6-Gingerol modulates miRNAs and PODXL gene expression via methyltransferase enzymes in NB4 cells: an in silico and in vitro study.

This investigation delves into the influence of predicted microRNAs on DNA methyltransferases (DNMTs) and the PODXL gene within the NB4 cell line, aiming to elucidate their roles in the pathogenesis of acute myeloid leukemia (AML). A comprehensive methodological framework was adopted to explore the therapeutic implications of 6-gingerol on DNMTs. This encompassed a suite of bioinformatics tools for protein structure prediction, docking, molecular dynamics, and ADMET profiling, alongside empirical assessments of miRNA and PODXL expression levels. Such a multifaceted strategy facilitated an in-depth understanding of 6-gingerol's potential efficacy in DNMT modulation. The findings indicate a nuanced interplay where 6-gingerol administration modulated miRNA expression levels, decreasing in DNMT1 and DNMT3A expression in NB4 cells. This alteration indirectly influenced PODXL expression, contributing to the manifestation of oncogenic phenotypes. The overexpression of DNMT1 and DNMT3A in NB4 cells may contribute to AML, which appears modulable via microRNAs such as miR-193a and miR-200c. Post-treatment with 6-gingerol, DNMT1 and DNMT3A expression alterations were observed, culminating in the upregulation of miR-193a and miR-200c. This cascade effect led to the dysregulation of tumor suppressor genes in cancer cells, including downregulation of PODXL, and the emergence of cancerous traits. These insights underscore the therapeutic promise of 6-gingerol in targeting DNMTs and microRNAs within the AML context.

O/W nanoemulsions encapsulated octacosanol: Preparation, characterization and anti-fatigue activity.

Octacosanol has various biological effects such as antioxidant, hypolipidemic and anti-fatigue. However, poor solubility has limited the application of octacosanol in food. The aim of this study was to prepare octacosanol nanoemulsions with better solubility, stability and safety and to investigate in vivo anti-fatigue effect. The food-grade formulation of the octacosanol nanoemulsions consisted of octacosanol, olive oil, Tween 80, glycerol and water with 0.1 %, 1.67 %, 23.75 %, 7.92 % and 66.65 % (w/w), respectively. The nanoemulsions had an average particle size of 12.26 ± 0.76 nm and polydispersity index of 0.164 ± 0.12, and showed good stability under different pH, cold, heat, ionic stress and long-term storage conditions. The results of animal experiments showed that the octacosanol nanoemulsions significantly prolonged the fatigue tolerance time, alleviated the fatigue-related biochemical indicators, and weakened the oxidative stress. Meanwhile, octacosanol nanoemulsions upregulated hepatic glycogen levels. Taken together, these findings suggested that octacosanol nanoemulsions have promising applications as anti-fatigue functional foods.

Streptomyces-Fungus Co-Culture Enhances the Production of Borrelidin and Analogs: A Genomic and Metabolomic Approach.

The marine Streptomyces harbor numerous biosynthetic gene clusters (BGCs) with exploitable potential. However, many secondary metabolites cannot be produced under laboratory conditions. Co-culture strategies of marine microorganisms have yielded novel natural products with diverse biological activities. In this study, we explored the metabolic profiles of co-cultures involving Streptomyces sp. 2-85 and Cladosporium sp. 3-22-derived from marine sponges. Combining Global Natural Products Social (GNPS) Molecular Networking analysis with natural product database mining, 35 potential antimicrobial metabolites annotated were detected, 19 of which were exclusive to the co-culture, with a significant increase in production. Notably, the Streptomyces-Fungus interaction led to the increased production of borrelidin and the discovery of several analogs via molecular networking. In this study, borrelidin was first applied to combat Saprolegnia parasitica, which caused saprolegniosis in aquaculture. We noted its superior inhibitory effects on mycelial growth with an EC50 of 0.004 mg/mL and on spore germination with an EC50 of 0.005 mg/mL compared to the commercial fungicide, preliminarily identifying threonyl-tRNA synthetase as its target. Further analysis of the associated gene clusters revealed an incomplete synthesis pathway with missing malonyl-CoA units for condensation within this strain, hinting at the presence of potential compensatory pathways. In conclusion, our findings shed light on the metabolic changes of marine Streptomyces and fungi in co-culture, propose the potential of borrelidin in the control of aquatic diseases, and present new prospects for antifungal applications.

Renoprotective effect of a novel combination of 6-gingerol and metformin in high-fat diet/streptozotocin-induced diabetic nephropathy in rats via targeting miRNA-146a, miRNA-223, TLR4/TRAF6/NLRP3 inflammasome pathway and HIF-1α.

BACKGROUND: MiRNA-146a and miRNA-223 are key epigenetic regulators of toll-like receptor 4 (TLR4)/tumor necrosis factor-receptor-associated factor 6 (TRAF6)/NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway, which is involved in diabetic nephropathy (DN) pathogenesis. The currently available oral anti-diabetic treatments have been insufficient to halt DN development and progression. Therefore, this work aimed to assess the renoprotective effect of the natural compound 6-gingerol (GR) either alone or in combination with metformin (MET) in high-fat diet/streptozotocin-induced DN in rats. The proposed molecular mechanisms were also investigated. METHODS: Oral gavage of 6-gingerol (100 mg/kg) and metformin (300 mg/kg) were administered to rats daily for eight weeks. MiRNA-146a, miRNA-223, TLR4, TRAF6, nuclear factor-kappa B (NF-κB) (p65), NLRP3, caspase-1, and hypoxia-inducible factor-1 alpha (HIF-1α) mRNA expressions were measured using real-time PCR. ELISA was used to measure TLR4, TRAF6, NLRP3, caspase-1, tumor necrosis factor-alpha (TNF-α), and interleukin-1-beta (IL-1ß) renal tissue levels. Renal tissue histopathology and immunohistochemical examination of fibronectin and NF-κB (p65) were performed. RESULTS: 6-Gingerol treatment significantly reduced kidney tissue damage and fibrosis. 6-Gingerol up-regulated miRNA-146a and miRNA-223 and reduced TLR4, TRAF6, NF-κB (p65), NLRP3, caspase-1, TNF-α, IL-1ß, HIF-1α and fibronectin renal expressions. 6-Gingerol improved lipid profile and renal functions, attenuated renal hypertrophy, increased reduced glutathione, and decreased blood glucose and malondialdehyde levels. 6-Gingerol and metformin combination showed superior renoprotective effects than either alone. CONCLUSION: 6-Gingerol demonstrated a key protective role in DN by induction of miRNA-146a and miRNA-223 expression and inhibition of TLR4/TRAF6/NLRP3 inflammasome signaling. 6-Gingerol, a safe, affordable, and abundant natural compound, holds promise for use as an adjuvant therapy with metformin in diabetic patients to attenuate renal damage and stop the progression of DN.

Tailoring the Molecular Structure of 6-Gingerol for Targeting the Phase Separation in Human Lysozyme.

Human lysozyme undergoes a phase-separation process to form insoluble amyloid-architects that cause several pathologies including systemic amyloidosis. Here we have tailored 6-gingerol by extending its molecular framework with active functional groups to specifically target lysozyme phase-transition events. Aggregation assay revealed that tailored 6-gingerol with 4-aromatic moieties (MTV4) substantially suppressed the conversion of the lysozyme low-density liquid phase (LDLP) to solid-phase structured amyloids. The data obtained from biophysical, computational, and microscopic imaging tools suggest direct intervention of MTV4 with the liquid-liquid phase separation. The CD data suggest that MTV4 was able to retain the native conformation of lysozyme. Both biomolecular and computational data reveal the interference of MTV4 with the aggregation-prone hydrophobic stretches within the lysozyme, thereby retaining the native structure and reversing the misfolded intermediates to active monomers. Also, MTV4 was able to induce rapid dissolution of preformed-toxic amyloid fibrils. These results reinforce the importance of the aromatic-aromatic interaction in preventing human lysozyme phase separation.

Exploring gingerol glucosides with enhanced anti-inflammatory activity through a newly identified α-glucosidase (ArG) from Agrobacterium radiobacter DSM 30147.

Gingerols are phenolic biomedical compounds found in ginger (Zingiber officinale) whose low aqueous solubility limits their medical application. To improve their solubility and produce novel glucosides, an α-glucosidase (glycoside hydrolase) from Agrobacterium radiobacter DSM 30147 (ArG) was subcloned, expressed, purified, and then confirmed to have additional α-glycosyltransferase activity. After optimization, the ArG could glycosylate gingerols into three mono-glucosides based on the length of their acyl side chains. Compound 1 yielded 63.0 %, compound 2 yielded 26.9 %, and compound 3 yielded 4.37 %. The production yield of the gingerol glucosides optimally increased in 50 mM phosphate buffer (pH 6) with 50 % (w/v) maltose and 1000 mM Li+ at 40 °C for an 24-h incubation. The structures of purified compound 1 and compound 2 were determined as 6-gingerol-5-O-α-glucoside (1) and novel 8-gingerol-5-O-α-glucoside (2), respectively, using nucleic magnetic resonance and mass spectral analyses. The aqueous solubility of the gingerol glucosides was greatly improved. Further assays showed that, unusually, 6-gingerol-5-O-α-glucoside had 10-fold higher anti-inflammatory activity (IC50 value of 15.3 ± 0.5 µM) than 6-gingerol, while the novel 8-gingerol-5-O-α-glucoside retained 42.7 % activity (IC50 value of 106 ± 4 µM) compared with 8-gingerol. The new α-glucosidase (ArG) was confirmed to have acidic α-glycosyltransferase activity and could be applied in the production of α-glycosyl derivatives. The 6-gingerol-5-O-α-glucoside can be applied as a clinical drug for anti-inflammatory activity.

Toxicity of 6-gingerol and Cymbopogon citratus against Pediculus humanus capitis De Geer (Phthiraptera: Pediculidae): Mortality, detoxifying enzymes, and morphological ultrastructure alterations in lice.

Pediculus humanus capitis (head louse), which causes pediculosis capitis, remains a global health concern. Plant products are efficient alternative pediculicides for treating the human ectoparasite P. h. capitis which is resistant to permethrin. The study evaluates the toxicity and mechanisms of 6-gingerol and Cymbopogon citratus leaf extract on P. h. capitis. Pediculus humanus capitis adult stages were exposed to three different dosages of 6-gingerol and C. citratus crude leaf extract on filter sheets for 5, 10, and 30 min, respectively. The biochemical approach was used to assess the activity of detoxifying enzymes including acetylcholinesterase (AChE), glutathione S-transferase (GST), and oxidase. Scanning electron microscope (SEM) was used to investigate the ultrastructure of the morphological body of lice. After 30 min, 6-gingerol and C. citratus leaf extract killed P. h. capitis completely. Bioassay periods significantly affected lice mortality (P < 0.05). The LC50 values for 6-gingerol and C. citratus extract were 1.79 µg/cm2 and 25.0 µg/cm2, respectively. 6-Gingerol and C. citratus leaf extract significantly lower AChE and GST activity (P < 0.05). Cymbopogon citratus also caused morphological ultrastructure changes in P. h. capitis, including an irregularly formed head, thorax, abdominal respiratory spiracles, and belly. 6-Gingerol and C. citratus leaf extracts could be used as an alternate pediculicide to decrease P. h. capitis populations.

Simple Method for Preparing Starch Inclusion Complexes with Enhanced Amylolysis Resistance and Antioxidant Properties.

Slow-digesting starch with bioactive functionality has been attracting much interest with the increasing incidence of type-2 diabetes and other diet-related illnesses. The present study demonstrates a simple method for preparing a starch inclusion complex with reduced enzymic digestion and enhanced antioxidant activities using debranched pea starch (PS) and 10-gingerol (10G). Enzymically debranched starch complexed more 10G and formed more structurally ordered starch-10G complexes compared to PS that had not been debranched. Debranching for 6 h resulted in starch with better complexing ability for 10G than starches debranched for longer times. The debranched starch-10G complexes had higher antioxidant activities and a much slower in vitro enzymic digestion profile (rate and hydrolysis extent) than the 10G complex prepared with starch that was not debranched. Our study demonstrates that debranched pea starch-10G complexes with slow-digesting and antioxidant properties are likely to be of interest for developing ingredients for healthier food choices.

Triacontanol delivery by nano star shaped polymer promoted growth in maize.

Plant Growth Regulators (PGRs) are functional compounds known for enhancing plant growth and development. However, their environmental impact is a concern due to poor water solubility and the need for substantial organic solvents. Recently, nano-delivery systems have emerged as a solution, offering a broad range of applications for small molecule compounds. This study introduces a nano-delivery system for Triacontanol (TA), utilizing a star polymer (SPc), aimed at promoting maize growth and improving physiological indicators. The system forms nearly spherical nanoparticles through TA's hydroxyl group and SPc's tertiary amine group. The TA/SPc nano-complex notably outperforms separate TA or SPc treatments in maize, increasing biomass, chlorophyll content, and nutrient absorption. It elevates chlorophyll content by 16.4%, 10.0%, and 6.2% over water, TA, and SPc treatments, respectively, and boosts potassium and nitrate ion uptake by up to 2 and 1.6 times compared to TA alone, leading to enhanced plant height and leaf growth. qRT-PCR analysis further demonstrated that the nano-complex enhanced cellular uptake through the endocytosis pathway by up-regulating endocytosis-related gene expression. The employment of TEM to observe vesicle formation during the internalization of maize leaves furnishes corroborative evidence for the participation of the endocytosis pathway in this process. This research confirms that SPc is an effective carrier for TA, significantly enhancing biological activity and reducing TA dosage requirements.

Metabolic engineering for compartmentalized biosynthesis of the valuable compounds in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is commonly used as a microbial cell factory to produce high-value compounds or bulk chemicals due to its genetic operability and suitable intracellular physiological environment. The current biosynthesis pathway for targeted products is primarily rewired in the cytosolic compartment. However, the related precursors, enzymes, and cofactors are frequently distributed in various subcellular compartments, which may limit targeted compounds biosynthesis. To overcome above mentioned limitations, the biosynthesis pathways are localized in different subcellular organelles for product biosynthesis. Subcellular compartmentalization in the production of targeted compounds offers several advantages, mainly relieving competition for precursors from side pathways, improving biosynthesis efficiency in confined spaces, and alleviating the cytotoxicity of certain hydrophobic products. In recent years, subcellular compartmentalization in targeted compound biosynthesis has received extensive attention and has met satisfactory expectations. In this review, we summarize the recent advances in the compartmentalized biosynthesis of the valuable compounds in S. cerevisiae, including terpenoids, sterols, alkaloids, organic acids, and fatty alcohols, etc. Additionally, we describe the characteristics and suitability of different organelles for specific compounds, based on the optimization of pathway reconstruction, cofactor supplementation, and the synthesis of key precursors (metabolites). Finally, we discuss the current challenges and strategies in the field of compartmentalized biosynthesis through subcellular engineering, which will facilitate the production of the complex valuable compounds and offer potential solutions to improve product specificity and productivity in industrial processes.

Phenotypical and biochemical characterization of tomato plants treated with triacontanol.

Biostimulants are heterogeneous products designed to support plant development and to improve the yield and quality of crops. Here, we focused on the effects of triacontanol, a promising biostimulant found in cuticle waxes, on tomato growth and productivity. We examined various phenological traits related to vegetative growth, flowering and fruit yield, the metabolic profile of fruits, and the response of triacontanol-treated plants to salt stress. Additionally, a proteomic analysis was conducted to clarify the molecular mechanisms underlying triacontanol action. Triacontanol application induced advanced and increased blooming without affecting plant growth. Biochemical analyses of fruits showed minimal changes in nutritional properties. The treatment also increased the germination rate of seeds by altering hormone homeostasis and reduced salt stress-induced damage. Proteomics analysis of leaves revealed that triacontanol increased the abundance of proteins related to development and abiotic stress, while down-regulating proteins involved in biotic stress resistance. The proteome of the fruits was not significantly affected by triacontanol, confirming that biostimulation did not alter the nutritional properties of fruits. Overall, our findings provide evidence of the effects of triacontanol on growth, development, and stress tolerance, shedding light on its mechanism of action and providing new insights into its potential in agricultural practices.

Positive Effect of 6-Gingerol on Functional Plasticity of Microglia in a rat Model of LPS-induced Depression.

Neuroinflammation has emerged as a crucial factor in the development of depression. Despite the well-known anti-inflammatory properties of 6-gingerol, its potential impact on depression remains poorly understood. This study aimed to investigate the antidepressant effects of 6-gingerol by suppressing microglial activation. In vivo experiments were conducted to evaluate the effect of 6-gingerol on lipopolysaccharide (LPS)-induced behavioral changes and neuroinflammation in rat models. In vitro studies were performed to examine the neuroprotective properties of 6-gingerol against LPS-induced microglial activation. Furthermore, a co-culture system of microglia and neurons was established to assess the influence of 6-gingerol on the expression of synaptic-related proteins, namely synaptophysin (SYP) and postsynaptic density protein 95 (PSD95), which are influenced by microglial activation. In the in vivo experiments, administration of 6-gingerol effectively alleviated LPS-induced depressive behavior in rats. Moreover, it markedly suppressed the activation of rat prefrontal cortex (PFC) microglia induced by LPS and the activation of the NF-κB/NLRP3 inflammatory pathway, while also reducing the levels of inflammatory cytokines IL-1ß and IL-18. In the in vitro experiments, 6-gingerol mitigated nuclear translocation of NF-κB p65, NLRP3 activation, and maturation of IL-1ß and IL-18, all of which were induced by LPS. Furthermore, in the co-culture system of microglia and neurons, 6-gingerol effectively restored the decreased expression of SYP and PSD95. The findings of this study demonstrate the neuroprotective effects of 6-gingerol in the context of LPS-induced depression-like behavior. These effects are attributed to the inhibition of microglial hyperactivation through the suppression of the NF-κB/NLRP3 inflammatory pathway.

Rapid and simultaneous determination of curcuminoids and gingerols in food products containing turmeric and ginger using paper spray mass spectrometry.

Turmeric and ginger are extensively employed as functional ingredients due to their high content of curcuminoids and gingerols, considered the key bioactive compounds found in these roots. In this study, we present an innovative and fast method for the assay of curcuminoids and gingerols in different foods containing the two spices, with the aim of monitoring the quality of products from a nutraceutical perspective. The proposed approach is based on paper spray tandem mass spectrometry coupled with the use of a labeled internal standard, which has permitted to achieve the best results in terms of specificity and accuracy. All the calculated analytical parameters were satisfactory; accuracy values are around 100% for all spiked samples and the precision data result lower than 15%. The protocol was applied to several real samples, and to demonstrate its robustness and reliability, the results were compared to those arising from the common liquid chromatographic method.

The effects of policosanol supplementation on blood glucose: A systematic review and dose-response meta-analysis of randomized controlled trials.

Previous studies have assessed how supplementing with policosanol affects blood sugar levels. The outcomes, nevertheless, were not constant. Multiple electronic databases were searched including ISI Web of Science, Cochrane Library, PubMed, Google Scholar, and Scopus until February 9, 2023. To assess the effects of policosanol on glucose, we employed a random-effects or fixed-effects meta-analysis approach to examine the weighted mean differences (WMDs) and associated 95 % confidence intervals (CI) before and after policosanol and placebo administration. The final analysis comprised a total of 25 trials with 2680 participants. Compared to the control group, policosanol supplementation significantly reduced blood glucose levels (WMD: -2.24 mg/dl; 95 % CI: -4.05, -0.42, P = 0.01). Findings from subgroup analysis revealed a significant reduction of policosanol supplementation on glucose levels in period of less than 24 weeks, and in individuals below 50 years of age. Additionally, the reduction was statistically significant in dosage of 10 mg/day. Our dose-response analysis indicates no evidence of a non-linear relationship between policosanol dose and duration and changes in glucose levels (P-nonlinearity = 0.52, and P-nonlinearity = 0.52, respectively). Policosanol supplementation might improve blood glucose. Further trials with more complex designs are required to confirm the findings.

UPLC-ESI-Q-TOF-MS/MS based metabolomics investigation on chemical constituent consistency of Zhenwu Decoction before and after compatibility.

Zhenwu Decoction (ZWD), a classic formula from Zhang Zhongjing's "Treatise on Typhoid Fever" in the Han Dynasty, consists of five traditional Chinese medicines: Aconiti Lateralis Radix Praeparata (ALRP), Paeoniae Radix Alba, Poria Cocos, Ginger, and Rhizoma Atractylodis Macrocephalae. To evaluate the chemical constituent consistency of ZWD before and after compatibility, an ultra-performance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry was established to comprehensively study the constituents of ZWD. By normalizing the peak area, the pairwise compatibility of ALRP and the other four medicinal herbs, as well as the compatibility of the entire formula were studied, respectively. Multivariate statistical analysis was used to identify the differences. The processed data were analyzed by principal component analysis and supervised orthogonal partial least squared discriminant analysis, and an S-plot was generated to compare the differences in the chemical composition of the two types of decoction samples. The results showed that during the decoction process of ZWD, a total of seven components were recognized as differential compounds before and after compatibility of ZWD, namely 6-gingerol, zingerone, benzoylhypaconine, hypaconitine, benzoylaconine, paeoniflorin and fuziline. The results of this study provide basic data reference for understanding the law of ZWD compatibility and are valuable for the compatibility study of other herbal medicines.

6-Gingerol ameliorates ulcerative colitis by inhibiting ferroptosis based on the integrative analysis of plasma metabolomics and network pharmacology.

6-Gingerol (6-G), an active ingredient of ginger with anti-inflammation and anti-oxidation properties, can treat ulcerative colitis (UC). However, its underlying mechanism is still unclear. In this study, the pharmacodynamic evaluation of 6-G for treating UC was performed, and the mechanism of 6-G in ameliorating UC was excavated by plasma metabolomics and network pharmacology analysis, which was further validated by experimental and molecular docking. The results showed that 6-G could notably reduce diarrhea, weight loss, colonic pathological damage, and inflammation in UC mice. Plasma metabolomic results indicated that 6-G could regulate 19 differential metabolites, and its metabolic pathways mainly involved linoleic acid metabolism and arachidonic acid metabolism, which were closely associated with ferroptosis. Moreover, 60 potential targets for 6-G intervention on ferroptosis in UC were identified by network pharmacology, and enrichment analysis revealed that 6-G suppressed ferroptosis by modulating lipid peroxidation. Besides, the integration of metabolomics and network pharmacology showed that the regulation of 6-G on ferroptosis focused on 3 key targets, including ALOX5, ALOX15, and PTGS2. Further investigation indicated that 6-G significantly inhibited ferroptosis by decreasing iron load and malondialdehyde (MDA), and enhanced antioxidant capacity by reducing the content of glutathione disulfide (GSSG) and increasing the levels of superoxide dismutase (SOD) and glutathione (GSH) in UC mice and RSL3-induced Caco-2 cells. Furthermore, molecular docking showed the high affinity of 6-G with the identified 3 key targets. Collectively, this study elucidated the potential of 6-G in ameliorating UC by inhibiting ferroptosis. The integrated strategy also provided a theoretical basis for 6-G in treating UC.

Conversion of gingerols to shogaols in ginger (Zingiber officinale roscoe) by puffing.

Effect of puffing on conversion of gingerols to shogaols, physicochemical properties as well as antioxidant and anti-inflammatory activities of puffed ginger was investigated. Puffing significantly increased extraction yield and the highest value was 12.52% at 980 kPa. The significant decrease in gingerols and increase in shogaols were occurred after puffing, respectively. Especially, 6-shogaol was dramatically increased from 4.84 to 99.10 mg/g dried ginger. Puffed ginger exhibited the higher antioxidant activities (analyzed by DPPH, ABTS, TPC, and TFC) than those of control, and they were significantly increased with increasing puffing pressure. In case of anti-inflammatory activity, puffed ginger did not inhibit NO production, but significantly inhibited TNF-α and IL-6 productions. Among gingerols and shogaols, 6-shogaol showed significantly strong correlations with both antioxidant and anti-inflammatory activities. Consequently, puffed ginger can be applied to functional food industry, which dramatically increased the contents of 6, 8, 10-shogaols, the main bioactive compounds in ginger.

Encapsulation of gingerol into nanoliposomes: Evaluation of in vitro anti-inflammatory and anti-cancer activity.

Nanoliposomes (NLs) are ideal carriers for delivering complex molecules and phytochemical products, but ginger by-products, despite their therapeutic benefits, have poor bioavailability due to their low water solubility and stability. Crude ginger extracts (CGEs) and 6-gingerol were individually encapsulated within NLs for in vitro activity assessment. In vitro evaluation of anti-proliferative and anti-inflammatory properties of encapsulated 6-gingerol and CGE was performed on healthy human periodontal ligament (PDL) fibroblasts and MDA-MB-231 breast cancer cells. Encapsulation efficiency and loading capacity of 6-gingerol reached 25.23% and 2.5%, respectively. NLs were found stable for up to 30 days at 4°C with a gradual load loss of up to 20%. In vitro cytotoxic effect of encapsulated 6-gingerol exceeded 70% in the MDA-MB-231 cell line, in a comparable manner with non-encapsulated 6-gingerol and CGE. The effect of CGE with an IC50 of 3.11 ± 0.39, 7.14 ± 0.80, and 0.82 ± 0.55 µM and encapsulated 6-gingerol on inhibiting IL-8 was evident, indicating its potential anti-inflammatory activity. Encapsulating 6-gingerol within NLs enhanced its stability and facilitated its biological activity. All compounds, including vitamin C, were equivalent at concentrations below 2 mg/mL, with a slight difference in antioxidant activity. The concentrations capable of inhibiting 50% of 2,2-diphenyl-1-picrylhydrazyl (DPPH) substrate were comparable.

Tandemly expanded OR17b in Himalaya ghost moth facilitates larval food allocation via olfactory reception of plant-derived tricosane.

Herbivorous insects utilize intricate olfactory mechanisms to locate food plants. The chemical communication of insect-plant in primitive lineage offers insights into evolutionary milestones of divergent olfactory modalities. Here, we focus on a system endemic to the Qinghai-Tibetan Plateau to unravel the chemical and molecular basis of food preference in ancestral Lepidoptera. We conducted volatile profiling, neural electrophysiology, and chemotaxis assays with a panel of host plant organs to identify attractants for Himalaya ghost moth Thitarodes xiaojinensis larvae, the primitive host of medicinal Ophiocordyceps sinensis fungus. Using a DREAM approach based on odorant induced transcriptomes and subsequent deorphanization tests, we elucidated the odorant receptors responsible for coding bioactive volatiles. Contrary to allocation signals in most plant-feeding insects, T. xiaojinensis larvae utilize tricosane from the bulbil as the main attractant for locating native host plant. We deorphanized a TxiaOR17b, an indispensable odorant receptor resulting from tandem duplication of OR17, for transducing olfactory signals in response to tricosane. The discovery of this ligand-receptor pair suggests a survival strategy based on food location via olfaction in ancestral Lepidoptera, which synchronizes both plant asexual reproduction and peak hatch periods of insect larvae.

6-Gingerol attenuates hepatic ischemia/reperfusion injury through regulating MKP5-mediated P38/JNK pathway.

6-Gingerol, the main bioactive compound of ginger, has antioxidant, anti-inflammatory, anti-cancer and neuroprotective effects. However, it is unclear whether 6-Gingerol has protective effects against hepatic ischemia/reperfusion (I/R) injury. In this study, the mouse liver I/R injury model and the mouse AML12 cell hypoxia/reoxygenation (H/R) model were established by pretreatment with 6-Gingerol at different concentrations to explore the potential effects of 6-Gingerol. Serum transaminase levels, liver necrotic area, cell viability, inflammatory response, and cell apoptosis were used to assess the effect of 6-Gingerol on hepatic I/R or cell H/R injury. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to detect the mRNA and protein expression. The results show that 6-Gingerol decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, liver necrosis, inflammatory cytokines IL-1ß, IL-6, MCP-1, TNF-α expression, Ly6g+ inflammatory cell infiltration, protein phosphorylation of NF-κB signaling pathway, Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) positive cells, cell apoptosis rate, the protein expression of pro-apoptotic protein BAX and C-Caspase3, increased cell viability, and expression of anti-apoptotic protein BCL-2. Moreover, 6-Gingerol could increase the mRNA and protein expression of mitogen activated protein kinase phosphatase 5 (MKP5) and inhibit the activation of P38/JNK signaling pathway. In MKP5 knockout (KO) mice, the protective effect of 6-gingerol and the inhibition of P38/JNK pathway were significantly weakened. Therefore, our results suggest that 6-Gingerol exerts anti-inflammatory and anti-apoptotic effects to attenuate hepatic I/R injury by regulating the MKP5-mediated P38/JNK signaling pathway.