The Role of Oxymatrine in Amelioration of Acute Lung Injury Subjected to Myocardial I/R by Inhibiting Endoplasmic Reticulum Stress in Diabetic RatsRead the full article
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Effect of Sheng-Jiang Powder on Gut Microbiota in High-Fat Diet-Induced NAFLD
Background and Aims. Nonalcoholic fatty liver disease (NAFLD) is an alarming global health problem that is predicted to be the major cause of cirrhosis, hepatocellular carcinoma, and liver transplantation by next decade. Gut microbiota have been revealed playing an important role in the pathogenesis of NAFLD. Sheng-Jiang Powder (SJP), an empirical Chinese medicine formula to treat NAFLD, showed great hepatoprotective properties, but the impact on gut microbiota has never been identified. Therefore, we performed this study to investigate the effect of SJP on gut microbiota in NAFLD mice. Methods. NAFLD was induced by 12 weeks’ high-fat diet (HFD) feeding. Mice were treated with SJP/normal saline daily for 6 weeks. Blood samples were obtained for serum biochemical indices and inflammatory cytokines measurement. Liver tissues were obtained for pathological evaluation and oil red O staining. The expression of lipid metabolism-related genes was quantified by RT-PCR and Western blotting. Changes in gut microbiota composition were analyzed by the 16s rDNA sequencing technique. Results. HFD feeding induced significant increase in bodyweight and serum levels of TG, TC, ALT, and AST. The pathological examination revealed obvious hepatic steatosis in HFD feeding mice. Coadministration of SJP effectively protected against bodyweight increase and lipid accumulation in blood and liver. Increased expression of PPARγ mRNA was observed in HFD feeding mice, but a steady elevation of PPARγ protein level was only found in SJP-treated mice. Meanwhile, the expression of FASN was much higher in HFD feeding mice. Microbiome analysis revealed obvious changes in gut microbiota composition among diverse groups. SJP treatment modulated the relative abundance of short-chain fatty acids (SCFAs) producing bacteria, including norank-f-Erysipelotrichaceae and Roseburia. Conclusions. SJP is efficient in attenuating HFD-induced NAFLD, and it might be partly attributed to the regulation of gut microbiota.
Hydroethanolic Extract from Bridelia atroviridis Müll. Arg. Bark Improves Haematological and Biochemical Parameters in Nicotinamide-/Streptozotocin-Induced Diabetic Rats
Bridelia atroviridis Müll. Arg. (B. atroviridis) is a plant used in Cameroonian traditional medicine to manage diabetes. The effects of hydroethanolic barks extract from B. atroviridis were evaluated on diabetes disorders including hematology, inflammatory, and oxidative stress parameters. The in vitro antioxidant capacity of the hydroethanolic bark extract (70 : 30) was evaluated. Nicotinamide-/streptozotocin-induced diabetic rats were daily treated with the B. atroviridis extract for fifteen days. Glycemia were evaluated every 5 days, insulin sensibility test was performed, and haematological, inflammatory, and oxidative stress parameters were analysed. Histomorphometry of the pancreas was realized. The extract was able to scavenge free radicals in vitro and decrease significantly the blood glucose levels. The treatment resulted in a significant alleviation of insulin resistance, anemia, leukocytopenia, and thrombocytopenia observed in untreated diabetic rats. The extract significantly decreased proinflammatory cytokines TNF-α, IL-1β, and IL-10. The rate of reduced glutathione was increased in the pancreas, whereas the catalase activity and nitrite concentration were decreased. Diabetic control showed a reduced size of Langerhans islet, whereas the size of islets was large in treated groups. The hydroethanolic extract of B. atroviridis was able to improve glycemia and alleviate haematological and inflammatory parameters disorders observed in diabetic conditions, probably due to its antidiabetic, anti-inflammatory, and antioxidant capacities.
Network Pharmacology-Based Study on the Mechanism of Gegen Qinlian Decoction against Colorectal Cancer
Purpose. Gegen Qinlian decoction (GQD) has been used to treat gastrointestinal diseases, such as diarrhea and ulcerative colitis (UC). A recent study demonstrated that GQD enhanced the effect of PD-1 blockade in colorectal cancer (CRC). This study used network pharmacology analysis to investigate the mechanisms of GQD as a potential therapeutic approach against CRC. Materials and Methods. Bioactive chemical ingredients (BCIs) of GQD were collected from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. CRC-specific genes were obtained using the gene expression profile GSE110224 from the Gene Expression Omnibus (GEO) database. Target genes related to BCIs of GQD were then screened out. The GQD-CRC ingredient-target pharmacology network was constructed and visualized using Cytoscape software. A protein-protein interaction (PPI) network was subsequently constructed and analyzed with BisoGenet and CytoNCA plug-in in Cytoscape. Gene Ontology (GO) functional and the Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis for target genes were then performed using the R package of clusterProfiler. Results. One hundred and eighteen BCIs were determined to be effective on CRC, including quercetin, wogonin, and baicalein. Twenty corresponding target genes were screened out including PTGS2, CCNB1, and SPP1. Among these genes, CCNB1 and SPP1 were identified as crucial to the PPI network. A total of 212 GO terms and 6 KEGG pathways were enriched for target genes. Functional analysis indicated that these targets were closely related to pathophysiological processes and pathways such as biosynthetic and metabolic processes of prostaglandins and prostanoids, cytokine and chemokine activities, and the IL-17, TNF, Toll-like receptor, and nuclear factor-kappa B (NF-κB) signaling pathways. Conclusion. The study elucidated the “multiingredient, multitarget, and multipathway” mechanisms of GQD against CRC from a systemic perspective, indicating GQD to be a candidate therapy for CRC treatment.
Fuzheng Huayu Recipe Prevented and Treated CCl4-Induced Mice Liver Fibrosis through Regulating Polarization and Chemotaxis of Intrahepatic Macrophages via CCL2 and CX3CL1
Background. Fuzheng Huayu recipe (FZHY) is an original Chinese patent medicine which was developed and marketed by our institute. It could markedly improve liver tissue inflammation and ameliorate hepatic fibrosis in the clinical study. The intrahepatic macrophages recruitment and polarization play an important role in the progress of liver inflammation and fibrosis. Whether FZHY exerted its antiliver fibrosis effects through regulating intrahepatic macrophages phenotypic ratios is still unknown. This study aims to explore the antifibrosis mechanism of FZHY on regulating the recruitment and polarization of intrahepatic macrophages. Methods. C57/B6 mice were used for the establishment of the CCl4-induced mice liver fibrosis model. Liver inflammation and fibrosis were evaluated by HE and Sirius red staining, hydroxyproline assays, and biochemical tests. The levels of chemokines and inflammatory cytokines in liver tissue were measured by RNA-Seq transcriptome analysis, western blot assay, RT-qPCR, and immunofluorescence assay. The macrophages recruitment and phenotypic polarization were observed by flow cytometry. Results. FZHY significantly improved liver inflammation and reduced liver fibrosis degree. TNF signaling pathway, involved in macrophages recruitment and phenotypic polarization, was discovered by RNA-Seq transcriptome analysis. In TNF signaling pathway, CCL2 expression was significantly decreased and CX3CL1 expression was significantly upregulated by FZHY in liver tissue and primary intrahepatic macrophages. The ratio of proinflammatory hepatic resident macrophage-Kupffer cells (F4/80+CD11b−CD86+) was downregulated by FZHY, while the proportion of anti-inflammatory Kupffer cells (F4/80+CD11b−CD206+) was upregulated. Meanwhile, the ratio of proinflammatory Ly6Chigh macrophages (F4/80+CD11b+Ly6Chigh) which were recruited from blood circulation by CCL2 was reduced by FZHY, while the ratio of restorative Ly6Clow macrophages (F4/80+CD11b+Ly6Clow) which were recruited from blood circulation or induced from Ly6Chigh macrophages polarization by CX3CL1 was significantly increased. Conclusions. FZHY could regulate the recruitment and polarization of intrahepatic macrophages via CCL2 and CX3CL1, so as to play its anti-inflammation and antifibrosis pharmacological effects in the liver.
A Microcosmic Syndrome Differentiation Model for Metabolic Syndrome with Multilabel Learning
Background. Metabolic syndrome (MS) is a complex multisystem disease. Traditional Chinese medicine (TCM) is effective in preventing and treating MS. Syndrome differentiation is the basis of TCM treatment, which is composed of location and/or nature syndrome elements. At present, there are still some problems for objective and comprehensive syndrome differentiation in MS. This study mainly proposes a solution to two problems. Firstly, TCM syndromes are concurrent, that is, multiple TCM syndromes may develop in the same patient. Secondly, there is a lack of holistic exploration of the relationship between microscopic indexes, and TCM syndromes. In regard to these two problems, multilabel learning (MLL) method in machine learning can be used to solve them, and a microcosmic syndrome differentiation model can also be built innovatively, which can provide a foundation for the establishment of the next model of multidimensional syndrome differentiation in MS. Methods. The standardization scale of TCM four diagnostic information for MS was designed, which was used to obtain the results of TCM diagnosis. The model of microcosmic syndrome differentiation was constructed based on 39 physicochemical indexes by MLL techniques, called ML-kNN. Firstly, the multilabel learning method was compared with three commonly used single learning algorithms. Then, the results from ML-kNN were compared between physicochemical indexes and TCM information. Finally, the influence of the parameter k on the diagnostic model was investigated and the best k value was chosen for TCM diagnosis. Results. A total of 698 cases were collected for the modeling of the microcosmic diagnosis of MS. The comprehensive performance of the ML-kNN model worked obviously better than the others, where the average precision of diagnosis was 71.4%. The results from ML-kNN based on physicochemical indexes were similar to the results based on TCM information. On the other hand, the k value had less influence on the prediction results from ML-kNN. Conclusions. In the present study, the microcosmic syndrome differentiation model of MS with MLL techniques was good at predicting syndrome elements and could be used to solve the diagnosis problems of multiple labels. Besides, it was suggested that there was a complex correlation between TCM syndrome elements and physicochemical indexes, which worth future investigation to promote the development of objective differentiation of MS.
Effects of Erbuzhuyu Decoction Combined with Acupuncture on Endometrial Receptivity Are Associated with the Expression of miR-494-3p
Background/Aim. Erbuzhuyu decoction (EBZYD) is a traditional Chinese medicine (TCM) formula and has been used in infertility treatment. Meanwhile, acupuncture is also used to treat female infertility. However, it is unclear whether EBZYD combined with acupuncture has better therapeutic effect. The aim of this study was to explore the effect of EBZYD combined with acupuncture and investigate its mechanism in superovulation mice. Methods. The mice received the treatment of EBZYD, acupuncture, EBZYD combined with acupuncture, or miR-494-3p agomir combined with EBZYD and acupuncture. The blastocysts’ number, endometrial microstructure, and endometrial thickness were observed, followed by the detection of endometrial receptivity-related factors, PI3K/Akt/mTOR pathway-related proteins, and miR-494-3p expression using quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Luciferase reporter assay was performed to confirm the targeting relationship between HOXA10 and miR-494-3p. Results. EBZYD combined with acupuncture treatment could increase the number of blastocysts, pinopodes, endometrial thickness, and the expression of endometrial receptivity-related factors, and the treatment effect of EBZYD combined with acupuncture was better than EBZYD or acupuncture alone. In addition, EBZYD combined with acupuncture treatment activated PI3K/Akt/mTOR pathway and inhibited the expression of miR-494-3p. HOXA10 is one of the target genes of miR-494-3p. Overexpression of miR-494-3p reversed the therapeutic effect of EBZYD combined with acupuncture and suppressed the expression of HOXA10 and the activity of PI3K/Akt/mTOR pathway. Conclusion. This study suggests that EBZYD combined with acupuncture could improve endometrial receptivity in superovulation mice via miR-494-3p/HOXA10 axis.