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

Abstract

BackgroundThe 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.MethodsC57BL/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.ResultsBM 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.ConclusionsFunctional foods such as BM offer a unique therapeutic strategy to improve obesity-associated peripheral inflammation and neuroinflammation.

Standardized fruit extract of Momordica charantia L protect against vincristine induced neuropathic pain in rats by modulating GABAergic action, antimitotoxic, NOS inhibition, anti-inflammatory and antioxidative activity

“…Therefore, we had targeted the effects of MC on TBARS, GSH, MPO, TNFalpha and IL 6 levels. Our results showed that the pretreatment with MC restored the depletion of GSH, along with a decrease of the augmented levels of TBARS, MPO, TNF-alpha and IL 6 due to vincristine administration and were in line with earlier reports (Kobori et al, 2008;Lii et al, 2009;Kenny et al, 2013;Nerurkar et al, 2011). The protective effect of MC may be attributed to the presence of bioactive compounds, which may be responsible for quenching of free radicals, or alternatively, it may be due to the up-regulation of antioxidant and anti-inflammatory systems.…”

“…Earlier, oil extracted from the seed of MC, when applied topically to the patients of spondylitis, rheumatoid arthritis and diabetic neuropathy demonstrated relief from pain (Pushpa Khanna, 2005). Moreover, study done by Nerurkar et al (2011) showed that the methanolic extract of bitter melon fruit [catechin (3% w/w), quercetin (0.62% w/w), trans-chalone (0.3% w/w), caffeine (0.25% w/w); while, GA, caffeic acid, and flavones (less than 0.01% w/w) in BM methanolic extracts] lowers the expression of neuro-inflammatory markers such as NF-κB1, IL-16, IL-22 as well as IL-17R in the brains of mice fed with high-fat diet. Further MC fruit extract showed relief from acetic acid induced writhing pain in rats (Ullah et al, 2012).…”

Food prospects and nutraceutical attributes of Momordica species: A potential tropical bioresources – A review

“…Various extracts of bitter gourd have potential antioxidant activity which might play an important role in diabetic-related enzymes and individuals with neuroinflammation and liver diseases. Nerurkar et al [67] reported that the administration of bitter melon fruit extract significantly reduced the neurodegenerative diseases as its role as antioxidant to reveal a mechanism for its neuroinflammation action. Cucurbitane-type triterpene glycoside 1 and 3 isolated from stems and fruits of M. charantia significantly inhibit the effect on Xanthine oxidase activity which is the key enzyme for the induction hyperuricemia and gout [68].…”

High‐fat diet protects the blood–brain barrier in an Alzheimer's disease mouse model

“…Most studies support the notion that HFD increases BBB permeability. In some, HFD‐induced changes in BBB permeability were evident by increased leakage of Evans blue dye in 16‐week‐old mice brain (Nerurkar et al, 2011). In others, obesity exacerbated early postischemic BBB disruption in 16‐week‐old mice fed HFD.…”