Integrating serum metabolomics and network analysis to explore the antidepressant activity of crocin in rats with chronic unexpected mild stress-induced depression.

CONTEXT: Crocin exhibits anti-depressant properties. However, its underlying mechanisms and its relationship with metabolomics remain unclear. OBJECTIVE: This study elucidates the mechanism of action and potential targets of crocin in treating chronic unexpected mild stress (CUMS)-induced depression in rats. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats underwent 4 weeks of CUMS to establish the depression model. The normal control (distilled water), crocin (25 mg/kg), and fluoxetine (5.4 mg/kg) groups were orally administered for 4-weeks. Behavioural tests evaluated the effects of crocin, while liquid chromatography-mass spectrometry metabolomics identified differential metabolites and their associated metabolic pathways. Subsequently, network pharmacology was utilized to predict the targets of crocin. RESULTS: Crocin significantly increased body weight (from 319.16 ± 4.84 g to 325.67 ± 2.84 g), sucrose preference (from 0.46 ± 0.09 to 0.70 ± 0.09), vertical activity (from 2.83 ± 1.94 to 8 ± 2.36), horizontal activity (from 1 ± 0.63 to 4.5 ± 3.08) and decreased immobilization time (from 13.16 ± 2.69 to 3.97 ± 3.00). Metabolomics analysis identified 7 metabolites and 5 associated metabolic pathways. From the combined analysis of network pharmacology and metabolomics, three targets (PRMT1, CYP3A4, and GLB1) are the overlapping targets and the two most important metabolic pathways are tryptophan metabolism and glycerolipid metabolism. DISCUSSION AND CONCLUSIONS: This study provides insights into the antidepressant therapeutic effect of crocin and its underlying mechanisms. The findings contribute to a better understanding of the metabolic mechanism involved in the anti-depressant effect of crocin, establishing a strong foundation for future research in this area.

Luteolin Induced Hippocampal Neuronal Pyroptosis Inhibition by Regulation of miR-124-3p/TNF-α/TRAF6 Axis in Mice Affected by Breast-Cancer-Related Depression.

Background: Breast-cancer-related depression (BCRD) is associated with an increased mortality rate among breast cancer (BC) survivors. Luteolin has many pharmacological effects, particularly in the treatment of BC. In this study, we aimed to explore the anti-BCRD activity of luteolin and its underlying functional mechanism. Methods: A BCRD mouse model was induced by injecting 4T1 cells and corticosterone (COR). Behavioral test, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, Nissl staining, immunofluorescence, reverse-transcription quantitative PCR (RT-qPCR), and western blotting were used to study the effect of luteolin in mice with BCRD in vivo. A COR-induced neuron injury model was established in HT-22 cells in vitro. The role of miR-124-3p in the anti-BCRD effects of luteolin was studied using a miR-124-3p inhibitor. Results: Luteolin significantly reduced the size and weight of the tumor, increased the mice entry frequency in the symmetrical sector, and reduced the duration of immobility in the tail suspension and forced swimming tests of mice affected by BCRD. Simultaneously, apoptosis of hippocampal neurons was inhibited, and the number of Nissl bodies increased with luteolin treatment. In addition, luteolin resulted in the upregulation of miR-124-3p expression in the hippocampus and downregulated the expression of tumor necrosis factor-α (TNF-α) and TNF receptor-associated factor 6 (TRAF6), as well as lowered the phosphorylation levels of nuclear factor-kappa B (NF-κB) and IkappaB (IκB). Luteolin also inhibited pyroptosis of hippocampal neurons in mice affected by BCRD, as revealed by the low protein levels of NOD-like receptor protein 3 (NLRP3), caspase-1, gasdermin D-N (GSDMD-N), interleukin (IL)-1ß, and IL-18. However, the miR-124-3p inhibitor significantly reversed the therapeutic effect of luteolin on COR-induced HT-22 cells. Conclusion: Our study demonstrated that the anti-BCRD function of luteolin was mediated by regulating the miR-124-3p/TNF-α/TRAF6-related pathway and inhibiting neuronal cell pyroptosis and subsequent inflammation. Therefore, luteolin may be a potential drug candidate in the treatments of BCRD.

Efficacy and safety of naotaifang capsules for hypertensive cerebral small vessel disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled clinical trial.

Background: Hypertensive cerebral small vessel disease (HT-CSVD) is a cerebrovascular clinical, imaging and pathological syndrome caused by hypertension (HT). The condition manifests with lesions in various vessels including intracranial small/arterioles, capillaries, and small/venules. Hypertensive cerebral small vessel disease has complex and diverse clinical manifestations. For instance, it can present as an acute stroke which progresses to cause cognitive decline, affective disorder, unstable gait, dysphagia, or abnormal urination. Moreover, hypertensive cerebral small vessel disease causes 25-30% of all cases of ischemic strokes and more than 50% of all cases of single or mixed dementias. The 1-year recurrence rate of stroke in cerebral small vessel disease patients with hypertension is 14%. In the early stage of development, the symptoms of hypertensive cerebral small vessel disease are concealed and often ignored by patients and even clinicians. Patients with an advanced hypertensive cerebral small vessel disease manifest with severe physical and mental dysfunction. Therefore, this condition has a substantial economic burden on affected families and society. Naotaifang (NTF) is potentially effective in improving microcirculation and neurofunction in patients with ischemic stroke. In this regard, this multicenter randomized controlled trial (RCT) aims to furtherly evaluate the efficacy and safety of naotaifang capsules on hypertensive cerebral small vessel disease. Methods: This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 388 eligible subjects were recruited from the First Hospital of Hunan University of Chinese Medicine, Hunan Academy of Chinese Medicine Affiliated Hospital, the First Hospital of Shaoyang University, the First Traditional Chinese Medicine Hospital of Changde, and Jiangmen Wuyi Hospital of Traditional Chinese Medicine from July 2020 to April 2022. After a 4-week run-in period, all participants were divided into the intervention group (represented by Y-T, N-T) and control group (represented by Y-C, N-C); using a stratified block randomized method based on the presence or absence of brain damage symptoms in hypertensive cerebral small vessel disease (represented by Y and N). The Y-T and N-T groups were administered different doses of naotaifang capsules, whereas Y-C and N-C groups received placebo treatment. These four groups received the treatments for 6 months. The primary outcome included Fazekas scores and dilated Virchow-robin spaces (dVRS) grades on magnetic resonance imaging (MRI). The secondary outcomes included the number of lacunar infarctions (LI) and cerebral microbleeds (CMB) on magnetic resonance imaging, clinical blood pressure (BP) level, traditional Chinese medicine (TCM) syndrome scores, mini-mental state examination (MMSE) scale, and safety outcomes. Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds on magnetic resonance imaging were tested before enrollment and after 6 months of treatment. The clinical blood pressure level, traditional Chinese medicine syndrome scores, mini-mental state examination scale and safety outcomes were tested before enrollment, after 3-month, 6-month treatment and 12th-month follow-up respectively. Conclusion: The protocol will comfirm whether naotaifang capsules reduce Fazekas scores, dilated Virchow-robin spaces grades, and the number of lacunar infarctions and cerebral microbleeds, clinical blood pressure, increase mini-mental state examination scores, traditional Chinese medicine syndrome scores of Qi deficiency and blood stasis (QDBS), and improve the quality of life of subjects. The consolidated evidence from this study will shed light on the benefits of Chinese herbs for hypertensive cerebral small vessel disease, such as nourishing qi, promoting blood circulation and removing blood stasis, and dredging collaterals. However, additional clinical trials with large samples and long intervention periods will be required for in-depth research. Clinical Trial registration: www.chictr.org.cn, identifier ChiCTR1900024524.

Activation of Hippocampal IR/IRS-1 Signaling Contributes to the Treatment with Zuogui Jiangtang Jieyu Decoction on the Diabetes-Related Depression.

BACKGROUND: Zuogui Jiangtang Jieyu decoction (ZJJ) is mainly used for the treatment of diabetes-related depression in current clinical applications and research. This study aims to investigate whether the brain IR/IRS-1 signaling pathway is involved in the therapeutic effect of ZJJ on depression-like behavior in diabetic rats. METHODS: Sprague-Dawley rats were fed with high-fat diet and subjected to streptozotocin injection to establish the diabetes animal model. After treatment with different doses of ZJJ (20.530 g/kg or 10.265 g/kg) for 4 weeks, the blood glucose level and peripheral insulin resistance were measured. The forced-swimming test (FST) and Morris water maze test (MWMT) were applied for the mood and cognitive function assessment. Then, the Western blot method was used to analyze the protein levels of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylonositol-3-kinase (PI3K), and protein kinase B (PKB, also as known as AKT) in the hippocampus of diabetic rats. Meanwhile, the immunofluorescence method was performed to analyze the above proteins' expression in the neuron and astrocyte. At last, the levels of glycogen, lactate, and ATP were tested by the ELISA method. Additionally, the insulin-sensitive glucose transporter 4 (GLUT4) and the lactate transporter monocarboxylate transporter 4 (MCT4) were analyzed by the Western blot method. RESULTS: ZJJ administration significantly decreased the level of blood glucose and improved the peripheral insulin resistance in diabetic rats. Besides, ZJJ attenuated the depression-like behavior and the cognitive dysfunction in rats with diabetes. Furthermore, we found the upregulation of protein expression of phospho-IR, phospho-IRS-1, phospho-PI3K, and phospho-AKT in the hippocampus of diabetic rats after being treated with ZJJ. Moreover, the above proteins are increased not only in the neuron but also in the astrocyte after ZJJ administration. In addition, ZJJ increased the content of ATP, glycogen, and lactate, as well as the expression of GLUT4 and MCT4 in the hippocampus of diabetic rats. CONCLUSIONS: These findings suggest that ZJJ improves the depression-like behavior of diabetic rats by activating the IR/IRS-1 signaling pathway in both hippocampal neuron and astrocyte. And the brain IR/IRS-1 signaling pathway plays an important role in astrocyte-neuron metabolic coupling, providing a potential mechanism by which the IR/IRS-1 signaling pathway may contribute to the treatment of ZJJ on diabetes-related depression.

[Effect of Baihe Dihuang Decoction on synaptic plasticity of hippocampus in rats with anxious depression].

To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.

[Effects of ELK-1/JNK/c-Fos on apoptosis of rat hippocampal neurons cultured in vitro with Zuogui Jiangtang Jieyu Formula in simulated diabetes mellitus complicated with depression].

OBJECTIVE: To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD). METHODS: The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes. RESULTS: Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P＜0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P＜ 0.05), and the neural network and dendritic junction were improved significantly. CONCLUSION: Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.

Xiaoyao Kangai Jieyu Fang, a Chinese Herbal Formulation, Ameliorates Cancer-Related Depression Concurrent with Breast Cancer in Mice via Promoting Hippocampal Synaptic Plasticity.

Diagnosis with breast cancer is a major life event that elicits increases in depressive symptoms for up to 50% of women. Xiaoyao Kangai Jieyu Fang (XYKAJY) is derived from a canonical TCM formula, Xiaoyao San (XYS), which has a history of nearly 1000 years for treating depression. The aim of this study was to investigate whether XYKAJY alleviates depression-like behavior and breast tumor proliferation in breast cancer mice then explore the mechanisms underlying its action on HPA axis and hippocampal plasticity further. XYKAJY was treated at the high dose of 1.95 g/mL and 0.488 g/mL, after 21 days of administration. Different behaviors, monoamine neurotransmitters, tumor markers, and the index of HPA axis were detected to evaluate depressive-like symptoms of breast cancer mice. Also, the pathological changes of the tumor, hippocampus, and the expressions of GR, NR2A, NR2B, CAMKII, CREB, and BDNF were detected. In this study, XYKAJY formulation significantly improved the autonomic behavior, reduced the incubation period of feeding, and reversed the typical depressive-like symptoms in breast cancer mice. Also, it reduced the content of CORT, ACTH, CRH, and CA125, CA153, CEA in the blood, protected the pathological changes of the hippocampus and tumor, upregulated the expression of GR, CREB, and BDNF in the hippocampus, and significantly decreased the expression of NR2A, NR2B, and CaMKII. These results provide direct evidence that XYKAJY effectively alleviates depression-like behaviors and tumor proliferation in vehicle mice with ameliorates hippocampus synaptic plasticity dysfunctions.

Chronic Unpredictable Mild Stress Aggravates Mood Disorder, Cognitive Impairment, and Brain Insulin Resistance in Diabetic Rat.

Diabetes-induced brain insulin resistance is associated with many mental diseases, including depression. Epidemiological evidences demonstrate the pathophysiologic link between stress, depression, and diabetes. This study was designed to determine whether chronic unpredictable mild stress- (CUMS-) induced changes in brain insulin resistance could contribute to deterioration in mood and cognitive functions in diabetic rats. Male SD rats were randomly assigned to three groups, including standard control group, the diabetes group, and the diabetes with CUMS group. After 7 weeks, emotional behaviors and memory performances as well as metabolic phenotypes were measured. In addition, we examined the changes in protein expression related to brain insulin signaling. Our results show that rats in diabetes with CUMS group displayed a decreased locomotor behavior in open-field test, an increased immobility time in forced swim test, and tail suspension test, and an impaired learning and memory in the Morris water maze when compared to animals in diabetes group. Further, diabetes with CUMS exhibited a significant decrease in phosphorylation of insulin receptor and an increase phosphorylation of IRS-1 in brain. These results suggest that the depression-like behaviors and cognitive function impairments in diabetic rats with CUMS were related to the changes of brain insulin signaling.

Standardization of preparation of rice fried Codonopsis Radix based on correlation analysis of functional component and shape index / 中国中药杂志

The quality standard of Chinese herbal medicine is the key in quality control, and the establishment of rice processing technology standard of rice fried Codonopsis Radix has important significance for the overall quality control. In this study, the color brightness (L*), red-green chromaticity coordinate (a*), yellow-blue chromaticity coordinate (b*) and total color value（E*ab）were determined by colorimeter and used as the shape indexes. Ethanol extractives, polysaccharide, lobetyolin and 5-hydroxymethyl furfural contents were determined by using high performance liquid chromatography (HPLC) and ultraviolet (UV), and used as chemical indexes in the analysis by normalization distance method. The two index methods were adopted to optimize the processing technology of rice fried Codonopsis Radix by taking processing temperature, processing time, rice types and rice dosage as factors. The correlation analysis between the two index methods was carried out by SAS 9.40 and JMP 11 software. The results showed that all the four factors had significant differences, and the best processing technology was as follows: polished round-grained rice as raw material, processing temperature at 140 °C, processing time of 10min, and the ratio of Codonopsis pilosula and rice is 100:30. Chemical indexes showed significant positive correlations with shape indexes, providing basis for the quality evaluation of rice fried Codonopsis Radix in processing.

Impacts of multicomponent environment on intrinsic dissolution rate of berberine in biopharmaceutics classification system of Chinese materia medica / 中国中药杂志

To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics classification system of Chinese materia medica(CMMBCS), investigate the effect of artificial multicomponent environment on IDR of berberine, by using a non-disintegrating disk, and summarize related rules by using the obtained data. Progressive levels design was used to investigate the effects of single component environment (puerarin, baicalin, and glycyrrhizic acid); double-component environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on IDR of berberine, laying a foundation for further researches on the absorption mechanism of multiple components.

In vitro and in vivo intestinal absorption of Huanglian decoction in multi-component environment / 中国中药杂志

The effect of drugs in the body is always inseparable with the dynamic processes of absorption, distribution, metabolism and excretion. For oral drug, absorption, as the first link to enter the body, is particularly valued. Traditional Chinese medicine has multiple components and multiple targets, and the nature of its single composition is different from that in the multicomponent environment. Alkaloids in Huanglian extract was used as the main object in this study to establish an analytical method for determining the content of alkaloids in Huanglian. In addition, the compositions of the Huanglian aqueous extract solution which can be absorbed through intestinal wall into blood, were initially determined by the means of everted gut sac and in intestinal perfusion with venous sampling experiment. This paper can provide data reference and support for the further study on the absorption and metabolism of Huanglian.

Overall intestinal permeability of multiple components in lotus leaf by in situ single pass intestinal perfusion models / 中国中药杂志

To investigate the overall intestinal permeability of multiple components in lotus leaves and make clear the interaction in composition absorption process. Rat single-pass intestinal perfusion technique was used, and the results showed that the Peff values of nuciferine, demethylanuciferine, rutin, quercetin, kaempferol from lotus leaf were greater than 0.5×10⁻⁴ cm•s⁻¹. In the biopharmaceutics classification system (BCS) intestinal permeability property, these ingredients were high permeable components, while the hyperin was low permeable component. However, in the multi-component environment of the lotus leaf extract, component permeation was changed. Semi quantitative analysis of the unclear components showed that under the multi-component environment, four in seven components with relatively high contents had a Peff value less than 0.5×10⁻⁴ cm•s⁻¹, indicating these 4 components were of low permeability, while other 3 components were of high permeability. The results could be valuable to make clear the overall intestinal permeability of multiple components in lotus leaf, and lay a foundation for studying the mechanism of the lipid-lowering effect of lotus leaf.

Study on biopharmaceutics classification system for Chinese materia medica of extract of Huanglian / 中国中药杂志

One of the advantages of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is expanding the classification research level from single ingredient to multi-components of Chinese herb, and from multi-components research to holistic research of the Chinese materia medica. In present paper, the alkaloids of extract of huanglian were chosen as the main research object to explore their change rules in solubility and intestinal permeability of single-component and multi-components, and to determine the biopharmaceutical classification of extract of Huanglian from holistic level. The typical shake-flask method and HPLC were used to detect the solubility of single ingredient of alkaloids from extract of huanglian. The quantitative research of alkaloids in intestinal absorption was measured in single-pass intestinal perfusion experiment while permeability coefficient of extract of huanglian was calculated by self-defined weight coefficient method.

Discussion on research thinking of traditional Chinese medicine standardization system based on whole process quality control / 中国中药杂志

The concept of "Quality by design" indicates that good design for the whole life cycle of pharmaceutical production enables the drug to meet the expected quality requirements. Aiming at the existing problems of the traditional Chinese medicine (TCM) industry, the TCM standardization system was put forward in this paper from the national strategic level, under the guidance by the idea of quality control in international manufacturing industry and with considerations of TCM industry's own characteristics and development status. The connotation of this strategy was to establish five interrelated systems: multi-indicators system based on tri-indicators system, quality standard and specification system of TCM herbal materials and decoction pieces, quality traceability system, data monitoring system based on whole-process quality control, and whole-process quality management system of TCM, and achieve the whole process systematic and scientific study in TCM industry through "top-level design-implement in steps-system integration" workflow. This article analyzed the correlation between the quality standards of all links, established standard operating procedures of each link and whole process, and constructed a high standard overall quality management system for TCM industry chains, in order to provide a demonstration for the establishment of TCM whole-process quality control system and provide systematic reference and basis for standardization strategy in TCM industry.

Clinical Observation of Short-segment Percutaneous Pedicle Screw Non-fusion Fixation Plus Electro-acupuncture for Treatment of Single Thoracolumbar Fracture / 广州中医药大学学报

Objective To investigate the feasibility of short-segment percutaneous pedicle screw non-fusion fixation plus electro-acupuncture for the treatment of single thoracolumbar fracture.Methods Forty-three patients with single thoracolumbar fracture were treated with short-segment percutaneous pedicle screw fixation without fusion,and then were given electro-acupuncture on points such as Jiaji (EX-B2),Huantiao (GB30),and Zhibian (BL54) after the operation.Before and after operation and during the follow-up,X-ray images of the spine at positive position and lateral position were taken for the measurement of vertebral anterior and posterior diameter ratio and the vetebral kyphosis Cobb's angle.Lumbago visual analogue scale (VAS) scores and Oswestry scores for lumbago function disorder were used for the evaluation of clinical efficacy.Results (1) All of the 43 patients were followed-up,and the follow-up period lasted for 10-27 months.(2) After the operation and at the end of follow-up,vertebral anterior and posterior diameter ratio and Cobb's angle were much improved (P ＜ 0.01compared with those before the operation),and the two indexes at the end of follow-up were improved as compared with those after the operation (P ＜ 0.05).(3) One week after the operation and at the end of follow-up,VAS scores and Oswestry scores were obviously improved as compared with those before treatment (P ＜ 0.01),and the two kinds of scores at the end of follow-up were also improved as compared with those after the operation (P ＜0.01).Conclusion Short-segment percutaneous pedicle screw fixation without fusion plus electro-acupuncture at points such as Jiaji is effective for the treatment of single thoracolumbar fracture by relieving pain in the waist and back,which ensures the satisfactory effect of operation.

Zuogui Jiangtang Jieyu Formulation Prevents Hyperglycaemia and Depressive-Like Behaviour in Rats by Reducing the Glucocorticoid Level in Plasma and Hippocampus.

Aim. To determine whether Zuogui Jiangtang Jieyu prescription (ZGJTJY) has hypoglycemic and antidepressant effects which are mediated by corticosterone through adjustment of 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and glucocorticoid (GR) levels. Materials and Methods. The diabetes-related depression rats were randomly divided into four groups: the model group, metformin (1.8 mg/kg) combined with fluoxetine (10.8 mg/kg) group, and ZGJTJY high and low dose groups. Four weeks after modeling, blood glucose, behavior, and cognitive function of depression were detected. The expressions of 11ß-HSD1 and GR in hippocampus were measured by western blotting and immunohistochemical experiments. Results. We found that (1) the treatment with ZGJTJY (10.26 g/kg) increases the motor activities and improves cognition ability. (2) ZGJTJY (10.26 g/kg) significantly relieves the disorder in blood and the relative indexes. (3) ZGJTJY (10.26 g/kg) can reduce hippocampal corticosterone expression levels and further improve hippocampus pathological changes. (4) ZGJTJY increased the expression of GR accompanied with decreasing 11ß-HSD1 in hippocampus. Conclusions. ZGJTJY inhibits the expression of 11ß-HSD1 and increases GR in hippocampus and subsequently modulates blood glucose levels, and therefore it is potential property that ZGJTJY could be of benefit for the treatment of behavior and cognitive function of diabetes-related depression.