gingerol and gingerdione

Antioxidant natural products and their analogs especially phenolic compounds, exhibit diverse biological properties, including anti-inflammatory, antioxidant, and anticancer activities. Ginger which is widely used worldwide for various beneficial effects also contains several phenolic antioxidants, and 6-gingerol is one of the natural products studied extensively. However, the molecular mechanism of synthetically synthesized 6-gingerdione (compound 1) from 6-gingerol was not known. In this study, compound 1 and methylated 6-gingerdione (compound 2) were obtained semi synthetically from 6-gingerol. Compound 1 and 2 are subjected to SwissADME prediction. Then the protective effect of compound 1 was analyzed in 2 % EtOH induced HepG2 cells and zebrafish larvae. Hydroxyl and nitric oxide scavenging assays reveal that compound 1 showed more antioxidant activity than compound 2 at 50 μM. Moreover, compound 1 exhibited good anti-inflammatory activity via lipoxygenase inhibition and proteinase inhibition. Apoptosis and oxidative stress in HepG2 cells were induced by 2 % EtOH and treated with compound 1. Compound 1 significantly inhibited the EtOH induced nitric oxide production, apoptosis, and ROS generation in HepG2 cells. Encouraged by the in-vitro antioxidant and anti-inflammatory activities, compound 1 was then investigated for its protective effect in 2 % EtOH induced ALD zebrafish larva. Compound 1 protected the zebrafish larvae from liver injury by suppressing inflammatory (COX-2, TNF-α, and IL-1β) and lipogenic genes (C/EBP-α, SREBP1, and IL-1β) while upregulating the antioxidant gene. Our findings indicate that compound 1 synthesized from 6-gingerol ameliorated liver injury that likely, contributes to its potential antioxidant and anti-inflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cytokines; Gene Expression; Hep G2 Cells; Humans; Larva; Liver; Nitric Oxide; Oxidative Stress; Zebrafish

Ginger is currently one of the most popular herbs commonly added to diverse foods, beverages, and dietary supplements. We evaluated the ability of a well-characterized ginger extract, and several of its phytoconstituents, to activate select nuclear receptors as well as modulate the activity of various cytochrome P450s and ATP-binding cassette (ABC) transporters because phytochemical-mediated modulation of these proteins underlies many clinically relevant herb-drug interactions (HDI). Our results revealed ginger extract activated the aryl hydrocarbon receptor (AhR) in AhR-reporter cells and pregnane X receptor (PXR) in intestinal and hepatic cells. Among the phytochemicals investigated, (

Topics: ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Herb-Drug Interactions; Neoplasm Proteins; Zingiber officinale

Bioactivity-guided fractionation of Zingiber Officinale (zingiberaceae) led us to isolate 14 compounds, -gingerol ( 1), -gingerol ( 2), -gingerol ( 3), -gingerol ( 4), -paradol ( 5), -shogaol ( 6), -shogaol ( 7), 1-dehydro- -gingerdione ( 8), -gingerdione ( 9), hexahydrocurcumin ( 10), tetrahydrocurcumin ( 11), gingerenone A ( 12), 1,7-bis-(4' hydroxyl-3' methoxyphenyl)-5-methoxyhepthan-3-one ( 13), and methoxy- -gingerol ( 14). Using the RAW 264.7 cell line, the inhibitory effects on nitric oxide production induced by lipopolysaccharide and the stimulatory effects on phagocytosis of these compounds were evaluated. Compounds 7, 8, and 9 significantly decreased lipopolysaccharide-induced nitric oxide production, and compounds 7 and 8 significantly reduced inducible nitric oxide synthase expression. Among them, compound 8 also showed significant stimulatory effects on phagocytosis.

Topics: Animals; Catechols; Cell Line; Cell Survival; Diarylheptanoids; Fatty Alcohols; Female; Guaiacol; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Phagocytosis; Plant Extracts; Zingiber officinale

The suppression of spontaneous Ca2+ spikes and isometric contractions by gingerols and their chemically related compounds was examined using the single sucrose gap method. Most of the congeners tested suppressed spontaneous contraction, which was not necessarily accompanied by the suppression of Ca2+ spikes. The most potent analogues for Ca2+ spike suppression were (+/-)-[6]-gingerol (0.3 mM) and (+/-)-yakuchinone-A (0.3 mM). These compounds also strongly inhibited spontaneous contraction. In contrast, (+/-)-[8]-gingerol (0.3 mM) inhibited the contraction without changing the Ca2+ spikes. These results suggest that the inhibition of spontaneous contraction induced by (+/-)-[6]-gingerol, but not by (+/-)-[8]-gingerol, is due to the Ca2+ spike suppression.

Topics: Animals; Calcium; Catechols; Fatty Alcohols; Guaiacol; In Vitro Techniques; Isometric Contraction; Male; Mice; Muscle, Smooth, Vascular; Portal Vein; Stereoisomerism; Structure-Activity Relationship

A series of structurally related pungent natural products including capsaicin, gingerol, and gingerdione among others were evaluated and found to be potent inhibitors of 5-HETE biosynthesis in intact human leukocytes, with IC50 values of 100 and 15 microM for capsaicin and gingerdione, respectively. Several compounds within this series were also found to inhibit PGE2 formation, with the most potent being gingerdione (IC50 = 18 microM). These and other data indicate that members of the capsaicin/gingerol family of pungent compounds can act as dual inhibitors of arachidonic acid metabolism, which could account in part for the antiinflammatory and analgesic properties of compounds within this group.

Topics: Arachidonate 5-Lipoxygenase; Arachidonate Lipoxygenases; Capsaicin; Catechols; Dinoprostone; Fatty Alcohols; Guaiacol; Humans; Hydroxyeicosatetraenoic Acids; In Vitro Techniques; Lipoxygenase Inhibitors; Neutrophils; Plant Extracts; Prostaglandins E