1.Optimization Strategy and Practice of Traditional Chinese Medicine Compound and Its Component Compatibility
Zhihao WANG ; Wenjing ZHOU ; Chenghao FEI ; Yunlu LIU ; Yijing ZHANG ; Yue ZHAO ; Lan WANG ; Liang FENG ; Zhiyong LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):299-310
Prescription optimization is a crucial aspect in the study of traditional Chinese medicine (TCM) compounds. In recent years, the introduction of mathematical methods, data mining techniques, and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables, including the proportions of different herbs, the specific extraction parts of each ingredient, and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context, it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues, such as the optimization of source material selection, dosage optimization of compatible herbs, and multi-objective optimization indicators, were discussed. Furthermore, the evaluation methods for component effects were summarized during the optimization process, so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.
2.Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway
Ying WANG ; Zihan GONG ; Wenqing LIANG ; Jingwen YANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):88-96
ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth, the rats were randomly divided into blank (NC) group, maternal-infant separation (MS) group, restraint stress (RS) group, maternal-infant separation combined with restraint stress (MRS) group, Wenyang group, Jieyu group, Wenyang Jieyu (XSF) group, and minocycline group. Maternal-infant separation was performed on day 5 (PD5), followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group, Xiaoyao group, XSF group and minocycline group were 5.85, 12.03, 16.71 g·kg-1 and 50 mg·kg-1, respectively. Restraint stress was applied on PD90. The model was evaluated using glucose, social interaction, open field, and O-maze behavior tests, as well as high-performance liquid chromatography to measure serotonin, dopamine, and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 (Iba-1) protein, a marker of hippocampal microglia, was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3) in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect mRNA expression levels of M1 markers, JAK2/STAT3 pathway-related genes, and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group, the MRS group exhibited depression-like behavior, with significantly decreased levels of neurotransmitters in the hippocampus (P<0.05, P<0.01), increased expression of Iba-1 (P<0.01), and elevated protein levels of JAK2 and STAT3 (P<0.05). The mRNA expression levels of CD68, CD11b, IL-1β, JAK2, and STAT3 were significantly increased (P<0.01), while IL-10 mRNA expression was significantly decreased (P<0.01). Compared with the MRS group, the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups, the hippocampal neurotransmitter content was significantly increased (P<0.05, P<0.01), and Iba-1 expression was significantly decreased (P<0.01). The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68, CD11b, JAK2, STAT3, and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups (P<0.05, P<0.01), while IL-10 mRNA expression was significantly increased (P<0.05, P<0.01). ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.
3.Exploring Mechanism of Hei Xiaoyaosan Regulating PI3K/Akt Pathway to Improve Learning and Memory Ability of Insomnia Rats with Liver Depression Syndrome Based on Transcriptomics
Jiamin LIU ; Yale WANG ; Hai HUANG ; Yue LI ; Xin FAN ; Pengpeng LIANG ; Shizhao ZHANG ; Mei YAN ; Guiyun LI ; Hongyan WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(16):114-125
ObjectiveBased on transcriptomics, to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group, model group, eszopiclone group (0.09 mg·kg-1), and low, medium, and high dose groups of Hei Xiaoyaosan (3.82, 7.65, 15.30 g·kg-1), with ten rats in each group. Except for the blank group, the other groups were induced insomnia rat model with liver depression by chronic restraint, tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine (PCPA). Each treatment group received intragastric administration according to the specified dosage, once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test, open field test, and Morris water maze test were used to test the sleep quality, depressive-like behavior, and learning and memory abilities of rats. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to detect the contents of 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA), brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF) and nitric oxide (NO) in hippocampus. Hematoxylin-eosin (HE) staining was performed to observe pathological changes of the hippocampal tissue, while terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group, as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on the intersecting genes. Subsequently, the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was utilized to assess the mRNA expression levels of phosphatase and tensin homolog (PTEN), B-cell lymphoma-2 (Bcl-2)-like protein 11 (BCL2L11), and mitogen-activated protein kinase 1 (MAPK1) in hippocampus, and Western blot was employed to evaluate the protein expressions of PI3K, phosphorylation (p)-PI3K, Akt, p-Akt, Bcl-2, Bcl-2-associated X protein (Bax), and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group, the model group exhibited a reduction in body weight, an increase in sleep latency, and a decrease in sleep duration (P<0.01). Additionally, rats showed obvious depression-like behavior, and their learning and memory abilities decreased. Furthermore, the contents of 5-HT, GABA, NO, BDNF and GDNF in hippocampus decreased (P<0.01). Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus, characterized by irregular cell shapes, a reduced cell count, deeply stained and pyknotic nuclei, increased vacuolar degeneration, and an elevated apoptosis rate (P<0.01). Compared with the model group, the body weight of the high and medium dose groups of Hei Xiaoyaosan increased, the sleep latency shortened and the sleep time prolonged (P<0.05, P<0.01). Additionally, depression-like behavior and learning and memory abilities of rats were significantly improved, the levels of 5-HT, GABA, NO, BDNF and GDNF in the hippocampus increased (P<0.05, P<0.01). These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons (P<0.01). Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN, BCL2L11, and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group, the expression levels of PTEN, BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased (P<0.01), while the protein expression levels of p-PI3K, p-Akt and Bcl-2 were decreased (P<0.01), and the protein expression levels of PTEN, Bax and cleaved Caspase-3 were increased (P<0.01). Compared with the model group, the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN, BCL2L11 and MAPK1 mRNAs (P<0.01), up-regulate the expressions of p-PI3K, p-Akt and Bcl-2 proteins (P<0.01), and down-regulate the protein expressions of PTEN, Bax and cleaved Caspase-3 (P<0.05, P<0.01). ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN, BCL2L11 and MAPK1, and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.
4.Comparative study of orthopaedic robot-assisted minimally invasive surgery and open surgery for limb osteoid osteoma.
Junwei FENG ; Weimin LIANG ; Yue WANG ; Zhi TANG ; MuFuSha A ; Baoxiu XU ; Niezhenghao HE ; Peng HAO
Chinese Journal of Reparative and Reconstructive Surgery 2024;38(1):40-45
OBJECTIVE:
To compare the accuracy and effectiveness of orthopaedic robot-assisted minimally invasive surgery versus open surgery for limb osteoid osteoma.
METHODS:
A clinical data of 36 patients with limb osteoid osteomas admitted between June 2016 and June 2023 was retrospectively analyzed. Among them, 16 patients underwent orthopaedic robot-assisted minimally invasive surgery (robot-assisted surgery group), and 20 patients underwent tumor resection after lotcated by C-arm X-ray fluoroscopy (open surgery group). There was no significant difference between the two groups in the gender, age, lesion site, tumor nidus diameter, and preoperative pain visual analogue scale (VAS) scores ( P>0.05). The operation time, lesion resection time, intraoperative blood loss, intraoperative fluoroscopy frequency, lesion resection accuracy, and postoperative analgesic use frequency were recorded and compared between the two groups. The VAS scores for pain severity were compared preoperatively and at 3 days and 3 months postoperatively.
RESULTS:
Compared with the open surgery group, the robot-assisted surgery group had a longer operation time, less intraoperative blood loss, less fluoroscopy frequency, less postoperative analgesic use frequency, and higher lesion resection accuracy ( P<0.05). There was no significant difference in lesion resection time ( P>0.05). All patients were followed up after surgery, with a follow-up period of 3-24 months (median, 12 months) in the two groups. No postoperative complication such as wound infection or fracture occurred in either group during follow-up. No tumor recurrence was observed during follow-up. The VAS scores significantly improved in both groups at 3 days and 3 months after surgery when compared with preoperative value ( P<0.05). The VAS score at 3 days after surgery was significantly lower in robot-assisted surgery group than that in open surgery group ( P<0.05). However, there was no significant difference in VAS scores at 3 months between the two groups ( P>0.05).
CONCLUSION
Compared with open surgery, robot-assisted resection of limb osteoid osteomas has longer operation time, but the accuracy of lesion resection improve, intraoperative blood loss reduce, and early postoperative pain is lighter. It has the advantages of precision and minimally invasive surgery.
Humans
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Robotics
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Osteoma, Osteoid/surgery*
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Orthopedics
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Blood Loss, Surgical
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Retrospective Studies
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Neoplasm Recurrence, Local
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Minimally Invasive Surgical Procedures
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Bone Neoplasms/surgery*
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Analgesics
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Treatment Outcome
5.Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumors: a report of 15 cases in a national medical center.
Huan LIANG ; Si Jie LI ; Jia Xin YANG ; Ming WU ; Dong Yan CAO ; Jin Hui WANG ; Tao WANG ; Xin Yue ZHANG
Chinese Journal of Obstetrics and Gynecology 2024;59(1):64-69
Objective: To evaluate the incidence, treatment, and survival outcomes of Swyer syndrome with gonadal non-dysgerminoma malignant germ cell tumor (MGCT-NDG). Methods: A retrospective study was performed on Swyer syndrome patients with MGCT-NDG between January 2011 and December 2022 in Peking Union Medical College Hospital to investigate their characteristics and outcomes. Results: A total of 15 patients (4.9%, 15/307) with Swyer syndrome were identified in 307 MGCT-NDG patients. The average age at diagnosis of MGCT-NDG and Swyer syndrome were (16.8±6.7) and (16.7±6.6) years, respectively. Six cases were preoperatively diagnosed as Swyer syndrome, of which 4 cases received bilateral gonadectomy with or without hysterectomy, while the other 2 cases underwent removal of gonadal tumor and unilateral gonadectomy with hysterectomy, respectively. Of the 9 patients postoperatively diagnosed as Swyer syndrome, unilateral gonadectomy, removal of gonadal tumor, and unilateral gonadectomy with hysterectomy were performed in 6 patients, 2 patients, and 1 patient, respectively. Mixed malignant germ cell tumor (MGCT;10 cases), yolk sac tumor (4 cases), and immature teratoma (1 case) were the pathological subtypes, in the descending order. There were International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ in 6 cases, stage Ⅱ in 3 cases, stage Ⅲ in 5 cases, and stage Ⅳ in 1 case, respectively. Eleven patients received reoperation for residual gonadectomy after a average delay of (7.9±6.2) months, including 8 MGCT-NDG patients and 1 gonadoblastoma patient, no tumor involved was seen in the remaining gonads in the other 2 cases. Ten patients experienced at least one recurrence, with a median event free survival of 9 months (5, 30 months), of which 2 patients received surgery only at the time of initial treatment. All patients with recurrence received surgery and combined with postoperative chemotherapy. After a median follow-up of 25 months (15, 42 months), 10 patients were disease-free, 3 patients died of the tumor, 1 died of side effects of leukemia chemotherapy, and 1 survived with disease. Conclusion: The incidence rate of Swyer syndrome in patients with MGCT-NDG is about 4.9%; timely diagnosis and bilateral gonadectomy should be emphasized to reduce the risk of reoperation and second carcinogenesis in this population.
Female
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Humans
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Retrospective Studies
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Gonadal Dysgenesis, 46,XY/surgery*
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Gonadoblastoma/surgery*
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Neoplasms, Germ Cell and Embryonal/surgery*
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Ovarian Neoplasms/pathology*
6.Recent advances in lamellar liquid crystal emulsification methods encapsulating natural active substances for functional cosmetics
Yi ZHANG ; Wei CHEN ; Yan-qi HAN ; Qian-wen SUN ; Yue GAO ; Jun YE ; Hong-liang WANG ; Li-li GAO ; Yu-ling LIU ; Yan-fang YANG
Acta Pharmaceutica Sinica 2024;59(2):350-358
Due to the high similarity with the lipid layer between human skin keratinocytes, functional cosmetics with layered liquid crystal structure prepared by liquid crystal emulsification technology encapsulating natural active substances have become a hot research topic in recent years. This type of functional cosmetic often has a fresh and natural skin feel, excellent skin barrier repair function and efficient moisturizing effect, etc., showing great potential in cosmetic application. However, the present research on the application of liquid crystal emulsification technology to functional cosmetics is still in the initial stage, and there are fewer relevant reports with reference values. Based on the mentioned above, this review provides a comprehensive summary of functional cosmetics with layered liquid crystal structures prepared by liquid crystal emulsification technology from the following aspects: the structure of human skin, the composition of lamellar liquid crystal, the advantages of liquid crystal emulsification technology containing natural active substances used in the field of functional cosmetics, the preparation process, main components, influencing factors during the preparation and the market functional cosmetics with lamellar liquid crystal structure. Finally, the prospect of the application of liquid crystal emulsification technology in functional cosmetics is presented, to provide useful references for those engaged in the research of liquid crystal emulsification technology-related functional cosmetics.
7.Research Progress of Traditional Chinese Medicine Intervention in Nrf2/HO-1 Signaling Pathway for Acute Pancreatitis: A Review
Wanling XIN ; Ning WANG ; Cenyi LIANG ; Yue ZU ; Sijia LI ; Minchao FENG ; Guozhong CHEN
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(5):265-271
Acute pancreatitis (AP) is a common clinical acute abdominal disease, which is characterized by acute onset, rapid development, severe disease, many complications, and high mortality rate. It can progress to severe AP (SAP) if not treated promptly in the early stage. The pathogenesis of AP is complex and involves multiple cellular and molecular levels. It is now clear that oxidative stress and reactive oxygen species (ROS) production are involved in the physiopathological process of AP, which is associated with a low quantity and activity of antioxidant enzymes in pancreatic cells. Nuclear factor E2-related factor 2 (Nrf2) serves as the ''golden key'' to maintain redox homeostasis in tissue cells and constitutes an important signaling pathway for antioxidant response and inflammation in vivo by collaborating with downstream antioxidant enzymes such as heme oxygenase-1 (HO-1). Traditional Chinese medicine has unique efficacy in treating diseases due to its multi-component, multi-target, multi-drug delivery, and multi-formulation characteristics. Based on the concept of synergy between traditional Chinese and Western medicine, traditional Chinese medicine is becoming a new craze in the treatment of AP. The level of oxidative stress and Nrf2/HO-1 signaling pathway in AP pancreatic tissue are in a dynamic change process, and the intervention of traditional Chinese medicine can clean ROS production, affect the inflammatory pathway, and reduce oxidative stress damage, so as to protect against pancreatic injury. This suggests that this pathway plays an important role in AP. This article reviews the recent literature on the regulation of the Nrf2/HO-1 signaling pathway by traditional Chinese medicine for AP and summarizes that the monomers of traditional Chinese medicine targeting this pathway are mainly heat-clearing and detoxifying, blood-activating and blood-stasis-removing, and Qi benefiting and middle warming, and the compounds of traditional Chinese medicine include Yinchenhao Decoction and QingYi Ⅱ, so as to provide a new direction for the prevention and treatment of AP and further drug development.
8.Syndromes and Mechanisms of Depression Induced by Second Hit in Mice
Zihan GONG ; Ying WANG ; Jingwen YANG ; Wenqing LIANG ; Danhua MENG ; Kaijie SHE ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):29-38
ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation (MS) combined with chronic restraint stress (RS) in mice. MethodOn postnatal day 0 (PD0), the offspring mice were randomized into a blank group (NC) and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21, the modeled mice were randomized into model, Wenyang, Jieyu, Wenyang Jieyu, and fluoxetine groups, with 15 mice in each group. The sucrose preference, tail suspension, and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone (ACTH) and corticosterone (CORT) levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine (5-HT) system, hypothalamic-pituitary-adrenal (HPA) axis, and brain-derived neurotrophic factor (BDNF) signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B (TrkB) in the hippocampus. ResultCompared with the NC group, the model group exhibited depression-like behavior, which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group, the model group showed elevated levels of CORT and ACTH in the plasma (P<0.01), which, however, were lowered by Wenyang Jieyu prescription and fluoxetine (P<0.05, P<0.01). Compared with the NC group, the model group showed inhibited expression of neurotransmitters in the hippocampus (P<0.05, P<0.01), while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters (P<0.05, P<0.01). Compared with NC group, the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis, and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group, the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus (P<0.05, P<0.01), which, however, were recovered in Wenyang, Jieyu, Wenyang Jieyu, and fluoxetine groups (P<0.05, P<0.01). ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis, thereby alleviating depression-like behavior in mice.
9.Wenyang Jieyu Prescription Regulates Hippocampal Neural Plasticity in Depressed Mice via NLRP3/Caspase-1/IL-1β Pathway
Danhua MENG ; Kaijie SHE ; Xiaoying MENG ; Zinhan GONG ; Wenqing LIANG ; Ying WANG ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):39-47
ObjectiveTo explore the effects of Wenyang Jieyu prescription (WJP) on neuroinflammation and synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 (PD0) were randomized into a control group and a modeling group. Maternal separation combined with restraint stress was employed to establish the mouse model of depression. After the removal of female mice, the modeled mice were randomized into model, Wenyang prescription (5.85 g·kg-1), Jieyu prescription (12.03 g·kg-1), WJP (16.71 g·kg-1), and fluoxetine (2.6 mg·kg-1) groups on the weaning day (PD21), with 15 mice in each group. The mice were administrated with corresponding drugs mixed with the diet from PD21 to PD111. The sucrose preference test, open field test, O-maze test, and novel object recognition test were then carried out to evaluate the depression state, memory, and learning ability of the mice. Immunohistochemistry (IHC) was employed to observe the ionized calcium-binding adapter molecule-1 (Iba-1) in hippocampal microglia. High performance liquid chromatography (HPLC) was employed to measure the content of noradrenaline (NE) and epinephrine (E) in the hippocampus. Enzyme-linked immunosorbent assay (ELISA) was employed to determine the content of interleukin (IL)-18 and IL-1β in the hippocampus. Western blot was employed to determine the protein levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), cysteine aspartate-specific protease-1 (Caspase-1), IL-1β, synaptophysin (Syn), and postsynaptic density 95 (PSD95). ResultCompared with control group, the model group showed decreased sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). The microglia in the model group presented amoeba-like appearance, the Iba1 increased. Moreover, the model group showed decreased content of NE and E (P<0.01), elevated levels of IL-1β and IL-18 (P<0.01), down-regulated protein levels of PSD95 and Syn (P<0.05, P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and IL-1β (P<0.05, P<0.01). Compared with model group, WJP and fluoxetine increased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). They recovered the microglia and the Iba1 decreased. Moreover, the drugs increased the content of NE and E (P<0.05, P<0.01), lowered the levels of IL-1β and IL-18 (P<0.01), up-regulated the protein levels of PSD95 and Syn (P<0.01), down-regulated the protein levels of NLRP3, ASC, Caspase-1, and IL-1β (P<0.05, P<0.01). ConclusionWJP can treat the depressive behavior induced by maternal separation combined with restraint stress in mice, with the performance outperforming Wenyang prescription and Jieyu prescription. It may alleviate the neuroinflammation induced by microglia and improve the synaptic plasticity by regulating the NLRP3 pathway and increasing neurotransmitters in the hippocampus.
10.Wenyang Jieyu Prescription Regulates Hippocampal Neuron Apoptosis and Improves Synaptic Plasticity in Depressed Mice via BDNF/Akt/mTOR Pathway
Danhua MENG ; Kaijie SHE ; Xiaoying MENG ; Zihan GONG ; Wenqing LIANG ; Ying WANG ; Yuan LIANG ; Guangxin YUE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(6):48-57
ObjectiveTo explore the mechanism of Wenyang Jieyu prescription in regulating hippocampal neuron apoptosis and improving synaptic plasticity in the mouse model of depression induced by maternal separation combined with restraint stress. MethodThe mice on postnatal day 0 (PD0) were randomly assigned into a control group (n=10) and a modeling group (n=50). Maternal separation combined with restraint stress was adopted to establish the mouse model of depression, and the modeled mice were randomized into model, Wenyang prescription, Jieyu prescription, Wenyang Jieyu prescription, and fluoxetine groups (n=10) on the weaning day (PD21). From PD21 to PD111, the mice were fed with the diets mixed with corresponding medicines. The sucrose preference test, open field test, O-maze test, and novel object recognition test were then conducted to evaluate the depression, memory, and learning abilities of mice. Immunohistochemistry (IHC) was employed to measure the atomic absorbance (AA) of postsynaptic density protein 95 (PSD95) in the hippocampus. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling (TUNEL) was employed to detect the apoptosis of hippocampal neurons. Western blot was employed to determine the protein levels of brain-derived neurotrophic factor (BDNF), phosphorylated tyrosine kinase receptor B/tyrosine kinase receptor B (p-TrkB/TrkB), phosphorylated protein kinase B/protein kinase B (p-Akt/Akt), phosphorylated mammalian target of rapamycin/mammalian target of rapamycin (p-mTOR/mTOR), B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), cysteinyl aspartate-specific proteinase-3 (Caspase-3), synaptophysin (Syn), and PSD95. ResultCompared with the control group, the modeling decreased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.01). Furthermore, it decreased the expression of PSD95, increased the neuron apoptosis in the hippocampus (P<0.01), down-regulated the protein levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-mTOR/mTOR, Bcl-2, PSD95, and Syn (P<0.01), and up-regulated the protein levels of Bax and Caspase-3 (P<0.05) in the hippocampus. Compared with the model group, Wenyang Jieyu prescription and fluoxetine increased the sucrose preference rate, time spent in central zone within 5 min, total movement distance, time spent in the open arm, and cognition index (P<0.05, P<0.01). Moreover, the drugs increased the expression of PSD95, reduced the neuron apoptosis (P<0.01), up-regulated the protein levels of BDNF, p-TrkB/TrkB, p-Akt/Akt, p-mTOR/mTOR, Bcl-2, PSD95, and Syn (P<0.01), and down-regulated the protein levels of Bax and Caspase-3 (P<0.01). ConclusionWenyang Jieyu prescription outperformed Wenyang prescription and Jieyu prescription in the treatment of the depressive behavior induced by maternal separation combined with restraint stress in mice. It exerted the therapeutic effect by reducing the hippocampal neuron apoptosis and improving the synaptic plasticity via the BDNF/Akt/mTOR pathway.

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