Network pharmacology and molecular docking reveal zedoary turmeric-trisomes in Inflammatory bowel disease with intestinal fibrosis

BACKGROUND Inflammatory bowel disease(IBD) is a complex chronic IBD that is closely associated with risk factors such as environment, diet, medications and lifestyle that may influence the host microbiome or immune response to antigens. At present, with the increasing incidence of IBD worldwide, it is of great significance to further study the pathogenesis of IBD and seek new therapeutic targets. Traditional Chinese medicine(TCM) treatment of diseases is characterized by multiple approaches and multiple targets and has a long history of clinical application in China. The mechanism underlying the effect of zedoary turmerictrisomes on inducing mucosal healing in IBD is not clear.AIM To explore the effective components and potential mechanism of zedoary turmeric-trisomes in the treatment of IBD with intestinal fibrosis using network pharmacology and molecular docking techniques.METHODS The chemical constituents and targets of Rhizoma zedoary and Rhizoma sanarum were screened using the TCMSP database. The GeneCards database was searched to identify targets associated with intestinal fibrosis in IBD. The intersection of chemical component targets and disease targets was obtained using the Venny 2.1 online analysis platform, and the common targets were imported into the STRING 11.0 database to construct a protein interaction regulatory network. A “zedoary turmeric-trisomes-chemical composition-target-disease” network diagram was subsequently constructed using Cytoscape 3.7.2 software, and the topological properties of the network were analyzed using the “Network Analysis” plug-in. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses of the common targets were performed using the DAVID 6.8 database to elucidate the mechanism of zedoary turmeric-trisomes in the treatment of IBD. Subsequently, molecular docking of the compounds and targets with the highest intermediate values in the “zedoary turmeric-trisomes-chemical composition-target-disease” network was performed using Sybyl-x 2.1.1 software.RESULTS A total of 5 chemical components with 60 targets were identified, as well as 3153 targets related to IBD and 44 common targets. The protein-protein interaction network showed that the core therapeutic targets included JUN, MAPK14, CASP3, AR, and PTGS2. The GO enrichment analysis identified 759 items, and the KEGG enrichment analysis yielded 52 items, including the cancer pathway, neuroactive ligand-receptor interaction, hepatitis B, and the calcium signaling pathway, reflecting the complex biological processes of the multicomponent, multitarget and multipathway treatment of diseases with zedoary turmeric-trisomes. Molecular docking showed that the compound bonded with the target through hydrogen bond interactions and exhibited good docking activity.CONCLUSION This study identified the potential mechanism of action of zedoary turmeric-trisomes in the treatment of inflammatory bowel fibrosis using network pharmacology and molecular docking technology, providing a scientific basis for further expansion of their clinical use.

Studies on the Formation and Transmission of n + 1 Gametes of Cabbage Primary Trisomics

The transmission rate of n ＋ 1 gamete is an important parameter for the genetic analysis of trisomics. To correctly use the trisomics of the cabbage to carry out gene orientation and other genetic studies, the n ＋ 1 gamete transmission rates by female parent and by male parent were determined. The results showed that the n ＋ 1 gamete transmission rates were 15.28% for tri-1, 12.68% for tri-2, 12.31% for tri-3, 30.51% for tri-4, 22.81% for tri-5, 7.46% for tri-6, 5.36% for tri-7, 42.37% for tri-8, and 9.23% for tri-9 by female parent, and were 12.12% for tri-1, 12.33% for tri-2, 7.81% for tri-3, 4.76% for tri-4, 8.93% for tri-5, 10.94% for tri-6, 1.54% for tri-7, 2.94% for tri-8, and 13.04% for tri-9 by male parent. The main factors affecting the male n ＋ 1 gamete formation and transmission were the rate of trivalent formation at prophase Ⅰ, the rate of 9-9-10-10 division at anaphase Ⅱ, and the pollen viability.

Obtaining and Cytological Identification of a Set of Primary Trisomics in Cabbage

Selection of primary trisomics of the cabbage （Brassica oleracea var.capitata L） forms an important basis for gene chromosome mapping and for other genetic studies. The cabbage self-fertilization line - 9601 was used as material, using the root-tip cell chromosome number and pollen mother cell chromosome number identification and karyotype analysis to select the primary trisomics from the progenies of 3x x 2x in the cabbage. Many aneuploid plants with one or two extra chromosomes were obtained and a set of primary trisomics （Tri-1, Tri-2, Tri-3, Tri-4, Tri-5, Tri-6, Tri-7, Tri-8, and Tri-9, in which the Tri-1 and Tri-4 were from 2n＋2 plants and others from 2n＋ 1 plants） was acquired from these plants. Each trisomic exhibited some unique features, such as plant height, plant type, leaf type, size of flower bud, and inflorescence. The triploid crossing by the diploid is a convenient and effective way to select trisomics in the cabbage.

Determination of n+1 Gamete Transmission Rate of Trisomics and Location of Gene Controlling 2n Gamete Formation in Chinese Cabbage(Brassica rapa)

A set of trisomics of Chinese cabbage was used for determining the n-I-1 gamete transmission rate and locating the gene controlling 2n gamete formation on the corresponding chromosome. The results showed that the transmission rates of extra chromosomes in different trisomics varied from 0% to 15.38% by male gametes and from 0% to 17.39% by female gametes. Of the nine F2 populations derived from the hybridizations between each trisomic and Bp058 （2n gamete material）, only Tri- 4xBp058 showed that the segregation ratio of plants without 2n gamete formation to plants with 2n gamete formation was 10.38：1, which fitted the expected segregation ratio of the trisomics （AAa） based on the 7.37% of n＋l gamete transmission through female and 5.88% through male. In other populations the segregation ratios varied from 2.48：1 to 3.72：1, which fitted the expected 3：1 segregation ratio of the bisomics （Aa）. These results suggested that the gene controlling 2n gamete formation in Chinese cabbage Bp058 was located on chromosome 4. Further trisomic analysis based on the chromosome segregation and the incomplete stochastic chromatid segregation indicated that the gene locus was tightly linked to the centromere.

STUDIES ON DUPLICATION OF A GIVEN CHROMOSOMAL SEGMENT IN RICE

The duplication of a given chromosomal segment or a gene locus, especially for the gene of a quantitative character and the multiple allele, is very significant for fixing heterosis, breeding cultivar with good yield and increasing resistance level.