1.Treatment of Hyperuricemia and Gouty Arthritis by Buyang Huanwu Tongfeng Decoction via Inhibition of PPAR-γ/NF-κB/AGEs/RAGE Pathway Based on Network Pharmacology
Yue CAO ; Wanmei YAO ; Tao YANG ; Man YANG ; Ruimin JIA ; Rongrong LU ; Xue FENG ; Biwang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):182-192
ObjectiveThis paper aims to investigate the potential molecular biological mechanism of Buyang Huanwu Tongfeng decoction in treating hyperuricemia and gouty arthritis by network pharmacology and molecular docking technology and preliminarily verify the mechanism through animal experiments. MethodsThe active ingredients and targets in the Buyang Huanwu Tongfeng decoction were obtained by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and ETCM databases. The DisGeNET and GeneCards databases were utilized to acquire disease targets associated with hyperuricemia and gouty arthritis. These disease targets were then intersected with drug targets to identify key targets. The R language ClusterProfiler package and Python were employed for conducting gene ontology(GO) enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis. The regulatory network diagram of the drug-key target-function-pathway was visualized using Cytoscape 3.9.1 software, and the protein-protein interaction (PPI) network for key targets was depicted. Finally, the hub gene was determined through topological analysis. Auto Dock, PyMOL, and other software were used for molecular docking to explore the possible therapeutic mechanism of Buyang Huanwu Tongfeng decoction for hyperuricemia and gouty arthritis. In animal experiments, a composite rat model of hyperuricemia induced by intraperitoneal injection of oteracil potassium combined with gouty arthritis induced by the modified Coderre method was established. Through hematoxylin-eosin(HE) staining, uric acid test, enzyme linked immunosorbent assay(ELISA), Western blot, and real-time polymerase chain reaction(Real-time PCR), the molecular mechanism and key targets of Buyang Huanwu Tongfeng decoction for treating hyperuricemia and gouty arthritis were observed. ResultsAfter screening and removing duplicate values, 76 active ingredients and 15 key targets were finally obtained. GO enrichment analysis yielded that the treatment of hyperuricemia and gouty arthritis with Buyang Huanwu Tongfeng decoction was significantly associated with acute inflammatory response, astrocyte activation, regulation of interleukin (IL)-8 production, nuclear receptor activity, and binding of growth factor receptor. KEGG pathway enrichment analysis obtained that the key target genes were significantly associated with the IL-17 signaling pathway, advanced glycosylation end/receptor of advanced glycation endproducts(AGE/RAGE) signaling pathway, anti-inflammatory, and other pathways. PPI network indicated that albumin(ALB), peroxisome proliferator-activated receptor-γ (PPAR-γ), IL-6, IL-1β, and C-reactive protein(CRP) were the key protein targets. The molecular docking results showed that ALB had the strongest binding force with beta-carotene (β-carotene). Biochemical results showed that blood uric acid decreased in the Buyang Huanwu Tongfeng decoction groups. HE staining results showed that the low-dose (7.76 g·kg-1·d-1), medium-dose (15.53 g·kg-1·d-1), and high-dose (31.05 g·kg-1·d-1) groups of Buyang Huanwu Tongfeng decoction had different degrees of remission, and the remission of the high-dose group was the most obvious. Fibroblastic tissue hyperplasia in synovial joints accompanied with inflammatory cell infiltration, as well as inflammatory cell infiltration in renal tissue of the high-dose group was significantly reduced, followed by the medium-dose and low-dose groups, and the expression of ALB, PPAR-γ, IL-6, IL-1β, and CRP was down-regulated to different degrees. ConclusionBy regulating the targets such as ALB, PPAR-γ, IL-6, IL-1β, and CRP, inhibiting the PPAR-γ/nuclear transcription factor (NF)-κB pathway, and reducing AGEs/RAGE-mediated inflammation, Buyang Huanwu Tongfeng decoction exerts anti-inflammatory and analgesic effects and activates blood circulation and diuresis in the treatment of hyperuricemia and gouty arthritis.
2.Herbal Textual Research on Spatholobi Caulis in Famous Classical Formulas
Yajie XIANG ; Yangyang LIU ; Jian FENG ; Chun YAO ; Erwei HAO ; Wenlan LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):238-248
Through consulting herbal medicine, medical books, and local chronicles from past dynasties to modern times, this paper systematically researched Spatholobi Caulis from name, origin, producing areas, harvesting, processing, usage, quality evaluation, functions and indications, providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research, Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning, Yunnan, and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them, K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians, mainly treating rheumatic pain and injuries caused by falls or blows, and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction, which had the functions of promoting blood circulation and replenishing blood, activating meridians and collaterals, and mainly used for treating anemia, irregular menstruation, and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently, the main production area of S. suberectus is Guangxi, while the main production area of K. interior is Yunnan. In the Qing dynasty, the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments, which was usually composed of the juice of it, safflower, angelica, and glutinous rice. But in modern times, Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface, with a higher number indicating better quality. Additionally, the presence of resinous secretions is also considered desirable. Based on the research findings, it is suggested that when developing famous classical formulas containing Spatholobi Caulis, the choice of the primary source should be S. suberectus or K. heteroclita, taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia, adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names, and the functions adjust to promote Qi circulation and relieve pain, disperse blood stasis and unblock collaterals, treating injuries caused by falls and bruises.
3.Varieties and Prescription Characteristics of Chinese Patent Medicines for Stroke in China
Jingdan ZHANG ; Wanping SUN ; Xiaoxia LIN ; Shuo ZHANG ; Xue ZHANG ; Jiahui YAO ; Yiming LIU ; Ming XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):270-274
ObjectiveTo explore the listed varieties and prescription characteristics of Chinese patent medicines for stroke in China, explore the medication rules of Chinese medicine for stroke, and provide guidance for further clinical research and development of Chinese patent medicines. MethodsExcel 2021 and the Ancient and Modern Medical Record Cloud Platform (V2.3.5) were used to systematically mine and analyze the varieties and prescriptions of Chinese patent medicines for stroke in China. ResultsA total of 244 Chinese patent medicines (two for different dosage forms of the same prescription), 1 736 approval documents for Chinese patent medicines, 792 manufacturers, and 83 varieties of protected Chinese patent medicines were finally included in the database. The top three dosage forms were capsules (75), pills (53), and tablets (42). There were 28 Chinese patent medicines for stroke in the National Essential Drug Catalogue (2018), 129 in the National Essential Medical Insurance, Industrial Injury Insurance and Maternity Insurance Drug Catalogue (2023), and 4 in the National Non-prescription Drug Catalogue. Among the 138 prescriptions screened out, Chinese patent medicines mainly treated stroke patients with the syndrome of Qi deficiency and blood stasis. The top three most frequent medicinal herbs were Chuanxiong Rhizoma (63), Pheretima (47), and Salviae Miltiorrhizae Radix et Rhizoma (47). The medicinal herbs used were mainly warm, pungent, with the meridian tropism to the liver meridian. The correlation analysis showed that the herb pair with the highest support was Astragali Radix-Chuanxiong Rhizoma, and that with the highest confidence was Carthami Flos-Chuanxiong Rhizoma. Five herb combinations were identified based on the cluster analysis. ConclusionThe Chinese patent medicines for stroke mainly treat patients with the syndrome of Qi deficiency and blood stasis. The medicinal herbs used in the prescriptions mainly have the functions of activating blood and resolving stasis, extinguishing wind and stopping convulsions. Drug compatibility usually focuses on activating blood and resolving stasis, as well as expelling phlegm and opening orifices. This review of the varieties and prescription characteristics of Chinese patent medicines for stroke helps optimize clinical decision-making, guide drug research and development, promote medical research and scientific progress, and provide more effective support and guarantee for the treatment of stroke patients.
4.Enzyme-directed Immobilization Strategies for Biosensor Applications
Xing-Bao WANG ; Yao-Hong MA ; Yun-Long XUE ; Xiao-Zhen HUANG ; Yue SHAO ; Yi YU ; Bing-Lian WANG ; Qing-Ai LIU ; Li-He ZHANG ; Wei-Li GONG
Progress in Biochemistry and Biophysics 2025;52(2):374-394
Immobilized enzyme-based enzyme electrode biosensors, characterized by high sensitivity and efficiency, strong specificity, and compact size, demonstrate broad application prospects in life science research, disease diagnosis and monitoring, etc. Immobilization of enzyme is a critical step in determining the performance (stability, sensitivity, and reproducibility) of the biosensors. Random immobilization (physical adsorption, covalent cross-linking, etc.) can easily bring about problems, such as decreased enzyme activity and relatively unstable immobilization. Whereas, directional immobilization utilizing amino acid residue mutation, affinity peptide fusion, or nucleotide-specific binding to restrict the orientation of the enzymes provides new possibilities to solve the problems caused by random immobilization. In this paper, the principles, advantages and disadvantages and the application progress of enzyme electrode biosensors of different directional immobilization strategies for enzyme molecular sensing elements by specific amino acids (lysine, histidine, cysteine, unnatural amino acid) with functional groups introduced based on site-specific mutation, affinity peptides (gold binding peptides, carbon binding peptides, carbohydrate binding domains) fused through genetic engineering, and specific binding between nucleotides and target enzymes (proteins) were reviewed, and the application fields, advantages and limitations of various immobilized enzyme interface characterization techniques were discussed, hoping to provide theoretical and technical guidance for the creation of high-performance enzyme sensing elements and the manufacture of enzyme electrode sensors.
5.Effect of hemodialysis on the biotransformation of oxo-eicosatetraenoic acids in peripheral tissues
Tong LIU ; Gollasch MAIK ; C. Luft FRIEDRICH ; Pan LIN ; Jun JI ; Yao MENG
Chinese Journal of Clinical Medicine 2025;32(1):93-100
Objective To analyze the differences of free and esterified oxo-eicosatetraenoic acids (oxo-ETEs) in blood cells and plasma from arterial and venous blood in hemodialysis (HD) patients. Methods Arterial and venous blood samples from 12 patients with end-stage renal disease (ESRD) before and after HD treatment at Charité – Universitätsmedizin Berlin, Germany, from June to December 2020 were collected. The esterified and free oxo-ETEs derived from arachidonic acid in blood cells and plasma were measured by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results Neither esterified nor free oxo-ETEs in blood cells displayed significant arteriovenous differences before and after HD. HD predominantly affected the metabolic levels of esterified and free oxo-ETEs in plasma. HD reduced the arteriovenous differences of esterified 12-oxo-ETE, free 15-oxo-ETE, and free 5-oxo-ETE in plasma, while raised the arteriovenous differences of esterified 15-oxo-ETE. Conclusions The oxo-ETEs in blood cells are relatively well-stabilized responding to HD treatment, whereas arteriovenous differences of free and esterified oxo-ETEs in plasma are present and active in response to HD treatment, potentially contributing to the cardiovascular disease.
6.Progress in the treatment of giant cell tumors of extremities with pathological fracture
Wenhao YAO ; Daoyang FAN ; Xieyuan JIANG ; Weifeng LIU
Chinese Journal of Surgery 2025;63(1):81-85
Giant cell tumor of bone (GCTB) is a common locally aggressive junctional primary bone tumor, whose clinical treatment becomes more difficult once combined with pathological fracture. Extended curettage and en-bloc resection are common surgical procedures for treating GCTB, and drugs such as receptor activator of nuclear factor-κB ligand(RANKL) inhibitors and bisphosphonates have been successfully used. Curettage is recommended for patients with Campanaccigrade Ⅱor Campanaccigrade Ⅲ with localized soft tissue invasion only and simple fractures with intact bone structure. Resection may be considered for Campanaccigrade Ⅲ with extensive soft tissue invasion or complex fractures with incomplete bone structure. RANKL inhibitors such as denosumab may be recommended if surgery is not possible or before performing resection. This article summarizes the common treatment modalities of pathological fractures combined with giant cell tumors of extremities, including the current status of surgical and pharmacological treatments, analyzing the choice of surgical modalities in different clinical situations, in order to provide clinical inspirations for diagnosis and treatment.
7.Isoliquiritigenin alleviates abnormal endoplasmic reticulum stress induced by type 2 diabetes mellitus
Kai-yi LAI ; Wen-wen DING ; Jia-yu ZHANG ; Xiao-xue YANG ; Wen-bo GAO ; Yao XIAO ; Ying LIU
Acta Pharmaceutica Sinica 2025;60(1):130-140
Isoliquiritigenin (ISL) is a chalcone compound isolated from licorice, known for its anti-diabetic, anti-cancer, and antioxidant properties. Our previous study has demonstrated that ISL effectively lowers blood glucose levels in type 2 diabetes mellitus (T2DM) mice and improves disturbances in glucolipid and energy metabolism induced by T2DM. This study aims to further investigate the effects of ISL on alleviating abnormal endoplasmic reticulum stress (ERS) caused by T2DM and to elucidate its molecular mechanisms.
8.Pharmacokinetic study of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland
Yu ZHANG ; Jiaming LI ; Dan PENG ; Ruoqiu FU ; Yue MING ; Zhengbi LIU ; Jingjing WANG ; Shiqi CHENG ; Hongjun XIE ; Yao LIU
China Pharmacy 2025;36(6):680-685
OBJECTIVE To explore the pharmacokinetic characteristics of 3 blood-absorbed components of Xiangshao sanjie oral liquid in rats with hyperplasia of mammary gland (HMG). METHODS Female SD rats were divided into control group and HMG group according to body weight, with 6 rats in each group. The HMG group was given estrogen+progesterone to construct HMG model. After modeling, two groups were given 1.485 g/kg of Xiangshao sanjie oral liquid (calculated by crude drug) intragastrically, once a day, for 7 consecutive days. Blood samples were collected before the first administration (0 h), and at 5, 15, 30 minutes and 1, 2, 4, 8, 12, 24 hours after the last administration, respectively. Using chlorzoxazone as the internal standard, the plasma concentrations of ferulic acid, paeoniflorin and rosmarinic acid in rats were detected by UPLC-Q/TOF-MS. The pharmacokinetic parameters [area under the drug time curve (AUC0-24 h, AUC0-∞), mean residence time (MRT0-∞), half-life (t1/2), peak time (tmax), peak concentration (cmax)] were calculated by the non-atrioventricular model using Phoenix WinNonlin 8.1 software. RESULTS Compared with the control group, the AUC0-24 h, AUC0-∞ and cmax of ferulic acid in the HMG group were significantly increased (P<0.05); the AUC0-24 h, AUC0-∞ , MRT0-∞ , t1/2 and cmax of paeoniflorin increased, but there was no significant difference between 2 groups (P>0.05); the AUC0-24 h and MRT0-∞ of rosmarinic acid were significantly increased or prolonged (P<0.05). C ONCLUSIONS In HMG model rats, the exposure of ferulic acid, paeoniflorin and rosmarinic acid in Xiangshao sanjie oral liquid all increase, and the retention time of rosmarinic acid is significantly prolonged.
9.Clinical Observation of Modified Huanglian Wendantang in Treatment of Cardiovascular Risk Factors in Patients with Metabolic Syndrome Under Guidance of Treating Disease before Its Onset
Yi HAN ; Yubo HAN ; Guoliang ZOU ; Ruinan WANG ; Chunli YAO ; Xinyu DONG ; Li LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):142-149
ObjectiveTo observe the clinical effect of modified Huanglian Wendantang on cardiovascular risk factors in patients with metabolic syndrome under the guidance of treating disease before its onset. MethodsA total of 82 patients with metabolic syndrome treated in the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from July 2023 to July 2024 were selected and allocated into an observation group (41 cases) and a control group (41 cases) by the random number table method. The control group received routine treatment, and the observation group was treated with modified Huanglian Wendantang on the basis of routine treatment. Both groups were treated for 8 weeks. The therapeutic effects on TCM symptoms after treatment in the two groups were evaluated. The levels of obesity degree indicators, blood pressure indicators, glucose and lipid metabolism indicators, inflammatory factors, and vascular endothelial function indicators before and after treatment in the two groups were measured, and the treatment safety was evaluated. ResultsAfter treatment, the total response rate of TCM symptoms in the observation group was 97.56% (40/41), which was higher than that (87.80%, 36/41) in the control group (χ2=5.205, P<0.05). After treatment, both groups showed declines (P<0.05) in systolic blood pressure (SBD), diastolic blood pressure (DBP), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting blood glucose, 2-hour postprandial blood glucose (2 h PG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), leptin (LEP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), endothelin-1 (ET-1), and inducible nitric oxide synthase (iNOS). Moreover, the declines in the observation group were more obvious than those in the control group (P<0.05, P<0.01). After treatment, both groups showed elevated levels of high density lipoprotein cholesterol (HDL-C), adiponectin (ADP), nitric oxide (NO), and endothelial nitric oxide synthase (eNOS) (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.01). ConclusionUnder the guidance of the thought of treating disease before its onset, modified Huanglian Wendantang was used to treat patients with metabolic syndrome. The decoction improved the clinical efficacy by ameliorating IR to improve insulin sensitivity, reducing inflammation, and protecting the vascular endothelial function. It inhibits cardiovascular risk factors without inducing adverse reactions, being worthy of clinical application and promotion.
10.Color Space Method Combined with Chemometrics to Determine Processing Degree of Angelicae Sinensis Radix Carbonisata
Liuying QIN ; Yao HUANG ; Lifan GAN ; Yuanjun LIU ; Congyou DENG ; Dongmei SUN ; Lijin LIANG ; Lin ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(9):201-210
ObjectiveTo study the changing law of appearance color and physicochemical properties of Angelicae Sinensis Radix Carbonisata(ASRC) during the processing by color space method combined with statistical analysis, so as to provide reference for determining the processing endpoint and evaluating the quality of the decoction pieces. MethodsTaking processing time(4, 8, 12, 16 min) and temperature(180, 200, 220, 240 ℃) as factors, ASRC decoction pieces with different processing degrees were prepared in a completely randomized design. Then, the brightness value(L*), red-green value(a*), yellow-blue value(b*), and total chromaticity value (E*ab) of the decoction pieces were determined by spectrophotometer, the color difference value(ΔE) was calculated, and the data of colorimetric values were analyzed by discriminant analysis. At the same time, the pH, charcoal adsorption, and contents of tannins, 5-hydroxymethylfurfural(5-HMF), tryptophan, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H and ligustilide of ASRC with different processing degrees were determined by pH meter, ultraviolet and visible spectrophotometry and ultra-high performance liquid chromatography(UPLC). Principal component analysis(PCA) was used to analyze the data of physicochemical indexes, after determining the processing technology of ASRC, the canonical discriminant function was established to distinguish the decoction pieces with different processing degrees, and leave-one-out cross validation was conducted. Finally, Pearson correlation analysis was used to explore the correlation between various physicochemical indexes and chromaticity values. ResultsWith the prolongation of the processing time, L*, a*, b* and E*ab all showed a decreasing trend, and the established discriminant model based on color parameters was able to distinguish ASRC with different processing degrees. The pH showed an increasing trend with the prolongation of processing time, and the charcoal adsorption, and the contents of tannins, 5-HMF, and tryptophan all showed an increasing and then decreasing trend. Among them, the charcoal adsorption, contents of tannin and 5-HMF reached their maximum values successively after processing for 8-12 min. While the contents of chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H and ligustilide decreased with the increase of processing time, with a decrease of 60%-80% at 8 min of processing. Therefore, the optimal processing time should be determined to be 8-12 min. PCA could clearly distinguish ASRC with different processing degrees, while temperature had no significant effect on the processing degree. The 12 batches of process validation results(10 min, 180-240 ℃) showed that except for 3 batches identified as class Ⅱ light charcoal, all other batches were identified as class Ⅲ standard charcoal, and the chromaticity values of each batch of ASRC were within the reference range of class Ⅱ-Ⅲ sample chromaticity values. The correlation analysis showed that the chromaticity values were negatively correlated with pH and charcoal adsorption, and positively correlated with contents of tryptophan, chlorogenic acid, ferulic acid, senkyunolide I, senkyunolide H, and ligustilide. And both pH and charcoal adsorption were negatively correlated with the contents of the above components, but the charcoal adsorption was positively correlated with the content of 5-HMF. ConclusionThe chromaticity values and the contents of various physicochemical indicators of ASRC undergo significant changes with the prolongation of processing time, and there is a general correlation between chromaticity values and various physicochemical indicators. Based on the changes in color and physicochemical indicators, the optimal processing time for ASRC is determined to be 8-12 min. This study reveals the dynamic changes of the relevant indexes in the processing of ASRC, which can provide a reference for the discrimination of the processing degree and the quantitative study of the processing endpoint.

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