Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway. (14th September 2019)

• Record Type: Journal Article
• Authors: Liu, Sisi; Li, Guangming; Tang, Haijie; Pan, Rui; Wang, Huili; Jin, Fujun; Yan, Xueqin; Xing, Yanyan; Chen, Guiling; Fu, Yongmei; Dong, Jun
• Is Part Of: Neuroscience letters. Volume 709(2019)
• Publication Date: 2019-09-14
• Subjects: MA madecassoside -- LPS lipopolysaccharide -- IL1-β Interleukin 1 beta -- TNF α tumor necrosis factor -- IL-6 interleukin 6 -- HO-1 heme oxygenase 1 -- Nrf2 nuclear factor erythroid 2-related factor 2 -- AD Alzheimer's disease -- PD Parkinson's disease -- HAND HIV-associated neurocognitive disorder -- TLR toll-like receptor -- Keap1 Kelchlike ECH-associated protein 1 -- GCLM glutathione cysteine ligase modulatory subunit -- NQO1 NAD(P)H quinone oxidoreductase 1 -- GST glutathione S-transferase -- SOD superoxide dismutase -- CA Centella asiatica -- NO nitric oxide -- PGE2 prostaglandin E2 -- CMC Carboxymethyl cellulose sodium salt -- ACSF artificial cerebrospinal fluid; Madecassoside -- Neuroinflammation -- Lipopolysaccharide -- Nrf2; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2019.134386
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Madecassoside (MA) attenuated lipopolysaccharide (LPS)-induced memory impairment in rats. MA reduced the LPS-stimulated levels of pro-inflammatory cytokines IL-6, IL-1β, and TNF-α in the rat cortex and hippocampus. MA could improve memory function in rats by activating Nrf2-HO-1 signaling to reduce the LPS-stimulated expression of pro-inflammatory cytokines." Abstract: Neuroinflammation is a predisposing factor for several neurodegenerative diseases. The purpose of this study was to evaluate the protective effect of madecassoside (MA) in lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in rats. MA has many protective effects such as antioxidant and anti-inflammatory properties. We investigated whether MA could improve neurocognitive dysfunction caused by intracerebroventricular injection of LPS. We examined the effects and mechanisms of action of MA on LPS-induced neuroinflammation in the cortex and hippocampus. Our study revealed that MA (120 mg/kg, i.g) treatment for 14 days reduced LPS-induced neurotoxicity by reducing cognitive impairments and suppressing the production of inflammatory cytokines such as interleukin 1 beta (IL-1β), tumor necrosis factor alpha(TNF-α), and interleukin 6(IL-6) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Furthermore, MA treatment enhanced protein levels of heme oxygenase (HO)-1 by upregulating Nrf2 in LPS-stimulated neurotoxicity. Collectively, these results suggest that MA is effective in preventing neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and activation of Keap1-Nrf2/HO-1 signaling. As such, MA may be a potential therapy for addressing memory impairment caused by neuroinflammation.