Ginger Studies Anti-inflammation Anti-cancer
active ingredients
gingerols and 6-shogaols
anti-inflammation,
anti-ulcer, protect mucus
Antioxidant
Anti-C.albicans
Anti-cancer via ROS, caspases activation, inhibition of MMP-9 via blockage of NF-kB signaling
6-shogaol inhibits microtubules
inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.
reducing MMP-9 expression and secretion
6-shogaol inhibits NFkB
6-shogaol exerts an anti-inflammatory effect through down-regulation of NF-κB signalling
gingerols enhance glucose uptake by increasing surface GLUT4
Front Cell Infect Microbiol. 2018 Aug 28;8:299. doi: 10.3389/fcimb.2018.00299. eCollection 2018.
Antibiofilm and Antivirulence Activities of 6-Gingerol and 6-Shogaol Against Candida albicans Due to Hyphal Inhibition.
Lee JH1, Kim YG1, Choi P2, Ham J2, Park JG3, Lee J1.
Author information
1
School of Chemical Engineering, Yeungnam University, Gyeongsan, South Korea.
2
Natural Products Research Institute, Korea Institute of Science and Technology, Gangneung, South Korea.
3
Advanced Bio Convergence Center, Pohang Technopark Foundation, Pohang, South Korea.
Abstract
Candida albicans is an opportunistic pathogen and responsible for candidiasis. C. albicans readily forms biofilms on various biotic and abiotic surfaces, and these biofilms can cause local and systemic infections. C. albicans biofilms are more resistant than its free yeast to antifungal agents and less affected by host immune responses. Transition of yeast cells to hyphal cells is required for biofilm formation and is believed to be a crucial virulence factor. In this study, six components of ginger were investigated for antibiofilm and antivirulence activities against a fluconazole-resistant C. albicans strain. It was found 6-gingerol, 8-gingerol, and 6-shogaol effectively inhibited biofilm formation. In particular, 6-shogaol at 10 μg/ml significantly reduced C. albicans biofilm formation but had no effect on planktonic cell growth. Also, 6-gingerol and 6-shogaol inhibited hyphal growth in embedded colonies and free-living planktonic cells, and prevented cell aggregation. Furthermore, 6-gingerol and 6-shogaol reduced C. albicans virulence in a nematode infection model without causing toxicity at the tested concentrations. Transcriptomic analysis using RNA-seq and qRT-PCR showed 6-gingerol and 6-shogaol induced several transporters (CDR1, CDR2, and RTA3), but repressed the expressions of several hypha/biofilm related genes (ECE1 and HWP1), which supported observed phenotypic changes. These results highlight the antibiofilm and antivirulence activities of the ginger components, 6-gingerol and 6-shogaol, against a drug resistant C. albicans strain.
KEYWORDS:
C. albicans; antivirulence; biofilm; gingerol; hyphae; shogaol
6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation
H Ling, H Yang, [...], and E-H Chew
Additional article information
Associated Data
Supplementary Materials
Abstract
BACKGROUND AND PURPOSE
Shogaols are reported to possess anti-inflammatory and anticancer activities. However, the antimetastatic potential of shogaols remains unexplored. This study was performed to assess the effects of shogaols against breast cancer cell invasion and to investigate the underlying mechanisms.
EXPERIMENTAL APPROACH
The anti-invasive effect of a series of shogaols was initially evaluated on MDA-MB-231 breast cancer cells using the matrigel invasion assay. The suppressive effects of 6-shogaol on phorbol 12-myristate 13-acetate (PMA)-induced matrix metalloproteinase-9 (MMP-9) gelatinolytic activity and nuclear factor-κB (NF-κB) activation were further determined.
NF-κB has been suggested to be a target for many biologically active natural products derived from plant foods such as curcumin, resveratrol, epigallocatechin gallate and sulforaphane (Surh et al., 2001; Woo et al., 2004). Moreover, studies have reported that 6-shogaol exerts an anti-inflammatory effect through down-regulation of NF-κB signalling (Pan et al., 2008a). However, to date, the molecular mechanism by which 6-shogaol inhibits the NF-κB activation cascade is not fully understood. Our present study had demonstrated that 6-shogaol exerted anti-NF-κB effect through inhibition of phosphorylation of IKKα and IKKβ subunits of the IKK complex. This led to blockade of IκBα phosphorylation and prevention of IκBα proteosomal degradation with a resulting decrease in p65 nuclear translocation and NF-κB transcriptional activation. Furthermore, 6-shogaol inhibited p65 phosphorylation at serine 536 without affecting total p65 expression. The phosphorylation of p65 at serine 536 has been suggested to play an important role in p65 nuclear localization and transcriptional activity (Ghosh and Karin, 2002; Viatour et al., 2005). Taken together, our findings demonstrate that the in vitro anti-invasive effect of 6-shogaol is mediated through its interference with NF-κB signalling.
In summary, our study has focused on the naturally occurring shogaols found in ginger. We have demonstrated that sublethal doses of 6-, 8- and 10-shogaol, by reducing MMP-9 expression and secretion, have an inhibitory effect on PMA-induced breast cancer cell invasion. Furthermore, we provide evidence that 6-shogaol impairs breast cancer cell invasion, at least in part, through targeting the NF-κB activation cascade (summarized in Figure 7). In recent years, an increasing number of natural products possessing anticancer properties have been unveiled. Coupled with the elucidation of their antitumour mechanism(s), the exploitation of their use in clinical chemotherapeutic strategies is promisingly realizing. In view of the impressive in vitro potency of 6-shogaol in reversing PMA-induced cancer cell invasion at non-cytotoxic concentrations, and as specific antimetastatic agents with minimal or no complications from their cytotoxicities are preferred, this series of naturally occurring phytochemicals are indeed worthy of further development as antimetastatic agents for clinical use.6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion by reducing matrix metalloproteinase-9 expression via blockade of nuclear factor-κB activation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010581/
6-Shogaol & 6-Gingerol
http://www.healthnutnews.com/new-study-shows-ginger-is-10000x-stronger-than-chemo-and-only-kills-cancer-cells
2 November 2015
[ Excerpts ]
NEW STUDY SHOWS GINGER IS 10,000X STRONGER THAN CHEMO (AND ONLY KILLS CANCER CELLS)
by
Erin Elizabeth
[ A study conducted by Georgia State University found that 6-Shogaol ( extract of ginger ) reduced mouse prostate tumor size by 56%... Another study showed it to be superior to chemotherapy against breast cancer stem cells, at concentrations that are non-toxic to normal cells. 6-shogaol increases apoptosis -- cancer cell death -- by inducing of autophagy, and it inhibits the formaton of breast cancer lumps... The cancer drug taxol is not nearly as effective as 6-shogaol, which is 10,000 times more effective at killing cancer stem cells, inhibits tumor formation, and prevents the formation of tumors. ]
Shogaol, also known as (6)-shogaol, is a pungent constituent of ginger similar in chemical structure to gingerol. Like zingerone, it is produced when ginger is dried or cooked.[1]
Shogaols are artifacts formed during storage or through excess heat, probably created by a dehydration reaction of the gingerols. The ratio of shogaols to gingerols sometimes is taken as an indication of product quality.[2]
The name 'shogaol' is derived from the Japanese name for ginger (生姜、shōga).
Shogaol is rated 160,000 SHU on Scoville scale. When compared to other pungent compounds, shogaol is moderately more pungent than piperine, but less than capsaicin.
Compound Scoville Heat Units (SHU)
Capsaicin 15,000,000[3]
(6)-Shogaol 160,000
Piperine 100,000
(6)-Gingerol 60,000
Pharmacology
Among ginger constituents, it has a very strong antitussive (anti-cough) effect.[medical citation needed] Both shogaol and gingerols reduced blood pressure and gastric contraction.[4] Shogaol has been shown to induce apoptosis (kill) in human colorectal carcinoma cells via reactive oxygen species.[5] It is broken down into 16 metabolites via the mercapturic acid pathway.[4] Acetylcysteine was found to reduce effectiveness of shogaol's apoptotic properties.[5]6-Shogaol ( Extract of Ginger ) vs Cancer http://www.rexresearch.com/6shogaol/6shogaol.html
http://www.ncbi.nlm.nih.gov/pubmed/17706603
Biochem Biophys Res Commun. 2007 Oct 12;362(1):218-23. Epub 2007 Aug 10.
Ginger ingredients reduce viability of gastric cancer cells via distinct mechanisms.
Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H.
Abstract
Ginger has been used throughout the world as spice, food and traditional herb. We found that 6-gingerol, a phenolic alkanone isolated from ginger, enhanced the TRAIL-induced viability reduction of gastric cancer cells while 6-gingerol alone affected viability only slightly. 6-Gingerol facilitated TRAIL-induced apoptosis by increasing TRAIL-induced caspase-3/7 activation. 6-Gingerol was shown to down-regulate the expression of cIAP1, which suppresses caspase-3/7 activity, by inhibiting TRAIL-induced NF-kappaB activation. As 6-shogaol has a chemical structure similar to 6-gingerol, we also assessed the effect of 6-shogaol on the viability of gastric cancer cells. Unlike 6-gingerol, 6-shogaol alone reduced the viability of gastric cancer cells. 6-Shogaol was shown to damage microtubules and induce mitotic arrest. These findings indicate for the first time that in gastric cancer cells, 6-gingerol enhances TRAIL-induced viability reduction by inhibiting TRAIL-induced NF-kappaB activation while 6-shogaol alone reduces viability by damaging microtubules.
http://pubs.acs.org/doi/abs/10.1021/jf504934m
J. Agric. Food Chem., 2015, 63 (6), pp 1730–1738
DOI: 10.1021/jf504934m
February 9, 2015
6-Shogaol, an Active Constituent of Dietary Ginger, Impairs Cancer Development and Lung Metastasis...
Ya-Ling Hsu, Jen-Yu Hung, Ying-Ming Tsai, Eing-Mei Tsai, Ming-Shyan Huang, Ming-Feng Hou, and Po-Lin Kuo
This study has two novel findings: it is not only the first to demonstrate that tumor-associated dendritic cells (TADCs) facilitate lung and breast cancer metastasis in vitro and in vivo by secreting inflammatory mediator CC-chemokine ligand 2 (CCL2), but it is also the first to reveal that 6-shogaol can decrease cancer development and progression by inhibiting the production of TADC-derived CCL2. Human lung cancer A549 and breast cancer MDA-MB-231 cells increase TADCs to express high levels of CCL2, which increase cancer stem cell features, migration, and invasion, as well as immunosuppressive tumor-associated macrophage infiltration. 6-Shogaol decreases cancer-induced up-regulation of CCL2 in TADCs, preventing the enhancing effects of TADCs on tumorigenesis and metastatic properties in A549 and MDA-MB-231 cells. A549 and MDA-MB-231 cells enhance CCL2 expression by increasing the phosphorylation of signal transducer and activator of transcription 3 (STAT3), and the activation of STAT3 induced by A549 and MDA-MB-231 is completely inhibited by 6-shogaol. 6-Shogaol also decreases the metastasis of lung and breast cancers in mice. 6-Shogaol exerts significant anticancer effects on lung and breast cells in vitro and in vivo by targeting the CCL2 secreted by TADCs. Thus, 6-shogaol may have the potential of being an efficacious immunotherapeutic agent for cancers.
6-Shogaol ( Extract of Ginger ) vs Cancer http://www.rexresearch.com/6shogaol/6shogaol.html
Metabolism of [6]-Shogaol in Mice and in Cancer Cells
Huadong Chen, Lishuang Lv, Dominique Soroka, Renaud F. Warin, Tiffany A. Parks, Yuhui Hu, Yingdong Zhu, Xiaoxin Chen and Shengmin Sang Abstract Ginger has received extensive attention because of its antioxidant, anti-inflammatory, and antitumor activities. However, the metabolic fate of its major components is still unclear. In the present study, the metabolism of [6]-shogaol, one of the major active components in ginger, was examined for the first time in mice and in cancer cells. Thirteen metabolites were detected and identified, seven of which were purified from fecal samples collected from [6]-shogaol-treated mice. Their structures were elucidated as 1-(4′-hydroxy-3′-methoxyphenyl)-4-decen-3-ol (M6), 5-methoxy-1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-one (M7), 3′,4′-dihydroxyphenyl-decan-3-one (M8), 1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-ol (M9), 5-methylthio-1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-one (M10), 1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-one (M11), and 5-methylthio-1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-ol (M12) on the basis of detailed analysis of their 1H, 13C, and two-dimensional NMR data. The rest of the metabolites were identified as 5-cysteinyl-M6 (M1), 5-cysteinyl-[6]-shogaol (M2), 5-cysteinylglycinyl-M6 (M3), 5-N-acetylcysteinyl-M6 (M4), 5-N-acetylcysteinyl-[6]-shogaol (M5), and 5-glutathiol-[6]-shogaol (M13) by analysis of the MSn (n = 1–3) spectra and comparison to authentic standards. Among the metabolites, M1 through M5, M10, M12, and M13 were identified as the thiol conjugates of [6]-shogaol and its metabolite M6. M9 and M11 were identified as the major metabolites in four different cancer cell lines (HCT-116, HT-29, H-1299, and CL-13), and M13 was detected as a major metabolite in HCT-116 human colon cancer cells. We further showed that M9 and M11 are bioactive compounds that can inhibit cancer cell growth and induce apoptosis in human cancer cells. Our results suggest that 1) [6]-shogaol is extensively metabolized in these two models, 2) its metabolites are bioactive compounds, and 3) the mercapturic acid pathway is one of the major biotransformation pathways of [6]-shogaol. …Shogaols have gained interest because of recent discoveries revealing their higher anticancer potencies over gingerols. It is reported that [6]-, [8]-, and [10]-gingerols had little to no effect but [6]-shogaol significantly inhibited the growth of A-2780 ovarian cancer cells (Rhode et al., 2007). Kim et al. (2008) reported that [6]-shogaol exhibited much stronger growth-inhibitory effects on A-549 human lung cancer cells, SK-OV-3 human ovarian cancer cells, SKMEL-2 human skin cancer cells, and HCT-15 human colon cancer cells than [4]-, [6]-, [8]-, and [10]-gingerols. A study from our group has also demonstrated that [6]-, [8]-, and [10]-shogaols exhibited much higher antiproliferative potency than [6]-, [8]-, and [10]-gingerols against H-1299 human lung cancer cells with IC50 values of 8 μM for [6]-shogaol and 150 μM for [6]-gingerol (Sang et al., 2009). Along with our collaborators, we have reported that [6]-shogaol was more effective than [6]-gingerol in inhibiting 12-O-tetradecanoylphorbol-13-acetate-induced tumor promotion in mice (Wu et al., 2010). Furthermore, Dugasani et al. (2010) found that [6]-shogaol showed the most potent antioxidative activity with an IC50 value of approximately 8 μM, whereas [6]-, [8]-, and [10]-gingerols had IC50 values of 28, 20, and 12 μM, respectively.
Br J Pharmacol. 2010 Dec; 161(8): 1763–1777.
doi: 10.1111/j.1476-5381.2010.00991.x
PMCID: PMC3010581
6-Shogaol, an active constituent of ginger, inhibits breast cancer cell invasion...
KEY RESULTS
Shogaols (6-, 8- and 10-shogaol) inhibited PMA-stimulated MDA-MB-231 cell invasion with an accompanying decrease in MMP-9 secretion. 6-Shogaol was identified to display the greatest anti-invasive effect in association with a dose-dependent reduction in MMP-9 gene activation, protein expression and secretion. The NF-κB transcriptional activity was decreased by 6-shogaol; an effect mediated by inhibition of IκB phosphorylation and degradation that subsequently led to suppression of NF-κB p65 phosphorylation and nuclear translocation. In addition, 6-shogaol was found to inhibit JNK activation with no resulting reduction in activator protein-1 transcriptional activity. By using specific inhibitors, it was demonstrated that ERK and NF-κB signalling, but not JNK and p38 signalling, were involved in PMA-stimulated MMP-9 activation.
CONCLUSIONS AND IMPLICATIONS
6-Shogaol is a potent inhibitor of MDA-MB-231 cell invasion, and the molecular mechanism involves at least in part the down-regulation of MMP-9 transcription by targeting the NF-κB activation cascade. This class of naturally occurring small molecules thus have potential for clinical use as antimetastatic treatments.
Toxicology and applied pharmacology 2014
Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells
Dae-Hee Lee, Dong-Wook Kim, [...], and Daeho Park
Additional article information
Abstract
Glioblastoma multiforme (GBM) is the most lethal and aggressive astrocytoma of primary brain tumors in adults. Although there are many clinical trials to induce the cell death of glioblastoma cells, most glioblastoma cells have been reported to be resistant to TRAIL-induced apoptosis. Here, we showed that gingerol as a major component of ginger can induce TRAIL-mediated apoptosis of glioblastoma. Gingerol increased death receptor (DR) 5 levels in a p53-dependent manner. Furthermore, gingerol decreased the expression level of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and increased pro-apoptotic protein, Bax and truncate Bid, by generating reactive oxygen species (ROS).We also found that the sensitizing effects of gingerol in TRAIL-induced cell death were blocked by scavenging ROS or overexpressing anti-apoptotic protein (Bcl-2). Therefore, we showed the functions of gingerol as a sensitizing agent to induce cell death of TRAIL-resistant glioblastoma cells. This study gives rise to the possibility of applying gingerol as an anti-tumor agent that can be used for the purpose of combination treatment with TRAIL in TRAIL-resistant glioblastoma tumor therapy.
Keywords: Gingerol, Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Glioblastoma, Apoptosis, Reactive oxygen species (ROS), p53
Introduction
Glioblastoma multiforme (GBM) is classified as a grade IV astrocytoma by the World Health Organization (WHO) and is a very aggressive malignant astrocytoma that makes up approximately 50% of all astrocytomas (Fuller, 2008; Ohgaki and Kleihues, 2005). As it is known from its name, GBM has morphologically multiple heterogeneous populations (Krakstad and Chekenya, 2010). Although there have been many radiotherapeutic and chemotherapeutic clinical trials to treat glioblastoma, prognosis of glioblastoma patients is very poor and the median survival rate is about 14.6 months (Stupp et al., 2005). Recently, combination therapies such as cocktail treatments that use more than 2 different anti-cancer drugs have been tried to increase the efficacy and survival rate (Doherty et al., 2006; Goudar et al., 2005; Rao et al., 2005; Reardon et al., 2006). For example, drugs that target both survival pathway and apoptotic pathway have simultaneously been used to improve the survival rate for GBM patients (Hawkins, 2004; Krakstad and Chekenya, 2010).
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been well known to mediate cellular apoptosis in a wide-range of tumor cell types (Aggarwal, 2003; Pitti et al., 1996). TRAIL binds to its receptor (death receptor (DR) 4/5) to induce receptor trimerization that can recruit downstream molecules such as Fas-associated protein with death domain (FADD) and eventually activate caspase cascade (caspases-8, 10, 9, and 3) to transmit cell death signaling (Aggarwal, 2003; Bellail et al., 2010). However, it has been reported that most glioblastoma cells showed resistance to apoptosis mediated by the TRAIL signaling pathway (Krakstad and Chekenya, 2010).
Gingerol, as a major pungent element of ginger, has been reported to exhibit anti-oxidant, analgesic, anti-pyretic, anti-inflammatory, and anti-tumorigenic activities (Oyagbemi et al., 2010; Shukla and Singh, 2007). Gingerol has also been known to show anti-inflammatory potential by decreasing the expression level of inducible nitric oxide synthase (iNOS) and TNF-α (D.H. Lee et al., 2009; T.Y. Lee et al., 2009). Furthermore, the anti-tumorigenic effects of gingerol have been known to be exerted by the induction of apoptosis of tumor cells (Bode et al., 2001; Chakraborty et al., 2012; Lee and Surh, 1998). However, the detailed molecular mechanism of gingerol-induced apoptosis is still not clear.
Here, we identified that gingerol functions as a sensitizing agent to induce TRAIL-mediated apoptosis of glioblastoma cells which were resistant to apoptosis by TRAIL signaling. Especially, in non-cytotoxic concentrations gingerol efficiently induced cell death by TRAIL in glioblastoma cell lines. Furthermore, we revealed that the sensitizing function of gingerol was performed by elevating the expression level of death receptor (DR) 5, by decreasing the expression of anti-apoptotic proteins (survivin, c-FLIP, Bcl-2, and XIAP) and by inducing the levels of pro-apoptotic proteins (Bax and truncate Bid) in a p53- and reactive oxygen species (ROS)-dependent manner. Our effort in identifying gingerol as the agent that sensitizes TRAIL-mediated apoptosis in glioblastoma and understanding the molecular mechanisms of gingerol-sensitization provides us which an opportunity to make more effective drug combination therapies which are non-toxic to GBM patients.Gingerol sensitizes TRAIL-induced apoptotic cell death of glioblastoma cells
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295120/#!po=9.61538
Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Pathway Signaling
Department of Pharmacology and University of Colorado Comprehensive Cancer Center, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado
Journal of Thoracic Oncology
Volume 2, Issue 6, June 2007, Pages 461-465
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo1L is a death ligand, a cytokine that activates apoptosis through cell surface death receptors. TRAIL is thought to be important in host tumor surveillance and metastasis suppression, and various therapeutic agonists that activate TRAIL receptors to induce tumor cell apoptosis are in clinical development. This review discusses recent findings about TRAIL pathway signaling and relates the signaling mechanisms to issues that need to be considered as we try to manipulate TRAIL signaling to treat cancer.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL, also known as Apo2L and TNFSF10) is a type II transmembrane protein belonging to the tumor necrosis factor (TNF) superfamily. TRAIL is expressed on the surface of natural killer (NK) and T cells, macrophages, and dendritic cells. As with other cytokines, the protein is synthesized in a pro-form with a signal sequence that is removed in the mature secreted protein. TRAIL can be anchored in the membrane via hydrophobic amino acids or can be released as a soluble protein. Both forms function as trimers and can induce apoptosis. TRAIL induces apoptosis by binding to and activating signaling by trimeric death receptors in a manner that is similar to that of other “death ligands,― such as FasL or TNFα, which signal through the Fas receptor (CD95) and TNF receptor (TNFR1), respectively. TRAIL binds to five different receptors. DR4 (TNFRSF10a, TRAILR1) and DR5 (TNFRSF10b, TRAILR2) are both are capable of signaling apoptosis, whereas two membrane-bound decoy receptors called DcR1 (TNFRSF10c) and DcR2 (TNFRSF10d) are unable to activate apoptotic signaling and inhibit TRAIL signaling. The fifth TRAIL-binding receptor is osteoprotogerin (TNFRSF11b), which is a soluble protein that may also function as a decoy/inhibitor by sequestering TRAIL extracellularly. Much current interest in TRAIL derives from its roles in cancer development and treatment. In particular, recombinant TRAIL1, 2 and agonistic antibodies that recognize TRAIL receptors3, 4 have been shown to kill many tumor cells while leaving most normal cells unscathed and displaying little toxicity when delivered systemically to animals and people. It is therefore hoped that these agents may be useful to treat cancer.5, 6, 7 This contrasts with other death ligands, such as TNFα or Fas ligand, which activate similar pathways using the same signaling proteins but display unacceptable toxicity when administered systemically.FUNCTIONS OF TRAIL
The creation of TRAIL-deficient and TRAIL receptor-deficient mice has allowed examination of the physiological functions of TRAIL. Knockout mice are viable and fertile with no obvious developmental defects. The TRAIL pathway is involved in the regulation of innate immunity8 and in the homeostasis of memory T cells.9 From the cancer perspective, TRAIL signaling is important in T cell- and natural killer cell-mediated tumor surveillance and metastasis suppression.10, 11, 12, 13 Although TRAIL receptor deficiency has no apparent effect on intestinal tumor development caused by p53 or APC loss,14 TRAIL-deficient animals have more hematological malignancies15 and are more susceptible to chemical carcinogens.13 TRAIL receptor-deficient animals are also less sensitive to damage caused by ionizing radiation.16 Together, these findings indicate that the TRAIL pathway has important roles in host anti-tumor defense and tumor suppression.Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Pathway Signaling - ScienceDirect
https://www.sciencedirect.com/science/article/pii/S1556086415307978
Planta Med. 2012 Sep;78(14):1549-55. Epub 2012 Jul 24.
Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes.
Li Y1, Tran VH, Duke CC, Roufogalis BD.
Faculty of Pharmacy, The University of Sydney, Sydney, Australia.
Abstract
In this study we investigate the active constituents of the rhizome of Zingiber officinale, Roscoe (ginger) and determine their activity on glucose uptake in cultured L6 myotubes and the molecular mechanism underlying this action. Freeze-dried ginger powder was extracted with ethyl acetate (1 kg/3 L) to give the total ginger extract, which was then separated into seven fractions, consisting of nonpolar to moderately polar compounds, using a short-column vacuum chromatographic method. The most active fraction (F7) was further purified for identification of its active components. The effect of the extract, fractions, and purified compounds on glucose uptake was evaluated using radioactive labelled 2-[1,2-³H]-deoxy-D-glucose in L6 myotubes. The pungent phenolic gingerol constituents were identified as the major active compounds in the ginger extract enhancing glucose uptake. (S)-[6]-Gingerol was the most abundant component among the gingerols, however, (S)-[8]-gingerol was the most potent on glucose uptake. The activity of (S)-[8]-gingerol was found to be associated primarily with an increase in surface distribution of GLUT4 protein on the L6 myotube plasma membrane, as detected by expression of hemagglutinin epitope-tagged GLUT4 in L6 muscle cells. The enhancement of glucose uptake in L6 rat skeletal muscle cells by the gingerol pungent principles of the ginger extract supports the potential of ginger and its pungent components for the prevention and management of hyperglycemia and type 2 diabetes.
Georg Thieme Verlag KG Stuttgart · New York.Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes. - PubMed - NCBI
https://www.ncbi.nlm.nih.gov/pubmed/22828920
Ginger ‘s Antiviral Prowess Proven in Research
BY CASE ADAMS, PHD · FEBRUARY 7, 2017
(Last Updated On: March 7, 2018)Photo Scot Nelson
Antiviral Ginger. Photo Scot Nelson
With common colds and influenza rampant, we need all the antiviral help we can get. Ginger root’s antiviral prowess is not just real: It has been proven out in the research.
This comes in addition to ginger’s centuries-long reputation for treating a number of medical conditions.
Ginger (Zingiber officinale) has also been used in traditional medicines around the world to reduce pain and fever. I discussed research showing that ginger matches NSAIDs for reducing pain.
Now we can add to these the use of ginger for fighting viruses of different kinds, including colds and flu. But how about other viruses such as H1N1, herpes and human respiratory syncytial viruses? Let’s take a quick look at the science.
In this article
Ginger inhibits Norwalk virus surrogate
Ginger inhibits human respiratory syncytial virus
Ginger fights influenza A
Ginger versus the common cold
Ginger versus herpes
Ginger fights retroviral nausea and vomiting
How to consume medicinal ginger
REFERENCES:
60
SHARES
Ginger inhibits Norwalk virus surrogate
In a 2016 study, researchers from the University of Minnesota tested ginger against a surrogate for the human norovirus, feline calicivirus. This is a surrogate because calicivirus is a type of Norwalk virus.
The researchers tested ginger along with cloves, fenugreek seeds, garlic, onion, and jalapeño peppers. The researchers found that the ginger extract significantly inhibited the calicivirus. They also found that ginger inactivated the calicivirus in a dose-dependent manner. Dose-dependency confirms ginger’s specific antiviral potency.
In addition to the ginger extracts, the clove extracts also inhibited the calicivirus.
Ginger inhibits human respiratory syncytial virus
Human respiratory syncytial virus (RSV) is one of the most common contagious virus infections that occur in children. Symptoms include fever, stuffy nose wheezing and runny nose. Many RSV illnesses are confused with the common cold. However a bout of RSV will typically last for longer, and will typically include wheezing. In younger children this can turn fatal.
Medical researchers from the College of Medicine at Kaohsiung Medical University determined that fresh ginger is an effective treatment against human respiratory syncytial virus.
The researchers tested both fresh and dried ginger against RSV-infected human liver and lung cells. They found that the fresh ginger inhibited the attachment of the virus on to the cells. They also found ginger stimulated the INF-beta secretions that help counteract viral infections among the cells of the mucous membranes.
Read more: Herbs and Other Natural Solutions to the Opioid Crisis
The inhibition of the virus occurred more readily among the alveolar (lung) cells – illustrating the potential for the ginger to inhibit RSV infections of the lungs.
Notably the researchers found that dried ginger did not have the same effectiveness upon the virus as the fresh ginger had. This indicates that some of the antiviral constituents of fresh ginger are lost during drying process.
Ginger fights influenza A
Researchers from Japan’s Toyama Medical and Pharmaceutical University tested ginger against an influenza A strain in the laboratory. They found that the ginger extract stimulated the production of TNF-alpha expression by the immune system. This provided the means for the ginger to inhibit replication of the virus.
Researchers from India’s Mahatma Gandhi Institute of Medical Sciences also studied ginger along with other natural compounds for inhibiting H1N1 influenza A. They found ginger’s allicin content helped inhibit the virus by interacting with its binding capacity.
Ginger versus the common cold
As mentioned, ginger has been a go-to remedy among traditional medicine for centuries. This has been supported by modern research as well. In 2015, researchers from the University of Minnesota Twin Cities tested a product called Phytorelief-CC. This contains a combination of Turmeric, Pomegranate and Ginger.
The researchers followed 124 people, half of whom took the combination when they had initial symptoms. The researchers found 27 percent of the group that took things other than the ginger had a full cold episode, while only 8 percent of those who took the ginger combination got colds. This means about a third of the colds.
Researchers from the UK’s Wellcome Research Laboratories tested ginger root against rhinovirus (common cold virus) in the laboratory. They found the ginger extracts inhibited rhinovirus. The most active antiviral components of the ginger extracts according to the researchers were the sesquiterpenes.
Ginger versus herpes
Researchers from Germany’s University of Heidelberg studied essential oils from various herbs against herpes simplex virus type 2. Other than ginger, these included anise, hyssop, thyme, chamomile and sandalwood. The researchers found that the ginger essential oil significantly inhibited the HSV-2 virus replication within RC-37 cells. The researchers found that plaque formation was halted by 90 percent by the ginger essential oils and the thyme oil.
Read more: Garlic and Ginger fight Drug Resistant Superbugs
The researchers tested this inhibitory effect at different stages of infection, and concluded that the ginger essential oil somehow interacted with the viral envelope.
Another study from the University of Heidelberg studied herpes simplex-1 against oils of ginger, thyme, hyssop, and sandalwood. The research found that all of these oils inhibited HSV-1 growth. Furthermore, they inhibited the growth of acyclovir-resistant strains of HSV-1. That means ginger can inhibit antiviral-resistant strains of herpes.
Ginger fights retroviral nausea and vomiting
A 2014 study tested 102 HIV-positive patients who were taking antiretroviral medication. Most of them were experiencing nausea and vomiting from the therapy. The researchers found that 500 milligrams of ginger twice a day significantly reduced their vomiting and nausea.
Whether this was due to the antiviral potency of ginger or simply its beneficial gastrointestinal effect is not known.
How to consume medicinal ginger
Fresh ginger can be consumed with foods, herbal tea, or blended into a smoothie. If adding to an herbal tea it should be put into the cup last – right before drinking if possible. Ginger can also be squeezed into fresh ginger juice, which may then be blended with water or fruit juice. Ayurvedic traditionalists have often suggested simply chewing fresh ginger root raw when sick.
Mu tea is one of the most famous and easily made cold and flu remedies. Mu tea is made by brewing up some ginger tea (steep ginger root in water after being brought to a boil). Then add some raw honey and fresh-squeezed lemon to the herba cuppa.
The research above indicates that using ginger essential oils is also a good strategy for fighting viral infections. A few drops of ginger essential oil can be used topically and internally. A very small test dose should precede consumption.
Read more: Natural Strategies to Reverse Dry Mouth
It should be noted that the ginger candies are not only made from dried ginger, but are typically blended with sugar which practically counteracts ginger’s benefits – as refined sugar tends to feed pathogens and inhibit immune response.
In addition to the sesquiterpenes found in the rhinovirus research, antiviral components in ginger include allicin, alliin and ajoene. Other research has determined that fresh ginger contains upwards of 477 different constituents. This of course includes many polyphenols and flavonoids that have shown anti-viral properties – many of which are also heat sensitive.
生姜抑制人呼吸道合胞病毒
人呼吸道合胞病毒（RSV）是儿童中最常见的传染性病毒感染之一。症状包括发烧，鼻塞喘息和流鼻涕。许多RSV疾病与普通感冒相混淆。但是，RSV发作通常会持续更长的时间，并且通常会包括喘息。对于年幼的孩子，这可能会致命。
高雄医科大学医学院的医学研究人员确定，新鲜生姜是一种有效的抗人呼吸道合胞病毒的治疗方法。
研究人员测试了新鲜和干燥的生姜对RSV感染的人肝和肺细胞的抵抗力。他们发现新鲜的生姜可以抑制病毒附着在细胞上。他们还发现姜刺激了INF-β分泌，有助于抵抗粘膜细胞之间的病毒感染。
对病毒的抑制在肺泡（肺）细胞中更容易发生-说明姜具有抑制肺部RSV感染的潜力。
值得注意的是，研究人员发现，干姜对病毒的功效不如新鲜生姜。这表明新鲜姜的一些抗病毒成分在干燥过程中会丢失。
生姜抗击甲型流感
日本富山医科大学的研究人员在实验室测试了生姜对甲型流感的抵抗力。他们发现，姜提取物可通过免疫系统刺激TNF-α表达的产生。这为生姜提供了抑制病毒复制的手段。
印度圣雄甘地医学科学研究所的研究人员还研究了生姜以及其他天然化合物可以抑制甲型H1N1流感。他们发现生姜中大蒜素的含量可以通过与其结合能力相互作用来抑制这种病毒。
生姜与普通感冒
如前所述，生姜已成为传统医学中数百年来的首选疗法。这也得到了现代研究的支持。 2015年，明尼苏达州双城大学的研究人员测试了一种名为Phytorelief-CC的产品。其中包含姜黄，石榴和姜。
研究人员追踪了124人，其中有一半在有最初症状时进行了联合治疗。研究人员发现，服用除生姜以外的东西的人群中有27％患有感冒，而服用生姜组合的人群中只有8％患了感冒。这意味着大约三分之一的感冒。
英国威康研究实验室的研究人员在实验室测试了姜根对鼻病毒（普通感冒病毒）的抵抗力。他们发现姜提取物抑制了鼻病毒。研究人员称，姜提取物中最活跃的抗病毒成分是倍半萜。
Ginger 's Antiviral Prowess Proven in Research | Journal of Plant Medicines
https://plantmedicines.org/ginger-antiviral/
Fresh ginger (Zingiber officinale) has anti-viral activity against human respiratory syncytial virus in human respiratory tract cell lines - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/S0378874112007404
Curr Opin Support Palliat Care. Author manuscript; available in PMC 2015 Jun 1.
Published in final edited form as:
Curr Opin Support Palliat Care. 2014 Jun; 8(2): 83–90.
Bone Cancer Pain: From Mechanism to Therapy
Patrick W. Mantyh*φ
Abstract
Purpose of Review
To review how common cancers such as breast, lung, and prostate cancers drive significant and frequently life altering pain when the cells metastasize to bones.
Recent Findings
Similar to cancer, the factors that drive bone cancer pain evolve and change with disease progression. Bone cancer pain has both a nociceptive and neuropathic component. The nociceptive component is driven by the release of algogenic substances by tumor and their associated stromal cells, acidosis caused by bone-destroying osteoclasts, and mechanical destabilization and fracture of the bone. The neuropathic component is induced by tumor cell growth which injures and destroys the distal ends of nerve fibers that normally innervate the bone as well as by inducing a highly pathological sprouting of both sensory and sympathetic nerve fibers.
Summary
There is both a nociceptive and neuropathic component of bone cancer pain. In bone cancer pain there is frequently a continual afferent drive of sensory nerve fibers that induces a peripheral and central sensitization. These mechanistic insights have begun to lead to advances in not only how we understand bone cancer pain but to the development of new therapies to treat bone cancer pain.
Keywords: tumor, stromal cells, metastasis, pain, nerve sprouting
骨癌疼痛:从机制到治疗
帕特里克·w·Mantyh *φ
*亚利桑那大学药学系，亚利桑那州图森市，AZ 85716
φArizona癌症中心,85716年亚利桑那州图森市亚利桑那大学
审核的目的
回顾乳腺癌、肺癌和前列腺癌等常见癌症在细胞转移到骨骼时，是如何显著且频繁地改变疼痛的。
最近发现
与癌症相似，导致骨癌疼痛的因素随着疾病的发展而演变和改变。骨癌疼痛既有伤害性的，也有神经性的。痛觉成分是由肿瘤及其相关基质细胞释放的致痛性物质、破坏骨质的破骨细胞引起的酸中毒以及机械破坏和骨折所驱动的。神经病理成分是由肿瘤细胞的生长引起的，肿瘤细胞的生长损伤和破坏了通常支配骨骼的神经纤维的远端，并通过诱导感觉和交感神经纤维的高度病理发芽。
总结
骨癌疼痛既有致痛性的，也有神经性的。在骨癌疼痛中，经常有感觉神经纤维的连续传入驱动，诱导周围和中枢敏化。这些机制上的见解已经开始引导我们不仅在如何理解骨癌疼痛方面取得进展，而且在开发治疗骨癌疼痛的新疗法方面取得进展。
关键词:肿瘤，间质细胞，转移，疼痛，神经发芽Bone Cancer Pain: From Mechanism to Therapy
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4068714/
4/12/2009 · Moreover, exosomes released by normal and tumor cells seem to differ in both functional and structural properties (). It is also conceivable that exosomes are actively released within tumor tissues or directly spilled into the blood stream but apparently without any specific commitment to tissue targeting ( 2 , 3 , 8 ).
