1.Artificial intelligence-based systematic study on the multidimensional pharmacological activity and molecular mechanism of the active ingredients of Artemisia argyi
Hongrong ZHANG ; Qi ZOU ; Zhongmin MA ; Zhaohui FANG
Journal of China Pharmaceutical University 2025;56(3):358-367
To investigate the pharmacological activities and potential mechanisms of action of the active components in Artemisia argyi with artificial intelligence technology, a search was conducted in the HIT, TCMSP, and TCMIO databases, obtaining 199 active components of A. argyi. A comprehensive set of algorithms, including KNN, MLP, RF, SVM, and models based on Lipinski’s and Veber’s rules, was employed to predict the toxicity and oral bioavailability of A. argyi compounds, identifying 14 components that are non-toxic and have good oral bioavailability. The synthetic accessibility score (SAscore) model was used to analyze the synthetic accessibility of the 14 components mentioned above, and molecular segments were fragmented using BRICS and RECAP algorithms. Mining of the STP and PM databases yielded 406 target proteins for the core components of A. argyi, and Cytoscape was used to screen out 5 core targets: SRC, EGFR, PTPN11, HRAS, and PDGFRB. GO and KEGG enrichment analyses indicated that the core targets were involved in 808 GO enrichment analysis entries and 71 signaling pathways, including EGFR tyrosine kinase inhibitor resistance, gap junction, phospholipase D, and JAK/STAT. Molecular docking results showed that active compounds of A. argyi have a good binding affinity with proteins SRC, EGFR, PTPN11, and HRAS. Cellular experiments have confirmed that ledol, an active component of A. argyi, can promote the proliferation of HUVEC cells within a certain concentration range and can increase the expression of EGFR protein. This study reveals the pharmacological characteristics and potential molecular mechanisms of the active components of A. argyi and lays a solid scientific foundation for its medicinal development.
2.Mechanism of Astragaloside Ⅳ in Regulating PI3K/Akt Molecular Pathway in Prevention and Treatment of Diabetes Complications: A Review
Kexin HU ; Jinru ZHU ; Qing WU ; Shengmao WANG ; Mengfan WANG ; Ai QIAN ; Zhaohui FANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):307-314
Diabetes mellitus (DM) is a metabolic disease caused by absolute or relative insulin deficiency and reduced insulin sensitivity in peripheral cells, posing a serious threat to global health. Chronic complications arising in the later stages of DM can lead to the decline or even loss of function in multiple organs, including the eyes, heart, liver, kidneys, nerves, and feet, making them the primary cause of mortality in DM patients. Although modern medicine has made some progress in the treatment of these complications, challenges such as high costs and adverse drug reactions remain. Thus, identifying highly effective drugs with minimal adverse effects has become a top priority. Astragalus membranaceus is a shining gem in the treasure trove of Chinese medicine. Numerous studies have shown that its primary active component, astragaloside Ⅳ, possesses various biological activities, including anti-inflammatory, antioxidant, and antiviral effects, as well as benefits for cardiac and cerebral function, nerve conduction, and myocardial protection. Meanwhile, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway plays a crucial role in regulating oxidative stress, inflammatory responses, apoptosis, and autophagy. Extensive research has highlighted the significant role of this pathway in various DM complications, leading to widespread studies on its interaction with astragaloside Ⅳ. This review summarizes research findings on how astragaloside Ⅳ alleviates pancreatic cytotoxicity in DM patients by modulating the PI3K/Akt pathway. Additionally, it highlights its protective effects on basic cardiac function, inhibition of retinal cell damage, improvement of cerebral nerve dysfunction, reduction of chronic kidney and liver damage, and mitigation of neurovascular toxicity in the lower limbs. These insights provide a valuable reference for the clinical application of A. membranaceus and its active monomer, astragaloside Ⅳ, in the treatment of DM and its complications.
3.Study on the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus
Xiaoying XIONG ; Wei QIAO ; Weibing ZHONG ; Fei TU ; Fang WU ; Fangfang ZHENG ; Guoliang SONG ; Zhaohui PEI ; Yandong LIU
Chongqing Medicine 2025;54(5):1161-1165,1171
Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P<0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P<O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P>0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.
4.The Effect of Banxia Xiexin Decoction (半夏泻心汤) on the Expression of LXRα in Liver Tissue and the JAK2/STAT3 Signaling Pathway in Gastric Antrum Tissue of Diabetic Gastroparesis Model Rats
Qi XU ; Nuobing RUAN ; Jinju LI ; Xijuan LYU ; Zhaohui FANG
Journal of Traditional Chinese Medicine 2025;66(2):178-187
ObjectiveTo explore the potential mechanism of Banxia Xiexin Decoction (半夏泻心汤, BXD) in the treatment of diabetic gastroparesis (DGP). MethodsA total of 29 SD rats were randomly divided into four groups, blank group (5 rats) and model group, BXD group and metformin group (8 rats in each group). Except for the blank group, rats were administered intraperitoneally with 1% streptozotocin (STZ) solution and were fed a high-sugar, high-fat diet to establish the DGP rat model. After successful modeling, the BXD group was treated with BXD at 6.68 g/(kg·d) by gavage, the metformin group was treated with metformin hydrochloride at 105 mg/(kg·d) by gavage, and the blank group and the model group were treated with normal saline at 6.68 ml/(kg·d) by gavage, for 8 weeks. After the last administration, fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG) were measured and gastric emptying rate was calculated. ELISA was used to detect the levels of gastrointestinal hormones motilin (MTL) and gastrin (GAS), as well as inflammatory factors including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-10 (IL-10) in gastric tissue. Oil red O staining was performed to observe liver pathological morphology. Hematoxylin and eosin (HE) staining was used to observe gastric antrum tissue morphology. Immunofluorescence staining was used to detect liver X receptor α (LXRα) levels in the liver. Western Blot was used to detect the protein levels of LXRα in liver tissue, and of janus kinase 2 (JAK2), phospho-janus kinase 2 (p-JAK2), signal transducer and activator of transcription 3 (STAT3) and phospho-signal transducer and activator of transcription 3 (p-STAT3) in gastric antrum tissue. Quantitative real-time polymerase chain reaction (qPCR) was used to measure the mRNA expression of LXRα in liver tissue and JAK2, STAT3 in gastric antrum tissue. ResultsCompared with the blank group, the model group showed significant hepatic fatty degeneration, gastric antrum tissue structure destruction, and increases in FBG, HbA1c, TC, and TG levels; the average fluorescence intensity, protein level, and mRNA expression of LXRα in liver tissue were reduced; the gastric emptying rate and gastric tissue GAS and MTL levels decreased; inflammatory factors including TNF-α, IL-6, IL-1β in gastric tissue increased, IL-10 decreased; in gastric antrum tissue, the mRNA expression of p-JAK2/JAK2, p-STAT3/STAT3, and JAK2 and STAT3 increased (P<0.01). Compared with the model group, both the BXD group and the metformin group showed improved liver and gastric antrum tissue pathology; FBG, HbA1c, TC, and TG levels decreased, while LXRα fluorescence intensity, protein level, and mRNA expression in liver tissue significantly increased; the gastric emptying rate and the levels of GAS and MTL in gastric tissue were markedly higher; the levels of TNF-α, IL-6, and IL-1β decreased, whereas IL-10 levels increased, p-JAK2/JAK2, p-STAT3/STAT3, and the mRNA expression of JAK2 and STAT3 in gastric antrum tissue decreased (P<0.05 or P<0.01). The BXD group showed higher level than the metformin group in FBG, HbA1c, and TG levels, lower level in gastric emptying rate and gastric tissue GAS content, and higher level in gastric tissue TNF-α, IL-6, IL-1β levels; there was also a decrease in IL-10 levels, and a reduction in LXRα fluorescence intensity and mRNA expression in liver tissue, as well as in p-JAK2/JAK2 levels in gastric antrum tissue (P<0.05 or P<0.01). ConclusionBXD can reduce blood glucose and lipid levels in DGP model rats while improving gastric function and alleviating gastric tissue inflammation. Its mechanism may be related to the regulation of LXRα expression in liver tissue and the JAK2/STAT3 pathway in gastric antrum tissue.
5.Clinical Study on Yangyin Yifei Decoction in Treating Type 2 Diabetes Mellitus Patients with Qi-Yin Deficiency and Elevated Keratin 19 Fragment
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(6):832-837
OBJECTIVE To observe the clinical efficacy of Yangyin Yifei Decoction in treating type 2 diabetes mellitus(T2DM)patients with of qi-yin deficiency and elevated serum keratin 19 fragment(Cyfra21-1).METHODS Sixty patients with T2DM of qi-yin deficiency type and elevated serum Cyfra21-1 who met the inclusion criteria were selected and randomly divided into an observation group and a control group,30 cases in each group.The control group was given oral hypoglycemic treatment with metformin hydrochlo-ride sustained-release tablets and dapagliflozin tablets,and the observation group was given Yangyin Yifei Decoction on the basis of the treatment of the control group.The treatment course of both groups was 12 weeks.Before and after treatment,the changes of traditional Chinese medicine(TCM)syndrome scores,fasting blood glucose(FBG)and 2-hour postprandial glucose(2 h PG),glycosylated he-moglobin(HbAlc),serum Cyfra21-1 and Cyfra21-1 specific T cell response,triglycerides(TG),total cholesterol(TC),alanine ami-notransferase(ALT),aspartate aminotransferase(AST),urea(UR),and creatinine(CREA)were observed in the two groups.RE-SULTS After treatment,FBG,2 h PG,HbAlc,and TCM syndrome scores of the two groups of patients decreased significantly(P<0.05,P<0.01),and the observation group was better than the control group(P<0.05,P<0.01);TG and TC in the observation group were significantly reduced(P<0.01),serum Cyfra21-1 was significantly decreased(P<0.01),and Cyfra21-1-specific T cells in PBMCs were significantly increased(P<0.01),which was better than the control group(P<0.01);there was no significant change in liver and kidney function in the two groups.CONCLUSION Yangyin Yifei Decoction combined with basic hypoglycemic regimen can significantly improve blood glucose and lipid metabolism in T2DM patients with qi-yin deficiency and elevated serum Cyfra21-1,enhance the function of Cyfra21-1-specific T cells,and improve the body's immunity,with high safety.
6.Medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus based on data mining and network pharmacology
Jinru ZHU ; Qing WU ; Kexin HU ; Mengfan WANG ; Zhaohui FANG
Chinese Journal of Pharmacoepidemiology 2025;34(3):260-272
Objective To explore the medication rules and mechanism of Xin'an physicians in the treatment of diabetes mellitus.Methods The prescriptions for the treatment of diabetes mellitus in Xin'an medical writings were collected.The core drug prescriptions were obtained by using IBM SPSS Modeler 18.0 for dispensing association rules as well as complex network analysis,and the cluster analysis of high-frequency traditional Chinese medicines was carried out by using IBM SPSS Statistics 25.0.The active ingredients and targets of the core drugs were extracted from the BATMAN-TCM database.The GeneCards database was used to search for diabetes gene targets,and after obtaining the intersecting targets,the STRING online platform was imported to construct the protein interactions network,and screened the core genes by using the Cytoscape 3.9.1 software,and imported into the DAVID database for GO function and KEGG pathway enrichment analysis.Results A total of 135 valid prescriptions were included,involving 184 flavors of traditional Chinese medicines,with cold and mild properties.Sweet,bitter and pungent flavors,and the main attributes of lung,spleen,kidney,stomach and heart meridians.The association rules mined 14 pairs of commonly used medicine pairs.Cluster analysis clustered the top 20 traditional Chinese medicines into five cluster groups.Complex network visualization analysis formed a core prescription consisting of honey-fried licorice root,ginseng,rhizoma anemarrhenae,ophiopogon japonicus,poria cocos.The core prescription drugs were screened for 164 effective active ingredients,1,498 action targets,1,995 diabetes gene targets,404 intersecting targets,10 core targets were extracted,and a total of 1,363 items covering BP were obtained from GO functional enrichment analysis,129 items involving CC,264 items containing MF,and 206 items of KEGG signaling pathway.Conclusion The prescriptions and medicines used by Xin'an doctors in the treatment of diabetes mellitus reflect the academic idea of"treating both the symptoms and the root cause"as well as the therapeutic thought of"using cold and warmth,supplementing with sweetness and warmth,opening up and lowering with bitterness,cultivating the earth and generating gold,and consolidating the root and cultivating the elements",which provide references for the treatment of diabetes mellitus in today's clinics.
7.The value of ultrasound super microvascularimaging combined with strain ratio in differential diagnosis of benign and malignant breast masses
Hongyan ZHU ; Zhaohui FANG ; Na HOU
Chinese Journal of Postgraduates of Medicine 2025;48(8):738-742
Objective:To analyze the significance of ultrasound super microvascular imaging (SMI) combined with strain ratio (SR) in the differential diagnosis of benign and malignant breast masses.Methods:A total of 110 patients with breast masses (110 lesions) admitted to Jiande Branch of the Second Affiliated Hospital of Zhejiang University from October 2022 to November 2024 were retrospectively selected, including 65 benign masses (benign group) and 45 malignant masses (malignant group). Both groups received SMI and strain elastography (SE) examination. The clinical and ultrasonic parameters SMI blood flow signal grade, vascular index (VI), global SR (ESR), local SR (LSR) and other indicators of the two groups were compared, and the independent risk of breast tumor malignancy was screened by Logistic regression. Receiver operating characteristic (ROC) curve was used to analyze the value of SMI blood flow signal grading, VI and ESR combined detection in the differential diagnosis of breast tumor malignancy.Results:The proportion of irregular shape, unclear boundary, microcalcification, convergence sign and angulation sign in the malignant group were higher than those in the benign group: 80.00%(36/45) vs. 55.38%(36/65), 57.78%(26/45) vs. 33.85%(22/65), 44.44%(20/45) vs. 13.85%(9/65), 55.56%(25/45) vs. 9.23%(6/65), 60.00%(27/45) vs. 15.38%(10/65), there were statistical differences ( P<0.05). The SMI blood flow signal grade in the malignant group was higher than that in the benign group, the VI, ESR and LSR in the malignant group were higher than those in the benign group: (6.53 ± 0.68)% vs. (3.14 ± 0.36)%, 4.62 ± 0.48 vs. 2.53 ± 0.27, 31.45 ± 3.29 vs. 20.16 ± 2.35, there were statistical differences ( P<0.05). Logistic regression analysis showed that irregular shape, unclear boundary, microcalcification, SMI blood flow signal grade, VI and ESR were independent risk factors for malignant breast mass ( P<0.05). ROC curve analysis results showed that the sensitivity, specificity and accuracy of SMI blood flow signal classification, VI and ESR combined in predicting breast tumor malignancy were 84.26%, 83.17% and 87.65%, respectively, and the area under the curve was 0.896, which were higher than the results predicted by each index alone. Conclusions:There are certain characteristic changes of SMI in benign and malignant breast masses. SMI combined with SR has good value in differential diagnosis of benign and malignant breast masses.
8.Advances in animal models of diabetic erectile dysfunction based on therapeutic approaches
Jiawen JING ; Qingbo MENG ; Zheng BI ; Fanjing WANG ; Yufan LI ; Zhaohui FANG
Chinese Journal of Clinical Pharmacology and Therapeutics 2025;30(9):1224-1232
Diabetic erectile dysfunction is a com-mon complication of diabetes that severely affects the quality of life of men and their sexual partners.Active participation in scientific research on diabet-ic erectile dysfunction is particularly important,and animal models are an important basis for exploring the pathogenesis of the disease,evaluating the effi-cacy of drug treatments,and developing new drugs.The pathogenesis of diabetic erectile dys-function is complex,and current treatments mainly focus on regulating blood sugar,anti-oxidative stress,PDE5 inhibitors,stem cell therapy,inhibiting neurovascular injury,anti-fibrosis,traditional Chi-nese medicine,and other aspects.In particular,cor-recting hyperglycemia is crucial for preventing or stopping the progression of the disease.This article summarizes and updates existing treatment meth-ods by reviewing the latest literature,and reviews the animal models used in different treatment methods,in order to provide a reference for animal experiments and clinical treatment.
9.Effects of circadian rhythm on anxiety,depression,and cognitive behavior in mice with chronic restraint stress
Meng QIANG ; Ning JIANG ; Hong HUANG ; Yiwen ZHANG ; Fang CHEN ; Zhaohui LI ; Xinmin LIU ; Guanghua LYU
Chinese Journal of Comparative Medicine 2025;35(2):45-57
Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P<0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P<0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P<0.05)and the daytime restraint group(P<0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P<0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P<0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P<0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P<0.01,P<0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P<0.05,P<0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.
10.Effects of circadian rhythm on anxiety,depression,and cognitive behavior in mice with chronic restraint stress
Meng QIANG ; Ning JIANG ; Hong HUANG ; Yiwen ZHANG ; Fang CHEN ; Zhaohui LI ; Xinmin LIU ; Guanghua LYU
Chinese Journal of Comparative Medicine 2025;35(2):45-57
Objective To investigate the effects of chronic restraint stress for 28 days(day and night)on mood and cognitive-like behavior in male and female ICR mice,to provide a basis for the selection of sex and restraint period in chronic restraint stress model animals.Methods A total of 72 male and female(1∶1)ICR mice were divided into six groups:male control,daytime restraint,and nighttime restraint groups,and female control,daytime restraint,and nighttime restraint groups.Mice in all but the control groups were bound for 10 h/d and restrained continuously for 28 days to establish a chronic restraint stress model.The emotional and cognitive behaviors induced by restraint in male and female mice at different times were observed by open field,Y maze,novel inhibition feeding,elevated cross maze,tail suspension,forced swimming,and dark-avoidance experiments.Results In the tail suspension experiment,the immobility time of male mice in the daytime restraint group was significantly increased compared with that in the control group(P<0.05),and the immobility times of male mice in the daytime and nighttime restraint groups were also significantly increased in the forced swimming experiment,compared with those in the control group(P<0.05).There was no significant difference between the female daytime restraint and female control groups in the novelty inhibition feeding experiment,but the feeding latency of the nighttime restraint group was significantly longer than that of the control group(P<0.05)and the daytime restraint group(P<0.05).The feeding latency of female mice was significantly longer than that of males during nighttime restraint(P<0.05).In the open field test,compared with the male control group,the female control group showed a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).Compared with the female control group,the female daytime restraint group exhibited a significant decrease in central area time and the ratio of central area time to peripheral area time(P<0.05).There was no significant difference between the groups in the elevated cross maze and Y maze experiments.There was no significant difference in dark latency between the daytime restraint group and the control group,but darkness latency was significantly shorter in the nighttime restraint group compared with those in the control group(P<0.05).When male and female mice were combined,the immobility time in the daytime restraint group was significantly increased in the tail suspension experiment(P<0.05),the immobility times of mice in the daytime and nighttime restraint groups were significantly increased in the forced swimming experiment(P<0.01,P<0.05),and the central zone time and the ratio of central area time to peripheral area time of daytime restraint mice were significantly shorter compared with those in the control group(P<0.05,P<0.01).There was no significant difference in the central zone time and the ratio of central area time to peripheral area time in the nighttime restraint groups,and no significant difference in average speed or total distance between the daytime and nighttime restraint groups.Conclusions Male mice exhibited depression after 28 d of chronic restraint stress during the daytime,while female mice were prone to anxiety after 28 d of chronic restraint stress.Male mice experienced learning and memory impairment after 28 d of chronic restraint stress during the night.

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