Objective: The ethanol-extracted alkaloids from the dry seeds of Piper longum L. (PLL) (family Piperaceae) PLA contain numerous compounds. We evaluate the potential of PLA for Parkinson’s disease (PD) treatment.

Background: At present, all current treatments for PD are only symptomatic and could not prevent the progressive degeneration of dopaminergic (DA) neurons. The PLA contain numerous compounds with demonstrated antioxidant, anti-inflammatory, and/or cytoprotective activity. PD involves chronic neuroinflammation and oxidative stress mediated by activated microglia. To evaluate the potential of PLA for PD treatment, we examined the inhibitory efficacy of PLAs against lipopolysaccharide (LPS)-induced activation of both cultured BV-2 microglia and mouse substantia nigra (SN) microglia, as well as the protective efficacy against LPS-induced death of nigral DA neurons.

Methods: In this study, The PLA is the ethanol extraction of the seeds of PLL. Thirty mice were randomly divided into three groups: Control/Sham, LPS (5 mg/kg), PLA (120 mg/kg PLA).

Results: BV-2 microglial and mouse SN microglia were activated by LPS as evidenced by morphological changes and increased expression of activation marker genes (Ox-6, p67phox, interleukin-1β, PGE2, and COX-2), while PLA cotreatment suppressed these inflammatory responses. PLA also suppressed LPS-induced reduction of cytosolic IκB and the nuclear translocation of NF-κB p65 in microglia as evidenced by fluorescence immunohistochemistry and Western blotting, suggesting that PLA blocked microglial activation by inhibiting the NF-κB pathway. Conditioned media (CM) from BV-2 cells pretreated with LPS and PLA was significantly less neurotoxic than CM from BV-2 cells pretreated with LPS alone, suggesting that PLA suppressed the release of pro-inflammatory cytokines. Furthermore, oral PLA protected nigral DA neurons in mice against systemic LPS.

Conclusions: PLA inhibited LPS-induced microglial activation in vitro and in vivo, likely by blocking LPS-triggered cytoplasmic IκB degradation and nuclear translocation of p65, resulting in reduced production and release of inflammatory mediators and downregulation of inflammation-related enzymes. Our results suggest that PLA has potential application as an anti-neuroinflammatory agent for the treatment of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/piper-longum-l-alkaloids-inhibit-lipopolysaccharide-stimulated-microglial-activation-and-protect-nigral-dopaminergic-neurons/