaluated for their antidepressant activity by inhibiting the reuptake of tritiated serotonin ([3H]-5-HT) and noradrenalinet ([3H]-NE) in rat brain synaptosomes. Compounds 2 and 3 exhibited weak antidepressant activities in the [3H]-5-HT mode.

Preparation and Antidepressant Activity Study of β-sitosterol and Its Derivatives from the Fruit of Sorbus pohuashanensis / 中国药房

OBJECTIVE： To prepare β-sitosterol （shorted fo r “Sit”） and its deri vatives from the fruit of Sorbus pohuashanensis，and to investigte their antidepressant activities. METHODS ：Using the fruit of S. pohuashanensis as raw material ， extracted with 75％ ethanol and 20％KOH solution ，Sit was obtained after extraction and crystallization. C 3 hydroxyl group of Sit was used as the structural modification site ，CH2Cl2 was used as the reaction solvent ，DMAP was used as catalyst ，EDCI was used as dehydrating agent ，4 kinds of organic acids （salicylic acid ，2-tetrahydrofuranic acid ，phenylalanine，sorbic acid ）were added to make the carboxylation reaction to produce ester derivatives Sit-S ，Sit-T，Sit-P and Sit-Sr. The chemical structure of its derivatives were elucidated by IR and NMR. The tail suspension test and the forced swimming model were used to preliminarily explore the antidepressant active components of Sit and 4 kinds of derivatives ；tail suspension test and the spontaneous exercise capacity test were used to screen effective dose of the compounds with antidepressant active. The compound was used alone or in combination with agomelatin [ 40 mg/kg，5-hydroxytryptamine（5-HT）and 5-HT 2C receptor antagonist] ，haloperidol [ 0.2 mg/kg，non-selective D2 receptor antagonist] and bicuculline [ 4 mg/kg，competitive γ-aminobutyric acid（GABA）antagonist]，respectively. Sixty minutes after intraperitoneal injection ，tail suspension test was performed. The levels of 5-HT，dopamine（DA）and GABA in brain tissues of mice were detected by ELISA. The blank control group was given intraperitoneal injection of 10％ propylene glycol solution. RESULTS：By spectrum technology ，the corresponding ester compounds were synthesized by the reaction of Sit with four kinds of organic acids. Among Sit and its four derivatives ，the immobility time of Sit-S group was the shortest in tail suspension test and forced swimming test ，which was significantly shorter than that of blank control group （P＜0.05）. Screening results of Sit-S showed that the effective antidepressant dose was 4 mg/kg， ＊ and it did not affect the spontaneous activity of mice compared with the blank control group （P＞0.05）. With this dose ，Sit-S could significantly shorten the immobility time of mice in tail hua1666@163.com suspension test （P＜0.01），and can s ignificantly increase the ·64levels of 5-HT，DA and GABA in the brain tissue of mice （P＜0.05 or P＜0.01），but its effect can be reversed by agomelatine ， haloperidol and bicuculline to different extent. CONCLUSIONS ：Sit salicylate derivatives Sit-S exhibits good antidepressant activity，and its mechanism of action may be mediated by increasing the levels of 5-HT，DA and GABA.

Prenylated ß-diketones, two new additions to the family of biologically active Hypericum perforatum L. (Hypericaceae) secondary metabolites.

Two novel ß-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures of ß-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these ß-diketones predominantly exist as two rapidly interconverting ß-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St. John's wort. It is therefore not surprising that A displayed a noteworthy biological activity profile as well (including brine shrimp toxicity, antinociceptive, antidepressant and acetylcholinesterase inhibitory activity). ß-Diketone A manifested the most outstanding potency as an acetylcholinesterase inhibitor with IC50 value of 1.51 µM pointing again to the ß-keto-enol moiety as a promising lead structure for the development of drugs that could lessen symptoms of Alzheimer's disease (such as dementia, depression and pain).