1.Mechanism of Dangui Shaoyaosan in Alleviating Inflammatory Responses in Diabetic Kidney Disease by Modulating Macrophage Polarization in Kidneys of db/db Mice
Luyu HOU ; Linlin ZHENG ; Wenjing SHI ; Zixuan WANG ; Shilong GUO ; Zhe LYU ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):1-10
ObjectiveTo observe the effects of Danggui Shaoyaosan on macrophage polarization and renal inflammation in db/db mice with diabetic kidney disease (DKD), and to explore its renal protective effects and underlying mechanisms. MethodsEight db/m mice were assigned to the normal group, and forty db/db mice were randomly divided into a model group, low-, medium-, and high-dose Danggui Shaoyaosan groups (8.39, 16.77, 33.54 g·kg-1), and an irbesartan group (0.025 g·kg-1). All mice were administered treatment by gavage for 12 consecutive weeks. General conditions of the mice were observed during the intervention. At the end of the 12-week intervention, 24-h urine samples were collected using metabolic cages, after which the mice were anesthetized for sample collection. Blood was collected by enucleation and centrifuged to obtain serum for the determination of glycated serum protein (GSP), serum creatinine (SCr), blood urea nitrogen (BUN), total cholesterol (TC), and triglycerides (TG). The urinary albumin-to-creatinine ratio (UACR) was measured. Renal pathological changes were observed using hematoxylin-eosin (HE) staining, periodic acid-Schiff (PAS) staining, and Masson staining. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and monocyte chemoattractant protein-1 (MCP-1) levels. Immunofluorescence (IF) was performed to detect F4/80 expression in renal tissue, and immunohistochemistry (IHC) was used to assess CD206 expression. Real-time quantitative polymerase chain reaction (Real-time PCR) was employed to measure the mRNA expression of TNF-α, IL-10, inducible nitric oxide synthase (iNOS), and arginase-1 (Arg-1). Western blot analysis was used to detect the protein expression of iNOS, Arg-1, CD86, and CD206 in renal tissue. ResultsCompared with the normal group, the model group showed increased levels of GSP, UACR, SCr, BUN, TC, and TG, elevated levels of the inflammatory factor TNF-α and the chemokine MCP-1, and decreased IL-10 levels (P<0.01). Pathological examination revealed glomerular hypertrophy, mesangial cell proliferation with marked mesangial expansion, inflammatory cell infiltration, vacuolar degeneration of renal tubular epithelial cells, prominent glycogen deposition, and increased collagen fiber deposition. In addition, relative F4/80 fluorescence intensity was enhanced, CD206 expression in the glomeruli and renal interstitium was reduced, and TNF-α and iNOS mRNA expression was increased. IL-10 and Arg-1 mRNA expression was decreased, iNOS and CD86 protein expression was increased, and Arg-1 and CD206 protein expression was decreased (P<0.05, P<0.01). Compared with the model group, the Danggui Shaoyaosan groups and the irbesartan group showed decreased levels of GSP, UACR, SCr, BUN, TC, and TG, reduced serum TNF-α and MCP-1 levels, and increased IL-10 levels. Renal pathological damage was improved to varying degrees. Relative F4/80 fluorescence intensity was reduced, CD206 expression in the glomeruli and renal interstitium was increased, and TNF-α and iNOS mRNA expression was decreased. IL-10 and Arg-1 mRNA expression was increased, iNOS and CD86 protein expression was reduced, and Arg-1 and CD206 protein expression was increased (P<0.05, P<0.01). ConclusionDanggui Shaoyaosan can improve renal function and alleviate renal pathological damage in db/db mice. Its mechanism may be related to inhibiting M1 pro-inflammatory macrophage polarization, promoting M2 anti-inflammatory macrophage polarization, reducing inflammatory responses, delaying the progression of renal fibrosis, improving renal pathological injury, and thereby exerting renal protective effects.
2.Mechanism of Danggui Shaoyaosan in Improving Inflammatory Response in Mice with Diabetic Kidney Disease Based on TLR4/p65/NLRP3 Signaling Pathway
Shilong GUO ; Ruijia LI ; Zixuan WANG ; Xinai WANG ; Luyu HOU ; Wenjing SHI ; Mengyuan TIAN ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):19-27
ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 (TLR4/NF-κB p65/NLRP3) signaling pathway in the renal tissues of db/db mice with spontaneous diabetes, and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease (DKD). MethodsThirty db/db mice were divided into five groups: A model group, Danggui Shaoyaosan low- (16.77 g·kg-1·d-1), medium- (33.54 g·kg-1·d-1), and high-dose (67.08 g·kg-1·d-1) intervention groups, as well as an irbesartan group (0.025 g·kg-1·d-1) by the random number table method, with 6 mice in each group. Additionally, 6 db/m mice were assigned to the normal group. After 8 weeks of intervention, the following parameters were determined by corresponding methods: body weight, fasting blood glucose (FBG), 24-hour urinary protein (24 h-UTP), and serum creatinine (SCr) levels, renal histopathological analysis by hematoxylin-eosin (HE) staining, Masson staining, and periodic acid-Schiff (PAS) staining, the protein and mRNA expression levels of TLR4, NF-κB p65, NLRP3, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-18 (IL-18) by Western blot and Real-time quantitative polymerase chain reaction (Real-time PCR), as well as TLR4, NF-κB p65, and NLRP3 protein expression in renal tissues by immunohistochemistry (IHC). ResultsCompared with the normal group, the model group exhibited increased body weight, FBG, 24 h-UTP, and SCr levels (P<0.05); disordered renal structure, thickened basement membrane, and interstitial inflammatory cell infiltration, elevated TLR4, NF-κB p65, NLRP3, TNF-α, IL-1β, IL-6, and IL-18 expression; as well as decreased IL-10 expression (P<0.05). Compared with the model group, these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees (P<0.05). ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.
3.Renal Protective Mechanism of Danggui Shaoyaosan in db/db Mice Based on RhoA/ROCK/NF-κB Signaling Pathway
Luyu HOU ; Yuanyuan ZHANG ; Wenjing SHI ; Shilong GUO ; Zixuan WANG ; Linlin ZHENG ; Dengzhou GUO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):30-38
ObjectiveTo investigate whether Danggui Shaoyaosan (DSS) inhibits oxidative stress and alleviates inflammation via the Ras homolog family member A (RhoA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK)/nuclear factor kappa-B (NF-κB) signaling pathway, thereby delaying the progression of diabetic kidney disease (DKD) and exerting a nephroprotective effect. MethodsEight db/m mice were assigned to the normal group, and forty 8-week-old db/db mice were randomly divided into the model group, DSS low-dose group (8.39 g·kg-1), DSS medium-dose group (16.77 g·kg-1), DSS high-dose group (33.54 g·kg-1), and irbesartan group (0.025 g·kg-1), with eight mice in each group. All groups were administered the corresponding treatment by gavage once daily for 12 weeks. The normal and model groups received an equal volume of saline. During administration, changes in body weight, fasting blood glucose (FBG), and 24 hour urinary protein (24 h UTP) were observed. After 12 consecutive weeks of administration, hematoxylin-eosin (HE) staining and Masson's trichrome staining were used to observe renal histopathological changes in each group. The levels of reactive oxygen species (ROS) in renal tissue were detected using the dihydroethidium (DHE) method. The expression levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in renal tissue were determined. Serum interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were measured using enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of RhoA, ROCK1, and NF-κB p65 in renal tissues were detected by Real-time quantitative polymerase chain reaction (Real-time PCR). Protein expression levels of fibronectin (FN), Collagen Ⅳ(Col Ⅳ), transforming growth factor-β1 (TGF-β1), RhoA, ROCK, and NF-κB p65 in renal tissues were determined by Western blot. ResultsCompared with the normal group, the model group showed significantly increased body weight, FBG, and 24 h UTP levels (P<0.01), elevated serum IL-1β and IL-6 levels, enlarged glomerular volume, diffuse mesangial expansion, increased mesangial matrix, and marked collagen fiber proliferation in renal tissues. SOD activity was decreased, while MDA, ROS, RhoA, ROCK1, and NF-κB p65 mRNA expression levels were increased (P<0.01), and the protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 were also elevated (P<0.01). Compared with the model group, the DSS low-, medium-, and high-dose groups and the irbesartan group showed reductions in body weight, FBG, and 24 h UTP, decreased serum IL-1β and IL-6 levels, varying degrees of improvement in renal histopathology, increased SOD activity, decreased MDA levels, reduced ROS expression, and significantly downregulated RhoA, ROCK1, and NF-κB p65 mRNA expression (P<0.05, P<0.01), as well as reduced protein expression levels of FN, Col Ⅳ, TGF-β1, RhoA, ROCK, and NF-κB p65 (P<0.05, P<0.01). ConclusionDSS can alleviate oxidative stress and inflammation, reduce extracellular matrix deposition, and delay renal fibrosis progression in db/db mice. Its mechanism may be related to the inhibition of the RhoA/ROCK/NF-κB signaling pathway, thereby exerting a therapeutic effect on DKD.
4.Molecular Mechanism of Danshen Tongluo Formula in Intervention of Coronary Artery Disease-dominated Panvascular Disease
Jiawen CHENG ; Chao LIU ; Jie WANG ; Yongmei LIU ; Wenjing LIAN ; Chengzhi HOU ; Chenyang ZHU ; Cheng MA
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(24):86-93
ObjectiveEndothelial cell dysfunction being the core link. This study explores the molecular mechanism of Danshen Tongluo formula in treating coronary artery disease-dominated panvascular disease with endothelial cell changes as the core through animal experiments and single-cell transcriptome sequencing. MethodsA rat model of coronary artery disease-dominated panvascular disease was established by ligating the left anterior coronary artery. Rats were randomized into a blank group, a model group, and a Danshen Tongluo formula (28 mg·kg-1·d-1) group. The efficacy was evaluated by examining the cardiac ultrasound, determination of the plasma level of N-terminal pro-brain natriuretic peptide, and pathological staining. After single-cell sequencing, SingleR package, public datasets, and related literature were used for annotation of the cells. Cell chat was used for intercellular communication and ligand-receptor analysis, and scmetabolism was used for metabolic analysis of endothelial cells. ResultsAnimal experiments showed that Danshen Tongluo formula reduced the N-terminal pro-brain natriuretic peptide ( NT-proBNP ) level (P<0.05), ameliorated myocardial cell damage and fibrosis, and increase left ventricular ejection fractions (LVEF) in the rat model of heart failure after myocardial infarction(P<0.05). Single-cell sequencing results showed that Danshen Tongluo formula increased the proportion of arterial endothelial cells, venous endothelial cells, and capillary-arterial endothelial cells, while reducing the proportion of capillary-venous endothelial cells. In addition, this formula increased the interaction intensity of endothelial cells with cardiomyocytes and M1 macrophages and reduced the interaction intensity of endothelial cells with fibroblasts and T cells. Danshen Tongluo formula upregulated CXCL12-CXCR4 signaling in endothelium-B cells and Ptprm-Ptprm signaling in endothelial endothelial cells, while downregulating Mif-(CD74+CXCR44) signaling in endothelium-M1 macrophages and Mif-(CD74+CD44) signaling in endothelium-M2 macrophages. It reduced the citric acid cycle, oxidative phosphorylation, and glycolysis and increased the glycolysis/oxidative phosphorylation ratio in endothelial cells. GO and KEGG enrichment analysis showed that arterial endothelial cells, venous endothelial cells, and venous capillary endothelial cells can all regulate oxidative phosphorylation, cell adhesion molecules, and tyrosine metabolism. Lymphatic endothelial cells regulate immunity and vascular constriction to participate in the metabolism of various amino acids and fatty acids. ConclusionDanshen Tongluo Formula can ameliorate coronary artery disease-dominated panvascular disease by changing the composition of endothelial cells and regulating the communication between myocardial endothelial cells and non-endothelial cells.
5.Analysis of goitrogenic effect of goitrogen in food
Haowen PAN ; Honglei XIE ; Xin HOU ; Meng ZHAO ; Wenjing CHE ; Jia LI ; Yue SU ; Lanchun LIU ; Zexu ZHANG ; Zongyu YUE ; Peng LIU
Chinese Journal of Endemiology 2024;43(1):77-81
Goiter is a kind of non-inflammatory and non-neoplastic hyperplasia and enlargement. Many studies have shown that substances such as thiocyanates and isothiocyanates can prevent the development of a variety of tumors. However, some studies have also found that such substances can lead to goiter. In this article, relevant information on common goitrogen in food are collected to explore their mechanism of action, laying a foundation for guiding residents to maintain a healthy and balanced diet.
6.Regulatory effect mechanism of Eucommia ulmoides on postpartum depression in rats
Yujie LI ; Wenjing CHEN ; Lan ZHANG ; Yingzhen WU ; Yongjie XU ; Xiaolan WANG ; Junlin HOU ; Liping YANG
China Pharmacy 2024;35(11):1303-1308
OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group, postpartum depression group, and low-dose and high-dose groups of E. ulmoides (1.34, 2.68 g/kg, calculated by crude drug), with 10 rats in each group. Except for the normal group, the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy; at the same time of modeling, the administration groups were given relevant medicine intragastrically, while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test, Morris water maze test and sucrose preference test. Additionally, the levels of corticosterone (CORT) in serum, corticotropin releasing factor (CRF) and urocortin (UCN) in hypothalamus, and adrenocorticotropic hormone (ACTH) in hypophysis were detected; meanwhile, the protein expressions of CRF receptor 1 (CRFR1), CRFR2, and voltage-dependent anion channel 1 (VDAC1) in hippocampal tissue were measured; the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined, and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group, the high-dose group of E. ulmoides showed improvements in appetite, mental state, and hair color in rats; their body weight had increased; the scores of vertical movement, horizontal movement and self-sorting significantly increased; from the 2ed to 4th day avoidance latency significantly shortened, and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目(No.82204789) significantly increased/prolonged (P<0.05); the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum (P<0.05); the levels of CRF, UCN, ACTH and CORT, phagocytic rate, protein expressions of CRFR2 and VDAC1, and the proportion of apoptosis cells in hippocampal tissue were decreased significantly (P<0.05); the proportion of JC-1 high potential cells significantly increased (P<0.05), and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis, decreasing the expression of CRFR2, thereby inhibiting the expression of VDAC1, and decreasing the apoptosis of neuronal cells.
7.Regulatory effect mechanism of Eucommia ulmoides on postpartum depression in rats
Yujie LI ; Wenjing CHEN ; Lan ZHANG ; Yingzhen WU ; Yongjie XU ; Xiaolan WANG ; Junlin HOU ; Liping YANG
China Pharmacy 2024;35(11):1303-1308
OBJECTIVE To explore the effect mechanism of Eucommia ulmoides on improving postpartum depression in rats. METHODS Pregnant rats were randomly divided into normal group, postpartum depression group, and low-dose and high-dose groups of E. ulmoides (1.34, 2.68 g/kg, calculated by crude drug), with 10 rats in each group. Except for the normal group, the rats in other groups suffered from fear stress to induce postpartum depression model during pregnancy; at the same time of modeling, the administration groups were given relevant medicine intragastrically, while the normal group and postpartum depression group were given physiological saline intragastrically for 21 days. Postpartum behaviors of rats during the experiment were assessed using the open field test, Morris water maze test and sucrose preference test. Additionally, the levels of corticosterone (CORT) in serum, corticotropin releasing factor (CRF) and urocortin (UCN) in hypothalamus, and adrenocorticotropic hormone (ACTH) in hypophysis were detected; meanwhile, the protein expressions of CRF receptor 1 (CRFR1), CRFR2, and voltage-dependent anion channel 1 (VDAC1) in hippocampal tissue were measured; the proportions of apoptotic cells and JC-1 high potential cells in hippocampal tissue were determined, and the morphology of hippocampal tissue was observed. RESULTS Compared with postpartum depression group, the high-dose group of E. ulmoides showed improvements in appetite, mental state, and hair color in rats; their body weight had increased; the scores of vertical movement, horizontal movement and self-sorting significantly increased; from the 2ed to 4th day avoidance latency significantly shortened, and the times of crossing the platform and the time of crossing the platform Δ 基金项目国家自然科学基金青年基金项目(No.82204789) significantly increased/prolonged (P<0.05); the ratio of glucose and water consumption significantly increased at 20 days of pregnancy and 30 days postpartum (P<0.05); the levels of CRF, UCN, ACTH and CORT, phagocytic rate, protein expressions of CRFR2 and VDAC1, and the proportion of apoptosis cells in hippocampal tissue were decreased significantly (P<0.05); the proportion of JC-1 high potential cells significantly increased (P<0.05), and the phenomenon of edema around neuronal cells was significantly improved. CONCLUSIONS E. ulmoides can improve postpartum depression by inhibiting excessive activation of hypothalamic-pituitary-adrenal axis, decreasing the expression of CRFR2, thereby inhibiting the expression of VDAC1, and decreasing the apoptosis of neuronal cells.
8.Formulation and Analysis on the Standard of Construction of Medication Safety Culture
Wenjing HOU ; Su SHEN ; Aiping WEN ; Jin LU ; Jiancun ZHEN ; Wei ZHANG ; Dan MEI ; Zhicheng GONG ; Yubo WU ; Qunhong SHEN ; Weiyi FENG ; Ling TAN ; Yanhua ZHANG ; Fang LIU ; Xiaole ZHANG
Herald of Medicine 2024;43(7):1079-1083
The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.
9.Research Progress in Environment-responsive Nano-drug Delivery System Based on Traditional Chinese Medicine Monomer in Tumor Therapy
Chunyan LYU ; Rui HAN ; Wenyu CUI ; Wenqian WANG ; Xiaoqing HOU ; Wenjing XIN ; Wenjun ZHANG
Herald of Medicine 2024;43(11):1799-1804
Traditional Chinese medicine monomer has certain curative effects in tumor treatment,but its low targeting and difficulty in gathering at the tumor site limit its application.As a new type of drug delivery method,environmentally responsive nano drug delivery system has the advantages of targeted drug delivery,reducing drug side effects,and environmentally responsive release,and has been widely used in tumor treatment.In this paper,by consulting and sorting out the relevant literature,the general situation of traditional Chinese medicine monomers in the treatment of tumors,the classification of environment-responsive traditional Chinese medicine monomer nano drug delivery system,and its application in tumor treatment are summarized in three aspects,to provide ideas for solving the limitations of traditional Chinese medicine monomer in the treatment of tumor.
10.Research progress on the relationship between blood pressure variability and cognitive impairment
Along HOU ; Wenbin CHENG ; Wenjing SUN ; Xiaohan CHEN ; Genru LI ; Jianhua ZHUANG ; You YIN
Chinese Journal of Clinical Medicine 2024;31(4):659-667
Cognitive impairment is a kind of senile disease that leads to the decline of personality and behavior ability of the elderly,which seriously affects the quality of daily life of patients.The prevalence rate of the disease increases year by year with the acceleration of the aging process of the society,and its incidence is affected by many risk factors.At this stage,the curative effect for middle and advanced patients is poor.So early identification and intervention to delay the progression of cognitive impairment have become the focus of relevant research.Blood pressure variability can lead to damage of target organs such as heart,brain tissue and kidney,which is closely related to cognitive impairment.In order to expand a new perspective of early intervention in cognitive impairment,this paper reviews the effects of blood pressure variability on different cognitive impairment and its possible pathogenic mechanism.

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