1.Effects of Hedysarum polybotrys polysacchcaide on FXR-FGF19 signal pathway in diabetes rats
Lei ZHANG ; Sheng-fang WAN ; Ya-ling LI ; Qian-kun LIANG ; Yi-hong TIAN ; Xin-xin MA ; Qian GUO
The Chinese Journal of Clinical Pharmacology 2025;41(1):76-80
Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P<0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.
2.Mechanism of Xiangmei Pills in treating ulcerative colitis based on UHPLC-Q-Orbitrap HRMS and 16S rDNA sequencing of intestinal flora.
Ya-Fang HOU ; Rui-Sheng WANG ; Zhen-Ling ZHANG ; Wen-Wen CAO ; Meng ZHAO ; Ya-Hong ZHAO
China Journal of Chinese Materia Medica 2025;50(4):882-895
The efficacy of Xiangmei Pills on rats with ulcerative colitis(UC) was investigated by characterizing the spectrum of the active chemical components of Xiangmei Pills. Rapid identification and classification of the main chemical components were performed,and the therapeutic effects of Xiangmei Pills on the proteins and intestinal flora of UC rats were analyzed to explore the mechanism of its action in treating UC. Fifty SD rats were acclimatized to feeding for 3 d and randomly divided into blank group, model group,mesalazine group(0. 4 g·kg~(-1)), low-dose group of Xiangmei Pills(1. 89 g·kg~(-1)), and high-dose group of Xiangmei Pills(5. 67 g·kg~(-1)), with 10 rats in each group. 5% dextrose sodium sulfate(DSS) was given by gavage to induce the male SD rat model with UC,and the corresponding medicinal solution was given by gavage after 10 days, respectively. The therapeutic effect of Xiangmei Pills on rats with UC was evaluated according to body mass, disease activity index(DAI), and hematoxylin-eosin(HE) staining, and the histopathological changes in the colon were observed. Ultra-high performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q-Orbitrap HRMS) technique was used to rapidly and accurately identify the main chemical constituents of Xiangmei Pills. Immunohistochemistry was used to detect the expression of aryl hydrocarbon receptor(AhR),interferon-γ(IFN-γ), mucin-2(MUC-2), and cytochrome P450 1A1(CYP1A1) in colon tissue. Interleukin-22(IL-22) expression in colon tissue was detected by immunofluorescence. The 16S r DNA high-throughput sequencing technique was used to study the modulatory effects of Xiangmei Pills on the intestinal flora structure of rats with UC. Pharmacodynamic results showed that compared with that of the blank group, the colon tissue of the model group was congested, and ulcers were visible in the mucosa; compared with that in the model group, the histopathology of the colon of the rats with UC in the groups of Xiangmei Pills were improved, with scattered ulcers and reduced inflammatory cell infiltration. Chemical analysis showed that a total of 45 components were identified by mass spectrometry information, including 15 phenolic acids, 8 coumarins, 15 organic acids, 3 amino acids, 2 flavonoids, and 2 other components. Compared with those in the blank group, the levels of Ah R, CYP1A1, MUC-2, and IL-22 proteins in the colon tissue of rats in the model group were significantly decreased, and the level of IFN-γ protein was significantly increased; the intestinal flora of rats in the model group was disorganized, with a decrease in the abundance of the flora; the relative abundance of Bacteroidetes,unclassified genera of Ascomycetes, Prevotella of the Prevotella family, and Prevotella decreased significantly, and that of Firmicutes decreased, but the difference was not statistically significant. The relative abundance of Bacteroidetes, Bifidobacterium, and Lactobacillus increased significantly. Compared with those of the model group, the levels of Ah R, CYP1A1, MUC-2, and IL-22proteins in the colonic tissue of the groups of Xiangmei Pills were significantly higher, and the levels of IFN-γ proteins were significantly lower. The recovery of the intestinal flora was accelerated, and the diversity of the intestinal flora was significantly increased. The relative abundance of Bacteroidetes was significantly increased, and that of unclassified genera of Ascomycetes,Lactobacillus, Prevotella of the Prevotella family, and Prevotella was significantly increased. The relative abundance of Bacteroidetes and Bifidobacterium was significantly decreased. This study demonstrated that Xiangmei Pills can effectively treat UC, mainly through the phenolic acid and organic acid components to stimulate the intestinal barrier, regulate protein expression and the relative abundance and diversity of intestinal flora, and play a role in the treatment of UC.
Animals
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Colitis, Ulcerative/metabolism*
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Drugs, Chinese Herbal/chemistry*
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Rats, Sprague-Dawley
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Male
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Rats
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Gastrointestinal Microbiome/genetics*
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Chromatography, High Pressure Liquid
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Humans
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Mass Spectrometry
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RNA, Ribosomal, 16S/genetics*
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Bacteria/drug effects*
3.Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production.
Ya-Jie CAI ; Jian-Hang LAN ; Shuo LI ; Yue-Ning FENG ; Fang-Hong LI ; Meng-Yu GUO ; Run-Ping LIU
Journal of Integrative Medicine 2025;23(4):429-444
OBJECTIVE:
Ulcerative colitis is closely associated with intestinal stem cell (ISC) loss and impaired intestinal mucus barrier. Sinisan (SNS), a compound Chinese herbal medicine, has a long history in the treatment of intestinal dysfunction, yet whether SNS can relieve acute experimental colitis by modulating ISC proliferation and secretory cell differentiation has not been studied. Our study tested the effect of SNS against acute colitis and focused on the mechanisms involving intestinal barrier recovery.
METHODS:
Network pharmacology analysis and blood entry component analysis of SNS were used to explore the underlying mechanism by which SNS affects the acute dextran sulfate sodium (DSS)-induced murine colitis model. RNA-sequencing was used to demonstrate the mechanism. Further, reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining, and alcian blue and periodic acid-Schiff staining were performed in vivo and in the colonic organoids to investigate the cell lineage differentiation-related mechanism of SNS. Furthermore, potential active ingredients from SNS were predicted by network pharmacology analysis.
RESULTS:
SNS dramatically suppressed DSS-induced acute colonic inflammation in mice. RNA-sequencing analysis revealed downregulation of inflammation and apoptosis-related genes, and upregulation of lipid metabolism and proliferation-related genes, such as Irf7, Pparα, Clspn and Hspa5. Additionally, ISC renewal and intestinal secretory cell lineage commitment were significantly promoted by SNS both in vivo and in vitro in colonic organoids, leading to enhanced mucin expression. Furthermore, potential active ingredients from SNS that mediated inflammation, lipid metabolism, proliferation, apoptosis, stem cells and secretory cells were predicted using a network pharmacology approach.
CONCLUSION
Our study shed light on the underlying mechanism of SNS in attenuating acute colitis from the perspective of ISC renewal and secretory lineage cell differentiation, suggesting a of novel therapeutic strategy against colitis. Please cite this article as: Cai YJ, Lan JH, Li S, Feng YN, Li FH, Guo MY, et al. Sinisan, a compound Chinese herbal medicine, alleviates acute colitis by facilitating colonic secretory cell lineage commitment and mucin production. J Integr Med. 2025; 23(4): 429-444.
Animals
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Drugs, Chinese Herbal/therapeutic use*
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Mice
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Colon/pathology*
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Mucins/metabolism*
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Mice, Inbred C57BL
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Cell Differentiation/drug effects*
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Male
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Colitis/metabolism*
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Cell Lineage/drug effects*
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Dextran Sulfate
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Stem Cells/drug effects*
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Disease Models, Animal
4.Association of Body Mass Index with All-Cause Mortality and Cause-Specific Mortality in Rural China: 10-Year Follow-up of a Population-Based Multicenter Prospective Study.
Juan Juan HUANG ; Yuan Zhi DI ; Ling Yu SHEN ; Jian Guo LIANG ; Jiang DU ; Xue Fang CAO ; Wei Tao DUAN ; Ai Wei HE ; Jun LIANG ; Li Mei ZHU ; Zi Sen LIU ; Fang LIU ; Shu Min YANG ; Zu Hui XU ; Cheng CHEN ; Bin ZHANG ; Jiao Xia YAN ; Yan Chun LIANG ; Rong LIU ; Tao ZHU ; Hong Zhi LI ; Fei SHEN ; Bo Xuan FENG ; Yi Jun HE ; Zi Han LI ; Ya Qi ZHAO ; Tong Lei GUO ; Li Qiong BAI ; Wei LU ; Qi JIN ; Lei GAO ; He Nan XIN
Biomedical and Environmental Sciences 2025;38(10):1179-1193
OBJECTIVE:
This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study.
METHODS:
A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants.
RESULTS:
Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m 2) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m 2) and obesity (≥ 28.0 kg/m 2) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m 2 ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses.
CONCLUSION
This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans
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Body Mass Index
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China/epidemiology*
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Male
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Female
;
Middle Aged
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Prospective Studies
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Rural Population/statistics & numerical data*
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Aged
;
Follow-Up Studies
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Adult
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Mortality
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Cause of Death
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Obesity/mortality*
;
Overweight/mortality*
5.Langerhans Cell Histiocytosis of Bone:Report of Eight Cases and Review of the Literature.
Ya BI ; Dan-Dan WU ; Fang-Ying YU ; Zhen-Hong FANG ; Bo HUANG
Acta Academiae Medicinae Sinicae 2025;47(2):325-332
Langerhans cell histiocytosis of bone is a rare tumor disease characterized by the large accumulation of CD1a+ and CD207+ dendritic cells in tissues of unknown cause.It mainly occurs in children aged 1-4 years old,with incidences of 4-6 per million in children and 1-2 per million in adults.Due to its low incidence,diverse clinical manifestations,and no obvious specificity of imaging manifestations,the definitive diagnosis and early treatment of this type of tumor are challenging.In this paper,we report 8 cases of Langerhans cell histiocytosis of bone and review the relevant literature published in the past five years to summarize the clinical characteristics,pathological features,diagnosis,treatment,and prognosis of this disease.
Humans
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Bone Diseases/therapy*
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Histiocytosis, Langerhans-Cell/therapy*
6.Validation and Forensic Application of a Domestic Human DNA Quantitative De-tection Kit
Jing CHEN ; Ya-Ping WANG ; Yun-Peng FENG ; Xiao-Xin HU ; Zhen-Jun JIA ; Hong-Di LIU ; An-Xin YAN ; Yong-Jiu LI ; Zhu PENG ; Zhi-Fang LIU ; Jian-Gang CHEN
Journal of Forensic Medicine 2025;41(3):252-259
Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.
7.Correlation of knee joint asymmetry with balance and walking ability in hemiplegic stroke patients
Zheng-Hua XIAO ; Jiang MA ; Hong LI ; Fang WANG ; Li-Ying GUO ; Xiao-Lin TAO ; Feng ZHANG ; Ya-Yong LI ; Xiao-Li YAN
Medical Journal of Chinese People's Liberation Army 2025;50(2):134-140
Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.
8.Granulomatous primary central nervous system vasculitis in a child.
Ya-Nan ZHANG ; Chang-Hong DING ; Shu-Hong REN ; Wei-Hua ZHANG ; Fang LIU ; Nan ZHANG ; Yu-Juan ZHANG
Chinese Journal of Contemporary Pediatrics 2025;27(9):1140-1142
A 14-year-old boy was admitted to the hospital due to a single episode of afebrile seizure and four hours of impaired consciousness. Three months prior to admission, he had a history of bilateral uveitis. Cerebrospinal fluid analysis revealed a mild elevation in white blood cell count. Cranial magnetic resonance imaging and contrast-enhanced scans showed multiple abnormal signals in both cerebral hemispheres, with punctate and nodular enhancement. Susceptibility-weighted imaging revealed multiple punctate hemorrhages within lesions in the bilateral frontal and left parietal lobes, suggestive of vasculitis. Brain biopsy demonstrated inflammatory granulomatous lesions. No secondary causes were identified, and the final diagnosis was granulomatous primary central nervous system vasculitis. The patient's condition improved after treatment with methylprednisolone sodium succinate and mycophenolate mofetil. This report describes a rare case of granulomatous central nervous system vasculitis in a child and provides valuable insights for the diagnosis and treatment of this disease.
Humans
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Male
;
Vasculitis, Central Nervous System/diagnosis*
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Adolescent
;
Magnetic Resonance Imaging
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Granuloma/diagnosis*
9.Metabolomic analysis of Agrimonia pilosa intervention in proliferation and apoptosis of H1299 cells based on UHPLC-Q-Orbitrap MS technology
Ze-hua TONG ; Wen-jun GUO ; Meng LI ; Ya-juan XU ; Hong-ming ZHANG ; Ze-yu DOU ; Sheng-xu XIE ; Wei-fang WANG
Chinese Pharmacological Bulletin 2025;41(5):970-978
Aim To investigate the effects of Agrimonia pilosa(AP)on the proliferation and apoptosis of non-small cell lung cancer(NSCLC)H1299 cells using non-targeted metabolomics and other methods,and to explore the underlying molecular mechanisms.Meth-ods Taking H1299 cells as the research object,the effect of AP on cell proliferation and apoptosis was de-tected through CCK-8 method,colony formation,LDH,Hoechst 33258 staining,AO/EB staining,flow cytometry detection,RT qPCR and other experiments.The main differential metabolites were detected by the metabolomics method of ultra-high phase liquid chro-matography and mass spectrometry(UHPLC-Q-Orbi-trap MS),and related metabolic pathways were ana-lyzed.Results Compared with the control group,AP treatment was able to significantly inhibit the prolifera-tion and colony formation of H1299 cells,while the re-lease of LDH increased in a dose-dependent manner.Fluorescence microscopy and flow cytometry and RT-qPCR analysis revealed that H1299 cells underwent crumpling and increased nuclear fragmentation after AP administration,blocked in G0/G1 phase,up-regulated apoptotic genes caspase-3 and Bax,and down-regulated apoptosis-inducing effects of Bcl-2.Metabolomics anal-ysis screened 35 differential metabolites,which were PC(O-30∶1),D-Glutamic acid,PE(18∶0/15∶0),etc.The main metabolic pathways involved includ-ed amino acid metabolism,glycerophospholipid metabo-lism and purine metabolism so on.Conclusions AP may exert its pharmacological effects by interfering with multiple metabolic pathways in H1299 cells,inhibiting cell proliferation and promoting apoptosis.
10.Effects of Hedysarum polybotrys polysacchcaide on FXR-FGF19 signal pathway in diabetes rats
Lei ZHANG ; Sheng-fang WAN ; Ya-ling LI ; Qian-kun LIANG ; Yi-hong TIAN ; Xin-xin MA ; Qian GUO
The Chinese Journal of Clinical Pharmacology 2025;41(1):76-80
Objective To study the effects of Hedysarum polysaccharides polysaccharide(HPS)on the farnesoid X receptor(FXR)-fibroblast growth factor-19(FGF19)signaling pathway of diabetes rats.Methods Twelve Wistar male rats were randomly selected as the normal group,and the other rats were fed with a single intraperitoneal injection of streptozotocin(50 mg·kg-1 STZ)and a high sugar and high-fat diet to replicate the diabetes rat model.Model rats were randomly divided into model group,positive control group(given 400 mg·kg-1·d-1 suspension of Bifidobacterium quadruplex live bacterial tablets by gavage),experimental-H,-M,-L groups(given 200,100,and 50 mg·kg-1·d-1 doses of HPS suspension by gavage);normal group,and model group were given equal volume of purified water by gavage once a day for 8 consecutive weeks.Glucose(Glu)was detected by a blood glucose meter;and serum total glyceride(TG)and total cholesterol(TC)were detected by enzyme-linked immunosorbent assay reagent kit;the expressions of FXR、fibroblast growth factor receptors 4(FGFR4)relative mRNA expression level and protein were detected by real-time fluorescence quantitative polymerase chain reaction method and Western blot.Results The Glu concentrations in the normal group,model group,positive control group,and experimental-H groups were(7.66±0.61),(29.25±1.64),(23.31±3.02)and(19.31±5.13)mmol·L-1,respectively;the TG content were(957.00±113.73),(1 345.00±246.44),(958.00±96.53)and(964.00±130.22)μmol·L-1,respectively;the TC content were(161.65±4.53),(302.19±5.35),(236.09±5.14)and(165.58±2.58)μmol·L-1,respectively;the expression of FXR relative mRNA expression level were 1.00±0.06,0.48±0.02,0.67±0.04 and 0.92±0.04,respectively;the expression of FGFR4 relative mRNA expression level were 1.00±0.04,0.17±0.01,0.48±0.04 and 0.41±0.03;respectively.The above indexes of the model group were compared with the control group,and the above indexes of the control group and the experimental-H group were compared with the model group,and the differences were statistically significant(all P<0.01).Conclusion HPS improves blood sugar,lowers blood lipids,and protects liver and intestinal tissues,possibly by regulating the FXR-FGF19 signaling pathway in intestinal tissue,and regulating bile acid synthesis.

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