<P>Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder that
eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive,
increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are
associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological
properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little
is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory-
mediated ailments.
Objective: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts
obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the
production of pro-inflammatory mediators.
Method: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate
(REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and
mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and
RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay.
BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective
effect was assessed using MTT assay.
Results: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression
of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and
RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was
correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS
root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in
microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity
either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y
cells against these inflammatory mediators.
Conclusions: These findings provided evidence that PS root extracts confer neuroprotection against Aβ-
induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a
potential therapeutic agent for inflammation-related neurological conditions including Alzheimer’s disease
(AD).</P>
Dynamic biophysical strain modulates proinflammatory gene induction in meniscal fibrochondrocytes
