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  3. Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway

Madecassoside ameliorates lipopolysaccharide-induced neurotoxicity in rats by activating the Nrf2-HO-1 pathway

  • Neurosci Lett. 2019 Sep 14:709:134386. doi: 10.1016/j.neulet.2019.134386.
Sisi Liu 1,  Guangming Li 1,  Haijie Tang 1,  Rui Pan 2,  Huili Wang 1,  Fujun Jin 1,  Xueqin Yan 1,  Yanyan Xing 1,  Guiling Chen 1,  Yongmei Fu 1,  Jun Dong 3
Affiliations

Affiliations

  • 1 Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
  • 2 Department of Orthopedics, The First Affiliated Hospital, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
  • 3 Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China; GHM Institute of CNS Regeneration, Jinan University, Guangzhou, Guangdong Province, China. Electronic address: [email protected].
PMID: 31330225 DOI: 10.1016/j.neulet.2019.134386
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.

Keywords

Lipopolysaccharide; Madecassoside; Neuroinflammation; Nrf2.

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