curcumin and shogaol

Ginger is a commonly used spice and herbal medicine worldwide. Besides its extensive use as a condiment, ginger has been used in traditional Chinese medicine for the management of various medical conditions. In recent years, ginger has received wide attention due to its observed antiemetic and anticancer activities. This paper reviews the potential role of ginger and its active constituents in cancer chemoprevention. The phytochemistry, bioactivity, and molecular targets of ginger constituents, especially 6-shogaol, are discussed. The content of 6-shogaol is very low in fresh ginger, but significantly higher after steaming. With reported anti-cancer activities, 6-shogaol can be served as a lead compound for new drug discovery. The lead compound derivative synthesis, bioactivity evaluation, and computational docking provide a promising opportunity to identify novel anticancer compounds originating from ginger.

Topics: Antiemetics; Antineoplastic Agents, Phytogenic; Catechols; Chemoprevention; Curcuma; Curcumin; Drug Discovery; Humans; Neoplasms; Steam; Structure-Activity Relationship; Zingiber officinale

In our study, anticancer effects of 6-gingerol, 6-shogaol from ginger and curcumin from turmeric were investigated and the results were compared with each other. We aimed to reveal their effects on microsomal prostaglandine E2 synthase 1 (mPGES-1) which is related with cancer progression and inflammation as well as β-catenin and glycogen synthase kinase 3β (GSK-3β) that are the main components of Wnt/GSK3 pathway. As it is known activation of GSK-3β and high levels of mPGES-1 pathway leads to cell proliferation and aggravates cancer progression. Therefore both of them are potential targets for cancer therapy. 6-shogaol and 6-gingerol' s effect on this pathway is not known very well up to now while curcumin that is known as an mPGES-1 inhibitor has anticancer properties via this pathway and many other pathways. Besides being in Zingiberaceae family, ginger's 6-gingerol and 6-shogaol have a molecular similarity with turmeric's curcumin. In our study we investigated their effects using a popular non small lung cancer cell line named A549 which expresses mPGES-1 and has active GSK3β pathway. IL-1β was used for inducing mPGES-1 and enabling the cancer characteristics such as cell proliferation. So compounds that inactivates or decreases the level of these components might be potential anticancer agents.. A549 cells were incubated with interleukin 1β (IL-1β) for 24 h in order to maintain mPGES-1 enzyme induction. Experiments were performed both on IL-1β and non-IL-1β group. Real time cell analysis was performed to determine the cytotoxicity. Samples for western blotting and RT-PCR were collected after 24 h incubation with compounds to determine the amount of mPGES-1, GSK-3β, p-GSK-3β, β-catenin protein and mRNA. PGE2 which is the end product of mPGES-1 was measured by using ELISA kit.. As a result of cell profile assay, cells exposed to IL-1β proliferate faster than non-IL-1β ones. This shows that induced mPGES-1 might play a role through GSK3β pathway and 24 h IC50 value of 6-shogaol is 62 μM. IL-1β increased protein and mRNA levels of mPGES-1, p-GSK-3β, β-catenin and GSK-3β in control group. Effects of curcumin and 6-shogaol on these parameters were against IL-1β's effect while 6-gingerol was not effective at all. Furthermore, 6-shogaol and curcumin might be effective on GSK3β pathway via lowering PGE2 levels.. We saw that 6-shogaol is as effective as curcumin on this pathway and our study shows that 6-shogaol might show its anticancer properties via mPGES-1 and GSK3β pathway. May be these results might used for designing in vivo studies in future.

Topics: A549 Cells; beta Catenin; Blotting, Western; Catechols; Cell Survival; Curcumin; Dinoprostone; Fatty Alcohols; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 beta; Humans; Interleukin-1beta; Models, Biological; Prostaglandin-E Synthases; RNA, Messenger; Signal Transduction

Twenty-nine phenolic compounds were isolated from the root bark of fresh (Yunnan) ginger and their structures fully characterized. Selected compounds were divided into structural categories and twelve compounds subjected to in-vitro assays including DPPH radical scavenging, xanthine-oxidase inhibition, monoamine oxidase inhibition, rat-brain homogenate lipid peroxidation, and rat pheochromocytoma PC12 cell and primary liver cell viability to determine their antioxidant and cytoprotective properties. Isolated compounds were also tested against nine human tumor cell lines to characterize anticancer potency. Several diarylheptanoids and epoxidic diarylheptanoids were effective DPPH radical scavengers and moderately effective at inhibiting xanthine oxidase. An enone-dione analog of 6-shogaol (compound 2) was isolated and identified to be most effective at protecting PC12 cells from H₂O₂-induced damage. Almost all tested compounds inhibited lipid peroxidation. Three compounds, 6-shogaol, 10-gingerol and an enone-diarylheptanoid analog of curcumin (compound 6) were identified to be cytotoxic in cell lines tested, with KB and HL60 cells most susceptible to 6-shogaol and the curcumin analog with IC₅₀<10 μM. QSAR analysis revealed cytotoxicity was related to compound lipophilicity and chemical reactivity. In conclusion, we observed distinct compounds in fresh ginger to have biological activities relevant in diseases associated with reactive oxygen species.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Biphenyl Compounds; Catechols; Curcumin; Cytoprotection; Fatty Alcohols; HL-60 Cells; Humans; Hydrogen Peroxide; Hydrophobic and Hydrophilic Interactions; KB Cells; Lipid Peroxidation; Neoplasms; PC12 Cells; Phenols; Phytotherapy; Picrates; Plant Bark; Plant Extracts; Plant Roots; Rats; Xanthine Oxidase; Zingiber officinale

Hexahydrocurcumin, 1-dehydro-[6]-gingerdione, 6-dehydroshogaol and 6-shogaol were evaluated for their antioxidant and anti-inflammatory activities in the present study. The relative antioxidant potencies of ginger compounds decreased in similar order of 1-dehydro-[6]-gingerdione, hexahydrocurcumin>6-shogaol>6-dehydroshogaol in both 1,1-diphenyl-2-picyrlhydrazyl (DPPH) radical-scavenging and trolox equivalent antioxidant capacity (TEAC) assays. All tested compounds could attenuate lipopolysaccharide (LPS)-elicited increase of prostaglandin E2 (PGE(2)) in murine macrophages (RAW 264.7) in a concentration-dependent manner but hexahydrocurcumin of 7μM and 6-shogaol of 7μM. The strongest inhibitory effect was observed for 6-dehydroshogaol and 6-shogaol at 14μM with the inhibition of 53.3% and 48.9%, respectively. Furthermore, both 6-dehydroshogaol and 1-dehydro-[6]-gingerdione significantly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in a concentration-dependent fashion. These results contribute to our theoretical understanding of the potential beneficial effects of consuming ginger as a food and/or dietary supplement.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Catechols; Cell Line; Curcumin; Cyclooxygenase 2; Guaiacol; Macrophages; Mice; Nitric Oxide Synthase Type II; Plant Extracts; Zingiber officinale

Oxidative stress has been implicated as a causative factor of atherosclerosis. Defense systems against oxidative stress are maintained by radical scavenging antioxidants and/or by regulating the expression of antioxidant genes by activating oxidative stress-sensitive transcription factor: nuclear factor (erythroid-derived 2)-like 2 (Nrf2). We investigated the anti-atherogenic effects of three synthesized compounds (shogaol A: radical scavenging antioxidant activity; shogaol N: Nrf2-activating activity; shogaol N + A: both activities) and curcumin (both activities) in apolipoprotein E (apoE)-deficient mice. We expected compounds with both activities to have additive or synergistic anti-atherogenic effects; however, atherosclerosis was exacerbated significantly by curcumin and slightly by shogaol N + A. Shogaol A, shogaol N, and shogaol N + A showed no significant effect on atherosclerosis development. Immunohistochemical analysis of the aorta revealed that expression of CD36, an Nrf2-regulated gene, was strongly induced by treatment with curcumin. The total antioxidant capacity of plasma collected from mice administered the three compounds was evaluated using a hydrophilic probe, pyranine. Shogaol N or shogaol N + A significantly enhanced the antioxidant capacity of plasma, whereas shogaol A and curcumin did not show this activity. The concentrations of the three shogaol derivatives in plasma were similar (approximately 100 nM), while that of curcumin was much lower. These results suggest that plasma antioxidant capacity is maintained at high levels via Nrf2 activation and that CD36 expression enhances atherosclerosis development.

Topics: Animals; Antioxidants; Aorta; Apolipoproteins E; Atherosclerosis; Caprylates; Catechols; CD36 Antigens; Curcumin; Free Radical Scavengers; Lauric Acids; Macrophages; Male; Mice; NF-E2-Related Factor 2; Oxidative Stress; Up-Regulation

We previously reported that 6-shogaol strongly suppressed lipopolysaccharide-induced overexpression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in murine macrophages. In this study, we further compared curcumin, 6-gingerol, and 6-shogaol's molecular mechanism of action and their anti-tumor properties. We demonstrate that topical application of 6-shogaol more effectively inhibited 12-O-tetradecanoylphorbol 13-acetate (TPA)-stimulated transcription of iNOS and COX-2 mRNA expression in mouse skin than curcumin and 6-gingerol. Pretreatment with 6-shogaol has resulted in the reduction of TPA-induced nuclear translocation of the nuclear factor-kappaB subunits. 6-Shogaol also reduced TPA-induced phosphorylation of IkappaBalpha and p65, and caused subsequent degradation of IkappaBalpha. Moreover, 6-shogaol markedly suppressed TPA-induced activation of extracellular signal-regulate kinase1/2, p38 mitogen-activated protein kinase, JNK1/2, and phosphatidylinositol 3-kinase/Akt, which are upstream of nuclear factor-kappaB and AP-1. Furthermore, 6-shogaol significantly inhibited 7,12-dimethylbenz[a]anthracene/TPA-induced skin tumor formation measured by the tumor multiplicity of papillomas at 20 wk. Presented data reveal for the first time that 6-shogaol is an effective anti-tumor agent that functions by down-regulating inflammatory iNOS and COX-2 gene expression in mouse skin. It is suggested that 6-shogaol is a novel functional agent capable of preventing inflammation-associated tumorigenesis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents, Non-Steroidal; Anticarcinogenic Agents; Catechols; Curcumin; Cyclooxygenase 2; Dose-Response Relationship, Drug; Fatty Alcohols; Female; Gene Expression Regulation, Enzymologic; Mice; Mice, Inbred ICR; Nitric Oxide Synthase Type II; Papilloma; RNA, Messenger; Signal Transduction; Skin; Skin Neoplasms; Tumor Burden

From the rhizome of Zingiber officinale L. (Zingiberaceae), four shogaols that protect IMR32 human neuroblastoma and normal human umbilical vein endothelial cells from beta-amyloid(25 - 35) insult at EC50 = 4.5 - 81 microM were isolated. The efficacy of cell protection from beta-amyloid(25 - 35) insult by these shogaols was shown to improve as the length of the side chain increases.

Topics: alpha-Tocopherol; Amyloid beta-Peptides; Catechols; Cell Line; Cell Survival; Curcumin; Dose-Response Relationship, Drug; Endothelium, Vascular; Humans; Neuroblastoma; Peptide Fragments; Plant Stems; Tumor Cells, Cultured; Umbilical Veins; Zingiber officinale