1.Effect of Astragali Radix on Gut Microbiota and GLP-1 in Newly Diagnosed Type 2 Diabetes Patients with Qi Deficiency Type
Keke HOU ; Lin CHEN ; Zhidan ZHANG ; Yunyi YANG ; Fangli ZHANG ; Yuanying XU ; Hongping YIN ; Lan DING ; Tao LEI ; Wenjun SHA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):161-170
ObjectiveTo investigate the therapeutic effect of Astragali Radix-mediated changes in gut microbiota on treating type 2 diabetes (T2DM). MethodsA 12-week randomized, placebo-controlled clinical trial enrolled eighty patients with newly diagnosed type 2 diabetes and poor glycemic control in the Qi deficiency type. All patients received insulin therapy. The observation group (40 cases) was administered with Astragali Radix Granules, while the control group (40 cases) received a placebo. Both treamtents were taken orally twice daily. Changes in gut microbiota were assessed by 16s rDNA sequencing. Serum glucagon-like peptide-1 (GLP-1) levels were measured using enzyme-linked immunosorbent assay (ELISA). Glucose metabolism indicators including fasting blood glucose (FPG), 2-hour postprandial blood glucose (2 h PG),glycated albumin(GA), and glycated hemoglobin (HbA1c) were evaluated. Pancreatic function was evaluated using fasting C-peptide (FCP), 2-hour postprandial C-peptide (2 h CP), and C-peptide area under the curve (AUCcp). Traditional Chinese medicine (TCM) syndrome scores, clinical efficacy, and safety indicators were also observed. ResultsIn terms of glucose metabolism indicators, compared with the baseline, both groups exhibited significantly lower FPG, 2 h PG, GA and HbA1C (P<0.01),while FCP, 2 h CP and AUCcp were significantly higher (P<0.01). Compared with the control group after the treatment, the observation group showed significantly lower FPG, 2 h PG, GA and HbA1C(P<0.05, P<0.01),and significantly higher FCP, 2 h CP and AUCcp (P<0.05, P<0.01), indicating that Astragali Radix can improve glucose metabolism. In terms of the diversity of gut microbiota, no significant differences were detected in the Chao1, Shannon and Simpson indexes of the two groups compared with their respective baselines. However, compared with the post-treatment control group, the observation group demonstrated significant increases in the Chao1, Shannon and Simpson indexes (P<0.05, P<0.01). The β-diversity analysis showed significant separation in gut microbiota composition before and after treatment in both groups, indicating that Astragali Radix can significantly alter the structure and improve the diversity of gut microbiota. At the phylum level, compared with the baseline, both groups showed a significant increase in the relative abundance of Bacteroidota(P<0.01). The relative abundance of the potentially harmful phylum Proteobacteria was significantly lower in the observation Group after treatment (P<0.01). Compared with the post-treatment control group, the observation group had a significantly higher relative abundance of Bacteroidota(P<0.01). No significant difference was found in Firmicutes/Bacteroidota (F/B) ratio between the two groups after treatment, and other phyla showed no significant differences. At the genus level, compared with the baseline, the observation group exhibited a significant increase in Bacteroides (P<0.01) and a significant decrease in Escherichia-Shigella (P<0.01), whereas no significant difference was seen in the control group . Compared with the control group after treatment, the observation group after treatment had a significantly higher relative abundance of Bacteroides (P<0.01). No significant differences were seen in other genera. Linear discriminant analysis (LDA) identified potential characteristics taxa: in the observation group, Bacteroidota at the phylum level and Bacteroides and Dubosiella at the genus level, in the control group, Proteobacteria at the phylum level as well as Barnesiella and Staphylococcus at the genus level. Correlation analysis based on a heatmap revealed that GLP-1 levels were positively correlated with Firmicutes, F/B ratio and Fusobacterium, and negatively correlated with Bacteroidota, Proteobacteria, Bacteroides and Escherichia-Shigella. In terms of clinical efficacy, compared with the control group, the total effective rate of the observation group was significantly higher (P<0.05). Compared with the baseline, the scores for shortness of breath, fatigue, weakness, spontaneous sweating and reluctance to speak significantly decreased in both groups (P<0.01). Compared with the control group after treatment, the score for weakness was significantly lower in the observation group (P<0.01),indicating that Astragali Radix could improve clinical symptoms and alleviate weakness symptoms. In terms of safety, compared with the baseline, alanine aminotransferase (ALT) levels significantly decreased in both groups (P<0.05,P<0.01),indicating that Astragali Radix did not induce any significant abnormalities in liver and kidney functions. ConclusionAstragali Radix demonstrates the potential to significantly improve the gut microbiota environment in patients of newly diagnosed type 2 diabetes with Qi deficiency. The therapeutic effect may contribute to glycemic control, possibly mediated by an elevation in GLP-1 level. These findings may support its further clinical investigations and potential applications.
2.The Mechanisms of Quercetin in Improving Alzheimer’s Disease
Yu-Meng ZHANG ; Yu-Shan TIAN ; Jie LI ; Wen-Jun MU ; Chang-Feng YIN ; Huan CHEN ; Hong-Wei HOU
Progress in Biochemistry and Biophysics 2025;52(2):334-347
Alzheimer’s disease (AD) is a prevalent neurodegenerative condition characterized by progressive cognitive decline and memory loss. As the incidence of AD continues to rise annually, researchers have shown keen interest in the active components found in natural plants and their neuroprotective effects against AD. Quercetin, a flavonol widely present in fruits and vegetables, has multiple biological effects including anticancer, anti-inflammatory, and antioxidant. Oxidative stress plays a central role in the pathogenesis of AD, and the antioxidant properties of quercetin are essential for its neuroprotective function. Quercetin can modulate multiple signaling pathways related to AD, such as Nrf2-ARE, JNK, p38 MAPK, PON2, PI3K/Akt, and PKC, all of which are closely related to oxidative stress. Furthermore, quercetin is capable of inhibiting the aggregation of β‑amyloid protein (Aβ) and the phosphorylation of tau protein, as well as the activity of β‑secretase 1 and acetylcholinesterase, thus slowing down the progression of the disease.The review also provides insights into the pharmacokinetic properties of quercetin, including its absorption, metabolism, and excretion, as well as its bioavailability challenges and clinical applications. To improve the bioavailability and enhance the targeting of quercetin, the potential of quercetin nanomedicine delivery systems in the treatment of AD is also discussed. In summary, the multifaceted mechanisms of quercetin against AD provide a new perspective for drug development. However, translating these findings into clinical practice requires overcoming current limitations and ongoing research. In this way, its therapeutic potential in the treatment of AD can be fully utilized.
3.Effect of target characteristics on prospective memory in patients with depressive disorder
Min CHEN ; Dongsheng LYU ; Zheng WANG ; You HOU
Sichuan Mental Health 2025;38(1):14-21
BackgroundMany studies have shown that patients with depressive disorder show impairments in prospective memory, while it is deemed necessary for facilitating their social reintegration, and the current research findings are inconsistent regarding the factors affecting prospective memory of patients with depressive disorder. ObjectiveTo explore the impact of target characteristics (emotional valence and salience) on prospective memory in patients with depressive disorder, so as to provide references for the training and recovery of prospective memory function in these patients. MethodsFrom January to December 2022, 53 patients with depressive disorder were recruited from the outpatient department of Inner Mongolia Autonomous Mental Health Center. Meanwhile, 45 healthy individuals were concurrently recruited from surrounding communities as control group. An experiment with a 2 (participant type: depressive disorder, healthy control) ×2 (target salience: salient, non-salient) ×3 (emotional valence: positive, neutral, negative) factorial design was conducted. The positive/neutral/negative emotional pictures from Chinese Affective Picture System (CAPS) were used for emotional stimulation. A dual-task experimental paradigm was adopted, and the response time and accuracy in prospective memory task and ongoing task were recorded for participants with different target characteristics. Results①In the prospective memory task, the main effect of participant type was statistically significant, with the depressive group showing lower accuracy (F=14.892, P<0.01) and longer response time (F=10.642, P=0.002) compared with control group. ② The main effect of target emotional valence on accuracy (F=7.575, P=0.001) and response time (F=3.196, P=0.044) in the prospective memory task was statistically significant. Simple effect analysis revealed that depressive group yielded a shorter response time and higher accuracy rate under negative conditions compared with positive and neutral conditions (P<0.05 or 0.01). ③ The main effect of target salience on accuracy (F=6.659, P=0.012) and response time (F=10.106, P=0.002) in the prospective memory task was also statistically significant, with higher accuracy and shorter response time for salient targets compared with non-salient targets. ConclusionPatients with depressive disorder demonstrate preferential attention to and processing of negative stimuli in prospective memory tasks, while increasing target salience may facilitate spontaneous processing of prospective memory task in patients with depressive disorder. [Funded by Inner Mongolia Health Commission Medical Health Science and Technology Project (number, 202202104)]
4.Treatment of Diabetes Mellitus with Traditional Chinese Medicine Classic Prescriptions: A Review
Yu WANG ; Hedi WANG ; Qiang CHEN ; Guanqun HOU ; Yanting LU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):266-277
As a chronic and lifelong disease, diabetes mellitus occurs across all age groups and gender groups. Since the disease requires lifelong treatment, it seriously affects the quality of life of patients. With the rising incidence on a global scale, diabetes mellitus has become a global problem that seriously affects public health. Moreover, the complications of this disease have aroused concern from the global medical research community, the World Health Organization, and the public. In the past, Western medicine was used in the clinical treatment of diabetes mellitus, which, however, had drug dependence, unsatisfactory efficacy, and side effects. Long-term oral administration of antidiabetics may cause liver and kidney function damage, hypoglycemia and other adverse symptoms. The treatment of diabetes mellitus has been faced with challenges such as limited efficacy and obvious side effects. Therefore, exploring more effective treatment means, especially tapping the potential of traditional Chinese medicine (TCM) in the treatment of diabetes mellitus, is a major issue to be solved. TCM has shown a great application value and a broad prospect in the treatment of diabetes mellitus because of multi-target regulation, a holistic view, synergistic effects, and high safety. TCM has a history of thousands of years in the prevention and treatment of diabetes mellitus, with rich experience accumulated and remarkable results achieved. Particularly, TCM demonstrates definite therapeutic effects on the complications. The application of TCM in the treatment of complications has been recognized and accepted by patients because of the definite therapeutic effect. In recent years, great progress has been achieved in the treatment of diabetes mellitus by the combination of Chinese and western medicine, which has made important contributions to the control of diabetes mellitus. This paper reviews the articles about the treatment of diabetes mellitus with TCM classic prescriptions, summarizes the treatment of clinical cases regarding the indications of these prescriptions, and provides an overview of the treatment mechanisms, aiming to offer fresh insights and strategies for the clinical diagnosis and treatment of diabetes mellitus.
5.Biomechanical characteristics of walking in patients with idiopathic scoliosis:cross-sectional analysis of three-dimensional motion capture
Yanyun GOU ; Meijin HOU ; Zheng JIANG ; Shaoqing CHEN ; Xiang CHEN ; Yuzhan GAO ; Xiangbin WANG
Chinese Journal of Tissue Engineering Research 2025;29(3):471-477
BACKGROUND:The biomechanical analysis of scoliosis cases is limited,with only independent analysis focusing on the spine or lower limbs,thus lacking a comprehensive evaluation of the multidimensional body.As a result,it becomes challenging to reflect the movement relationship between the trunk and lower limbs during daily activities,which hinders comprehensive clinical treatment guidance. OBJECTIVE:To explore the relationship between different segments of the spine and the kinematics/kinetics of the lower limbs during gait activities by measuring spinal kinematics in scoliosis patients,to provide a comprehensive and multi-level assessment of the biomechanical differences between scoliosis patients and the normal population,consequently offering evidence-based guidance for the prevention and treatment of scoliosis. METHODS:A cross-sectional study was conducted from July 2020 to June 2021 at the Rehabilitation Hospital Affiliated to Fujian University of Traditional Chinese Medicine in Fuzhou University City.A total of 28 scoliosis patients and 28 normal individuals in the same age group were included.Three-dimensional motion capture system was used to capture gait kinematic data at a sampling frequency of 100 Hz.Two force plates(AMTI 400600,sampling frequency 1 500 Hz)were embedded in a 10-meter-long 2.4-meter-wide level ground walkway(with an effective data collection length of 4 m)to collect kinetic data.The differences in spatial-temporal parameters,kinematics,and kinetics of gait between the two groups were compared.Immediately after inclusion,all subjects underwent full spinal X-ray measurements to compare the differences between the scoliosis and normal groups. RESULTS AND CONCLUSION:(1)Patients with scoliosis exhibited reduced relative rotational range of motion between the shoulder and trunk,as well as between the thorax and pelvis,compared to the normal group(P<0.05).However,the rotational range of motion in the pelvis was larger in patients with scoliosis compared to the normal group(P<0.05).(2)Patients with scoliosis showed decreased range of motion in the hip and knee joints,as well as reduced peak torque in hip joint flexion and extension,and lower peak values of ground reaction forces in the concave and convex directions,in comparison to the normal group(P<0.05).(3)Patients with scoliosis demonstrated greater asymmetry indices in knee joint range of motion,relative rotational range of motion between the shoulder and trunk,and between the thorax and pelvis,when compared to the normal group(P<0.05).(4)These findings illustrate a rigid movement pattern among the shoulder,thorax,and pelvis in patients with scoliosis during level walking.There is a reduction in range of motion in the hip and knee joints,as well as decreased peak torque values in hip joint flexion and extension,and ground reaction forces in the concave and convex directions.These characteristics can serve as foundational elements for assessing rehabilitation and developing treatment plans.
6.Identification and drug sensitivity analysis of key molecular markers in mesenchymal cell-derived osteosarcoma
Haojun ZHANG ; Hongyi LI ; Hui ZHANG ; Haoran CHEN ; Lizhong ZHANG ; Jie GENG ; Chuandong HOU ; Qi YU ; Peifeng HE ; Jinpeng JIA ; Xuechun LU
Chinese Journal of Tissue Engineering Research 2025;29(7):1448-1456
BACKGROUND:Osteosarcoma has a complex pathogenesis and a poor prognosis.While advancements in medical technology have led to some improvements in the 5-year survival rate,substantial progress in its treatment has not yet been achieved. OBJECTIVE:To screen key molecular markers in osteosarcoma,analyze their relationship with osteosarcoma treatment drugs,and explore the potential disease mechanisms of osteosarcoma at the molecular level. METHODS:GSE99671 and GSE284259(miRNA)datasets were obtained from the Gene Expression Omnibus database.Differential gene expression analysis and Weighted Gene Co-expression Network Analysis(WGCNA)on GSE99671 were performed.Functional enrichment analysis was conducted using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes separately for the differentially expressed genes and the module genes with the highest positive correlation to the disease.The intersection of these module genes and differentially expressed genes was taken as key genes.A Protein-Protein Interaction network was constructed,and correlation analysis on the key genes was performed using CytoScape software,and hub genes were identified.Hub genes were externally validated using the GSE28425 dataset and text validation was conducted.The drug sensitivity of hub genes was analyzed using the CellMiner database,with a threshold of absolute value of correlation coefficient|R|>0.3 and P<0.05. RESULTS AND CONCLUSION:(1)Differential gene expression analysis identified 529 differentially expressed genes,comprising 177 upregulated and 352 downregulated genes.WGCNA analysis yielded a total of 592 genes with the highest correlation to osteosarcoma.(2)Gene Ontology enrichment results indicated that the development of osteosarcoma may be associated with extracellular matrix,bone cell differentiation and development,human immune regulation,and collagen synthesis and degradation.Kyoto Encyclopedia of Genes and Genomes enrichment results showed the involvement of pathways such as PI3K-Akt signaling pathway,focal adhesion signaling pathway,and immune response in the onset of osteosarcoma.(3)The intersection analysis revealed a total of 59 key genes.Through Protein-Protein Interaction network analysis,8 hub genes were selected,which were LUM,PLOD1,PLOD2,MMP14,COL11A1,THBS2,LEPRE1,and TGFB1,all of which were upregulated.(4)External validation revealed significantly downregulated miRNAs that regulate the hub genes,with hsa-miR-144-3p and hsa-miR-150-5p showing the most significant downregulation.Text validation results demonstrated that the expression of hub genes was consistent with previous research.(5)Drug sensitivity analysis indicated a negative correlation between the activity of methotrexate,6-mercaptopurine,and pazopanib with the mRNA expression of PLOD1,PLOD2,and MMP14.Moreover,zoledronic acid and lapatinib showed a positive correlation with the mRNA expression of PLOD1,LUM,MMP14,PLOD2,and TGFB1.This suggests that zoledronic acid and lapatinib may be potential therapeutic drugs for osteosarcoma,but further validation is required through additional basic experiments and clinical studies.
7.Synthesis and anti-breast cancer activity of novel cyclic mono-carbonyl curcumin analogues
Xianhu FENG ; Yongjie CHEN ; Lin CHEN ; Yi HOU ; Wanjun CAO ; Qiang SU
China Pharmacy 2025;36(5):563-567
OBJECTIVE To design and synthesize mono-carbonyl curcumin analogues(MCACs) and investigate the activities of them against breast cancer. METHODS The analogues F1, F2, and F3 were obtained by aldol condensation reaction, and their antitumor activities(including the activities of human breast cancer cell MCF-7 and human lung cancer cell A549) were detected by MTT assay [evaluated with half inhibitory concentration(IC50)]. The results of MTT assay were compared with those of curcumin. Bioinformatics methods were used to collect the core targets of analogues F1, F2 and F3 acting on breast cancer, and then molecular docking verification was carried out. The cell experiments were conducted to investigate the effects of high, medium and low concentrations (16, 8, 4 μmol/L) of F1, F2 and F3 on the expression of the first core target protein as well as the effects of medium concentration of F1, F2 and F3 on the expression of cleaved-caspase-3. RESULTS Compared with curcumin, IC50 of analogues F1, F2 and F3 to A549 and MCF-7 cells(except for IC50 of analogue F2 to A549 cells) were decreased significantly(P< 0.05 or P<0.01); among them, IC50 of analogue F2 to MCF-7 cell was the lowest, being(9.67±1.27) μmol/L. Bioinformatics analysis showed that index of affinity of analogues F1, F2 and F3 with the first core target epidermal growth factor receptor (EGFR), protein kinase B (AKT) and AKT were 5.909 2, 8.402 5 and 6.486 6, respectively; high concentration of F1 could significantly reduce the phosphorylation level of EGFR protein in MCF-7 cells(P<0.01), while low, medium, and high concentrations of F2 and high concentration of F3 could significantly reduce the phosphorylation level of AKT protein in MCF-7 cells(P<0.05 or P<0.01). Medium concentration of F1, F2, and F3 could significantly increase the expression level of cleaved- caspase-3 protein in MCF-7 cells(P<0.01). CONCLUSIONS Designed and synthesized MCACs F1, F2 and F3 all have good anti- breast cancer activity, and F2 has better anti-breast cancer activity.
8.Predicting Clinically Significant Prostate Cancer Using Urine Metabolomics via Liquid Chromatography Mass Spectrometry
Chung-Hsin CHEN ; Hsiang-Po HUANG ; Kai-Hsiung CHANG ; Ming-Shyue LEE ; Cheng-Fan LEE ; Chih-Yu LIN ; Yuan Chi LIN ; William J. HUANG ; Chun-Hou LIAO ; Chih-Chin YU ; Shiu-Dong CHUNG ; Yao-Chou TSAI ; Chia-Chang WU ; Chen-Hsun HO ; Pei-Wen HSIAO ; Yeong-Shiau PU ;
The World Journal of Men's Health 2025;43(2):376-386
Purpose:
Biomarkers predicting clinically significant prostate cancer (sPC) before biopsy are currently lacking. This study aimed to develop a non-invasive urine test to predict sPC in at-risk men using urinary metabolomic profiles.
Materials and Methods:
Urine samples from 934 at-risk subjects and 268 treatment-naïve PC patients were subjected to liquid chromatography/mass spectrophotometry (LC-MS)-based metabolomics profiling using both C18 and hydrophilic interaction liquid chromatography (HILIC) column analyses. Four models were constructed (training cohort [n=647]) and validated (validation cohort [n=344]) for different purposes. Model I differentiates PC from benign cases. Models II, III, and a Gleason score model (model GS) predict sPC that is defined as National Comprehensive Cancer Network (NCCN)-categorized favorable-intermediate risk group or higher (Model II), unfavorable-intermediate risk group or higher (Model III), and GS ≥7 PC (model GS), respectively. The metabolomic panels and predicting models were constructed using logistic regression and Akaike information criterion.
Results:
The best metabolomic panels from the HILIC column include 25, 27, 28 and 26 metabolites in Models I, II, III, and GS, respectively, with area under the curve (AUC) values ranging between 0.82 and 0.91 in the training cohort and between 0.77 and 0.86 in the validation cohort. The combination of the metabolomic panels and five baseline clinical factors that include serum prostate-specific antigen, age, family history of PC, previously negative biopsy, and abnormal digital rectal examination results significantly increased AUCs (range 0.88–0.91). At 90% sensitivity (validation cohort), 33%, 34%, 41%, and 36% of unnecessary biopsies were avoided in Models I, II, III, and GS, respectively. The above results were successfully validated using LC-MS with the C18 column.
Conclusions
Urinary metabolomic profiles with baseline clinical factors may accurately predict sPC in men with elevated risk before biopsy.
9.Mechanism of Modified Shengjiangsan in Improving Diabetic Kidney Disease by Activating Mitochondrial Autophagy Based on PINK1/Parkin Signaling Pathway
Jiaxin LI ; Liya ZHOU ; Yishuo ZHANG ; Ziqiang CHEN ; Yijun HOU ; Jian SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):121-128
ObjectiveTo investigate the mechanism by which modified Shengjiangsan (MSJS) improves diabetic kidney disease (DKD) by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). After successful modeling, the rats were randomly divided into six groups: a normal control group, a model group, low-, medium-, and high-dose MSJS groups (7.7, 15.4, 30.8 g·kg-1, respectively), and an irbesartan group (0.384 g·kg-1). Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose, body weight, and kidney weight were recorded. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to determine urinary microalbumin (mALB), and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Histopathological changes in renal tissues were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy (TEM). The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta (LC3B) and cytochrome c oxidase subunit Ⅳ (COX Ⅳ). ResultsCompared with the normal control group, the model group exhibited significant increases in renal index, blood glucose, and 24-hour urinary microalbumin (24 h mALB) (P<0.05, P<0.01). The levels of serum SCr and BUN were significantly elevated (P<0.01), and the serum levels of TNF-α, IL-1β, and IL-6 were markedly upregulated (P<0.01). Histopathological examination revealed glomerular hypertrophy, mesangial expansion and increased deposition, podocyte foot process flattening and fusion, a decreased number of autophagosomes accompanied by mitochondrial swelling, vacuolar degeneration of renal tubular epithelial cells, and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B, PTEN-induced putative kinase 1 (PINK1), and E3 ubiquitin-protein ligase (Parkin) were significantly decreased (P<0.05, P<0.01), while expression of the selective autophagy adaptor protein p62 was significantly increased (P<0.01). Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group, the MSJS treatment groups and the irbesartan group showed significant reductions in renal index, blood glucose, and 24 h mALB (P<0.05, P<0.01). The serum SCr and BUN levels decreased significantly (P<0.05) and TNF-α, IL-1β, and IL-6 levels were significantly downregulated (P<0.05, P<0.01). Histopathological damage was alleviated, including reduced glomerular hypertrophy, decreased mesangial deposition, and attenuated podocyte foot process fusion. The number of autophagosomes increased, and mitochondrial swelling was improved. The expression levels of LC3B, PINK1, and Parkin in renal tissues were significantly upregulated, whereas p62 expression was significantly downregulated (P<0.05, P<0.01) in MSJS groups. Immunofluorescence signal intensity was enhanced, and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.
10.Mechanism of Modified Shengjiangsan in Improving Diabetic Kidney Disease by Activating Mitochondrial Autophagy Based on PINK1/Parkin Signaling Pathway
Jiaxin LI ; Liya ZHOU ; Yishuo ZHANG ; Ziqiang CHEN ; Yijun HOU ; Jian SUN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):121-128
ObjectiveTo investigate the mechanism by which modified Shengjiangsan (MSJS) improves diabetic kidney disease (DKD) by activating mitochondrial autophagy. MethodsSixty SPF-grade male Sprague-Dawley rats aged 7-8 weeks were selected. A DKD model was established using a high-sugar, high-fat diet combined with intraperitoneal injection of streptozotocin (STZ). After successful modeling, the rats were randomly divided into six groups: a normal control group, a model group, low-, medium-, and high-dose MSJS groups (7.7, 15.4, 30.8 g·kg-1, respectively), and an irbesartan group (0.384 g·kg-1). Each group received either normal saline or the corresponding drug by gavage once daily for 28 consecutive days. Blood glucose, body weight, and kidney weight were recorded. Serum creatinine (SCr) and blood urea nitrogen (BUN) levels were detected using an automatic blood analyzer. Enzyme-linked immunosorbent assay (ELISA) was used to determine urinary microalbumin (mALB), and serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). Histopathological changes in renal tissues were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and transmission electron microscopy (TEM). The expression levels of mitochondrial autophagy-related proteins in renal tissues were analyzed by Western blot. Immunofluorescence co-localization was employed to detect the co-expression of microtubule-associated protein 1 light chain 3 beta (LC3B) and cytochrome c oxidase subunit Ⅳ (COX Ⅳ). ResultsCompared with the normal control group, the model group exhibited significant increases in renal index, blood glucose, and 24-hour urinary microalbumin (24 h mALB) (P<0.05, P<0.01). The levels of serum SCr and BUN were significantly elevated (P<0.01), and the serum levels of TNF-α, IL-1β, and IL-6 were markedly upregulated (P<0.01). Histopathological examination revealed glomerular hypertrophy, mesangial expansion and increased deposition, podocyte foot process flattening and fusion, a decreased number of autophagosomes accompanied by mitochondrial swelling, vacuolar degeneration of renal tubular epithelial cells, and inflammatory cell infiltration in the renal interstitium. The expression levels of autophagy-related proteins LC3B, PTEN-induced putative kinase 1 (PINK1), and E3 ubiquitin-protein ligase (Parkin) were significantly decreased (P<0.05, P<0.01), while expression of the selective autophagy adaptor protein p62 was significantly increased (P<0.01). Immunofluorescence signal intensity and LC3B-COX Ⅳ co-expression were both diminished. Compared with the model group, the MSJS treatment groups and the irbesartan group showed significant reductions in renal index, blood glucose, and 24 h mALB (P<0.05, P<0.01). The serum SCr and BUN levels decreased significantly (P<0.05) and TNF-α, IL-1β, and IL-6 levels were significantly downregulated (P<0.05, P<0.01). Histopathological damage was alleviated, including reduced glomerular hypertrophy, decreased mesangial deposition, and attenuated podocyte foot process fusion. The number of autophagosomes increased, and mitochondrial swelling was improved. The expression levels of LC3B, PINK1, and Parkin in renal tissues were significantly upregulated, whereas p62 expression was significantly downregulated (P<0.05, P<0.01) in MSJS groups. Immunofluorescence signal intensity was enhanced, and LC3B-COX Ⅳ co-expression was increased. ConclusionMSJS alleviates the inflammatory response in DKD rats and exerts renal protective effects by regulating the PINK1/Parkin signaling pathway and activating mitochondrial autophagy.

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