1.Medication rules of Astragali Radix in ancient Chinese medical books based on "disease-medicine-dose" pattern.
Jia-Lei CAO ; Lü-Yuan LIANG ; Yi-Hang LIU ; Zi-Ming XU ; Xuan WANG ; Wen-Xi WEI ; He-Jia WAN ; Xing-Hang LYU ; Wei-Xiao LI ; Yu-Xin ZHANG ; Bing-Qi WEI ; Xian-Qing REN
China Journal of Chinese Materia Medica 2025;50(3):798-811
This study employed the "disease-medicine-dose" pattern to mine the medication rules of traditional Chinese medicine(TCM) prescriptions containing Astragali Radix in ancient Chinese medical books, aiming to provide a scientific basis for the clinical application of Astragali Radix and the development of new medicines. The TCM prescriptions containing Astragali Radix were retrieved from databases such as Chinese Medical Dictionary and imported into Excel 2020 to construct the prescription library. Statical analysis were performed for the prescriptions regarding the indications, syndromes, medicine use frequency, herb effects, nature and taste, meridian tropism, dosage forms, and dose. SPSS statistics 26.0 and IBM SPSS Modeler 18.0 were used for association rules analysis and cluster analysis. A total of 2 297 prescriptions containing Astragali Radix were collected, involving 233 indications, among which sore and ulcer, consumptive disease, sweating disorder, and apoplexy had high frequency(>25), and their syndromes were mainly Qi and blood deficiency, Qi and blood deficiency, Yin and Yang deficiency, and Qi deficiency and collateral obstruction, respectively. In the prescriptions, 98 medicines were used with the frequency >25 and they mainly included Qi-tonifying medicines and blood-tonifying medicines. Glycyrrhizae Radix et Rhizoma, Angelicae Sinensis Radix, Ginseng Radix et Rhizoma, Atractylodis Macrocephalae Rhizoma, and Citri Reticulatae Pericarpium were frequently used. The medicines with high frequency mainly have warm or cold nature, and sweet, pungent, or bitter taste, with tropism to spleen, lung, heart, liver, and kidney meridians. In the treatment of sore and ulcer, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to promote granulation and heal up sores. In the treatment of consumptive disease, Astragali Radix was mainly used with the dose of 37.30 g and combined with Ginseng Radix et Rhizoma to tonify deficiency and replenish Qi. In the treatment of sweating disorder, Astragali Radix was mainly used with the dose of 3.73 g and combined with Glycyrrhizae Radix et Rhizoma to consolidate exterior and stop sweating. In the treatment of apoplexy, Astragali Radix was mainly used with the dose of 7.46 g and combined with Glycyrrhizae Radix et Rhizoma to dispell wind and stop convulsions. Astragali Radix can be used in the treatment of multiple system diseases, with the effects of tonifying Qi and ascending Yang, consolidating exterior and stopping sweating, and expressing toxin and promoting granulation. According to the manifestations of different diseases, when combined with other medicines, Astragali Radix was endowed with the effects of promoting granulation and healing up sores, tonifying deficiency and Qi, consolidating exterior and stopping sweating, and dispelling wind and replenishing Qi. The findings provide a theoretical reference and a scientific basis for the clinical application of Astragali Radix and the development of new medicines.
Drugs, Chinese Herbal/history*
;
Humans
;
Medicine, Chinese Traditional/history*
;
History, Ancient
;
Astragalus Plant/chemistry*
;
China
;
Astragalus propinquus
2.Pharmacokinetics and tissue distribution of fluorescent-labeled Astragalus polysaccharides in mice.
Xiao-Huan WANG ; Peng-Xin LI ; Ting-Ting GONG ; Yun-Qian LU ; Bo YANG ; Xiang-Tao WANG
China Journal of Chinese Materia Medica 2025;50(7):1959-1968
In this study, the reductive amination method was used to label IR783 on Astragalus polysaccharides(APS) for the first time, which was verified by ultraviolet-visible spectroscopy and infrared spectroscopy. Quantitative analysis methods of APS-IR783 in plasma and various tissue were established using a multifunctional microplate reader. The pharmacokinetics and tissue distribution of APS-IR783 in mice were investigated after a single intravenous injection of 30 mg·kg~(-1) APS-IR783, and pharmacokinetic parameters were calculated using DAS 2.0 software. The results showed that the APS used had a mass fraction of 93.69%, a relative molecular weight of 1.55×10~5, and a polydispersity index(PDI, M_w/M_n) of 1.73, close to a homogeneous polysaccharide. The IR783 labeling yield reached 86.50%, and the content of IR783 in APS-IR783 was 0.72%. After a single intravenous injection of 30 mg·kg~(-1), the pharmacokinetic parameters of APS in mouse plasma were as follows: T_(max) was(0.67±0.26) h; C_(max) was(1 599.29±159.30) mg·L~(-1); T_(1/2α) and T_(1/2β) were(2.29±3.06) h and(0.44±0.05) h, respectively; AUC_(0-t) was(23 398.91±2 907.03) mg·h·L~(-1); AUC_(0-∞) was(27 710.55±3 506.55) mg·h·L~(-1); MRT_(0-∞) was(34.38±12.59) h; CL was 0.001 L·h~(-1)·kg~(-1); V_z was(0.042±0.017) L·kg~(-1). The in vivo biodistribution study demonstrated that the in vivo exposure ratios of APS in different tissue were in the following order: spleen > liver > kidney > lung > heart > small intestine > muscle > large intestine > brain > stomach, where the top five tissue accounted for 87.54% of the total area under the curve(AUC). This study successfully labeled APS with a water-soluble near-infrared fluorescent probe of IR783 for the first time and revealed the pharmacokinetics and tissue distribution of APS in mice. The paper provides detailed in vivo behavior of APS after intravenous injection, which lays the foundation for the development and utilization of APS and related natural medicines.
Animals
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Mice
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Polysaccharides/chemistry*
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Tissue Distribution
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Astragalus Plant/chemistry*
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Male
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Drugs, Chinese Herbal/chemistry*
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Fluorescent Dyes/pharmacokinetics*
;
Female
3.Functional characterization of flavonoid glycosyltransferase AmGT90 in Astragalus membranaceus.
Guo-Qing PENG ; Bing-Yan XU ; Jian-Ping HUANG ; Zhi-Yin YU ; Sheng-Xiong HUANG
China Journal of Chinese Materia Medica 2025;50(6):1534-1543
Astragalus membranaceus(A. membranaceus), a traditional tonic, contains flavonoids as one of its main bioactive components and key indicators for quality standard detection. These compounds predominantly exist in glycosylated forms after glycosylation modification within the plant. The catalytic products of flavonoid glycosyltransferases in A. membranaceus have been reported to be mostly monoglycosides, and only AmUGT28 catalyzes luteolin to form diglycosides. In this study, we cloned a glycosyltransferase gene, AmGT90, from A. membranaceus, with an ORF length of 1 335 bp, encoding 444 amino acids, and the protein had a relative molecular mass of 50.5 kDa. Phylogenetic tree analysis indicated that AmGT90 belongs to the UGT74 family. In vitro enzymatic reaction showed that AmGT90 had broad substrate specificity and could catalyze the glycosylation of various flavonoids, including isoflavones, flavones, flavanones, and chalcones. AmGT90 not only catalyzed the formation of monoglycosides but also diglycosides. In addition, the mechanism of AmGT90 catalyzing the formation of diglycosides from luteolin was preliminarily explored. The experimental results showed that AmGT90 may preferentially recognize C4'-OH of luteolin and then recognize C7-OH to form diglycosides. This study reported a glycosyltransferase from A. membranaceus capable of converting flavonoids into monoglycosides and diglycosides. This finding not only enhances our understanding of the biosynthetic pathways of flavonoid glycosides in A. membranaceus but also introduces a new component for glycoside production through synthetic biology.
Glycosyltransferases/chemistry*
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Flavonoids/chemistry*
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Astragalus propinquus/classification*
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Phylogeny
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Glycosylation
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Plant Proteins/chemistry*
;
Substrate Specificity
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Cloning, Molecular
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Amino Acid Sequence
4.Astragali Radix-Curcumae Rhizoma drug pair inhibits growth of osteosarcoma by affecting cell adhesion and angiogenesis via PI3K/Akt/HIF-1α pathway.
Dao-Tong YUAN ; Zhi-Meng ZHANG ; Rui GONG ; Xi-Min JIN ; Can-Ran WANG ; Jie ZHAO
China Journal of Chinese Materia Medica 2025;50(8):2217-2228
This study aims to investigate the optimal ratio of Astragali Radix-Curcumae Rhizoma(AC) for inhibiting the proliferation of 143B osteosarcoma cells, and to investigate the mechanism by which AC inhibits osteosarcoma growth and metastasis through angiogenesis and cell adhesion mediated by the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/hypoxia inducible factor-1α(HIF-1α) pathway. A subcutaneous 143B tumor-bearing nude mouse model was successfully established and randomly divided into the model group, and the AC 1∶1, 2∶1, and 4∶1 groups. Body weight, tumor volume, and tumor weight were recorded. Real-time quantitative polymerase chain reaction(RT-qPCR) and Western blot were used to detect the mRNA and protein expression levels of PI3K, Akt, phosphorylated Akt(p-Akt), HIF-1α, vascular endothelial growth factor A(VEGFA), transforming growth factor-β1(TGF-β1), epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), vimentin, matrix metalloproteinase 2(MMP2), matrix metalloproteinase 9(MMP9), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and caspase-3 in the hypoxic core region of the tumor tissue. A cell hypoxia model was established, and the effects of AC-medicated serum(model group, AC 1∶1, 2∶1, and 4∶1 groups) on angiogenesis, proliferation, adhesion, invasion, and migration of 143B osteosarcoma cells were examined through CCK-8, flow cytometry, Transwell assay, cell adhesion assay, and HUVEC tube formation assay. The results showed that compared with the model group, the tumor weight and volume were smallest in the 2∶1 group. The expression levels of PI3K, Akt, p-Akt, HIF-1α, VEGFA, and TGF-β1 were significantly decreased, and the protein expression of E-cadherin was significantly increased, while the protein expression of N-cadherin, vimentin, MMP2, and MMP9 was significantly decreased. Additionally, the protein expression of Bax and caspase-3 was significantly increased, and Bcl-2 protein expression was significantly decreased. In vitro experiments showed that after intervention with AC-medicated serum at a 2∶1 ratio, the cell activity, adhesion, invasion, and migration of 143B cells were significantly reduced, apoptosis was significantly increased, and HUVEC tube formation was significantly decreased. In conclusion, the 2∶1 ratio of AC showed the most effective inhibition of 143B cell growth. AC can inhibit the growth and metastasis of osteosarcoma 143B cells by regulating the PI3K/Akt/HIF-1α signaling pathway, inhibiting angiogenesis and reducing cell adhesion, invasion, and migration.
Osteosarcoma/pathology*
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Animals
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Proto-Oncogene Proteins c-akt/genetics*
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Hypoxia-Inducible Factor 1, alpha Subunit/genetics*
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Humans
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Mice
;
Cell Adhesion/drug effects*
;
Cell Proliferation/drug effects*
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Neovascularization, Pathologic/metabolism*
;
Drugs, Chinese Herbal/administration & dosage*
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Phosphatidylinositol 3-Kinases/genetics*
;
Cell Line, Tumor
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Mice, Nude
;
Signal Transduction/drug effects*
;
Astragalus Plant/chemistry*
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Bone Neoplasms/physiopathology*
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Male
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Rhizome/chemistry*
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Mice, Inbred BALB C
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Angiogenesis
5.Transcriptome analysis and catechin synthesis genes in different organs of Spatholobus suberectus.
Wei-Qi QIN ; Quan LIN ; Ying LIANG ; Fan WEI ; Gui-Li WEI ; Qi GAO ; Shuang-Shuang QIN
China Journal of Chinese Materia Medica 2025;50(12):3297-3306
To study the differences in transcript levels among different organs of Spatholobus suberectus and to explore the genes encoding enzymes related to the catechin biosynthesis pathway, this study utilized the genome and full-length transcriptome data of S. suberectus as references. Transcriptome sequencing and bioinformatics analysis were performed on five different organs of S. suberectus-roots, stems, leaves, flowers, and fruits-using the Illumina NovaSeq 6000 platform. A total of 115.28 Gb of clean data were obtained, with GC content values ranging from 45.19% to 47.54%, Q20 bases at 94.17% and above, and an overall comparison rate with the reference genome around 90%. In comparisons between the stem and root, stem and leaf, stem and flower, and stem and fruit, 10 666, 9 674, 9 320, and 5 896 differentially expressed genes(DEGs) were identified, respectively. The lowest number of DEGs was found in the stem and root comparison group. KEGG enrichment analysis revealed that the DEGs were mainly concentrated in the pathways of phytohormone signaling, phenylalanine biosynthesis, etc. A total of 39 genes were annotated in the catechin biosynthesis pathway, with at least one highly expressed gene found in all organs. Among these, PAL1, PAL2, C4H1, C4H3, 4CL1, 4CL2, and DFR2 showed high expression in the stems, suggesting that they may play important roles in the biosynthesis of flavonoids in S. suberectus. This study aims to provide important information for the in-depth exploration of the regulation of catechin biosynthesis in S. suberectus through transcriptome analysis of its different organs and to provide a reference for the further realization of S. suberectus varietal improvement and molecular breeding.
Catechin/biosynthesis*
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Gene Expression Profiling
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Gene Expression Regulation, Plant
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Plant Proteins/metabolism*
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Fabaceae/metabolism*
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Transcriptome
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Flowers/metabolism*
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Plant Stems/metabolism*
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Plant Leaves/metabolism*
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Plant Roots/metabolism*
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Fruit/metabolism*
6.Pollen-food allergy syndrome: association between allergen cross-reactivity and symptom severity.
Yuqiao ZHANG ; Fengxia YANG ; Xiaohui YAN ; Xueliang SHEN ; Ningyu FENG ; Ting YAO ; Shurong LI ; Xiyuan YAN ; Ruixia MA
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1156-1162
Objective:To investigate the clinical characteristics and major allergens of patients with pollen-food allergy syndrome(PFAS) and their correlation with the severity of symptoms, and to provide a basis for identifying high-risk patients, optimizing the allergen testing process and developing individualized dietary management strategies. Methods:The clinical data of 166 patients with PFAS admitted to our hospital from January 2021 to July 2023 were retrospectively analyzed. The clinical symptoms, pollen types and food allergy of the patients were analyzed by questionnaire survey and serum specific IgE detection. phi coefficient, Apriori algorithm modeling and multivariate logistic regression analysis were used to evaluate the association between allergen and symptom severity. Results:Artemisia pollen was the most common allergen in this area, with a positive rate of 96.39%. Peach and mango were the most common food allergens, which caused allergic reactions in 24.10% and 22.89% of patients, respectively. Oral mucosal symptoms were the main symptoms. Correlation analysis showed that there was a correlation between pollen allergens and allergenic food. Association rule analysis showed that when the patient was allergic to the combination of peanuts and trees, the probability of high severity of symptoms was 82.35%. Multivariate analysis showed that ragweed allergy was significantly positively correlated with the severity of PFAS symptoms. Conclusion:Artemisia pollen and related food allergens play an important role in the pathogenesis of PFAS. Association rule mining and network map analysis revealed direct associations between peanut and tree combination allergy and symptom severity, as well as potential links between other inhaled allergens and specific food allergies. Ragweed and peach allergy are independent risk factors for the aggravation of PFAS symptoms, which can be used as early warning indicators. These results help to improve the screening of high-risk patients and the construction of regional allergen databases.
Humans
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Food Hypersensitivity/immunology*
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Allergens/immunology*
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Retrospective Studies
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Pollen/immunology*
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Cross Reactions
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Immunoglobulin E/blood*
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Rhinitis, Allergic, Seasonal/immunology*
;
Artemisia/immunology*
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Male
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Female
;
Adult
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Prunus persica/immunology*
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Arachis/immunology*
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Middle Aged
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Surveys and Questionnaires
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Oral Allergy Syndrome
7.A GA-BP neural network model based on spectrum-effect relationship for assessing spectrum-effect score and quality evaluation of Cassia seeds extract.
Haiyan YAN ; Heng WANG ; Chuncai ZOU
Journal of Southern Medical University 2025;45(10):2092-2103
OBJECTIVES:
To construct a GA-BP neural network model based on the spectrum-effect relationship of Cassia seeds extract and test its performance for quality control of Cassia seeds using spectrum-effect score.
METHODS:
The HPLC fingerprints of Cassia seeds extract (0.1, 0.2, and 0.4 g/mL) were established. In a mouse model of 5-Fu-induced liver injury treated with 0.4, 0.8, and 1.6 g/kg of Cassia seeds extract, the pharmacodynamics parameters were measured to calculate the comprehensive efficacy using AHP-EWM. A GA-BP neural network model between the fingerprints and comprehensive efficacy was constructed, and the corresponding predicted comprehensive efficacy was obtained. The spectrum-effect relationship between the fingerprints and the measured and predicted comprehensive efficacy was established using grey correlation method followed by Gaussian fitting analysis. The spectral efficiency score was calculated using the relative peak area of the fingerprints and the correlation degree of the spectral efficiency. The reliability of the data was tested using the Z-ratio score method. The limit range of the spectral efficiency score was determined and the quality of the verification samples was evaluated.
RESULTS:
The error between the predicted value using the GA-BP neural network model and the measured value of the comprehensive efficacy was less than 0.2. Gaussian fitting analysis showed good fitting between the spectrum-effect relationship data of the measured and predicted comprehensive efficacy. The limit of the spectral efficiency score was 6.16-7.30. The prediction results for each verification group were consistent with the experimental results and within the limit of spectral efficiency score, and the results of Z-ratio score analysis demonstrated good data reliability.
CONCLUSIONS
The GA-BP neural network model can effectively predict the comprehensive efficacy of Cassia seeds extract, and the established spectrum-effect scoring method can be used for quality evaluation of samples.
Neural Networks, Computer
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Animals
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Seeds/chemistry*
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Mice
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Cassia/chemistry*
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Quality Control
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Drugs, Chinese Herbal/pharmacology*
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Plant Extracts/pharmacology*
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Male
8.Astragali Radix-Notoginseng Radix et Rhizoma medicine pair prevents cardiac remodeling by improving mitochondrial dynamic balance.
Pingping LIN ; Hong CHEN ; Zekun CUI ; Boyang YU ; Junping KOU ; Fang LI
Chinese Journal of Natural Medicines (English Ed.) 2025;23(1):54-63
Astragali Radix (AR) and Notoginseng Radix et Rhizoma (NR) are frequently employed in cardiovascular disease treatment. However, the efficacy of the AR-NR medicine pair (AN) in improving cardiac remodeling and its underlying mechanism remains unclear. This study aimed to evaluate AN's cardioprotective effect and potential mechanism on cardiac remodeling using transverse aortic constriction (TAC) in mice and angiotensin II (Ang II)-induced neonatal rat cardiomyocytes (NRCMs) and fibroblasts in vitro. High-performance liquid chromatography-quadrupole-time of flight tandem mass spectrometry (HPLC-Q-TOF-MS/MS) characterized 23 main components of AN. AN significantly improved cardiac function in the TAC-induced mice. Furthermore, AN considerably reduced the serum levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin T (CTn-T), and interleukin-6 (IL-6) and mitigated inflammatory cell infiltration. Post-AN treatment, TAC-induced heart size approached normal. AN decreased cardiomyocyte cross-sectional area and attenuated the upregulation of cardiac hypertrophy marker genes (ANP, BNP, and MYH7) in vivo and in vitro. Concurrently, AN alleviated collagen deposition in TAC-induced mice. AN also reduced the expression of fibrosis-related indicators (COL1A1 and COL3A1) and inhibited the activation of the transforming growth factor-β1 (TGF-β1)/mothers against decapentaplegic homolog 3 (Smad3) pathway. Thus, AN improved TAC-induced cardiac remodeling. Moreover, AN downregulated p-dynamin-related protein (Drp1) (Ser616) expression and upregulated mitogen 2 (MFN-2) and optic atrophy 1 (OPA1) expression in vivo and in vitro, thereby restoring mitochondrial fusion and fission balance. In conclusion, AN improves cardiac remodeling by regulating mitochondrial dynamic balance, providing experimental data for the rational application of Chinese medicine prescriptions with AN as the main component in clinical practice.
Animals
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Drugs, Chinese Herbal/pharmacology*
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Myocytes, Cardiac/metabolism*
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Mice
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Rats
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Male
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Mitochondrial Dynamics/drug effects*
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Ventricular Remodeling/drug effects*
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Astragalus Plant/chemistry*
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Mice, Inbred C57BL
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Rhizome/chemistry*
;
Panax notoginseng/chemistry*
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Rats, Sprague-Dawley
;
Natriuretic Peptide, Brain/genetics*
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Humans
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Angiotensin II
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Astragalus propinquus
9.Combination of Astragalus-Salvia and Ophiopogon-Dendrobium herb pairs alleviates Sjögren's Syndrome via inhibiting the JAK1/STAT3 and PI3K/AKT pathways in NOD/Ltj mice.
Peng SUN ; Lili ZHU ; Yang YU ; Sijing HU ; Mengyi SHAN ; Xuan ZHAO ; Xinchang WANG ; Qiaoyan ZHANG ; Luping QIN
Chinese Journal of Natural Medicines (English Ed.) 2025;23(6):733-741
Sjögren's syndrome (SS) is an autoimmune disease characterized primarily by oral and periocular dryness. Astragalus-Salvia (AS) and Ophiopogon-Dendrobium (OD) represent two frequently utilized herb pairs in SS treatment. While the combination of AS-OD herb pairs demonstrates clinical efficacy in alleviating SS symptoms, its underlying mechanism remains unclear. This investigation sought to assess the therapeutic effects and elucidate the potential mechanisms of AS-OD in non-obese diabetic (NOD)/Ltj mice with SS. The study utilized NOD/Ltj mice as SS models, administering AS-OD treatment for 10 weeks at doses of 113.1, 226.2, and 339.3 mg·d-1·20 g-1. Results demonstrated that AS-OD improved SS symptoms, evidenced by enhanced salivary flow rate, decreased anti-SSA/Ro and anti-SSB/La antibody levels, increased swimming duration, and reduced lactate (LA) and blood urea nitrogen (BUN) levels in NOD/Ltj mice. AS-OD reduced lymphocyte infiltration, enhanced Aquaporin-5 (AQP5) expression in the submandibular gland, decreased inflammatory cytokine levels in the submandibular gland, and reduced the T helper type 17/regulatory T lymphocyte (Th17/Treg) cell ratio in the spleen. Transcriptomic and proteomic analyses indicated AS-OD's involvement in regulating phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and Janus kinase 3/signal transducer and activator of transcription 3 (JAK1/STAT3) pathways, with inhibitory effects validated in both NOD/Ltj mice submandibular gland and A-253 cells. Furthermore, AS-OD enhanced cell viability and reduced A-253 cell apoptosis through the PI3K/AKT pathway. In A-253 cells, AS-OD reduced inflammatory cytokine levels, CXC chemokine ligand 9/10 (CXCL9/10), and T-cell chemotaxis by inhibiting the JAK1/STAT3 pathway. AS-OD mitigates SS by suppressing inflammation and immune responses through the PI3K/AKT and JAK1/STAT3 pathways.
Animals
;
STAT3 Transcription Factor/genetics*
;
Sjogren's Syndrome/immunology*
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Mice, Inbred NOD
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Proto-Oncogene Proteins c-akt/genetics*
;
Phosphatidylinositol 3-Kinases/genetics*
;
Mice
;
Drugs, Chinese Herbal/administration & dosage*
;
Signal Transduction/drug effects*
;
Janus Kinase 1/genetics*
;
Humans
;
Female
;
Astragalus Plant/chemistry*
;
Male
10.The novel combination of astragaloside IV and formononetin protects from doxorubicin-induced cardiomyopathy by enhancing fatty acid metabolism.
Xinyue YU ; Zhaodi HAN ; Linling GUO ; Shaoqian DENG ; Jing WU ; Qingqing PAN ; Liuyi ZHONG ; Jie ZHAO ; Hui HUI ; Fengguo XU ; Zunjian ZHANG ; Yin HUANG
Chinese Journal of Natural Medicines (English Ed.) 2025;23(10):1171-1182
Astragali Radix (AR), a traditional Chinese medicine (TCM), has demonstrated therapeutic efficacy against various diseases, including cardiovascular conditions, over centuries of use. While doxorubicin serves as an effective chemotherapeutic agent against multiple cancers, its clinical application remains constrained by significant cardiotoxicity. Research has indicated that AR exhibits protective properties against doxorubicin-induced cardiomyopathy (DIC); however, the specific bioactive components and underlying mechanisms responsible for this therapeutic effect remain incompletely understood. This investigation seeks to identify the protective bioactive components in AR against DIC and elucidate their mechanisms of action. Through network medicine analysis, astragaloside IV (AsIV) and formononetin (FMT) were identified as potential cardioprotective agents from 129 AR components. In vitro experiments using H9c2 rat cardiomyocytes revealed that the AsIV-FMT combination (AFC) effectively reduced doxorubicin-induced cell death in a dose-dependent manner, with optimal efficacy at a 1∶2 ratio. In vivo, AFC enhanced survival rates and improved cardiac function in both acute and chronic DIC mouse models. Additionally, AFC demonstrated cardiac protection while maintaining doxorubicin's anti-cancer efficacy in a breast cancer mouse model. Lipidomic and metabolomics analyses revealed that AFC normalized doxorubicin-induced lipid profile alterations, particularly by reducing fatty acid accumulation. Gene knockdown studies and inhibitor experiments in H9c2 cells demonstrated that AsIV and FMT upregulated peroxisome proliferator activated receptor γ coactivator 1α (PGC-1α) and PPARα, respectively, two key proteins involved in fatty acid metabolism. This research establishes AFC as a promising therapeutic approach for DIC, highlighting the significance of multi-target therapies derived from natural herbals in contemporary medicine.
Animals
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Doxorubicin/adverse effects*
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Saponins/administration & dosage*
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Isoflavones/pharmacology*
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Rats
;
Cardiomyopathies/prevention & control*
;
Mice
;
Fatty Acids/metabolism*
;
Myocytes, Cardiac/metabolism*
;
Triterpenes/administration & dosage*
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Male
;
Drugs, Chinese Herbal/administration & dosage*
;
Humans
;
Cardiotonic Agents/administration & dosage*
;
Mice, Inbred C57BL
;
Cell Line
;
Astragalus Plant/chemistry*
;
Astragalus propinquus

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