Background: The pathogenesis of inflammatory bowel disease (IBD) is linked to an intricate association of environmental, microbial, and host-related factors. Polysaccharide affects host immunity by regulating the composition and metabolism of gut microbiota is the common mechanism of disease resistance. However, the efficacy and mechanism of Schisandra chinensis polysaccharide (SCP) in the treatment of inflammatory bowel disease have not been studied. Objective: To explore the effect and mechanism of SCP on dextran sodium sulfate (DSS) - induced ulcerative colitis (UC) in mice. Materials/Methods: In this study, we established a mouse model of UC, and used SCP for treatment intervention. The biochemical indexes related to inflammation were determined by ELISA kit, and the therapeutic effect of SCP on UC was clarified. Then, 16S rDNA sequencing was used to study the effect of SCP on the composition and diversity of gut microbiota. At the same time, GC-MS was used to determine the content of short chain fatty acids in intestinal contents. Finally, the relationship among gut microbiota, short chain fatty acids and inflammatory factors was analyzed, and to comprehensively explain the effect and mechanism of SCP on UC. Results: The results showed that SCP could significantly improve the physiological state of UC mice and regulate the level of inflammatory factors to normal levels. Meanwhile, SCP could significantly regulate the imbalance of gut microbiota and increase the content of SCFAs. In addition, the results of the correlation between gut microbiota and SCFAs showed that butyric acid, isobutyric acid and valeric acid had the highest correlation with gut microbiota. Conclusion: In conclusion, this research showed that SCP can inhibit inflammatory bowel disease by regulating the composition and metabolism of gut microbiota, and indicating that SCP may be used as adjuvant therapy for IBD patients.
Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.
Rhizome of Curcuma wenyujin, which is called EZhu in China, is a traditional Chinese medicine used to treat blood stasis for many years. However, the underlying mechanism of EZhu is not clear at present. In this study, plasma metabolomics combined with network pharmacology were used to elucidate the therapeutic mechanism of EZhu in blood stasis from a metabolic perspective. The results showed that 26 potential metabolite markers of acute blood stasis were screened, and the levels were all reversed to different degrees by EZhu preadministration. Metabolic pathway analysis showed that the improvement of blood stasis by Curcuma wenyujin rhizome was mainly related to lipid metabolism (linoleic acid metabolism, ether lipid metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism) and amino acid metabolisms (tryptophan metabolism, lysine degradation). The component-target-pathway network showed that 68 target proteins were associated with 21 chemical components in EZhu. Five metabolic pathways of the network, including linoleic acid metabolism, sphingolipid metabolism, glycerolipid metabolism, arachidonic acid metabolism, and steroid hormone biosynthesis, were consistent with plasma metabolomics results. In conclusion, plasma metabolomics combined with network pharmacology can be helpful to clarify the mechanism of EZhu in improving blood stasis and to provide a literature basis for further research on the therapeutic mechanism of EZhu in clinical practice.
Schisandra chinensis (SC) is a well-known important traditional Chinese medicine (TCM) that has been used to treat liver disease in China for a long time. However, its overall effects and mechanism of action are unclear. The present study aimed to explore the potential mechanism of SC in protection against alcoholic liver injury (ALI). In this research, to enable a full assessment of metabolic changes in ALI in Sprague-Dawley rats and to increase our understanding of physiological changes in normal and pathological states, ultra-high performance liquid chromatography combined with quadrupole time of flight mass spectrometry (UHPLC-Q/TOF-MS) was used to probe potential biomarkers to learn more about ALI and to evaluate the overall effect of SC for ALI in rats. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to investigate global metabolomic alterations and to evaluate the therapeutic effects of SC in rats. The component–target–pathway network of SC was then constructed on the basis of the network pharmacology, and the liver injury-relevant signaling pathways were thus dissected and validated. The results showed that SC has conspicuous therapeutic efficacy for ALI, as suggested by the results of the pathological section and biochemical index assays, such as those for Alanine aminotransferase (ALT), Aspartate transaminase (AST), Alkaline phosphatase (AKP), γ-glutamyl transferase (γ-GT/GGT), Reactive oxygen species (ROS), and Malondialdehyde (MDA). Furthermore, 21 kinds of potential biomarkers were identified in plasma samples of ALI rats, and 20 kinds of potential biomarkers were identified in their bile samples. The biomarkers were mainly related to inflammation and dysfunctions of amino acids and energy metabolism. The recovery of these dysfunctions partly led to the curative effect of SC on ALI.