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.

Pseudorabies virus causes splenic injury via inducing oxidative stress and apoptosis related factors in mice.

Pseudorabies virus (PRV) is an immunosuppressive virus that causes significant damage to the pig industry. This study aimed to investigate the effects of PRV on oxidative stress and apoptotic related in the spleen of mice to provide basis knowledge for further research on the pathogenesis of PRV in mice model. 36 mice were randomly two groups, the control group which only received 200 µL PBS and infection group which was subcutaneously infected with 200 µL of 1 × 103 TCID50/100 µL PRV, respectively. Spleen tissues in each group were collected for further experiments at 48, 72, and 96 h post-infection (hpi). Pathological observation was performed by hematoxylin and eosin Y staining. Biochemical and Flow cytometry methods were used to determine the reactive oxygen species profile and apoptosis of the spleen post-infection and apoptosis detection. In addition, q-PCR and Western blot were adopted to measure the apoptotic conditions of the spleen infected with PRV. The results indicated that the reactive oxygen species (ROS) level in the PRV infection group was remarkedly increased (p < 0.01) at a time-dependent pattern. Furthermore, the Malondialdehyde levels in the spleen of mice in the infection group increased (p < 0.01) in a time-dependent mode. However, the activity of Catalase, Superoxide dismutase, and glutathione peroxidase and the content of Glutathione in the infection group were decreased with the control group (p < 0.01) at a time-dependent manner. In addition, the ratio of splenocyte apoptosis in the infection group significantly increased (p < 0.01) in a time-dependent manner. In conclusion, PRV infection causes apoptosis of the spleen via oxidative stress in mice.

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.

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.

Glycine Nano-Selenium Enhances Immunoglobulin and Cytokine Production in Mice Immunized with H9N2 Avian Influenza Virus Vaccine.

This study was performed to investigate the immune enhancement effect of glycine nano-selenium, a microelement on H9N2 avian influenza virus vaccine (H9N2 AIV vaccine) in mice. Fifty (50) Specific Pathogen Free Kunming mice aged 4−6 weeks (18−20 g Body weight) were randomly divided into five groups: control normal group, which received no immunization + 0.5 mL 0.9% normal saline, positive control group, which received H9N2 AIV vaccine + 0.5 mL 0.9% normal saline, 0.25 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.25 mg/kg selenium solution, 0.5 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 0.5 mg/kg selenium solution, and 1 mg/kg selenium group, which received H9N2 AIV vaccine + 0.5 mL 1 mg/kg selenium solution. Hematoxylin and eosin staining, enzyme linked immunosorbent assay (ELISA), and quantitative real time polymerase chain reaction (qRT-PCR) methods were used to investigate the pathological changes, immunoglobulin levels, and cytokine gene expressions in this study. The results showed that all tested doses (0.25 mg/kg, 0.5 mg/kg and 1.00 mg/kg) of glycine nano-selenium did not lead to poisoning in mice. In addition, when compared to the positive control group, glycine nano-selenium increased the immunoglobin indexes (IgA, IgG, IgM and AIV-H9 IgG in serum) as well as the mRNA levels of IL-1ß, IL-6 and INF-γ in the liver, lungs, and spleen (p < 0.05). In summary, glycine nano-selenium could enhance the efficacy of avian influenza vaccine.

Seasonal Prevalence of Gastrointestinal Parasites in Macaques (Macaca thibetana) at Mount Emei Scenic Area in China.

The aim of the study was to elucidate the prevalence of intestinal parasites in macaques at the Mt. Emei Scenic Area of Sichuan, China. A total of 168 fecal samples were collected from yellow (n = 31), black (n = 19), new (n = 57), Leidongping (n = 57) and Wuxiangang (n = 4) macaques from 2019 to 2020. The fecal samples were tested for various gastrointestinal parasites following the microscopic detection method. The results showed that the total prevalence rate of the intestinal parasite was 51.19% (86/168), whereas the intestinal parasite with the highest prevalence was Gongylonema spp. (26.79%) for helminth and Entamoeba spp. (18.45%) for protozoa. Interestingly, the highest prevalence of intestinal parasites was observed during the summer season (86.21%), and the lowest was observed during the winter season (7.14%). There was a positive correlation observed between the human contact frequency and total prevalence rate of the intestinal parasites (p < 0.05); however, there was no correlation between the human contact frequency and total prevalence of the intestinal parasites at different seasons (p > 0.05). In conclusion, the dominant parasites Gongylonema spp. and Entamoeba spp. cause various diseases that may be transmitted to humans and other animals; therefore, there is a need for a proper management system, such as parasite control measures and population protection in the Mt. Emei Scenic Area of Sichuan, China.

Antibacterial Activity of Two Metabolites Isolated From Endophytic Bacteria Bacillus velezensis Ea73 in Ageratina adenophora.

Ageratina adenophora, as an invasive and poisonous weed, seriously affects the ecological diversity and development of animal husbandry. Weed management practitioners have reported that it is very difficult to control A. adenophora invasion. In recent years, many researchers have focused on harnessing the endophytes of the plant as a useful resource for the development of pharmacological products for human and animal use. This study was performed to identify endophytes with antibacterial properties from A. adenophora. Agar well diffusion method and 16S rRNA gene sequencing technique were used to screen and identify endophytes with antibacterial activity. The response surface methodology and prep- high-performance liquid chromatography were used to determine the optimizing fermentation conditions and isolate secondary metabolites, respectively. UV-visible spectroscopy, infrared spectroscopy, nuclear magnetic resonance, and high-resolution mass spectrum were used to determine the structures of the isolated metabolites. From the experiment, we isolated a strain of Bacillus velezensis Ea73 (GenBank no. MZ540895) with broad-spectrum antibacterial activity. We also observed that the zone of inhibition of B. velezensis Ea73 against Staphylococcus aureus was the largest when fermentation broth contained 6.55 g/L yeast extract, 6.61 g/L peptone, 20.00 g/L NaCl at broth conditions of 7.95 pH, 51.04 h harvest time, and a temperature of 27.97°C. Two antibacterial peptides, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), were successfully extracted from B. velezensis Ea73. These two peptides exhibited mild inhibition against S. aureus and Escherichia coli. Therefore, we isolated B. velezensis Ea73 with antibacterial activity from A. adenophora. Hence, its metabolites, Cyclo (L-Pro-L-Val) and Cyclo (L-Leu-L-Pro), could further be developed as a substitute for human and animal antibiotics.

Bacillus toyonensis SAU-19 and SAU-20 Isolated From Ageratina adenophora Alleviates the Intestinal Structure and Integrity Damage Associated With Gut Dysbiosis in Mice Fed High Fat Diet.

This study was performed to identify potential probiotic endophytes from Ageratina adenophora and evaluate their ameliorating effects on gut injury and integrity damage associated with microbiota dysbiosis in mice fed high fat diet. Using morphological and biochemical tests, and 16S rRNA gene sequencing technique, two bacteria endophytes were identified as strains of Bacillus toyonensis and were named Bacillus toyonensis SAU-19 (GenBank No. MW287198) and Bacillus toyonensis SAU-20 (GenBank No. MW287199). Sixty (60) mice were divided into five groups, group 1 was the negative control fed normal diet (NS), group 2 was fed High fat diet (HF), Group 3 was fed High fat diet + 106 Lactobacillus rhamnosus (LGG), group 4 was fed High fat + 106 Bacillus toyonensis SAU-19 and group 5 fed High fat diet + 106 Bacillus toyonensis SAU-20. After 35 days, histological and immunohistochemistry examination were performed in the ileum tissues. Furthermore, DAO and antioxidants activities were measured in serum, mRNA expressions of tight junction proteins (occludin and ZO-1) and inflammation related cytokines (IL-1ß, TFN-α, IL-2, IL-4, and IL-10) in the ileum tissues as well as sIgA levels and total bacteria (Escherichia coli, Salmonella, Staphylococcus, and Lactobacillus) in the small intestine and cecum content. The results showed an increase in the DAO activity, oxidative stress parameter (MDA), pro-inflammation cytokines (IL-1ß, TFN-α, IL-2), reduce immunity (sIgA), and destroyed intestinal structure and integrity (reduce tight junction proteins) in the high fat diet group and this was associated with destruction of the gut microbiota composition (increasing pathogenic bacteria; E. coli, Salmonella, Staphylococcus and reducing beneficial bacteria, Lactobacillus spp.) in mice (P < 0.05). However, the administration of Bacillus toyonensis SAU-19 and SAU-20 reverted these effects. Our findings indicated that, Bacillus toyonensis SAU-19 and SAU-20 isolated from A. adenophora could prevent the excess weight gain from high fat diet feeding, improved antioxidant status and alleviated the intestine integrity damage as well as reduce the population of enteric bacteria such as E. coli, Salmonella, and S. aureus and increasing the population of beneficial bacteria such as Lactobacillus in the gut of mice fed high fat diet, therefore, can serve as a potential probiotics in humans and animals.

Anti-Inflammatory Activity and Mechanism of Cryptochlorogenic Acid from Ageratina adenophora.

Ageratina adenophora is an invasive plant known for its toxicity to livestock. Current research on this plant has shifted from toxicity prevention to the beneficial utilization of plant resources. This study was performed to investigate the effects and mechanisms of cryptochlorogenic acid (CCGA) isolated from Ageratina adenophora on the inflammatory responses induced by lipopolysaccharide (LPS) in RAW264.7 cells. RAW264.7 cells were pretreated with CCGA (200, 100, and 50 µg/mL) and subsequently stimulated with LPS (1 µg/mL) for 16 h. The cytotoxicity of CCGA was tested using the Cell Counting Kit (CCK8). The mechanism of action of CCGA in attenuating inflammation was also identified using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription-polymerase chain reaction, and Western blot. The results showed that CCGA had a maximal safe concentration of 200 mg/mL. Moreover, CCGA reduced the level of nitric oxide (NO) and iNOS in LPS-induced RAW264.7 cells (p < 0.01). In addition, CCGA reduced the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, IL-6, and IL-8) and cyclooxygenase-2 (COX-2) in LPS-induced RAW264.7 cells at both the mRNA and protein levels (p < 0.01). CCGA prevented the activation of nuclear factor-kappa B (NF-kB) in LPS-induced RAW264.7 cells via the inhibition of IKK and IκB phosphorylation and the degradation of IκB proteins (p < 0.01). This finding indicated that CCGA isolated from A. adenophora may be a potential candidate for the treatment of inflammation-related diseases.

Oral Administration of Bacillus toyonensis Strain SAU-20 Improves Insulin Resistance and Ameliorates Hepatic Steatosis in Type 2 Diabetic Mice.

In this study, the ameliorative effects of Bacillus toyonensis-SAU-20 (B. toyo SAU-20), a new probiotic strain isolated and identified by our laboratory from Ageratina adenophora, on the development of insulin resistance and hepatic steatosis in type 2 diabetic (T2DM) mice was investigated. Thirty Specific-pathogen free Kunming (SPFKM) mice were randomly allocated to three groups: control, high fat diet/streptozotocin (HFD/STZ), and HFD/STZ+B. toyo SAU-20 groups with oral administration of B. toyo SAU-20 for 35 days. Biochemistry parameters, glucose tolerance, and insulin resistance were measured in the blood whereas histological analysis, inflammatory cytokines and lipogenic genes in the liver tissues. The results showed that, the levels of serum glucose, lipid profile, mRNA expression of lipogenic related genes and pro-inflammatory cytokines were significantly increased in T2DM mice. However, after B. toyo SAU-20 administration, the elevation of these parameters was significantly suppressed (P<0.05). In addition, the feeding of B. toyo SAU-20 significantly improved the morphological changes of the liver with significant alleviation of dyslipidemia, oxidative stress status and inflammation (P<0.05) indicating the ameliorating effect of B. toyo SAU-20 in hepatic steatosis in T2DM. Therefore, we concluded that, B. toyo SAU-20 alleviated insulin resistance and hepatic steatosis by improving the lipid profiles, antioxidant status and downregulating lipogenic genes as well as pro-inflammation cytokines expression.

Endophytic Fungi: An Effective Alternative Source of Plant-Derived Bioactive Compounds for Pharmacological Studies.

Plant-associated fungi (endophytic fungi) are a biodiversity-rich group of microorganisms that are normally found asymptomatically within plant tissues or in the intercellular spaces. Endophytic fungi promote the growth of host plants by directly producing secondary metabolites, which enhances the plant's resistance to biotic and abiotic stresses. Additionally, they are capable of biosynthesizing medically important "phytochemicals" that were initially thought to be produced only by the host plant. In this review, we summarized some compounds from endophyte fungi with novel structures and diverse biological activities published between 2011 and 2021, with a focus on the origin of endophytic fungi, the structural and biological activity of the compounds they produce, and special attention paid to the exploration of pharmacological activities and mechanisms of action of certain compounds. This review revealed that endophytic fungi had high potential to be harnessed as an alternative source of secondary metabolites for pharmacological studies.

Assessment of antiviral activity and mechanism of rhein on newcastle disease virus (La Sota strain IV) in vitro.

Current research is focused on the development of drug candidates from natural products. Rhein a Traditional Chinese Medicine (TCM) from Polygonaceae (rhubarb) has exhibited antioxidant, anti-inflammatory and anticancer activities, however no work has reported its antiviral potential, thus this study was performed to investigate the antiviral activities of rhein on new castle disease virus (NDV) in vitro.NDV infection of chicken embryo fibroblasts (CEFs) was prepared using 10-day-old specific pathogen free chicken embryos. Cytotoxicity and anti-viral activities of rhein were assessed using the MTT method. The interaction between NDV and cell membrane proteins were also detected using virus overlay protein binding assay (VOPBA). In addition NDV genes expressions in CEFs were measured using real-time fluorescent quantitative (RTFQ) PCR.The results showed that rhein effectively inhibit NDV activities maximal safe concentration of 0.125 mg/ml. This finding indicated that, rhein could be used as future antiviral drug against NDV.[Formula: see text].

Bacillus toyonensis SAU-19 Ameliorates Hepatic Insulin Resistance in High-Fat Diet/Streptozocin-Induced Diabetic Mice.

Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (T2DM). This study was performed to investigate the antidiabetic effect of Bacillus toyonensis SAU-19 and its possible mechanisms of action in mice with type 2 diabetes mellitus (T2DM). Thirty SPFKM mice were randomly assigned to three groups: control, diabetic model, and diabetes + Bacillus toyonensis SAU-19 group. After 35 days, blood was collected for biochemical analysis and liver tissue samples for histopathological analysis using H&E staining, qPCR, and ELISA. The results showed that the administration of B. toyonensis SAU-19 significantly improved the blood glucose, hepatic insulin resistance, and morphological changes of the liver characterized by significant improvement of dyslipidemia, glycogen synthesis, and antioxidant status (p < 0.05), indicating the strains' ameliorating effects on hepatic insulin resistance in T2DM. In conclusion, the probiotic strain (B. toyonensis SAU-19) inhibits T2DM by reducing insulin resistance, improving antioxidant status, and downregulating genes related to glucose synthesis; hence, it may be used in treating diabetes and other metabolic disorders. This study provides the basis for further studies into the molecular mechanisms of B. toyonensis SAU-19 in treating T2DM.

An Overview: The Toxicity of Ageratina adenophora on Animals and Its Possible Interventions.

Ageratina adenophora is one of the major invasive weeds that causes instability of the ecosystem. Research has reported that A. adenophora produces allelochemicals that inhibit the growth and development of food crops, and also contain some toxic compounds that cause toxicity to animals that consume it. Over the past decades, studies on the identification of major toxic compounds of A. adenophora and their toxic molecular mechanisms have been reported. In addition, weed control interventions, such as herbicides application, was employed to reduce the spread of A. adenophora. However, the development of therapeutic and prophylactic measures to treat the various A. adenophora-induced toxicities, such as hepatotoxicity, splenotoxicity and other related disorders, have not been established to date. The main toxic pathogenesis of A. adenophora is oxidative stress and inflammation. However, numerous studies have verified that some extracts and secondary metabolites isolated from A. adenophora possess anti-oxidation and anti-inflammation activities, which implies that these extracts can relieve toxicity and aid in the development of drug or feed supplements to treat poisoning-related disorders caused by A. adenophora. Furthermore, beneficial bacteria isolated from rumen microbes and A. adenophora can degrade major toxic compounds in A. adenophora so as to be developed into microbial feed additives to help ameliorate toxicity mediated by A. adenophora. This review presents an overview of the toxic mechanisms of A. adenophora, provides possible therapeutic strategies that are available to mitigate the toxicity of A. adenophora and introduces relevant information on identifying novel prophylactic and therapeutic measures against A. adenophora-induced toxicity.

Ageratina adenophora Disrupts the Intestinal Structure and Immune Barrier Integrity in Rats.

The aim of this study was to investigate the effects of Ageratina adenophora on the intestines morphology and integrity in rat. Rats were randomly divided into two groups and were fed with 10 g/100 g body weight (BW) basal diet and 10 g/100 g BW experimental diet, which was a mixture of A. adenophora powder and basal diet in a 3:7 ratio. The feeding experiment lasted for 60 days. At days 28 and 60 of the experiment, eight rats/group/timepoint were randomly selected, weighed, and sacrificed, then blood and intestinal tissues were collected and stored for further analysis. The results showed that Ageratina adenophora caused pathological changes and injury in the intestine, elevated serum diamine oxidase (DAO), D-lactate (D-LA), and secretory immunoglobulin A (sIgA) levels, reduced occludin levels in intestinal tissues, as well as increased the count of intraepithelial leukocytes (IELs) and lamina propria leukocytes (LPLs) in the intestine (p < 0.05 or p < 0.01). In addition, the mRNA and protein (ELISA) expressions of pro-inflammation cytokines (IL-1ß, IL-2, TNF-α, and IFN-ϒ) were elevated in the Ageratina adenophora treatment groups, whereas anti-inflammatory cytokines such as IL-4 and IL-10 were reduced (p < 0.01 or p < 0.05). Therefore, the results obtained in this study indicated that Ageratina adenophora impaired intestinal function in rats by damaging the intestine structure and integrity, and also triggered an inflammation immune response that led to intestinal immune barrier dysfunction.

Toxic mechanisms and pharmacological properties of euptox A, a toxic monomer from A. adenophora.

A. adenophora (Spreng.) R.M. King & H. Rob. is as invasive plant known to cause toxicity in humans and animals. The plant's toxic activities have been associated with some toxic phytochemicals present in the plant. One of the major phytochemicals that have been reported to induce toxicity in various organs is euptox A (9-oxo-10, 11-dehydroageraphorone). Previous studies have reported that the main target organs of euptox A are the liver and spleen. Although, many studies have reported on euptox A toxicity in rats and mice, the mechanism of action and the beneficial uses of this toxin as well as it potential uses have not been fully established in literatures. Therefore, this review firstly, aims at elaborating on the toxic effects and mechanism of action of euptox A to give basic knowledge to researchers to help in the development of strategies that will reduce its toxicity to the environment. Secondly, this paper will also report on some beneficial uses of euptox A in recent years as well as suggest some future potential applications of this toxin to help in the utilization of this plant resource.

Ageratina adenophora Inhibits Spleen Immune Function in Rats via the Loss of the FRC Network and Th1-Th2 Cell Ratio Elevation.

The objective of this study was to determine the impact of Ageratina adenophora (A. adenophora) on splenic immune function in a rat model. Rats were fed with 10 g/100 g normal feed and an experimental feed, which was composed of 3:7 A. adenophora powder and normal feed for 60 days. On days 14, 28, and 60, subsets of rats (n = 8 rats/group/time point) were selected for blood and spleen tissue sample collection. The results showed that the proportion of CD3+ T cells in the spleen was decreased at day 60 (vs. control). Also, mRNA and protein expression of chemokines CCL21 and CCL19 and functional protein gp38 in spleen decreased significantly versus the control at day 60. In addition, ER-TR7 antigen protein expression was also decreased at day 60. Levels of T-helper (Th)1 cells significantly increased, whereas those of Th2 cells decreased significantly versus the control at day 60 in spleen. The finding revealed that A. adenophora could affect splenic immune function in rats by altering the fibroblast reticulocyte (FRC) network, as well as by causing an imbalance in Th1/Th2 cell ratios. This research provides new insights into potential mechanisms of spleen immunotoxicity due to exposures to A. Adenophora.

Glycine nano-selenium prevents brain oxidative stress and neurobehavioral abnormalities caused by MPTP in rats.

BACKGROUND: Parkinson's disease (PD) is a common degenerative disease of the central nervous system in the elderly. In recent years, the results of clinical and experimental studies have shown that oxidative stress is one of the important pathogenesis of PD. Selenium is one of the minor elements reported to possess antioxidant properties. Thus, the purpose of this study was to investigate the recovery effect of glycine nano-selenium on neurobehavioral abnormalities and oxidative stress caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in rat. MATERIALS AND METHODS: SD male rats weighing 280-310 g were purchased from the Chengdu Dossy Experimental Animals Company, China. All rats were housed in a temperature-controlled room, with a 12 h light-dark cycles and had free access to food and water ad libitum. Rats were randomly divided into 4 groups with 8 animals in each group: the control group (normal saline), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine group (MPTP), MPTP + 0.05 mg/kg glycine nano-selenium (MPTP + 0.05 Se), MPTP + 0.1 mg/kg glycine nano-selenium (MPTP + 0.1 Se). Behavioral assessment, clinical symptoms, Immunohistochemistry analysis of tyrosine hydroxylase (TH) and antioxidant activity were accessed to determine the protective effects glycine nano-selenium have on PD rats. RESULTS: From the results, Rats showed a decrease in spontaneous motor behavior and an increase in pole test score. Also, the number of TH+ neurons were also significantly decreased (P < 0.05) after treated with MPTP for 7 days indicating that MPTP could successfully induce neurobehavioral abnormalities in rats. Furthermore, the lipid peroxide (MDA) levels of the PD model group were significantly increased and the antioxidant activities (SOD and GSH-PX) were significantly inhibited (P < 0.05) compared to the control group indicating the important role oxidative stress played in dopaminergic neuron death and neurobehavioral abnormalities in PD rats. Compared with the PD model group, glycine nano-selenium administration could significantly improve behavior and increase the number of TH+ neurons (P < 0.05) to protect against the loss of dopaminergic neurons. At the same time, glycine nano-selenium could decrease the MDA levels and increase the activities of SOD and GSH-PX significantly (P < 0.05). CONCLUSION: In conclusion, PD rat model was successfully developed by intraperitoneal injection of MPTP and the intragastric administration of glycine nano-selenium reduced neurobehavioral abnormalities by decreasing oxidative stress in rat brain.