Non-targeted metabolomics and explainable artificial intelligence: Effects of processing and color on coniferyl aldehyde levels in Eucommiae cortex.

Eucommia ulmoides, a plant native to China, is valued for its medicinal properties and has applications in food, health products, and traditional Chinese medicine. Processed Eucommiae Cortex (EC) has historically been a highly valued medicine. Ancient doctors had ample experience processing EC, especially with ginger juice, as documented in traditional Chinese medical texts. The combination of EC and ginger juice helps release and transform the active ingredients, strengthening the medicine's effectiveness and improving its taste and shelf life. However, the lack of quality control standards for Ginger-Eucommiae Cortex (G-EC), processed from EC and ginger, presents challenges for its industrial and clinical use. This study optimized G-EC processing using the CRITIC and Box-Behnken methods. Metabolomics showed 517 chemical changes between raw and processed G-EC, particularly an increase in coniferyl aldehyde (CFA). Explainable artificial intelligence techniques revealed the feasibility of using color to CFA content, providing insights into quality indicators.

Insights into the microbial assembly and metabolites associated with ginger (Zingiber officinale L. Roscoe) microbial niches and agricultural environments.

Ginger, a vegetable export from China, is well-known for its spicy flavour and use in traditional Chinese medicine. By examining the interactions of ginger plants' microbiome and metabolome, we can gain insights to advance agriculture, the environment, and other fields. Our study used metataxonomic analysis to investigate ginger plants' prokaryotic and fungal microbiomes in open fields and greenhouses. We also conducted untargeted metabolomic analysis to identify specific metabolites closely associated with ginger microbiome assembly under both agricultural conditions. Various bacteria and fungi were classified as generalists or specialists based on their ability to thrive in different environments and microbial niches. Our results indicate that ginger plants grown in greenhouses have a greater prokaryotic diversity, while those grown in open fields exhibit a greater fungal diversity. We have identified specific co-occurring prokaryotic and fungal genera associated with ginger plant agroecosystems that can enhance the health and growth of ginger plants while maintaining a healthy environment. In the open field these genera include Sphingomonas, Methylobacterium-Methylorubrum, Bacillus, Acidovorax, Rhizobium, Microbacterium, unclassified_f_Comamonadaceae, Herbaspirillum, Klebsiella, Enterobacter, Chryseobacterium, Nocardioides, Subgroup_10, Enterococcus, Pseudomonas, Devosia, g_unclassified_f_Chaetomiaceae, Pseudaleuria, Mortierella, Cheilymenia, and Pseudogymnoascus. In the greenhouse, the enriched genera were Rhizobium, Stenotrophomonas, Aureimonas, Bacillus, Nocardioides, Pseudomonas, Enterobacter, Delftia, Trichoderma, Mortierella, Cheilymenia, Schizothecium, and Actinomucor. Our research has identified several previously unknown microbial genera for ginger plant agroecosystems. Furthermore, our study has important implications for understanding the correlation between ginger's microbiome and metabolome profiles in diverse environments and may pave the way for future research. Specific microbial genera in crop production environments are associated with essential metabolites, including Safingol, Docosatrienoic acid, P-acetaminophen, and Hypoglycin B.

A genome assembly of ginger (Zingiber officinale Roscoe) provides insights into genome evolution and 6-gingerol biosynthesis.

Ginger is cultivated in tropical and subtropical regions and is one of the most crucial spices worldwide owing to its special taste and scent. Here, we present a high-quality genome assembly for 'Small Laiwu Ginger', a famous cultivated ginger in northern China. The ginger genome was phased into two haplotypes, haplotype A (1.55Gb), and haplotype B (1.44Gb). Analysis of Ty1/Copia and Ty3/Gypsy LTR retrotransposon families revealed that both have undergone multiple retrotransposon bursts about 0-1 million years ago. In addition to a recent whole-genome duplication event, there has been a lineage-specific expansion of genes involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, thereby enhancing 6-gingerol biosynthesis. Furthermore, we focused on the biosynthesis of 6-gingerol, the most important gingerol, and screened key transcription factors ZoMYB106 and ZobHLH148 that regulate 6-gingerol synthesis by transcriptomic and metabolomic analysis in the ginger rhizome at four growth stages. The results of yeast one-hybrid, electrophoretic mobility shift, and dual-luciferase reporter gene assays showed that both ZoMYB106 and ZobHLH148 bind to the promoters of the key rate-limiting enzyme genes ZoCCOMT1 and ZoCCOMT2 in the 6-gingerol synthesis pathway and promote their transcriptional activities. The reference genome, transcriptome, and metabolome data pave the way for further research on the molecular mechanism underlying the biosynthesis of 6-gingerol. Furthermore, it provides precious new resources for the study on the biology and molecular breeding of ginger.

Hepatoprotective effects of moderate-intensity interval training along with ginger juice in an old male rat model.

Aging is a natural process coupled with oxidative stress and chronic inflammation, gradually associated with losing organ function over time. Therefore, the objective of the current work was to peruse the protective effects of 8-week moderate-intensity interval training (MIIT) and ginger extract supplementation on some biomarkers of oxidative stress, inflammation, and lipid metabolism in the liver of elderly males Wistar rats (animal study with ethical code IR.BMSU.REC.1401.015). A total of thirty-two 22-month-aged male Wistar rats were randomly assigned to four groups: (1) control, (2) MIIT, (3) ginger, and (4) MIIT + ginger. After 8 weeks of treadmill training and ginger extract supplementation, the biochemical parameters (liver enzyme and lipid profile), inflammatory mediators (leucine-rich α-2 glycoprotein 1 (LRG1), tumor necrosis factor-alpha, and interleukin-6), pro-oxidant (malondialdehyde), antioxidant biomarkers (catalase, superoxide dismutase, total antioxidant capacity), some lipid metabolism regulators (carnitine palmitoyltransferase 1, adipose triglyceride lipase, acetyl-CoA carboxylase, CD36, and AMP-activated protein kinase), and liver histopathological changes were appraised. The acquired findings pointed out that MIIT combined with ginger extract appreciably diminished the serum levels of LRG1, liver enzymes, and lipid profile relative to the other groups after 8 weeks of intervention. Furthermore, ginger + MIIT caused a great improvement in the liver levels of antioxidant biomarkers, pro-oxidant, pro-inflammatory biomarkers, lipid metabolism regulators, and liver tissue impairment compared to the other groups. The findings suggested that MIIT + ginger was more effective in improving examined indices relative to the other groups.

Hepatorenal Toxicity of Inorganic Arsenic in White Pekin Ducks and Its Amelioration by Using Ginger.

The toxic metalloid arsenic is known to cause liver and kidney injury in many humans and animals. The goal of this paper was to exemplify the antagonism of ginger against arsenic (As)-induced hepato-renal toxicity. In addition, the pathways Nrf2/Keap1 and NF/κB were studied to reveal the molecular mechanism of the stress. One hundred twenty 7-day-old White Pekin ducks were randomly allocated into five groups, having 24 birds in each. Each group contained three replicates having 8 birds in each replicate and maintained for 90 days. The groups were as follows: T-1 [control-basal diet with normal water], T-2 [T1 + As at 28 ppm/L of water], T-3 [T2 + ginger powder at 100 mg/kg feed], T-4 [T2 + ginger powder at 300 mg/kg feed], and T-5 [T2 + ginger powder at 1 g/kg feed]. It was observed that there was a significant increase in oxidative parameters whereas a significant decrease in antioxidant parameters in hepato-renal tissues in T-2. The exposure to As not only decreased the mRNA expression of antioxidant parameters like Nrf2, SOD-1, CAT, GPX, and HO-1and anti-inflammatory markers like IL-4 and IL-10 but also increased the m-RNA expression of NF-κB, Keap-1 and pro-inflammatory markers like IL-2, Il-6, IL-18, IL-1ß, and TNF-α. There was also an accumulation of As in hepatic and renal tissue, confirmed by residual analysis of these tissues. By correlating the above parameters, As at 28 ppm showed significant toxic effects, and ginger powder at 1 g/kg feed effectively counteracted the toxic effects of As in ducks.

Glyphosate-induced liver and kidney dysfunction, oxidative stress, immunosuppression in Nile tilapia, but ginger showed a protection role.

The water-borne herbicides are involved in the toxicity of aquatic animals resulting in impaired health status and low productivity. Dietary medicinal herbs present a practical solution to relieve the impacts of herbicides toxicity on the performances of aquatic animals. Herein, we investigated the toxicity of commercial glyphosate-induced oxidative stress, immunosuppression, liver and kidney dysfunction, and the protective role of ginger or ginger nanoparticles in Nile tilapia. Fish were allocated into four groups: the first group presented the control without glyphosate toxicity and ginger feeding, the second group intoxicated with glyphosate at 0.6 mg/L and fed ginger free diet, the third group intoxicated with glyphosate and fed ginger at 2.5 g/kg, and the fourth group intoxicated with glyphosate and fed ginger nanoparticles at 2.5 g/kg. Fish were kept under the experimental conditions for four weeks, and the samples of blood and tissues were collected after 2 and 4 weeks. Markedly, fish exposed to glyphosate showed the highest ALT and AST activities, glucose and cortisol levels, and malondialdehyde levels (MDA) in gills and tissues. While fish in the control and fish intoxicated with glyphosate and fed ginger nanoparticles had the lowest ALT and AST activities, glucose and cortisol levels, and MDA levels after 2 and 4 weeks (P < 0.05). Fish fed dietary ginger had lower ALT and AST activities, glucose and cortisol levels, and MDA levels than the glyphosate intoxicated group after 2 and 4 weeks (P < 0.05). Interestingly, fish-fed ginger nanoparticles showed lower urea and creatinine levels and higher total protein, albumin, and globulin than the glyphosate intoxicated group (P < 0.05) and similar to the control (P > 0.05). Further, fish intoxicated with glyphosate and fed ginger nanoparticles had the highest GSH, lysozyme activity, and immunoglobulin levels after 2 and 4 weeks (P < 0.05). In conclusion, ginger nanoparticles are superior to the standard ginger form in enhancing the antioxidative and immune responses of Nile tilapia exposed to glyphosate.

Herbal Formulation Comprised of Methanol Extracts of Tribulus terristris L. and Zingiber officinale Roscoe Has Antihypertensive Effects.

People prefer to use medicinal plants rather than chemical compounds because they are low cost and have fewer adverse events. Zingiber officinale Roscoe is a natural dietary rhizome with anti-oxidative, anti-inflammatory and anti-carcinogenic properties. Tribulus terrestris L. has been used for the treatment of impotence, to enhance sexual drive and performance and for its diuretic and uricosuric effects. The aim of this study was to evaluate the combined effect of 2 extracts, Tribulus terristris and Zingiber officinale (TZ) for antioxidant, enzyme modulation, liver function, kidney function, blood profile and anti-hypertensive effects, which may pave the way for possible therapeutic applications. Antioxidant potential was measured with the 2,2-diphenyl-1-picryl-hydrazyl-hydrate free radical method antioxidant assay (DPPH) and kojic acid was used as the standard drug for tyrosine inhibition assay. The effect of TZ on biochemical parameters of the liver (alanine transferase [ALT], alkaline phosphatase [ALP], aspartate aminotransferase [AST], total serum protein, total serum albumin, serum bilirubin), kidney (blood urea and creatinine) and hematology (hemoglobin, red blood cells [RBC], platelets, thin-layer chromatography, neutrophils, eosinophils, lymphocytes, monocytes, mean corpuscular volume, mean corpuscular hemoglobin and mean corpuscular hemoglobin concentration) of Wister rats were studied by administering 100, 250 and 500 mg/kg-1 body weight TZ dose orally for 28 days. Antihypertensive effects were measured by the invasive method. The results showed that the scavenging percentage of TZ was 78.5 to 80.4, with an IC50 value of 1166.7 µg/ ml and tyrosinase inhibition was 72% compared with 93% for kojic acid. Different doses (100, 250 and 500 mg/kg) did not show an increase in serum biomarkers of liver and renal parameters. A significant increase in hemoglobin, erythrocytes, hematocrit, white blood cells (WBC) and lymphocytes with no significant increase/decrease in platelet count was observed but blood pressure was significantly decreased. Therefore, we concluded that TZ is safe and can be used in the treatment of hypertension.

8-paradol from ginger exacerbates PINK1/Parkin mediated mitophagy to induce apoptosis in human gastric adenocarcinoma.

Gastric cancer (GC) occurs in the gastric mucosa, and its high morbidity and mortality make it an international health crisis. Therefore, novel drugs are needed for its treatment. The use of natural products and their components in cancer treatments has shown promise. Therefore, this study aimed to evaluate the effect of 8-paradol, a phenolic compound isolated from ginger (Zingiber officinale Roscoe), on GC and determine its underlying mechanisms of action. In this study, repeated column chromatography was conducted on ginger EtOH extract to isolate gingerol and its derivatives. The cytotoxicity of the eight ginger compounds underwent a (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) tetrazolium reduction (MTT) assay. 8-paradol showed the most potent cytotoxicity effect among the isolated ginger compounds. The underlying mechanism by which 8-paradol regulated specific proteins in AGS cells was evaluated by proteomic analysis. To validate the predicted mechanisms, AGS cells and thymus-deficient nude mice bearing AGS xenografts were used as in vitro and in vivo models of GC, respectively. The results showed that the 8-paradol promoted PINK1/Parkin-associated mitophagy, mediating cell apoptosis. Additionally, the inhibition of mitophagy by chloroquine (CQ) ameliorated 8-paradol-induced mitochondrial dysfunction and apoptosis, supporting a causative role for mitophagy in the 8-paradol-induced anticancer effect. Molecular docking results revealed the molecular interactions between 8-paradol and mitophagy-/ apoptosis-related proteins at the atomic level. Our study provides strong evidence that 8-paradol could act as a novel potential therapeutic agent to suppress the progression of GC by targeting mitophagy pathway.

Revisiting the therapeutic potential of gingerols against different pharmacological activities.

The rhizomes of ginger have been in use in many forms of traditional and alternative medicines. Besides being employed as condiment and flavoring agent, it is used in the treatment of nausea, osteoarthritis, muscle pain, menstrual pain, chronic indigestion, Alzheimer's disease, and cancer. Ginger rhizome contains volatile oils, phenolic compounds and resins, and characterization studies showed that [6]-gingerol, [6]-shogaol, and [6]-paradol are reported to be the pharmacologically active components. Gingerol is a major chemical constituent found as volatile oil in the rhizomes of ginger. It has several medicinal benefits and used for the treatment of rheumatoid arthritis, nausea, cancer, and diabetes. Many studies have been carried out in various parts of the world to isolate and standardize gingerol for their use as a complementary medicine. The present review summarizes wide range of research studies on gingerol and its pharmacological roles in various metabolic diseases.

Synthesis and characterization of Ni0.5Al0.5Fe2O4 nanoparticles for potent antifungal activity against dry rot of ginger (Fusarium oxysporum).

Current study signifies the use of nanoparticles as alternative in plant disease management to avoid harmful effect of pesticide and fungicide residue. Synthesis of nanoparticles (Ni0.5Al0.5Fe2O4) by hydrothermal method and studied their X-ray diffraction analysis (XRD), Raman spectra, and UV spectra and further successfully evaluated for antifungal activity against a soil and seed borne pathogenic fungus (Fusarium oxysporum).Among various pests, fungal pathogens are the main cause of crop destruction and we developed nanoparticles (Ni0.5Al0.5Fe2O4) which is successfully evaluated for antimycotic activity against dry rot (F. oxysporum) of ginger which causes 50-70% losses in the ginger plant. In vitro and in vivo analysis designated that the nanoparticles (Ni0.5Al0.5Fe2O4) has shown an excellent antifungal activity against F. oxysporum at 0.5 mg/ml concentration. Similarly, no disease incidence was recorded when Ni0.5Al0.5Fe2O4 nanoparticles used at 0.5 mg/ml concentration under in vivo conditions. In plants various environmental stresses (biotic and abiotic) leads to excessive production of reactive oxygen species (ROS) causing progressive oxidative damage and ultimately leads to cell death. The role of ROS in nanoparticles (Ni0.5Al0.5Fe2O4) represents by reduction in the growth inhibition of F. oxysporum. We speculated in light of these results that the cytotoxic effect of Ni0.5Al0.5Fe2O4 nanoparticles on F. oxysporum may be mediated through ROS. We can suggest the role of nanoparticles (Ni0.5Al0.5Fe2O4) gives a promising result as a fungicidal activity and could be a novel family of future new generation fungicide.

Effect of Ginger on Inflammatory Diseases.

Ulcerative colitis, Crohn's disease, rheumatoid arthritis, psoriasis, and lupus erythematosus are some of common inflammatory diseases. These affections are highly disabling and share signals such as inflammatory sequences and immune dysregulation. The use of foods with anti-inflammatory properties such as ginger (Zingiber officinale Roscoe) could improve the quality of life of these patients. Ginger is a plant widely used and known by its bioactive compounds. There is enough evidence to prove that ginger possesses multiple biological activities, especially antioxidant and anti-inflammatory capacities. In this review, we summarize the current knowledge about the bioactive compounds of ginger and their role in the inflammatory process and its signaling pathways. We can conclude that the compounds 6-shoagol, zingerone, and 8-shoagol display promising results in human and animal models, reducing some of the main symptoms of some inflammatory diseases such as arthritis. For lupus, 6-gingerol demonstrated a protective attenuating neutrophil extracellular trap release in response to phosphodiesterase inhibition. Ginger decreases NF-kß in psoriasis, and its short-term administration may be an alternative coadjuvant treatment. Ginger may exert a function of supplementation and protection against cancer. Furthermore, when receiving chemotherapy, ginger may reduce some symptoms of treatment (e.g., nausea).

Biologically synthesized black ginger-selenium nanoparticle induces apoptosis and autophagy of AGS gastric cancer cells by suppressing the PI3K/Akt/mTOR signaling pathway.

BACKGROUND: Despite being a promising strategy, current chemotherapy for gastric cancer (GC) is limited due to adverse side effects and poor survival rates. Therefore, new drug-delivery platforms with good biocompatibility are needed. Recent studies have shown that nanoparticle-based drug delivery can be safe, eco-friendly, and nontoxic making them attractive candidates. Here, we develop a novel selenium-nanoparticle based drug-delivery agent for cancer treatment from plant extracts and selenium salts. RESULTS: Selenium cations were reduced to selenium nanoparticles using Kaempferia parviflora (black ginger) root extract and named KP-SeNP. Transmission electron microscopy, selected area electron diffraction, X-ray diffraction, energy dispersive X-ray, dynamic light scattering, and Fourier-transform infrared spectrum were utilized to confirm the physicochemical features of the nanoparticles. The KP-SeNPs showed significant cytotoxicity in human gastric adenocarcinoma cell (AGS cells) but not in normal cells. We determined that the intracellular signaling pathway mechanisms associated with the anticancer effects of KP-SeNPs involve the upregulation of intrinsic apoptotic signaling markers, such as B-cell lymphoma 2, Bcl-associated X protein, and caspase 3 in AGS cells. KP-SeNPs also caused autophagy of AGS by increasing the autophagic flux-marker protein, LC3B-II, whilst inhibiting autophagic cargo protein, p62. Additionally, phosphorylation of PI3K/Akt/mTOR pathway markers and downstream targets was decreased in KP-SeNP-treated AGS cells. AGS-cell xenograft model results further validated our in vitro findings, showing that KP-SeNPs are biologically safe and exert anticancer effects via autophagy and apoptosis. CONCLUSIONS: These results show that KP-SeNPs treatment of AGS cells induces apoptosis and autophagic cell death through the PI3K/Akt/mTOR pathway, suppressing GC progression. Thus, our research strongly suggests that KP-SeNPs could act as a novel potential therapeutic agent for GC.

Antibacterial activity of green gold and silver nanoparticles using ginger root extract.

Recent studies demonstrated that the speed of synthesis, biocompatibility, and antimicrobial activity of gold (Au) and silver (Ag) metals is enhanced when biosynthesized in nano-sized particles. In the present study, Au- and Ag-based nanoparticles (NPs) were synthesized via a biological process using aqueous Ginger root extract and characterized by various spectroscopic methods. The NPs have hexagonal and spherical shapes. The average particle size for Au and Ag NPs was 20 and 15 nm, respectively. The dynamic light scattering (DLS) technique has shown that the zeta potential values of synthesized NPs were 4.8 and - 7.11 mv, respectively. Gas chromatography-mass spectrometry (GC-MS) analysis of Ginger root extract revealed 25 compounds. The synthesized NPs showed significant activity against Staphylococcus aureus and Escherichia (E). coli in vitro, with IC50 and IC90 values for Au and Ag NPs, respectively, noted to be 7.5 and 7.3 µg/ml and 15 and 15.2 µg/ml for both bacterial strains. The protein leakage level was tremendous and morphological changes occurred in bacteria treated with biosynthesized NPs. These results suggest that the biosynthesized metallic NPs have the suitable potential for application as antibacterial agents with enhanced activities.

The anti-oxidative potential of ginger extract and its constituent on meat protein isolate under induced Fenton oxidation.

Ginger extract has been reported to possess antioxidant properties. However, components isolated from ginger have been rarely reported to inhibit oxidation. Herein, the antioxidant properties of ginger and purified components derived from it (6-gingerol, zingerone, rutin, quercetin, and kaempferol) were confirmed by using HPLC and were further used to investigate its effect on lamb meat. Myofibrillar proteins isolated (MPI) from lamb meat were incubated with ginger and its constituents under induced Fenton oxidation (1.0 mmol/L FeCl3, 0.1 mmol/L Asc, and 20 mmol/L H2O2) for 1, 3,5, and 7 h. Incubating meat protein isolate in the absence of ginger extract or its components resulted in a substantial drop in sulfhydryl groups, an increase in protein carbonyl content, and a corresponding increase in TBARS content. However, ginger extract and its constituents demonstrated antioxidant properties, which might be attributed to their hydroxyl groups and suitable solubilizing side chains. Overall, ginger extract exhibited the highest antioxidant capabilities of all treated samples, suggesting that ginger extracts may be used as a natural antioxidant in meat and lipid/protein-containing processed products. SIGNIFICANCE OF THE STUDY: Ginger extract is also frequently used as a herbal medicine due to its anti-inflammatory, anti-cancer, and antibacterial qualities. Nonvolatile pungent chemicals found in ginger, such as gingerol, shogaols, paradols, and zingerone, as well as kaempferol, rutin, and other phenolic compounds, have been confirmed in ginger extract and have been shown to have antioxidant action driven by free radical elimination. Despite these findings, ginger extract and its pure constituent components have seldom been shown to have the ability to slow protein and lipid oxidation in meat and meat-related products. The effect of ginger extracts on the oxidative stability of myofibriller protein isolate has never been investigated. Exploiting the phenolic content of ginger extract may result in a discovery that would have a huge influence on both the ginger and meat industries as well as other food processing sectors. The first aim of our study was to confirm the presence of six selected phenolic compounds (rutin, kaempferol, 6-gingerol, zingerone, naringenin, and quercetin) in ginger as reported by literature, and the second objective was to determine the efficacy of ginger extracts and its purified constituents on myofibrillar protein isolate treated under induced Fenton oxidation.

[6]-Gingerol induces Caspase-Dependent Apoptosis in Bladder Cancer cells via MAPK and ROS Signaling.

The anti-cancer effects of [6]-gingerol ([6]-GIN), the main active polyphenol of ginger (Zingiber officinale), were investigated in the human bladder cancer cell line 5637. [6]-GIN inhibited cell proliferation, increased sub­G1 phase ratios, and depolarized mitochondrial membrane potential. [6]-GIN-induced cell death was associated with the downregulation of B­cell lymphoma 2 (BCL­2) and survivin and the upregulation of Bcl­2­associated X protein (Bax). [6]-GIN activated caspase­3 and caspase-9 and regulated the activation of mitogen-activated protein kinases (MAPKs). Further, [6]-GIN also increased the intracellular reactive oxygen species (ROS) levels and TG100-115 or tranilast increased [6]-GIN­induced cell death. These results suggest that [6]-GIN induced apoptosis in the bladder cancer cell line 5637 and therefore has the potential to be used in the development of new drugs for bladder cancer treatment.

Nanoencapsulation of Ru(p-cymene) Complex Bearing Ginger-based Natural Product into Liposomal Nanoformulation to Improve Its Cellular Uptake and Antiproliferative Activity.

The organometallic compounds are prospective candidates in the row of developing metallochemotherapeutics with the aim of overcoming the limitations of platinum drugs. In order to explore the anticancer properties of organometallic compounds with the natural medicines, two Ru(II)-p-cymene complexes containing the natural products, viz., 6-gingerol (6G) and benzylated-6-gingerdione (B-6GD) have been synthesized and characterized well. The phenolic group of the Ru(6G) complex facilitates its higher cell-free antioxidant activity than its analogue complex. Also, the same complex shows higher cytotoxicity toward A549 lung and HeLa-S3 cervical cancer cells than the Ru(B-6GD) complex but lower cytotoxicity toward A2058 metastatic melanoma cancer cells. Both complexes are shown to easily accumulate in melanoma cancer cells, and their degree of cytotoxicity in the same cells is found to be positively correlated with cell uptake. The cytotoxicity of complexes arises from their intracellular activity, mainly due to the induction of singlet oxygen production in cancer cells. The subcellular fractionation study shows that mitochondria and ER-Golgi membranes might be their predominant targets. Also, the mechanistic investigation revealed that Ru(B-6GD) induces caspase-dependent non-apoptotic cell death whereas Ru(6G) can induce caspase-independent non-apoptotic cell death. Furthermore, both complexes are found to moderately alter the adhesion properties of cancer cells, which is beneficial for antimetastatic treatment. Despite the potential pharmacological activity, Ru(6G) is encapsulated into polymer-supported liposomes to reduce its toxicity and further improve its anticancer potency. The π-conjugated yne-ene chain of polydiacetylene aids in the development of a stable nanoformulation, which achieved a slow release of the complex. Most importantly, the cancer cell uptake of the liposome-encapsulated Ru(6G) complex is 20 times enhanced and the total ROS formation in cancer cells is significantly increased compared to the non-encapsulated complex. However, the nanoformulation does not alter the antimetastatic potency of the encapsulated complex.

Synergistic Anti-Inflammatory Activity of Ginger and Turmeric Extracts in Inhibiting Lipopolysaccharide and Interferon-γ-Induced Proinflammatory Mediators.

This study aims to investigate the combined anti-inflammatory activity of ginger and turmeric extracts. By comparing the activities of individual and combined extracts in lipopolysaccharide and interferon-γ-induced murine RAW 264.7 cells, we demonstrated that ginger-turmeric combination was optimal at a specific ratio (5:2, w/w) in inhibiting nitric oxide, tumour necrosis factor and interleukin 6 with synergistic interaction (combination index < 1). The synergistic inhibitory effect on TNF was confirmed in human monocyte THP-1 cells. Ginger-turmeric combination (5:2, w/w) also upregulated nuclear factor erythroid 2−related factor 2 activity and heme oxygenase-1 protein expression. Additionally, 6-shogaol, 8-shogaol, 10-shogaol and curcumin were the leading compounds in reducing major proinflammatory mediators and cytokines, and a simplified compound combination of 6-s, 10-s and curcumin showed the greatest potency in reducing LPS-induced NO production. Our study provides scientific evidence in support of the combined use of ginger and turmeric to alleviate inflammatory processes.

Michael acceptor-dependent pro-oxidative intervention against angiogenesis by [6]-dehydroshogaol, a pungent constituent of ginger.

Accumulating evidence suggests that ginger and its pungent constituents harbor a wealth of biological activities including cancer chemopreventive activity. However, relatively few researches focus on [6]-dehydroshogaol (6-DHS) compared with other ginger pungent constituents such as [6]-shogaol (6S). In this work, we selected three ginger compounds, 6-DHS, 6S and [6]-paradol (6P) differentiated by the presence and number of the Michael acceptor units, to probe structural basis and mechanism of 6-DHS in inhibiting angiogenesis, a key step for tumor growth and metastasis. It was found that their antiangiogenic activity is significantly dependent on the presence and number of Michael acceptor units. Benefiting from its two Michael acceptor units, 6-DHS is the most potent inhibitor of thioredoxin reductase and depletor of glutathione, thereby being the most active generator of reactive oxygen species, which is responsible for its strongest ability to inhibit angiogenesis. This work highlights 6-DHS being a Michael acceptor-dependent pro-oxidative angiogenesis inhibitor.

Effects of ginger (Zingiber officinale) on gingival fibroblasts: An in vitro study.

OBJECTIVES: Ginger, the powdered rhizome of the herb Zingiber officinale, is commonly used as a traditional medicine in many areas around the world. Anti-inflammatory actions of its extract have been previously reported. The aim of this study was to investigate the effect of ginger extract on matrix metalloproteinase (MMP) and interleukin (IL) expression from human gingival fibroblasts (HGFs) in vitro. MATERIAL AND METHODS: HGFs were obtained from subcultures of biopsies from clinically healthy gingival tissues of 10 patients. Ginger extract was prepared from commercial powder of rhizome of Z. officinale (GZO) and its effect on cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide cytotoxicity assay. Cells were then incubated and treated (except for the control samples) with either GZO, lipopolysaccharides (LPS), and GZO before or after LPS stimulation. Culture supernatants of all five samples were collected for the Milliplex analysis to measure MMP-1, MMP-2, MMP-8, MMP-9, IL-1ß, and IL-8. One-way analysis of variance and Duncan multiple range tests were used to compare the mean values of all groups. RESULTS: The gingerextract showed minimal cytotoxicity to HGFs even with the maximum tested concentration. Compared to the control group, GZO treatment alone caused little or no effect on the levels of expression of MMP-1, MMP-2, MMP-8, MMP-9, IL-1ß, and IL-8. While GZO treatment after LPS stimulation significantly reduced the expression of MMP-1, MMP-2, MMP-8, MMP-9, and IL-8 when compared to LPS alone. Comparing the control to LPS stimulation after GZO treatment, significant differences were detected for all tested MMPs and cytokines. CONCLUSIONS: These findings suggest a potential role for ginger extract in inhibiting MMP and IL HGFs' expression in inflamed gingival tissues.

Characterization of the MicroRNA Profile of Ginger Exosome-like Nanoparticles and Their Anti-Inflammatory Effects in Intestinal Caco-2 Cells.

Plant-derived exosome-like nanoparticles (PELNs) have been shown to enter mammalian cells for disease treatment. Although abundant miRNAs are contained in ginger exosome-like nanoparticles (GELNs), little is known about their type and function. Herein, we extracted GELNs with desirable particle sizes (156 ± 36 nm) and a negative surface charge (-26.6 ± 5 mV). The miRNA profiles in ginger and GELNs were analyzed using high-throughput sequencing, and the results of the sequencing were validated by real-time quantitative polymerase chain reaction (RT-qPCR). There were 27 miRNAs with higher expression levels in the GELNs, and they were mainly involved in the regulation of inflammatory and cancer-related pathways. Furthermore, GELNs could be specifically internalized by intestine cells via caveolin-mediated endocytosis and micropinocytosis, as well as counteract lipopolysaccharide (LPS)-induced inflammation by downregulating NF-κß, IL-6, IL-8, and TNF-α expression. Importantly, the positive effects were further proved to be possibly related to the miRNAs enriched in the GELNs. Overall, these results indicated that PELNs could target human digestive organs and play a cross-kingdom physiological regulation role through miRNAs.