1.Comparison of Wild and Cultivated Bupleurum scorzonerifolium Based on Traditional Quality Evaluation
Changsheng YUAN ; Feng ZHOU ; Xingyu LIU ; Yu SHI ; Yihan WANG ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Huaizhong GAO ; Yanmeng LIU ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):203-214
ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots(BSR), and explore the underlying molecular mechanisms, providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin(YLW) served as the quality reference, we conducted comparative analysis among YLW, locally domesticated wild germplasm in Yulin(YLC3), Daqing germplasm introduced and cultivated in Yulin(YLDQC3), and locally cultivated germplasm in Daqing(DQC3). A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed, including macroscopic traits(appearance, odor), microscopic features(proportions of cork, phloem, xylem), cell wall component contents(hemicellulose, cellulose, lignin), carbohydrate contents(starch, water-soluble polysaccharides), marker compound contents(ethanol-soluble extracts, total saponins, liposoluble extracts, and saikosaponins A, B2, C, D), metabolomics, and transcriptomics, in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically, Yulin-produced BSR(YLW, YLC3, YLDQC3) exhibited significantly greater weight, length, and upper and middle diameters than Daqing-produced BSR(DQC3). Odor-wise, YLW and YLC3 had a a fragrance taste, YLDQC3 had a rancid oil odor, and DQC3 had a sweet and fragrant taste. Microscopically, Yulin germplasm(YLW, YLC3) and Daqing germplasm(YLDQC3, DQC3) shared similar structural features, respectively. However, Yulin germplasm showed significantly higher proportions of cork and phloem, as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents, Yulin germplasm contained significantly higher levels of ethanol-soluble extracts, total saponins, and saikosaponins A, B2, C, D, while Daqing germplasm had significantly higher levels of hemicellulose, starch, and liposoluble extracts. After introduction to Yulin, the Daqing germplasm(YLDQC3) showed increased starch, water-soluble polysaccharides and liposoluble extracts contents, decreased cell wall component content, but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm, while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway, including one acetyl-coenzyme A(CoA) acetyltransferase gene(ACAT), one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene(HMGS), two hydroxymethylglutaryl-CoA(HMG-CoA) reductase genes(HMG), one phosphomevalonate kinase gene(PMK), one 1-deoxy-D-xylose-5-phosphate synthase gene(CLA), one hydroxymethylbuten-1-aldol synthase gene(HDR), two farnesyl pyrophosphate synthase genes(FPPS), one squalene synthase gene(SQS), one β-amyrin synthase gene(BAS), 102 cytochrome P450(CYP450) gene family members, and 32 uridine diphosphate-glucuronosyltransferase(UGT) gene family members. ConclusionAmong the three cultivated types, YLC3 most closely resembles YLW in appearance, microscopic features, contents of major bioactive constituents, metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm, and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings, it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.
2.Comparison of Wild and Cultivated Polygalae Radix Based on Traditional Quality Evaluation
Yihan WANG ; Yanmeng LIU ; Huaizhu LI ; Yongliang LI ; Shan GUAN ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):215-224
ObjectiveBased on the traditional quality evaluation methods summarized in previous dynasties, this paper systematically contrasted the quality differences between wild Polygalae Radix(WPR) and cultivated Polygalae Radix(CPR) from the aspects of character, microscope and chemical composition by modern scientific and technological means, providing a basis for high-quality production and quality control. MethodsCPR and local WPR in Yulin city, Shaanxi province from 1 to 6 years were collected, and a systematic comparative analysis was conducted using traditional pharmacognosy research methods combined with modern multi-omics analysis techniques, including character traits(length, weight, diameter), cross-sectional microscopic features(proportions of cork, phloem, xylem, etc), cell wall component content(hemicellulose, cellulose, lignin), extracts content(water-soluble extract and alcohol-soluble extract), carbohydrate content(starch, water-soluble polysaccharides), contents of total flavonoids, total saponins and specific marker compounds(3,6′-disinapoyl sucrose, polygalaxanthone Ⅲ, tenuifoliside A, tenuifoliside C, sibiricose A5 and A6) and other indexes. Ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to conduct comparative analysis of secondary metabolites in WPR and CPR, and multivariate statistical analysis such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were combined to screen the key differential components of them. ResultsIn terms of appearance, there were significant differences between WPR and CPR. The characteristics of WPR conformed to the "thick wrinkles on the epidermis" recorded in ancient books, featuring a wrinkled surface and grayish-brown appearance. However, CPR had a finer texture and a yellowish white appearance, with weight, length, and diameter increasing with longer cultivation periods. In terms of microscopy, WPR exhibited a thick cork layer with fissures in the phloem, whereas CPR had a thinner cork layer with uniformly arranged cork cells. Younger PR specimens showed numerous phloem fissures in cross-sections, while older specimens display progressively denser arrangements of phloem parenchyma cells. In terms of the contents of various major components, the contents of water-soluble extract, starch and total saponins in WPR were inversely proportional to the root diameter, while the contents of water-soluble extract, water-soluble polysaccharides and total saponins in CPR decreased with the increase of planting years. The content of xanthones in WPR was significantly higher than that of CPR, while the contents of other major components showed no significant change pattern. Among the six indicator components, the average content of sibiricose A5 in WPR was significantly higher than that of CPR, followed by slightly higher content of tenuifoliside A. In CPR, the relative content of 3,6′-disinapoyl sucrose and tenuifoliside A was the highest. The former showed an increase in volatility with increasing cultivation years, while the latter showed a decrease in volatility. The results of differential compound analysis based on UPLC-Q-TOF-MS showed that there were significant differences in metabolites between WPR and CPR samples. Among them, the seven compounds with the largest differences among WPR samples of different thicknesses were polygalasaponins, and for CPR with different planting years, the main differential compounds were oligosaccharide esters. ConclusionThere are differences between WPR and CPR in character, microscopic structure and chemical composition, and some components are inversely proportional with the increase of diameter and cultivation duration due to the distribution characteristics. However, the longer the cultivation years of PR, the closer it is to the "thick wrinkles on the epidermis" of WPR, which has been respected by generations. It is suggested that this traditional character combined with modern component contents should be used as the index of artificial cultivation and quality control of PR.
3.Comparison of Wild and Cultivated Gardeniae Fructus Based on Traditional Quality Evaluation
Yuanjun SHANG ; Bo GENG ; Xin CHEN ; Qi WANG ; Guohua ZHENG ; Chun LI ; Zhilai ZHAN ; Junjie HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):225-234
ObjectiveBased on traditional quality evaluation of Gardeniae Fructus(GF) recorded in historical materia medica, this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics, microscopic features, and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length, diameter and individual fruit weight of wild and cultivated GF, and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF, and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently, the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China, the starch content was measured by anthrone colorimetric method, the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method, the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection(HPLC-ELSD), and the contents of representative components in them were measured by ultra-performance liquid chromatography(UPLC). Finally, correlation analysis was conducted between quality traits and phenotypic traits, combined with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), key differential components between wild and cultivated GF were screened. ResultsIn terms of traits, the wild GF fruits were smaller, exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger, displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF, while the blue-yellow value(b*) of wild GF was significantly higher than that of cultivated GF. In the microstructure, the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals, while the endocarp contained stone cell class round, polygonal or tangential prolongation, undeveloped seeds were visible within the fruit. In contrast, the mesocarp of cultivated GF contained few calcium oxalate cluster crystals, or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like, with the innermost layer arranged in a grid pattern. Seeds were basically mature, and only a few immature seeds existed in some batches. Regarding primary metabolite content, wild GF exhibited significantly higher total polysaccharide level than cultivated GF(P<0.01). In category-specific component content, wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF(P<0.01). Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside and chlorogenic acid compared to cultivated GF(P<0.01). Conversely, the contents of genipin 1-gentiobioside, geniposide and genipin were significantly lower in wild GF(P<0.01). ConclusionThere are significant differences between wild and cultivated GF in terms of traits, microstructure, and contents of primary and secondary metabolites. At present, the quality evaluation system of cultivated GF remains incomplete, and this study provides a reference for guiding the production of high-quality GF medicinal materials.
4.Advances in the impact of obesity on ocular diseases
Di ZHANG ; Huixian WANG ; Xu ZHANG ; Wenjing LI
International Eye Science 2025;25(1):88-93
Obesity is a risk factor and pathological basis for various chronic non-communicable diseases and is an important risk factor leading to human mortality and disability. The harm of obesity to the body includes not only various systemic diseases but also some ocular diseases. Currently, the higher pursuit of life and visual quality has led to increased attention to the etiology and prevention of ocular diseases, and the impact of obesity on ocular diseases has been gradually discovered. This article reviews the impact of obesity on certain ocular diseases to deepen the understanding of obesity's impact on ocular diseases and provide a reference for the prevention and treatment of ocular diseases.
5.Textual Research on Historical Evolution and Key Information of Classical Famous Formula of Da Qinjiaotang
Na LI ; Jianying BAI ; Fuping LI ; Xiufen ZHANG ; Di LU ; Yishuo BAI ; Cuixiang WANG ; Kun SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):201-211
Da Qinjiaotang is the 54th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas (the first batch) ,and it originated from the Collection of Writings on the Mechanism of Disease, Suitability of Qi, and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla, Glycyrrhizae Radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora, Asari Radix et Rhizoma, Notopterygium incisum, Saposhnikoviae Radix, Scutellariae Radix, Gypsum, Angelica dahurica, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke, peripheral facial paralysis, cervical spondylosis, rheumatic arthritis, neurodermatitis, and other multisystem diseases. Therefore, following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas, the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data, involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution, composition, dosage, method of preparation, and preparation of the original medicinal materials of Da Qinjiaotang, a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes, stroke (144) was the most, accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon", featuring "hands and feet cannot move, stiff tongue hinders speaking", as well as other symptoms, such as slant of the mouth, hemiplegia, numbness of the limbs, paroxysmal pain, and acerbic syncope. The treatment scope was expanded, covering tendon dryness, clonic convulsion, spasm syndrome, and arthralgia syndrome. At the same time, it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors, created the theory of "hot stroke", and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs, 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula, with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL, decocted once, and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang, the paper clarified its historical evolution and confirmed its key information, so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.
6.Clinical efficacy of escitalopram combined with transcutaneous cervical vagus nerve stimulation therapy for patients with major depressive disorder and its effect on plasma IL-6 and IL-10 levels
Jin LI ; Jinbo SUN ; Di WU ; Wenjun WU ; Runzhu SUN ; Shanshan XUE ; Yapeng CUI ; Huaning WANG ; Yihuan CHEN
Sichuan Mental Health 2025;38(1):7-13
BackgroundInvasive vagus nerve stimulation therapy has been approved for the adjunctive treatment of treatment-resistant depression, which may contribute to the anti-inflammatory properties of vagus nerve stimulation (VNS), whereas the efficacy of non-invasive transcutaneous cervical vagus nerve stimulation (tcVNS) in treating major depressive disorder (MDD) and its impact on plasma inflammatory factors remain unclear. ObjectiveTo observe the effect of escitaloprom combined with tcVNS on the status of depression, anxiety and sleep quality as well as the plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) in MDD patients, in order to provide references for the recovery and treatment of MDD patients. MethodsFrom August 21, 2019 to April 17, 2024, 45 patients who met the diagnostic criteria for MDD in the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) were recruited from the psychosomatic outpatient clinic of the First Affiliated Hospital of Air Force Military Medical University. Subjects were divided into study group (n=23) and control group (n=22) using random number table method. All patients were treated with escitalopram. On this basis, study group added a 30-minute tcVNS therapy once a day for 4 weeks. While control group was given corresponding sham stimulation, and the duration of each stimulation lasted 30 seconds. Before and after 4 weeks of treatment, Hamilton Depression Scale-17 item (HAMD-17) was used to assess depressive symptoms, and HAMD-17 anxiety/somatization subfactor and insomnia subfactor were used to assess patients' anxiety/somatization symptoms and sleep quality. Levels of plasma IL-6 and IL-10 were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe generalized estimating equation model yielded a significant time effect for HAMD-17 total score, anxiety/somatization subfactor score and insomnia subfactor score in both groups (Wald χ2=315.226, 495.481, 82.420, P<0.01). After 4 weeks of treatment, HAMD-17 total score and anxiety/somatization subfactor score of study group were lower than those of control group, with statistically significant differences (Wald χ2=4.967, 32.543, P<0.05 or 0.01), while no statistically significant difference was found in the insomnia subfactor score between two groups (Wald χ2=0.819, P=0.366). Significant time effects were reported on plasma IL-6 and IL-10 levels in both groups (Wald χ2=21.792, 5.242, P<0.05 or 0.01). Compared with baseline data, a reduction in plasma IL-6 levels was detected in both groups (Wald χ2=22.015, 6.803, P<0.01), and an increase in plasma IL-10 levels was reported in study group (Wald χ2=5.118, P=0.024) after 4 weeks of treatment. ConclusionEscitalopram combined with tcVNS therapy is effective in improving depressive symptoms, anxiety/somatization symptoms and sleep quality in patients with MDD. Additionally, it helps reduce plasma IL-6 levels and increase IL-10 levels. [Funded by Shaanxi Provincial Key Research and Development Program-General Project (number, 2023-YBSF-185), www.clinicaltrials.gov number, NCT04037111]
7.Textual Research on Historical Evolution and Key Information of Classical Famous Formula of Da Qinjiaotang
Na LI ; Jianying BAI ; Fuping LI ; Xiufen ZHANG ; Di LU ; Yishuo BAI ; Cuixiang WANG ; Kun SU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(7):201-211
Da Qinjiaotang is the 54th formula of the 100 formulas in the Catalogue of Ancient Classical Formulas (the first batch) ,and it originated from the Collection of Writings on the Mechanism of Disease, Suitability of Qi, and Safeguarding of Life Discussed in Plain Questions. Da Qinjiaotang is composed of Gentiana macrophylla, Glycyrrhizae Radix et Rhizoma, Ligusticum chuanxiong, Angelica sinensis, Paeonia lactiflora, Asari Radix et Rhizoma, Notopterygium incisum, Saposhnikoviae Radix, Scutellariae Radix, Gypsum, Angelica dahurica, Atractylodis Macrocephalae Rhizoma, Rehmanniae Radix, Rehmanniae Radix Praeparata, Poria, and Angelicae Pubescentis Radix. It is a classical formula for treating strokes. Da Qinjiaotang is widely used in modern clinical practices for treating ischemic stroke, peripheral facial paralysis, cervical spondylosis, rheumatic arthritis, neurodermatitis, and other multisystem diseases. Therefore, following the Principles of Textual Research on the Key Information of Ancient Classical Famous Formulas, the authors collected the ancient Chinese medical literature of Da Qinjiaotang by the method of bibliometrics and screened out 177 valid data, involving 100 ancient books of traditional Chinese medicine. Based on the historical evolution, composition, dosage, method of preparation, and preparation of the original medicinal materials of Da Qinjiaotang, a systematic study was carried out. It was found that among the 175 records of the main diseases and syndromes, stroke (144) was the most, accounting for 82.29% of the total diseases and syndromes. Later generations mostly followed the practice of LIU Wansu in using Da Qinjiaotang to treat stroke caused by "weak blood and inability to nourish tendon", featuring "hands and feet cannot move, stiff tongue hinders speaking", as well as other symptoms, such as slant of the mouth, hemiplegia, numbness of the limbs, paroxysmal pain, and acerbic syncope. The treatment scope was expanded, covering tendon dryness, clonic convulsion, spasm syndrome, and arthralgia syndrome. At the same time, it was found that there was a controversy between "internal wind" and "external wind" in the treatment of stroke by Da Qinjiaotang. LIU Wansu thought that stroke was caused by internal factors, created the theory of "hot stroke", and used Da Qinjiaotang to treat "internal wind". Many doctors in later generations focused on treating the "external wind" of "internal deficiency and evil". There were 76 valid data on the composition of drugs, 59 of which had doses for each drug. It was suggested to use the modern conversion dosage of the original formula, with 41.30 g per dose. The drug should be boiled in 600 mL water until 300 mL, decocted once, and taken in a warm state after removing the dregs anytime. Through the analysis and study of the ancient books about Da Qinjiaotang, the paper clarified its historical evolution and confirmed its key information, so as to provide the ancient literature evidence for the research and development of the classical famous formula Daqinjiaotan and its better clinical application.
8.Advances in research on fine motion control of prosthesis fingers with brain-computer interface
Di GAN ; Hui HUANG ; Chengzhi LI ; Shiyu ZHANG ; Shiyuan WANG ; Tao WANG
Chinese Journal of Clinical Medicine 2025;32(1):114-119
The deficiency of fingers due to various reasons leads to a certain degree of loss of full or part hand functions. Physical and mental health of patients are seriously affected, and patients have varying degrees of reduced quality of life. Prosthesis fingers play an important role in completing the body shape and enhancing patients’ self-confidence and self-esteem. However, how to make prosthesis fingers perform coordinated movements and restore complete functions is a crucial problem that urgently needs to be solved. This paper reviews the methods of brain-computer interface controlled fine finger movements and elaborates on the origin, current situation, and advancements of the development of this technology, laying a foundation for subsequent research, with the expectation of helping patients solve the problems arising from the insufficiency or absence of finger functions.
9.Preliminary exploration of differentiating and treating multiple system atrophy from the perspective of the eight extraordinary meridians
Di ZHAO ; Zhigang CHEN ; Nannan LI ; Lu CHEN ; Yao WANG ; Jing XUE ; Xinning ZHANG ; Chengru JIA ; Xuan XU ; Kaige ZHANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):392-397
Multiple system atrophy (MSA) is a rare neurodegenerative disease with complex clinical manifestations, presenting substantial challenges in clinical diagnosis and treatment. Its symptoms and the eight extraordinary meridians are potentially correlated; therefore, this article explores the association between MSA symptom clusters and the eight extraordinary meridians based on their circulation and physiological functions, as well as their treatment strategies. The progression from deficiency to damage in the eight extraordinary meridians aligns with the core pathogenesis of MSA, which is characterized by "the continuous accumulation of impacts from the vital qi deficiency leading to eventual damage". Liver and kidney deficiency and the emptiness of the eight extraordinary meridians are required for the onset of MSA; the stagnation of qi deficiency and the gradual damage to the eight extraordinary meridians are the key stages in the prolonged progression of MSA. The disease often begins with the involvement of the yin and yang qiao mai, governor vessel, thoroughfare vessel, and conception vessel before progressing to multiple meridian involvements, ultimately affecting all eight extraordinary meridians simultaneously. The treatment approach emphasizes that "the direct method may be used for joining battle, but indirect method will be needed in order to secure victory" and focuses on "eliminate pathogenic factors and reinforce healthy qi". Distinguishing the extraordinary meridians and focusing on the primary symptoms are pivotal to improving efficacy. Clinical treatment is aimed at the target, and tailored treatment based on careful clinical observation ensures precision in targeting the disease using the eight extraordinary meridians as the framework and core symptoms as the specific focus. Additionally, combining acupuncture, daoyin therapy, and other method may help prolong survival. This article classifies clinical manifestations based on the theory of the eight extraordinary meridians and explores treatment.
10.Analysis of Potential Active Components and Molecular Mechanism of Baoxin Granules Regulating Ferroptosis in Treatment of Heart Failure
Yu CHEN ; Maolin WANG ; Yun WANG ; Yifan ZHAO ; Jing XU ; Hongwei WU ; Fang WANG ; Xiaoang ZHAO ; Youming LI ; Jixiang TIAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):202-209
ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, molecular docking and cell experiments, the active ingredients, possible targets and molecular mechanisms of Baoxin granules(BXG) regulating ferroptosis in the treatment of heart failure(HF) were explored. MethodsBXG intestinal absorption fluid was prepared by everted gut sac and the chemical composition contained therein were identified by UPLC-Q-TOF-MS. According to the obtained components, the potential targets of BXG were predicted, and the HF-related targets and related genes of ferroptosis were retrieved at the same time, and the intersecting targets were obtained by Venn diagram. In addition, the protein-protein interaction(PPI) network and the component-target network were constructed, and the core components and core targets were obtained by topological analysis. Then Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on the core targets, and molecular docking validation of the key targets and main components was carried out by AutoDockTools 1.5.7. H9c2 cells were used to establish a oxygen-glucose deprivation model, and the protective effect of BXG on cells was investigated by detecting cell viability, cell survival rate and reactive oxygen species(ROS) level. The protein expression levels of signal transducer and activator of transcription 3(STAT3), phosphorylation(p)-STAT3 and glutathione peroxidase 4(GPX4) were detected by Western blot to clarify the regulatory effect of BXG on ferroptosis. ResultsA total of 61 chemical components in BXG intestinal absorption fluid were identified, and network pharmacology obtained 27 potential targets of BXG for the treatment of HF, as well as 139 signaling pathways. BXG may act on core targets such as STAT3, tumor protein p53(TP53), epidermal growth factor receptor(EGFR), JUN and prostaglandin-endoperoxide synthase 2(PTGS2) through core components such as glabrolide and limonin, which in turn intervene in lipid and atherosclerosis, phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt), endocrine resistance and other signaling pathways to exert therapeutic effects on HF. Molecular docking showed that the docking results of multiple groups of targets and compounds were good. In vitro cell experiments showed that compared with the blank group, the cell viability and survival rate of the model group were significantly decreased, the level of ROS was significantly increased(P<0.01), the expression levels of STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 proteins were significantly decreased(P<0.05, P<0.01). Compared with the model group, the cell viability and survival rate of the BXG group were significantly increased, the ROS level was significantly decreased(P<0.01), the STAT3, p-STAT3, p-STAT3/STAT3 and GPX4 protein levels were significantly increased(P<0.05, P<0.01). ConclusionBXG may inhibit the occurrence of ferroptosis by up-regulating the expression of STAT3 and GPX4, thus exerting a therapeutic effect on HF, and flavonoids may be the key components of this role.


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