Phytochemical activators of Nrf2: a review of therapeutic strategies in diabetes.

Insulin resistance (IR) is fundamental to the development of type 2 diabetes (T2D), and altered mitochondrial function and abnormal lipid distribution are closely associated with IR or T2D. Excess oxidative stress-induced mitochondrial damage leads to an imbalance in redox homeostasis, which is considered the major contributor to the progression of diabetes. A key cellular defense mechanism, namely, the nuclear factor-E2 p45-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, plays an essential protective role in combating excess oxidative stress. A series of phytochemicals are reported to improve IR and restore mitochondrial function against excess oxidative stress by activating the Nrf2-ARE signaling pathway to maintain cellular reactive oxygen species (ROS) homeostasis. The present review focuses on key knowledge gaps in the Nrf2-ARE system targeted by phytochemicals and its correlation to diabetes both in the in vitro and in vivo models and recent achievements in human clinical trials to evaluate its efficiency and safety. In addition, we provide an overview of recent research progress in nutrigenomics, precision nutrition and the interactions occurring in gut microbiota associated with the Nrf2-ARE signaling pathway and diabetes chemoprevention by phytochemicals and finally propose a future research strategy for regulating redox and microbiota balance via the Nrf2-ARE pathway. The present review aims to help us comprehensively understand the critical chemopreventive role of the Nrf2-ARE pathway targeted by phytochemicals in diabetes.

Beneficial Effects of Theaflavins on Metabolic Syndrome: From Molecular Evidence to Gut Microbiome.

In recent years, many natural foods and herbs rich in phytochemicals have been proposed as health supplements for patients with metabolic syndrome (MetS). Theaflavins (TFs) are a polyphenol hydroxyl substance with the structure of diphenol ketone, and they have the potential to prevent and treat a wide range of MetS. However, the stability and bioavailability of TFs are poor. TFs have the marvelous ability to alleviate MetS through antiobesity and lipid-lowering (AMPK-FoxO3A-MnSOD, PPAR, AMPK, PI3K/Akt), hypoglycemic (IRS-1/Akt/GLUT4, Ca2+/CaMKK2-AMPK, SGLT1), and uric-acid-lowering (XO, GLUT9, OAT) effects, and the modulation of the gut microbiota (increasing beneficial gut microbiota such as Akkermansia and Prevotella). This paper summarizes and updates the bioavailability of TFs, and the available signaling pathways and molecular evidence on the functionalities of TFs against metabolic abnormalities in vitro and in vivo, representing a promising opportunity to prevent MetS in the future with the utilization of TFs.

Edible oleogels stabilized solely by stigmasterol: effect of oil type and gelator concentration.

BACKGROUND: Phytosterols are considered to be one of the most promising gelators for obtaining oleogel because of their additional health benefits and natural coexist with vegetable oils. Previous studies have confirmed that individual phytosterols are not capable of structuring vegetable oils unless they act synergistically with other components. However, based on the self-assembly properties of stigmasterol (ST) in organic solvents, we speculate that it can also structure vegetable oils as a gelator alone. RESULTS: For the first time, the present study confirmed the feasibility of using ST alone as a gelator for structuring of vegetable oils, including rapeseed oil (RSO), olive oil (OLO) and flaxseed oil (FSO). RSO had the lowest ST gelation concentration (4%, w/w), and the oil-binding capacity and firmness value of the oleogels were the highest. The rheological results showed that all the samples were gelatinous (G' > G″). The results of differential scanning calorimeter and X-ray diffraction further confirmed that the properties of RSO-based oleogels are superior to those prepared by OLO and FSO. The microscopic results also confirmed that the crystal structure of RSO oleogels was more uniform, smaller and more densely distributed. CONCLUSION: The structural properties of the oleogels were positively correlated with the ST concentration, and various analysis indicators showed that the performance of the oleogel based on RSO was better than that of OLO and FSO. In summary, the present study used ST as a gelator to successfully prepare oleogels with excellent properties, which provides a feasible reference for researchers in related fields. © 2022 Society of Chemical Industry.

Effect of Garlic Organic Sulfides on Gene Expression Profiling in HepG2 Cells and Its Biological Function Analysis by Ingenuity Pathway Analysis System and Bio-Plex-Based Assays.

Garlic organic sulfides are dietary bioactive components with multiple biofunctions to prevent chronic diseases/inflammation and promote human health. DADS (diallyl disulfide), DATS (diallyl trisulfide), and DTS (diallyl tetrasulfide) are typical organic sulfides with similar structures from garlic. However, the structure-activity relationship of garlic organic sulfides remained unknown. The aim of the present study was to investigate the effect of DADS, DATS, and DTS on the gene expression profiling of human hepatocellular carcinoma cells (HepG2) by application of microarray and specialized analysis software, GO, Bio-Plex-based cytokines assay and IPA and analyze their structure-activity relationship according to antioxidant, anti-inflammatory, and metabolic-related properties. According to the microarray data, with the increase of S atom in garlic organic sulfides, its biological activity was gradually enhanced. In the general catalog of GO, garlic organic sulfides mainly affect biological process, molecular function, and cellular component. RT-qPCR results indicated that the microarray data is trustworthy, and the structure-activity analysis data found that more sulfur atoms have more powerful properties; thus, microarray data of DTS was preceded to the subsequent IPA analysis. The results of IPA analysis showed that the top 5 signaling pathways and molecular functions were disturbed by DTS; the molecular functions with the highest scores affected by DTS are cancer, cell apoptosis, and cell proliferation, which imply that the occurrence or metabolism of these diseases is related to the differential expression of the above-mentioned related genes and the activation of signaling channels, and the core of the most significant molecular network is inflammation. Finally, the results found that the secretions of 6 cytokines in macrophages were significantly inhibited by DTS treatment. This is the first study that analyzed the structure-activity relationship of garlic organic sulfides, which will provide useful genetic information for its multi-biofunction and promote their clinical application in the near future.

Physicochemical studies of nanocrystals of starches from two rice (Oryza sativa L.) types and their characteristics using various modern instrument techniques.

BACKGROUND: Starch nanocrystals have received considerable attention, due to their biodegradability, nontoxicity and renewable and abundant sources. The objective of this research is to compare the morphology, physicochemical characteristics and rheological properties of native (NSNC) and waxy rice starch nanocrystals (WSNC). RESULTS: Both NSNC and WSNC exhibited a platelet-like shape, and they tended to show square-like platelet morphology with increasing initial amylopectin content. Compared to native starches, three weight loss stages of NSNC and WSNC in thermogravimetric analysis curves were observed, while the thermal depolymerization of NSNC started earlier than that of WSNC. The relative crystallinity of NSNC and WSNC was 38.6% and 48.3%, respectively, which were markedly higher than that of native starches. Fourier transform infrared spectra revealed that NSNC presented the highest ratio of 1045/1014 cm-1 bands among the tested samples, which was probably due to the re-association of retrograded amylose to double-helices structure in NSNC. Moreover, the introduction of sulfur atoms on the surface of NSNC and WSNC was confirmed from the results of X-ray photoelectron spectroscopy. At 5% (w/v) and 10% (w/v) concentration levels, all SNC suspensions exhibited a shear-thinning behavior as the shear rate increased from 0.1 to 100 s-1 . CONCLUSIONS: Starch nanocrystals obtained from native and waxy rice starch can be potentially used as reinforcement in biodegradable nanocomposites for packaging, fat replacers, thickening agents and emulsion stabilizers. © 2020 Society of Chemical Industry.

Novel Biocompatible Polysaccharide-Based Eutectogels with Tunable Rheological, Thermal, and Mechanical Properties: The Role of Water.

The natural deep eutectic solvent (NADES) is an excellent solvent for insoluble natural products and medicines. Eutectogels formed by gelation of NADESs are interesting materials that deserve attention. In this study, xanthan gum was used as a gelator to gel choline chloride-xylitol with different water contents in virtue of the excellent solubility of choline chloride-xylitol (1:1) to quercetin. We observed that water was critical to the formation of eutectogels. An MTT assay indicated that our eutectogel had excellent biocompatibility as its corresponding hydrogel. According to rheological tests, xanthan gum-based eutectogels had better viscoelastic properties, higher thermal stability, and more defined shear thinning behavior than its corresponding hydrogel. Texture profile analysis showed that eutectogels with less water content had higher hardness and adhesiveness. Meanwhile, Differential scanning calorimeter (DSC) results suggested that the various rheological and texture properties of eutectogels could be attributed to changes in the water state, which was influenced by the hydrogen bonding network of NADES. This biocompatible eutectogel with tunable properties was expected to find applications in novel drug delivery vehicles, which are widely used in the fields of medicine and food.

Aqueous two-phase system based on natural quaternary ammonium compounds for the extraction of proteins.

Aqueous two-phase systems, based on the use of natural quaternary ammonium compounds, were developed to establish a benign biotechnological route for efficient protein separation. In this study, aqueous two-phase systems of two natural resources betaine and choline with polyethyleneglycol (PEG400/600) or inorganic salts (K2 HPO4 /K3 PO4 ) were formed. It was shown that in the K2 HPO4 -containing aqueous two-phase system, hydrophobic interactions were an important driving force of protein partitioning, while protein size played a vital role in aqueous two-phase systems that contained polyethylene glycol. An extraction efficiency of more than 90% for bovine serum albumin in the betaine/K2 HPO4 aqueous two-phase system can be obtained, and this betaine-based aqueous two-phase system provided a gentle and stable environment for the protein. In addition, after investigation of the cluster phenomenon in the betaine/K2 HPO4 aqueous two-phase systems, it was suggested that this phenomenon also played a significant role for protein extraction in this system. The development of aqueous two-phase systems based on natural quaternary ammonium compounds not only provided an effective and greener method of aqueous two-phase system to meet the requirements of green chemistry but also may help to solve the mystery of the compartmentalization of biomolecules in cells.

Enzymatic synthesis of phytosterol esters catalyzed by Candida rugosa lipase in water-in-[Bmim]PF6 microemulsion.

A water-in-ionic liquid microemulsion ([Bmim]PF6/Tween20/H2O) was applied as reusable reaction medium to esterify phytosterols with fatty acid by Candida rugosa lipase (CRL) successfully. Two kinds of commercial CRLs, AY30 and AYS which cannot effectively catalyze esterification in conventional reaction system were found effective in the microemulsion system. Effects of reaction parameters on esterification were investigated; results showed that the conversion rate of 87.9 and 95.1 % was obtained in 24 and 48 h of reaction, respectively, under the optimized condition: the molar ratio of water to Tween 20 (w 0 value) at 5.4, Tween 20 at a concentration of 305 mM, 50 °C,pH 7.4, 10 % of enzyme loading (w/w, with respect to total reactants), and phytosterols/lauric acid molar ratio of 1:2. Moreover, by using n-hexane as the extraction agent, the lipase-encapsulated microemulsion could be reused at least seven times (>168 h) without significant changes in the conversion rate, while achieving a purpose of simple separation and purification.

Enzymatic selective synthesis of 1,3-DAG based on deep eutectic solvent acting as substrate and solvent.

In this study, enzymatic selective esterification of oleic acid with glycerol based on deep eutectic solvent acting as substrate and solvent was studied. As choline chloride (ChCl) or betaine can effectively change the chemical reaction characteristics of glycerol when they are mixed with a certain molar ratio of glycerol, several factors crucial to the lipase catalytic esterification of glycerol with oleic acid was investigated. Results showed that, betaine had more moderate effects than ChCl on the lipase, and water content had an important influence of the esterification and the enzyme selectivity. Significant changes of the glyceride compositions and enzyme selectivity were found in ChCl adding system compared with pure glycerol system; optimum accumulation of DAG especially 1,3-DAG because of the eutectic effect of ChCl was found in this system. Furthermore, in a model 1,3-DAG esterification synthesis system catalyzed by Novozym 435, high content (42.9 mol%) of the 1,3-DAG could be obtained in ChCl adding system within 1 h.

The Impact of Oil Type on the Performance of ß-Amyrin-Based Oleogels: Formation, Physicochemical Properties, and Potential Correlation Analysis.

Pentacyclic triterpenes show potential as oleogelators, but their combination with various vegetable oils has limited research. This study selected linseed, rapeseed, sunflower, coconut, and palm oils to combine with the triterpenoid compound ß-amyrin for the preparation of oleogels. The stability, crystal network structure, and other properties of each oleogel were evaluated. The correlation between different oil types and the properties of corresponding oleogels was explored. The results showed that ß-amyrin formed stable oleogels with five vegetable oils under suitable temperature conditions, wherein especially the LO-based oleogel not only exhibited higher oil-binding capacity and hardness, but also demonstrated excellent stability at the microscopic level and notable rheological properties. Further analysis revealed a close correlation between the physicochemical properties of the oleogels and lipid characteristics, indicating that oleogels prepared from long-chain highly unsaturated fatty acids exhibit high stability. The above results indicate that ß-amyrin can be a novel candidate oleogelator and that the oil type can modify the properties of ß-amyrin-based oleogels. This study provides the latest reference for the application of pentacyclic triterpenoids in food.

Self-constructed water-in-oil Pickering emulsions as a tool for increasing bioaccessibility of betulin.

Self-constructed water-in-oil emulsions can be stabilized by a natural pentacyclic triterpenoid, betulin. A higher betulin concentration (3%) results in smaller emulsion droplet sizes. Microscopy, confocal laser scanning microscopy and rheology indicate that the stabilizing mechanism is attributed to betulin crystals on the emulsion interface and within the continuous phase, thereby enabling excellent freeze/thaw and thermal stability. The betulin Pickering emulsion (1%) significantly increased betulin bioaccessibility (22.4%) compared to betulin alone (0.2%) and betulin-oil physical mixture (7.9%). A higher level of betulin at 3% leads to smaller emulsion particle size, potentially resulting in a greater surface area. This, in return, promotes a higher release of free fatty acids (FFA), contributing to the release and solubilization of betulin from emulsions. Additionally, it leads to the formation of micelles, further increasing betulin bioaccessibility (29.3%). This study demonstrates Pickering emulsions solely stabilized by phytochemical betulin provides an innovative way to improve its bioaccessibility.

Effect of Digestion on Ursolic Acid Self-Stabilized Water-in-Oil Emulsion: Role of Bile Salts.

Exploring the effect of bile salts on the properties of emulsion carriers containing hydrophobic bioactive compounds is particularly critical to understanding the stability and bioavailability of these hydrophobic bioactive compounds in the digestive process. In this study, the effects of bile salts on the stability and digestive characteristics of the ursolic acid (UA) self-stabilized water-in-oil (W/O) emulsion were investigated via static and dynamic (with or without enzyme) in vitro simulated digestive systems. The results showed that under the static system, the basic conditions had less interference, while the bile salts had a significant effect on the appearance and microstructure of the emulsion. The primary mechanism of emulsion instability is hydrophobic binding and depletion flocculation. Under the dynamic condition, it was found that the low concentrations of bile salts can promote the release amount and the rate of free fatty acids via displacement, while high concentrations of bile salts inhibit the decomposition of lipid, which may be related to the secondary coverage formed at the interface by the bile salts. These findings provide a theoretical basis for understanding the digestive behavior of the UA emulsion and its interaction with bile salts, which are conducive to developing and designing new emulsions to improve the bioaccessibility of UA.

Multi-Index Comprehensive Assessment Optimized Critical Flavonoids Extraction from Semen Hoveniae and Their In Vitro Digestive Behavior Evaluation.

Critical flavonoids from Semen Hoveniae have huge potential bioactivities on hypoglycemic. A multi-index comprehensive assessment based on Analytic Hierarchy Process (AHP) method was performed to optimize the extraction process of flavonoids from Semen Hoveniae, which taking dihydromyricetin, taxifolin, myricetin and quercetin as indexes, and, then, an in vitro simulated gastrointestinal digestion model was established to investigate the changes of flavonoids contents and their antioxidant capacity before and after digestion. The results showed that three influence factors acted significantly with the order of ethanol concentration > solid-liquid ratio > ultrasound time. The optimized extraction parameters were as follows: 1:37 w/v of solid-liquid ratio, 68% of ethanol concentration and 45 min for ultrasonic time. During in vitro digestion, the order of remaining ratio of four flavonoids in the extract was dihydromyricetin > taxifolin > myricetin > quercetin in gastric digestion, and remaining ratio of taxifolin was 34.87% while others were restructured in intestinal digestion. Furthermore, the 1,1-dipheny-2-picryhydrazyl free radical (DPPH ·) scavenging ability and oxygen radical absorption capacity (ORAC) of extract were more stable in gastric digestion. After an hour's intestinal digestion, the extract had no DPPH antioxidant capacity, but amazingly, its ORAC antioxidant capacity was retained or increased, which implied that substances were transformed and more hydrogen donors were produced. This study has carried out a preliminary discussion from the perspective of extraction and put forward a new research idea, to improve the in vivo bioavailability of the critical flavonoids from Semen Hoveniae.

Extraction of Ursolic Acid from Apple Peel with Hydrophobic Deep Eutectic Solvents: Comparison between Response Surface Methodology and Artificial Neural Networks.

Extracting ursolic acid (UA) from plant resources using organic solvents is incompatible with food applications. To address this, in this study, 15 edible hydrophobic deep eutectic solvents (HDESs) were prepared to extract UA from apple peel, the extraction conditions were optimized, and the optimization strategies were compared. It was found that the solubility of UA in the HDESs can be 9 times higher than the traditional solvent such as ethanol. The response surface optimization concluded that temperature had the greatest effect on the extraction and the optimized test conditions obtained as follows: temperature of 49 °C, time of 32 min, solid-liquid ratio of 1:16.5 g/mL, respectively. Comparing the response surface methodology (RSM) and artificial neural networks (ANN), it was concluded that ANN has more accurate prediction ability than RSM. Overall, the HDESs are more effective and environmentally friendly than conventional organic solvents to extract UA. The results of this study will facilitate the further exploration of HDES in various food and pharmaceutical applications.

Natural deep eutectic ready to use extract of astilbin: Super high in vitro bioaccessibility, α-amylase and α-glucosidase enzyme inhibition kinetics.

Astilbin, a natural flavonoid, possesses multiple functionalities, while the poor bioavailability seriously restricts its application in functional food and medicine. Therefore, in this study, a natural deep eutectic solvent (NaDES) with choline chloride: lactic acid (CHCL-LAC) is selected to deliver astilbin by evaluating the bioaccessibility and antioxidant capacity during in vitro gastrointestinal digestion, and the inhibitory effect with underlying mechanism of astilbin-CHCL-LAC against α-amylase/α-glucosidase were investigated. The CHCL-LAC showed significant high astilbin bioaccessibility (84.1% bioaccessible) and DPPH and ORAC antioxidant capacity with 75.7% and 57.7% respectively after 3 h in vitro digestion, which may be attributed by hydrogen bond based supramolecule formed between astilbin and CHCL-LAC. Moreover, significant inhibitions of astilbin-CHCL-LAC on α-amylase (IC50 of 0.67 g/L) and α-glucosidase (IC50 of 0.64 g/L) were observed in mixed competitive and non-competitive manners. The dominant binding force between enzymes and astilbin were the hydrogen and hydrophobic interaction. This is the first time that the underlying mechanisms for astilbin delivered by NaDESs were revealed, suggesting that CHCL-LAC-based NaDESs are promising ready-to-use vehicles of natural inhibitors for carbohydrate-hydrolyzing enzymes.

Effect and mechanism of edible oil co-digestion on the bioaccessibility and bioavailability of ursolic acid.

Ursolic acid (UA), a pentacyclic triterpenoid, has gained attentions due to its various health-promoting benefits, but exhibits poor bioavailability. This could be enhanced by changing the food matrix of UA in which it is present. In this study, several UA systems were constructed to investigate the bioaccessibility and bioavailability of UA in combination with in vitro simulated digestion and Caco-2 cell models. The results showed that the bioaccessibility of UA was significantly improved after adding rapeseed oil. Caco-2 cell models showed that the UA-oil blend was more advantageous than UA emulsion in total absorption. The results indicate that the location of UA distribution in oil determines the ease of UA release into the mixed micellar phase. This paper brings a new research idea and basis for the design of improving the bioavailability of hydrophobic compounds.

The Regulatory Effect of Phytochemicals on Chronic Diseases by Targeting Nrf2-ARE Signaling Pathway.

Redox balance is essential to maintain the body's normal metabolism. Once disrupted, it may lead to various chronic diseases, such as diabetes, neurodegenerative diseases, cardiovascular diseases, inflammatory diseases, cancer, aging, etc. Oxidative stress can cause or aggravate a series of pathological processes. Inhibition of oxidative stress and related pathological processes can help to ameliorate these chronic diseases, which have been found to be associated with Nrf2 activation. Nrf2 activation can not only regulate the expression of a series of antioxidant genes that reduce oxidative stress and its damage, but also directly regulate genes related to the above-mentioned pathological processes to counter the corresponding changes. Therefore, targeting Nrf2 has great potential for the prevention or treatment of chronic diseases, and many natural phytochemicals have been reported as Nrf2 activators although the defined mechanisms remain to be elucidated. This review article focuses on the possible mechanism of Nrf2 activation by natural phytochemicals in the prevention or treatment of chronic diseases and the regulation of oxidative stress. Moreover, the current clinical trials of phytochemical-originated drug discovery by targeting the Nrf2-ARE pathway were also summarized; the outcomes or the relationship between phytochemicals and chronic diseases prevention are finally analyzed to propose the future research strategies and prospective.

Formation and structure evolution of starch nanoplatelets by deep eutectic solvent of choline chloride/oxalic acid dihydrate treatment.

In this study, we report a top-down approach to fabricate starch nanoplatelets (SNPs) based on a deep eutectic solvent (DES) comprised of choline chloride and oxalic acid dihydrate. When subjecting waxy maize starch (WMS) to 2 h of DES treatment, the SNPs of oxalate half-ester were successfully fabricated. The formation mechanism of SNPs was studied by monitoring the changes in nanoplatelet morphology, amylopectin chain distribution, long-range crystallinity, and semi-crystalline lamellar structure of the DES-treated WMS at various treatment times. During the DES treatment, relative crystallinity values of WMS gradually decreased from 28.7 to 25.2%. With increasing DES treatment time from 0 to 1.5 h, the thickness of crystalline lamellae decreased from 6.38 to 5.57 nm, whereas the opposite trend was observed for the thickness of amorphous lamellae. The method developed in this work offers a green and efficient route to prepare non-toxic starch nanomaterials.

Molecular Mechanism Underlying the Regulatory Effect of Vine Tea on Metabolic Syndrome by Targeting Redox Balance and Gut Microbiota.

Metabolic syndrome (MS) is a metabolic disorder that arises from the increasing prevalence of obesity. The pathophysiology seems to be largely attributable to the imbalance of lipid and glucose metabolism, redox signaling pathways, and gut microbiota. The increased syndromes, such as type 2 diabetes and cardiovascular disease demands natural therapeutic attention for those at high risk. Vine tea, as a traditional medicinal and edible resource rich in flavonoids, especially for dihydromyricetin (DHM), exhibits promising health benefits on the intervention of MS, but the specific molecular mechanism has not been systematically elucidated. The present article aims to summarize the regulatory effects and biological targets of vine tea or DHM on MS, and analyze the underlying potential molecular mechanisms in cells, animals, and humans, mainly by regulating the redox associated signaling pathways, such as Nrf2, NF-κB, PI3K/IRS2/AKT, AMPK-PGC1α-SIRT1, SIRT3 pathways, and the crosstalk among them, and by targeting several key biomarkers. Moreover, vine tea extract or DHM has a positive impact on the modulation of intestinal microecology by upregulating the ratio of Firmicutes/Bacteroidetes (F/B) and increasing the relative abundance of Akkermansia muciniphila. Therefore, this review updated the latest important theoretical basis and molecular evidence for the development and application of vine tea in dietary functional products or drugs against MS and also imputed the future perspectives to clarify the deep mechanism among vine tea or DHM, redox associated signaling pathways, and gut microbiota.

Genomic and Transcriptomic Analysis Reveal Multiple Strategies for the Cadmium Tolerance in Vibrio parahaemolyticus N10-18 Isolated from Aquatic Animal Ostrea gigas Thunberg.

The waterborne Vibrio parahaemolyticus can cause acute gastroenteritis, wound infection, and septicemia in humans. Pollution of heavy metals in aquatic environments is proposed to link high incidence of the multidrug-resistant (MDR) pathogen. Nevertheless, the genome evolution and heavy metal tolerance mechanism of V. parahaemolyticus in aquatic animals remain to be largely unveiled. Here, we overcome the limitation by characterizing an MDR V. parahaemolyticus N10-18 isolate with high cadmium (Cd) tolerance using genomic and transcriptomic techniques. The draft genome sequence (4,910,080 bp) of V. parahaemolyticus N10-18 recovered from Ostrea gigas Thunberg was determined, and 722 of 4653 predicted genes had unknown function. Comparative genomic analysis revealed mobile genetic elements (n = 11) and heavy metal and antibiotic-resistance genes (n = 38 and 7). The bacterium significantly changed cell membrane structure to resist the Cd2+ (50 µg/mL) stress (p < 0.05). Comparative transcriptomic analysis revealed seven significantly altered metabolic pathways elicited by the stress. The zinc/Cd/mercury/lead transportation and efflux and the zinc ATP-binding cassette (ABC) transportation were greatly enhanced; metal and iron ABC transportation and thiamine metabolism were also up-regulated; conversely, propanoate metabolism and ribose and maltose ABC transportation were inhibited (p < 0.05). The results of this study demonstrate multiple strategies for the Cd tolerance in V. parahaemolyticus.