Abstract
α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 μM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis.
Highlights
Since ancient time, the applications of naturally existing herbs effectively treating memory deteriorations and cognitive declines had been well-documented in the Traditional Chinese Medicine (Park et al, 2002; Yao et al, 2009; Liu et al, 2011; Zhu et al, 2015)
As it is well known that activated microglia mediates inflammation in the central nervous system (CNS) (Olson and Miller, 2004; Prinz et al, 2006; Graeber et al, 2011), and the activation of which is accompanied by changes in cell morphology and motility (Hanisch and Kettenmann, 2007; Liaury et al, 2012)
We showed the anti-inflammatory effects of a natural product and sought to unravel the underlying link between its anti-inflammation and the previously studied neurogenesis-promoting effect
Summary
The applications of naturally existing herbs effectively treating memory deteriorations and cognitive declines had been well-documented in the Traditional Chinese Medicine (Park et al, 2002; Yao et al, 2009; Liu et al, 2011; Zhu et al, 2015). Acori Tatarinowii (AT) as one of the three herbs constitute the formula in particular exhibits neuron-protective effect (Lee et al, 2003; Lin et al, 2012) Further investigation in this natural herb revealed its major active constituent asarone exists as stereoisomers (α- and β-asarone), both of which promoted neurogenesis in AD model mice (Mao et al, 2015). It was reported that α-asarone displayed anti-inflammatory effect in the LPS-activated microglia as well as in the Parkinson’s model mice (Kim et al, 2015) Such dual-functional product may serve great advantages in the treatment of AD. Microglia morphology and motility change in response to inflammatory stimuli had been reported in many in vitro studies (Rangroo Thrane et al, 2012; Gyoneva et al, 2014). In comparison to the pro-inflammatory cytokine expressions, microglia behavioral responses are more sensitive to changes in the inflammatory stimuli
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