1.Zingiberis Rhizoma Alleviates Inflammatory Bowel Disease Through Regulating TLR4/MAPK Signaling Pathway in Ly6Chi Monocytes/Macrophages
Yalan LI ; Chonghao ZHANG ; Huachen LIU ; Jialong SU ; Na LI ; Mengyu ZHOU ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):66-75
ObjectiveTo investigate the potential mechanisms of Zingiberis Rhizoma in treating inflammatory bowel disease (IBD) by integrating network pharmacology with in vitro and in vivo experiments. MethodsTraditional Chinese Medicine Systems Pharmacology Database And Analysis Platform (TCMSP), Traditional Chinese Medicine Integrated Database (TCMID) Database were used to obtain the active component targets of Zingiberis Rhizoma. GeneCards was used to obtain the IBD targets. DAVID was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses on core targets. Cytoscape 3.10.2 was used to establish the "active component-disease target-signaling pathway" interaction network. Mice were randomly assigned to control, model, and Zingiberis Rhizoma (400 mg·kg-1) groups. An IBD model was induced via dextran sulfate sodium (DSS). The colonic tissue was collected post-treatment to assess histology, expression of Ly6C+ monocytes/macrophages, and mRNA levels of Toll-like receptor 4 (TLR4), and inflammatory cytokines. The effect of Zingiberis Rhizoma aqueous extract on RAW264.7 cell viability was evaluated. Furthermore, the effects of the extract at 100, 10, and 1 mg·L-1 on LPS-induced differentiation of RAW264.7 cells into Ly6Chi monocytes/macrophages, mRNA levels of TLR4 and inflammatory cytokines, and protein levels of factors in the TLR4/mitogen-activated protein kinase (MAPK) signaling pathway. ResultsA total of 241 targets were identified for Zingiberis Rhizoma and 6 787 for IBD, with 122 shared targets among Zingiberis Rhizoma, ulcerative colitis (UC), and Crohn's disease (CD). The enrichment analyses yielded 297 GO terms and 88 KEGG pathways. Associations were noted between Zingiberis Rhizoma's active component targets and IBD targets. In vivo experiments: Compared with the control group, the model group showed decreased body weight and disease activity index (DAI)(P<0.01), shortened colon length, damaged mucosal epithelium with inflammatory cell infiltration, raised pathological scores (P<0.05), increased Ly6Chi and Ly6Clo monocytes/macrophages (P<0.05), and up-regulated mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.05) and protein levels of TLR4, phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), and phosphorylated p38 MAPK (p-p38 MAPK) (P<0.05). Zingiberis Rhizoma intervention reversed these changes and reduced Ly6Chi monocytes/macrophages (P<0.01). In vitro experiments: compared with the control, LPS increased the proportion and number of Ly6Chi monocytes/macrophages and mRNA levels of TLR4, TNF-α, IL-1β, and IL-6 (P<0.01) and enhanced the expression of TLR4, p-ERK1/2, and p-p38 MAPK (P<0.05). Zingiberis Rhizoma reduced Ly6Chi monocytes/macrophages (P<0.05), down-regulated the mRNA levels of inflammatory cytokines (P<0.05), and suppressed the TLR4/MAPK pathway (P<0.05). ConclusionZingiberis Rhizoma alleviates IBD by suppressing the TLR4/ERK/p38 MAPK signaling pathway and reducing inflammatory cytokine levels in Ly6Chi monocytes/macrophages.
2.Mume Fructus Restores Intestinal Mucosal Epithelial Barrier Through MEK/ERK Signaling Pathway in Mouse Model of Inflammatory Bowel Disease
Huachen LIU ; Chonghao ZHANG ; Yalan LI ; Jie LIU ; Jialong SU ; Na LI ; Shaoshuai LIU ; Qing WANG ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):76-85
ObjectiveTo clarify the repair effect of Mume Fructus on the intestinal mucosal epithelial barrier in the mouse model of inflammatory bowel disease (IBD) and explore the repair mechanism. MethodsThirty-six male C57BL/6 mice were randomly assigned into six groups: normal, model, low-, medium-, and high-dose (200, 400, and 800 mg·kg-1) Mume Fructus, and sulfasalazine (300 mg·kg-1). Except the normal group, the rest groups had free access to 2% dextran sulfate sodium (DSS) solution for seven days to establish the IBD model, followed by a seven-day drug intervention. The body weight change and disease activity index (DAI) were recorded. After the last administration, spleen and colon tissue samples were collected to analyze the differences in colon length and spleen index. Hematoxylin-eosin staining was used to observe the morphology of the colon tissue. The level of diamine oxidase (DAO) in the serum was measured by the DAO assay kit. Immunohistochemistry was employed to determine the expression of tight junction proteins such as Claudin-1, Occludin, and zonula occludens-1 (ZO-1) in the colon tissue. Real-time PCR was performed to measure the mRNA levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the colon tissue. Finally, Western blot was employed to determine the protein levels of mitogen-activated protein kinase kinase (MEK), extracellular signal-regulated kinase (ERK), phosphorylated (p)-MEK, and phosphorylated ERK in the colon tissue. ResultsCompared with the normal group, the model group exhibited decreases in body weight and colon length (P<0.01), increases in DAI, spleen index, and serum DAO level (P<0.01), damaged colonic epithelium and goblet cells, and obvious infiltration of inflammatory cells. In addition, the model group exhibited higher positive expression of Claudin-1, Occludin, and ZO-1 (P<0.01), higher mRNA levels of TNF-α and IL-1β (P<0.01), and higher protein levels of p-MEK and p-ERK (P<0.05, P<0.01) than the normal group. However, sulfasalazine and three doses of Mume Fructus markedly decreased the body weight and DAI (P<0.05), recovered the colon length and spleen index, alleviated colon tissue damage, lowered the level of DAO in the serum (P<0.01), and down-regulated the mRNA levels of TNF-α and IL-1β (P<0.01) and the protein levels of p-MEK and p-ERK (P<0.05). Sulfasalazine and low- and medium-dose Mume Fructus increased the positive expression of Occludin, Claudin-1, and ZO-1 (P<0.05, P<0.01). Furthermore, high-dose Mume Fructus elevated the protein expression of Occludin (P<0.05). ConclusionMume Fructus can restore the expression of intestinal epithelial tight junction proteins by inhibiting the phosphorylation of proteins in the MEK/ERK signaling pathway and down-regulating the levels of TNF-α and IL-1β, thus repairing the intestinal mucosal barrier in the mouse model of IBD.
3.Regulatory Effect of Modified Wumeiwan on Th17/Treg Balance and Intestinal Microbiota in Ulcerative Colitis with Dampness-heat Obstruction Syndrome in Human Flora-associated Model
Chonghao ZHANG ; Peiguang MA ; Huachen LIU ; Jialong SU ; Jie LIU ; Yalan LI ; Guichuan XU ; Na LI ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):86-93
ObjectiveTo investigate the modulating effect of modified Wumeiwan (MWMW) on the ulcerative colitis (UC)-associated intestinal helper T cell 17 (Th17)/regulatory T cell (Treg) balance and intestinal flora by using a human flora-associated model of UC patients with dampness-heat obstruction syndrome, thus providing a new idea for the UC-related research and therapeutic strategies. MethodsThe 24 male C57BL/6J mice were randomized into normal control, model, and MWMW groups (n=8). Model and MWMW groups were first treated with an antibiotic cocktail (vancomycin, 0.1 g·kg-1; neomycin sulfate, 0.2 g·kg-1; ampicillin, 0.2 g·kg-1; metronidazole, 0.2 g·kg-1) for 21 days. At the end of antibiotic treatment, the gavage of fecal microbiota suspension from UC patients with dampness-heat obstruction syndrome was started at a dose of 0.2 mL·d-1 for 19 consecutive days, by which a human flora-associated model of UC was obtained. The MWMW group was administrated daily with MWMW liquid (12.5 g·kg-1), while the normal control and model groups were administrated by gavage with an equal amount of sterile water for 7 consecutive days. The symptoms of dampness-heat obstruction were observed. The colon length and spleen index were measured and calculated, and the proportions of Th17 and Treg cells were detected by flow assay. The intestinal flora was analyzed by 16S rRNA high-throughput sequencing. ResultsCompared with the normal control group, the model group showed shortened colon (P<0.05) and increased spleen index (P<0.01). Compared with the model group, the MWMW group showed prolonged colon (P<0.01) and decreased spleen index (P<0.05). After the intervention of MWMW, the Th17 proportion and Th17/Treg ratio in the colon decreased (P<0.01), and the proportion of Treg cells increased (P<0.05). The number of species and alpha and beta diversity of intestinal flora in mice were regulated by MWMW (P<0.05). In terms of intestinal flora composition, MWMW increased the relative abundance of several phyla (Firmicutes, Proteobacteria, Fusobacteriota, Actinobacteriota, and Gemmatimonadota), the genus Bacteroides, and two species (Bacteroides thetaiotaomicron and B. fragilis) in model mice. Moreover, Spearman's correlation analysis showed that the relative abundance of B. thetaiotaomicron and B. fragilis were negatively correlated with the Th17 level (P<0.05). In addition, the above changes in intestinal flora caused the changes in microbial genes involved in 14 pathways, such as glycolysis, amino acid degradation, inorganic nutrient metabolism, biosynthesis of pyrimidine deoxyribonucleotides, antibiotic resistance, and degradation of polysaccharides. ConclusionsThe human flora-associated model successfully simulated the changes (marked by a decrease in the abundance of Bacteroides) of intestinal flora in UC patients with dampness-heat obstruction syndrome. MWMW can enrich the abundance of beneficial bacteria such as B. thetaiotaomicron and B. fragilis and promote the synergistic intestinal immune modulation with the metabolic functions centered on glycolysis, amino acid metabolism, and nucleotide synthesis through bacterial polysaccharide utilization sites to reduce the Th17/Treg ratio, thereby exerting a protective effect on UC.
4.Evolution of Medication Patterns in Traditional Chinese Medicine for Treating Inflammatory Bowel Disease
Chen WANG ; Xiaoyu CAO ; Yalan LI ; Shaoshuai LIU ; Guiying PENG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):94-102
ObjectiveTo explore the evolution of medication patterns and syndrome-herb associations of traditional Chinese medicine (TCM) in treating inflammatory bowel disease (IBD), providing a theoretical foundation for precise syndrome differentiation and treatment in clinical practice. MethodsMedical case literature on TCM treatment of IBD from 1960 to 2024 was retrieved to establish a database. Frequency statistics, cluster analysis, change point detection, and association rule mining were employed to comprehensively analyze the syndrome distribution, therapeutic methods, medication patterns, and their temporal variations. ResultsA total of 685 medical cases were included. Common syndromes were dampness-heat (66.42%) and spleen deficiency (56.20%). Primary therapeutic methods included heat clearing (63.65%), spleen invigorating (47.45%), and dampness draining (36.79%). High-frequency herbs included Coptidis Rhizoma (354), Paeoniae Radix Alba (303), Aucklandiae Radix (292), Codonopsis Radix (253), and Glycyrrhizae Radix et Rhizoma (244). Initial prescription clustering revealed three core therapeutic method combinations: heat clearing and detoxifying (represented by Baitouweng Tang), spleen invigorating and Qi reinforcing (represented by Shenling Baizhusan), and cold-heat regulation (represented by Wumeiwan combined with Shaoyao tang). Temporal analysis identified 2008 as a key transition point in TCM treatment of IBD, with significantly increased usage frequency of heat-clearing and dampness-drying herbs such as Fraxini Cortex, Phellodendri Chinensis Cortex, Sophorae Flavescentis Radix, and Scutellariae Radix as well as hemostatic herbs such as carbonized Sanguisorbae Radix, Bletillae Rhizoma, Agrimoniae Herba, and Notoginseng Radix et Rhizoma. Follow-up efficacy analysis showed median improvement rates of 64.0% at the first follow-up, 76.0% at the second follow-up, and 78.7% at the third follow-up. Syndrome-drug association analysis revealed specific herb pairs with significant therapeutic advantages, including Notoginseng Radix et Rhizoma + Coicis Semen, Sanguisorbae Radix + Coptidis Rhizoma, and Codonopsis Radix + Aconii Lateralis Radix Praeparaia. ConclusionTCM medication patterns for treating IBD demonstrate distinct temporal evolution characteristics, with significantly increased usage frequency of herbs such as Fraxini Cortex, Notoginseng Radix et Rhizoma, and Agrimoniae Herba. Significant therapeutic method-herb associations and syndrome-herb association patterns exist, with the formation of specific herb pairs, providing evidence-based support for precise syndrome differentiation and treatment of IBD.
5.Tibetan medicine Twelve Flavors Yishou San alleviated lipopolysaccharide-induced acute lung injury through inhibiting neutrophil infiltration
Wenling RONG ; Yaxuan LI ; Yanfei HONG ; Jiaqi CUI ; Jing FENG ; Zhulang CHU ; Guiying PENG ; Qingjia REN ; Qinghong DU
China Modern Doctor 2024;62(33):56-63,124
Objective To explore the immune mechanism of Tibetan medicine Twelve Flavors Yishou San in intervening with acute lung injury.Methods Construct a lipopolysaccharide(LPS)-induced acute lung injury rat model and treated it with Twelve Flavors Yishou San.The intervention effect of Twelve Flavors Yishou San on LPS induced acute lung injury was determined through lung pathological sections and blood gas analysis.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of pro-inflammatory cytokine tumor necrosis factor-α(TNF-α)and anti-inflammatory cytokine interleukin(IL)-10 in rat's bronchoalveolar lavage fluid.Flow cytometry was used to detect changes in immune cells in rat's bronchoalveolar lavage fluid,lungs,spleen and peripheral blood.Results LPS successfully induced an acute lung injury model in rats,and Twelve Flavors Yishou San could alleviate the exudation of inflammatory cells,elevated oxygen partial pressure in LPS induced acute lung injury to varying degrees.The ELISA results of rat bronchoalveolar lavage fluid showed that compared with normal control group,the TNF-α level in the bronchoalveolar lavage fluid of rats with acute lung injury was increased and the IL-10 level was decreased,while the Twelve Flavors Yishou San could alleviate this effect.The results of flow cytometry showed that Twelve Flavors Yishou San could significantly reduce neutrophil infiltration in rat bronchoalveolar lavage fluid,but had no significant effect on macrophages and adaptive immune response.Conclusion Twelve Flavors Yishou San can alleviate LPS induced acute lung injury by inhibiting neutrophil infiltration,providing an important experimental basis for fully understanding the therapeutic mechanism of Twelve Flavors Yishou San.
6.Value of plasma soluble leukocyte differentiation antigen 14 subtype combined with neutrophil gelatinase associated lipocalin in early diagnosis and prognostic prediction of sepsis in children
Mengsha ZHU ; Bo HUANG ; Honglei NIU ; Peng GUO ; Guiying ZHANG
Chinese Pediatric Emergency Medicine 2021;28(6):477-481
Objective:To explore the value of plasma soluble leukocyte differentiation antigen 14 subtype(Presepsin) combined with neutrophil gelatinase associated lipocalin(NGAL) in the early diagnosis and prognosis of sepsis in children.Methods:A total of 94 children with sepsis admitted to our hospital from June 2017 to October 2020 were selected, 41 children with shock were classified as septic shock group, and 53 children without shock were classified as sepsis group.Another 41 healthy children in our hospital during the same period were selected as the control group.The plasma levels of Presepsin, NGAL, procalcitonin(PCT) and C-reactive protein(CRP)were detected in three groups.The pediatric critical illness score and sequential organ failure(SOFA)score of children with sepsis were recorded.According to the mortality of the children within 28 days of admission, they were divided into survival group( n=75)and death group( n=19). The plasma levels of Presepsin, NGAL, PCT and CRP, pediatric critical illness score and SOFA score were compared between the survival group and the death group.Pearson test and receiver operating characteristic curve were used to analyze the correlation between plasma Presepsin, NGAL and pediatric critical illness score, SOFA score, and the predictive value of early diagnosis and prognosis of sepsis in children. Results:The levels of plasma Presepsin, NGAL, PCT and CRP in sepsis group and septic shock group were higher than those in control group, and those in septic shock group were higher than those in sepsis group( P<0.05). The plasma levels of Presepsin, NGAL, PCT, CRP and SOFA scores in death group were higher than those in survival group, and the pediatric critical illness score in death group was lower than that in survival group( P<0.05). Plasma Presepsin and NGAL were negatively correlated with pediatric critical illness score( r=-0.676, P<0.001; r=-0.664, P<0.001), and positively correlated with SOFA score( r=0.781, P<0.001; r=0.749, P<0.001). When the plasma Presepsin level was 468.91 ng/L, the sensitivity of area under curve(AUC) for sepsis diagnosis was 85.6% and the specificity was 77.5%.When the plasma NGAL level was 38.94 ng/mL, the sensitivity of AUC for sepsis diagnosis was 82.4%, and the specificity was 65.8%.The AUC of plasma Presepsin combined with NGAL for early diagnosis of sepsis was 0.912(95% CI 0.865 to 0.959), which was higher than of plasma Presepsin of 0.857(95% CI 0.785 to 0.928) and the AUC of NGAL of 0.761(95% CI 0.680 to 0.841). When the plasma Presepsin level was 816.92 ng/L, the sensitivity for predicting the prognosis of sepsis was 73.2% and the specificity was 76.1%.When the plasma NGAL level was 51.27 ng/mL, the sensitivity for predicting the prognosis of sepsis was 67.4% and the specificity was 68.0%.The AUC of plasma Presepsin combined with NGAL to predict the prognosis of sepsis was 0.891(95% CI 0.816 to 0.966), which was higher than the AUC of plasma Presepsin of 0.795(95% CI 0.698 to 0.892) and NGAL of AUC 0.714(95% CI 0.577 to 0.851). Conclusion:Clinical detection of plasma Presepsin and NGAL levels is helpful to early diagnosis of sepsis and judge the severity of the disease in children, which has guiding significance in evaluating the prognosis, and is beneficial to improve the prognosis.
7.A case report of subcutaneous panniculitis-like T cell lymphoma with fever and erythema on the body as the initial symptoms
Yi ZHAN ; Peng ZHANG ; Fangfang ZHANG ; Qianjin LU ; Rong XIAO ; Guiying ZHANG
Journal of Central South University(Medical Sciences) 2017;42(11):1348-1352
Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a very rare form of peripheral α/β T cell skin lymphoma that is localized primarily in the subcutaneous adipose tissues.It is characterized by single or multiple painful subcutaneous nodules or lumps,often affecting the limbs.The patient presented to the Department of Dermatology,Second Xiangya Hospital,Central South University,who suffered from intermittent fever and erythema on the body,finally was diagnosed as SPTCL after histopathological examinations for twice.
8.miR-136-5p effect on A20 expression in interleukin-17-stimulated astrocytes
Xiongzhi SHI ; Shaohui ZONG ; Jichen HE ; Xiaoming PENG ; Yunbing GAO ; Guiying DENG
Chinese Journal of Tissue Engineering Research 2017;21(16):2587-2592
BACKGROUND: miRNA plays a critical regulatory role in the development and plasticity of spinal cord, and pathological changes after spinal cord injury. OBJECTIVE: To study the effect of miR-136-5p on the A20 expression in mouse astrocytes stimulated by interleukin-17 (IL-17). METHODS: C57BL/6 mouse astrocytes were cultured in vitro, identified by immunofluorescence staining, and then stimulated by 100 μg/L IL-17 for 0, 3, 6, 12 and 24 hours, respectively. The relative mRNA expression levels of IL-6 and tumor necrosis factor-α were detected by RT-PCR to determine the optimal stimulation time of IL-17. The mouse astrocytes were respectively stimulated by 10, 20, 50, 100 and 200 μg/L IL-7 for 6 hours, and similarly, the relative mRNA expression levels of IL-6 and tumor necrosis factor-α were detected to determine the optimal concentration of IL-17. At 6 hours after IL-17 (50 μg/L) stimulation, the mRNA expression levels of miR-136-5p and A20 in mouse astrocytes were detected by RT- PCR, and the protein expression level of A20 was detected by western blot assay. In addition, the lentiviral expression vector (miR-136-5p-inhibition) was constructed and transfected into the mouse astrocytes that were also stimulated by IL-7 to detect the expression levels of miR-136-5p, A20 mRNA and A20 protein. RESULTS AND CONCLUSION: Compared with the blank control group, the expression level of miR-136-5p in the miR-136-5p-inhibition group was significantly decreased after 6-hour IL-17 stimulation (P < 0.05). The expression levels of A20 mRNA and protein in each group were significantly decreased after 6-hour IL-17 (50 μg/L) stimulation (P < 0.05). The expression levels of A20 mRNA and protein in the miR-136-5p-inhibition group were significantly higher than those in the blank control group (P < 0.05), while there were no significant differences in the expression level of A20 protein between blank control and negative groups (P > 0.05). To conclude, miR-136-5p makes certain effect on the expression of A20 protein in astrocytes after IL-17 stimulation.
9.Health literacy management by family doctors on action-awareness merging of diabetic patients:effect analysis
Derong PENG ; Xinping ZHAO ; Fenhong YANG ; Wei SHEN ; Guiying WU
Chinese Journal of Hospital Administration 2017;33(3):235-238
Objective To intervene and appraise the health literacy of diabetic patients entering contracts with family doctors in pilot communities,and learn the effect and feasibility of health literacy management by family doctors for diabetic patients.Methods By means of community intervention study and questionnaire survey,560 diabetic patients as mentioned above in Shanghai were subject to a baseline assessment on their health literacy,followed by management and routine follow-up on their diabetic health literacy.At the end of six months of comprehensive intervention,their health literacy was appraised again to observe the effects of such management.Results Six months of guidance and management found the average scoring of the health literacy of these patients 23.46 over the baseline,an increase of 36.8% of the patients in their compliance of the four basic diabetic diet behaviors,and an increase of 27.8% of them in regular and quantitative exercises.Conclusions It is feasible for community family doctors to carry out the health literacy management for diabetic patients contracted,and health literacy management can change the awareness and behaviors of such patients to some extent.
10.Effects of Dachengqi Decoction on Pulmonary Histology and Total IgE Levels in Mice with Allergic Asthma
Daling ZHONG ; Jiajia WU ; Genmao LI ; Dongyu GE ; Jun WU ; Guiying PENG
Chinese Journal of Information on Traditional Chinese Medicine 2016;23(7):58-60
Objective To explore the effects ofDachengqiDecoction on morphological changes, lung and spleen indexes, and total IgE levels of mice with allergic asthma; To discuss it relevant mechanism of action.MethodsThe method of OVA sensitization and provocation was used to establish allergic asthma mice models. 20 C57BL/6 mice were randomly divided into control group, model group,Dachengqi Decoction group and dexamethasone positive group. Each medication group was given relevant medicine for gavage. Lung and spleen indexes in each group were detected. The total IgE levels in serum of mice were detected by ELISA, and HE staining was used to conduct pathological observation.Results Compared with control group, the lung index and level of IgE in model group increased significantly and pulmonary histological results showed abundant inflammatory cells infiltrated in the bronchus; compared with the model group, the lung index as well as the levels of IgE decreased significantly in the Dachengqi Decoction and dexamethasone positive group (P<0.05), and the lung tissue organization form was improved significantly.ConclusionDachengqi Decoction has inhibiting effects on pulmonary inflammation of mice with asthma.

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