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1.
J Neuroimmune Pharmacol ; 19(1): 20, 2024 May 17.
Article in English | MEDLINE | ID: mdl-38758335

ABSTRACT

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.


Subject(s)
Catechols , Depression , Fatty Alcohols , Lipopolysaccharides , Microglia , Neuronal Plasticity , Rats, Sprague-Dawley , Animals , Fatty Alcohols/pharmacology , Microglia/drug effects , Microglia/metabolism , Rats , Lipopolysaccharides/toxicity , Male , Catechols/pharmacology , Neuronal Plasticity/drug effects , Depression/drug therapy , Depression/chemically induced , Depression/metabolism , Coculture Techniques , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Disease Models, Animal , Neuroprotective Agents/pharmacology , Cells, Cultured , Antidepressive Agents/pharmacology
2.
Sci Rep ; 14(1): 12096, 2024 05 27.
Article in English | MEDLINE | ID: mdl-38802434

ABSTRACT

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.


Subject(s)
Fatty Alcohols , Fruit , Solanum lycopersicum , Solanum lycopersicum/drug effects , Solanum lycopersicum/metabolism , Solanum lycopersicum/growth & development , Fatty Alcohols/pharmacology , Fruit/drug effects , Fruit/metabolism , Fruit/chemistry , Proteomics/methods , Phenotype , Plant Proteins/metabolism , Plant Leaves/drug effects , Plant Leaves/metabolism , Germination/drug effects , Salt Stress , Seeds/drug effects , Seeds/metabolism , Seeds/growth & development
3.
Food Chem ; 452: 139425, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38744128

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents , Antioxidants , Catechols , Fatty Alcohols , Plant Extracts , Zingiber officinale , Zingiber officinale/chemistry , Catechols/chemistry , Catechols/analysis , Antioxidants/chemistry , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Fatty Alcohols/chemistry , Fatty Alcohols/analysis , Fatty Alcohols/pharmacology , Plant Extracts/chemistry , Plant Extracts/pharmacology , Animals , Mice
4.
Food Funct ; 15(11): 6054-6067, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38753306

ABSTRACT

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.


Subject(s)
Catechols , Colitis, Ulcerative , Fatty Alcohols , Ferroptosis , Metabolomics , Molecular Docking Simulation , Network Pharmacology , Animals , Ferroptosis/drug effects , Mice , Fatty Alcohols/pharmacology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/metabolism , Catechols/pharmacology , Male , Humans , Disease Models, Animal , Zingiber officinale/chemistry , Mice, Inbred C57BL , Caco-2 Cells
5.
J Mass Spectrom ; 59(6): e5036, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38726689

ABSTRACT

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.


Subject(s)
Curcuma , Fatty Alcohols , Tandem Mass Spectrometry , Zingiber officinale , Zingiber officinale/chemistry , Curcuma/chemistry , Tandem Mass Spectrometry/methods , Fatty Alcohols/analysis , Reproducibility of Results , Limit of Detection , Catechols/analysis , Food Analysis/methods , Curcumin/analysis , Curcumin/analogs & derivatives , Paper
6.
J Pharm Biomed Anal ; 246: 116222, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38763106

ABSTRACT

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.


Subject(s)
Drugs, Chinese Herbal , Metabolomics , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/analysis , Spectrometry, Mass, Electrospray Ionization/methods , Chromatography, High Pressure Liquid/methods , Tandem Mass Spectrometry/methods , Metabolomics/methods , Fatty Alcohols/analysis , Fatty Alcohols/chemistry , Principal Component Analysis , Catechols/analysis , Catechols/chemistry , Zingiber officinale/chemistry , Glucosides/analysis , Glucosides/chemistry , Monoterpenes/analysis , Monoterpenes/chemistry , Benzoates/analysis , Benzoates/chemistry , Bridged-Ring Compounds/analysis , Bridged-Ring Compounds/chemistry , Multivariate Analysis , Paeonia/chemistry , Aconitum/chemistry , Aconitine/analogs & derivatives
7.
Diabetes Res Clin Pract ; 212: 111709, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38768866

ABSTRACT

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.


Subject(s)
Blood Glucose , Dietary Supplements , Fatty Alcohols , Randomized Controlled Trials as Topic , Humans , Blood Glucose/drug effects , Blood Glucose/metabolism , Blood Glucose/analysis , Fatty Alcohols/administration & dosage , Fatty Alcohols/therapeutic use , Dose-Response Relationship, Drug
8.
Sci Rep ; 14(1): 7747, 2024 04 02.
Article in English | MEDLINE | ID: mdl-38565569

ABSTRACT

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.


Subject(s)
Catechols , Fatty Alcohols , MAP Kinase Signaling System , Reperfusion Injury , Mice , Animals , Reperfusion Injury/drug therapy , Liver , Ischemia , Anti-Inflammatory Agents/pharmacology , Apoptosis Regulatory Proteins/pharmacology , Apoptosis , RNA, Messenger/pharmacology
9.
Biomacromolecules ; 25(5): 2914-2924, 2024 May 13.
Article in English | MEDLINE | ID: mdl-38676646

ABSTRACT

With the increasing number of diabetic patients in the world, there is an urgent requirement to reduce the incidence of diabetes. It is considered that a viable prophylactic treatment for type 2 diabetes mellitus is to reduce starch digestibility and oxidative stress. In this study, a novel type of slowly digested starch [pea starch (PS)-gingerol complex] was fabricated to evaluate its in vitro enzymatic digestibility and antioxidant activities. Theoretical and experimental analyses showed that PS can encapsulate gingerols with long alkyl chains to form starch-gingerol complexes, which are further stacked into a mixture of V6- and V7-crystallites. These complexes, in particular the PS-10-gingerol complex, showed high resistance to amylolysis and good antioxidant activities. This study demonstrates that these novel starch-gingerol complexes have the potential to deliver antioxidants encapsulated in starch with slow-digesting properties and reduce oxidative stress. Moreover, this new type of slowly digested starch with antioxidant properties showed great potential in the prevention of type 2 diabetes.


Subject(s)
Antioxidants , Catechols , Diabetes Mellitus, Type 2 , Fatty Alcohols , Starch , Starch/chemistry , Antioxidants/chemistry , Fatty Alcohols/chemistry , Catechols/chemistry , Diabetes Mellitus, Type 2/prevention & control , Oxidative Stress/drug effects , Humans
10.
Int J Biol Macromol ; 268(Pt 1): 131503, 2024 May.
Article in English | MEDLINE | ID: mdl-38663697

ABSTRACT

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.


Subject(s)
Larva , Moths , Receptors, Odorant , Animals , Moths/physiology , Receptors, Odorant/genetics , Receptors, Odorant/metabolism , Smell/physiology , Insect Proteins/genetics , Insect Proteins/metabolism , Insect Proteins/chemistry , Phylogeny , Chemotaxis , Fatty Alcohols/pharmacology , Fatty Alcohols/chemistry
11.
Biochem Biophys Res Commun ; 708: 149786, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38493545

ABSTRACT

Ectopic lipid deposition (ELD) and mitochondrial dysfunction are common causes of metabolic disorders in humans. Consuming too much fructose can result in mitochondrial dysfunction and metabolic disorders. 6-Gingerol, the main component of ginger (Zingiber officinale Roscoe), has been proven to alleviate metabolic disorders. This study seeks to examine the effects of 6-gingerol on metabolic disorders caused by fructose and uncover the underlying molecular mechanisms. In this study, the results showed that 6-Gingerol ameliorated high-fructose-induced metabolic disorders. Moreover, it inhibited CD36 membrane translocation, increased CD36 expression in the mitochondria, and decreased the O-GlcNAc modification of CD36 and OGT expression in vitro and vivo. In addition, 6-Gingerol enhanced the performance of mitochondria in the skeletal muscle and boosted the respiratory capability of L6 myotubes. This study provides a theoretical basis and new insights for the development of lipid-lowering drugs in clinical practice.


Subject(s)
Metabolic Diseases , Mitochondrial Diseases , Humans , Muscle, Skeletal/metabolism , Mitochondria/metabolism , Fatty Alcohols/pharmacology , Fatty Alcohols/metabolism , Catechols/pharmacology , Fructose/metabolism , Metabolic Diseases/metabolism , Mitochondrial Diseases/metabolism
12.
Int J Pharm ; 654: 123992, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38479485

ABSTRACT

Linagliptin is a dipeptidyl peptidase-4 inhibitor used for the management of type-2 diabetes. US FDA-approved products are available exclusively as oral tablets. The inherent drawbacks of the oral administration route necessitate exploring delivery strategies via other routes. In this study, we investigated the feasibility of transdermal administration of linagliptin through various approaches. We compared chemical penetration enhancers (oleic acid, oleyl alcohol, and isopropyl myristate) and physical enhancement techniques (iontophoresis, sonophoresis, microneedles, laser, and microdermabrasion) to understand their potential to improve transdermal delivery of linagliptin. To our knowledge, this is the first reported comparison of chemical and physical enhancement techniques for the transdermal delivery of a moderately lipophilic molecule. All physical enhancement techniques caused a significant reduction in the transepithelial electrical resistance of the skin samples. Disruption of the skin's structure post-treatment with physical enhancement techniques was further confirmed using characterization techniques such as dye binding, histology, and confocal microscopy. In vitro permeation testing (IVPT) demonstrated that the passive delivery of linagliptin across the skin was < 5 µg/sq.cm. Two penetration enhancers - oleic acid (93.39 ± 8.34 µg/sq.cm.) and oleyl alcohol (424.73 ± 42.86 µg/sq.cm.), and three physical techniques - iontophoresis (53.05 ± 0.79 µg/sq.cm.), sonophoresis (141.13 ± 34.22 µg/sq.cm.), and laser (555.11 ± 78.97 µg/sq.cm.) exceeded the desired target delivery for therapeutic effect. This study established that linagliptin is an excellent candidate for transdermal delivery and thoroughly compared chemical penetration and physical transdermal delivery strategies.


Subject(s)
Fatty Alcohols , Linagliptin , Skin Absorption , Administration, Cutaneous , Linagliptin/metabolism , Oleic Acid/metabolism , Skin/metabolism , Iontophoresis/methods , Drug Delivery Systems/methods
13.
Phytomedicine ; 128: 155347, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38493717

ABSTRACT

BACKGROUND: Bile acid (BA) enterohepatic circulation disorders are a main feature of chronic cholestatic diseases. Promoting BA metabolism is thus a potential method of improving enterohepatic circulation disorders, and treat enterohepatic inflammation, oxidative stress and fibrosis due to cholestasis. PURPOSE: To investigate the effect of JiaGaSongTang (JGST) and its blood-absorbed ingredient 6-gingerol on α-naphthylisothiocyanate (ANIT)-induced chronic cholestasis, as well as elucidate the underlying regulatory mechanism. METHODS: Chronic cholestasis was induced in mice via subcutaneous injection of ANIT (50 mg/kg) every other day for 14 d. Treatment groups were administered JGST orally daily. Damage to the liver and intestine was observed using histopathological techniques. Biochemical techniques were employed to assess total BA (TBA) levels in the serum, liver, and ileum samples. Liquid chromatograph-mass spectrometry/mass spectrometry (LC-MS/MS) was used to analyze fecal BA components. Bioinformatic methods were adopted to screen the core targets and pathways. The blood-absorbed ingredients of JGST were scrutinized via LC-MS/MS. The effects of the major JGST ingredients on farnesoid X receptor (FXR) transactivation were validated using dual luciferase reporter genes. Lastly, the effects of the FXR inhibitor, DY268, on JGST and 6-gingerol pharmacodynamics were observed at the cellular and animal levels. RESULTS: JGST ameliorated pathological impairments in the liver and intestine, diminishing TBA levels in the serum, liver and gut. Fecal BA profiling revealed that JGST enhanced the excretion of toxic BA constituents, including deoxycholic acid. Bioinformatic analyses indicated that JGST engaged in anti-inflammatory mechanisms, attenuating collagen accumulation, and orchestrating BA metabolism via interactions with FXR and other pertinent targets. LC-MS/MS analysis identified six ingredients absorbed to the bloodstream, including 6-gingerol. Surface plasmon resonance (SPR) and dual luciferase reporter gene assays confirmed the abilities of 6-gingerol to bind to FXR and activate its transactivation. Ultimately, in both cellular and animal models, the therapeutic efficacy of JGST and 6-gingerol in chronic cholestasis was attenuated in the presence of FXR inhibitors. CONCLUSION: The findings, for the first time, demonstrated that 6-gingerol, a blood-absorbed ingredient of JGST, can activate FXR to affect BA metabolism, and thereby attenuate ANIT-induced liver and intestinal injury in chronic cholestasis mice model via inhibition of inflammation, oxidative stress, and liver fibrosis, in part in a FXR-dependent mechanism.


Subject(s)
1-Naphthylisothiocyanate , Bile Acids and Salts , Catechols , Cholestasis , Fatty Alcohols , Liver , Receptors, Cytoplasmic and Nuclear , Animals , Bile Acids and Salts/metabolism , Receptors, Cytoplasmic and Nuclear/metabolism , Cholestasis/drug therapy , Cholestasis/metabolism , Male , Mice , Catechols/pharmacology , Liver/drug effects , Liver/metabolism , Fatty Alcohols/pharmacology , Drugs, Chinese Herbal/pharmacology , Mice, Inbred C57BL , Humans , Chronic Disease , Disease Models, Animal
14.
Int J Pharm ; 655: 124035, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38527564

ABSTRACT

Lacidipine (LCD) is a potent antihypertensive agent. Fatty-based nanovesicles (FNVs) were designed to improve LCD low solubility and bioavailability. LCD-FNVs were formulated according to different proportions of cetyl alcohol, cremophor®RH40, and oleic acid adopting Box-Behnken Design. The optimized LCD-FNVs, composed of cetyl alcohol 48.4 mg, cremophor®RH40 120 mg, and oleic acid 40 mg, showed minimum vesicle size (124.8 nm), maximum entrapment efficiency % (91.04 %) and zeta potential (-36.3 mV). The optimized FNVs were then used to formulate the lyophilized orally fast-disintegrating sponge (LY-OFDS). The LY-OFDS had a very short disintegration time (58 sec), remarkably high % drug release (100 % after 15 mins), and increased the drug transbuccal permeation by over 9.5-fold compared to the drug suspension. In-vivo evaluation of antihypertensive activity in rats showed that the LY-OFDS reduced blood pressure immediately after 5 min and reached normal blood pressure 4.5-fold faster than the marketed oral tablets. In the In-vivo pharmacokinetic study in rabbits, the LY-OFDS showed 4.7-fold higher bioavailability compared with the marketed oral tablet. In conclusion, the LY-OFDS loaded with LCD-FNVs is a safe, and non-invasive approach that can deliver LCD effectively to the blood circulation via the buccal mucosa giving superior immediate capabilities of lowering high blood pressure and increasing the drug bioavailability.


Subject(s)
Dihydropyridines , Fatty Alcohols , Oleic Acid , Polyethylene Glycols , Rats , Rabbits , Animals , Antihypertensive Agents , Solubility , Biological Availability , Drug Delivery Systems , Administration, Oral , Particle Size
15.
Am J Physiol Gastrointest Liver Physiol ; 326(5): G591-G606, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38469632

ABSTRACT

Ulcerative colitis (UC) is an idiopathic inflammatory disease of the large intestine, which impacts millions worldwide. Current interventions aimed at treating UC symptoms can have off-target effects, invoking the need for alternatives that may provide similar benefits with less unintended consequences. This study builds on our initial data, which showed that panaxynol-a novel, potent, bioavailable compound found in American ginseng-can suppress disease severity in murine colitis. Here we explore the underlying mechanisms by which panaxynol improves both chronic and acute murine colitis. Fourteen-week-old C57BL/6 female mice were either given three rounds of dextran sulfate sodium (DSS) in drinking water to induce chronic colitis or one round to induce acute colitis. Vehicle or panaxynol (2.5 mg/kg) was administered via oral gavage three times per week for the study duration. Consistent with our previous findings, panaxynol significantly (P < 0.05) improved the disease activity index and endoscopic scores in both models. Using the acute model to examine potential mechanisms, we show that panaxynol significantly (P < 0.05) reduced DSS-induced crypt distortion, goblet cell loss, and mucus loss in the colon. 16S Sequencing revealed panaxynol altered microbial composition to suppress colitis-enriched genera (i.e., Enterococcus, Eubacterium, and Ruminococcus). In addition, panaxynol significantly (P < 0.05) suppressed macrophages and induced regulatory T-cells in the colonic lamina propria. The beneficial effects of panaxynol on mucosal and crypt architecture, combined with its microbial and immune-mediated effects, provide insight into the mechanisms by which panaxynol suppresses murine colitis. Overall, this data is promising for the use of panaxynol to improve colitis in the clinic.NEW & NOTEWORTHY In the current study, we report that panaxynol ameliorates chemically induced murine colitis by improving colonic crypt and mucosal architecture, suppressing colitis-enriched microbes, reducing macrophages, and promoting the differentiation of regulatory T-cells in the colonic lamina propria. This study suggests that this novel natural compound may serve as a safe and effective treatment option for colitis patients.


Subject(s)
Colitis , Dextran Sulfate , Gastrointestinal Microbiome , Intestinal Mucosa , Mice, Inbred C57BL , Animals , Female , Mice , Intestinal Mucosa/drug effects , Intestinal Mucosa/pathology , Intestinal Mucosa/microbiology , Intestinal Mucosa/immunology , Gastrointestinal Microbiome/drug effects , Colitis/drug therapy , Colitis/chemically induced , Colitis/pathology , Colitis/immunology , Colitis/microbiology , Fatty Alcohols/pharmacology , Diynes/pharmacology , Disease Models, Animal , Colon/drug effects , Colon/pathology , Colon/immunology , Colon/microbiology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/immunology , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/pathology , Colitis, Ulcerative/microbiology
17.
Basic Clin Pharmacol Toxicol ; 134(4): 498-506, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38379124

ABSTRACT

Psoriasis is a chronic inflammatory skin disease. Topical medicines are the preferred treatment for mild to moderate psoriasis, but the effect of excipients used in semi-solid preparations on psoriasis-like skin inflammation is not fully understood. In the present study, we investigated the effect of stearyl alcohol, a commonly used excipient, on imiquimod (IMQ)-induced psoriasis-like skin inflammation in mice. Psoriasis-like skin inflammation was induced by topical IMQ treatment on the back of mice. Skin lesion severity was evaluated by using psoriasis area and severity index (PASI) scores. The skin sections were stained by haematoxylin-eosin and immunohistochemistry. Stearyl alcohol (20% in vaseline) treatment significantly reduced the IMQ-induced increase of PASI scores and epidermal thickness in mice. IMQ treatment increased the number of Ki67- and proliferating cell nuclear antigen (PCNA)-positive cells in the skin, and the increases were inhibited by stearyl alcohol (20% in vaseline) treatment. Stearyl alcohol treatment (1%, 5%, 10% in vaseline) dose-dependently ameliorated IMQ-induced increase of PASI scores and epidermal thickness in mice. Hexadecanol (20% in vaseline), stearic acid (20% in vaseline) and vaseline treatment had no significant effect on IMQ-induced psoriasis-like skin inflammation in mice. In conclusion, stearyl alcohol has the effect of improving IMQ-induced psoriasis-like skin inflammation in mice.


Subject(s)
Dermatitis , Fatty Alcohols , Psoriasis , Mice , Animals , Imiquimod/adverse effects , Psoriasis/chemically induced , Psoriasis/drug therapy , Dermatitis/pathology , Skin , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/pathology , Petrolatum/adverse effects , Disease Models, Animal , Mice, Inbred BALB C
18.
J Food Sci ; 89(3): 1485-1497, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38317483

ABSTRACT

To recognize the key ester-related volatile compounds, 5 types of peaches including 54 late-ripening peach materials were examined by headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry and E-nose. Here, a large number of esters were identified to be released by ripe peach fruits and were mainly characterized by fruity, green, and fatty notes. The variety and content of esters had greatly changed within or between cultivars, indicating that the fruit volatiles were highly differentiated depending on the specific genotypes and cultivation conditions. The ester types showed that fatty acid-derived C6 alcohols and methyl-/ethyl- short-chain alcohol were the main ester precursors, which were more likely to be utilized and well selected by alcohol acyltransferases, whereas the preference of acyl donors was not observed. The common peach type, which exhibited a unique volatile profile, displayed broader diversity and more abundant characteristics in ester-related volatiles than the other four types. A total of 19 key esters were identified as the main components and the content of most esters showed no significant difference among different peach types. Some key esters had even been enriched in nectarines. Moreover, the multiple discriminant analysis revealed a possible relationship between peach types and the domestication of the peach evolution. This study investigated ester-related volatiles released by different types of peach fruits and can be further used to evaluate the peach qualities, providing an important reference for peach breeding and processing.


Subject(s)
Prunus persica , Volatile Organic Compounds , Esters/analysis , Volatile Organic Compounds/analysis , Plant Breeding , Fruit/chemistry , Fatty Alcohols/analysis , Ethanol/analysis
19.
Eur J Pharmacol ; 967: 176399, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38331338

ABSTRACT

Ginger has been used for thousands of years for the treatment of many illnesses, from nausea to migraines. Recently, an interest has grown in ginger compounds in the context of autoimmune and inflammatory diseases due to their significant anti-inflammatory effects. Nevertheless, the effects and mechanism of action of these phytochemicals in human immune cells, particularly in dendritic cells (DCs) are unclear. In the present study, we investigated the effects of 6-gingerol and 6-shogaol, the major compounds found in ginger rhizome, on the functionality of primary human monocyte-derived DCs (moDCs). Here we report for the first time that 6-gingerol and 6-shogaol dampen the immunogenicity of human DCs by inhibiting their activation, cytokine production and T cell stimulatory ability. In particular, the bioactive compounds of ginger dose-dependently inhibited the upregulation of activation markers, and the production of different cytokines in response to synthetic Toll-like receptor (TLR) ligands. Moreover, both compounds could significantly reduce the Escherichia coli-triggered cytokine production and T cell stimulatory capacity of moDCs. We also provide evidence that the ginger-derived compounds attenuate DC functionality via inhibiting the nuclear factor-κB (NF-kB), mitogen activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR) signaling cascades. Further, 6-shogaol but not 6-gingerol activates the AMP-activated protein kinase (AMPK) and nuclear factor erythroid 2-related factor 2 (NRF2) pathways that might contribute to its anti-inflammatory action. Altogether, our results indicate that ginger-derived phytochemicals exert their anti-inflammatory activities via multiple mechanisms and suggest that 6-shogaol is more potent in its ability to suppress DC functionality than 6-gingerol.


Subject(s)
Fatty Alcohols , Zingiber officinale , Humans , Catechols/pharmacology , Plant Extracts/pharmacology , Cytokines/metabolism , Anti-Inflammatory Agents/pharmacology , Toll-Like Receptors , Dendritic Cells/metabolism
20.
Plant Sci ; 341: 111992, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38301931

ABSTRACT

Long and very long chain fatty alcohols are produced from their corresponding acyl-CoAs through the activity of fatty acyl reductases (FARs). Fatty alcohols are important components of the cuticle that protects aerial plant organs, and they are metabolic intermediates in the synthesis of the wax esters in the hull of sunflower (Helianthus annuus) seeds. Genes encoding 4 different FARs (named HaFAR2, HaFAR3, HaFAR4 and HaFAR5) were identified using BLAST, and studies showed that four of the genes were expressed in seed hulls. In this study, the structure and location of sunflower FAR proteins were determined. They were also expressed exogenously in Saccharomyces cerevisiae to evaluate their substrate specificity based on the fatty alcohols synthesized by the transformed yeasts. Three of the four enzymes tested showed activity in yeast. HaFAR3 produced C18, C20 and C22 saturated alcohols, whereas HaFAR4 and HaFAR5 produced C24 and C26 saturated alcohols. The involvement of these genes in the synthesis of sunflower seed wax esters was addressed by considering the results obtained.


Subject(s)
Helianthus , Oxidoreductases , Oxidoreductases/metabolism , Helianthus/metabolism , Seeds/metabolism , Fatty Alcohols/metabolism
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