ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg^-1）， high-dose paeonol group （480 mg·kg^-1）， and silybin group （36.8 mg·kg^-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.

OBJECTIVE To provide a reference for optimizing and promoting the quality standards of Shechuan naolitong granules. METHODS Fifteen batches of Shechuan naolitong granules were used as samples to establish HPLC fingerprints using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine （2012 edition）. Similarity evaluation and common peak identification were performed， and orthogonal partial least squares discriminant analysis （OPLS-DA） was used to assess quality differences among different batches and to screen quality differential components. Using salvianolic acid B（SAB） as the internal reference， quantitative analysis of multi-components by single-marker （QAMS） was developed to simultaneously determine geniposidic acid （GA）， chlorogenic acid （CA）， vaccarin （VA）， ferulic acid （FA） and senkyunolide I （SI）. The results were compared with those obtained by the external standard method. RESULTS A total of 13 common peaks were identified in the HPLC fingerprints of 15 batches of samples， and the similarities of the spectra were all above 0.96. Seven chromatographic peaks were identified as GA （peak 3）， CA （peak 6）， VA （peak 8）， FA （peak 9）， SI （peak 11）， SAB（peak 12） and TA（peak 13）. OPLS-DA indicated that the differential quality markers among 15 batches were peaks 5， 11 （SI）， and 12 （SAB）.Using SAB as the internal reference， the relative correction factors for GA， CA， VA， FA and SI were calculated as 1.058 4， 0.594 3， 0.643 3， 0.342 7 and 0.262 8， respectively. The mean content of GA， CA， VA， FA， SI and SAB across the 15 batches of samples were 0.155 0， 0.085 4， 0.140 3， 0.071 8， 0.072 7， 1.276 3 mg/g， respectively， showing no significant difference compared with the ESM （P＞0.05）. CONCLUSIONS The established HPLC fingerprint and QAMS are simple， efficient and economical， providing a reference for the quality control and further development of Shechuan naolitong granules.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.

Objective To explore the effect and mechanism of Shenqi Jieyu Formula(SQJYF)on depression and anxiety-like behavior in adult offspring rats after maternal separation(MS).This was done by observing the levels of metabolites in the hippocampus and prefrontal cortex of the Papez circuit through magnetic resonance spectroscopy(MRS).Methods Twenty-four Sprague-Dawley rats at 16 days of pregnancy were divided into the normal,model,SQJYF,and fluoxetine groups using the random number table method,with six rats per group.MS was performed 4 h a day from the first to the 21st day afterbirth.Starting from the 15th day,the corresponding medications(SQJYF group:12.5 g/kg,fluxetine group:2.33 mg/kg)were administered to mother rats once a day for 7 consecutive days.Normal breastfeeding was performed during the gavage.The offspring rats were weaned on the 22nd day.According to the experimental grouping of mother rats,one male and one female offspring rat of each mother rat were randomly selected using the random number table method,with six rats per group.They were divided into normal,model,SQJYF,and fluoxetine female and male rat groups,respectively.After 8 weeks of feeding,the offspring rats in each group were subjected to forced swimming test(FST),the sucrose water consumption test,and open field tests(OFT),and the elevated plus maze(EPM)test was conducted.The relative values of N-acetyl-aspartate(NAA),choline(Cho),glutamic acid(Glu),myo-inositol(mI),and creatine(Cr)in the hippocampus and prefrontal cortex were detected using MRS.Results Compared with that of the normal female and male rat groups,the weight of the rats in the model group was decreased as well as sucrose water consumption and the horizontal and vertical scores of OFT,whereas the immobility time of FST increased.Compared with the normal female and male rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of the female and male rats in the model group decreased(all P＜0.01).The proportion of rats entering the open arm and open arm residence time of the model female rat group in the EPM test decreased,whereas the Cho/Cr value of the right hippocampus of the female rats in the model group increased(P＜0.05).Compared with the model female and male rat group,the weight of the rats in the SQJYF and fluoxetine groups increased,the immobility time of FST decreased,but the sucrose water consumption and the horizontal and vertical OFT scores increased(P＜0.01).The proportion of rats entering the open arm and open arm residence time in the EPM increased in the SQJYF and fluoxetine female rat groups compared to those of the model female rat group(P＜0.01).Compared with the model female rat group,the NAA/Cr and Glu/Cr values in the bilateral hippocampus and prefrontal cortex of female rats in the SQJYF and fluoxetine groups increased.The NAA/Cr and Glu/Cr values in the right hippocampus and prefrontal cortex of male rats in the SQJYF and fluoxetine groups were higher than those in the model group(P＜0.05),whereas the Cho/Cr value in the right hippocampus of female and male rats in the SQJYF and fluoxetine groups decreased(P＜0.05).Conclusion MS in early life can lead to depression and anxiety-like behavior in adult offspring.However,SQJYF may exert antidepressant and anti-anxiety effects by regulating the metabolite levels in related brain regions of the Papez circuit.