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Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition.

ABSTRACT: Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced decreased viability, accumulated reactive oxygen species, mitochondrial membrane potential loss, and apoptosis in SH-SY5Y cells. Network pharmacology analysis predicted that the targets of LC were most likely directly related to oxidative stress and the regulation of inflammatory factor-associated signaling pathways. Further study demonstrated that LC attenuated nitrite, TNF-α, and IL-1β production and decreased inducible nitric oxide synthase and cyclooxygenase expression in lipopolysaccharide-induced BV-2 cells. LC could directly inhibit NLRP3 inflammasome activation by decreasing the expression levels of NLRP3, ASC, cleaved Caspase-1, and NF-κB p65. Our results provide a new understanding of how LC inhibits the NLRP3 inflammasome in microglia, providing neuroprotection. These findings might guide the development of effective LC-based therapeutic strategies for NDs.

SUBMITTER: Cao J

PROVIDER: S-EPMC10897105 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition.

Cao Jie J Li Lanqin L Zhang Runge R Shu Zhou Z Zhang Yaxin Y Sun Weiguang W Zhang Yonghui Y Hu Zhengxi Z

Natural products and bioprospecting 20240226 1

Neurodegenerative diseases (NDs) are common chronic diseases arising from progressive damage to the nervous system. Here, in-house natural product database screening revealed that libertellenone C (LC) obtained from the fermentation products of Arthrinium arundinis separated from the gut of a centipede collected in our Tongji campus, showed a remarkable neuroprotective effect. Further investigation was conducted to clarify the specific mechanism. LC dose-dependently reversed glutamate-induced de ...[more]

PMID: 38407685

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Project description: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.

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Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition.

Publications

Libertellenone C attenuates oxidative stress and neuroinflammation with the capacity of NLRP3 inhibition.

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