shogaol and 6-paradol

As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (

Topics: Catechols; Dementia; Drug Discovery; Fatty Alcohols; Guaiacol; Humans; Ketones; Models, Molecular; Plant Extracts; Protective Agents; Sesquiterpenes; Structure-Activity Relationship; Zingiber officinale

Zingiberis Rhizoma (ZR) and Zingiberis Rhizoma Carbonisata (ZRC), as two forms of ginger-based herbal drugs used in China for at least 2000 years, have been recorded in Chinese Pharmacopoeia and applied for specific indications in traditional Chinese medicine (TCM).. The present study aimed to explore the underlying therapeutic and processing mechanism of the absorbed components of ZR and ZRC on deficiency-cold and hemorrhagic syndrome (DCHS) using network pharmacological technique combined with pharmacokinetics strategy.. In this study, a rapid and sensitive approach was conceived to simultaneously determine the seven components (zingiberone, 6-gingerol, 8-gingerol, 6-shogaol, 6-paradol, diacetyl-6-gingerol and 10-gingerol) in rat serum by HPLC-DAD-MS. The network pharmacological technique was employed to evaluate the effect of the absorbed components of ZR and ZRC on DCHS. Also, the vitro experiments were carried out to validate the functions of the seven compounds on coagulation and other major haematological effects.. The values of intra-assay and inter-assay precision were determined to be less than 7.44%, with an accuracy value ranging from 83.64% to 107.99%. Analysis of rat plasma revealed that the extraction recoveries and matrix effects of the seven analytes were >85.76%. The method for validation following oral administration of ZR and ZRC to rats was proved to be a success in the pharmacokinetic study of the seven ingredients. Pharmacokinetics showed that ZR processing could enhance the absorption and utilization of 6-shogaol, 6-paradol and diacetyl-6-gingerol, meanwhile reduce the absorption of 6-gingerol, 8-gingerol, and 10-gingerol. Through the pathway enrichment analysis, it was found that the significant biological process of ZR and ZRC on DCHS was primarily associated with complement, coagulation cascades and platelet activation pathways. The vitro experiments indicated that zingiberone, 6-paradol and diacetyl-6-gingerol had a hemostatic effect by upregulating the expression of one or more targets such as TNF-α, FⅩa, FⅫ, FⅧ, ICAM-1, vWF and ITGB3. While 6-gingerol, 6-shogaol, 8-gingerol and 10-gingerol played a critical role in promoting blood circulation by increasing the expression of TM and/or PORC, and/or reducing the expression of ITGB3.. In brief, network pharmacological technique in combination with pharmacokinetics strategy provided an applicable method for pharmacological mechanism study of ZR and ZRC, which, also, could be used as reference for quality control of the two drugs. In a broader sense, this combined strategy might even be valuable in uncovering the therapeutic and processing mechanism of Chinese herbs on a systematic level.

Topics: Animals; Diacetyl; Drugs, Chinese Herbal; Network Pharmacology; Rats

Grains of paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. Anti-obesity effect of GP intake was demonstrated in a previous report. Aim of the present study was to isolate some compounds in GP and clarify the anti-obesity mechanism.. Ten vanilloid compounds were isolated. Among them, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol and 6-shogaol were identified as the major constituents in GP extract. Moreover, the extract and 6-gingerol, which is one of the principal components of GP extract, were orally administered to rats to investigate the effect on sympathetic nerve activity (SNA) in brown adipose tissue (BAT). The injection of GP extract and 6-gingerol decreased BAT-SNA, whereas capsaicin, which is a major component of chili pepper, activates the sympathetic nervous system.. This study suggested that GP extract and 6-gingerol were largely unrelated to the anti-obesity effect by the activation of interscapular BAT-SNA and had a different anti-obesity mechanism to capsaicin. © 2018 Society of Chemical Industry.

Topics: Adipose Tissue, Brown; Animals; Catechols; Fatty Alcohols; Guaiacol; Humans; Ketones; Molecular Structure; Obesity; Plant Extracts; Rats; Seeds; Sympathetic Nervous System; Zingiberaceae

Paradols are unsaturated ketones produced by biotransformation of shogaols in gingers. Among them, 6-paradol has been investigated as a new drug candidate due to its anti-inflammatory, apoptotic, and neuroprotective activities. In this study, the inhibitory effects of 6-paradol on the activities of cytochrome P450 (CYP) enzymes were investigated with human liver microsomes and recombinant CYP isozymes. 6-Paradol showed concentration-dependent inhibitory effects on CYP1A2, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 isozymes, with IC

Topics: Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Guaiacol; Humans; Ketones; Microsomes, Liver; Pharmaceutical Preparations; Recombinant Proteins; Zingiber officinale

The anti-diabetic activity of ginger powder (

Topics: 3T3-L1 Cells; Adipocytes; AMP-Activated Protein Kinases; Animals; Blood Glucose; Catechols; Cell Line; Diabetes Mellitus, Type 2; Diet, High-Fat; Glucose; Glucose Tolerance Test; Guaiacol; Humans; Hyperglycemia; Immunoblotting; Ketones; Lipids; Male; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Phosphorylation; Phytotherapy; Zingiber officinale

Oily extracts of Sichuan and Melegueta peppers evoke pungent sensations mediated by different alkylamides [mainly hydroxy-alpha-sanshool (alpha-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these pungent sensations.. The structure-activity relationships of these molecules on TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using calcium and voltage imaging on dissociated dorsal root ganglia neurons and human embryonic kidney 293 cells expressing the wild-type channels or specific cysteine mutants using glutathione trapping as a model to probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' aversive responses were measured in a taste brief-access test.. For TRPA1 activation, the cis C6 double bond in the polyenic chain of alpha-SOH was critical, whereas no structural specificity was required for activation of TRPV1. Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not responsive to alpha-SOH.. The pungent nature of components of Sichuan and Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and may explain the aversive properties of these compounds.

Topics: Amides; Animals; Animals, Newborn; Catechols; Cells, Cultured; Female; Guaiacol; Humans; Ketones; Male; Mice; Mice, Knockout; Plant Oils; Structure-Activity Relationship; Transient Receptor Potential Channels; TRPA1 Cation Channel; TRPV Cation Channels; Zanthoxylum; Zingiberaceae