Ageratina adenophora causes intestinal integrity damage in goats via the activation of the MLCK/ROCK signaling pathway.

As a global toxin invasive species, the whole herb of Ageratina adenophora (A. adenophora) contains various sesquiterpenes, which can cause various degrees of toxic reactions characterized by inflammatory damage when ingested by animals. Current studies on the toxicity of A. adenophora have focused on parenchymatous organs such as the liver and spleen, but few studies have been conducted on the intestine as the organ that is first exposed to A. adenophora and digests and absorbs its toxic components. In this study, after feeding goats with 40 % A. adenophora herb powder for 90 d, we found that the intestinal structure of goats showed pathological changes characterized, and the damage to the small intestinal segments was more severe than that of the large intestine. The MLCK/ROCK signaling pathway was activated, the cytoskeleton underwent centripetal contraction, the composition of tight junctions between intestinal epithelial cells was altered table, Occludin, Claudin-1 and Zonula occluden (ZO-1) amount was decreased, and the intestinal mechanical barrier was disrupted. The intestinal damage markers diamine oxidase (DAO) and D-lactate (D-LA) levels were elevated. In addition, we also found that intestinal bacteria translocate and enter the portal vein to colonize the liver and mesenteric lymph nodes. The expression of intestinal pro-inflammatory factors and anti-inflammatory factors was changed, the intestinal immune function was disrupted. The present study is the first to analyze the mechanism of poisoning of A. adenophora from the intestinal tract in compound-gastric animals.

Study on the chronic inflammatory injury caused by Ageratina adenophora on goat liver using metabolomics.

Ageratina adenophora (A. adenophora) is an invasive plant that is harmful to animals. The plants toxic effects on the liver have been studied in detail, however, the inflammation aspects of the hepatotoxicity are rarely discussed in literature. Therefore, in this study, we investigated the level of inflammation and the associated changes in liver metabolism caused by A. adenophora ingestion. Goat were fed with A. adenophora powder which accounts for 40% of the forage for 90 d. After the feeding period, the liver tissues were collected and the level of inflammation was detected using H & E staining and the changes in metabolites by LC-MS/MS. The results indicated that A. adenophora changes the liver metabolites, The test group shown 153 different metabolites in liver of which 71 were upregulated and 82 down regulated. We also found two differential metabolic pathways: neuroactive ligand-receptor interaction and pyrimidine metabolism. The changes in the pathway suggested an association with inflammation and with pathological processes such as oxidative stress and apoptosis. In addition, we observed an increase in the levels of serum liver function indexes (AST and ALT), indicating the liver injury. Furthermore, inflammatory cell infiltration and cell degeneration were observed in histopathological sections. In conclusion, this study reveals that A. adenophora causes chronic inflammation and upregulate metabolites related to inflammation in the liver. The study complements the research content of A. adenophora hepatotoxicity and provides a basis for further research by analyzing changes in the liver metabolites.

Ageratina adenophora damages the rumen epithelium via inducing the expression of inflammatory factors in goats.

The aim of this experiment was to investigate the effects of Ageratina adenophora on the expression of epithelium tight junction proteins and inflammatory factors in the rumen of goats. Twelve goats were randomly divided into three groups. The first group was the blank control group (n = 3, C) which was fed normal diet. The second group was fistulas control group (n = 3, RFC), which was fitted with rumen fistulas, and fed normal diet. The third group was the A. adenophora test group (n = 6, AA), which was fitted with rumen fistulas and fed a mixture of 60% of normal diet and 40% of A. adenophora grass powder. The feeding experiment lasted for 90 d, after which all goats were sacrificed and samples were collected from the rumen dorsal sac and ventral sac. The relative expression of mRNA of inflammatory factors in the rumen epithelium (tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ], interleukin 1 beta [IL-1ß], IL-2, IL-4, IL-6, and IL-10) and tight junction protein genes (occludin, claudin-1, and ZO-1) was measured by quantitative real-time fluorescence PCR. Expression of tight junction proteins in the rumen epithelium was measured by Western blot. A correlation was established between the expression of inflammatory factors and tight junction protein genes using Graph Pad Prism. The results showed that A. adenophora caused a significant increase in the mRNA expression levels of TNF-α, IFN-γ, IL-1ß, IL-2, IL-6, and IL-10 in the rumen epithelial (P < 0.05 or P < 0.01). The expression of tight junction proteins at both gene and protein levels was significantly decreased (P < 0.05 or P < 0.01). Furthermore, the correlation analysis revealed that the changes in tight junction protein expression in the test group were closely related to the upregulation of the expression of inflammatory factors TNF-α and IFN-γ in rumen epithelial cells. In conclusion, the expression of inflammatory factors was increased and the expression of tight junction proteins was decreased in goats after feeding on A. adenophora, which caused some damage to the rumen epithelium.

The article aims to investigate the toxic effects of Ageratina adenophora, an invasive plant on the integrity of the rumen epithelium by measuring the changes in the expression of inflammatory factors and tight junction proteins after the consumption of A. adenophora in goats. The results showed that A. adenophora causes damage to the rumen epithelium by increasing the expression of pro-inflammatory markers like TNF-α and IFN-γ and reducing the expression of tight junction proteins such as occludin and claudin-1 in goats.

Hepatotoxicity effects of Ageratina adenophora, as indicated by network toxicology combined with metabolomics and transcriptomics.

Ageratina adenophora (A. adenophora), one of the prominent invasive plants in the Asian continent has shown toxicity in animals. However, studies examining the gene expression and metabolic profiles of animals that ingest A. adenophora have not yet been reported in the literature. Therefore, considering the wide distribution of A. adenophora, it is necessary to elucidate the toxic mechanisms of A. adenophora via multiomics approach. In this study, we identified and evaluated the toxic mechanisms of action associated with bioactive compounds in A. adenophora by using network toxicology studies combined with metabolomics and transcriptomics and found that 2-deoxo-2-(acetyloxy)- 9-oxoageraphorone, 10Hß-9-oxo-agerophorone, 10Hα-9-oxo-agerophorone, nerolidol, 9-oxo-10,11-dehydro-agerophorone were the main active toxic compounds in A. adenophora. In addition, using metabolomics approach we identified differential metabolites such as L-pyroglutamic acid, 1-methylhistidine, prostaglandin F2alpha and hydrocortisone from A. adenophora and these metabolites were involved in amino acid metabolism, lipid metabolism and signal conducting media regulation. Based on network toxicological analysis, we observed that, A. adenophora can affect the Ras signaling, Phospholipase D signaling and MAPK signaling pathways by regulating EGFR, PDGFRB, KIT and other targets. From the results of this study we concluded that A. adenophora induces liver inflammatory damage by activating the EGFR expression and Ras/Raf/MEK/ERK signaling pathways as well as affect nutrients metabolism and neuron conduction.

Network pharmacology- and molecular docking-based analyses of the antihypertensive mechanism of Ilex kudingcha.

Herein, network pharmacology was used to identify the active components in Ilex kudingcha and common hypertension-related targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted, and molecular docking was performed to verify molecular dynamic simulations. Six active components in Ilex kudingcha were identified; furthermore, 123 target genes common to hypertension were identified. Topological analysis revealed the strongly associated proteins, with RELA, AKT1, JUN, TP53, TNF, and MAPK1 being the predicted targets of the studied traditional Chinese medicine. In addition, GO enrichment analysis revealed significant enrichment of biological processes such as oxidative stress, epithelial cell proliferation, cellular response to chemical stress, response to xenobiotic stimulus, and wound healing. Furthermore, KEGG enrichment analysis revealed that the genes were particularly enriched in lipid and atherosclerosis, fluid shear stress and atherosclerosis, and other pathways. Molecular docking revealed that the key components in Ilex kudingcha exhibited good binding potential to the target genes RELA, AKT1, JUN, TP53, TNF, and IL-6. Our study results suggest that Ilex kudingcha plays a role in hypertension treatment by exerting hypolipidemic, anti-inflammatory, and antioxidant effects and inhibiting the transcription of atherosclerosis-related genes.

Endophytic Fungi Isolated from Ageratina adenophora Exhibits Potential Antimicrobial Activity against Multidrug-Resistant Staphylococcus aureus.

Multidrug-resistant bacteria such as Staphylococcus aureus (MRSA) cause infections that are difficult to treat globally, even with current available antibiotics. Therefore, there is an urgent need to search for novel antibiotics to tackle this problem. Endophytes are a potential source of novel bioactive compounds; however, the harnessing of novel pharmacological compounds from endophytes is infinite. Therefore, this study was designed to identify endophytic fungi (from Ageratina adenophora) with antibacterial activity against multidrug-resistant bacteria. Using fungal morphology and ITS-rDNA, endophytic fungi with antibacterial activities were isolated from A. adenophora. The results of the ITS rDNA sequence analysis showed that a total of 124 morphotype strains were identified. In addition, Species richness (S, 52), Margalef index (D/, 7.3337), Shannon-Wiener index (H/,3.6745), and Simpson's diversity index (D, 0.9304) showed that A. adenophora have abundant endophytic fungi resources. Furthermore, the results of the agar well diffusion showed that the Penicillium sclerotigenum, Diaporthe kochmanii, and Pestalotiopsis trachycarpicola endophytic fungi's ethyl acetate extracts showed moderate antibacterial and bactericidal activities, against methicillin-resistant Staphylococcus aureus (MRSA) SMU3194, with a MIC of 0.5-1 mg/mL and a MBC of 1-2 mg/mL. In summary, A. adenophora contains endophytic fungi resources that can be pharmacologically utilized, especially as antibacterial drugs.