1.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P0.01), significantly decreased fractional shortening (FS) (P0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P0.05, P0.01), significantly increased FS (P0.05, P0.01), significantly decreased LVDD and LVDS (P0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P0.01), and significantly decreased BV at high, medium, and low shear rates (P0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P0.05, P0.01), while HDL levels were significantly decreased (P0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P0.05, P0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P0.05, P0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P0.05, P0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
2.Ameliorative Effect of Wendantang Combined with Danshenyin and Dushentang on Ischemic Heart Disease with Phlegm-stasis Syndrome in Mice Based on Circulating Monocytes
Fenghe YANG ; Ziqi TIAN ; Zhiqian SONG ; Shitao PENG ; Wenjie LU ; Tao LIN ; Chun WANG ; Zhangchi NING
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):22-32
ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang (WDD) on mice with ischemic heart disease (IHD) presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group, WDD low-dose group (WDD-L), WDD medium-dose group (WDD-M), WDD high-dose group (WDD-H), and atorvastatin calcium tablet group, with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91, 17.81, 35.62 g·kg-1, and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg-1, twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration, the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin (HE) staining. Serum N-terminal pro-B-type natriuretic peptide (pro-BNP) content was measured by enzyme-linked immunosorbent assay (ELISA). Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group, model serum group, WDD-L drug-containing serum group, WDD-M drug-containing serum group, and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group, the model group showed a significantly increased cardiac index (P<0.01), significantly decreased fractional shortening (FS) (P<0.01), and significantly increased left ventricular end-diastolic internal diameter (LVDD) and left ventricular end-systolic internal diameter (LVDS) (P<0.01). Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated (P<0.01), and whole-blood viscosity (BV) at high, medium, and low shear rates was significantly increased (P<0.01). Compared with the model group, the WDD groups showed significantly reduced cardiac index (P<0.05, P<0.01), significantly increased FS (P<0.05, P<0.01), significantly decreased LVDD and LVDS (P<0.01), markedly improved cardiomyocyte morphology, significantly reduced inflammatory infiltration, significantly decreased serum pro-BNP levels (P<0.01), and significantly decreased BV at high, medium, and low shear rates (P<0.01), with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group, TC, TG, and LDL levels were significantly increased in the model group (P<0.05, P<0.01), while HDL levels were significantly decreased (P<0.05). After WDD-H treatment, TC, TG, and LDL levels were significantly reduced and HDL levels were significantly increased in mice (P<0.05, P<0.01). Compared with the sham-operation group, classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group (P<0.01), whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased (P<0.01). After WDD administration, all circulating monocyte subsets in blood and bone marrow were significantly alleviated (P<0.05, P<0.01), with the WDD-M group showing the optimal effect. In vitro, compared with the blank group, CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group (P<0.01), and CD36 expression was significantly upregulated on RAW264.7 cells (P<0.01). Compared with the model serum group, all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation (P<0.01). WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines (P<0.05, P<0.01), with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.
3.Comparison of Wild and Cultivated Gardeniae Fructus Based on Traditional Quality Evaluation
Yuanjun SHANG ; Bo GENG ; Xin CHEN ; Qi WANG ; Guohua ZHENG ; Chun LI ; Zhilai ZHAN ; Junjie HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):225-234
ObjectiveBased on traditional quality evaluation of Gardeniae Fructus(GF) recorded in historical materia medica, this study systematically compared the quality differences between wild and cultivated GF from morphological characteristics, microscopic features, and contents of primary and secondary metabolites. MethodsVernier calipers and analytical balances were used to measure the length, diameter and individual fruit weight of wild and cultivated GF, and the aspect ratio was calculated. A colorimeter was used to determine the chromaticity value of wild and cultivated GF, and the paraffin sections of them were prepared by safranin-fast green staining and examined under an optical microscope to observe their microstructure. Subsequently, the contents of water-soluble and alcohol-soluble extracts of wild and cultivated GF were detected by hot immersion method under the general rule 2201 in volume Ⅳ of the 2020 edition of the Pharmacopoeia of the People's Republic of China, the starch content was measured by anthrone colorimetric method, the content of total polysaccharides was determined by phenol-sulfuric acid colorimetric method, the sucrose content was determined by high performance liquid chromatography coupled with evaporative light scattering detection(HPLC-ELSD), and the contents of representative components in them were measured by ultra-performance liquid chromatography(UPLC). Finally, correlation analysis was conducted between quality traits and phenotypic traits, combined with multivariate statistical analysis methods such as principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA), key differential components between wild and cultivated GF were screened. ResultsIn terms of traits, the wild GF fruits were smaller, exhibiting reddish yellow or brownish red hues with significant variation between batches. While the cultivated GF fruits are larger, displaying deeper orange-red or brownish red. The diameter and individual fruit weight of cultivated GF were significantly greater than those of wild GF, while the blue-yellow value(b*) of wild GF was significantly higher than that of cultivated GF. In the microstructure, the mesocarp of wild GF contained numerous scattered calcium oxalate cluster crystals, while the endocarp contained stone cell class round, polygonal or tangential prolongation, undeveloped seeds were visible within the fruit. In contrast, the mesocarp of cultivated GF contained few calcium oxalate cluster crystals, or some batches exhibited extremely numerous cluster crystals. The stone cells in the endocarp were predominantly round-like, with the innermost layer arranged in a grid pattern. Seeds were basically mature, and only a few immature seeds existed in some batches. Regarding primary metabolite content, wild GF exhibited significantly higher total polysaccharide level than cultivated GF(P<0.01). In category-specific component content, wild GF exhibited significantly higher levels of total flavonoids and total polyphenols compared to cultivated GF(P<0.01). Analysis of 12 secondary metabolites revealed that wild GF exhibited significantly higher levels of Shanzhiside, deacetyl asperulosidic acid methyl ester, gardenoside and chlorogenic acid compared to cultivated GF(P<0.01). Conversely, the contents of genipin 1-gentiobioside, geniposide and genipin were significantly lower in wild GF(P<0.01). ConclusionThere are significant differences between wild and cultivated GF in terms of traits, microstructure, and contents of primary and secondary metabolites. At present, the quality evaluation system of cultivated GF remains incomplete, and this study provides a reference for guiding the production of high-quality GF medicinal materials.
4.Construction and practice of the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine
Zhipeng WU ; Yuqin ZHANG ; Chun YAO ; Minggang WANG ; Na WANG ; Mengru PENG ; Ningfang MO ; Yaqing ZHENG ; Rongzhen ZHANG ; Dewen MAO
Journal of Clinical Hepatology 2025;41(2):370-374
Hepatic encephalopathy is a difficult and critical disease with rapid progression and limited treatment methods in the field of liver disease, and it is urgently needed to make breakthroughs in its pathogenesis. Selection of appropriate prevention and treatment strategies is of great importance in delaying disease progression and reducing the incidence and mortality rates. This article reviews the theory of “turbid toxin pathogenesis” and related prevention and treatment strategies for hepatic encephalopathy in traditional Chinese medicine/Zhuang medicine, proposes a new theory of “turbid toxin pathogenesis”, analyzes the scientific connotations of “turbid”, “toxin”, and the theory of “turbid toxin pathogenesis”, and constructs the “four-step” prevention and treatment strategies for hepatic encephalopathy, thereby establishing the new clinical prevention and treatment regimen for hepatic encephalopathy represented by “four prescriptions and two techniques” and clarifying the effect mechanism and biological basis of core prescriptions and techniques in the prevention and treatment of hepatic encephalopathy, in order to provide a reference for the prevention and treatment of hepatic encephalopathy.
5.Role of autophagy in treatment of paracetamol-induced liver injury
Guojing XING ; Lifei WANG ; Longlong LUO ; Xiaofeng ZHENG ; Chun GAO ; Xiaohui YU ; Jiucong ZHANG
Journal of Clinical Hepatology 2025;41(2):389-394
N-acetyl-p-aminophenol (APAP) is an antipyretic analgesic commonly used in clinical practice, and APAP overdose can cause severe liver injury and even death. In recent years, the incidence rate of APAP-induced liver injury (AILI) tends to increase, and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI, involving the mechanisms such as APAP protein conjugates, oxidative stress, JNK activation, mitochondrial dysfunction, inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI, in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.
6.The Impairment Attention Capture by Topological Change in Children With Autism Spectrum Disorder
Hui-Lin XU ; Huan-Jun XI ; Tao DUAN ; Jing LI ; Dan-Dan LI ; Kai WANG ; Chun-Yan ZHU
Progress in Biochemistry and Biophysics 2025;52(1):223-232
ObjectiveAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties with communication and social interaction, restricted and repetitive behaviors. Previous studies have indicated that individuals with ASD exhibit early and lifelong attention deficits, which are closely related to the core symptoms of ASD. Basic visual attention processes may provide a critical foundation for their social communication and interaction abilities. Therefore, this study explores the behavior of children with ASD in capturing attention to changes in topological properties. MethodsOur study recruited twenty-seven ASD children diagnosed by professional clinicians according to DSM-5 and twenty-eight typically developing (TD) age-matched controls. In an attention capture task, we recorded the saccadic behaviors of children with ASD and TD in response to topological change (TC) and non-topological change (nTC) stimuli. Saccadic reaction time (SRT), visual search time (VS), and first fixation dwell time (FFDT) were used as indicators of attentional bias. Pearson correlation tests between the clinical assessment scales and attentional bias were conducted. ResultsThis study found that TD children had significantly faster SRT (P<0.05) and VS (P<0.05) for the TC stimuli compared to the nTC stimuli, while the children with ASD did not exhibit significant differences in either measure (P>0.05). Additionally, ASD children demonstrated significantly less attention towards the TC targets (measured by FFDT), in comparison to TD children (P<0.05). Furthermore, ASD children exhibited a significant negative linear correlation between their attentional bias (measured by VS) and their scores on the compulsive subscale (P<0.05). ConclusionThe results suggest that children with ASD have difficulty shifting their attention to objects with topological changes during change detection. This atypical attention may affect the child’s cognitive and behavioral development, thereby impacting their social communication and interaction. In sum, our findings indicate that difficulties in attentional capture by TC may be a key feature of ASD.
7.Advances in oral distant targeted nanodelivery systems
Min SUN ; Chuan-sheng HUANG ; Li-ping WANG ; Xu-li RUAN ; Yun-li ZHAO ; Xin-chun WANG
Acta Pharmaceutica Sinica 2025;60(1):72-81
Due to patient compliance and convenience, oral medication is likely the most common and acceptable method of drug administration. However, traditional dosage forms such as tablets or capsules may lead to low drug bioavailability and poor therapeutic efficiency. Therefore, with advancements in material science and micro/nano manufacturing technology, various carriers have been developed to enhance drug absorption in the gastrointestinal tract. In this context, we initially discuss the key biological factors that hinder drug transport and absorption (including anatomical, physical, and biological factors). Building on this foundation, recent progress in both conventional and innovative oral drug delivery routes aimed at improving drug bioavailability and targeting is reviewed. Finally, we explore future prospects for oral drug delivery systems as well as potential challenges in clinical translation.
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.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.
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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