beta-escin and Disease-Models--Animal

Escin is a natural mixture of triterpene saponins extracted from the seeds of Aesculus wilsonii Rehd. And has been reported to possess the therapeutic effects against neuropathic pain (NP). However, the underlying mechanisms remain unclear.. The present study aimed to investigate the therapeutic effects and explore the underlying mechanisms of escin on rats of NP induced by chronic constriction injury (CCI) of sciatic nerve.. Rats were treated with escin (7, 14, and 28 mg/kg, i. g.) daily from the third day after the surgery (day 0) for consecutive 14 days. Regular behavior and thermal threshold were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of inflammatory factors and biochemical factors in dorsal root ganglion (DRG). Inflammatory pain responses and nerve injuries were induced by the CCI model. Tonic pain model and acute inflammatory model induced by formalin or carrageenan were established to evaluated the pharmacological effects of escin on acute inflammatory pain. Corresponding behaviors were monitored and relevant gene expression such as c-fos, mu opioid receptor (MOR) and KCNK1 were detected by qRT-PCR. Investigate the neuroprotective effects of escin on PC12 cell injury induced by lipopolysaccharide (LPS). Cell morphology was observed under inverted microscope and neuroprotective effect of escin on cell activity was assessed by MTT assay.. Escin could widen thermal threshold, downregulate the concentration of inflammatory factors like tumor necrosis factor (TNF)-α and interleukin (IL)-1β, suppress the gene expression of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB), decrease the level of glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) remarkably. In addition, escin significantly lowered the duration of licking, numbers of flinches and increase in paw edema, showing great therapeutic effects on inflammatory pain responses. Moreover, the activity of injured PC12 cells was significantly improved after escin administrated.. Escin exerted the ameliorative effects on NP induced by CCI which may be related to downregulating the release of pro-inflammatory cytokines, suppressing TLR-4/NF-κB signal pathway, thereafter decreasing the level of GFAP and NGF.

Topics: Analgesics; Animals; Behavior, Animal; Cytokines; Disease Models, Animal; Escin; Ganglia, Spinal; Glial Fibrillary Acidic Protein; Inflammation Mediators; Male; Mice; Nerve Growth Factor; NF-kappa B; Pain Threshold; PC12 Cells; Rats; Rats, Sprague-Dawley; Sciatic Neuropathy; Sciatica; Signal Transduction; Toll-Like Receptor 4

This study aims to investigate whether Escin (ES) can protect against Cyclophosphamide (CPM)-induced cardiac damage. The experimental rats were categorized as Control, CPM (200 mg/kg), ES (10 mg/kg), and CPM + ES Groups, each having 6 members. Their heart tissues were stained with Hematoxylin and Eosin and the structural changes were investigated under the light microscope. The biochemical markers of ischemia modified albumin (IMA), creatine kinase (CK-MB), antioxidant activity indicators Catalase (CAT), and superoxide dismutase (SOD) activities were measured using blood samples. Besides, the effects of CPM, ES, and CPM + ES upon CAT and SOD activities were shown via molecular docking studies. In the Single-Dose CPM group, CK-MB and IMA levels significantly increased while SOD and CAT levels significantly decreased. However, the heart tissues were damaged. CK-MB and IMA levels significantly decreased in CP+ ES Group. On the other hand, SOD, and CAT levels significantly increased and reduced the damage remarkably. Our findings showed that ES treatment successfully reduced the toxic effects upon the rats. The conclusion is that ES treatment can help protect the heart tissue against CPM-induced toxicity. Both in-vivo results and molecular modeling studies showed that the negative effects of CPM upon SOD activity were bigger than that of CAT.

Topics: Animals; Antioxidants; Biomarkers; Cardiotoxicity; Catalase; Creatine Kinase, MB Form; Cyclophosphamide; Disease Models, Animal; Escin; Heart Diseases; Male; Molecular Docking Simulation; Myocytes, Cardiac; Oxidative Stress; Protein Conformation; Rats, Sprague-Dawley; Serum Albumin, Human; Structure-Activity Relationship; Superoxide Dismutase

Molecular imaging of lung diseases, including asthma, is limited and either invasive or non-specific. Central to the inflammatory process in asthma is the recruitment of eosinophils to the airways, which release proteases and proinflammatory factors and contribute to airway remodeling. The aim of this study was to establish a new approach to non-invasively assess lung eosinophilia during the course of experimental asthma by combining non-invasive near-infrared fluorescence (NIRF) imaging with the specific detection of Siglec-F, a lectin found predominantly on eosinophils.. An ovalbumin (OVA)-based model was used to induce asthma-like experimental allergic airway disease (EAAD) in BALB/c mice. By means of a NIRF imager, we demonstrate that 48 h-72 h after intravenous (i.v.) application of a NIRF-labeled anti-Siglec-F antibody, mice with EAAD exhibited up to 2 times higher fluorescence intensities compared to lungs of control mice. Furthermore, average lung intensities of dexamethasone-treated as well as beta-escin-treated mice were 1.8 and 2 times lower than those of untreated, EAAD mice, respectively and correlated with the reduction of cell infiltration in the lung. Average fluorescence intensities measured in explanted lungs confirmed the in vivo findings of significantly higher values in inflamed lungs as compared to controls. Fluorescence microscopy of lung cryosections localized the i.v. applied NIRF-labeled anti-Siglec-F antibody predominantly to eosinophils in the peribronchial areas of EAAD lungs as opposed to control lungs.. We show that monitoring the occurrence of eosinophils, a prominent feature of allergic asthma, by means of a NIRF-labeled antibody directed against Siglec-F is a novel and powerful non-invasive optical imaging approach to assess EAAD and therapeutic response in mice over time.

Topics: Animals; Antigens, Differentiation, Myelomonocytic; Asthma; Dexamethasone; Disease Models, Animal; Eosinophilia; Escin; Female; Gene Expression Regulation; Macrophages; Mice; Mice, Inbred BALB C; Optical Imaging; Sialic Acid Binding Immunoglobulin-like Lectins; Treatment Outcome

Parkinson's disease (PD) is a progressive neurodegenerative disorder that results mainly due to the death of dopaminergic neurons in the substantia nigra (SN), and subsequently has an effect on one's motor function and coordination. The current investigation explored the neuroprotective potential of escin, a natural triterpene-saponin on chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/probenecid (MPTP/p) induced mouse model of PD. Administration of MPTP led to the depleted striatal dopamine content, impaired patterns of behavior, enhanced oxidative stress and diminished expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and vesicular monoamine transporter-2 (VMAT-2). The expressions of interleukin-6 and -10, glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (IBA-1), tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) in SN were also enhanced. Oral treatment of escin significantly attenuated MPTP/p induced dopaminergic markers depletion, physiological abnormalities, oxidative stress and inhibit neuroinflammatory cytokine expressions in SN. The result of our study confirmed that escin mediated its protection against experimental PD through its antioxidant and anti-inflammatory properties.

Topics: Animals; Antiparkinson Agents; Disease Models, Animal; Dopamine; Dopamine Plasma Membrane Transport Proteins; Encephalitis; Escin; Male; Mice; Mice, Inbred C57BL; Motor Activity; Neostriatum; Oxidative Stress; Parkinsonian Disorders; Probenecid; Substantia Nigra; Tyrosine 3-Monooxygenase; Vesicular Monoamine Transport Proteins

Escin, a natural mixture of triterpenoid saponins isolated from the seed of the horse chestnut (Aesculus hippocastanum), has been demonstrated to possess glucocorticoid (GC)‑like anti‑edematous and anti‑inflammatory effects. The aim of the present study was to investigate whether escin exhibits synergistic protective effects on blood‑retinal barrier (BRB) breakdown when combined with GCs in a rat model of retinal ischemia. Low concentrations of escin and triamcinolone acetonide (TA) alone did not affect BRB permeability. However, when administered together, low‑dose escin and TA significantly reduced BRB permeability following ischemia. Furthermore, low‑dose escin and TA alone did not affect the expression of occludin in the ischemic retina; however, when administered together, they significantly increased occludin expression in the ganglion cell layer of the ischemic retina. This indicates that escin and GCs have synergistic protective effects on BRB breakdown and the molecular mechanisms may be correlated with the upregulation of occludin. Therefore, the administration of escin may allow a reduction in the dose of GCs for the treatment of macular edema. The combination of escin with GCs is potentially a beneficial treatment method for BRB breakdown and warrants further investigation.

Topics: Animals; Blood-Retinal Barrier; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Synergism; Escin; Glucocorticoids; Ischemia; Male; Occludin; Permeability; Protective Agents; Rats; Rats, Sprague-Dawley; Retinal Vessels; Triamcinolone Acetonide

Current standard medications for the treatment of allergic inflammation consist primarily of glucocorticoids and anti-histamines, but adverse side effects or insufficient responsiveness by patient subpopulations illustrate the need for safe and novel alternatives. Thus, there is a demand to develop a porcine model that is able to mimic mast cell-mediated type I hypersensitivity. Previously, we found that escin, a pharmacologically active mix of triterpene saponins from horse chestnut extracts, exerts anti-allergic effects in murine models and merits further investigation as an anti-allergic therapeutic.. We developed a new porcine model of allergic dermatitis based on a clinical prick test protocol. Histamine clearly provoked erythema and swelling at the prick site, whereas the mast cell-degranulating compound 48/80 even more pronounced caused wheal and flare reactions known from the human prick response. This model was used to test the anti-allergic efficacy of orally applied escin.. Oral pretreatment of animals with escin strongly inhibited the allergic skin response induced by compound 48/80 in a dose-dependent manner. Additional in vitro data from murine mast cells indicate an engagement of the glucocorticoid receptor pathway upon treatment with escin.. This model provides a valuable and easy-to-set-up tool for preclinical studies of mast cell-inhibiting compounds. The successful implementation of this model supports the development of oral escin applications as a novel anti-allergic therapy.

Topics: Animals; Anti-Allergic Agents; Dermatitis, Atopic; Disease Models, Animal; Dose-Response Relationship, Immunologic; Escin; Female; Histamine; Male; p-Methoxy-N-methylphenethylamine; Skin Tests; Swine

Escin exerts potent glucocorticoid-like anti-inflammatory effects. The aim of this study was to investigate whether the anti-inflammatory effect of escin is through the up-regulation of glucocorticoids and if escin induces pathological changes in immune organs. Mice were administrated with escin intravenously for 7 days before observing the relevant parameters. The results showed that escin exhibits a potent anti-inflammatory effect, but does not increase corticosterone secretion in mice, and does not increase immune cell apoptosis in the spleen and thymus of mice. These findings suggest that the anti-inflammatory effect of escin is not dependent on the release of corticosterone.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Capillary Permeability; Corticosterone; Disease Models, Animal; Escin; Injections, Intravenous; Male; Mice; Spleen; Thymus Gland

Motility disorders are frequently observed in intestinal inflammation. We previously reported that in vitro treatment of intestinal smooth muscle tissue with IL-1beta decreases the expression of CPI-17, an endogenous inhibitory protein of smooth muscle serine/threonine protein phosphatase, thereby inhibiting contraction. The present study was performed to examine the pathophysiological importance of CPI-17 expression in the motility disorders by using an in vivo model of intestinal inflammation and to define the regulatory mechanism of CPI-17 expression by proinflammatory cytokines. After the induction of acute ileitis with 2,4,6,-trinitrobenzensulfonic acid, CPI-17 expression declined in a time-dependent manner. This decrease in CPI-17 expression was parallel with the reduction of cholinergic agonist-induced contraction of smooth muscle strips and sensitivity of permeabilized smooth muscle fibers to Ca(2+). Among the various proinflammatory cytokines tested, TNF-alpha and IL-1beta were observed to directly inhibit CPI-17 expression and contraction in cultured rat intestinal tissue. Moreover, both TNF-alpha and IL-1beta inhibited CPI-17 expression and contraction of smooth muscle tissue isolated from wild-type and IL-1alpha/beta double-knockout mice. However, IL-1beta treatment failed to inhibit CPI-17 expression and contraction in TNF-alpha knockout mice. In beta-escin-permeabilized ileal tissues, pretreatment with anti-phosphorylated CPI-17 antibody inhibited the carbachol-induced Ca(2+) sensitization in the presence of GTP. These findings suggest that CPI-17 was downregulated during intestinal inflammation and that TNF-alpha plays a central role in this process. Downregulation of CPI-17 may play a role in motility impairments in inflammation.

Topics: Animals; Carbachol; Disease Models, Animal; Down-Regulation; Escin; Gastrointestinal Motility; Ileitis; Interleukin-1beta; Intestinal Diseases; Intracellular Signaling Peptides and Proteins; Male; Mice; Muscle Proteins; Muscle, Smooth; Phosphoproteins; Rats; Trinitrobenzenesulfonic Acid; Tumor Necrosis Factor-alpha

Postoperative peritoneal adhesions are common, serious complications of general abdominal and gynecologic surgery that can lead to chronic abdominal pain, intestinal obstruction, and infertility. As yet, there are no ideal drugs that may be prescribed for patients to prevent adhesion formation effectively. In this study the effects of escin, a natural drug, on the various steps of adhesion formation were investigated. The effects of escin on increased vascular permeability induced by acetic acid in a mouse model of acute inflammation, granuloma formation in a subchronic inflammatory rat model, gastrointestinal transit in rats with intestinal paralysis, intestinal motility in postoperative patients, and postoperative adhesion formation in a rat model were observed. It was shown that escin could inhibit acute inflammation and granuloma formation, cause acceleration of gastrointestinal transit, help recover intestinal motility, and attenuate the formation of postoperative adhesions. The findings suggest that escin attenuates the formation of postoperative adhesions by inhibiting inflammation and promoting gastrointestinal transit. Thus it may be concluded that both inhibition of inflammation and increased gastrointestinal motility during the early postoperative period have a positive effect on decreasing the formation of adhesions.

Topics: Adult; Animals; Capillary Permeability; Disease Models, Animal; Escin; Female; Gastrointestinal Transit; Granuloma; Humans; Ileus; Injections, Intravenous; Male; Mice; Middle Aged; Postoperative Complications; Rats; Rats, Sprague-Dawley; Tissue Adhesions

Topics: Adult; Animals; Chronic Disease; Disease Models, Animal; Drug Evaluation; Escin; Humans; Male; Microcirculation; Middle Aged; Platelet Aggregation Inhibitors; Prostate; Prostatitis; Rabbits; Saponins

Topics: Animals; Aspirin; Dextrans; Disease Models, Animal; Edema; Escin; Nucleic Acids; Ovalbumin; Phenylbutazone; Rabbits; Rats; Sodium

In pathogenetically different models the antiedemic effect of extractum hippocastani semen (EHS) for intravenous and oral use was to be demonstrated. The histamine-induced edema of the skin, the postischemic edema of muscle and the cerebral edema provoked by cold injury were used. In all the models tested, it was possible to obtain reproducible numerical results which made statistical evaluation of the experiments possible. Antiedemic protective effects could be demonstrated in all investigations, whereas in one model a curative effect could be proved, too.

Topics: Brain Edema; Cold Temperature; Disease Models, Animal; Edema; Escin; Histamine; Ischemia; Muscles; Muscular Diseases; Plant Extracts; Plants, Medicinal; Skin Diseases