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
  • 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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