1.Discussion on the decoction and dosing methods of rhubarb root and rhizome in classical prescriptions
Zilin REN ; Changxiang LI ; Yuxiao ZHENG ; Xin LAN ; Ying LIU ; Yanhui HE ; Fafeng CHENG ; Qingguo WANG ; Xueqian WANG
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):48-54
The purpose of this paper is to explore the decoction and dosing methods of rhubarb root and rhizome in classical prescriptions and to provide a reference basis for the clinical use of rhubarb root and rhizome. By collating the relevant classical prescriptions of rhubarb root and rhizome in Shanghan Lun and Jingui Yaolüe, the relationship between its decoction and dosing methods and the syndrome was analyzed. The decoction of rhubarb root and rhizome in classical prescriptions can be divided into three categories: simultaneous decoction, decoction later, and other methods (impregnation in Mafei decoction, decoction with water from the well spring first taken in the morning, and pills). If it enters the blood level or wants to slow down, rhubarb root and rhizome should be decocted at the same time with other drugs. If it enters the qi level and wants to speed up, rhubarb root and rhizome should be decocted later. If it wants to upwardly move, rhubarb root and rhizome should be immersed in Mafei decoction. If it wants to suppress liver yang, rhubarb root and rhizome should be decocted with water from the well spring first taken in the morning. If the disease is prolonged, rhubarb root and rhizome should be taken in pill form. The dosing methods of rhubarb root and rhizome can be divided into five categories: draught, twice, three times, before meals, and unspecified. For acute and serious illnesses with excess of pathogenic qi and adequate vital qi, we choose draught. For gastrointestinal diseases, we choose to take the medicine twice. For achieving a moderate and long-lasting effect, we choose to take the medicine three times. If the disease is located in the lower part of the heart and abdomen, we choose to take it before meals. The use of rhubarb root and rhizome in clinical practice requires the selection of the appropriate decoction and dosing methods according to the location of the disease, the severity of the disease, the patient′s constitution, and the condition after taking the medicine.
2.Observation of the therapeutic effect of rituximab combined with traditional Chinese medicine syndrome differentiation on treating steroid-dependent nephrotic syndrome in children and the regularity of traditional Chinese medicine use
Xia ZHANG ; Xuejun LI ; Tingting XU ; Guang LI ; Yifan LI ; Chundong SONG ; Wensheng ZHAI ; Xianqing REN ; Ying DING
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):80-90
Objective:
To investigate the efficacy, safety, and traditional Chinese medicine (TCM) medication patterns of rituximab (RTX) combined with TCM on treating children with steroid-dependent nephrotic syndrome (SDNS).
Methods:
One hundred and forty-three children with SDNS who visited the Pediatric Nephrology Department of the First Affiliated Hospital of Henan University of Chinese Medicine from January 2018 to December 2022 were enrolled. A cohort study design was adopted, with " RTX treatment" as the exposure factor. Children who met this exposure factor were assigned to the RTX cohort (RTX, glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment), whereas those who did not were assigned to the basic treatment cohort (glucocorticoid, immunosuppressive agent, combined with traditional Chinese medicine syndrome differentiation treatment ), and followed up for 6 months. The frequency of urinary protein recurrences, urinary protein remission duration, proportion and duration of steroid reduction and cessation, cumulative usage of steroids, proportion of recurrence, recurrence amount of steroid used, efficacy of TCM syndrome, and laboratory and safety indicators after treatment, and height and CD19+ B cell count before and after treatment were compared between the two cohorts. The medication patterns of TCM in the two cohorts were analyzed using frequency statistics, association rule analysis, and systematic clustering analysis.
Results:
Compared with the basic treatment cohort, the RTX cohort showed a decrease in the frequency of urinary protein recurrence, extended sustained remission of urinary protein, an increase in the proportion of steroid reduction and cessation, a shorter duration of steroid reduction and cessation, a decrease in cumulative steroid dosage, a lower recurrence rate, a decrease in CD19+ B cell count, and a decrease in 24-h urinary total protein quantification and the level of cholesterol (P<0.05). No significant difference in the recurrence amount of steroid used, height, TCM syndrome efficacy, albumin, aspartate transaminase, blood urea nitrogen, platelet count, and safety indicators between the two cohorts. Children with SDNS were mostly characterized by qi and yin deficiency syndrome, followed by spleen and kidney yang deficiency syndrome. A total of 175 TCMs were included, including 28 high-frequency drugs such as Huangqi, Fuling, Gancao, Baizhu, Dangshen, and Jiuyurou. The primary use of medication is to nourish the qi and spleen, nourish the kidney, and warm yang. The analysis of association rules yielded eight binary associations and ten three-phase associations, with Huangqi, Baizhu, Fuling, and Dangshen, being the most closely related. Cluster analysis identified four TCM combinations, primarily focusing on tonifying kidney and replenishing essence, benefiting qi and nourishing yin, and removing blood stasis.
Conclusion
RTX combined with TCM syndrome differentiation treatment can reduce the recurrence frequency of SDNS, prolong the remission period, reduce the glucocorticoid dosage, and have no marked effect on height growth. No apparent adverse reactions were observed. TCM should focus on nourishing qi and yin while removing blood stasis.
3.Effects and mechanism of paeoniflorin on oxidative stress of ulcerative colitis mice
Xin DAI ; Ying WANG ; Xinyue REN ; Dingxing FAN ; Xianzhe LI ; Jiaxuan FENG ; Shilei LOU ; Hui YAN ; Cong SUN
China Pharmacy 2025;36(4):427-433
OBJECTIVE To investigate the effects and potential mechanism of paeoniflorin on oxidative stress of ulcerative colitis (UC) mice based on adenosine monophosphate-activated protein kinase (AMPK)/nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. METHODS Male BALB/c mice were randomly divided into control group, model group, inhibitor group (AMPK inhibitor Compound C 20 mg/kg), paeoniflorin low-, medium- and high-dose groups (paeoniflorin 12.5, 25, 50 mg/kg), high- dose of paeoniflorin+inhibitor group (paeoniflorin 50 mg/kg+Compound C 20 mg/kg), with 8 mice in each group. Except for the control group, mice in all other groups were given 4% dextran sulfate sodium solution for 5 days to establish the UC model. Subsequently, mice in each drug group were given the corresponding drug solution intragastrically or intraperitoneally, once a day, for 7 consecutive days. The changes in body weight of mice were recorded during the experiment. Twenty-four hours after the last administration, colon length, malondialdehyde (MDA) content, and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in colon tissues were measured; histopathological morphology of colon tissues, tight junctions between intestinal epithelial cells, and histopathological scoring were all observed and evaluated; the mRNA expressions of AMPK and Nrf2, as well as the protein expressions of heme oxygenase-1(HO-1), occludin and claudin-1, were all determined in colon tissue. RESULTS Compared with model group, paeoniflorin groups exhibited recovery from pathological changes such as inflammatory cell infiltration and crypt damage in the colon tissue, as well as improved tight junction damage between intestinal epithelial cells. Additionally, significant increases or upregulations were observed in body weight, colon length, activities of SOD and GSH-Px, phosphorylation level of AMPK, and protein expression of Nrf2, HO-1, occludin, claudin-1, and mRNA expressions of AMPK and Nrf2; concurrently, MDA content and histopathological scores were significantly reduced (P< 0.05 or P<0.01). In contrast, the inhibitor group showed comparable (P>0.05) or worse (P<0.05 or P<0.01) indicators compared to the model group. Conversely, the addition of AMPK inhibitor could significantly reverse the improvement of high- dose paconiflorin (P<0.01). CONCLUSIONS Paeoniflorin can repair intestinal epithelial cell damage in mice, improve tight junctions between epithelial cells, upregulate the expression of related proteins, and promote the expression and secretion of antioxidant-promoting molecules, thereby ameliorating UC; its mechanism may be associated with activating AMPK/Nrf2 antioxidant pathway.
4.Establishment and Evaluation of Mouse Model of Ischemic Heart Disease with Qi and Yin Deficiency Syndrome Based on Proteomics
Qiuyan ZHANG ; Ying LI ; Yunxiao GAO ; Longxiao HU ; Yue YUAN ; Xiaoxiao CHEN ; Yali SHI ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):52-61
ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease(IHD) with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol(ISO). MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass, with 12 mice in each group. The model groups 1, 4, and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg-1·d-1 for four consecutive days, the model groups 2, 5, and 8 received ISO at a dose of 10 mg·kg-1·d-1 for seven consecutive days, while the model groups 3, 6, and 9 were given ISO at a dose of 15 mg·kg-1·d-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process, body mass, 24-hour food and water intake, grip strength, and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography, the serum levels of norepinephrine(NE), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP) were determined via enzyme-linked immunosorbent assay(ELISA). The content of adenosine triphosphate(ATP) in myocardial tissue was measured by biochemical analysis, while histopathological changes in myocardial tissue were observed via hematoxylin-eosin(HE) staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition(DDA) proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment, and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg-1·d-1 for 14 consecutive days. Under this condition, compared with the normal group, the model group demonstrated significant reductions in body mass, food intake, water intake, grip strength, total distance and average speed of exercise, ejection fraction(EF), fractional shortening(FS), serum levels of NE and cGMP, and myocardial ATP content(P<0.01), while immobility time, cAMP level, and the cAMP/cGMP value were significantly increased(P<0.05, P<0.01). HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement, inflammatory cell infiltration, myocardial fiber rupture, and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group, with 52 up-regulated and 89 down-regulated. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the cellular components(CC) were mainly related to mitochondria and the inner mitochondrial membrane, the biological processes(BP) were associated with complement activation, platelet activation, and responses to metal ions, suggesting that the potential functional pathways involved the complement and coagulation cascade, as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome, and the underlying mechanisms may be related to the regulation of iron ions by complement C3, C5 and Cp, and plays a role in the regulation through the BP of complement activation, platelet activation, and responses to metal ions, and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.
5.Establishment and Evaluation of Mouse Model of Ischemic Heart Disease with Qi and Yin Deficiency Syndrome Based on Proteomics
Qiuyan ZHANG ; Ying LI ; Yunxiao GAO ; Longxiao HU ; Yue YUAN ; Xiaoxiao CHEN ; Yali SHI ; Junguo REN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):52-61
ObjectiveTo explore the optimal construction method and the biological basis for establishing a mouse model of ischemic heart disease(IHD) with Qi and Yin deficiency syndrome by intraperitoneal injection of isoproterenol(ISO). MethodsA total of 144 male C57BL/6J mice were randomly assigned into three normal groups and nine model groups according to body mass, with 12 mice in each group. The model groups 1, 4, and 7 were administered ISO via intraperitoneal injection at a dose of 5 mg·kg-1·d-1 for four consecutive days, the model groups 2, 5, and 8 received ISO at a dose of 10 mg·kg-1·d-1 for seven consecutive days, while the model groups 3, 6, and 9 were given ISO at a dose of 15 mg·kg-1·d-1 for 14 consecutive days. The normal groups were administered an equivalent volume of normal saline via intraperitoneal injection. After the modeling process, body mass, 24-hour food and water intake, grip strength, and spontaneous activity of the mice were measured. Cardiac function was assessed using echocardiography, the serum levels of norepinephrine(NE), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP) were determined via enzyme-linked immunosorbent assay(ELISA). The content of adenosine triphosphate(ATP) in myocardial tissue was measured by biochemical analysis, while histopathological changes in myocardial tissue were observed via hematoxylin-eosin(HE) staining. An orthogonal experimental design was applied for intuitive analysis and variance analysis to screen the optimal modeling conditions of the mouse model of IHD with Qi and Yin deficiency syndrome. A data-dependent acquisition(DDA) proteomic technique was employed to quantitatively detect differentially expressed proteins in myocardial tissue between the optimal model group and the normal group. And bioinformatics analysis was conducted to explore the potential biological mechanisms underlying the Qi and Yin deficiency model of IHD. ResultsOrthogonal results showed that the injection cycle had a great influence on model establishment, and the optimal modeling condition was identified as intraperitoneal injection of ISO at 15 mg·kg-1·d-1 for 14 consecutive days. Under this condition, compared with the normal group, the model group demonstrated significant reductions in body mass, food intake, water intake, grip strength, total distance and average speed of exercise, ejection fraction(EF), fractional shortening(FS), serum levels of NE and cGMP, and myocardial ATP content(P<0.01), while immobility time, cAMP level, and the cAMP/cGMP value were significantly increased(P<0.05, P<0.01). HE staining results revealed that myocardial tissue in the model group had disordered cell arrangement, inflammatory cell infiltration, myocardial fiber rupture, and fibrous tissue proliferation. Proteomic analysis identified 141 differentially expressed proteins in the model group compared with the normal group, with 52 up-regulated and 89 down-regulated. Gene Ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the cellular components(CC) were mainly related to mitochondria and the inner mitochondrial membrane, the biological processes(BP) were associated with complement activation, platelet activation, and responses to metal ions, suggesting that the potential functional pathways involved the complement and coagulation cascade, as well as porphyrin metabolism. ConclusionContinuous intraperitoneal injection of ISO at a dose of 15 mg·kg-1 for 14 days successfully establishes a mouse model of IHD with Qi and Yin deficiency syndrome, and the underlying mechanisms may be related to the regulation of iron ions by complement C3, C5 and Cp, and plays a role in the regulation through the BP of complement activation, platelet activation, and responses to metal ions, and the signaling pathways of the complement and coagulation cascade and porphyrin metabolism.
6.Determination method of clopidogrel and its metabolites in rat plasma and its pharmacokinetic study
Huan YI ; Lan MIAO ; Changying REN ; Li LIN ; Mingqian SUN ; Qing PENG ; Ying ZHANG ; Jianxun LIU
China Pharmacy 2025;36(13):1599-1603
OBJECTIVE To establish a method for determining the contents of clopidogrel (CLP), clopidogrel carboxylate (CLP-C), clopidogrel acyl-β-D-glucuronide (CLP-G) and contents of clopidogrel active metabolite (CAM) in rat plasma, and to investigate their in vivo pharmacokinetic characteristics. METHODS The Shisedo CAPCELL ADME column was used with a mobile phase consisting of water and acetonitrile (both containing 0.1% formic acid) in a gradient elution. The flow rate was 0.4 mL/min, and the column temperature was maintained at 20 ℃. The injection volume was 2 μL. The analysis was performed in positive ion mode using electrospray ionization with multiple reaction monitoring. The ion pairs for quantitative analysis were m/z 322.1→211.9 (for CLP), m/z 308.1→197.9 (for CLP-C), m/z 322.1→154.8 (for CLP-G), m/z 504.1→154.9 [for racemic CAM derivative (CAMD)]. Six rats were administered a single intragastric dose of CLP (10 mg/kg). Blood samples were collected before medication and at 0.08, 0.33, 0.66, 1, 2, 4, 6, 10, 23 and 35 hours after medication. The established method was used to detect the serum contents of various components in rats. Pharmacokinetic parameters were then calculated using WinNonlin 6.1 software. RESULTS The linear ranges for CLP, CLP-C and CAMD were 0.08-20.00, 205.00-8 000.00, and 0.04-25.00 ng/mL, respectively (r≥0.990). The relative standard deviations for both intra-day and inter-day precision tests were all less than 15%, and the relative errors for accuracy ranged from -11.68% to 14.40%. The coefficients of variation for the matrix factors were all less than 15%, meeting the requirements for bioanalytical method validation. The results of the pharmacokinetic study revealed that, following a single intagastric administration of CLP in rats, the exposure to the parent CLP in plasma was extremely low. Both the area under the drug concentration-time curve (AUC0-35 h) and the peak concentration of the parent CLP were lower than those of its metabolites. The AUC0-35 h of the active metabolite CAM was approximately 43 times that of CLP, though it had a shorter half-life (2.53 h). The inactive metabolite CLP-C exhibited the highest exposure level, but it reached its peak concentration the latest and was eliminated slowly. The AUC0-35 h of CLP-G was about four times that of CAM, and its half-life was similar to that of CLP-C. CONCLUSIONS This study successfully established an liquid chromatography-tandem mass spectrometry method for the determination of CLP and its three metabolites, and revealed their pharmacokinetic characteristics in rats. Specifically, the parent drug CLP was rapidly eliminated, while the inactive metabolites CLP-C and CLP-G exhibited long half-lives, and active metabolite CAM displayed a transient exposure pattern.
7.Pharmacokinetic interactions between empagliflozin and donafenib/lenvatinib in rats
Ying LI ; Zihan LIU ; Wenyu DU ; Jing AN ; Congyang DING ; Yue ZHAO ; Bingnan REN ; Zefang YU ; Yajing LI ; Zhanjun DONG
Journal of Clinical Hepatology 2025;41(9):1853-1860
ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug, and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups: empagliflozin group 1 and 2, donafenib group, lenvatinib group, donafenib pretreatment+empagliflozin group, lenvatinib pretreatment + empagliflozin group, empagliflozin pretreatment+donafenib group, and empagliflozin pretreatment+lenvatinib group, with 6 rats in each group. The doses of empagliflozin, donafenib, and lenvatinib were 2.5 mg/kg, 40 mg/kg, and 1.2 mg/kg, respectively. The rats in the empagliflozin group, donafenib group, and lenvatinib group were given a blank solvent by gavage for 7 consecutive days, followed by a single dose of empagliflozin, donafenib, or lenvatinib on day 7 after the administration of the blank solvent; the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days, followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points, and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib, lenvatinib, and empagliflozin, and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug (area under the plasma concentration-time curve [AUC], time to peak [Tmax], peak concentration [Cmax], and half-life time [t1/2]). The independent-samples t test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. ResultsCompared with the empagliflozin group, the donafenib pretreatment+empagliflozin group had significant increases in the AUC0-t and AUC0-∞ of empagliflozin (P=0.011 and 0.008), while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin, with a slightly shorter Tmax (P=0.019). Compared with the donafenib group, the empagliflozin pretreatment+donafenib group had significant increases in the AUC0-t and AUC0-∞ of donafenib (P=0.027 and 0.025), as well as a significant increase in Cmax (P=0.015) and significant reductions in CLz/F and Vz/F (P=0.005 and 0.004); compared with the lenvatinib group, the empagliflozin pretreatment+lenvatinib group had a reduction in the t1/2 of lenvatinib by approximately 5 hours (P=0.002), with a trend of reduction in AUC0-t (P0.05). ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs, leading to a significant increase in the exposure levels of both drugs, and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.
8.Constructing core outcome set for clinical research on traditional Chinese medicine treatment of post-stroke aphasia.
Ya-Nan MA ; Min-Jie XU ; Yu-Ai YANG ; Jian CHEN ; Qiao-Sheng REN ; Ying LI ; Jing-Ling CHANG
China Journal of Chinese Materia Medica 2025;50(1):238-253
According to the principle and current domestic and international construction processes of core outcome set(COS) and the characteristics of post-stroke aphasia, this study built COS with evidence-based support for traditional Chinese medicine(TCM) treatment of post-stroke aphasia. Firstly, a comprehensive review was conducted on the articles about the TCM treatment of post-stroke aphasia that were published in the four major Chinese databases, three major English databases, and three clinical registration centers over the past five years. The articles were analyzed and summarized, on the basis of which the main part of the COS for clinical research on the TCM treatment of post-stroke aphasia was formed. Secondly, clinical doctors and related nursing personnel were interviewed, and important outcome indicators in the clinical diagnosis and treatment process were supplemented to form a pool of core outcome indicators. Two rounds of Delphi surveys were carried out to score the importance of the core outcome indicators in the pool. Finally, a consensus meeting of experts was held to establish the COS for clinical research on the TCM treatment of post-stroke aphasia. The final COS included a total of 268 studies [236 randomized controlled trials(RCTs), 21 Meta-analysis, and 11 clinical registration protocols] and 20 open questionnaire survey results. After two rounds of Delphi surveys, a total of 14 outcome indicators and their corresponding measurement tools were included in the expert consensus meeting. The final expert consensus meeting determined the COS for post-stroke aphasia, which included 9 indicator domains and 12 outcome indicators.
Humans
;
Aphasia/therapy*
;
Stroke/complications*
;
Medicine, Chinese Traditional
;
Drugs, Chinese Herbal/therapeutic use*
;
Treatment Outcome
9.Interactions between Xuefu Zhuyu Decoction and atorvastatin based on human intestinal cell models and in vivo pharmacokinetics in rats.
Xiang LI ; Huan YI ; Chang-Ying REN ; Hao-Hao GUO ; Hong-Tian YANG ; Ying ZHANG
China Journal of Chinese Materia Medica 2025;50(11):3159-3167
The study aims to explore the herb-drug interaction between Xuefu Zhuyu Decoction(XFZY) and atorvastatin(AT). Reverse transcription polymerase chain reaction(RT-PCR) was used to analyze the transcription levels of proteins related to drug metabolism and transport in LS174T cells, detect the intracellular drug uptake under various substrate concentrations and incubation time, and optimize the model reaction conditions of transporter multidrug resistance protein 1(MDR1)-specific probe Rhodamine 123 and AT to establish a cell model for investigating the human intestinal drug interaction. The cell counting kit-8(CCK-8) method was adopted to evaluate the cytotoxicity of XFZY on LS174T cells. After a single and continuous 48 h culture with XFZY, AT or Rhodamine 123 was added for co-incubation. The effect and mechanism of XFZY on human intestinal absorption of AT were analyzed by measuring the intracellular drug concentrations and transcription levels of related transporters and metabolic enzymes. The results of in vitro experiments show that a single co-culture with a high concentration of XFZY significantly increases the intracellular concentrations of Rhodamine 123 and AT. A high concentration of XFZY co-culture for 48 h increases the AT uptake level, significantly induces the CYP3A4 and UGT1A1 gene expression levels, and inhibits the OATP2B1 gene expression level. To compare with the evaluation results of the in vitro human cell model, the pharmacokinetic experiment of XFZY combined with AT was carried out in rats. Sprague-Dawley(SD) rats were randomly divided into a blank control group and an XFZY group. After 14 days of continuous intragastric administration, AT was given in combination. The liquid chromatography-mass spectrometry(LC-MS)/MS method was used to detect the concentrations of AT and metabolites 2-hydroxyatorvastatin acid(2-HAT), 4-hydroxyatorvastatin acid(4-HAT), atorvastatin lactone(ATL), 2-hydroxyatorvastatin lactone(2-HATL), and 4-hydroxyatorvastatin lactone(4-HATL) in plasma samples, and the pharmacokinetic parameters were calculated. Pharmacokinetic analysis in rats shows that continuous administration of XFZY does not significantly change the pharmacokinetic characteristics of AT in rats, but the AUC_(0-6 h) values of AT and metabolites 2-HAT, 4-HAT, and 2-HATL increase by 21.37%, 14.94%, 12.42%, and 6.68%, respectively. The metabolic rate of the main metabolites shows a downward trend. The study indicates that administration combined with XFZY can significantly increase the uptake level of AT in human intestinal cells and increase the exposure level of AT and main metabolites in rats to varying degrees. The mechanism may be mainly due to the inhibition of intestinal MDR1 transport activity.
Animals
;
Drugs, Chinese Herbal/administration & dosage*
;
Atorvastatin/administration & dosage*
;
Humans
;
Rats
;
Rats, Sprague-Dawley
;
Male
;
Intestines/cytology*
;
Intestinal Mucosa/metabolism*
;
Herb-Drug Interactions
;
Cytochrome P-450 CYP3A/metabolism*
;
Intestinal Absorption/drug effects*
10.Investigation of therapeutic effects and mechanisms of Shenqi Buqi Granules on patients with chronic heart failure of Qi deficiency based on proteomics.
Zhi-Bo WANG ; Ying LI ; Lan MIAO ; Jun-Guo REN ; Jian-Xun LIU
China Journal of Chinese Materia Medica 2025;50(11):3168-3179
This study explored the efficacy and mechanisms of Shenqi Buqi Granules in treating chronic heart failure(CHF) of Qi deficiency using proteomics and bioinformatics methods. A total of 18 healthy participants(health group) and 19 patients with Qi deficiency-type CHF(experimental group) were enrolled and treated with Shenqi Buqi Granules for 12 weeks. Clinical indicators, including Qi deficiency scores, complete blood count, biochemical parameters, lipid profiles, and cardiac function, were collected from pre-and post-experimental groups. Serum proteomics analysis was performed. Differential proteins were screened through differential analysis and K-means clustering. Further analyses, including subcellular localization, Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and protein-protein interaction(PPI) network construction, were conducted to identify pathways and proteins associated with Shenqi Buqi Granules treatment. Spearman correlation analysis focused on proteins most correlated with the core phenotype of CHF of Qi deficiency. The results show that Shenqi Buqi Granules treatment reduced Qi deficiency scores and brain natriuretic peptide levels of pre-experimental group. A total of 1 594 proteins were quantified in the proteomics analysis, with 98 proteins showing differential expression between healthy group and experimental group before and after treatment. Subcellular localization analysis revealed 6 protein sources, while KEGG pathway enrichment highlighted biological processes including angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. Core genes identified included CD34, CSF1, CALM1, CALML3, PPP1CA, PFN1, and 3 ribosomal large subunit proteins. Correlation analysis between core proteins and Qi deficiency scores revealed that CD34(r=-0.67, P<0.05) and PPP1CA(r=0.62, P<0.01) were most strongly associated with Qi deficiency scores. This study suggests that Shenqi Buqi Granules improves Qi deficiency scores and CHF symptoms by regulating angiogenesis, immune inflammation, calcium homeostasis, cytoskeletal regulation, protein synthesis, and energy metabolism. CD34 and PPP1CA are identified as core proteins involved in the therapeutic effects of Shenqi Buqi Granules on Qi deficiency.
Humans
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Drugs, Chinese Herbal/therapeutic use*
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Heart Failure/metabolism*
;
Male
;
Female
;
Proteomics
;
Middle Aged
;
Qi
;
Aged
;
Protein Interaction Maps/drug effects*
;
Adult
;
Chronic Disease


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