1.Mechanisms of Shenmai Injection in Improving Cisplatin Resistance in Non-small Cell Lung Cancer
Hanyu DONG ; Chun WANG ; Chunying LIU ; Wenjun LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):131-142
ObjectiveTo investigate whether Shenmai injection (SMI) improves cisplatin resistance in non-small cell lung cancer (NSCLC) by modulating lipid metabolism and inducing ferroptosis. MethodsHuman lung adenocarcinoma cisplatin-resistant A549/DDP cells were divided into the following groups: Blank group, cisplatin group (23.3 μmol·L-1 cisplatin), SMI group (20 g·L-1 SMI), cisplatin combined with SMI group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI), cisplatin combined with ferroptosis inhibitor/inducer Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin), and cisplatin combined with SMI and Ferrostatin-1/Erastin group (23.3 μmol·L-1 cisplatin + 20 g·L-1 SMI + 10 μmol·L-1 Ferrostatin-1/5 μmol·L-1 Erastin). Network pharmacology, transcriptomics and metabolomics, Cell Counting Kit-8 (CCK-8) assay, transmission electron microscopy (TEM), colorimetric assays, and Western blot analysis were employed to evaluate the effects of these treatments on A549/DDP cell viability, lipid droplet formation, lipid metabolite levels, mitochondrial function, lipid peroxidation, glutathione (GSH) content, total and ferrous iron content, and effects on ferroptiosis and autophagy related protein expression levels. ResultsSMI improved cisplatin resistance in NSCLC mainly by targeting lipid metabolism-related pathways in A549/DDP cells, affecting tumor cell lipid metabolism via autophagy, ferroptosis, and glycerophospholipid metabolism pathways. Compared with the cisplatin group, the cisplatin combined with SMI group showed significantly decreased cell viability (P<0.01), increased lipid droplet accumulation (P<0.01), and reduced mitochondrial maximal respiration, basal respiration, mitochondrial membrane potential, GSH content, total iron, and ferrous iron (all P<0.01). Mitochondrial reactive oxygen species (ROS) was significantly elevated(P<0.01), and lipid peroxidation levels were significantly increased. Protein expression analysis showed significant downregulation of solute carrier family 7 member 11 (SLC7A11) and p62 (P<0.05,P<0.01) and upregulation of ferritin heavy chain (FTH) and microtubule-associated protein 1 light chain 3Ⅱ (LC3Ⅱ) (P<0.05,P<0.01). Compared with the cisplatin combined with SMI group, addition of Ferrostatin-1 significantly increased cell viability (P<0.05), decreased mitochondrial ROS levels (P<0.05), alleviated mitochondrial shrinkage, and reduced lipid peroxidation. Conversely, addition of Erastin further decreased cell viability (P<0.01). ConclusionSMI improves cisplatin resistance in NSCLC by inducing oxidative stress, which may trigger ferroptosis through upregulation of lipophagy.
2.Thromboelastographic features of patients with primary liver cancer and their value in assessing coagulation function
Chunjuan YE ; Chun ZHANG ; Jialu LI ; Sinan LIU ; Zheng WANG
Journal of Clinical Hepatology 2026;42(1):111-116
ObjectiveTo investigate the clinical application value of thromboelastographic parameters in assessing coagulation function by analyzing the thromboelastographic features of patients with primary liver cancer (PLC), and to provide a basis for coagulation management and prognostic evaluation in liver cancer patients. MethodsA retrospective analysis was performed for 1 253 PLC patients who were admitted to The First Affiliated Hospital of Xi’an Jiaotong University from May 2015 to December 2022. According to the presence or absence of cirrhosis, the patients were divided into non-cirrhosis group with 262 patients and cirrhosis group with 991 patients, and according to the presence or absence of HBV infection, they were divided into HBV infection group with 1 055 patients and non-HBV infection group with 198 patients. The patients were stratified based on the severity of liver cirrhosis (Child-Pugh class and MELD score) and liver reserve function (indocyanine green retention rate at 15 minutes [ICGR15]), and thromboelastography was used to measure thromboelastographic parameters (reaction time [R], coagulation formation time [K], α-angle, maximum thrombosis amplitude [MA], and coagulation composite index [CI]) and conventional coagulation markers. The t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between two groups. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the Kruskal-Wallis H test was used for comparison between multiple groups, and the Bonferroni correction method was used for further comparison between two groups. The chi-square test was used for comparison of categorical data between grouips, and the Spearman test was used for correlation analysis. ResultsAmong the 991 patients in the cirrhosis group, 826 had Child-Pugh class A (5 — 6 points), and 165 had Child-Pugh class B (7 — 9 points); 812 had an MELD score of <10, and 179 had an MELD score of ≥10; 679 had an ICGR15 of <10%, and 294 had an ICGR15 of ≥10%. Compared with the patients with Child-Pugh class A, the patients with Child-Pugh class B had a significantly longer K time and significant reductions in α-angle, MA, and CI (all P <0.001); compared with the MELD score <10 group, the MELD score ≥10 group had a significantly longer K time and significant reductions in α-angle, MA, and CI (all P<0.001); compared with the ICGR15 <10% group, the ICGR15 ≥10% group had a significantly longer K time and a significant reduction in MA (both P <0.001). Among the 1 253 patients, MA was strongly positively correlated with fibrinogen and platelet count (r=0.675 and 0.667, both P<0.001); The MA had a weak correlation with Child-Pugh score, MELD score, and ICGR15 (r=-0.112, -0.250, and -0.117, all P<0.001), while the K time,α-angle and CI were weakly correlated with the MELD score (r=0.222, -0.184, and -0.183, all P<0.001),R time was negatively correlated with ICGR15 (r=-0.080, P=0.005). The HBV infection group had significantly higher MA and CI than the non-HBV infection group (P<0.05). ConclusionThromboelastography can sensitively identify the hypocoagulable state associated with the progression of liver cirrhosis and the hypercoagulable tendency in HBV-related liver cancer, which provides an important reference for individualized anticoagulant therapy in clinical practice.
3.Mechanism of Shenmai Injection to Improve Cisplatin Resistance in NSCLC Based on Endoplasmic Reticulum Stress Through PERK/ATF4/CHOP Signaling Pathway
Shengnan GUO ; Hao CAO ; Dan WANG ; Wenjun LIU ; Jianguang WANG ; Jialu LYU ; Chun WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(4):70-78
ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer (NSCLC) based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase (PERK)/activated transcription factor 4 (ATF4)/C/EBP homologous protein (CHOP) signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line (A549/cisplatin) were randomly divided into four groups: Blank control group (0.9% sodium chloride), cisplatin group (5 µg·g-1cisplatin), Shenmai injection group (5.2 mg·g-1 Shenmai injection), and combination therapy group (5.2 mg·g-1 Shenmai injection +5 µg·g-1cisplatin). The drug intervention lasted for 4 weeks, and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin (HE) staining was performed to observe tumor tissue pathology. Transmission electron microscopy (TEM) was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK, ATF4, and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein (BIP), PERK, phosphorylated PERK (p-PERK), eukaryotic translation initiation factor 2α (eIF2α), phosphorylated eIF2α (p-eIF2α), ATF4, CHOP, B-cell lymphoma -2 (Bcl-2), and Bcl-2 Associated X protein (Bax). A549/cis cells were divided into blank group: Blank control group (normal culture medium), cisplatin group (23.3 µmol·L-1 cisplatin), Shenmai Injection group (20 g·L-1 Shenmai injection), and combination therapy group (20 g·L-1 Shenmai injection+23.3 µmol·L-1 cisplatin). Cell counting kit-8 (CCK-8) method was used to detect cell viability, TEM was used to observe the morphology of endoplasmic reticulum, and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group, the combination therapy group showed increased body weight (P<0.05), decreased tumor volume (P<0.05), and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK, ATF4, and CHOP increased (P<0.05). Western blot revealed elevated protein expression levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP, and Bax (P<0.05), while Bcl-2 expression decreased (P<0.05). As shown in the in vitro experiment, compared with the cisplatin group, the combination therapy group exhibited a reduced cell survival rate (P<0.05). TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP, p-PERK/PERK, p-eIF2α/eIF2α, ATF4, CHOP and Bax (P<0.05), with decreased Bcl-2 expression (P<0.05). ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC, which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.
4.Herbal Textual Research on Longan Arillus in Famous Classical Formulas
Yanmeng LIU ; Yihan WANG ; Erwei HAO ; Chun YAO ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):300-309
This article systematically analyzed the historical evolution of the name, origin, harvesting and others of Longan Arillus by referring to the ancient and modern literature, in order to provide a foundation for developing famous classical formulas containing this herb. After textual research, it indicated that Longan Arillus was first recorded under the name of longan in Shennong Bencaojing of the Han dynasty. During the Ming and Qing dynasties, Longan Arillus gradually replaced longan as the standard name recorded in the materia medica, with additional aliases including Yizhi, Lizhinu and Yuanyan. The source of Longan Arillus used in the past dynasties was the arillus of the Sapindaceae plant Dimocarpus longan. The production regions recorded in the past dynasties were mainly Fujian, Guangdong, Guangxi, Hainan, Sichuan and others. Since the Qing dynasty, Longan Arillus produced in Fujian, Guangdong and Guangxi have been regarded as the finest and authentic varieties, with Fujian, Guangxi, and Guangdong remaining the primary authentic production areas today. In ancient times, the fruits were primarily harvested in August of the lunar calendar. However, modern longan cultivation typically involves harvesting ripe fruits during summer and autumn. Post-harvest processing involves removing moisture through sun-drying or baking before drying for medicinal use. Throughout history, processing methods have primarily focused on raw product, though techniques such as wine soaking and powdering have also been employed. Since modern times, it has been concluded that its quality is the best one with thick flesh, sweet taste, brownish-yellow color and tender texture. Longan Arillus possesses a sweet and warm nature, entering the heart and spleen meridians. Its primary functions are tonifying the heart and spleen, nourishing the blood and calming the spirit, which is consistent in ancient and modern times. Based on the textual research, it is suggested to use the arillus of D. longan when developing the famous classical formulas containing Longan Arillus. Processing methods should be selected according to the formula requirements, where no specific processing is indicated, the raw products is recommended for medicinal use.
5.Mechanism of Intervening with Diarrhea-predominant Irritable Bowel Syndrome in Rats with Spleen Deficiency by Xingpi Capsules Through Regulating 5-HT-RhoA/ROCK2 Pathway
Gang WANG ; Lingwen CUI ; Xiangning LIU ; Rongxin ZHU ; Mingyue HUANG ; Ying SUN ; Boyang JIAO ; Ran WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):60-69
ObjectiveTo investigate the efficacy of Xingpi capsules (XPC) in treating diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen deficiency and elucidate its potential molecular mechanisms. MethodsA rat model of IBS-D with spleen deficiency was established by administering senna leaf in combination with restrained stress and swimming fatigue for 14 d. Ten specific pathogen free (SPF)-grade healthy rats were used as the normal control group. After successful modeling, SPF-grade rats were randomly divided into a model group, a pinaverium bromide group (1.5 mg·kg-1), and low- and high-dose XPC groups (0.135 and 0.54 g·kg-1), with 10 rats in each group. Rats in the normal control group and the model group were given distilled water by gavage, while the remaining groups were administered corresponding drug solutions by gavage once a day for 14 consecutive days. The rat body weights and fecal condition were observed every day, and the Bristol score was recorded. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of 5-hydroxytryptamine (5-HT) in serum and colon tissue. Transmission electron microscopy was used to observe the microvilli and tight junctions in the colon. The integrity of the colonic barrier, intestinal motility, and expression of related pathway proteins were evaluated by hematoxylin-eosin (HE) staining, immunohistochemistry, and Western blot. ResultsCompared with those in the normal control group, rats in the model group showed a significantly decreased body weight and increased diarrhea rate, diarrhea grade, and Bristol score (P<0.01). HE staining revealed incomplete colonic mucosa in the model group, with evident congestion and edema observed. Electron microscopy results indicated decreased density and integrity of the colonic barrier, shedding and disappearance of microvilli, and significant widening of tight junctions. The expression levels of colonic tight junction proteins Occludin and Claudin-5 were downregulated (P<0.01), and the levels of 5-HT in serum and colon tissue were elevated (P<0.01). The small intestine propulsion rate significantly increased (P<0.01), and the expression of contractile proteins Ras homolog family member A (RhoA) and Rho-associated coiled-coil containing protein kinase 2 (ROCK2) in colon and phosphorylation of myosin light chain (MLC20) were upregulated (P<0.01). Compared with the model group, the treatment groups showed alleviated diarrhea, diarrhea-associated symptoms, and pathological manifestations of colon tissue to varying degrees. Specifically, high-dose XPC exhibited effectively relieved diarrhea, promoted recovery of colonic mucosal structure, significantly reduced congestion and edema, upregulated expression of Occludin and Claudin-5 (P<0.01), decreased levels of 5-HT in serum and colon tissue (P<0.05,P<0.01), significantly slowed small intestine propulsion rate (P<0.01), and significantly downregulated expression of contractile proteins RhoA and ROCK2 in colon and phosphorylation of MLC20 (P<0.05,P<0.01). ConclusionXPC effectively alleviates symptoms of spleen deficiency and diarrhea and regulates the secretion of brain-gut peptide. The characteristics of XPC are mainly manifested in alleviating IBS-D with spleen deficiency from the aspects of protecting intestinal mucosa and inhibiting smooth muscle contraction, and the mechanism is closely related to the regulation of the 5-HT-RhoA/ROCK2 pathway expression.
6.Herbal Textual Research on Spatholobi Caulis in Famous Classical Formulas
Yajie XIANG ; Yangyang LIU ; Jian FENG ; Chun YAO ; Erwei HAO ; Wenlan LI ; Zhilai ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(6):238-248
Through consulting herbal medicine, medical books, and local chronicles from past dynasties to modern times, this paper systematically researched Spatholobi Caulis from name, origin, producing areas, harvesting, processing, usage, quality evaluation, functions and indications, providing a reference for the development and utilization of famous classical formulas containing Spatholobi Caulis. According to the research, Spatholobi Caulis was first recorded in the Annals of Shunning Prefecture from the Qing dynasty. It was originally a medicinal herb commonly used in Shunning, Yunnan, and was named from the red juice resembling chicken blood that flowed out after the vein was cut off. The mainstream original plants of each dynasty were Kadsura heteroclita and Spatholobus suberectus. Among them, K. heteroclita mainly focused on dispersing blood stasis and unblocking meridians, mainly treating rheumatic pain and injuries caused by falls or blows, and it is mostly used as the raw material of Jixueteng ointments. S. suberectus was commonly used as decoction pieces in decoction, which had the functions of promoting blood circulation and replenishing blood, activating meridians and collaterals, and mainly used for treating anemia, irregular menstruation, and rheumatic bone pain. The production area of Spatholobi Caulis recorded in the Qing dynasty was Yunnan. Currently, the main production area of S. suberectus is Guangxi, while the main production area of K. interior is Yunnan. In the Qing dynasty, the usage of Spatholobi Caulis was an individual prescription with other herbs before making ointments, which was usually composed of the juice of it, safflower, angelica, and glutinous rice. But in modern times, Spatholobi Caulis is mostly sliced and dried for use. The quality of Spatholobi Caulis is often determined by the number of reddish-brown concentric circles on the cut surface, with a higher number indicating better quality. Additionally, the presence of resinous secretions is also considered desirable. Based on the research findings, it is suggested that when developing famous classical formulas containing Spatholobi Caulis, the choice of the primary source should be S. suberectus or K. heteroclita, taking into consideration the therapeutic effects of the formula. It is also recommended that the latest plant classification be referenced in the next edition of Chinese Pharmacopoeia, adjusting the primary source of Kadsurae Caulis to K. heteroclita to avoid confusion caused by inconsistent original names, and the functions adjust to promote Qi circulation and relieve pain, disperse blood stasis and unblock collaterals, treating injuries caused by falls and bruises.
7.Jiawei Xiaoyao San exerts anti-liver cancer effects via exosomal miRNA pathway
Xiaoming LIU ; Jinlai CHENG ; Rushuang LI ; Niuniu LI ; Qiuyun QIN ; Meng XIA ; Chun YAO
Chinese Journal of Tissue Engineering Research 2025;29(19):4052-4062
BACKGROUND:Previous studies by our research group discovered that Jiawei Xiaoyao San has a significant anti-liver cancer effect,but the specific mechanism of action was unclear. OBJECTIVE:To investigate the regulatory effects of the traditional Chinese medicine formula Jiawei Xiaoyao San on the levels of miRNAs in plasma exosomes of rats with diethylnitrosamine chronically induced primary liver cancer,based on high-throughput sequencing combined with bioinformatics. METHODS:SD rats were randomly divided into a blank control group,a liver cancer model group,and a Jiawei Xiaoyao San treatment group.Liver cancer models were induced by continuous administration of diethylnitrosamine for 12 weeks.Starting from the 17th week,rats in the Jiawei Xiaoyao San treatment group were administered Jiawei Xiaoyao San once daily until the end of the 20th week,while rats in the blank control and liver cancer model groups were given an equivalent volume of saline.Anti-hepatocellular carcinoma effects were validated by assessing the morphological structure of rat liver tissues,along with the expression of the hepatocellular carcinoma markers,Glypican-3 protein and serum alpha-fetoprotein.Plasma exosomes from each group of rats were isolated using ultracentrifugation.High-throughput sequencing technology was used to screen for differentially expressed miRNAs in rat plasma exosomes.Bioinformatics was used to predict the potential biomarkers through which Jiawei Xiaoyao San exerts its anti-liver cancer effects via liver cancer-derived exosomal miRNAs,followed by functional analysis. RESULTS AND CONCLUSION:(1)Jiawei Xiaoyao San significantly improved the morphological structure of liver tissues in a rat model of liver cancer.Compared with the liver cancer model group,the expression of liver cancer markers Glypican-3 protein and serum alpha-fetoprotein was significantly reduced in the Jiawei Xiaoyao San treatment group.(2)Bioinformatics analysis showed that in the Jiawei Xiaoyao San group,upregulated miR-223-3p in the liver cancer model group had target binding sites with genes E2F1 and NCOA1,which were closely related to liver cancer survival and prognosis.Therefore,Jiawei Xiaoyao San has a therapeutic effect on liver cancer,possibly by targeting negative regulation of NCOA1/E2F1 through liver cancer plasma-derived exosomal miR-223-3p,thereby playing anti-liver cancer effect.
8.The application strategies of non-uniform sampling in the structure elucidation of small molecule compounds—an instantiation using fuziline
Li-li ZHANG ; Ke ZHANG ; Jie LIU ; Chun-wang MENG ; Rui FENG ; Liang XIONG
Acta Pharmaceutica Sinica 2025;60(1):218-224
Two-dimensional nuclear magnetic resonance (2D NMR) is a widely used technique for structural analysis of small molecular compounds. It can obtain information about the hydrogen-hydrogen correlation, hydrogen-carbon single bond correlation, hydrogen-carbon remote correlation, and hydrogen-hydrogen spatial arrangement of compounds. Thus, 2D NMR has an irreplaceable role in the structure elucidation of small molecular products. However, the sample amount of trace components in phytochemical research is very low, and the traditional sampling method (uniform sampling) has problems of poor spectral quality and too long measure time. Increasing the number of scans results in several hours of the acquisition time for a single two-dimensional spectrum, which in turn causes strain on the NMR machine. The non-uniform sampling (NUS) technique can shorten the acquisition time to a large extent and not affect the quality of 2D NMR data, which greatly improves the efficiency of 2D NMR acquisition. In this paper, fuziline, a small molecular compound in the lateral roots of
9.Relationship between peer victimization and depressive symptoms among secondary vocational health school students: the chain mediating role of positive mental health and social media addiction
Houyi LI ; Chun XU ; Shasha HU ; Bo XIANG ; Kezhi LIU
Sichuan Mental Health 2025;38(2):159-165
BackgroundStudents in secondary vocational health school are at the age of puberty and prone to depressive symptoms. Peer victimization and social media addiction are found to be crucial in influencing the development of depression, and positive mental health has been proven to alleviate depressive symptoms, whereas there remains a striking lack of research on the mediating role of positive mental health and social media addiction in the relationship between peer victimization and depressive symptoms among secondary vocational health school students. ObjectiveTo explore the relationship between peer victimization and depressive symptoms and investigate the mediating role of positive mental health and social media addiction, so as to provide references for the prevention of depression among secondary vocational health school students. MethodsFrom October to December 2020, a cluster sampling framework was utilized to recruit 7 307 students from a secondary vocational health school in Luzhou City, Sichuan Province. Assessments were performed using Multidimensional Peer Victimization Scale (MPVS), Warwick-Edinburgh Mental Well-being Scale (WEMWBS), Bergen Social Media Addiction Scale (BSMAS) and Patient Health Questionnaire Depression Scale-9 item (PHQ-9). Spearman correlation analysis was calculated to determine correlations between scores of scales, Process 4.0 was employed to test the mediation effect, and the bias-corrected Bootstrap procedure was used to test the significance of the mediation effect. ResultsA total of 7 044 (96.40%) valid questionnaires were collected. And 4 391(62.34%)students were found to have depressive symptoms. Correlation analysis revealed that PHQ-9 score was positively correlated with BSMAS score and MPVS score (r=0.404, 0.506, P<0.01). WEMWBS score was negatively correlated with PHQ-9 score, BSMAS score and MPVS score (r=-0.587, -0.259, -0.358, P<0.01). BSMAS score was positively correlated with MPVS score (r=0.328, P<0.01). Positive mental health played a mediating role in the relationship between peer victimization and depressive symptoms, with an indirect effect value of 0.130 (95% CI: 0.119~0.141), accounting for 30.81% of the total effect. Social media addiction also mediated the relationship between peer victimization and depressive symptoms, with an indirect effect value of 0.052 (95% CI: 0.045~0.059), accounting for 12.34% of the total effect. Positive mental health and social media addiction exhibited a chained mediation effect on the relationship between peer victimization and depressive symptoms, with an indirect effect value of 0.012 (95% CI: 0.010~0.014) and accounting for 2.84% of the total effect. ConclusionPeer victimization can affect the presence of depressive symptoms among secondary vocational health school students both directly and indirectly through either separate or chained mediation of positive mental health and social media addiction.
10.Analysis of Mechanism of Xingpi Capsules in Treatment of Functional Dyspepsia Based on Transcriptomics
Rongxin ZHU ; Mingyue HUANG ; Keyan WANG ; Xiangning LIU ; Yinglan LYU ; Gang WANG ; Fangfang RUI ; Qiong DENG ; Jianteng DONG ; Yong WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):164-172
ObjectiveTo investigate the ameliorative effect of Xingpi capsules on functional dyspepsia(FD) and the potential mechanism. MethodsSixty SPF-grade male SD neonatal rats(7 days old) were randomly divided into the normal group(n=12) and the modeling group(n=48), and the FD model was prepared by iodoacetamide gavage in the modeling group. After the model was successfully prepared, the rats in the modeling group were randomly divided into the model group, the low-dose and high-dose groups of Xingpi capsules(0.135, 0.54 g·kg-1) and the domperidone group(3 mg·kg-1), with 12 rats in each group. Rats in the normal and model groups were gavaged with distilled water, and rats in the rest of the groups were gavaged with the corresponding medicinal solution, once a day for 7 d. The general survival condition of the rats was observed, and the water intake and food intake of the rats were measured, the gastric emptying rate and the small intestinal propulsion rate were measured at the end of the treatment, the pathological damage of the rat duodenum was examined by hematoxylin-eosin(HE) staining, and the expressions of colonic tight junction protein(Occludin) and zonula occludens protein-1(ZO-1) were detected by immunofluorescence. The differentially expressed genes in the duodenal tissues of the model group and the normal group, and the high-dose group of Xingpi capsules and the model group were detected by transcriptome sequencing after the final administration, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were carried out. The transcriptomic results were validated by Western blot, immunofluorescence, and real-time fluorescence quantitative polymerase chain reaction(Real-time PCR), and the active ingredients of Xingpi capsules were screened for molecular docking with the key targets. ResultsCompared with the normal group, the general survival condition of rats in the model group was poorer, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly reduced(P<0.05), inflammatory infiltration was seen in duodenal pathology, and the fluorescence intensities of Occludin and ZO-1 in the colon were significantly reduced(P<0.01). Compared with the model group, the general survival condition of rats in the high-dose group of Xingpi capsules improved significantly, and the water intake, food intake, gastric emptying rate and small intestinal propulsion rate were all significantly increased(P<0.05), the duodenal pathology showed a decrease in inflammatory infiltration, and the fluorescence intensities of colonic Occludin and ZO-1 were significantly increased(P<0.01). Transcriptomic results showed that Xingpi capsules might exert therapeutic effects by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) through the key genes such as Slc5a1, Abhd6. The validation results showed that compared with the normal group, the phosphorylation levels of PI3K and Akt proteins, the protein expression level of interleukin(IL)-1β, and the fluorescence intensities of IL-6 and IL-1β were significantly increased in the model group(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3, Slc5a9 and other key genes were significantly increased(P<0.01). Compared with the model group, the phosphorylation levels of PI3K and Akt, the protein expression level of IL-1β and the fluorescence intensities of IL-6 and IL-1β in the high-dose group of Xingpi capsules were significantly reduced(P<0.05, P<0.01), and the mRNA levels of Slc5a1, Abhd6, Mgam, Atp1a1, Slc7a8, Cdr2, Chrm3 and Slc5a9 were significantly reduced(P<0.05). Weighted gene co-expression network analysis and molecular docking results showed that E-nerolidol and Z-nerolidol in Xingpi capsules were well bound to ABDH6 protein, and linarionoside A, valerosidatum and senkirkine were well bound to Slc5a1 protein. ConclusionXingpi capsules can effectively improve the general survival and gastrointestinal motility of FD rats, its specific mechanism may be related to the inhibition of PI3K/Akt signaling pathway to alleviate the low-grade inflammation of duodenum, and E-nerolidol, Z-nerolidol, linarionoside A, valerosidatum and senkirkine may be its key active ingredients.

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