1.Effects of Tripterygium wilfordii multiglycoside on renal injury in rats with diabetic nephropathy
Chong ZHANG ; Chundong SONG ; Mo WANG ; Shuang LIANG ; Xiaoxiao GUO ; Hanhan ZHANG ; Peijia LI ; Ke SONG ; Chenchen CHEN
China Pharmacy 2025;36(7):815-819
OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside (TWM) on renal injury in diabetic nephropathy (DN) rats through tumor protein p53/microRNA-214 (miR-214)/UNC-51-like kinase 1 (ULK1) axis. METHODS Male SD rats were randomly divided into normal group (n=6) and modeling group (n=28); the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group, valsartan group [8.33 mg/(kg·d)] and TWM group[6.25 mg/(kg·d)], with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline, once a day, for 6 consecutive weeks. After the last medication, liver and renal function indexes [24 h urinary total protein (24 h-UTP), blood urea nitrogen (BUN), serum creatinine (SCr), albumin (ALB), alanine transaminase (ALT)], blood lipid indexes (triglycerides, total cholesterol) and blood glucose index (fasting blood glucose) in urine/blood sample of rats were detected in each group. Renal pathologic change was observed, protein and mRNA expressions of p53, ULK1, Beclin-1 and microtubule-associated protein 1 light chain 3 (LC3), and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group, the renal tubular epithelium of rats in the model group showed obvious edema, cell swelling, accompanied by lymphocyte infiltration; the levels of 24h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1, Beclin-1 protein and mRNA were significantly decreased or down-regulated (P<0.01). Compared with the model group, the histopathological damage of the kidney in rats was improved in administration groups; the levels of 24 h-UTP, BUN, SCr, ALT and glycolipid indexes, the expressions of p53 protein and mRNA, as well as the expression of miR-214 were all significantly decreased or down-regulated, while ALB level, LC3-Ⅱ/LC3-Ⅰ, the expressions of LC3 mRNA, the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated (P<0.01). CONCLUSIONS TG can alleviate renal damage in DN rats, and improve their liver and renal function, as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.
2.Fitting Degrees of Animal Models of Chronic Glomerulonephritis with Clinical Characteristics in Western Medicine and Traditional Chinese Medicine
Siqing WU ; Lin GUO ; Beibei ZHANG ; Mingsan MIAO ; Jinxin MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(3):259-264
Chronic glomerulonephritis (CGN) is a common clinical chronic glomerular disease caused by autoimmune reaction, the pathogenesis of which is complex and has not been fully elucidated. There is no specific treatment method in modern medicine. The establishment of an animal model of CGN in accordance with its characteristics in western medicine and traditional Chinese medicine will help to reveal the pathogenesis of CGN, rate drugs, and improve the treatment plan. Based on the clinical diagnostic criteria of CGN, the paper establishes the syndrome differentiation criteria of CGN for Chinese and western medicine. Through summarizing the literature on animal models of CGN and making a further analysis, it is found that the CGN models are mainly modeled using rats with the methods of single-factor induction or two-factor induction, and the main manifestation of the disease characteristics is nephritis-related symptoms. The single-factor-induced or two-factor-induced CGN rat models have a high fitting degree with the clinical characteristics in western medicine, but the fitting degree is insufficient with the clinical characteristics in traditional Chinese medicine. In addition, the CGN models with syndromes of traditional Chinese medicine are dominated by Qi deficiency in the spleen and kidney and Qi deficiency in the lung and kidney, while models for Yang deficiency in the spleen and kidney, Yin deficiency in the liver and kidney, and deficiency of both Qi and Yin are slightly insufficient. Therefore, it is important to prepare a new and improved animal model of CGN, so that a preclinical model can be provided for the exploration of the pathogenesis of CGN in western medicine and traditional Chinese medicine and its therapeutic research.
3.Characteristic Analysis of Effective Components and Compounds of TCM for Prevention and Treatment of Breast Cancer Based on Wnt/β-catenin Signaling Pathway Targeting
Haoyang WANG ; Lin GUO ; Hui ZHAO ; Lihua CAO ; Na LI ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):282-290
Breast cancer is a kind of malignant tumor with a complex mechanism, and its morbidity and mortality are increasing year by year, which seriously threatens women's health. At present, the main clinical treatments are surgical resection, radiotherapy, chemotherapy, and drug therapy, but they are often accompanied by side effects and adverse reactions, which affect the therapeutic effect. Traditional Chinese medicine (TCM) has the advantages of multi-component and multi-target treatment in the fight against breast cancer. The wnt/β-catenin signaling pathway is one of the classic pathways in cancer research. Abnormally activated Wnt/β-catenin signaling pathway inhibits β-catenin degradation by blocking the formation of Axin/glycogen synthase kinase 3β/adenomatous polyposis coli complex, thus promoting β-catenin nuclear metastasis, and it binds to T cell transcription factor/lymphoenhancer factor-1 to initiate downstream target genes and further interfere with the proliferation, migration, and invasion of tumor cells to affect the tumor process. Previous studies have shown that TCM monomers and compounds can mediate the Wnt/β-catenin signaling pathway to inhibit the malignant phenotype of breast cancer cells, thus playing an anti-breast cancer role, and the biochemical process involved in the regulation of therapeutic drugs has not been systematically combed. By analyzing and collating Chinese and foreign literature at the present stage, this paper discussed the association mechanism between Wnt/β-catenin signaling pathway and breast cancer and analyzed the internal mechanism of TCM monomers and compounds in mediating Wnt/β-catenin signaling pathway to exert anti-breast cancer effect. The statistical results showed that the flavonoids, alkaloids, and terpenoids in TCM monomers could target the Wnt/β-catenin signaling pathway and block the further development of malignant phenotype of breast cancer cells. TCM compounds with functions of clearing heat and detoxifying, promoting blood circulation and removing blood stasis, and tonifying kidney and liver were commonly used to intervene in the Wnt/β-catenin signaling pathway to prevent breast cancer. Compared with the current inhibitors of Wnt/β-catenin signaling pathway, the application of TCM monomers and compounds is expected to bring low-toxicity and high-efficiency breast cancer treatment drugs to the clinical practice, and the existing results provide a reference for the subsequent screening, research, and development of TCM small-molecule compounds and TCM compounds against breast cancer.
4.Mechanism of inhibitory effect of total flavonoids from Taraxacum mongolicum on obesity in mice by regulating intestinal flora
Yixue GAO ; Lin GUO ; Linyan LANG ; Jing WU ; Haoyang WANG ; Jing YANG ; Mingsan MIAO ; Zhanzhan LI
China Pharmacy 2025;36(3):293-299
OBJECTIVE To investigate the mechanism of the inhibitory effect of total flavonoids from Taraxacum mongolicum on high-fat diet-induced obesity in mice through modulation of intestinal flora. METHODS Twenty-four C57BL/6J mice were randomly divided into blank group, model group and T. mongolicum total flavonoid group, with 8 mice in each group. Except for the blank group, the other 2 groups were given a high-fat diet, while T. mongolicum total flavonoid group was given T. mongolicum total flavonoid [400 mg/(kg·d)] intragastrically, once a day, for 8 consecutive weeks. During the experiment, the food intake of each group of mice was recorded. After the last medication, the body mass, fat weight, blood lipid level and pathological changes of liver and epididymal fat in mice were evaluated to observe the effect of T. mongolicum total flavonoid on the treatment of obesity in mice. The changes in abundance and structure of intestinal flora in mice were detected by amplicon sequencing; the effects of T. mongolicum total flavonoids on fat metabolism related genes were analyzed by qPCR. RESULTS Compared with model group, the body weight of mice in T. mongolicum total flavonoids group was decreased significantly (P<0.05); the levels of total lipid cholesterol, triglycerides, and LDL cholesterol were all decreased significantly (P<0.01), and the level of HDL cholesterol was increased significantly (P<0.01); the fat indexes of inguinal white adipose tissue and epididymal white wind_lz@hactcm.edu.cn adipose tissue were significantly reduced (P<0.05); significant improvement in hepatocellular steatosis and adipose cytopathy were significantly improved; mRNA expressions of COX7A1 and COX8B were significantly upregulated (P<0.05). The results of bacterial colony detection showed that compared with the model group, there was a rising trend in the diversity of the bacterial colony in T. mongolicum total flavonoids group, and the Sobs index characterization and β diversity were increased significantly (P<0.05). Relative abundances of Blautia, norank_f_Ruminococcaceae, Bilophila, Alistipes, classified_f_Ruminococcaceae, Parabacteroides, norank_f_Desulfovibrionaceae, Anaerotruncus were significantly up-regulated(P<0.05), while those of Faecalibaculum, Erysipelatoclostridium, GCA-900066575, Tuzzerella, Lactobacillus, norank_f_norank_o_RF39, achnospiraceae_FCS020_group were significantly down-regulated (P<0.05). CONCLUSIONS T. mongolicum total flavonoids can reduce body mass, fat weight and blood lipid levels, and repair the pathological damage to liver and epididymal fat in obese mice, which is related to improving intestinal flora disorders caused by high-fat diet.
5.Mechanism of Xinnao shutong capsule alleviating cerebral ischemia-reperfusion injury in rats by regulating ferroptosis
Huani LI ; Changhe LIU ; Xiaoyan GUO ; Xin ZHONG ; Wei ZHANG ; Wenjing GE
China Pharmacy 2025;36(3):306-311
OBJECTIVE To study the mechanism of Xinnao shutong capsule alleviating cerebral ischemia reperfusion injury (CIRI) in rats by regulating the ferroptosis pathway. METHODS SD rats were randomly divided into sham operation group, model group, Xinnao shutong low-dose, high-dose group (220, 440 mg/kg), Ginkgo biloba leaves extract group (positive control, 150 mg/kg). Each group of rats was orally administered with the corresponding medication/normal saline for 7 consecutive days. Transient occlusion of the middle cerebral artery was adopted to induce the CIRI model; the samples were taken 24 h after the operation; the cerebral infarction area of rats was detected, and the cerebral infarction rate was calculated. The pathological changes of brain tissues were observed, and the levels of lipid peroxide (LPO), malondialdehyde (MDA) and glutathione (GSH) in cerebral tissue were detected; mRNA and protein expressions of nuclear factor-erythroid 2-related factor 2 (Nrf2), heme oxygenase 1(HO-1) and glutathione peroxidase 4 (GPX4) were all detected in cerebral tissue of rats. RESULTS Compared with model group, the cerebral infarction rate, the content of total iron in cerebral tissue and serum level of LPO (except for Ginkgo biloba leaves extract group and Xinnao shutong low-dose group) were all decreased significantly in G. biloba leaves extract group and Xinnao shutong groups (P<0.05 or P<0.01); the serum level of GSH, the protein and mRNA expressions of Nrf2, HO-1 and GPX4 were all increased significantly (P<0.05 or P<0.01). The pathological damage to brain tissue was reduced, the number of nerve cells increased, the edema was alleviated, and the nuclear membrane was flattened. CONCLUSIONS Xinnao shutong capsule can inhibit ferroptosis and reduce CIRI, the mechanism of which may be associated with the activation of the Nrf2/HO-1/GPX4 signaling pathway.
6.Mitochondrial Quality Control Regulating Pathogenesis of Sarcopenia and Its Intervention by Traditional Chinese Medicine: A Review
Ting DAI ; Yan CHEN ; Changsheng GUO ; Jing GAO ; Xiaodong FENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):279-286
Sarcopenia is a clinical syndrome characterized by a decrease in skeletal muscle strength and quality, often accompanied by adverse outcomes such as falls, loss of function and weakness. The pathogenesis of sarcopenia is complex, and studies have shown that dysfunction due to impaired mitochondrial quality control is an important pathological factor in the occurrence and development. Traditional Chinese medicine(TCM) has been widely favoured for regulating mitochondrial homeostasis and preventing sarcopenia by virtue of its multi-target and multi-pathway advantages. They can play a role in the prevention and treatment of sarcopenia by regulating the mitochondrial quality control system to inhibit the occurrence of mitochondrial oxidative stress, regulate the balance of mitochondrial dynamics, inhibit mitochondrial autophagy, promote mitochondrial biosynthesis, resist the occurrence of mitochondrial apoptosis, and maintain the mitochondrial calcium and protein homeostasis. Based on this, the paper reviewed the relationship between mitochondrial quality control and sarcopenia, as well as the mechanism of TCM in intervening the mitochondrial quality control system to treat sarcopenia, in order to provide a new idea for the prevention and treatment of sarcopenia by TCM and to a theoretical basis for the clinical research on TCM intervention in sarcopenia.
7.Effect of interleukin-8 regulation on monocyte chemotactic protein-1 secretion and expression through the NF-kappaB/p65 signaling pathway on the migration of residual epithelial cells in the lens capsule
Wei SI ; Su XU ; Yuhang ZHANG ; Yi MAO ; Keyu GUO ; Yanzhong HU ; Fengyan ZHANG
International Eye Science 2025;25(4):537-543
AIM: To investigate the effect of interleukin-8(IL-8)on the regulation of monocyte chemotactic protein-1(MCP-1)secreted by lens epithelial cells(LEC)during cell migration in the development of posterior capsule opacification(PCO).METHODS: A rat lens capsule model was established and cultured in medium supplemented with 10% fetal bovine serum. Upon migration of LEC to 30%-50% of the posterior capsule, serum was removed. The capsule was subsequently divided into two groups: a control group and an IL-8(15 ng/mL)treatment group. LEC migration was captured at multiple time points. The secretion and mRNA expression of MCP-1 were quantified using ELISA and RT-qPCR, respectively. Immunofluorescence was used to assess MCP-1 expression in the different experimental groups. SRA01/04 cells were divided into three groups: control, IL-8(15 ng/mL), and IL-8(15 ng/mL)+200 μmol/L Bindarit(BND)groups, with migration measured by the Transwell assay. Additionally, SRA01/04 cells were divided into negative control(NC), NC+15 ng/mL IL-8, and 15 ng/mL IL-8+p65 siRNA groups, and MCP-1 secretion and mRNA expression were further analyzed by ELISA and RT-qPCR.RESULTS:LEC migration in the rat lens capsule cultured in vitro showed that the cells migration of the 15 ng/mL IL-8 group significantly increased at 48, 72 and 96 h(all P<0.05). ELISA results revealed that MCP-1 levels in SRA01/04 cells from the 15 ng/mL IL-8-treated group were markedly higher than those in the control group at both 12 and 24 h(all P<0.05). RT-qPCR analysis also demonstrated a significant increase in MCP-1 mRNA expression in the 15 ng/mL IL-8 group at both time points(all P<0.05). Immunofluorescence staining indicated greater MCP-1 expression in capsular epithelial cells of the 15 ng/mL IL-8 group at 24 h(P=0.007). Transwell assays further confirmed increased cell migration in the 15 ng/mL IL-8 group compared to the control group(P=0.001), while the migration reduced in the 15 ng/mL IL-8+200 μmol/L BND group compared to the 15 ng/mL IL-8 group(P=0.003). Moreover, ELISA and RT-qPCR results demonstrated a significant increase in MCP-1 secretion and mRNA expression in the NC+15 ng/mL IL-8 group at both 12 and 24 h compared to the NC group(all P<0.01). In contrast, MCP-1 secretion and mRNA expression were reduced in the 15 ng/mL IL-8+p65 siRNA group compared to the NC+15 ng/mL IL-8 group at both time points(all P<0.01).CONCLUSION: IL-8 promotes the migration of residual epithelial cells and regulates the secretion and expression of MCP-1 in LEC. The mechanism underlying IL-8's effects appears to be mediated through the activation of the NF-κB/p65 signaling pathway.
8.A Randomized Controlled Trial of Stone Needle Thermocompression and Massage for Treating Chronic Musculoskeletal Pain in the Shoulder and Back:A Secondary Analysis of Muscle Elasticity as a Mediator
Jingjing QIAN ; Yuanjing LI ; Li LI ; Yawei XI ; Ying WANG ; Cuihua GUO ; Jiayan ZHOU ; Yaxuan SUN ; Shu LIU ; Guangjing YANG ; Na YUAN ; Xiaofang YANG
Journal of Traditional Chinese Medicine 2025;66(9):935-940
ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back, and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group, with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes, three times per week; the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement, as the primary outcome, was assessed using the Global Pain Scale (GPS) at baseline, after 2 weeks of treatment, and again 2 weeks post-treatment. To explore potential mechanisms, a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration, the between-group mean difference was -8.8 [95% CI (-18.2, -0.7), P<0.05]. Part of the therapeutic effect was mediated by changes in deep muscle elasticity, with a mediation effect size of -1.5 [95% CI (-2.0, -0.9), P = 0.024], accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back, partly through a mediating effect of improved deep muscle elasticity.
9.Treatment of Recurrent Pediatric Cough and Asthma Based on the Theory of "Mutual Dependence of Ascending and Descending" from the Perspectives of Deficiency,Phlegm,and Blood Stasis
Yu LIU ; Ying DING ; Yongbin YAN ; Xuran GUO ; Linlin LIU
Journal of Traditional Chinese Medicine 2025;66(9):963-967
Guided by the theory of "mutual dependence of ascending and descending", recurrent pediatric cough and asthma are considered to result from the imbalance of the ascending and descending of zang-fu organ qi, which is closely associated with deficiency, phlegm, and blood stasis. In clinical practice, the disease is treated based on differentiation during the initial stage, progression stage, and stable stage. In the initial stage, the pathogenesis is attributed to lung deficiency complicated by external pathogens and liver qi rising to attack the lung; the treatment should focus on restraining the lung and calming the liver, using the self-formulated Longchai Yuchuan Fomulation (龙柴愈喘方). During the progression stage, the disorder is due to the spleen failing to ascend clear qi and the kidney failing to grasp qi, leading to phlegm formation from deficiency; treatment should focus on tonifying spleen yang, supplementing kidney qi, and resolving phlegm and fluid retention, using a modified combination of Linggui Zhugan Decoction (苓桂术甘汤) and Jinkui Shenqi Pill (金匮肾气丸). In the stable stage, qi deficiency leads to poor consolidation, with phlegm turbidity and blood stasis; the treatment should aim at tonifying qi, transforming phlegm, and dispelling blood stasis, using a modified version of Guizhi Fuling Pill (桂枝茯苓丸).
10.Objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease
Zhaoxi DONG ; Yang SHI ; Jiaming SU ; Yaxuan WEN ; Zheyu XU ; Xinhui YU ; Jie MEI ; Fengyi CAI ; Xinyue ZANG ; Yan GUO ; Chengdong PENG ; Hongfang LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):398-411
Objective:
To investigate the objective characteristics of tongue manifestation in different stages of damp-heat syndrome in diabetic kidney disease (DKD).
Methods:
A cross-sectional study enrolled 134 patients with DKD G3-5 stages who met the diagnostic criteria for damp-heat syndrome in DKD. The patients were treated at Dongzhimen Hospital, Beijing University of Chinese Medicine, from May 2023 to January 2024. The patients were divided into three groups: DKD G3, DKD G4, and DKD G5 stage, with 53, 33, and 48 patients in each group, respectively. Clinical general data (gender, age, and body mass index) and damp-heat syndrome scores were collected from the patients. The YZAI-02 traditional Chinese medicine (TCM) AI Tongue Image Acquisition Device was used to capture tongue images from these patients. The accompanying AI Open Platform for TCM Tongue Diagnosis of the device was used to analyze and extract tongue manifestation features, including objective data on tongue color, tongue quality, coating color, and coating texture. Clinical data and objective tongue manifestation characteristics were compared among patients with DKD G3-5 based on their DKD damp-heat syndrome status.
Results:
No statistically significant difference in gender or body mass index was observed among the three patient groups. The DKD G3 stage group had the highest age (P<0.05). The DKD G3 stage group had a lower score for symptoms of poor appetite and anorexia(P<0.05) than the DKD G5 group. No statistically significant difference was observed in damp-heat syndrome scores among the three groups. Compared with the DKD G5 stage group, the DKD G3 stage group showed a decreased proportion of pale color at the tip and edges of the tongue (P<0.05). The DKD G4 stage group exhibited an increased proportion of crimson at the root of the tongue, a decreased proportion of thick white tongue coating at the root, a decreased proportion of pale color at the tip and edges of the tongue, an increased hue value (indicating color tone) of the tongue color in the middle, an increased brightness value (indicating color lightness) of the tongue coating color in the middle, and an increased thickness of the tongue coating (P<0.05). No statistically significant difference was observed in other tongue color proportions, color chroma values, body characteristics, coating color proportions, coating color chroma values, and coating texture characteristics among the three groups.
Conclusion
Tongue features differ in different stages of DKD damp-heat syndrome in multiple dimensions, enabling the inference that during the DKD G5 stage, the degree of qi and blood deficiency in the kidneys, heart, lungs, liver, gallbladder, spleen, and stomach is prominent. Dampness is more likely to accumulate in the lower jiao, particularly in the kidneys, whereas heat evil in the spleen and stomach is the most severe. These insights provide novel ideas for the clinical treatment of DKD.


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