No abstract

No abstract

No abstract

Neuroinflammation plays a pivotal role in the pathogenesis of Parkinson’s disease. Ginsenoside Rg1, the most active ingredient of ginseng, has been reported to exert neuroprotective effects via estrogen and glucocorticoid receptors. The present study evaluated the involvement of the G protein-coupled estrogen receptor (GPER) in the anti-inflammatory effects of ginsenoside Rg1 against lipopolysaccharide (LPS)-induced microglia activation in the BV2 microglial cell line and ventral mesencephalic primary microglial culture. The pharmacological blockade and lentivirus-mediated small interfering RNA (siRNA) knockdown of GPER were used to study the underlying mechanism. Rg1 attenuated LPS-induced upregulation of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) mRNA and protein levels. The GPER antagonist G15 blocked the inhibitory effects of Rg1 and the GPER-specific agonist G1 on LPS-induced microglia activation. Rg1 mimicked the effects of G1 by inhibiting the LPS-induced activation of nuclear transcription factor-kappa B (NF-κB) and mitogen activated protein kinase signaling pathways, which was also blocked by G15. Moreover, lentivirus-mediated siRNA knockdown of GPER inhibited the anti-inflammatory effects of Rg1. Taken together, our results indicate that GPER is involved in the anti-inflammatory effects of Rg1 against LPS-induced microglia activation. These findings provide a new biological target of Rg1 for the treatment of neuroinflammatory disorders.

Background Multiple studies have evaluated the associations between 5,10‐methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and migraine risk with conflicting results. Therefore, we conducted a meta‐analysis on this theme. Methods We searched the electronic databases of PubMed, EmBase, ScienceDirect, and Cochrane Library for all relevant studies published until April 6, 2018. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) in allelic, dominant, recessive, homozygous, and heterozygous models were calculated using random effects model to assess the strength of associations. We also performed subgroup analyses stratified by ethnicity and migraine subtypes, respectively. Results Twenty‐six studies (20 in Caucasians, 3 in Asians, 2 in Indians, and 1 in Pakistanis) with 10,228 migraineurs and 28,608 controls were included in this meta‐analysis. In the overall population, the allele 677T and TT genotype were associated with an increased risk for total migraine and migraine with aura (MA) (total migraine: T vs C: OR = 1.19, 95%CI = 1.06‐1.33, P = .004; TT vs CC: OR = 1.32, 95%CI = 1.07‐1.64, P = .011; MA: T vs C: OR = 1.28, 95%CI = 1.09‐1.51, P = .003; TT vs CC: OR = 1.51, 95%CI = 1.09‐2.08, P = .012), but not for migraine without aura (MO). Subgroup analysis stratified by ethnicity revealed similar findings in Caucasians. In Asians, the association was detected only in recessive model in total migraine (TT vs CT + CC: OR = 1.80, 95%CI = 1.14‐2.85, P = .012). Results in Indians did not suggest any association in either total migraine or its subtypes. Pooled results of 5 studies (4 in Caucasians and 1 in Indians) on A1298C polymorphism indicated a significant association between the CC genotype and migraine risk (CC vs AA: OR = 1.78, 95%CI = 1.03‐3.07, P = .038), which only appeared for MO (CC vs AA: OR = 2.83, 95%CI = 1.30‐6.16, P = .009). Conclusions Our meta‐analysis suggested that allele 677T in MTHFR C677T polymorphism might be a genetic risk factor for MA in Caucasians, and genotype 1298CC might contribute to MO susceptibility.