Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide

Abstract

BackgroundAlkaloids from Piper longum (PLA), extracted from P. longum, have potent anti-inflammatory effects. The aim of this study was to investigate whether PLA could protect dopaminergic neurons against inflammation-mediated damage by inhibiting microglial activation using a lipopolysaccharide (LPS)-induced dopaminergic neuronal damage rat model.MethodsThe animal behaviors of rotational behavior, rotarod test and open-field test were investigated. The survival ratio of dopaminergic neurons and microglial activation were examined. The dopamine (DA) and its metabolite were detected by high performance liquid chromatography (HPLC). The effects of PLA on the expression of interleukin (IL)-6, interleukin (IL)-1β and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA). Reactive oxygen species (ROS) and nitric oxide (NO) were also estimated.ResultsWe showed that the survival ratio of tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the substantia nigra pars compacta (SNpc) and DA content in the striatum were reduced after a single intranigral dose of LPS (10 μg) treatment. The survival rate of TH-ir neurons in the SNpc and DA levels in the striatum were significantly improved after treatment with PLA for 6 weeks. The over-activated microglial cells were suppressed by PLA treatment. We also observed that the levels of inflammatory cytokines, including TNF-α, IL-6 and IL-1β were decreased and the excessive production of ROS and NO were abolished after PLA treatment. Therefore, the behavioral dysfunctions induced by LPS were improved after PLA treatment.ConclusionThis study suggests that PLA plays a significant role in protecting dopaminergic neurons against inflammatory reaction induced damage.

Estrogen receptor activation contributes to RNF146 expression and neuroprotection in Parkinson's disease models

“…Although the present work focused on liquiritigenin as an RNF146 inducer and neuroprotective agent, further studies characterizing other inducers could shed further light on RNF146 induction mechanisms and their therapeutic potential. Piperlonguminine is of particular interest because this compound is brain-permeable and neuroprotective in rotenone and lipopolysaccharide animal models [ 27 ]. Its property to stimulate autophagy would be additional therapeutic advantege especially for neurodegenerative disease with abnormal protein aggregation.…”

Lipopolysaccharide animal models of Parkinson’s disease: Recent progress and relevance to clinical disease

“…Unilateral administration of a single dose of LPS into the SN or striatum which are the most common regions for stereotaxic administration of LPS, induces degeneration of dopaminergic neurons in the SN and their neuronal projections to the striatum. Intranigral administration of 10 ​μg of LPS in rats induces a 50–80% reduction in the number of tyrosine hydroxylase (TH) positive cells in the SN compared to shams at 4 weeks post-treatment ( Bao et al., 2018 ; Chen et al., 2017 ; Fu et al., 2015 ; He et al., 2016a ; Wang et al., 2015a ). This lesion to the nigrostriatal pathway was illustrated by increased rotational behaviour in the apomorphine and amphetamine induced rotational test which was not evident in the sham group.…”

“…This lesion to the nigrostriatal pathway was illustrated by increased rotational behaviour in the apomorphine and amphetamine induced rotational test which was not evident in the sham group. Moreover, striatal dopamine was reduced by 34–50%, along with motor function which was assessed with the rotarod test, commonly used to evaluate motor skills based on the ability of the animals to maintain themselves on a rotating rod ( Bao et al., 2018 ; Chen et al., 2017 ; Fu et al., 2015 ; He et al., 2016a ; Wang et al., 2015a ). Furthermore, according to Choi et al.…”

“…42% and 54% ↓ NE neurons in LC (7m, 10m), 28% ↓ Neun + in motor cortex (7m) and 30% ↓ in hippocampus (10m) 26 ↑ gut permeability 23 Rats 5 ​mg/kg (once) 15d 28 TH protein 50% ↓ 28 Not assessed Not assessed Not assessed Not assessed Not assessed Intranasal (no studies for rats) C57BL/6 mice 1 ​mg/ml (every other day) 21d 32 , 1m 29,30,31 , 5m 33 TH neurons 38–55% 29,30,31 , 79% ↓ 33 ≈40% ↓ 33 2.2 29 and 2.4-fold 30 in α-syn protein ↓ voluntary movement in the open field 29,30,33 and bradykinesia (pole test) 30,31 44% ↓ in TH protein and 2.75-fold ↑ in α-syn protein in OB 30 , 31.9% ↓ in TH neurons in OB 32 , 1.75-fold ↑ in α-syn protein in OB 33 Not assessed Abbreviation s : TH, tyrosine hydroxylase; SN, substantia nigra; OB, olfactory bulb; LC, locus coeruleus; NE, noradrenaline; α-syn, α-synuclein. Reference s : 1 ( Chen et al., 2017 ); 2 ( Wang et al., 2015c , Wang et al., 2015b , Wang et al., 2015a ); 3 ( He et al., 2016b , He et al., 2016a ); 4 ( Fu et al., 2015 ); 5 ( Bao et al., 2018 ); 6 ( Hritcu and Ciobica, 2013 ); 7 ( Hritcu and Gorgan, 2014 ); 8 ( Zheng et al., 2013b , Zheng et al., 2013a …”

A selective and sensitive UFLC-MS/MS method for the simultaneous determination of five alkaloids fromPiper longumL. and its application in the pharmacokinetic study of 6-OHDA-induced Parkinson's disease rats

“…It was also found that the activity of superoxide dismutase (SOD) was enhanced in PD rat aer administration of PLA. [4][5][6][7][8][9] SOD plays a signicant role in protecting cells from oxidative stress and preventing neuronal apoptosis.…”