Momordica charantia (bitter melon) attenuates high-fat diet-associated oxidative stress and neuroinflammation

被引:110
|
作者
Nerurkar, Pratibha V. [1 ]
Johns, Lisa M. [1 ]
Buesa, Lance M. [1 ]
Kipyakwai, Gideon [1 ]
Volper, Esther [2 ]
Sato, Ryuei [1 ]
Shah, Pranjal [1 ]
Feher, Domonkos [3 ]
Williams, Philip G. [3 ]
Nerurkar, Vivek R. [2 ]
机构
[1] Univ Hawaii Manoa, Lab Metab Disorders & Alternat Med, Dept Mol Biosci & Bioengn, Coll Trop Agr & Human Resources, Honolulu, HI 96822 USA
[2] Univ Hawaii Manoa, John A Burns Sch Med, Retrovirol Res Lab, Dept Trop Med Med Microbiol & Pharmacol, Honolulu, HI 96813 USA
[3] Univ Hawaii Manoa, Coll Nat Sci, Dept Chem, Honolulu, HI 96822 USA
基金
美国国家卫生研究院;
关键词
BODY-MASS INDEX; CENTRAL-NERVOUS-SYSTEM; SATURATED-FAT; INSULIN-RESISTANCE; KAPPA-B; BRAIN; INFLAMMATION; OBESITY; TRANSCRIPTION; ACTIVATION;
D O I
10.1186/1742-2094-8-64
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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-kappa B1, and glial cells activation markers such as Iba1, CD11b, GFAP and S100 beta. 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-kappa B1, 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.
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页数:19
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