1.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
2.Mechanism of Different Dosage Forms of Kaixinsan in Improving Mitochondrial Function for Prevention and Treatment of Cognitive Disorder Based on AMPK/PGC-1α/SIRT3 Pathway
Shuyue KANG ; Yanzi YU ; Jiaqun SUN ; Wenxuan CHEN ; Yaqin YANG ; Qi WANG ; Weirong LI ; Limei YAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):15-24
ObjectiveTo explore the effects of different dosage forms of Kaixinsan (KXS) on the morphology and function of mitochondria in rat models of Alzheimer's disease (AD) and potential mechanisms of action. MethodsMale SD rats were randomly assigned to a sham group, model group, treatment groups receiving KXS decoction, powders, and granules (3.08 g·kg-1), as well as donepezil group (0.51×10-3 g·kg-1), with 10 rats in each group. AD model was created using intracerebroventricular injection of streptozocin (STZ). After 30 days of administration, behavioral assessments were conducted, and mitochondrial morphology was observed using transmission electron microscopy. Mitochondrial respiratory chain complex content was measured via enzyme-linked immunosorbent assay (ELISA). Changes in mitochondrial membrane potential were measured via JC-1 staining, and superoxide dismutase (SOD) activity and reactive oxygen species (ROS) levels were measured via biochemical assays. The mRNA expression of adenosine 5'-monophosphate-activated protein kinase (AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and silent information regulator 3 (SIRT3) was detected by real-time fluorescent quantitative polymerase chain reaction (Real-time PCR), and Western blot was used to examine the protein expression levels of optic atrophy protein1 (OPA1), mitochondrial fission protein 1 (FIS1), AMPK, p-AMPK, PGC-1α, and SIRT3. ResultsCompared with the sham group, rats in the model group had significantly lower recognition index, spontaneous alternation rate, escape latency, number of platform crossings, time spent in the target quadrant, and percentage of distance traveled in the target quadrant distance (P<0.05, P<0.01). Significant mitochondrial damage was observed in the hippocampal tissue, with a marked decrease in mitochondrial respiratory chain complex content (P<0.01) and reduced mitochondrial membrane potential (P<0.05). Additionally, the SOD activity was reduced, while ROS levels were elevated (P<0.01). The mRNA expression of PGC-1α and SIRT3 was significantly downregulated (P<0.01), along with decreased protein expression levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, whereas FIS1 protein expression was significantly upregulated (P<0.05, P<0.01). Compared with the model group, rats in KXS-treated groups (various dosage forms) showed significant improvement in behavioral indexes (P<0.05, P<0.01), reduced hippocampal mitochondrial damage, and more organized mitochondrial cristae. Mitochondrial respiratory chain complex content was significantly increased (P<0.05, P<0.01), and mitochondrial membrane potentials were elevated (P<0.05). SOD activity was elevated, and ROS levels were significantly reduced (P<0.05, P<0.01). Furthermore, the mRNA expression of PGC-1α and SIRT3 was upregulated, with increased protein levels of OPA1, p-AMPK/AMPK, PGC-1α, and SIRT3, while FIS1 protein expression levels were significantly reduced (P<0.05, P<0.01). Across the KXS-treated groups, the granule group showed a higher spontaneous alternation rate than the decoction and powder groups (P<0.05). ConclusionKXS decoction, powders, and granules can improve the learning and memory ability of rats, with granules being the most effective. The mechanism of action may involve activation of the AMPK/PGC-1α/SIRT3 signaling pathway, improvement of the mitochondrial function, and subsequent amelioration of the brain energy metabolism disorders.
3.Relationship between serum levels of vitamin D and BDNF and restless leg syndrome in maintenance hemodialysis patients
Hui WANG ; Chen WANG ; Lan LING ; Yanzi XU
International Journal of Laboratory Medicine 2024;45(13):1602-1605,1610
Objective To investigate the relationship between serum levels of vitamin D(VD)and brain derived neurotrophic factor(BDNF)and restless leg syndrome(RLS)in maintenance hemodialysis patients.Methods A total of 168 end-stage renal disease patients admitted to the hospital for maintenance hemodialy-sis treatment from May 2021 to May 2022 were regarded as the observation group.According to whether they had concurrent RLS,they were separated into concurrent RLS group and non concurrent RLS group.In addi-tion,121 healthy volunteers who came to the hospital for physical examination were regarded as the control group.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of VD and BDNF in ser-um,multivariate Logistic regression was applied to analyze the influencing factors of RLS in maintenance he-modialysis patients.Receiver operating characteristic(ROC)curve was plotted to analyze the predictive value of single and combined detections of VD and BDNF for RLS in maintenance hemodialysis patients.Results Compared with the control group,the serum levels of VD and BDNF in the observation group were reduced(P<0.05).Compared with the non concurrent RLS group,the continuous dialysis time and serum ferritin level in the non concurrent RLS group were increased,while serum VD and BDNF levels were reduced(P<0.05).Multivariate Logistic regression analysis showed that VD and BDNF were protective factors for RLS in maintenance hemodialysis patients,while continuous dialysis time and ferritin were risk factors for RLS in maintenance hemodialysis pa-tients(P<0.05).The area under the curve of the combined prediction of VD and BDNF for RLS in mainte-nance hemodialysis patients was 0.889,which was superior to those of single detection(Zcombination-VD=3.748,Zcombination-BDNF=2.245,P<0.05),and the sensitivity of the combined detection was 86.11%,and the specificity was 79.55%.Conclusion The levels of VD and BDNF in serum are protective factors for RLS in maintenance hemodialysis patients.The combination of the two could effectively predict RLS in maintenance hemodialysis patients.
4.New nor-ent-halimane and nor-clerodane diterpenes from Callicarpa integerrima with anti-MRSA activity
Mengru WANG ; Qi WANG ; Yanzi MA ; Aurang Muhammad ZEB ; Xiaoli LI ; Feng SHEN ; Weilie XIAO
Chinese Journal of Natural Medicines (English Ed.) 2024;22(11):1003-1010
Two new nor-ent-halimane diterpenes and three previously unreported nor-clerodane diterpenes,designated callicain-tides A-E(1-5),were isolated from Callicarpa integerrima.Compounds 1 and 2 feature a distinctive 5/6-membered ring system,while compounds 3-5 are characterized by progressively truncated carbon skeletons,containing 18,17,and 16 carbons,respectively.In addition,four known compounds 6-9 were also identified.Their structures were elucidated using advanced spectroscopic tech-niques,including nuclear magnetic resonance(NMR),high-resolution electrospray ionization mass spectrometry(HR-ESI-MS),ultra-violet(UV),infrared radiation(IR),optical rotatory dispersion(ORD),DP4+analysis and electronic circular dichroism(ECD),sup-ported by quantum chemical calculations.Compounds 1-9 were evaluated for their anti-MRSA activity.Among them,compound 6 demonstrated significant anti-MRSA activity,with a minimum inhibitory concentration(MIC)of 16 μg·mL-1.
5.Study on hypoglycemic effect and intestinal effect of Polygonatum sibiricum polysaccharides in diabetic mice
Qunli REN ; Xinqun ZHANG ; Miao WANG ; Xiaolan LI ; Yanzi YAO ; Yinghui RAN ; Qian WANG
Journal of Pharmaceutical Practice and Service 2022;40(6):510-514
Objective To study the hypoglycemic effect of Polygonatum sibiricum polysaccharides on type 2 diabetic mice and its effects on intestinal flora and pathological structure of small intestine. Methods Fifty male mice were used, except 10 were fed normally, the others were fed with high-fat and high-sugar diet for 6 weeks, and then injected with streptozotocin intraperitoneally to make type 2 diabetes mice model. After successful modeling, they were randomly divided into model group and Polygonatum sibiricum polysaccharides (500, 250, 125 mg/kg) group and the model group mice were given normal saline. The changes of bodyweight and blood glucose of mice in each group were recorded. After 4 weeks, feces were collected and sequenced by a 16S rRNA high-throughput sequencing, and the pathological changes of small intestine were observed by HE staining. Results In diabetic mice, the weight decreased. After given Polygonatum sibiricum polysaccharides, the weight of mice increased by 14.24%,11.97% and 8.78%, and the blood glucose decreased by 26.6%, 22.3% and 13.3%, respectively after high, medium and low doses of Polygonatum sibiricum polysaccharides were administered. In addition, the pathological disorder and swelling of intestinal histopathology were improved. There were significant differences in intestinal microorganisms between the model group and the Polygonatum sibiricum polysaccharides. Verrucomicrobiae in the model group increased significantly, while the microorganism abundance of Firmicutes and Bacteroidetes in the healthy group and Polygonatum sibiricum polysaccharides group was higher. Conclusion Polygonatum sibiricum polysaccharides has a significant hypoglycemic effect on diabetic mice and a certain protective effect on their intestines, the mechanism may be achieved by increasing the richness of beneficial bacteria and improving the immune function of mice, it’s in a certain dose-effect relationship, and its immune function needs further study.
6.Therapeutic effect of vacuum sealing drainage on chronic traumatic subcutaneous hematoma
Qinghai DI ; Jiacheng ZHANG ; Yanzi WANG ; Jing WANG ; Weizhi XU ; Xiufeng GE
Chinese Journal of Plastic Surgery 2022;38(12):1323-1326
Objective:To study the clinical effect of vacuum sealing drainage in the treatment of chronic traumatic subcutaneous hematoma.Methods:Patients of chronic traumatic subcutaneous hematoma who were admitted to the Department of Burns and Plastic Surgery of Jiaozhou Central Hospital of Qingdao from June 2018 to June 2021 were included and randomly divided into the control group and the experimental group according to the random number table method. The subcutaneous hematoma was incised for debridement, and the blood clots, exudates, necrotic tissues, and pseudosynovium in the cavity were removed. The control group was treated with vaseline oil gauze filling drainage and dressing change method, and the experimental group was treated with vacuum sealing drainage and dressing change method. During the treatment, the closing time of subcutaneous hematoma cavity was observed and compared between the two groups.Results:A total of 42 patients with chronic traumatic subcutaneous hematoma were enrolled, 21 in the control group and 21 in the experimental group, including 11 males and 10 females in the control group, aged (46.2±12.4) years; 13 males and 8 females in the experimental group, aged (44.3±10.6) years. After treatment, all the subcutaneous hematoma spaces were closed in the 42 patients. The closing time of subcutaneous hematoma cavity in the experimental group was (15.52±1.69) days, which was significantly shorter than that in the control group (24.14±2.57) days. There was a significant difference between the two groups ( P<0.01). Conclusions:After incision and debridement of chronic traumatic subcutaneous hematoma, vacuum sealing drainage and dressing change can actively and fully drain the exudate in the cavity, residual blood clots, necrotic tissues, and pseudosynovium, promote the growth of new granulation tissue, which is more conducive to the closure of the cavity of subcutaneous hematoma, and shorten the clinical treatment cycle.
7.Therapeutic effect of vacuum sealing drainage on chronic traumatic subcutaneous hematoma
Qinghai DI ; Jiacheng ZHANG ; Yanzi WANG ; Jing WANG ; Weizhi XU ; Xiufeng GE
Chinese Journal of Plastic Surgery 2022;38(12):1323-1326
Objective:To study the clinical effect of vacuum sealing drainage in the treatment of chronic traumatic subcutaneous hematoma.Methods:Patients of chronic traumatic subcutaneous hematoma who were admitted to the Department of Burns and Plastic Surgery of Jiaozhou Central Hospital of Qingdao from June 2018 to June 2021 were included and randomly divided into the control group and the experimental group according to the random number table method. The subcutaneous hematoma was incised for debridement, and the blood clots, exudates, necrotic tissues, and pseudosynovium in the cavity were removed. The control group was treated with vaseline oil gauze filling drainage and dressing change method, and the experimental group was treated with vacuum sealing drainage and dressing change method. During the treatment, the closing time of subcutaneous hematoma cavity was observed and compared between the two groups.Results:A total of 42 patients with chronic traumatic subcutaneous hematoma were enrolled, 21 in the control group and 21 in the experimental group, including 11 males and 10 females in the control group, aged (46.2±12.4) years; 13 males and 8 females in the experimental group, aged (44.3±10.6) years. After treatment, all the subcutaneous hematoma spaces were closed in the 42 patients. The closing time of subcutaneous hematoma cavity in the experimental group was (15.52±1.69) days, which was significantly shorter than that in the control group (24.14±2.57) days. There was a significant difference between the two groups ( P<0.01). Conclusions:After incision and debridement of chronic traumatic subcutaneous hematoma, vacuum sealing drainage and dressing change can actively and fully drain the exudate in the cavity, residual blood clots, necrotic tissues, and pseudosynovium, promote the growth of new granulation tissue, which is more conducive to the closure of the cavity of subcutaneous hematoma, and shorten the clinical treatment cycle.
8. Chitosan membrane type under the negative pressure therapy for infected wounds multi-resistant bacteria flora changes of examination
Qinghai DI ; Jiacheng ZHANG ; Yanzi WANG ; Weizhi XU ; Xiufeng GE ; Jing WANG
Chinese Journal of Plastic Surgery 2019;35(4):398-401
Objective:
To evaluate the outcome of negative pressure closed drainage with chitosan membrane in the treatment of multiple drug-resistant bacterial infections.
Methods:
From January 2015 to December 2017, 108 patients with skin ulcer wound complicated by multiple drug-resistant bacterial infection were admitted in the department of burn and plastic surgery, Qingdao Jiaozhou Central Hospital. Among them, 36 patients had pressure ulcers, 40 cases had diabetic foot wounds, and 32 were traumatic skin ulcer wounds. Patients were divided into group A or group B for different treatments. In group A, besides the basic surgical dressing change, patients were treated by negative pressure closed drainage with chitosan membrane. The patients in Group B were only treated with basic surgical dressing change. The changes of wound were closely observed during the phases, and the wound bacterial culture and antimicrobial drug sensitivity test were performed regularly. The therapeutic effects of the 2 groups were compared. The changes of bacterial species of wound infection and the healing time were recorded.
Results:
In group A, the healing time of wound infection was: pressure ulcers (14.00±1.28) days, diabetic foot wounds (13.40±1.27) days, traumatic skin ulcer wounds (12.44±1.55) days. In group B, the wound healing time was: pressure ulcers (25.17±2.73) days, diabetic foot wounds (23.85±1.73) days, traumatic skin ulcer wounds (19.81±1.94) days. The wound healing time of group A was shorter than group B. In group A, the multiple drug-resistant bacteria was replaced by non-multiple drug-resistant bacteria, or there was no pathogenic bacterial growth. The differences between the two groups was statistically significant (all
9.Clinical value of tuberculosis protein chip in the diagnosis of tuberculosis infection
Ke WANG ; Hongying DAI ; Yin ZHANG ; Yanzi ZHANG ; Tianjin ZHU ; Zhigui TANG ; Yongqiang. YUAN
Chinese Journal of Laboratory Medicine 2016;39(10):776-778
Objective To investigate the Mycobacterium tuberculosis infection status and Clinical Characteristics in Yongchuan District, Chongqing by Tuberculosis Protein Chip.Methods Compared the conventional method to detect Mycobacterium tuberculosis in infectious department outpatient of Yongchuan Hospital , Chongqing Medical University from July 2014 to June 2015.Tuberculosis protein chip was selected to detect the Mycobacterium tuberculosis infection in Yongchuan area.Chi-square Test was applied to analyze the results.Results The positive rate of Tuberculosis Protein Chip, T-SPOT.BT, DNA Chip, Golden immnnochromatog-raphy, Acid-fast staining were 81.5%, 90.7%, 89.5%, 63.5% and 38.3%respectively on 162 cases of Pulmonary tuberculosis.The five methods were considered significant difference on the diagnosis of Pulmonary tuberculosis ( P<0.05 ).The positive rate of Tuberculosis Protein Chip, T-SPOT, Golden immnnochromatog-raphy were 90.6%,T-SPOT 94.3%and 47.2% respectively on 53 cases of extrapulmonary tuberculosis, it was a significant difference with the three methods(P<0.05),but there was no significant difference with Tuberculosis Protein Chip and T-SPOT.BT ( P>0.05 ).The highest positive rates of anti-LAM was 94%.Conclusion The results of Tuberculosis protein chip are reliable on pulmonary tuberculosis and extrapulmonary tuberculosis diagnosis.
10.Effect of CYP3A4* 1G genetic polymorphism on fentanyl pharmacodynamies in healthy female volunteers
Wei ZHANG ; Haoyong ZHANG ; Quancheng KAN ; Lirong ZHANG ; Yanzi CHANG ; Zhisong LI ; Zhongyu WANG ; Yan LI ; Qinjun CHU
Chinese Journal of Anesthesiology 2012;32(1):67-69
Objective To investigate the effects of CYP3A4* 1G genetic polymorphism on fentanyl pharmadynamics after intravenous injection in healthy female velunteers,Methods Twenty-eight healthy female volunteers aged 18-25 yr weighing 45-70 kg were enrolled in this study.The CYP3A4 * 1G genetic polymorphic sites were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).The volunteers were assigned into 3 groups according to their genotypes:group Ⅰ wild homozygote ; group Ⅱ mutation heterozygote and group Ⅲ mutation homozygote.Fentanyl 5 μg/kg was injected iv over 1 min.Pain threshold was measured using electrical stimulation before and at 45,150 and 240 min after fentanyl injection.Results Pain threshold was significantly higher at 45 and 150 min after iv fentanyl injection in mutation homozygote group than in mutation heterozygote group and wild homozygote group.There was no significant difference in pain threshold between mutation heterozygote group and wild homozygote group.Conclusion CYP3A4* 1G genetic mutation can enhance the analgesic efficacy of fentanyl after intravenous injection in healthy female volunteers.

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