Objective: Epidemiological studies reveal that exposure to fine particulate matter (aerodynamic diameter ≤ 2.5 μm, PM Methods: EVs were isolated from the serum of healthy subjects, quantified Results: PM Conclusions EVs treatment promotes cell survival and attenuates PM
A549 Cells ; Air Pollutants/toxicity* ; Apoptosis/drug effects* ; Cell Survival/drug effects* ; Extracellular Vesicles ; Humans ; Male ; Middle Aged ; Particulate Matter/toxicity* ; Protective Agents/pharmacology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Serum

Animals ; Aquaporins/metabolism* ; Disease Models, Animal ; Glycoproteins/pharmacology* ; Humans ; Lung/metabolism* ; Protective Agents/pharmacology* ; Respiratory Distress Syndrome/physiopathology* ; Sus scrofa ; Trypsin Inhibitors/pharmacology* ; Up-Regulation

BACKGROUND: Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders. METHODS: Methanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries. RESULTS: Level of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), HO and nitrite increased in liver tissues of CCl treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-β (TGF-β), Smad-3 and collagen type 1 (Col1-α) increased with CCl induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl in rats retrieved the normal expression of these markers and prevented hepatic injuries. CONCLUSION Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.
Animals ; Carbon Tetrachloride ; adverse effects ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; pathology ; Endoplasmic Reticulum Stress ; drug effects ; Fibrosis ; drug therapy ; genetics ; Inflammation ; drug therapy ; genetics ; Liver ; drug effects ; enzymology ; metabolism ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Urticaceae ; chemistry

Animals ; Apoptosis ; Biflavonoids ; pharmacology ; Catechin ; pharmacology ; Grape Seed Extract ; pharmacology ; Kidney ; drug effects ; Male ; Oxidative Stress ; Proanthocyanidins ; pharmacology ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Sodium Fluoride ; adverse effects

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Dyslipidemias ; drug therapy ; Glycemic Load ; drug effects ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Stilbenes ; pharmacology

Objective: This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats. Methods: Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured. Results: AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB . Conclusion Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .
Aflatoxin B1 ; toxicity ; Animals ; Biflavonoids ; administration & dosage ; pharmacology ; Catechin ; administration & dosage ; pharmacology ; Chemical and Drug Induced Liver Injury ; drug therapy ; etiology ; Male ; Poisons ; toxicity ; Proanthocyanidins ; administration & dosage ; pharmacology ; Protective Agents ; administration & dosage ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Ionizing radiation causes the massive apoptosis of human tissue cells,leading to dysfunction of the gastrointestinal tract and hematopoietic system.Thus,high-efficiency,low-toxicity radiation protection drugs are urgently needed.Toll-like receptor agonists have been developed based on the anti-apoptotic mechanism of tumor cells in recent years,which exert their radioprotective effects by activating downstream pathways,mainly nuclear factor-κB.Here we elucidate several agonists of Toll-like receptors involved in radiation protection,with an attempt to inform the research and development of new radiation protection agents.
Apoptosis ; Humans ; NF-kappa B ; Radiation Protection ; Radiation, Ionizing ; Radiation-Protective Agents/pharmacology* ; Toll-Like Receptors/agonists*

To identify and verify the active ingredients from Astragalus membranaceus on hypertensive cardiac remodeling based on network pharmacology and heart RNA-sequencing data. The monomers of A. membranaceus and their intervention target database were established by using network pharmacology. The genes associated to cardiac remodeling were then screened by analyzing cardiac RNA-sequencing data. An overlap between genes related to cardiac remodeling and targets of ingredients form A. membranaceus was collected to obtain monomers with protective effect on hypertensive cardiac remodeling. Angiotensin Ⅱ(AngⅡ)-induced mouse cardiac remodeling model was used to validate the protective effect of active ingredients from A. membranaceus on hypertensive cardiac remodeling. Finally, a total of 81 monomers and 1 197 targets were enrolled in our database. Mouse RNA-sequencing data showed that 983 genes were significantly up-regulated and 465 genes were down-regulation in myocardial tissues of the cardiac remodeling mice as compared with blank group mice, respectively. Ninety-two genes were found via overlapping between genes related to cardiac remodeling and targets, involving 59 monomers from A. membranaceus. Further research found that vanillic acid(VA) could intervene 27 genes associated with hypertensive cardiac remodeling, ranking top 1. Meanwhile, VA could significantly inhibit AngⅡ-induced increase in ratio of heart weight to body weight and heart weight to tibial length, ANP and BNP mRNA levels in myocardial tissues, myocardial tissue damage, cardiac fibrosis level and cardiac hypertrophy level in vivo. Those results showed that network pharmacology screen-based VA has protective effect on AngⅡ-induced cardiac remodeling.
Angiotensin II ; Animals ; Astragalus propinquus/chemistry* ; Heart ; Hypertension/genetics* ; Mice ; Protective Agents/pharmacology* ; Vanillic Acid/pharmacology* ; Ventricular Remodeling/genetics*

OBJECTIVE: To investigate the effects of 1,25-dihydroxyvitamin D3 (1,25-VitD3) supplementation on cerebral injury after ischemia/reperfusion (I/R) in mice with middle cerebral artery occlusion (MCAO). METHODS: Male C57BL6 mice were randomly divided into Sham group, Vehicle group and 1,25-VitD3 group, with 10 mice in each group. Vehicle group and 1,25-VitD3 group were given MCAO for 1 hour, and then killed after reperfusion for 24 hours. Mice in 1,25-VitD3 group were treated with 1,25-VitD3 at the dose of 100 ng/(kg·d) by injected intraperitoneally for 5 days before MCAO operation. Cerebral ischemic penumbra areas of each group were collected for TTC staining, RT-PCR, TTC staining and immunohistochemistry assay. The function defect of mice was evaluated by using neurological function score. RESULTS: Compared with the sham group, the volume of cerebral infarction in Vehicle group was increased significantly, and the expressions of IL-6, IL-1beta and Gp91phox in brain tissues were increased significantly (P＜0.05); compared with Vehicle group, supplementation of 1,25-VitD3 reduced the volume of cerebral infarction by about 50% in I/R mice (P＜0.05), and the expressions of IL-6, IL-1beta and Gp91phox in brain tissues of 1,25-VitD3 group were decreased significantly (P＜0.05). The expression of Foxp3, a T-regulatory cell marker, was significantly increased in the brain of mice (P＜0.05), while the expression of Rorc, a transcription factor, was significantly decreased (P＜0.05), suggesting that Th17/gamma Delta T-cell response was reduced and the number of neutrophils in the brain injury site of mice was significantly reduced (P＜0.05). CONCLUSION Vitamin D could alleviate the development of cerebral infarction after arterial occlusion (MCAO) reperfusion, and its mechanism may be through regulating the inflammatory response in mouse brain I/R.
Animals ; Brain ; Cytokines ; metabolism ; Infarction, Middle Cerebral Artery ; drug therapy ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; NADPH Oxidase 2 ; metabolism ; Protective Agents ; pharmacology ; Random Allocation ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; T-Lymphocytes ; Th17 Cells ; Vitamin D ; pharmacology

BACKGROUND: Parkinson's disease is a neurodegenerative disorder, and recent studies suggested that oxidative stress contributes to the degeneration of dopamine cell in Parkinson's disease. Glutamine also has a positive role in reducing oxidative stress damage. In this study, we hypothesized that glutamine offers protection against oxidative stress injury in 1-methyl-4-phenylpyridinium (MPP)-induced Parkinson's disease cell model. METHODS: MPP was used to induce PD models in PC12 cells and classified into control, M0 (MPP), G0 (glutamine), and M0+G0 groups. CCK-8 and AO/EB staining assays were used to examine cell proliferation and apoptosis, respectively. Western blotting was applied to examine the protein expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR. RESULTS: We showed that glutamine suppressed cytotoxicity induced by MPP in PC12 cells. MPP decreased the superoxide dismutase and glutathione peroxidase activity and increased the malondialdehyde content, which were restored by glutamine. Moreover, MPP increased the expression of PI3K, P-Akt, Akt, P-mTOR, and mTOR, which were inhibited by glutamine. And the antioxidant capacity of glutamine on PC12 cells could be improved by LY294002 and inhibited by IGF-1. CONCLUSION These results suggest that glutamine strengthens the antioxidant capacity in PC12 cells induced by MPP through inhibiting the activation of the PI3K/Akt signaling pathway. The effects of glutamine should be investigated and the protective mechanism of glutamine in PD must be explored in future studies.
1-Methyl-4-phenylpyridinium ; administration & dosage ; Analysis of Variance ; Animals ; Cell Culture Techniques ; Disease Models, Animal ; Glutamine ; pharmacology ; Oxidative Stress ; drug effects ; Parkinson Disease ; Phosphatidylinositol 3-Kinases ; metabolism ; Protective Agents ; pharmacology ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats