arbutin and Disease-Models--Animal

Focal ischemia causes irreversible brain damage if cerebral blood flow is not restored promptly. Acute phase excitotoxicity and pro-oxidant and inflammatory events in the sub-chronic phase elicit coagulative necrosis, vascular injury, cerebral oedema, and neurobehavioral deficits. Earlier, in pre-clinical studies arbutin protected behavioral functions and improved therapeutic outcomes in different models of brain and metabolic disorders. Arbutin is natural hydroquinone that might protect against ischemia-reperfusion (I/R) injury. In this study, cerebro-protective effects of arbutin were evaluated in the middle cerebral artery occlusion-reperfusion (MCAo/R) mouse model. Mice were administered arbutin (50, 100 mg/kg, i.p.) for 21 days, and subjected to MCAo/R or sham surgery on day 14. Results showed brain infarction, blood-brain barrier dysfunction, oedema, and neurological deficits 24 h post-MCAo/R injury that were prevented by arbutin. Behavioral evaluations over the sub-chronic phase revealed MCAo/R triggered spatial and working memory deficits. Arbutin protected the memory against MCAo/R injury and decreased hydroxy-2'-deoxyguanosine, protein carbonyls, inflammatory cytokines (tumor necrosis factor-α, myeloperoxidase, matrix metalloproteinase-9, inducible nitric oxide synthase), and enhanced glutathione levels in the ischemia ipsilateral hemisphere. Arbutin decreased brain acetylcholinesterase activity, glutamate, and enhanced GABA levels against MCAo/R. Arbutin can alleviate I/R pathogenesis and protects neurobehavioral functions in the MCAo/R mouse model.

Topics: Animals; Arbutin; Blood-Brain Barrier; Brain; Chromatography, High Pressure Liquid; Disease Models, Animal; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Infarction, Middle Cerebral Artery; Male; Maze Learning; Memory, Short-Term; Mice; Neuroprotective Agents; Neurotransmitter Agents; Permeability; Reperfusion Injury

Alcoholic liver disease (ALD) is a pervasive ailment due to the excessive consumption of alcohol and there is no operative drug for its treatment. The current exploration was intended to examine the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats via the modulation of the Nrf-2/HO-1 signaling cascade. Wistar rats were challenged with the 3 g/kg/day (40% v/v) of ethanol for 4 weeks to provoke the ALD and concomitantly supplemented with 40 mg/kg of arbutin. The liver function markers enzymes, inflammatory cytokines, and oxidative stress markers levels were scrutinized by using the respective assay kits. The mRNA expression of Nrf-2/HO-1 signaling proteins was studied by reverse-transcription polymerase chain reaction. The histological alterations of liver tissues were examined. HepG2 cells were used for the in vitro studies. The levels of oxidative stress markers and liver marker enzymes were examined by using kits. Reactive oxygen species (ROS) and apoptotic cell death was detected by using fluorescent staining. There were no major differences in the body weight and liver weight of experimental animals. Arbutin treatment appreciably reduced the liver marker enzymes, upregulated superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and the hydroxyl scavenging ability, and diminished the tumor necrosis factor-α and interleukin-6 levels in the serum of ethanol provoked animals. Arbutin triggered Nrf-2/HO-1 signaling cascade liver tissues of ethanol-provoked animals. Histological findings proved the preventing effects of arbutin. Arbutin did not demonstrate toxicity to the HepG2 cells. It reduced the aspartate aminotransferase and alanine aminotransferase, ROS, apoptotic cell death, lipid peroxidation and improved the antioxidants' levels in the ethanol-challenged HepG2 cells. In conclusion, our findings unveiled the hepatoprotective efficacy of arbutin against ethanol-provoked liver injury in rats. It could be a promising agent to treat alcoholic liver disease in the future.

Topics: Alanine Transaminase; Animals; Antioxidants; Apoptosis; Arbutin; Aspartate Aminotransferases; Chemical and Drug Induced Liver Injury; Cytokines; Disease Models, Animal; Ethanol; Heme Oxygenase (Decyclizing); Hep G2 Cells; Humans; Lipid Peroxidation; Liver Diseases, Alcoholic; NF-E2-Related Factor 2; Oxidative Stress; Rats; Rats, Wistar; Reactive Oxygen Species; Signal Transduction

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Arbutin is a glycoside reported for its anti-oxidant, anti-inflammatory and anti-tumor properties. However, the cardioprotective effect of Arbutin is not well established. The study aims to understand the effect of arbutin on isoproterenol (ISO)-induced cardiac hypertrophy in mice. The animals were pretreated with Arbutin for a week and ISO was administered for 10 days and then sacrificed. Cardiac injury markers such as creatinine kinase and lactate dehydrogenase concentrations were measured in the serum. The mRNA expression of cardiac hypertrophy markers namely atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured using qRT-PCR. The levels of pro-inflammatory cytokines TNF-α and IL-6 were quantified by ELISA in isolated tissues and serum. Other tissue anti-oxidant parameters such as GST, GSH, SOD and TBARS were also measured. TUNEL assay was performed to detect apoptosis. Histology studies were performed using H & E and Masson trichome staining. Immunoblot analysis was used to quantify the protein expression of TLR-4 and NF-κB. ISO-alone-treated group showed significant increase in CK-MB, LDH along with increase in hypertrophic markers ANP and BNP, TNF-α and IL-6 levels in serum and tissues and increased cardiomyocyte apoptosis. Anti-oxidant parameters were significantly decreased and TLR-4 and NF-κB protein expression was found to be upregulated in comparison to the control group. Pretreatment with Arbutin-exhibited significant inhibition of TLR-4/NF-κB pathway with decreased levels of pro-inflammatory cytokines and enhanced myocardial anti-oxidant status. Our study demonstrated that pretreatment with Arbutin exhibits marked protective effects on ISO-induced cardiac hypertrophy in mice. Thus, Arbutin may be used as potential pharmacological interventions in the management of cardiac hypertrophy.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arbutin; Atrial Natriuretic Factor; Cardiomegaly; Cardiotoxicity; Disease Models, Animal; Interleukin-6; Isoproterenol; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; NF-kappa B; Oxidative Stress; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Neuroinflammation, glial activation, and oxidative injury are the main pathological mechanisms of demyelination in multiple sclerosis (MS). Arbutin, a natural polyphenol compound, possesses antioxidant, anti-inflammatory, and neuroprotective properties whose therapeutic potential has not been studied in the experimental animal models of MS. In the present study, the efficiency of arbutin on lysolecthin (LPC)-induced local demyelination model was investigated. Demyelination was induced by micro-injection of 2 μl LPC (1%) into the rat optic chiasm and the treated group received daily injection of arbutin (50 mg/kg, i.p) during 2 weeks. Visual-evoked potential (VEP) recordings were used to functionally assess the visual pathway. Gene expression analysis was done to evaluate the arbutin effect on the inflammatory, stress oxidative-related mediators, and myelin markers. The myelin-specific staining was performed to assess demyelination and GFAP staining as an astrocyte marker. We found that arbutin significantly reduced P1-latency of VEPs waves and demyelination at 7 and 14 days post-demyelination. Arbutin decreased inflammatory cytokines (IL-1B, IL-17, TNF-α) and iNOS mRNA expression level. In addition, the expression level of anti-inflammatory cytokine (IL-10) and antioxidant mediators (Nrf-2 and HO-1) was enhanced by arbutin treatment. Arbutin increased MBP and Olig2 expression levels in demyelination context. Finally, arbutin attenuated GFAP as an astrocyte marker. Finally, this study demonstrates that arbutin improves functional recovery and myelin repair in the demyelinated optic chiasm through attenuation of inflammation, astrocyte activation, and oxidative stress. These findings might open new promising avenues for treating demyelinating disorders such as multiple sclerosis. Graphical abstract.

Topics: Animals; Arbutin; Astrocytes; Cytokines; Demyelinating Diseases; Disease Models, Animal; Evoked Potentials, Visual; Lysophosphatidylcholines; Male; Microglia; Optic Chiasm; Rats; Rats, Wistar; Recovery of Function

Arbutin as a natural soluble glycosylated phenol possesses a wide range of pharmacological activities including anti-inflammatory and anti-oxidant effects. The present study was designed to evaluate the effect of arbutin supplementation on seizures behavior, memory performance, glial activation, release of inflammatory factors and neuroprotection in pentylenetetrazole-induced kindling model. Chemical kindling was induced by repetitive injections of PTZ at subconvulsive doses (36 mg/kg). Arbutin at doses of 25 or 50 mg/kg was administrated intraperitoneally (i.p.), 10 days before PTZ injection and its application was continued 1 h before each PTZ injection. High performance liquid chromatography (HPLC) analysis was performed to measure the arbutin content in hippocampus. After monitoring the behavioral signs of seizures, Morris water maze task was used to assess the spatial learning and memory of animals. Gene expression analysis was carried out to evaluate the effect of arbutin on expression of inflammatory mediators and astrocyte activation. Furthermore, immunostaining was used to assess the protein levels of astrocytes and neurons in hippocampus. The results of HPLC analysis showed that high amount of arbutin can be detected in hippocampus of arbutin + PTZ receiving animals. The seizure behavioral manifestations and memory dysfunction were reduced by arbutin in a dose-dependent manner. The mRNA levels of TNF-α, IL-6 and GFAP were significantly downregulated in animals treated by arbutin. Additionally, the levels of astrocytes activation and neuronal damage were attenuated in arbutin treated animals. These results suggest that arbutin attenuates glial activation, memory impairment and release of inflammatory mediators in model of chronic epilepsy.

Topics: Animals; Antigens, Nuclear; Arbutin; Astrocytes; Cognitive Dysfunction; Cytokines; Disease Models, Animal; Epilepsy; Glial Fibrillary Acidic Protein; Hippocampus; Interleukin-6; Kindling, Neurologic; Male; Mice; Nerve Tissue Proteins; Pentylenetetrazole; Seizures; Spatial Learning; Spatial Memory; Tumor Necrosis Factor-alpha

The main goal of this study was to evaluate the effects of arbutin (AR) on lipopolysaccharide (LPS)-induced lung injury. A lung injury rat model was established by intravenous LPS administration. We found that levels of inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) in both serum and lung tissue were significant increased after LPS challenge. In addition, pathological conditions were examined in rat lungs, and it was demonstrated that AR-pretreatment reduced LPS-induced malondialdehyde (MDA) levels and increased LPS-induced superoxide dismutase (SOD) activity. Moreover, the expression of sirtuin1 (SIRT1), nuclear erythroid factor 2-related factor 2 (Nrf-2), heme oxygenase-1 (HO-1) as well as the phosphorylation of NF-κBp65 and IκBα were increased with LPS-induced lung injury, and were significantly restored by AR treatment. Together, our results indicated that SIRT1 is a potential therapeutic target in LPS-induced lung injury, and that AR may be a novel therapeutic in patients with acute lung injury.

Topics: Acute Lung Injury; Animals; Arbutin; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Lipopolysaccharides; Malondialdehyde; NF-E2-Related Factor 2; Rats; Rats, Sprague-Dawley; Sirtuin 1; Superoxide Dismutase; Transcription Factor RelA

Chinese yam (CY), used as both a traditional Chinese medicine and a nutritious food, is an excellent candidate for treating septic cardiomyopathy (SCM). Adenosine, arbutin and allantoin are the major active components in the aqueous extract of CY. The aim of the present study was to interpret the roles of CY, adenosine, arbutin and allantoin in SCM treatment. Firstly, significant physiological indexes were examined to assess the model and treatment effects of CY, adenosine, arbutin and allantoin. Then, a metabolomic approach was utilized to reveal the metabolic disorders in SCM concerning the intervention of CY/adenosine/arbutin/allantoin. The integrated results demonstrated that adenosine, arbutin and allantoin are responsible for the efficacy of CY on SCM treatment by regulating amino acid, arachidonic acid, sphingolipid, glycerophospholipid and glycol metabolism. Moreover, adenosine and/or arbutin could be used as a substitute for CY in treating SCM, and allantoin efficacy was slightly weaker. This integrated metabolomic approach performed excellently in understanding the herbal function and the roles of its components.

Topics: Adenosine; Allantoin; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arbutin; Biomarkers; Cardiomyopathies; Cardiotonic Agents; China; Dietary Supplements; Dioscorea; Disease Models, Animal; Energy Metabolism; Female; Immunologic Factors; Male; Metabolomics; Plant Extracts; Plant Tubers; Principal Component Analysis; Random Allocation; Rats, Wistar; Sepsis

Turnera diffusa Willd. ex Schult. has been used for the treatment of several human disorders including peptic ulcer.. The current study is an attempt to evaluate the anti-ulcerogenic activities of arbutin, a major constituent of Turnera diffusa on two ulcer models. The possible involvement of lipid peroxidation, nitric oxide, IL-6, IL-10, TNF-α and mucus barrier mechanism has been investigated.. Effects of arbutin on ulcer index, gastric juice acidity, mucus content and histochemistry, gross and histological gastric lesions, nitric oxide, cytokines levels (IL-6, IL-10 and TNF-α), and thiobarbituric acid reactive substances (TBARS), were evaluated in aspirin or ethanol-induced ulcer in vivo. Acute toxicity of arbutin was also examined in rodent model. MTT assay was used to assess the cytotoxicity of the compound on normal liver cells (WRL-68).. Pre-treatment with arbutin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of edema, inflammation and leucocytes infiltration on both models. Arbutin significantly (P<0.05) lowered the elevated TBARS level into gasteric homogenate. Arbutin did not produce significant inhibition of NO. This natural compound has modulated the levels of interleukin-6, interleukin-10 and TNF-α. No in vitro or in vivo toxicities for arbutin were observed.. Thus it can be concluded that Turnera diffusa possesses anti-ulcer activity, which could be attributed to lipid peroxidation inhibitory, immuno modulatory and anti-oxidant mechanisms of arbutin but not to the intervention with nitric oxide inflammation pathway.

Topics: Animals; Anti-Ulcer Agents; Antioxidants; Arbutin; Aspirin; Cell Line; Cytoprotection; Disease Models, Animal; Ethanol; Female; Gastric Acid; Gastric Mucosa; Humans; Hydrogen-Ion Concentration; Immunologic Factors; Interleukin-10; Interleukin-6; Lipid Peroxidation; Liver; Male; Mucus; Nitric Oxide; Omeprazole; Phytotherapy; Plant Extracts; Plants, Medicinal; Proton Pump Inhibitors; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Thiobarbituric Acid Reactive Substances; Tumor Necrosis Factor-alpha; Turnera