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Systemic studies dealing with 6-Shogaol (C17H24O3) safety in experimental animals is lacking. Therefore, the aim of current study was to determine the safe dose of 6- Shogaol that can be used in mice model and to assess the potential toxicity that may be initiated by the higher concentrations of this substance by means of clinical observations and evaluation of histopathological changes in liver, kidney and spleen. Sixty mice were divided into 6 groups; groups 1 and 2 served as negative and vehicle control respectively, whereas animals of groups 3, 4, 5 and 6 were treated with 10, 20, 40, and 100 mg/kg b.w. Shogaol respectively. The animals were investigated daily for any sign indicative for activity alterations and toxicity along with their body weight measurement throughout experiment for 14 days. At the end of the experiment, the animals were euthanized and the liver, spleen and kidney were collected for histopathological examination. The results obtained from this study showed that the 10, 20 and 40 mg/kg b.w. doses of Shogaol were safe compared to the 100 mg/kg b.w. dose which resulted in mild clinical activity alterations, reduction in body weight gain and histopathological changes, probably attributed to Shogoal toxicity, in 30% of the total mice treated by this dose. No mortality was observed in all groups. These results may provide a new insight into the safe doses of this phenolic constituent of ginger in experimental animals and open the way for more future studies related to its medicinal benefits. [ABSTRACT FROM AUTHOR]

Objective(s): This study aimed to investigate the effect of Shogaol on dextran sodium sulfate (DSS)- induced ulcerative colitis (UC) in mice compared to an immune-suppressant chemotherapeutic medicine, known as 6-thioguanine (6-TG). Materials and Methods: Thirty-six adult BALB/c mice were divided into six groups: group 1 (positive control): no DSS exposure and no treatment; group 2 (negative control): DSS exposure without treatment; group 3 (vehicle control): DSS exposure and olive oil treatment; group 4: DSS exposure and 0.3 mg/kg 6-TG treatment; group 5: DSS exposure and 20 mg/kg Shogaol treatment; and group 6: DSS exposure and 40 mg/kg Shogaol treatment. At day 16, the mice were euthanized and UC was evaluated according to colon length, histologically index score and expression scores of the epidermal growth factor receptor (EGFR). Results: The disease activity index (DAI) and histological index scores of mice treated with 40 mg/kg body weight (BW) Shogaol were approximately lower than the corresponding scores of mice treated with 6-TG. In addition, the rate of healing in the former mice was approximately 3 folds higher than that of the latter ones as indicated by the lack of EGFR expression in colonic glands and macrophages. Conclusion: These findings showed that the therapeutic effect of 40 mg/kg BW Shogaol could be better than 6-TG in the treatment of UC, and it may draw the attention regarding the priority of using this cheap plant-derived substance for treatment of the inflammatory bowel diseases because treatment with 6-TG is usually associated with adverse side effects. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gingerols and shogaols are compounds found in ginger (Zingiber officinale Roscoe); shogaols are found in lower concentration than gingerols but exhibit higher biological activities. This work studied the effects of different drying methods including open sun drying (OSD) solar tunnel drying (STD) and hot air drying (HAD) with various temperature on the formation of six main active compounds in ginger rhizomes, namely 6-, 8-, and 10-gingerols and 6-, 8-, and 10-shogaols, as well as essential oil content. Antioxidant and antimicrobial activity of dried ginger was also evaluated. High performance liquid chromatography (HPLC) analysis showed that after HAD with variable temperature (120, 150 and 180 °C), contents of 6-, 8-, and 10-gingerols decreased, while contents of 6-, 8-, and 10-shogaol increased. High formation of 6-, 8-, and 10-shogaol contents were observed in HAD (at 150 °C for 6 h) followed by STD and OSD, respectively. OSD exhibited high content of essential oil followed by STD and HAD method. Ginger-treated with HAD exhibited the highest DPPH (IC50 of 57.8 mg/g DW) and FRAP (493.8 µM of Fe(II)/g DM) activity, compared to STD and OSD method. HAD ginger exhibited potent antimicrobial activity with lower minimum inhibition concentration (MIC) value against bacteria strains followed by STD and OSD, respectively. Ginger extracts showed more potent antimicrobial activity against Gram positive bacteria than Gram negative bacteria strains. Result of this study confirmed that conversion of gingerols to shogaols was significantly affected by different drying temperature and time. HAD at 150 °C for 6 h, provides a method for enhancing shogaols content in ginger rhizomes with improving antioxidant and antimicrobial activities. [ABSTRACT FROM AUTHOR]

Tracking the impact of commonly applied post-harvesting and industrial processing practices on the compositional integrity of ginger rhizome was implemented in this work. Untargeted metabolite profiling was performed using digitally-enhanced HPTLC method where the chromatographic fingerprints were extracted using ImageJ software then analysed with multivariate Principal Component Analysis (PCA) for pattern recognition. A targeted approach was applied using a new, validated, simple and fast HPTLC image analysis method for simultaneous quantification of the officially recognized markers 6-, 8-, 10-gingerol and 6-shogaol in conjunction with chemometric Hierarchical Clustering Analysis (HCA). The results of both targeted and untargeted metabolite profiling revealed that peeling, drying in addition to storage employed during processing have a great influence on ginger chemo-profile, the different forms of processed ginger shouldn't be used interchangeably. Moreover, it deemed necessary to consider the holistic metabolic profile for comprehensive evaluation of ginger during processing. [ABSTRACT FROM AUTHOR]

Decision makers responsible for quality management along the food chain need to reflect on their analytical tools that should ensure quality of food and especially superfood. The “4ables” in target analysis (stable, extractable, separable, detectable) focusing on marker compounds do not cover all relevant information about the sample. On the example of ginger, a streamlined quantitative bioprofiling was developed for effect-directed analysis of 17 commercially available ginger and ginger-containing products via high-performance thin-layer chromatography (HPTLC-UV/Vis/FLD-bioassay). The samples were investigated concerning their active profile as radical scavengers, antimicrobials, estrogen-like activators and acetylcholinesterase/tyrosinase inhibitors. The [6]-gingerol and [6]-shogaol content of the different products ranged 0.2–7.4 mg/g and 0.2–3.0 mg/g, respectively. Further, multipotent compounds were discovered, characterized, and for example, assigned as [8]- and [10]-gingerol via HPTLC-ESI-HRMS. The developed bioprofiling is a step forward to new analytical methods needed to inform on the true product quality influenced by cultivation, processing, and storage. [ABSTRACT FROM AUTHOR]

Nine new gingerols, including three 6-oxo-shogaol derivatives [(Z)-6-oxo-[6]-shogaol (1), (Z)-6-oxo-[8]-shogaol (2), (Z)-6-oxo-[10]-shogaol (3)], one 6-oxoparadol derivative [6-oxo-[6]-paradol (4)], one isoshogaol derivative [(E)-[4]-isoshogaol (5)], and four paradoldiene derivatives [(4E,6Z)-[4]-paradoldiene (8), (4E,6E)-[6]-paradoldiene (9), (4E,6E)-[8]-paradoldiene (10), (4E,6Z)-[8]-paradoldiene (11)], together with eight known analogues, were isolated from the rhizoma of Zingiber officinale. Their structures were elucidated on the basis of spectroscopic data. It was noted that the isolation of 6-oxo-shogaol derivatives represents the first report of gingerols containing one 1,4-enedione motif. Their structures were elucidated on the basis of spectroscopic and HRESIMS data. All the new compounds were evaluated for their cytotoxic activities against human cancer cells (MCF-7, HepG-2, KYSE-150). [ABSTRACT FROM AUTHOR]

Nuclear factor-kappaB (NF-κB) and activator protein 1 (AP-1) is a major transcription factor which regulates many biological and pathological processes such as inflammation and cell proliferation, which are major implicates in cancer progression. [6]-Shogaol ([6]-SHO) is a major constituent of ginger, exhibits various biological properties such as anti-oxidants, anti-inflammation and anti-tumor. Recently, we proven that [6]-SHO prevents oral squamous cell carcinoma by activating proapoptotic factors in in vitro and in vivo experimental model. However, the preventive efficacy of [6]-SHO in 7,12-dimethylbenz[ a ]anthracene (DMBA) induced hamster buccal pouch carcinogenesis (HBP) has not been fully elucidated, so far. Hence, we aimed to investigate the effect of [6]-SHO on inflammation and cell proliferation by inhibiting the translocation of NF-κB and AP-1 in DMBA induced HBP carcinogenesis. In this study, we observed upregulation of inflammatory markers (COX-2, iNOS, TNF-α, interleukin-1 and -6), cell proliferative markers (Cyclin D1, PCNA and Ki-67) and aberrant activation of NF-κB, AP-1, IKKβ, c-jun, c-fos and decreased IκB-α in DMBA induced hamsters. Conversely, oral administration of [6]-SHO strongly inhibited constitutive phosphorylation and degradation of IκB and inhibit phosphorylation of c-jun, c-fos, resulting in inhibition of nuclear translocation of NF-κBp65 and AP-1. Thus, inhibition of NF-κB and AP-1 activation by [6]-SHO attenuates inflammation and cell proliferative response in DMBA induced hamsters. Our finding suggested that [6]-SHO is a novel functional agent capable of preventing DMBA induced inflammation and cell proliferation associated tumorigenesis by modulating multiple signalling molecules. [ABSTRACT FROM AUTHOR]

Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders with a risk that increases with aging. ANDs are generally characterized by common neuropathological conditions of the central nervous system, such as oxidative stress, neuroinflammation, and protein misfolding. Recently, efforts have been made to overcome ANDs because of the increase in age-dependent prevalence. Ginger, the rhizome of Zingiber officinale Roscoe, is a popular food spice and has a long history of use in traditional medicine for treating various disease symptoms. The structure-activity relationships of ginger phytochemicals show that ginger can be used to treat ANDs by targeting different ligand sites. This review shows that ginger and its constituents, such as 6-gingerol, 6-shogaol, 6-paradol, zingerone, and dehydrozingerone, are effective for ameliorating the neurological symptoms and pathological conditions of ANDs through by modulating cell death or cell survival signaling molecules. From this review, we conclude that the active ingredients in ginger have therapeutic potential in ANDs. [ABSTRACT FROM AUTHOR]

Ginger (Zingiber officinale Roscoe) has long been a popular ingredient in both medicinal and culinary settings. However, while ginger, and the related galangal, were once both popular ingredients in Britain (e.g., from roughly the 9th to the 17th centuries), they essentially disappeared from savoury culinary recipes thereafter, as spiced foods fell out of fashion (though the dried spice continued to be used in sweet baked products). However, the desirable pungency and flavour attributes of ginger, together with renewed interest in the spice's medicinal properties, combined with the growing popularity of Asian cuisines that make extensive use of ginger (in savoury recipes), has resulted in a recent resurgence in sales of this once popular spice. From a culinary perspective, the volatiles in ginger help to lift the taste of the dishes to which they are added while the spice's pungency may offer a means of substituting for some of the less healthy ingredients currently in our food. [ABSTRACT FROM AUTHOR]

Marine cultured fish often suffer from Cryptocaryon irritans infection, which causes enormous mortality. C. irritans is resistant to oxidative damage induced by zinc. To develop an effective drug to control the parasite, a putative thioredoxin glutathione reductase (CiTGR) from C. irritans was cloned and characterized. CiTGR was designed as a target to screen for inhibitors by molecular docking. The selected inhibitors were tested both in vitro and in vivo. The results showed that CiTGR is located in the nucleus of the parasite, possesses a common pyridine-oxidoreductases redox active center, and lacks a glutaredoxin active site. Recombinant CiTGR exhibited high TrxR activity but low glutathione reductase activity. Shogaol was found to significantly suppress TrxR activity and enhance toxicity of zinc on C. irritans (P < 0.05). The abundance of C. irritans on the fish body decreased significantly after oral administration of shogaol (P < 0.05). These results implied that CiTGR could be used to screen for drugs that weaken the resistance of C. irritans to oxidative stress, which is critical for controlling the parasite in fish. This paper deepens the understanding of the interaction between ciliated parasites and oxidative stress. [Display omitted] • Marine cultured fish suffer from cryptocaryoniasis, caused by Cryptocaryon irritans. • C. irritans thioredoxin glutathione reductase (CiTGR) was cloned and characterized. • CiTGR can counteract oxidative stress in C. irritans. • CiTGR were designed to screen inhibitors for thioredoxin reductase activity. • The inhibitor shogaol weakens CiTGR function and enhances oxidative damage. [ABSTRACT FROM AUTHOR]

The prevalence of obesity has increased rapidly worldwide. Obesity is characterized by excessive adipose tissue in the body, which is related to hyperplasia and hypertrophy in adipocytes. Ginger (Zingiber officinale Roscoe) is a medicinal plant that possesses an anti-obesogenic effect mostly attributed to gingerols, the most abundant bioactive compounds in ginger. The anti-adipogenic and lipolytic effects of these phenols have been shown when investigated individually. Therefore, the present study aimed to evaluate the lipolytic and anti-adipogenic activity of a mix of the main ginger phenols 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, 8-shogaol and 10-shogaol on the 3T3-L1 cell line. A total of four study groups were designed: Negative control (3T3-L1 preadipocytes); positive control (mature 3T3-L1 adipocytes); phenols-pre (3T3-L1 cells stimulated with the phenols mix during adipogenic differentiation); and phenols-post (mature 3T3-L1 adipocytes stimulated with the phenols mix). MTT viability cell assay and Oil Red O staining were performed. Glycerol concentration supernatants were determined using the VITROS 350 Chemistry System. Expression of mRNA was measured using qPCR. The treatment with a 2 µg/ml ginger phenol dose reduced the lipid content by 45.52±7.8 and 35.95±0.76% in the phenols-pre and -post group, respectively, compared with that in the positive control group. The phenols-post group presented a higher glycerol concentration in the supernatant compared with that in the positive control and the phenols-pre groups. The mRNA expression levels of CCAAT/enhancer-binding protein alpha, peroxisome proliferator activated receptor-γ, fatty acid-binding protein 4 and fatty acid synthase were higher in the phenols-pre and lower in the phenols-post groups, compared with those in the positive control group. To the best of our knowledge, the current study demonstrated for the first time the anti-adipogenic and lipolytic effects of a mix of the main bioactive compounds found in ginger, and it also established the basis to use this mix of phenols in in vivo studies and clinical trials. [ABSTRACT FROM AUTHOR]

• Current strategies (over the last 5 years) towards Gingerol extraction are given. • Innovative techniques for the purification of Gingerol are highlighted. • The most recent outcomes for the effective extraction are stated. • MAME technique exhibits extraction yield of 6-shogaol as high as 97%. Currently, ginger is one the most consumed plants when dealing with the treatments of various illnesses. So far, it is known that various biologically active molecules, such as gingerols, shogaols and zingerone, among others, are the main responsible for specific biological activities, opening a new window for its utilization as a nutraceutical in foods. In pioneering extraction processes, solvent extraction has been initially used for these applications; however, the drawbacks of this typical extraction method compared with other emergent separation techniques make it possible for the exploration of new extraction pathways, including microwave, ultrasound, supercritical, subcritical and pressurized-assisted extraction, along with three phase partitioning, high-speed counter current chromatography and magnetic solid phase extraction. To the best of our knowledge, there is no report documenting the recent studies and cases of study in this field. Therefore, we comprehensively review the progress and the latest findings (over the last five years) on research developments, including patents and emerging extraction methods, aiming at the purification of biologically active molecules (gingerols, shogaols and zingerone) contained in ginger. Over the course of this review, particular emphasis is devoted to breakthrough strategies and meaningful outcomes in ginger components extraction. Finally, dosage and safety concerns related to ginger extracts are also documented. [ABSTRACT FROM AUTHOR]

Two kinds of extraction methods ultrasonic-assisted micellar extraction (UAME) and microwave-assisted micellar extraction (MAME) coupled with ultra-high performance liquid chromatography with ultraviolet detector (UHPLC-UV) were developed and evaluated for extraction and determination of zingerone, 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol in Rhizoma Zingiberis and Rhizoma Zingiberis Preparata. A biosurfactant, hyodeoxycholic acid sodium salt, was used in micellar extraction. Several experimental parameters were studied separately by a univariate method. The result indicated that the MAME was more efficient than UAME. The optimal conditions of MAME were as follows: 100 mM of hyodeoxycholic acid sodium salt was used as surfactant, the irradiation time was set at 10 s and the extraction temperature was set at 60 °C. The validation results indicated that the limits of detection were in the range of 3.80-8.11 ng/mL. The average recoveries were in the range of 87.32-103.12% for the two samples at two spiking levels. Compared with other reported methods, the proposed MAME-UHPLC-UV method was more effective, quicker (10 s) and more eco-friendly. [ABSTRACT FROM AUTHOR]

6-shogaol is a phytochemical of dietary ginger, we found that 6-shogaol could induced both autophagic and apoptotic death in human colon adenocarcinoma (HT-29) cells. Results of this study showed that 6-shogal induced cell cycle arrest, autophagy, and apoptosis in HT-29 cells in a time sequence. After 6 h, 6-shogal induced apparent G2/M arrest, then the HT-29 cells formed numerous autophagosomes in each phase of the cell cycle. After 18 h, increases in acidic vesicles and LAMP-1 (Lysosome-associated membrane proteins 1) showed that 6-shogaol had caused autophagic cell death. After 24 h, cell shrinkage and Caspase-3/7 activities rising, suggesting that apoptotic cell death had increased. And after 48 h, the result of TUNEL assay indicated the highest occurrence of apoptosis upon 6-shogaol treatment. It appeared that apoptosis is triggered by autophagy in 6-shogaol treated HT-29 cells, the damage of autophagic cell death initiated apoptosis program. [ABSTRACT FROM AUTHOR]

An ionic liquid-based microwave-assisted extraction (ILMAE) method was developed to extract 6-, 8-, 10-gingerols and 6-, 8-, and 10-shogaols from ginger ( Zingiber officinale Roscoe). A series of water-miscible ionic liquids (ILs) with different kinds of anions and cations were investigated. Results indicated that among the investigated ILs, the carbon chains of alkyl cations remarkably affected the extraction efficiency of the six compounds and 1-decyl-3-methylimidazolium bromide ([C 10 MIM]Br) was the optimal IL. The selected conditions for ILMAE were as follows: [C 10 MIM]Br concentration, 0.80 M; extraction temperature, 75 °C; irradiation time, 30 min; and irradiation power, 400 W, in the case of solid–liquid ratio of 0.1:10 g/mL. This study showed that compared with the total extraction yield of 0.595 ± 0.031% by methanol marinated extraction and 0.673 ± 0.043% by methanol-based microwave-assisted extraction, ILMAE attained higher yield of 0.716 ± 0.051%; and ILMAE obtained a shorter time of 30 min for extraction of gingerols and shogaols from ginger. This study provides a basis for separating and purifying bioactive components from ginger. Moreover, the use of small amounts of [C 10 MIM]Br as extraction solution in the method was considered environmentally friendly. [ABSTRACT FROM AUTHOR]

The article focuses on a study regarding standard method performance requirements (SMPRs) for quantitation of select nonvolatile ginger constituents. It mentions the use of gingerols, shogaol and gingerdiones for SMPRs and states that dietary ingredients includes vitamins, herbs and amino acid. It also metnions that statistical variation in the analytical outcome influenced by typical laboratory variables.

Sortilin-related receptor 1 (SORL1) is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate amyloid beta (Aβ). Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, research regarding the activation of SORL1 has not yet been reported. Here, we aimed to investigate whether 6-shogaol contributes to the increases in SORL1 that are related to Alzheimer's disease (AD). To clarify the effect of 6-shogaol as a possible activator of SORL1, we used SORL1 siRNA as a blockade of SORL1 in hippocampal neuronal cells (HT22). We found that SORL1 siRNA treatment naturally inhibited SORL1 and led to increases in β-secretase APP cleaving enzyme (BACE), secreted APP-β (sAPPβ) and Aβ. In contrast, 6-shogaol-mediated activation of SORL1 significantly downregulated BACE, sAPPβ, and Aβ in both in vitro HT22 cells and in vivo APPSw/PS1-dE9 Tg mice. Therefore, SORL1 activation by 6-shogaol provides neuronal cell survival through the inhibition of Aβ production. These results indicate that 6-shogaol should be regarded as an SORL1 activator and a potential preventive agent for the treatment of AD. [ABSTRACT FROM AUTHOR]

The traditional Japanese herbal medicine hangeshashinto (HST) has beneficial effects for the treatment of oral ulcerative mucositis (OUM) in cancer patients. However, the ingredient-based mechanism that underlies its pain-relieving activity remains unknown. In the present study, to clarify the analgesic mechanism of HST on OUM-induced pain, we investigated putative HST ingredients showing antagonistic effects on Na + channels in vitro and in vivo. A screen of 21 major ingredients using automated patch-clamp recordings in channel-expressing cells showed that [6]-gingerol and [6]-shogaol, two components of a Processed Ginger extract, considerably inhibited voltage-activated Na + currents. These two ingredients inhibited the stimulant-induced release of substance P and action potential generation in cultured rat sensory neurons. A submucosal injection of a mixture of [6]-gingerol and [6]-shogaol increased the mechanical withdrawal threshold in healthy rats. In a rat OUM model, OUM-induced mechanical pain was alleviated 30 min after the swab application of HST despite the absence of anti-bacterial and anti-inflammatory actions in the OUM area. A swab application of a mixture of [6]-gingerol and [6]-shogaol induced sufficient analgesia of OUM-induced mechanical or spontaneous pain when co-applied with a Ginseng extract containing abundant saponin. The Ginseng extract demonstrated an acceleration of substance permeability into the oral ulcer tissue without an analgesic effect. These findings suggest that Na + channel blockage by gingerol/shogaol plays an essential role in HST-associated analgesia of OUM-induced pain. This pharmacological mechanism provides scientific evidence supporting the use of this herbal medicine in patients suffering from OUM-induced pain. [ABSTRACT FROM AUTHOR]

Zingiberis Rhizoma is a typical Chinese herb in 'hot' property. Nowadays, increasing attention has been aroused for its essential role in both health care and treatment of 'cold' syndrome. And research about characteristics of Zingiberis Rhizoma is able to provide an important reference for its deeper understand and successful clinic application. However, cognition level about the 'hot' property of Zingiberis Rhizoma is superficial, and mechanism behind the 'hot' presentation is still elusive and unclear. In this study, the 'hot' property of Zingiberis Rhizoma was investigated at a monomer level with assistance of microcalorimetry, an objective and sensitive method in evaluating biological activity. Three bioactive compounds including 6-gingerol, 8-gingerol and 6-shogaol were selected, and their thermal activities were explored with mitochondria as target. The power-time curves were recorded, and five thermal parameters ( k, P , T , Q and P ) were obtained. With PCA, P was calculated to be the main parameter to measure the bioactivities of 6-gingerol, 8-gingerol and 6-shogaol. Finally, the bioactivities of three subjects were compared with sequence to be 6-gingerol > 8-gingerol > 6-shogaol. Generally, our study is promising to offer a reference to the research about characteristics of Zingiberis Rhizoma or other herbs and is of great interest for clinic practice. [ABSTRACT FROM AUTHOR]

Inflammation is the natural way our bodies respond to infection or injury. However, if it fails to subside, inflammation can damage the body and contribute to several illnesses. Although non-resolving inflammation is not the primary factor, it is still considered to significantly contribute to several diseases such as chronic obstructive pulmonary disease (COPD), asthma, inflammatory bowel disease, rheumatoid arthritis, cancer, neurodegenerative disease, and so on. Phosphodiesterase 4 inhibitor is an established treatment to treat inflammation worldwide. However, the non-selective PDE4 was reported to exhibit adverse reactions such as nausea and diarrhoea. This study aims to identify compounds with higher selectivity for PDE4B over PDE4D and determine their binding mode and interaction through molecular docking. In this present study, three x-ray crystall structures representing PDE4B and PDE4D each were downloaded from Protein Data Bank and redock with their co-crytallized ligand to calculate the RMSD as the validation step for the docking procedure. The protein structures with the lowest RMSD (PDB ID: 3W5E for PDE4B and PDB ID: 3G58 for PDE4D) were docked with gingerols and shogaols. Binding energies were obtained and the ratios between the binding energy of PDE4B and PDE4D were calculated. 10-gingerol had been found to have the lowest binding energy and the highest selectivity of PDE4B compared to PDE4D among the compounds. Thus, the binding interaction was further investigated, and found that 10-gingerol form a hydrogen bond with invariant glutamine residue which is GLN 443 in PDE4B and GLN 535 in PDE4D. Besides, 10-gingerol also formed hydrophobic bonds between PHE 446 in PDE4B and PHE 538 in PDE4D while with isoleucine and phenylalanine residues (ILE410 and PHE414 in PDE4B and ILE502 and PHE506) on the other side. 10-gingerol also showed hydrophobic interaction with non-conserved residues in CR3 region, which is with LEU502 in PDE4B. This interaction was absent with the CR3 region in PDE4D which in turn determined the PDE4B selectivity of 10-gingerol. These results showed that 10-gingerol is a potential candidate as a selective PDE4B inhibitor as a new anti-inflammatory drug. [ABSTRACT FROM AUTHOR]

In the present study, the chemical investigation of the bioactive fractions of the rhizomes of Zingiber officinale has resulted in the identification of twenty-nine compounds including one new compound, O-methyldehydrogingerol (1). Some of the isolates were subjected into the evaluation of their antiplatelet aggregation and vasorelaxing bioactivities. Among the tested compounds, [6]-gingerol (13) and [6]-shogaol (17) exhibited potent anti-platelet aggregation bioactivity. In addition, [10]-gingerol (15) inhibited the Ca2+-dependent contractions in high K+ medium. According to the results in the present research, the bioactivity of ginger could be related to the anti-platelet aggregation and vasorelaxing mechanism.

Gingerols and shogaols are compounds found in ginger (Zingiber officinale Roscoe); shogaols are found in lower concentration than gingerols but exhibit higher biological activities. This work studied the effects of different drying methods including open sun drying (OSD) solar tunnel drying (STD) and hot air drying (HAD) with various temperature on the formation of six main active compounds in ginger rhizomes, namely 6-, 8-, and 10-gingerols and 6-, 8-, and 10-shogaols, as well as essential oil content. Antioxidant and antimicrobial activity of dried ginger was also evaluated. High performance liquid chromatography (HPLC) analysis showed that after HAD with variable temperature (120, 150 and 180 °C), contents of 6-, 8-, and 10-gingerols decreased, while contents of 6-, 8-, and 10-shogaol increased. High formation of 6-, 8-, and 10-shogaol contents were observed in HAD (at 150 °C for 6 h) followed by STD and OSD, respectively. OSD exhibited high content of essential oil followed by STD and HAD method. Ginger-treated with HAD exhibited the highest DPPH (IC50 of 57.8 mg/g DW) and FRAP (493.8 µM of Fe(II)/g DM) activity, compared to STD and OSD method. HAD ginger exhibited potent antimicrobial activity with lower minimum inhibition concentration (MIC) value against bacteria strains followed by STD and OSD, respectively. Ginger extracts showed more potent antimicrobial activity against Gram positive bacteria than Gram negative bacteria strains. Result of this study confirmed that conversion of gingerols to shogaols was significantly affected by different drying temperature and time. HAD at 150 °C for 6 h, provides a method for enhancing shogaols content in ginger rhizomes with improving antioxidant and antimicrobial activities.

Background: Zingiber officinale Roscoe (Ginger) belongs to the Zingiberaceae family, which is renowned for its rich nutritional and phytochemical composition, and has been validated for its anti-diabetic and anti-inflammatory properties via in vitro, in vivo, and clinical studies. Nonetheless, a comprehensive review of these pharmacological studies, especially clinical studies, together with an analysis of the mechanism of action of the bioactive compounds is still lacking. This review provided a comprehensive and updated analysis of the anti-diabetic efficacy of Z. officinale and its compounds ginger enone, gingerol, paradol, shogaol, and zingerone., Methods: The present systematic review was conducted using the PRISMA guidelines. Scopus, ScienceDirect, Google Scholar, and PubMed were the main databases used for retrieving information from inception to March 2022., Results: From the findings obtained, Z. officinale can be regarded as a therapeutic species showing significant improvement in clinical studies on glycemic parameters (Fasting blood glucose (FBG), hemoglobin A1C (HbA1c), and insulin resistance). In addition, the bioactive compounds of Z. officinale act via several mechanisms as revealed by in vitro and in vivo studies. Overall, these mechanisms were by increasing glucose-stimulated insulin secretion, sensitising insulin receptors and raising glucose uptake, translocation of GLUT4, inhibition of advanced glycation end product-induced increase of reactive oxygen species, regulation of hepatic gene expression of enzymes associated with glucose metabolism, regulation of the level of pro-inflammatory cytokines, amelioration of the pathological injuries of kidneys, protective effect on the morphology of β-cells as well as its antioxidant mechanisms, among others., Conclusion: Z. officinale and its bioactive compounds displayed promising results in in vitro and in vivo systems, nevertheless, it is highly recommended that human trials be conducted on these compounds since clinical studies are the core of medical research and considered the final stages of the drug development process., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net)

Natural killer (NK) cell, a kind of lymphocyte cells, plays an important role in attacking infectious, immature, and cancer cell. Its function could be modulated by food bioactive compounds. This experiment was conducted to investigate the effects of ginger root bioactive compounds such as oleoresin, gingerol, and shogaol on cytolitic response of NK cell in vitro. Lymphocyte cells were isolated by centrifugation on ficoll-hypaque density (1,77 ?0,001 g/ml) method. Leukemic cells line K-562 as target cells(TC) labelled by [3H]-timidin, together with lymphocyte as effector cell (EC) were cultured in two ratio levels of EC : TC equal to 1:50 and 1:100), and two culture conditions, for 4 hours, respectively. Paraquate dichloride (1,1-dimethyl-4,4-bipyridilium dichloride) 3 mM was used to induce stress oxidative circumstance. Cytolytic capacity of NK cells was determined by percentage of TC lysed by NK cells, in normal and oxidative stress conditions. Statistical analysis showed that the effects of ginger bioactive compounds on cytolytic response of NK cell depended on the culture conditions, as shown by cultures in the presence of oleoresin, and gingerol, but not shogaol. In the lymphocyte culture without stress oxidative, oleoresin, gingerol and shogaol compounds increased significantly cytolytic response of NK cells cultured at a ratio of TC : EC equal to 1:50, with the highest increament of 65 % at oleoresin concentration of 50 ?g/ml. However, in culture at a ratio of TC : EC equals to 1:100, only oleoresin at a concentration of 50 ?g/ml increased significantly cytolytic response of NK cells with the highest increament of 8 %. Shogaol did not affect significantly NK cells cytolytic response. Under stress oxidative conditions, shogaol increased significantly cytolytic response of NK cells cultured at a ratio of TC:EC equal to 1:50, but the highest increament of 56 % , was by oleoresin at concentration of 50 ?g/ml. Meanwhile, oleoresin and gingerol did not increased significantly cytolytic response of NK cells. At a culture- ratio of TC: EC equal to 1:100, gingerol increased significantly cytolytic response of NK cells of 21 % at a concentration of 50 ?g/ml. However, oleoresin did not increased significantly cytolytic response of NK cells. In contrast, shogaol decreased significantly cytolytic response of NK cell with the highest decreament of 16 % at 200 ?g/ml. These findings verified that ginger root bioactive compounds increased cytolityc response of NK cells in destroying cancer cells, at certain conditions and concentrations, especially at low concentrations.

Background Stimulation of transient receptor potential ankyrin 1 ( TRPA1), which abundantly expressed in enterochromaffin cells ( ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal ( GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto ( TU-100) has been reported to be beneficial for postoperative ileus ( POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine ( SI). Methods The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. Key Results Orally administered TRPA1 agonists, aryl isothiocyanate ( AITC) and cinnamaldehyde ( CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool ( GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5- HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5- HT from RIN-14B cells in a dose- and TRPA1-dependent manner. Conclusions & Inferences Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5- HT and/or ECC are involved in the effect of TRPA1 on motility. [ABSTRACT FROM AUTHOR]

Allergic dermatitis (AD) clinically presents with skin erythematous plaques, eruption, and elevated serum IgE, and T helper cell type 2 and 1 (Th2 and Th1) cytokine levels. 6-Shogaol [1-(4-hydroxy-methoxyphenyl)-4-decen-one], a pungent compound isolated from ginger , has shown anti-inflammatory effects, but its inhibitory effects on AD are unknown. The aim of this study was to examine whether 6-shogaol inhibits AD-like skin lesions and their underlying mechanism in vivo and in vitro. An AD-like response was induced by tumor necrosis factor-α (TNF-α) + IFN-γ in human keratinocytes or by 2,4-dinitrochlorobenzene (DNCB) in mice. In vivo, 6-shogaol inhibited the development of DNCB-induced AD-like skin lesions and scratching behavior, and showed significant reduction in Th2/1-mediated inflammatory cytokines, IgE, TNF-α, IFN-γ, thymus and activation-regulated chemokine, IL-1, 4, 12, and 13, cyclooxygenase-2, and nitric oxide synthase levels. In vitro, 6-shogaol inhibited reactive oxygen species (ROS) and mitogen-activated protein kinases (MAPKs) signaling, and increased the levels of total glutathione, heme oxygenase-1, and quinone 1 via nuclear factor erythroid 2 related factor 2 (Nrf2) activation. 6-Shogaol can alleviate AD-like skin lesions by inhibiting immune mediators via regulating the ROS/MAPKs/Nrf2 signaling pathway, and may be an effective alternative therapy for AD. [ABSTRACT FROM AUTHOR]

6-Shogaol can be extracted from ginger and has been shown to exert anti-inflammatory and antioxidant activities, which are potentially relevant to the treatment of central nervous system disorders. Oxidative stress and inflammation are closely associated with ischemic injury and can eventually result in neuronal death. The aim of this study was to evaluate if 6-shogaol exerts neuroprotective activity. To this end, we determined its effects on oxidative stress and inflammation in a mouse model of middle cerebral artery occlusion (MCAO)-induced brain damage. In this model, MCAO was induced in C57BL/6 mice (30–35 g, 9 weeks) for 1 h, followed by 24 h reperfusion. Mice were treated orally with 6-shogaol (0.1 ml, 5 or 20 mg/kg) once daily for 7 consecutive days prior to MCAO. We found that 6-shogaol significantly reduced neurological deficit scores and the mean infarct area. Moreover, 6-shogaol improved the behavioral deficits in the MCAO group. In addition, 6-shogaol pretreatment dampened MCAO-mediated production of reactive oxygen species and inflammatory cytokines. Mechanistic studies revealed that 6-shogaol inhibits the cysteinyl leukotriene 1 receptor (CysLT1R) and mitogen-activated protein kinase (MAPK) signaling proteins, thus providing a potential pharmacological mechanism for our observations. These results suggest that 6-shogaol can ameliorate the outcomes of MCAO and could thus be used as a potential preventive of stroke. [ABSTRACT FROM AUTHOR]

Although 6-shogaol, a constituent of ginger, has been reported to have anti-inflammatory and anti-oxidant effects on neuronal cells, the effects of 6-shogaol on Alzheimer’s disease (AD) have not yet been investigated. Here we aimed to determine whether 6-shogaol exerts neuroprotective effects against AD. Specifically, we investigated the effects of 6-shogaol on the cysteinyl leukotriene 1 receptor (CysLT1R), a major factor in AD pathogenesis. Moreover, we clarified the relationship between CysLT1R and cathepsin B, a cysteine protease. We used in vitro and in vivo models to determine whether 6-shogaol inhibits CysLT1R/cathepsin B in an amyloid-beta (Aβ; 1–42)-induced model of neurotoxicity. We first confirmed that CysLT1R and cathepsin B are upregulated by Aβ (1-42) and that CysLT1R activation induces cathepsin B. In contrast, we found that 6-shogaol-mediated inhibition of CysLT1R downregulates cathepsin B in both in vitro and in vivo models. Furthermore, we found that 6-shogaol-mediated inhibition of CysLT1R/cathepsin B reduces Aβ deposition in the brain and ameliorates behavioral deficits in APPSw/PS1-dE9 Tg mice. Our results indicate that 6-shogaol is a CysLT1R/cathepsin B inhibitor and is a novel potential therapeutic agent for the treatment of various neurodegenerative diseases, including AD. [ABSTRACT FROM AUTHOR]

Ginger ( Zingiber officinale ) is a well-known herb used in ethnomedicine. [6]-shogaol, a phenolic nature is a major constituent of ginger. In this study, we investigated the anticancer activity of [6]-shogaol in Laryngeal cancer (Hep-2) cells. We demonstrated the effects of [6]-shogaol on the cell growth and apoptosis in Hep-2 cells were analyzed by the generation of reactive oxygen species (ROS), the level of mitochondrial membrane potential ( ΔYm ), DNA damage and apoptotic morphological changes were analyzed by AO/EtBr, AO and Hoechst staining. Further, apoptotic protein expressions were analyzed by western blot analysis. Our results indicated that [6]-shogaol induces apoptosis as evidenced by loss of cell viability, enhanced ROS, lipid peroxidation results in altered mitochondrial membrane potential, increased DNA damage in Hep-2 cells. Further, the prooxidant role of [6]-shogaol inhibit Bcl-2 expression with the simultaneous up-regulation of Bax, Cytochrome c, Caspase-9 and -3 protein expressions were observed in Hep-2 cells. Thus, [6]-shogaol induces apoptosis in Hep-2 cells through inducing oxidative damage and modulate apoptotic marker expressions. Therefore, [6]-shogaol might be used as a therapeutic agent for the treatment of laryngeal cancer. [ABSTRACT FROM AUTHOR]

This study aims to investigate the relationship between constituent contents and anti-inflammatory activities of heat processed gingers, and to optimize heat process to enhance ginger’s anti-inflammatory capacity. After 3 h of heat treatment at 75, 100, and 125°C, the gingerols content was reduced by 6.8, 12.6, and 42.7%, respectively, and the shogaols content was increased by 2.95, 4.85, and 9.34 fold, respectively. After 3 h of heat treatment at 150°C, the gingerols content was dramatically reduced by 89.5% and the increased shogaols content was even lower than treatment at 125°C. The tumor necrosis factor-α-, prostaglandin E2, and nitric oxide-inhibitory capacities of ginger could be increased by heat treatment. However, at high temperature, the enhanced ability would be decreased. The enhanced tumor necrosis factor-α-, prostaglandin E2-, and nitric oxide-inhibitory capacities of ginger was attenuated after 40, 60, and 180 min of heat treatment at 150°C, respectively. The results indicated that the TNF-α-inhibitory capacity of ginger was the most susceptible to heat. Only the prostaglandin E2-inhibitory capacity correlated with the shogaols content, which implies that heat derived shogaols contributed primarily to the prostaglandin E2-inhibitory capacity enhancement. We suggest that the optimal heat process condition is 125°C for 40–60 min for ginger to reach the maximum tumor necrosis factor-α-, prostaglandin E2-, and nitric oxide-inhibitory capacities. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI), the causative factor for acute respiratory distress syndrome, results in significant morbidity and mortality. Due to a lack of effective therapeutic options for ALI, the development of novel therapies is urgently needed. NF-κB, an inflammatory mediator necessary for the evolution of ALI, could serve as an important target for novel agents to prevent disease progression. The present study was designed to evaluate the protective effect of 6-shogaol against lipopolysaccharide (LPS)-induced ALI in mice, and its mechanism of action. Our results suggest that 6-shogaol significantly attenuates elevated levels of various proinflammatory cytokines, such as tumor necrosis factor alpha (TNFα), IL-1β and IL-6. Moreover, the influx of neutrophils, increased protein concentration and edema were also suppressed in mice pretreated with 6-shogaol. These observations were also confirmed by histopathological examination of lung tissues, which suggests that 6-shogaol significantly improves the pathological condition to normal in a dose-dependent manner. A docking study of 6-shogaol was also performed, with the NF-κB p50 homodimer bound to a κB site, to determine its possible inhibitory effects. Our results show that 6-shogaol was efficiently accommodated in the deep cleft of the active site, lined with residues Tyr57, Val58 and Cys59, Tyr143, Lys145 and Lys146 of Chain B of p50 NF-κB. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of microencapsulation of ginger ( Zingiber officinale Roscoe) extract using maltodextrin (MD) and/or gum arabic (GA) as microencapsulation agents on its 6-gingerol content, total phenolic and antioxidant activity. Four slurries containing 95 mL/100 mL of ginger extract (2 g solids/100 mL) and 5 g/100 mL of a blend of maltodextrin:gum arabic of weight ratios (4:1, 1:4, 5:0, and 0:5 g:g) were prepared and they were separately spray dried at 160 °C inlet air temperature to produce ginger extract powders. Ginger extract contained 20.6 ± 0.2 (mg/g solids) 6-gingerol, 7.7 ± 0.6 (mg/g solids) gallic acid equivalents and had an antioxidant activity of 19.9 ± 0.8 (μmol Trolox/g solids). Microencapsulation resulted in a decline in the quantity of 6-gingerol present in ginger extract regardless of the maltodextrin and gum arabic blend. Microencapsulation of ginger extract also reduced gallic acid equivalents and antioxidant activity. Ginger extract dried with maltodextrin:gum arabic (1:4 g:g) and (0:5 g:g) had larger particle size than that dried with maltodextrin:gum arabic (4:1 g:g) and (5:0 g:g). Maltodextrin:gum arabic (4:1 g:g) and (5:0 g:g) had better morphological properties than maltodextrin:gum arabic (4:1 g:g) and (5:0 g:g). Microencapsulated ginger extract powder may be used as a novel food ingredient. [ABSTRACT FROM AUTHOR]

Oxidative stress is a central component of many chronic diseases. The Kelch-like ECH-associated protein 1 (Keap1)–nuclear factor erythroid 2 p45-related factor 2 (Nrf2) system is a major regulatory pathway of cytoprotective genes against oxidative and electrophilic stress. Activation of the Nrf2 pathway plays crucial roles in the chemopreventive effects of various inducers. In this study, we developed a novel class of potent Nrf2 activators derived from ginger compound, [6]-shogaol (6S), using the Tg [ glutathione S-transferase pi 1 ( gstp1 ) :green fluorescent protein ( GFP )] transgenic zebrafish model. Investigation of structure–activity relationships of 6S derivatives indicates that the combination of an α , β -unsaturated carbonyl entity and a catechol moiety in one compound enhances the Tg ( gstp1:GFP ) fluorescence signal in zebrafish embryos. Chemical reaction and in vivo metabolism studies of the four most potent 6S derivatives showed that both α , β -unsaturated carbonyl entity and catechol moiety act as major active groups for conjugation with the sulfhydryl groups of the cysteine residues. In addition, we further demonstrated that 6S derivatives increased the expression of Nrf2 downstream target, heme oxygenase-1, in both a dose- and time-dependent manner. These results suggest that α , β -unsaturated carbonyl entity and catechol moiety of 6S derivatives may react with the cysteine residues of Keap1, disrupting the Keap1–Nrf2 complex, thereby liberating and activating Nrf2. Our findings of natural product-derived Nrf2 activators lead to design options of potent Nrf2 activators for further optimization. [ABSTRACT FROM AUTHOR]

Z ingiber officinale Roscoe, one of the most widely used spices, has been reported to have anti-obesity and anti-diabetes effects. In the present study, we investigated the effects of 6-shogaol, a bioactive compound present in ginger, on the adipogenic process in 3 T3- L1 preadipocytes. The anti-adipogenic effects of 6-shogaol was significantly higher than the more widely investigated 6-gingerol, another major ginger constituent. We observed that 6-shogaol inhibited the expression of two master regulators of adipogenesis, PPARγ and C/ EBPα, and also stimulated lipolysis in mature 3 T3- L1 adipocytes. Collectively, these results suggest that 6-shogaol, not 6-gingerol, is the major compound present in ginger responsible for its reported anti-adipogenic properties. Practical Applications Ginger is widely consumed all over the world, and has been associated with various health benefits. At least some of these benefits have been previously attributed to 6-gingerol. In the present study, we observed that 6-shogaol has more potent anti-adipogenic effects than 6-gingerol in 3 T3- L1 cells. This is the first study to investigate the anti-obesity effect of 6-shogaol in vitro, and provides a new perspective on future development of ginger-based anti-obesity strategies. [ABSTRACT FROM AUTHOR]