Antidepressant-Like Effect And Chemical Constituents Of Piper Sarmentosum Roxb.

Depression is a common mental illness with prominent and persistent low mood as its major clinical feature.Depression is a major cause of disability,and it is one of the mental disease that endangering the people’s physical and mental health seriously.It is reported that depression is a worldwide mental disorder with a lifetime prevalence of 16%.Piperis Sarmentosi Herba is the stems,leaves or whole plant of Piper sarmentosum Roxb.(PS),which belongs to the Piper genus of piperaceae,also called“ha ju”,“jia lao”,etc.There are abundance plant resources of PS,and it is distributed in the tropical areas of China,such as Yun nan,Guang xi,Fu jian,Hai nan and Gui zhou Province.The flavor and character of PS are spicy and warm.Functions & Indications: expelling wind-damp,dissipating cold,line spirit and relieve pain,activate collaterals,for the treatment of cold and cough,rheumatism pain,abdominal distention,diarrhea and dysentery,swollen feet and bruises.It is reported that PS has biological activities,including: antioxidant,anti-atherosclerosis,osteoporotic and fracture healing,larvicidal activity and antibiotics.The other plants belong to the Piper genus,such as Piper methysticum,Piper laetispicum C.DC and Piper boehmeriaefolium(Miq.)C.DC.var.tonkinense.C.DC.were reported to have antidepressants-like effect.Plants of the same genus could have the same chemical constituents and pharmacological activity.Thus,we study the chemical components and antidepressants-like effect of PS in this subject.We focus on the following areas:1 Study on antidepressants-like effect of Piper sarmentosumThe antidepressants-like effect of Piper sarmentosum was studied with OFT,FST and TST.In OFT,PS treatments had no effect on spontaneous activity.This indicates that PS had neither excitating nor inhibiting activities on central nervous system.The result in FST showed a significantly reduced the immobility time in PS treatment groups(50,100,200 mg/kg)compared with controls.The result in TST showed a significantly reduced the immobility time in PS treatment groups(100,200mg/kg)compared with controls.All these results indicated that PS had significant antidepressant-like effect.In order to further find the active part of PS,we studied the antidepressant-like effect of different fractions of PS extracts with OFT,FST and TST.The result in FST showed a significantly reduced the immobility time in PSS group(30,60,120 mg/kg),PSR group(50 mg/kg)and PSY group(12.5,25,50 mg/kg)compared with controls.The result in TST showed a significantly reduced the immobility time in PSY group(12.5,25,50 mg/kg)compared with controls.All these results indicated that PSY was the active part of Piper sarmentosum.2 Study on mechanism of PS active part in antidepressants-like effectIn our present study,the CUMS caused hyperactivity of the HPA axis in rats,as indicated by the elevation of serum CORT,and administration of PSY significantly reversed the CMUS-induced increase of serum CORT levels.Moreover,there is also a dose-dependent effect of PSY(from 12.5 mg/kg to 50 mg/kg)to reduce serum CORT.It is indicated that the antidepressant-like effect of PSY were accompanied by alterations in the HPA axis.Then we studied the effect of PSY on BDNF,the results demonstrated that treatment with PSY reversed the CUMS-induced reduction of BDNF m RNA expression(7.5,15,30 mg/kg)and protein levels(15,30 mg/kg)in the hippocampus of rats.Our results indicated that antidepressant-like effect of PSY were related to the alteration of BNDF levels.At last,we also examined the changes in CREB and ERK activities.The results confirm that exposure to CUMS was able to inactivate the CREB and ERK 1/2 as signaling and transcription factors in the hippocampus through phosphorylation,and it was also demonstrated that administration of PSY(7.5,15,30 mg/kg)was able to reverse CUMS-induced decrease in phosphorylation of CREB and ERK 1/2,as well as classic antidepressant fluoxetine.These results suggest the involvement of CREB and ERK in the antidepressant-like effect of PSY.3 Study on chemical constituents of Piper sarmentosumThe air-dried and powdered aerial parts of Piper sarmentosum were extracted with 80% ethanol.The extracts was suspended in H2 O and further partitioned into four fractions: petroleum ether(PSS),dichloromethane(PSR),ethyl acetate(PSY),butyl alcohol(PSZ).The PSS and PSY were subjected to different sorts of methods,such as chromatography column,preparative thin layer chromatography,semi-preparative HPLC and ODS.The PSS and PSY afforded 26 kinds of compouds,which were elucidated 21 compounds including a novel compound,an alkaloid named piperlotine M.The major types of the isolated chemical constituents were: alkaloids,sterols,lignans,phenolic acids,fatty acids and so on.4 Conclusions and innovations(1)We found the antidepressant-like effect of Piper sarmentosum for the first time.(2)Research the antidepressant-like effect mechanism of Piper sarmentosum,and we have found the involvement of HPA,BDNF,CREB and ERK in the antidepressant-like effect of Piper sarmentosum.(3)We studied the chemical constituents of Piper sarmentosum and found a novel compound,named piperlotine M.