ObjectiveThis study aims to explore the mechanism of action of Huangqi Guizhi Wuwutang in treating rheumatoid arthritis （RA）-associated sarcopenia by regulating autophagy and improving skeletal muscle homeostasis based on network pharmacology，bioinformatics，machine learning，and animal experiments. MethodsActive ingredients and targets of Huangqi Guizhi Wuwutang were screened using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP），PubChem，and SwissTargetPrediction databases. RA-related datasets were retrieved from the GEO database，and differential genes were screened. Sarcopenia-related targets were searched through GeneCards and the Comparative Toxicology Database （CTD），and autophagy-related gene sets were downloaded from the Human Autophagy Database （HADb）. Their intersection was analyzed to identify autophagy-related therapeutic targets，followed by enrichment analysis. A protein-protein interaction （PPI） network was constructed using the STRING database，and key targets were selected using multiple methods. Machine learning was applied to predict models based on the expression profiles of intersecting targets，and nomogram models were constructed based on key targets. Molecular docking of the top four active ingredients with key targets was performed using AutoDockVina. A collagen-induced arthritis （CIA） rat model was established using bovine type Ⅱ collagen，with SD rats divided into groups including a blank group，a model group，and low-，medium-，and high-dose groups of Huangqi Guizhi Wuwutang （2.44，4.88，and 9.76 g·kg^-1） and administered for five consecutive weeks. Joint scores and gastrocnemius muscle mass were recorded and analyzed after modeling. Hematoxylin and eosin （HE） staining and Masson's staining were used to observe pathological changes in muscle tissue. Immunofluorescence staining was applied to observe the protein expression levels of myosin heavy chain （MYHC） and insulin-like growth factor-1 （IGF-1） in skeletal muscle. Western blot was used to detect the protein expression levels of autophagy-related proteins ATG5，Beclin1，LC3B，muscle-specific proteins （MuRF1），MaFbx，and MYHC. Real-time quantitative reverse transcription PCR （Real-time PCR） was performed to measure the mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，MaFbx，and MYHC in muscle tissue. ResultsNetwork pharmacology revealed that Huangqi Guizhi Wuwutang shared 25 common targets with autophagy genes related to RA-associated sarcopenia. The PPI network and machine learning identified six key targets，which were primarily involved in autophagy and inflammatory pathways. Animal experiments showed that compared to the blank group，the model group had significantly higher joint scores （P<0.01） and lower gastrocnemius muscle index （P<0.01）. HE staining indicated a significant reduction in the cross-sectional area of gastrocnemius muscle fibers，with notable inflammatory cell infiltration and muscle atrophy in the model group. Masson's staining revealed obvious collagen fiber proliferation and deposition，with significant muscle fibrosis in the model group. The protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx were significantly increased （P<0.01），while the protein expression of MYHC and IGF1 was significantly downregulated （P<0.01）. Compared with the model group，the high-dose group of Huangqi Guizhi Wuwutang showed significantly reduced protein and mRNA expression levels of ATG5，Beclin1，LC3B，MuRF1，and MaFbx （P<0.01） and increased protein expression levels of MYHC and IGF1 （P<0.01）. The cross-sectional area of muscle fibers increased，and the muscle cell morphology approached normal. Moreover，pathological abnormalities in the gastrocnemius muscle were significantly improved，with reduced collagen fiber proliferation （P<0.01）. ConclusionHuangqi Guizhi Wuwutang can mediate autophagy by regulating the expression of ATG5，Beclin1，LC3B，and IGF1，thereby reducing skeletal muscle catabolism and improving skeletal muscle homeostasis，which contributes to the treatment of RA-associated sarcopenia. The findings provide insight into the mechanisms underlying the effects of Huangqi Guizhi Wuwutang in the treatment of RA-related sarcopenia and offer a reference for its enhanced clinical application.

This paper systematically combed and verified the name， origin， producing area， quality evaluation， harvesting， processing of Euryales Semen in famous classical formulas by consulting relevant ancient materia medica， medical books， prescription books and modern literature. The results showed that Euryales Semen was first collected by materia medica under the name of Jitoushi， and since the Ming dynasty， Qianshi has been used as a proper name and continues to this day， with other aliases such as Yanhuishi. Euryale ferox， a plant of the Nymphaeaceae family， is the same as that used in the past dynasties. However， due to long-term artificial domestication， the varieties vary with the origin， including Beiqian and Suqian. The medicinal part of Euryales Semen is mature seed kernel， its origin of ancient records mainly includes Shandong， Jiangsu， Henan and other places， since the Ming and Qing dynasties， Euryales Semen produced in Suzhou has been highly praised. Since modern times， it has gradually summarized and formed the best quality evaluation method of Euryales Semen with full grains， white cross-section， powdery enough and no broken powder. The harvesting time in the past dynasties was mainly August or in autumn. The main processing methods in the past dynasties included peeling for powder， pounding powder after steaming， drying and frying. Up to now， two mainstream processing methods of cleansing and stir-frying have been formed. Based on the research results， it is recommended that the mature seed kernel of E. ferox be used in famous classical formula Yihuangtang. Combined with the processing requirements of the original formula， it is suggested to refer to the stir-frying method in the general principles of processing of the current edition of Chinese Pharmacopoeia.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology has the characteristics of high specificity and high throughput, making it rapidly applied and developed in the field of clinical testing. Its application in the monitoring of therapeutic drugs can effectively improve the quantitative accuracy and sensitivity, and formulate a personalized and optimal dosing plan for patients. However, this technology still faces some challenges, and automation, quality control, and quantitative traceability will be the future development direction.

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.