Isorhamnetin attenuates high-fat and high-fructose diet induced cognitive impairments and neuroinflammation by mediating MAPK and NFκB signaling pathways.

Isorhamnetin (ISO), a flavonoid compound isolated from sea-buckthorn (Hippophae rhamnoides L.) fruit, has anti-inflammatory effects. However, the effects of ISO on neuroinflammation and cognitive function are still unclear. The purpose of this study was to evaluate the protective effect of ISO on cognitive impairment in obese mice induced by a high-fat and high fructose diet (HFFD). It has been found that oral administration of ISO (0.03% w/w and 0.06% w/w) for 14 weeks significantly reduced the body weight, food intake, liver weight, liver lipid level, and serum lipid level of HFFD-fed mice. ISO can also significantly prevent HFFD-induced neuronal working, spatial, and long-term memory impairment. Notably, the ISO treatment activated the CREB/BDNF pathway and increased neurotrophic factors in the brains of mice. Furthermore, ISO inhibited HFFD-induced microglial overactivation and down-regulated inflammatory cytokines in both serum and the brain. It can also inhibit the expression of p-JNK, p-p38, and p-NFκB protein in the mouse brain. In conclusion, these results indicated that ISO mitigated HFFD-induced cognitive impairments by inhibiting the MAPK and NFκB signaling pathways, suggesting that ISO might be a plausible nutritional intervention for metabolic syndrome-related cognitive complications.

[1]  O. Valverde,et al.  Neuroinflammatory and behavioral susceptibility profile of mice exposed to social stress towards cocaine effects , 2020, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[2]  V. Rishi,et al.  Quercetin alleviates cognitive decline in ovariectomized mice by potentially modulating histone acetylation homeostasis. , 2020, The Journal of nutritional biochemistry.

[3]  Xuebo Liu,et al.  Sea-buckthorn flavonoids alleviate high-fat and high-fructose diet-induced cognitive impairment by inhibiting insulin resistance and neuroinflammation. , 2020, Journal of agricultural and food chemistry.

[4]  R. Liu,et al.  Effects of alternate-day fasting, time-restricted fasting and intermittent energy restriction DSS-induced on colitis and behavioral disorders , 2020, Redox biology.

[5]  Xingjun Tian,et al.  Diversity in sea buckthorn (Hippophae rhamnoides L.) accessions with different origins based on morphological characteristics, oil traits, and microsatellite markers , 2020, PloS one.

[6]  Xuebo Liu,et al.  Protective Effects of Sesamol on Systemic Inflammation and Cognitive Impairment in Aging Mice. , 2020, Journal of agricultural and food chemistry.

[7]  G. Xing,et al.  Contribution of microglial reaction to increased nociceptive responses in high-fat-diet (HFD)-induced obesity in male mice , 2019, Brain, Behavior, and Immunity.

[8]  Shih-Chao Lin,et al.  Isorhamnetin ameliorates inflammatory responses and articular cartilage damage in the rats of monosodium iodoacetate-induced osteoarthritis , 2019, Immunopharmacology and immunotoxicology.

[9]  Xianli Meng,et al.  Total flavonoids from sea buckthorn ameliorates lipopolysaccharide/cigarette smoke‐induced airway inflammation , 2019, Phytotherapy research : PTR.

[10]  ChaoNan Liu,et al.  Inhibition of tumor necrosis factor alpha and increased of interleukin 10 by Lactobacillus: a molecular mechanism protection against TNBS-induced ulcerative colitis in chicks , 2019, Immunopharmacology and immunotoxicology.

[11]  Y. Yoo,et al.  Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation , 2018, International journal of molecular medicine.

[12]  Xuebo Liu,et al.  Lycopene attenuates western-diet-induced cognitive deficits via improving glycolipid metabolism dysfunction and inflammatory responses in gut–liver–brain axis , 2018, International Journal of Obesity.

[13]  Chunyun Li,et al.  Anti-inflammatory effects of isorhamnetin on LPS-stimulated human gingival fibroblasts by activating Nrf2 signaling pathway. , 2018, Microbial pathogenesis.

[14]  Xuebo Liu,et al.  Supplementation of lycopene attenuates lipopolysaccharide-induced amyloidogenesis and cognitive impairments via mediating neuroinflammation and oxidative stress. , 2018, The Journal of nutritional biochemistry.

[15]  Jeong-Woo Park,et al.  Protein kinase C downregulation induces senescence via FoxO3a inhibition in HCT116 and HEK293 cells. , 2017, Biochemical and biophysical research communications.

[16]  Gyu Hwan Park,et al.  Effect of high-fat diet on cognitive impairment in triple-transgenic mice model of Alzheimer's disease. , 2017, Biochemical and biophysical research communications.

[17]  R. Liu,et al.  Fabrication and Optimization of Self-Microemulsions to Improve the Oral Bioavailability of Total Flavones of Hippophaë rhamnoides L. , 2017, Journal of food science.

[18]  F. Ferretti,et al.  Simple vs. Complex Carbohydrate Dietary Patterns and the Global Overweight and Obesity Pandemic , 2017, International journal of environmental research and public health.

[19]  Xuebo Liu,et al.  EGCG ameliorates high‐fat– and high‐fructose‐induced cognitive defects by regulating the IRS/AKT and ERK/CREB/BDNF signaling pathways in the CNS , 2017, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[20]  X. Xia,et al.  Pharmacokinetics study of isorhamnetin in rat plasma by a sensitive electrochemical sensor based on reduced graphene oxide , 2017 .

[21]  Mi-Kyung Lee,et al.  Seabuckthorn Leaves Extract and Flavonoid Glycosides Extract from Seabuckthorn Leaves Ameliorates Adiposity, Hepatic Steatosis, Insulin Resistance, and Inflammation in Diet-Induced Obesity , 2017, Nutrients.

[22]  K. Mawatari,et al.  Effects of Low-Dose Non-Caloric Sweetener Consumption on Gut Microbiota in Mice , 2017, Nutrients.

[23]  Guang-yan Dai,et al.  Voluntary Exercise Promotes Glymphatic Clearance of Amyloid Beta and Reduces the Activation of Astrocytes and Microglia in Aged Mice , 2017, Front. Mol. Neurosci..

[24]  Xuebo Liu,et al.  Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy , 2017, Scientific Reports.

[25]  Xuebo Liu,et al.  Sesamol ameliorates high-fat and high-fructose induced cognitive defects via improving insulin signaling disruption in the central nervous system. , 2017, Food & function.

[26]  Ila P Karve,et al.  The contribution of astrocytes and microglia to traumatic brain injury , 2016, British journal of pharmacology.

[27]  J. Walsh,et al.  High-Fat Diet Induces Hepatic Insulin Resistance and Impairment of Synaptic Plasticity , 2015, PloS one.

[28]  G. A. Limb,et al.  IL-1β induces IL-6 production in retinal Müller cells predominantly through the activation of p38 MAPK/NF-κB signaling pathway. , 2015, Experimental cell research.

[29]  Wei-ting Zhong,et al.  Isorhamnetin protects mice from lipopolysaccharide-induced acute lung injury via the inhibition of inflammatory responses , 2015, Inflammation Research.

[30]  S. Chirumbolo.  Anti-Inflammatory Action of Isorhamnetin , 2014, Inflammation.

[31]  Young Woo Kim,et al.  Isorhamnetin protects against oxidative stress by activating Nrf2 and inducing the expression of its target genes. , 2014, Toxicology and applied pharmacology.

[32]  Bu-Yeo Kim,et al.  Cardiotonic pill attenuates white matter and hippocampal damage via inhibiting microglial activation and downregulating ERK and p38 MAPK signaling in chronic cerebral hypoperfused rat , 2013, BMC Complementary and Alternative Medicine.

[33]  Young Woo Kim,et al.  O-Methylated flavonol isorhamnetin prevents acute inflammation through blocking of NF-κB activation. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[34]  J. Ávila,et al.  Role of Neuroinflammation in Adult Neurogenesis and Alzheimer Disease: Therapeutic Approaches , 2013, Mediators of inflammation.

[35]  F. Islam,et al.  Amelioration of cognitive impairment and neurodegeneration by catechin hydrate in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type , 2013, Neurochemistry International.

[36]  S. Koppula,et al.  Regulation of Microglia Activity by Glaucocalyxin-A: Attenuation of Lipopolysaccharide-Stimulated Neuroinflammation through NF-κB and p38 MAPK Signaling Pathways , 2013, PloS one.

[37]  M. J. Kim,et al.  Britanin suppresses LPS-induced nitric oxide, PGE2 and cytokine production via NF-κB and MAPK inactivation in RAW 264.7 cells. , 2013, International immunopharmacology.

[38]  R. Straub,et al.  Role of peripheral nerve fibres in acute and chronic inflammation in arthritis , 2013, Nature Reviews Rheumatology.

[39]  A. Killcross,et al.  Effect of western and high fat diets on memory and cholinergic measures in the rat , 2012, Behavioural Brain Research.

[40]  J. Joseph,et al.  Anti-inflammatory and neuroprotective effects of an orally active apocynin derivative in pre-clinical models of Parkinson’s disease , 2012, Journal of Neuroinflammation.

[41]  Tin-Tin Win-Shwe,et al.  Acute administration of toluene affects memory retention in novel object recognition test and memory function‐related gene expression in mice , 2012, Journal of applied toxicology : JAT.

[42]  J. Pasco,et al.  Prevalence of Obesity and the Relationship between the Body Mass Index and Body Fat: Cross-Sectional, Population-Based Data , 2012, PloS one.

[43]  B. Popkin,et al.  Global nutrition transition and the pandemic of obesity in developing countries. , 2012, Nutrition reviews.

[44]  K. Reuhl,et al.  Effects of green tea polyphenol (-)-epigallocatechin-3-gallate on newly developed high-fat/Western-style diet-induced obesity and metabolic syndrome in mice. , 2011, Journal of agricultural and food chemistry.

[45]  L. Fratiglioni,et al.  Midlife overweight and obesity increase late-life dementia risk , 2011, Neurology.

[46]  E. Schomburg,et al.  In Vivo Imaging Reveals Distinct Inflammatory Activity of CNS Microglia versus PNS Macrophages in a Mouse Model for ALS , 2011, PloS one.

[47]  S. Bhaskar,et al.  Quercetin regulates oxidized LDL induced inflammatory changes in human PBMCs by modulating the TLR-NF-κB signaling pathway. , 2011, Immunobiology.

[48]  H. Vapaatalo,et al.  Effects of Flavonoids on Prostaglandin E2 Production and on COX-2 and mPGES-1 Expressions in Activated Macrophages , 2011, Planta medica.

[49]  L. Sorkin,et al.  Peripheral inflammation induces tumor necrosis factor dependent AMPA receptor trafficking and Akt phosphorylation in spinal cord in addition to pain behavior , 2010, PAIN®.

[50]  Todd D. Gould,et al.  The open field test. , 2009 .

[51]  Q. Pittman,et al.  Microglial activation and TNFα production mediate altered CNS excitability following peripheral inflammation , 2008, Proceedings of the National Academy of Sciences.

[52]  H. Kallio,et al.  Effects of sea buckthorn berries on infections and inflammation: a double-blind, randomized, placebo-controlled trial , 2008, European Journal of Clinical Nutrition.

[53]  R. Meisel,et al.  The effects of energy-rich diets on discrimination reversal learning and on BDNF in the hippocampus and prefrontal cortex of the rat , 2007, Behavioural Brain Research.

[54]  J. Kyriakis,et al.  Dissection of a Signaling Pathway by Which Pathogen-associated Molecular Patterns Recruit the JNK and p38 MAPKs and Trigger Cytokine Release* , 2007, Journal of Biological Chemistry.

[55]  J. Deleo,et al.  Complete Freunds adjuvant‐induced peripheral inflammation evokes glial activation and proinflammatory cytokine expression in the CNS , 2004, The European journal of neuroscience.

[56]  Suzanne Craft,et al.  Insulin and neurodegenerative disease: shared and specific mechanisms , 2004, The Lancet Neurology.

[57]  Z. Meng,et al.  Effect of Sulfur Dioxide Inhalation on the Glutathione Redox System in Mice and Protective Role of Sea Buckthorn Seed Oil , 2003, Archives of environmental contamination and toxicology.

[58]  S. Cuzzocrea,et al.  Pharmacological actions of melatonin in acute and chronic inflammation. , 2002, Current topics in medicinal chemistry.