title: Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation.
abstract: BACKGROUND
  The rising epidemic of obesity is associated with cognitive decline and is considered as one of the major risk factors for neurodegenerative diseases. Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases. Increased metabolic flux to the brain during overnutrition and obesity can orchestrate stress response, blood-brain barrier (BBB) disruption, recruitment of inflammatory immune cells from peripheral blood and microglial cells activation leading to neuroinflammation. The lack of an effective treatment for obesity-associated brain dysfunction may have far-reaching public health ramifications, urgently necessitating the identification of appropriate preventive and therapeutic strategies. The objective of our study was to investigate the neuroprotective effects of Momordica charantia (bitter melon) on high-fat diet (HFD)-associated BBB disruption, stress and neuroinflammatory cytokines.
  
  
  METHODS
  C57BL/6 female mice were fed HFD with and without bitter melon (BM) for 16 weeks. BBB disruption was analyzed using Evans blue dye. Phosphate-buffered saline (PBS) perfused brains were analyzed for neuroinflammatory markers such as interleukin-22 (IL-22), IL-17R, IL-16, NF-κB1, and glial cells activation markers such as Iba1, CD11b, GFAP and S100β. Additionally, antioxidant enzymes, ER-stress proteins, and stress-resistant transcription factors, sirtuin 1 (Sirt1) and forkhead box class O transcription factor (FoxO) were analyzed using microarray, quantitative real-time RT-PCR, western immunoblotting and enzymatic assays. Systemic inflammation was analyzed using cytokine antibody array.
  
  
  RESULTS
  BM ameliorated HFD-associated changes in BBB permeability as evident by reduced leakage of Evans blue dye. HFD-induced glial cells activation and expression of neuroinflammatory markers such as NF-κB1, IL-16, IL-22 as well as IL-17R were normalized in the brains of mice supplemented with BM. Similarly, HFD-induced brain oxidative stress was significantly reduced by BM supplementation with a concomitant reduction in FoxO, normalization of Sirt1 protein expression and up-regulation of Sirt3 mRNA expression. Furthermore, plasma antioxidant enzymes and pro-inflammatory cytokines were also normalized in mice fed HFD with BM as compared to HFD-fed mice.
  
  
  CONCLUSIONS
  Functional foods such as BM offer a unique therapeutic strategy to improve obesity-associated peripheral inflammation and neuroinflammation.
authors.affiliation: Laboratory of Metabolic Disorders and Alternative Medicine, Department of Molecular Biosciences and Bioengineering, College of Tropical Agriculture and Human Resources, University of Hawaii at Manoa, Honolulu, HI 96822, USA. pratibha@hawaii.edu
authors.forename: Pratibha V
authors.initials: PV
authors.lastname: Nerurkar
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Johns
authors.forename: Lance M
authors.initials: LM
authors.lastname: Buesa
authors.forename: Gideon
authors.initials: G
authors.lastname: Kipyakwai
authors.forename: Esther
authors.initials: E
authors.lastname: Volper
authors.forename: Ryuei
authors.initials: R
authors.lastname: Sato
authors.forename: Pranjal
authors.initials: P
authors.lastname: Shah
authors.forename: Domonkos
authors.initials: D
authors.lastname: Feher
authors.forename: Philip G
authors.initials: PG
authors.lastname: Williams
authors.forename: Vivek R
authors.initials: VR
authors.lastname: Nerurkar
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D004041:Dietary Fats / Q000009:adverse effects*; D019587:Dietary Supplements; D004660:Encephalitis / Q000188:drug therapy*; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D029777:Momordica charantia / Q000737:chemistry*; D019636:Neurodegenerative Diseases / Q000209:etiology / Q000503:physiopathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009765:Obesity / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000737:chemistry; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011897:Random Allocation; D056564:Sirtuin 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D004041:Dietary Fats; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D018696:Neuroprotective Agents; D010636:Phenols; D010936:Plant Extracts; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1