• Biomolecules & Therapeutics
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• 제31권1호
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• pp.27-39
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• 2023

Extensive research supported the therapeutic potential of curcumin, a naturally occurring compound, as a promising cytokine-suppressive anti-inflammatory drug. This study aimed to investigate the synergistic anti-inflammatory and anti-cytokine activities by combining 6-shogaol and 10-shogaol to curcumin, and associated mechanisms in modulating lipopolysaccharides and interferon-γ-induced proinflammatory signaling pathways. Our results showed that the combination of 6-shogaol-10-shogaolcurcumin synergistically reduced the production of nitric oxide, inducible nitric oxide synthase, tumor necrosis factor and interlukin-6 in lipopolysaccharides and interferon-γ-induced RAW 264.7 and THP-1 cells assessed by the combination index model. 6-shogaol-10-shogaol-curcumin also showed greater inhibition of cytokine profiling compared to that of 6-shogaol-10-shogaol or curcumin alone. The synergistic anti-inflammatory activity was associated with supressed NFκB translocation and downregulated TLR4-TRAF6-MAPK signaling pathway. In addition, SC also inhibited microRNA-155 expression which may be relevant to the inhibited NFκB translocation. Although 6-shogaol-10-shogaol-curcumin synergistically increased Nrf2 activity, the anti-inflammatory mechanism appeared to be independent from the induction of Nrf2. 6-shogaol-10-shogaol-curcumin provides a more potent therapeutic agent than curcumin alone in synergistically inhibiting lipopolysaccharides and interferon-γ induced proinflammatory mediators and cytokine array in macrophages. The action was mediated by the downregulation of TLR4/TRAF6/MAPK pathway and NFκB translocation.

• Preventive Nutrition and Food Science
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• 제17권2호
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• pp.166-171
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• 2012

6-Shogaol, a dehydrated form of 6-gingerol, is a minor component in ginger (Zingiber officinale Roscoe) and has recently been reported to have more potent bioactivity than 6-gingerol. Based on the thermal instability of gingerols (their dehydration to corresponding shogaols at high temperature), we aimed to develop an optimal process to maximize the 6-shogaol content during ginger extraction by modulating temperature and pH. Fresh gingers were dried under various conditions: freeze-, room temperature (RT)- or convection oven-drying at 60 or $80^{\circ}C$, and extracted by 95% ethanol at RT, 60 or $80^{\circ}C$. The content of 6-shogaol was augmented by increasing both drying and extraction temperatures. The highest production of 6-shogaol was achieved at $80^{\circ}C$ extraction after drying at the same temperature and the content of 6-shogaol was about 7-fold compared to the lowest producing process by freezing and extraction at RT. Adjustment of pH (pH 1, 4, 7 and 10) for the 6-shogaol-richest extract (dried and extracted both at $80^{\circ}C$) also affected the chemical composition of ginger and the yield of 6-shogaol was maximized at the most acidic condition of pH 1. Taken together, the current study shows for the first time that a maximized production of 6-shogaol can be achieved during practical drying and extraction process of ginger by increasing both drying and extracting temperatures. Adjustment of pH to extraction solvent with strong acid also helps increase the production of 6-shogaol. Our data could be usefully employed in the fields of food processing as well as nutraceutical industry.

• 한국식품과학회지
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• 제46권5호
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• pp.588-592
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• 2014

본 연구는 다진 생강에 다량 함유된 6-gingerol을 뇌질환 개선 등의 기능성이 보고된 6-shogaol로 변환시키기 위하여 $CO_2$를 이용한 6.4MPa의 가압조건에서 가열 온도와 시간을 변수로 두고 중심합성설계법을 이용한 최적반응표면분석법을 적용하였다. 적용 온도 $70-130^{\circ}C$ ($X_1$)와 적용 시간 95-265분($X_2$)을 독립변수로, 6-gingerol함량($Y_1$, mg/g dried ginger)와 6-shogaol함량($Y_2$, mg/g dried ginger)을 종속변수로 설정하였다. 그 결과 온도와 시간이 대체적으로 증가할수록 6-gingerol은 감소하였으며 반대로 6-shogaol은 증가하였다. 도출된 반응표면 설계를 분석한 결과 압력이 6.4 MPa일 경우 적용 온도($X_1$)는 $130^{\circ}C$, 적용 시간($X_2$)는 204분이었다. 최적반응표면분석 결과 예측된 6-gingerol과 6-shogaol 함량은 각각 건조시킨 생강을 기준으로 0.13, 3.85 mg/g이며, 이때 만족도는 0.991이었다. 본 실험 결과를 통하여 도출된 가압조건에서의 열처리 방법은 스팀 등을 이용한 물리적 열처리 기술에 비해 소요 시간과 소모되는 에너지를 줄일 수 있었고, 6-gingerol에서 6-shogaol로의 변환율이 탁월하기 때문에 친환경적이고 효율적인 6-shogaol을 얻을 수 있는 기술임을 확인할 수 있었다.

• Biomolecules & Therapeutics
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• 제27권2호
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• pp.152-159
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• 2019

Multiple sclerosis (MS) is an autoimmune disease characterized by progressive neuronal loss, neuroinflammation, axonal degeneration, and demyelination. Previous studies have reported that 6-shogaol, a major constituent of ginger (Zingiber officinale rhizome), and its biological metabolite, 6-paradol, have anti-inflammatory and anti-oxidative properties in the central nervous system (CNS). In the present study, we investigated whether 6-shogaol and 6-paradol could ameliorate against experimental autoimmune encephalomyelitis (EAE), a mouse model of MS elicited by myelin oligodendrocyte glycoprotein ($MOG_{35-55}$) peptide immunization with injection of pertussis toxin. Once-daily administration of 6-shogaol and 6-paradol (5 mg/kg/day, p.o.) to symptomatic EAE mice significantly alleviated clinical signs of the disease along with remyelination and reduced cell accumulation in the white matter of spinal cord. Administration of 6-shogaol and 6-paradol into EAE mice markedly reduced astrogliosis and microglial activation as key features of immune responses inside the CNS. Furthermore, administration of these two molecules significantly suppressed expression level of tumor necrosis $factor-{\alpha}$, a major proinflammatory cytokine, in EAE spinal cord. Collectively, these results demonstrate therapeutic efficacy of 6-shogaol or 6-paradol for EAE by reducing neuroinflammatory responses, further indicating the therapeutic potential of these two active ingredients of ginger for MS.

• 한국식품과학회지
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• 제51권5호
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• pp.447-451
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• 2019

건조한 생강을 아임계수 추출 기술을 이용하여 6-gingerol, 6-shogaol을 추출하고 유효성분의 추출 효율과 영향을 비교 분석하였다. 추출 결과, 건조를 할 경우, 건조 조건에 따라 6-shogaol이 증가하기도 했으나 극한 조건으로 건조하여 생강의 수분함량이 매우 낮아질 경우, 오히려 생강 조직 사이의 공간이 감소하고 그로 인한 추출 용매의 mass transfer가 낮아져 6-gingerol과 6-shogaol 함량은 모두 감소하였다. 또한 비교적 높은 온도인 60, $80^{\circ}C$에서 4시간의 건조를 시킬 경우, 6-shogaol은 열분해가 되었다. 결과적으로 생강의 $60^{\circ}C$, 2시간이 가장 적절한 건조 조건이었다. 특히, 생강의 건조 조건과 유효성분의 추출 경향은 높은 상관관계를 나타내었다. 이는 오직 물만을 사용하여 유효성분을 추출하는 친환경적이며 안전하고 독성이 없는 아임계수 추출 방법이 최적화된 생강 시료의 건조 조건에서 6-shogaol의 유효성분을 선택적으로 추출할 수 있는 잠재성과 우수성을 확인한 결과이며, 다양한 식물에서 유효성분을 추출하거나 가공하는 식품 산업에 응용하여 사용될 수 있을 것이다.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.417-424
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• 2023

Parkinson's disease (PD) which has various pathological mechanisms, recently, it is attracting attention to the mechanism via microbiome-gut-brain axis. 6-Shogaol, a representative compound of ginger, have been known for improving PD phenotypes by reducing neuroinflammatory responses. In the present study, we investigated whether 6-shogaol and ginger attenuate degeneration induced by Proteus mirabilis (P. mirabilis) on the intestine and brain, simultaneously. C57BL/6J mice received P. mirabilis for 5 days. Ginger (300 mg/kg) and 6-shogaol (10 mg/kg) were treated by gavage feeding for 22 days including the period of P. mirabilis treatment. Results showed that 6-shogaol and ginger improved motor dysfunction and dopaminergic neuronal death induced by P. mirabilis treatment. In addition, they suppressed P. mirabilis-induced intestinal barrier disruption, pro-inflammatory signals such as toll-like receptor and TNF-α, and intestinal α-synuclein aggregation. Moreover, ginger and 6-shogaol significantly inhibited neuroinflammation and α-synuclein in the brain. Taken together, 6-shogaol and ginger have the potential to ameliorate PD-like motor behavior and degeneration of dopaminergic neurons induced by P. mirabilis in mice. Here, these findings are meaningful in that they provide the first experimental evidence that 6-shogaol might attenuate PD via regulating gut-brain axis.

• The Korean Journal of Physiology and Pharmacology
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• 제22권6호
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• pp.627-636
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• 2018

Endometriosis (EM) is one of the most common gynaecological disorder affecting women in their reproductive age. Mechanisms involved in the pathogenesis of EM remains poorly understood, however inflammatory responses have been reported to be significantly involved. The efficacy of 6-shogaol on proliferation of endometriotic lesions and inflammatory pathways in experimentally-induced EM model was explored in this study. EM was stimulated in Sprague-Dawley rats by implantation of autologous endometrium onto the peritoneum abdominal wall. Separate groups were treated with 6-shogaol (50, 100 or 150 mg/kg b.wt/day) via oral gavage for one month period. Gestrinone (GTN) group received GTN (0.5 mg/kg/day) as positive control. Five weeks after implantation, the spherical volume of ecto-uterine tissues was determined. Treatment with 6-shogaol significantly reduced the implant size. Histological analysis reported atrophy and regression of the lesions. 6-shogaol administration effectively down-regulated $NF-{\kappa}B$ signaling, VEGF and VEGFR-2 (Flk-1) expression in the endometriotic lesions. Excess production of $IL-1{\beta}$ and IL-6 (pro-inflammatory cytokines), PGE2 and nitric oxide (NO) were reduced. Overall, the results of the study reveal the efficacy of 6-shogaol against endometriosis via effectively suppressing proliferation of the lesions and modulating angiogenesis and $COX-2/NF-{\kappa}B$-mediated inflammatory cascades.

• 한국약용작물학회지
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• 제24권1호
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• pp.7-13
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• 2016

Background : Ginger has been extensively used in foods and traditional medicines in Asian countries. Despite its frequent consumption in daily life, the mechanism of potential interactions between ginger components-drug has not been examined. To elucidate the mechanism of governing the effects of 6-shogaol, a primary constituent of dried ginger, on human cytochrome P450 (CYP) isoenzymes an incubation studies were carried out using pooled human liver microsome (HLM). Methods and Results : CYP isoenzyme specific substrate was incubated with multiple concentrations of inhibitor, HLM and cofactors. 6-shogaol showed a potent inhibitory effect on CYP2C9, CYP1A2 and CYP2C19 with half maximal inhibitory concentration ($IC_{50}$) values of 29.20, 20.68 and $18.78{\mu}M$ respectively. To estimate the value of the inhibition constant ($K_i$) and the mode of inhibition, an incubation study with varying concentrations of each CYP isoenzyme-specific probe was performed. 6-shogaol inhibited CYP2C9 and CYP2C19 noncompetitively ($K_i=29.02$ and $19.26{\mu}M$ respectively), in contrast, the inhibition of CYP1A2 was best explained by competitive inhibition ($K_i=6.33{\mu}M$). Conclusions : These findings suggest that 6-shogaol may possess inhibitory effects on metabolic activities mediated by CYP1A2, CYP2C9 and CYP2C19 in humans.

• Archives of Pharmacal Research
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• 제18권2호
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• pp.136-137
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• 1995

• Molecules and Cells
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• 제27권2호
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• pp.211-215
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• 2009

Toll-like receptors (TLRs) play a critical role in sensing microbial components and inducing innate immune and inflammatory responses by recognizing invading microbial pathogens. Lipopolysaccharide-induced dimerization of TLR4 is required for the activation of downstream signaling pathways including nuclear factor-kappa B ($NF-{\kappa}B$). Therefore, TLR4 dimerization may be an early regulatory event in activating ligand-induced signaling pathways and induction of subsequent immune responses. Here, we report biochemical evidence that 6-shogaol, the most bioactive component of ginger, inhibits lipopolysaccharide-induced dimerization of TLR4 resulting in the inhibition of $NF-{\kappa}B$ activation and the expression of cyclooxygenase-2. Furthermore, we demonstrate that 6-shogaol can directly inhibit TLR-mediated signaling pathways at the receptor level. These results suggest that 6-shogaol can modulate TLR-mediated inflammatory responses, which may influence the risk of chronic inflammatory diseases.