Objective: 1) to examine whether the phyto-neurosteroid: Ginsenoside Rg3 recently demonstrated to activate the epigenetic SIRTI signaling, will rescue the motor impairment in rodent model of PD: 2) to investigate whether Ginsensoide Rg3 neuroprotection is related to its anti-inflammatory action in  antagonizing CD-11b, the inflammation biomarker of microglia activation, and its neurotrophic effect in resetting  expression of NF:: Nerve Growth factor (NGF) and Neurotrophin (NF-3).

Background: Growing body of evidence supports microglia activation  coupled with dysregulatino of NF-mediated neural plasticity , contributes towards loss of dopamine neurons (DA) in PD.  Very few studies address the  issue whether epigenetics regulation of neuroinflammation and NF signal may be neuroprotective in PD. 

Methods: We evaluated the pharmacological actions of Ginsenoside Rg3 in : 1) the in vitro model of MPTP model involving exposure of rodent mesencephalic dopamine neurons to neurotoxic doses of MPTP; 2) the in vivo  MPTP model in the C57/BL mice treated weekly with MPTP. We measured the motor performance with standardized behavioral paradigms of climbing pole and locomotor activity counts. DA tyrosine hydroxylase (TH+) neurons and microglia activation biomarker: CD-11b  were quantified with immuno-histochemistry.  NG-3 and Nerve Growth factor:NGF expression were determined with Western blot, real-time PCR assays..

Results: In the vitro model, ginsenoside Rg3 restored DA  (TH+) neuronal loss . In the subchronic MPTP model, ginsensoide Rg3 administered orally at daily dosages of 5 mg/kg, 10 mg/kg and 20 mg/kg significantly blocked (p < 0.05) decline in TH(+) neurons in the striatum and substantia nigra, when compared with the placebo group. Ginsenoside Rg3 significantly improved the motor deficits and antagonized the up-regulation of CD-11b in the MPTP group. The changes in motor functions CD-11b expression were linked directly to up-regulation of mRNA levels of NF-3 and NGF .

Conclusions: Our  results of Ginsenoside Rg3 in ]MPTP PD model provide evidence that SIRTI epigenetic targeting  rescues  motor dysfunction , reduces neuroinflammation , and restores NF dysregulation in PD, Controlled trial of Ginsenoside Rg3 in PD  is warranted to establish Rg3 efficacy in PD.

References: Chu S. Chen J, Sayed F, Et al SIRTI deficiency in microglia contributes to Cognitive decline in Aging and neurodegeneration via Epigenetic regulation of Il-1beta.  Neurobiol. Dis. 2015: 35(1); 807-818.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/study-of-neuroprotective-effects-of-ginsenside-rg3-the-prototypal-epigenetic-sirtuin-1-activator-in-targeting-microglia-activation-and-neurotrophic-factor-nf-neural-plasticity-in-mptp-model-of-p/