OBJECTlVE To investigate the antidepressant effect and reIated mechanism of the totaI fIavonoids extract parts( Iicorice fIavonoids,LF)from Glycyrrhiza uralensisFisch. cuItivated IocaIIy in Ningxia. METHODS Forced swimming test( FST)and taiI suspension test( TST)were adopted to study the antidepressant pharmacoIogicaI effect in the acute stress-induced depression modeI in mice. The Km mice were intragastricaIIy administered with LF(5,30 and 180 mg·kg-1 )once daiIy,for 21 con-secutive days. One hour after the first,seventh and Iast administrations,the mice were submitted to FST by recording the immobiIity period within the Iast 4 min of the totaI 6 min in both tests and the resuIts were expressed as decrease in immobiIity period with respect to vehicIe controI. In TST,the other group of Km mice was used to evaIuate the antidepressant effect in same protocoI. In the antagonism of reserpine-induced symptoms test( ART),ICR mice were administered intragastricaIIy with LF( 50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days. One hour after the Iast administration,the mice received reserpine(4 mg·kg-1 ,ip),and ptosis or akinesia was measured 1 h after reserpine injection whiIe rectaI temperature was measured 4 h after the reserpine injection respectiveIy. The same protocoI was adopted in yohimbine toxicity potentiation test(YTT)as in ART. Thirty minutes fter the Iast adminis-tration,the mice received the threshoId IethaI dosage of yohimbine(30 mg·kg-1 ,sc)respectiveIy,and the death number of the mice was caIcuIated in 24 h after the yohimbine administration. In the 5-hydroxy-L-tryptophan(5-HTP)induced head-twitches test(HTT)in mice,after being administered intragastricaIIy with LF(50,150 and 400 mg·kg-1 )once daiIy for 7 consecutive days,the mice received pargiIine (100 mg·kg-1 ,ip)the next day,and 30 min Iater,5-HTP(10 mg·kg-1 ,ip)was intraperitoneaIIy injec-ted to induced the head twitch respectiveIy,and the times of head twitch in a 30 min period after 5-HTP treatment were observed at 6 time points. After HTT,the mice were sacrificed quickIy,and the mono-amine oxidase(mAO)activity in the brain cortex,hippocampus and thaIamus was examined to evaIuate the antidepressant effect of fIavonoids with mAO inhibition. RESULTS Compared with the vehicIe controI,LF significantIy decreased the immobiIity period in both FST and TST(P﹤0.05). LF(50,150 and 400 mg·kg-1 )antagonized the ptosis and akinesia symptoms respectiveIy in 1 h after reserpine administration( P ﹤ 0. 05 ), but faiIed to antagonize hypothermia produced 4 h after reserpine administration. AIso,at the same dosage,LF did not synergeticaIIy produce the enhancement of death by subcutaneous injection of yohimbine at the threshoId IethaI dosage. LF(150 and 400 mg·kg-1 )couId significantIy and synergeticaIIy increase 5-HTP induced head-twitches response(P﹤0.05),but LF couId not promote mAO activity in the cortex,hippocampus and thaIamus at the same dosage. CONCLUSlON LF exerts antidepressant-Iike effect on the modeI of acute despair test. The mechanism might be reIated to direct enhancement of the serotonergic neuraI function in the brain.

Objective:To investigate the effect and possible mechanism of circular RNA(circRNA)cerebellar degeneration-related protein 1 antisense transcript(CDR1-AS)on proliferation,apoptosis and immune factors expressions of lung cancer cells.Methods:Using BEAS-2B in adjacent tissues and bronchial epithelial cells as controls,qRT-PCR was used to detect expressions of CDR1-AS and miR-1277 in lung cancer tissues and lung cancer cell lines(NCI-H23,H1299,NCI-H446).Taking lung cancer H1299 cells as research object,after they were transfected with CDR1-AS small interfering RNA(si-CDR1-AS)or miR-1277 mimic,or co-transfected with si-CDR1-AS and miR-1277 inhibitor,CCK-8 experiment,clone formation experiment and flow cytometry were used to detect cell viability,clone formation number and apoptosis rate,respectively.ELISA was used to detect expressions of immune factors(TNF-α,IFN-γ)in cell culture supernatant.Dual-luciferase reporter gene experiment was used to verify the regulatory relation-ship between CDR1-AS and miR-1277.Results:Compared with adjacent tissues or BEAS-2B cells,expression of CDR1-AS in lung cancer tissues or cell lines(NCI-H23,H1299,NCI-H446)was increased(P<0.05),while expression of miR-1277 was decreased(P<0.05).After silencing CDR1-AS or overexpressing miR-1277,activity of H1299 cells,the number of clones and the secretion of TNF-α were decreased(P<0.05),while apoptosis rate and secretion of IFN-γ were increased(P<0.05).CDR1-AS targeted and bound to miR-1277,and expression of miR-1277 was increased in H1299 cells that silenced CDR1-AS(P<0.05).Down-regulation of miR-1277 reversed effects of silencing CDR1-AS on proliferation,apoptosis and expressions of immune factors in H1299 cells.Conclu-sion:Expression of CDR1-AS is up-regulated in lung cancer tissues and cell lines,silencing its expression can inhibit proliferation and tumor cell immune escape of lung cancer H1299 cells,and induce cell apoptosis by targeting up-regulation of miR-1277.