Studies On The Chemical Constituents And Anti-depression Activity Of The Petroleum Ether Fraction Of Radix

RATIONALES:Depression is the main type of mood disorder.It is predicted that by 2020,the depression will become the second disabling disease,and more and more attention has been paid to its harmfulness by the medical and health sector.Although the anti depression effect of chemical synthetic drugs is great,but the side effect is obvious.On the contrary,the effect of traditional Chinese medicine is mild,but it has few side effects.So it is very important to search for the treatment of depression from Chinese Traditional Medicine(TCM).In our previous research,which studying on the petroleum ether fraction of XYS and guiding by serum drug chemistry,found that there were 20 compounds in serum,and 13 of them are from Radix Burpleuri.Further study found that four acetylene compounds of them from Radix Bupleuri showed strong antidepressant activity.Therefore,other acetylene compounds whether has anti depression activity?Whether the compounds from petroleum ether part of the Radix Bupleuri in XYS can also play a role in anti depression?So it is necessary for them to carry on the further research on dosage-effect/toxicity.OBJECTIVE:To isolate the acetylene compounds of radix bupleuri and study their anti depression activity.To research the dialectical relationship between anti depression activity and toxicity of the petroleum ether of radix bupleuri(CH-A).In order to provide a basis to be more fully utilize of the radix bupleuri,and provide a reference for the development of new anti depression drugs.METHODS:The traditional methods of planting separation were used for preparation of the acetylene components of Radix Bupleuri.In vitro monoamine reuptake inhibition experiments were performed to study the antidepressant activity of these acetylene compounds.The amount of antidepressant activity was studied by observing the effects of different doses of CH-A on the behavior of CUMS model rats.The relationship between dose and toxicity was studied by analyzing the effects of different doses of CH-A on liver and kidney related biochemical indexes in CUMS model rats and normal rats.And then the dialectical relationship between the amount and anti depression effect or toxic effect of CH-A was discussed.RESULTS:1.Four acetylene components were isolated and identified as(2Z,8E,10E)-pentadeca-2,8,10-trien-4,6-diyn-1-yl acetate(RB-5),(2E,8E,10E)-pentadeca-2,8,10-trien-4,6-diyn-1-yl acetate(RB-6),(2E,8E,10E)-pentadeca-2,8,10-trien-4,6-diyn-1-ol(RB-7),(2E,8E,10E)-heptadeca-2,8,10-trien-4,6-diyn-1-ol(RB-8).In vitro monoamine reuptake inhibition experiments showed that four compounds could effectively inhibit NE and 5-HT reuptake behavior.2.It has obvious anti depression effect for CUMS model rats when the dosage of CH-A is in the range of 25-100 g/kg.The rats in the CUMS model group did not appear liver or renal injury within the dose range of 1-100 g/kg.While normal rats showed damage in normal rats when the dosage is higher than 25 g/kg,and the renal toxicity was found in normal rats when the dosage was 100 g/kg.CONCLUSION:1.CH-A shows anti depression activity,and the four acetylene compounds may be the effective components and substance basis of the antidepressant effect of CH-A.2.Equivalent dose of CH-A showed liver and kidney toxicity in normal rats,but showed antidepressant effect in CUMS model rats.