1.Effect of Modified Wenyang Sanjie Prescription on Th1/Th2 Balance and Tumor Microangiogenesis in Lung Cancer Tumor-bearing Mice
Xinxin WANG ; Junhui GUO ; Honglin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):127-134
ObjectiveTo study the tumor inhibition and T helper cell (Th)1/Th2 balance regulation effect of modified Wenyang Sanjie prescription on lung cancer tumor-bearing mice and to elaborate its mechanism. MethodsA mouse model bearing a lung cancer tumor was established by subcutaneous injection of Lewis lung cancer cells into the armpit and was randomly divided into lung cancer model group, low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription, and positive control group, with 12 mice per group. The low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription were given modified Wenyang Sanjie prescription by dosing at 2.5, 5, 10 g·kg-1, once a day, respectively. The positive control group was intraperitoneally injected with cisplatin (2 mg·kg-1), once every other day, for a total of 30 days. Serum interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA), and spleen index, thymus index, and tumor growth inhibition rate were calculated. Tumor microvascular density was determined by immunohistochemistry, and tumor hypoxia inducible-factor (HIF)-1α, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) mRNA were determined by Real-time quantitative polymerase chain reaction (PCR). The protein levels of HIF-1α, EGFR, and VEGF were determined by Western blot. ResultsCompared with lung cancer model group, IFN-γ and IL-2 were increased in the modified Wenyang Sanjie prescription groups and positive control group, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). Compared to the low-dose group of modified Wenyang Sanjie prescription, IFN-γ and IL-2 were increased in the medium-dose and high-dose groups of modified Wenyang Sanjie prescription, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). IFN-γ and IL-2 were increased in the high-dose group of modified Wenyang Sanjie prescription compared to the medium-dose group of modified Wenyang Sanjie prescription, and IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). ConclusionModified Wenyang Sanjie prescription can significantly inhibit microangiogenesis, regulate Th1/Th2 balance, inhibit tumor growth, and significantly inhibit the progression of lung cancer in mice.
2.Effect of Modified Wenyang Sanjie Prescription on Th1/Th2 Balance and Tumor Microangiogenesis in Lung Cancer Tumor-bearing Mice
Xinxin WANG ; Junhui GUO ; Honglin LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):127-134
ObjectiveTo study the tumor inhibition and T helper cell (Th)1/Th2 balance regulation effect of modified Wenyang Sanjie prescription on lung cancer tumor-bearing mice and to elaborate its mechanism. MethodsA mouse model bearing a lung cancer tumor was established by subcutaneous injection of Lewis lung cancer cells into the armpit and was randomly divided into lung cancer model group, low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription, and positive control group, with 12 mice per group. The low-dose, medium-dose, and high-dose groups of modified Wenyang Sanjie prescription were given modified Wenyang Sanjie prescription by dosing at 2.5, 5, 10 g·kg-1, once a day, respectively. The positive control group was intraperitoneally injected with cisplatin (2 mg·kg-1), once every other day, for a total of 30 days. Serum interferon (IFN)-γ, interleukin (IL)-2, IL-4, IL-6, and IL-10 were determined by enzyme-linked immunosorbent assay (ELISA), and spleen index, thymus index, and tumor growth inhibition rate were calculated. Tumor microvascular density was determined by immunohistochemistry, and tumor hypoxia inducible-factor (HIF)-1α, epidermal growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF) mRNA were determined by Real-time quantitative polymerase chain reaction (PCR). The protein levels of HIF-1α, EGFR, and VEGF were determined by Western blot. ResultsCompared with lung cancer model group, IFN-γ and IL-2 were increased in the modified Wenyang Sanjie prescription groups and positive control group, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). Compared to the low-dose group of modified Wenyang Sanjie prescription, IFN-γ and IL-2 were increased in the medium-dose and high-dose groups of modified Wenyang Sanjie prescription, while IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). IFN-γ and IL-2 were increased in the high-dose group of modified Wenyang Sanjie prescription compared to the medium-dose group of modified Wenyang Sanjie prescription, and IL-4, IL-6, IL-10, spleen index, thymus index, tumor weight, and tumor microvascular density were decreased, as well as HIF-1α, EGFR, and VEGF mRNA and protein levels (P<0.05). ConclusionModified Wenyang Sanjie prescription can significantly inhibit microangiogenesis, regulate Th1/Th2 balance, inhibit tumor growth, and significantly inhibit the progression of lung cancer in mice.
3.Study on activation mechanism of SGCs in representation along the distribution of stomach meridian in IBS-D mice.
Na LI ; Junhui REN ; Lu GUAN ; Yashuang XU ; Liyan ZHONG ; Xiaomei SHAO ; Jianqiao FANG ; Junying DU ; Junfan FANG
Chinese Acupuncture & Moxibustion 2025;45(5):593-600
OBJECTIVE:
To explore the peripheral neural mechanism underlying representation along the distribution of stomach meridian induced by intestinal inflammatory reaction using diarrhea predominant-irritable bowel syndrome (IBS-D) mice.
METHODS:
Among 62 healthy male C57BL/6 mice of clean grade, 12 mice were randomly selected and divided into a control group and a model group, 6 mice in each group, additionally, 12 mice were randomly selected and divided into a Tianshu group, a Liangqiu group and a Zusanli group, 4 mice in each group. In the model group, citrobacter was administered orally to establish IBS-D model. In the control group and the model group, the visceral pain threshold was observed using fecal colorectal distension (fCRD) induced electromyography of external oblique muscle, the positive cell number of neutrophil in the colonic muscularis was detected by myeloperoxidase (MPO) staining, the number, location and distribution rule of Evans blue (EB) extravasation points were observed by injection of EB staining solution into the tail vein. In the Tianshu group, the Liangqiu group and the Zusanli group, fluorescent dye Dil was injected at bilateral "Tianshu" (ST25), "Liangqiu" (ST34) and "Zusanli" (ST36) respectively, to observe the dye-positive cell number in different dorsal root ganglion (DRG) segments. In the control group and the model group, the activation of satellite glial cells (SGCs) in different DRG segments was observed by immunofluorescence.
RESULTS:
Compared with the control group, in the model group, the area under curve of electromyography of external oblique muscle was increased at fCRD of 25, 50 and 75 μL distilled water (P<0.001, P<0.01); the MPO-positive cell number of neutrophil in the colonic muscularis was increased (P<0.01). Few EB extravasation points could be found in the control group, while there were much more EB extravasation points observed in the model group, which was specially distribution in the area of stomach meridian, from "Huaroumen" (ST24) to "Zusanli" (ST36), as well as the surface area dominated by L2-L5 segment of the spinal cord. The Dil-positive cells were mainly exhibited in the DRG of T11, L5 and L4 segments in the Tianshu group, the Liangqiu group and the Zusanli group, respectively. Compared with the control group, the ratio of glial fibrillary acidic protein (GFAP)/glutamine synthetase (GS) co-expression was increased in the DRG of T11, L4 and L5 segments in the model group (P<0.05, P<0.01).
CONCLUSION
The activation of SGCs within DRG of T11, L4 and L5 segments may relate closely to the occurrence of the representation along the stomach meridian distribution in IBS-D mice.
Animals
;
Male
;
Mice
;
Irritable Bowel Syndrome/therapy*
;
Mice, Inbred C57BL
;
Meridians
;
Stomach/physiopathology*
;
Humans
;
Acupuncture Points
;
Disease Models, Animal
4.Investigation and nursing countermeasures on the current situation of oral instrument cleaning,disinfection,and sterilization management in 348 medical institutions in Henan Province
Yuzhen CUI ; Zhuoya YAO ; Junhui GENG ; Manchun LI ; Meng ZHAN ; Lina DING ; Enshe JIANG
Chinese Journal of Nursing 2025;60(5):596-602
Objective To investigate the current status of cleaning,disinfection,and sterilization management of dental instruments in medical institutions in Henan Province,analyze potential issues in hospital infection control,and propose targeted nursing strategies.Methods A convenience sampling method was used to survey the cleaning,disinfection,and sterilization management of dental instruments in 352 medical institutions in Henan Province from February to April 2024.A self-made questionnaire was designed,covering aspects such as the handling model and personnel configuration for dental instruments,training for cleaning,disinfection,and sterilization personnel,configuration and maintenance of cleaning and disinfection equipment,use and management of small pressure steam sterilizers,and reprocessing status of dental instruments.Results A total of 352 questionnaires were distributed,with 348 valid responses.Among the 34 primary medical institutions,only 10(29.41%)had a centralized cleaning,disinfection,and sterilization model for dental instruments;13(38.24%)had dedicated personnel for cleaning,disinfection,and sterilization of dental instruments;25(73.53%)were equipped with pressure water guns.Compari-sons among medical institutions of different levels showed statistically significant differences(P<0.001).In the 348 medical institutions,194(55.75%)arranged pre-job training for nursing personnel;143(41.09%)performed mainte-nance on cleaning and disinfection equipment once a year;52(14.94%)did not perform pre-treatment on contaminated dental instruments after use.Among the 104 institutions using small pressure steam sterilizers,21(20.19%)used Type N small pressure steam sterilizers.Conclusion The centralized management rate of dental instruments and the basic equipment configuration rate in primary medical institutions in Henan Province are relatively low.There are issues such as insufficient personnel training,neglect of equipment maintenance,improper management of small pressure steam sterilizer usage,and incomplete reprocessing procedures in medical institutions at all levels.It is recommended that nursing managers further strengthen the training of nurses in the disinfection supply center,standardize the cleaning,disinfection,and sterilization workflow for dental instruments,in order to prevent and control hospital infections.
5.The Effects of Prone Position Ventilation in Patients Receiving Extracorporeal Membrane Oxygenation:a Meta-analysis
Lili LI ; Jing WU ; Junhui WANG ; Hangyan YE ; Chaonan WO ; Miaojie YU ; Fei LI ; Huiping YAO
Chinese Circulation Journal 2025;40(10):999-1005
Objectives:To analyze the effects of prone position ventilation in patients receiving extracorporeal membrane oxygenation(ECMO).Methods:A systematic search was conducted in databases including CNKI,Wanfang Data,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,and Web of Science,from the inception of each database to October 2024,to identify studies on prone position ventilation for ECMO patients.Two researchers independently screened the literature,extracted data,and assessed the quality of the studies.Meta-analysis was performed using RevMan 5.4 software.Results:A total of 10 studies were included in this analysis,comprising 2 randomized controlled trials and 8 cohort studies.A total of 1 513 patients were included,674 were in the prone position ventilation group and 839 were in the supine position ventilation group.Analysis results of 6 studies showed that compared with supine position ventilation,prone position ventilation could increase the successful weaning rate of ECMO(OR=1.47,95%CI:1.07-2.01,P=0.02).Analysis results of 8 studies showed that compared with supine position ventilation,prone position ventilation could prolong the duration of ECMO treatment(mean difference[MD]=4.86 days,95%CI:0.95-8.77,P=0.01).Analysis results of 6 studies showed that the length of stay in the intensive care unit in the prone position ventilation group was significantly longer than that in the supine position ventilation group(MD=5.16 days,95%CI:1.08-9.25,P=0.01).Analysis results of 5 studies showed that the total length of hospital stay in the prone position ventilation group was significantly longer than that in the supine position ventilation group(MD=7.72 days,95%CI:2.10-13.34,P<0.01).Analysis results of 6 studies showed that compared with supine position ventilation,prone position ventilation could prolong the duration of mechanical ventilation(MD=6.06 days,95%CI:0.63-11.49,P=0.03).Prone position ventilation had no obvious advantage in improving patient survival rate.Conclusions:Prone position ventilation can improve the successful weaning rate from ECMO and prolong the duration of ECMO treatment as well as the duration of mechanical ventilation,but it has no significant impact on patient survival rate.Due to the generally small sample size in the studies,further research with larger sample sizes is needed to confirm the effective impact of prone position ventilation in patients receiving ECMO treatment.
6.The Effects of Prone Position Ventilation in Patients Receiving Extracorporeal Membrane Oxygenation:a Meta-analysis
Lili LI ; Jing WU ; Junhui WANG ; Hangyan YE ; Chaonan WO ; Miaojie YU ; Fei LI ; Huiping YAO
Chinese Circulation Journal 2025;40(10):999-1005
Objectives:To analyze the effects of prone position ventilation in patients receiving extracorporeal membrane oxygenation(ECMO).Methods:A systematic search was conducted in databases including CNKI,Wanfang Data,China Biomedical Literature Database,PubMed,Embase,Cochrane Library,and Web of Science,from the inception of each database to October 2024,to identify studies on prone position ventilation for ECMO patients.Two researchers independently screened the literature,extracted data,and assessed the quality of the studies.Meta-analysis was performed using RevMan 5.4 software.Results:A total of 10 studies were included in this analysis,comprising 2 randomized controlled trials and 8 cohort studies.A total of 1 513 patients were included,674 were in the prone position ventilation group and 839 were in the supine position ventilation group.Analysis results of 6 studies showed that compared with supine position ventilation,prone position ventilation could increase the successful weaning rate of ECMO(OR=1.47,95%CI:1.07-2.01,P=0.02).Analysis results of 8 studies showed that compared with supine position ventilation,prone position ventilation could prolong the duration of ECMO treatment(mean difference[MD]=4.86 days,95%CI:0.95-8.77,P=0.01).Analysis results of 6 studies showed that the length of stay in the intensive care unit in the prone position ventilation group was significantly longer than that in the supine position ventilation group(MD=5.16 days,95%CI:1.08-9.25,P=0.01).Analysis results of 5 studies showed that the total length of hospital stay in the prone position ventilation group was significantly longer than that in the supine position ventilation group(MD=7.72 days,95%CI:2.10-13.34,P<0.01).Analysis results of 6 studies showed that compared with supine position ventilation,prone position ventilation could prolong the duration of mechanical ventilation(MD=6.06 days,95%CI:0.63-11.49,P=0.03).Prone position ventilation had no obvious advantage in improving patient survival rate.Conclusions:Prone position ventilation can improve the successful weaning rate from ECMO and prolong the duration of ECMO treatment as well as the duration of mechanical ventilation,but it has no significant impact on patient survival rate.Due to the generally small sample size in the studies,further research with larger sample sizes is needed to confirm the effective impact of prone position ventilation in patients receiving ECMO treatment.
7.Reserpine-induced depressive behaviors and neural impairment in rats:role of brain-derived neurotrophic factor/AKT1 signaling suppression
Guili ZHOU ; Junhui HE ; Li YANG ; Rongfei ZHOU ; Guining WEI ; Kedao LAI ; Li LI ; Renbin HUANG
Chinese Journal of Comparative Medicine 2025;35(10):11-19,38
Objective To elucidate the molecular mechanism of reserpine-induced depression using network toxicology,molecular docking techniques,behavioral assessments of animal models,and histopathological analyses.Methods Core targets were screened using multi-database network toxicology,followed by the construction of a protein-protein interaction network and validation of core targets through molecular docking.Sprague Dawley rats were divided randomly into control and reserpine(0.5 mg/kg)groups,and administered the corresponding treatments once daily for 4 consecutive days.Behavioral changes were assessed using the forced-swim and open-field tests.Serum neurotransmitters were quantified by enzyme-linked immunosorbent assay and neuropathological damage was observed via tissue staining.Target gene expression regulation was verified by Western blot.Results Network toxicology screening and molecular docking simulation demonstrated that reserpine exhibited significant binding affinity with the dopamine D2 receptor,cyclic-AMP response element binding protein,and serine/threonine-protein kinase 1(AKT1).Animal experiments demonstrated that reserpine-treated rats displayed depression-like behaviors,including motor inhibition(P<0.01),with decreased serum levels of norepinephrine and 5-hydroxytryptamine(P<0.01),respectively.Pathological observations revealed microglial proliferation in the cerebral cortex,increased apoptosis,and reduced Nissl bodies in the hippocampal CA1 region.Down-regulation of brain-derived neurotrophic factor(BDNF)in brain tissue and decreased expression of hippocampal AKT1 and phosphorylated AKT1 were also observed.Conclusions Reserpine influences monoamine transmitter metabolism and neuronal structural integrity via the inhibition of BDNF and AKT1 protein expression,resulting in depressive-like behavior and cerebral nerve damage in rats.
8.Efficacy of Weiyan Tongluo Granules in Patients with Chronic Atrophic Gastritis of Spleen Deficiency and Blood Stasis Type:A Multi-Center,Double-Blind,Double-Dummy,Randomized Controlled Trial
Xiaotao JIANG ; Jie LIN ; Yushan ZOU ; Zehong YANG ; Jinglin PAN ; Zhekun XIONG ; Changlong WANG ; Yuancheng HUANG ; Shuye WANG ; Yanhua YAN ; Junhui ZHENG ; Yi WEN ; Fengbin LIU ; Peiwu LI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(6):822-831
OBJECTIVE To evaluate the efficacy and safety of Weiyan Tongluo Granules in treating chronic atrophic gastritis(CAG)and explore its potential mechanisms.METHODS From June 2020 to December 2022,100 CAG patients with spleen defi-ciency and blood stasis syndrome were enrolled and randomly divided into a trial group(n=50)and a control group(n=50)using a random number table.The trial group received Weiyan Tongluo Granules plus a folic acid placebo,while the control group received fo-lic acid tablets plus a traditional Chinese medicine granule placebo.The treatment course for both groups was 24 weeks,with 8 and 10 dropouts in the trial and control groups,respectively.Post-treatment comparisons included OLGA/OLGIM staging reversal rates,low-grade intraepithelial neoplasia regression rate,SSDPRO-CG(Patient-Reported Outcome Scale for Chronic Gastritis in Spleen-Stomach Diseases)scores,TCM syndrome scores,and safety indicators.Serum levels of PG I,PGⅡ,PGR,and G-17 were measured via ELISA before and after treatment.Gastric mucosal p-NF-κB and CDX2 protein expression levels were analyzed by Western blot,while mRNA levels of IL-1β,IL-6,VIL1,and MUC2 were quantified via qPCR.RESULTS After treatment,the trial group showed sig-nificantly higher OLGA and OLGIM stage reversal rates than the control group(P<0.05,P<0.01),though no significant difference was observed in low-grade intraepithelial neoplasia regression.Both groups exhibited significant improvements in physiological domain scores and total SSDPRO-CG scores(P<0.01),with the trial group outperforming the control group in physiological,independence,psychological domains,and total scores(P<0.05,P<0.01).TCM syndrome scores(total and sub-items:gastric distension,pain,poor appetite,bloating)decreased significantly in both groups(P<0.01),while the trial group showed greater reductions in loose stools and dull complexion(P<0.01).After-treatment,the trial group had significantly lower TCM syndrome scores than the control group(P<0.05,P<0.01).Serum PG I,PGⅡ,PGR,G-17,gastric mucosal p-NF-κB,CDX2,and IL-1β,IL-6,VIL1,MUC2 mRNA levels improved significantly in the trial group(P<0.05,P<0.01),while the control group improved only in PGⅡ(P<0.05,P<0.01).The trial group's improvements in these biomarkers surpassed the control group's(P<0.05,P<0.01).No treatment-related adverse events occurred in either group.CONCLUSION Weiyan Tongluo Granules ameliorate gastric mucosal pathology,clinical symptoms,psychological state,and quality of life in CAG patients without significant adverse effects.Its mechanism may involve sup-pressing the NF-κB pathway to reduce IL-1β and IL-6 expression,downregulating CDX2 to inhibit VIL1 and MUC2 transcription,thereby reversing the vicious cycle of inflammation-intestinal metaplasia.
9.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.
10.Mahoniae Caulis Alkaloids Ameliorate Depression by Regulating Synaptic Plasticity via cAMP Pathway
Junhui HE ; Chunlian JIA ; Kedao LAI ; Guili ZHOU ; Rongfei ZHOU ; Yi LI ; Dongmei LI ; Jiaxiu XIE ; Guining WEI ; Juying ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):132-140
ObjectiveTo explore the mechanisms associated with Mahoniae Caulis alkaloids (MA) in ameliorating depression by network pharmacology, molecular docking, and animal experiments. MethodsThe component targets of MA were obtained through Swiss Target Prediction and TCMIP database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. The depression targets were collected through TCMIP, Genecards, HPO, DrugBank and OMIM database. Protein-protein interaction (PPI) network was constructed by protein interaction analysis (STRING) database. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed through Bioinformatics (DAVID) database. The docking of components and targets was performed by AGFR. The mouse model of depression was established by intraperitoneal injection of corticosterone (CORT) once a day for 35 consecutive days. Sixty mice were randomly allocated into control (0.9% normal saline), model (CORT, 20 mg·kg-1), positive control (fluoxetine hydrochloride, 3.6 mg·kg-1), and MA (10, 5, and 2.5 mg·kg-1) groups. Each group was administrated with corresponding medicine or normal saline once a day for 28 consecutive days. The depression-like behavior of mice was observed. The pathological changes of prefrontal cortex in mice were observed by hematoxylin-eosin staining. Terminal deoxynucleotidyl dUTP transferase nick end labeling (TUNEL) was employed to observe the apoptosis of neurons in the prefrontal cortex. Enzyme-linked immunosorbent assay was employed to assess the serum levels of brain-derived neurotrophic factor (BDNF), dopamine (DA), 5-hydroxytryptamine (5-HT), and norepinephrine (NE) in mice. The mRNA levels of cyclic adenosine monophosphate (cAMP) pathway-related factors and inflammatory factors were determined by Real-time PCR. Western blot was employed to determine the expression of cAMP pathway-related factors and connexin 43 (Cx43). ResultsA total of 434 component targets and 545 depression targets were obtained, including 84 common targets, among which 10 core targets were screened out. GO analysis predicted 34 biological processes, 15 cell components, and 11 molecular functions. The KEGG pathways were mainly related to gap junction and cAMP signaling pathway. The core components had good binding affinity with the core targets. The results of animal experiments showed that compared with the control group, CORT prolonged the immobility time of mice in forced swimming and tail suspension tests (P<0.01), lowered the serum levels of NE, BDNF, and 5-HT (P<0.05), up-regulated the mRNA levels of nuclear factor-κB (NF-κB) and interleukin-6 (IL-6) in the brain tissue (P<0.05), and down-regulated the mRNA levels of cyclic adenosine monophosphate effector binding protein (CREB) and BDNF (P<0.05) and the protein levels of protein kinase (PRKACA), phosphorylation (p)-CREB/CREB, BDNF, and Cx43 (P<0.05) in the brain tissue. Compared with the model group, high-dose MA reduced the immobility time of mice in forced swimming (P<0.05) and tail suspension (P<0.01) tests, raised the serum levels of NE, BDNF, and 5-HT (P<0.01), down-regulated the mRNA level of NF-κB (P<0.01), and up-regulated the mRNA level of BDNF (P<0.01) and protein levels of PRKACA, p-CREB/CREB, BDNF, and Cx43 (P<0.05). ConclusionMA alleviates the CORT-induced depressive behavior of mice. It may play an antidepressant role by regulating cAMP signaling pathway and gap junction pathway, improving synaptic plasticity and gap junction function, and reducing neuroinflammation.

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