Abstract
Excessive microglial stimulation has been recognized in several neurodegenerative diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotropic lateral sclerosis (ALS), HIV-associated dementia (HAD), multiple sclerosis (MS), and stroke. When microglia are stimulated, they produce proinflammatory mediators and cytokines, including nitric oxide (NO) derived from inducible NO synthase (iNOS), prostaglandin E2 (PGE2) derived from cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-12 (IL-12), and interleukin-6 (IL-6). These inflammatory reactions are related to the nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. Therefore, the modulation of NF-κB and MAPK is vital to prevent microglial activation and confer resistance against neuronal injury. In this study, steppogenin (1) isolated from Cudrania tricuspidata suppressed the neuroinflammatory responses to lipopolysaccharide (LPS). Steppogenin (1) inhibited the production of proinflammatory mediators and cytokines in LPS-challenged BV2 and rat primary microglial cells. Moreover, western blot analysis and immunofluorescence revealed that the nuclear translocation of NF-κB was inhibited in LPS-induced BV2 and rat primary microglial cells. The LPS-stimulated activation of BV2 and rat primary microglial cells was inhibited by steppogenin (1) through the suppression of c-Jun NH2-terminal kinase (JNK) and p38 MAPK signaling. These results suggested that steppogenin (1) exerted antineuroinflammatory effects against acute neuroinflammation in BV2 and rat primary microglial cells by suppressing the activation of NF-κB and MAPK signaling and the production of proinflammatory mediators and cytokines.
Highlights
Cudrania tricuspidata, a member of the Moraceae family, is a deciduous broad-leaved thorny tree grown throughout East Asia in Korea, China, and Japan
We evaluated the effects of steppogenin (1) on the mRNA expression of tumor necrosis factor-α (TNF-α), IL-1β, IL-12, and IL-6 in LPS-treated BV2 microglial cells (Figure 3)
We showed that steppogenin suppressed inducible NF-kB activation and the subsequent induction of proinflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), IL-1β, IL-6, TNF-α, IL-12 and that it blocked the neuronal disorders including Alzheimer’s disease, Parkinson’s disease, and stroke [33,34,35]
Summary
A member of the Moraceae family, is a deciduous broad-leaved thorny tree grown throughout East Asia in Korea, China, and Japan. In Korean traditional medicine, the C. tricuspidata has been used to treat impotency, insomnia, and poor health [1]. C. tricuspidata root bark and bark have been used in oriental medicine to treat neuritis and inflammation [2]. In recent studies of the pharmacological effects of C. tricuspidata, the extracts have been shown to possess a variety of biological effects, including antioxidant [6], Molecules 2017, 22, 2130; doi:10.3390/molecules22122130 www.mdpi.com/journal/molecules hepatoprotective [7], neuroprotective [8], monoamine oxidase-A inhibitory [9], antiatherosclerotic, tricuspidata, the extracts have been shown to possess a variety of biological effects, including andantioxidant anti-inflammatory activities [10]. [6], hepatoprotective [7], neuroprotective [8], monoamine oxidase-A inhibitory [9], Microglial cells, considered to be the macrophages antiatherosclerotic, and anti-inflammatory activities [10].of the central nervous system (CNS), play a vital role in neuronal recovery and normal brain development
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