6-Shogaol, a ginger product, modulates neuroinflammation: A new approach to neuroprotection

Graduate School of East-West Medical Science, Kyung Hee University Global Campus, #1732 Deogyeong-daero, Giheung-gu, Yongin, Gyeonggi-do 446-701, Republic of Korea.
Neuropharmacology (Impact Factor: 5.11). 03/2012; 63(2):211-23. DOI: 10.1016/j.neuropharm.2012.03.016
Source: PubMed


Inflammatory processes in the central nervous system play an important role in a number of neurodegenerative diseases mediated by microglial activation, which results in neuronal cell death. Microglia act in immune surveillance and host defense while resting. When activated, they can be deleterious to neurons, even resulting in neurodegeneration. Therefore, the inhibition of microglial activation is considered a useful strategy in searching for neuroprotective agents. In this study, we investigated the effects of 6-shogaol, a pungent agent from Zingiber officinale Roscoe, on microglia activation in BV-2 and primary microglial cell cultures. 6-Shogaol significantly inhibited the release of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). The effect was better than that of 6-gingerol, wogonin, or N-monomethyl-l-arginine, agents previously reported to inhibit nitric oxide. 6-Shogaol exerted its anti-inflammatory effects by inhibiting the production of prostaglandin E(2) (PGE(2)) and proinflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), and by downregulating cyclooxygenase-2 (COX-2), p38 mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF-κB) expression. In addition, 6-shogaol suppressed the microglial activation induced by LPS both in primary cortical neuron-glia culture and in an in vivo neuroinflammatory model. Moreover, 6-shogaol showed significant neuroprotective effects in vivo in transient global ischemia via the inhibition of microglia. These results suggest that 6-shogaol is an effective therapeutic agent for treating neurodegenerative diseases.

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Available from: Dong Hyun Kim, Dec 26, 2013
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    • "This compound has been shown to protect hippocampal neurons via an increase in choline acetyltransferase and the choline transporter11. In in vitro and in vivo inflammatory models, 6-shogaol protected microglia against lipopolysaccharide-induced toxicity by inhibiting the production of NO, prostaglandin E, and proinflammatory cytokines such as TNF-α and interleukin-1β via the downregulation of COX-2, iNOS, p38 mitogen-activated protein kinase, and nuclear factor kappa B (NF-κB) expression12. Moreover, 6-shogaol exhibited neuroprotective effects via the inhibition of microglia in an in vivo model of transient global ischemia12. "
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    ABSTRACT: Aim: 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger, has shown various neurobiological and anti-inflammatory effects. The aim of this study was to examine the effects of 6-shogaol on neuroinflammatory-induced damage of dopaminergic (DA) neurons in Parkinson's disease (PD) models. Methods: Cultured rat mesencephalic cells were treated with 6-shogaol (0.001 and 0.01 μmol/L) for 1 h, then with MPP+(10 μmol/L) for another 23 h. The levels of TNF-α and NO in medium were analyzed spectrophotometrically. C57/BL mice were administered 6-shogaol (10 mg·kg−1·d−1, po) for 3 d, and then MPTP (30 mg/kg, ip) for 5 d. Seven days after the last MPTP injection, behavioral testings were performed. The levels of tyrosine hydroxylase (TH) and macrophage antigen (MAC)-1 were determined with immunohistochemistry. The expression of iNOS and COX-2 was measured using RT PCR. Results: In MPP+-treated rat mesencephalic cultures, 6-shogaol significantly increased the number of TH-IR neurons and suppressed TNF-α and NO levels. In C57/BL mice, treatment with 6-shogaol reversed MPTP-induced changes in motor coordination and bradykinesia. Furthermore, 6-shogaol reversed MPTP-induced reductions in TH-positive cell number in the substantia nigra pars compacta (SNpc) and TH-IR fiber intensity in stratum (ST). Moreover, 6-shogaol significantly inhibited the MPTP-induced microglial activation and increases in the levels of TNF-α, NO, iNOS, and COX-2 in both SNpc and ST. Conclusion: 6-Shogaol exerts neuroprotective effects on DA neurons in in vitro and in vivo PD models.
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    • "A recent study has demonstrated that 6-shogaol, not 6-gingerol, suppresses LPS-induced iNOS, COX-2, IL- 1b and TNF-a expression through downregulation of p38 mitogenactivated protein kinase (MAPK) signalling and NF-jB activation in both of BV2 and primary microglial cells (Ha et al., 2012). Additionally , the inhibition of 6-shogaol on microglial activation mitigated ischemia-induced neurological damages in vivo has been published (Ha et al., 2012). Although 6-gingerol and 6-shogaol have been demonstrated, respectively, to attenuate LPS-induced iNOS and COX-2 expression in murine macrophages by blocking NF-jB activation (Lee, Lee, Chen, & Chang, 2009; Pan et al., 2008; Tripathi, Fig. 4. Representative HPLC chromatogram of the selected gingerol-related compounds (A) and fresh ginger ethanolic extract (B). "
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