Comprehensive evaluation and screening of phytochemical compounds and their hypolipidemic activities of lotus leaf based on HPLC-Q-TOF-MS and spectral-effect analysis.

This study aimed to identify and quantify the primary components in lotus leaf and to explore the hypolipidemic components through spectral-effect relationships and chemometric methods. Utilizing a data-dependent acquisition-diagnostic fragment ion/characteristic neutral loss screening strategy (DFI-NLS), a reliable HPLC-Q-TOF-MS analysis was conducted, identifying 77 compounds, including 36 flavonoids, 21 alkaloids, 3 terpenoids, 11 organic acids, 4 phenols, 1 lignin and 1 unsaturated hydrocarbon. A straightforward HPLC-DAD method was developed for the simultaneous determination of seven major components in lotus leaf, and quercetin-3-O-glucuronide (Q3GA) was identified as the most abundant component. The HPLC fingerprints of 36 lotus leaf sample batches were assessed using chemometric approaches such as principal component analysis and hierarchical cluster analysis. The hypolipidemic effect of these samples was analyzed by measuring total cholesterol (TC) and total triglycerides (TG) levels in palmitic acid (PA) and oleic acid (OA)-induced lipid modeling in HepG-2 cells, employing partial least squares regression and grey relation analysis to investigate the spectral-effect relationship of the lotus leaf. The in vivo hypolipidemic effect of these compounds was assessed using an egg yolk powder-induced high-fat zebrafish model. The findings indicated that peak No.11 (Q3GA) in the chemical fingerprint was significantly associated with hypolipidemic activity, suggesting it as a potential hypolipidemic compound in lotus leaf. In summary, this study facilitates the exploration of the phytochemical compounds and their bioactive properties in the lotus leaf.

Hypericum perforatum L. attenuates depression by regulating Akkermansia muciniphila, tryptophan metabolism and NFκB-NLRP2-Caspase1-IL1ß pathway.

BACKGROUND: Gut microbiota dysbiosis significantly contributes to progression of depression. Hypericum perforatum L. (HPL) is traditionally used in Europe for treating depression. However, its mechanism remains largely underexplored. PURPOSE: This study aims to investigate the pivotal gut microbiota species and microbial signaling metabolites associated with the antidepressant effects of HPL. METHODS: Fecal microbiota transplantation was used to assess whether HPL mitigates depression through alterations in gut microbiota. Microbiota and metabolic profiling of control, chronic restraint stress (CRS)-induced depression, and HPL-treated CRS mice were examined using 16S rRNA gene sequencing and metabolomics analysis. The influence of gut microbiota on HPL's antidepressant effects was assessed by metabolite and bacterial intervention experiments. RESULTS: HPL significantly alleviated depression symptoms in a manner dependent on gut microbiota and restored gut microbial composition by enriching Akkermansia muciniphila (AKK). Metabolomic analysis indicated that HPL regulated tryptophan metabolism, reducing kynurenine (KYN) levels derived from microbiota and increasing 5-hydroxytryptophan (5-HTP) levels. Notably, supplementation with KYN activated the NFκB-NLRP2-Caspase1-IL1ß pathway and increased proinflammatory IL1ß in the hippocampus of mice with depression. Interestingly, mono-colonization with AKK notably increased 5-hydroxytryptamine (5-HT) and decreased KYN levels, ameliorating depression symptoms through modulation of the NFκB-NLRP2-Caspase1-IL1ß pathway. CONCLUSIONS: The promising therapeutic role of HPL in treating depression is primarily attributed to its regulation of the NFκB-NLRP2-Caspase1-IL1ß pathway, specifically by targeting AKK and tryptophan metabolites.

Antimicrobial activities of lavandulylated flavonoids in Sophora flavences against methicillin-resistant Staphylococcus aureus via membrane disruption.

INTRODUCTION: The continuous emergence and rapid spread of multidrug-resistant bacteria have accelerated the demand for the discovery of alternative antibiotics. Natural plants contain a variety of antibacterial components, which is an important source for the discovery of antimicrobial agents. OBJECTIVE: To explore the antimicrobial activities and related mechanisms of two lavandulylated flavonoids, sophoraflavanone G and kurarinone in Sophora flavescens against methicillin-resistant Staphylococcus aureus. METHODS: The effects of sophoraflavanone G and kurarinone on methicillin-resistant Staphylococcus aureus were comprehensively investigated by a combination of proteomics and metabolomics studies. Bacterial morphology was observed by scanning electron microscopy. Membrane fluidity, membrane potential, and membrane integrity were determined using the fluorescent probes Laurdan, DiSC3(5), and propidium iodide, respectively. Adenosine triphosphate and reactive oxygen species levels were determined using the adenosine triphosphate kit and reactive oxygen species kit, respectively. The affinity activity of sophoraflavanone G to the cell membrane was determined by isothermal titration calorimetry assays. RESULTS: Sophoraflavanone G and kurarinone showed significant antibacterial activity and anti-multidrug resistance properties. Mechanistic studies mainly showed that they could target the bacterial membrane and cause the destruction of the membrane integrity and biosynthesis. They could inhibit cell wall synthesis, induce hydrolysis and prevent bacteria from synthesizing biofilms. In addition, they can interfere with the energy metabolism of methicillin-resistant Staphylococcus aureus and disrupt the normal physiological activities of the bacteria. In vivo studies have shown that they can significantly improve wound infection and promote wound healing. CONCLUSION: Kurarinone and sophoraflavanone G showed promising antimicrobial properties against methicillin-resistant Staphylococcus aureus, suggesting that they may be potential candidates for the development of new antibiotic agents against multidrug-resistant bacteria.

Wheat Germ-Derived Peptide Alleviates Dextran Sulfate Sodium-Induced Colitis in Mice.

This study explores the protective properties and potential mechanisms of wheat-germ-derived peptide APEPEPAF (APE) against ulcerative colitis. Colitis mice induced by dextran sulfate sodium (DSS) were used as the animal model. The results showed that the APE peptide could alleviate colitis symptoms including weight loss, colon shortening, and histopathological changes. This peptide attenuated the generation of inflammatory cytokines by inhibiting the phosphorylation of protein kinase PKCζ (Thr410) and NF-κB transcriptional activity in DSS-induced mice, suggesting that APE ameliorates colitis inflammation by regulating the PKCζ/NF-κB signaling pathway. APE also preserved the barrier function of the colon by dose-dependently promoting the expression of tight junction proteins (claudin-1, zonula occluded-1, and occludin). In addition, APE significantly decreased the abundance of Bacteroides and increased the abundance of Dubosiella and Lachnospiraceae_UCG-006 to improve the intestinal flora imbalance in DSS-induced colitis mice. Therefore, wheat germ peptide APE can be used as a novel agent and dietary supplement to treat ulcerative colitis..

Emulsifying properties of wheat germ protein: Effect of different ultrasonic treatment.

The effect of ultrasonic treatment on emulsifying properties of wheat germ protein (WGP) was studied in this paper. WGP was subjected to low frequency (20 kHz), high intensity ultrasonic treatment at different power (200, 400, 600, 800 W) for 10 min, or different time (2, 4, 6, 8, 10, 15, 20 min) at 400 W. The emulsifying activity index and emulsion stability index of WGP were significantly improved, and the emulsion droplet was smaller and more uniform after ultrasound treatment. Ultrasound increased the adsorbed WGP concentration at the oil-water interface and reduced the interfacial tension, which explained the improved emulsifying properties of WGP. The investigation on molecular properties and protein conformation showed that ultrasound processing increased solubility, but decreased particle size and surface charge of WGP. Ultrasound processing resulted in the unfolding of the protein molecular structure indicated by the increase of surface hydrophobicity and surface free sulfhydryl group levels, and the decrease of intrinsic fluorescence intensity. Correlation analysis showed that the changes in WGP solubility, particle size, and surface hydrophobicity were the main driven factors for the improved emulsifying properties of WGP.

A review on processing methods and functions of wheat germ-derived bioactive peptides.

Wheat germ protein is a potential resource to produce bioactive peptides. As a cheap, safe, and healthy nutritional factor, wheat germ-derived bioactive peptides (WGBPs) provide benefits and great potential for biomedical applications. The objective of this review is to reveal the current research status of WGBPs, including their preparation methods and biological functions, such as antibacterial, anti-tumor, immune regulation, antioxidant, and anti-inflammatory properties, etc. We also reviewed the information in terms of the preventive ability of WGBPs to treat serious infectious diseases, to offer their reference to further research and application. Opinions on future research directions are also discussed. Through the review of previous research, we find that there are still some scientific issues in the basic research and industrialization process of WGBPs that deserve further exploration. Firstly, based on current complex enzymolysis, the preparation and production of WGBPs need to be combined with other advanced technology to achieve efficient and large-scale production. Secondly, studies on the bioavailability, biosafety, and mechanism against different diseases of WGBPs need to be carried out in different in vitro and in vivo models. More human experimental evidence is also required to support its industrial application as a functional food and nutritional supplement.HighlightsThe purification and identification of wheat germ-derived bioactive peptides.The main biological activities and potential mechanisms of wheat germ hydrolysates/peptides.Possible absorption and transport pathways of wheat germ hydrolysate/peptide.Wheat germ peptide shows a variety of health benefits according to its amino acid sequence.Current food applications and future perspectives of wheat germ protein hydrolysates/peptide.

Akkermansia muciniphila attenuates LPS-induced acute kidney injury by inhibiting TLR4/NF-κB pathway.

Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4/NF-κB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-κB p65, and downstream IκBα were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4/NF-κB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.

Exploration of Antimicrobial Ingredients in Psoralea corylifolia L. Seed and Related Mechanism against Methicillin-Resistant Staphylococcus aureus.

With the abuse of antibiotics, bacterial antibiotic resistance is becoming a major public healthcare issue. Natural plants, especially traditional Chinese herbal medicines, which have antibacterial activity, are important sources for discovering potential bacteriostatic agents. This study aimed to develop a fast and reliable method for screening out antimicrobial compounds targeting the MRSA membrane from Psoralea corylifolia Linn. seed. A UPLC-MS/MS method was applied to identify the prenylated flavonoids in major fractions from the extracts of Psoralea corylifolia Linn. seed. The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of different fractions and compounds. The morphological and ultrastructural changes of MRSA were determined by scanning electron microscopy (SEM). The membrane-targeting mechanism of the active ingredients was explored by membrane integrity assays, membrane fluidity assays, membrane potential assays, ATP, and ROS determination. We identified eight prenylated flavonoids in Psoralea corylifolia Linn. seed. The antibacterial activity and mechanism studies showed that this type of compound has a unique destructive effect on MRSA cell membranes and does not result in drug resistance. The results revealed that prenylated flavonoids in Psoralea corylifolia Linn. seeds are promising candidates for the development of novel antibiotic agents to combat MRSA-associated infections.

A peptide from wheat germ abolishes the senile osteoporosis by regulating OPG/RANKL/RANK/TRAF6 signaling pathway.

BACKGROUND: Oxidative stress played a key role in the development of bone brittleness and is an important pathogenic factor of senile osteoporosis. A variety of animal and plant-derived peptides have been shown to have significant anti-osteoporosis effects in vivo and in vitro. PURPOSE: In this study, we aim to explore the possible mechanism of wheat germ peptide ADWGGPLPH on senile osteoporosis. STUDY DESIGN: Naturally, aged rats were used as animal models of senile osteoporosis. METHODS: Wheat germ peptide ADWGGPLPH was administered from 9-months-old to 21-months-old, and the effect of ADWGGPLPH on preventing senile osteoporosis was evaluated by measuring serum biochemical indexes, bone histomorphometry, bone biomechanics, and other indexes to elucidate the mechanism of ADWGGPLPH in delaying senile osteoporosis by detecting the expression of osteoporosis-related proteins. RESULTS: The results showed that ADWGGPLPH could effectively reduce the level of oxidative stress and improve the microstructure and bone mineral density in senile osteoporosis rats. In addition, ADWGGPLPH could improve the proliferation and differentiation activity of osteoblasts and effectively inhibit osteoclasts' differentiation by regulating the OPG/RANKL/RANK/TRAF6 pathway. CONCLUSION: ADWGGPLPH from wheat germ exhibited a notably effect on senile osteoporosis and has a high potential in the development of the nutrient regimen to against senile osteoporosis.

Gut microbiota and metabonomics used to explore the mechanism of Qing'e Pills in alleviating osteoporosis.

CONTEXT: The traditional Chinese medicine Qing'e Pills (QEP) has been used to treat postmenopausal osteoporosis (PMO). OBJECTIVE: We evaluated the regulatory effects of QEP on gut microbiota in osteoporosis. MATERIALS AND METHODS: Eighteen female SD rats were divided into three groups: sham surgery (SHAM), ovariectomized (OVX) and ovariectomized treated with QEP (OVX + QEP). Six weeks after ovariectomy, QEP was administered to OVX + QEP rats for eight weeks (4.5 g/kg/day, i.g.). After 14 weeks, the bone microstructure was evaluated. Differences in gut microbiota were analysed via 16S rRNA gene sequencing. Changes in endogenous metabolites were studied using UHPLC-Q-TOF/MS technology. GC-MS was used to detect short-chain fatty acids. Furthermore, we measured serum inflammatory factors, such as IL-6, TNF-α and IFN-γ, which may be related to gut microbiota. RESULTS: OVX + QEP exhibited increased bone mineral density (0.11 ± 0.03 vs. 0.21 ± 0.02, p< 0.001) compared to that of OVX. QEP altered the composition of gut microbiota. We identified 19 potential biomarkers related to osteoporosis. QEP inhibited the elevation of TNF-α (38.86 ± 3.19 vs. 29.43 ± 3.65, p< 0.05) and IL-6 (83.38 ± 16.92 vs. 45.26 ± 3.94, p< 0.05) levels, while it increased the concentrations of acetic acid (271.95 ± 52.41 vs. 447.73 ± 46.54, p< 0.001), propionic acid (28.96 ± 5.73 vs. 53.41 ± 14.26, p< 0.01) and butyric acid (24.92 ± 18.97 vs. 67.78 ± 35.68, p< 0.05). CONCLUSIONS: These results indicate that QEP has potential of regulating intestinal flora and improving osteoporosis. The combination of anti-osteoporosis drugs and intestinal flora could become a new treatment for osteoporosis.

A Review of Bile Acid Metabolism and Signaling in Cognitive Dysfunction-Related Diseases.

Bile acids are commonly known as one of the vital metabolites derived from cholesterol. The role of bile acids in glycolipid metabolism and their mechanisms in liver and cholestatic diseases have been well studied. In addition, bile acids also serve as ligands of signal molecules such as FXR, TGR5, and S1PR2 to regulate some physiological processes in vivo. Recent studies have found that bile acids signaling may also play a critical role in the central nervous system. Evidence showed that some bile acids have exhibited neuroprotective effects in experimental animal models and clinical trials of many cognitive dysfunction-related diseases. Besides, alterations in bile acid metabolisms well as the expression of different bile acid receptors have been discovered as possible biomarkers for prognosis tools in multiple cognitive dysfunction-related diseases. This review summarizes biosynthesis and regulation of bile acids, receptor classification and characteristics, receptor agonists and signaling transduction, and recent findings in cognitive dysfunction-related diseases.

Bioactive components and anti-diabetic properties of Moringa oleifera Lam.

Moringa oleifera Lam. is a perennial tropical deciduous tree with high economic and pharmaceutical value. As an edible plant, M. oleifera Lam. is rich in nutrients, such as proteins, amino acids, mineral elements and vitamins. Besides, it also contains an important number of bioactive phytochemicals, such as polysaccharides, flavonoids, alkaloids, glucosinolates and isothiocyanates. M. oleifera for long has been used as a natural anti-diabetic herb in India and other Asian countries. Thus, the anti-diabetic properties of Moringa plant have evolved highly attention to the researchers. In the last twenty years, a huge number of new chemical structures and their pharmacological activities have been reported in particularly the anti-diabetic properties. The current review highlighted the bioactive phytochemicals from M. Oleifera. Moreover, evidence regarding the therapeutic potential of M. oleifera for diabetes including experimental and clinical data was presented and the underlying mechanisms were revealed in order to provide insights for the development of novel drugs.

Assessment the flavor of soybean meal hydrolyzed with Alcalase enzyme under different hydrolysis conditions by E-nose, E-tongue and HS-SPME-GC-MS.

In the present study, E-nose, E-tongue, and headspace-solid phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) technology combined with Principal Component Analysis (PCA) were employed to evaluate the flavor characteristics of the volatile and the non-volatile substances generated during the enzymatic hydrolysis of the soybean meal by Alcalase. The results showed that the enzymatic hydrolysis effectively reduced the content of soybean odorous substance 1-octene-3-ol and led to better flavor. However, the excessive enzymatic hydrolysis resulted in the deterioration of the enzymatic hydrolysates flavor. In addition, both radar graph and PCA of E-tongue were able to provide the distribution of flavor substances during the enzymatic hydrolysis of the soybean meal. These results provided a theoretical basis for the improvement of the flavors of the soybean meal and its derived products.

The Effects of Erchen Decoction on Gut Microbiota and Lipid Metabolism Disorders in Zucker Diabetic Fatty Rats.

Obesity is a chronic metabolic disease caused by genetic and environmental factors that has become a serious global health problem. There is evidence that gut microbiota is closely related to the occurrence and development of obesity. Erchen Decoction (ECD), a traditional Chinese medicine, has been widely used for clinical treatment and basic research of obesity and related metabolic diseases in recent years. It can significantly improve insulin resistance (IR) and lipid metabolism disorders. However, there is no microbiological study on its metabolic regulation. In this study, we investigated the effects of ECD on obesity, especially lipid metabolism and the composition and function of gut microbiota in Zucker diabetic fatty (ZDF) rats, and explored the correlation between the biomarkers of gut microbiota and metabolite and host phenotype. The results showed that ECD could reduce body weight, improve IR and lipid metabolism, and reduce the concentration of free fatty acids (FFA) released from white adipose tissue (WAT) due to excessive lipolysis by interfering with the insulin receptor substrate 1 (IRS1)/protein kinase B (AKT)/protein kinase A (PKA)/hormone-sensitive triglyceride lipase (HSL) signaling pathway in ZDF rats. Additionally, ECD gradually adjusted the overall structure of changed gut microbiota, reversed the relative abundance of six genera, and changed the function of gut microbiota by reducing the content of propionic acid, a metabolite of gut microbiota, in ZDF rats. A potentially close relationship between biomarkers, especially Prevotella, Blautia, and Holdemania, propionic acid and host phenotypes were demonstrated through correlation analysis. The results suggested that the beneficial effects of ECD on obesity, especially lipid metabolism disorders, are related to the regulation of gut microbiota in ZDF rats. This provides a basis for further research on the mechanism and clinical application of ECD to improve obesity via gut microbiota.

Ferric ammonium citrate (FAC)-induced inhibition of osteoblast proliferation/differentiation and its reversal by soybean-derived peptides (SDP).

Ferric citrate has been used to treat hyperphosphatemia, a prevalent symptom in patients with chronic kidney disease while ferric ammonium citrate (FAC), a more dissolvable format, is widely used as food additive. However, excess iron is associated with osteoporosis. Dietary soybean products have been shown to prevent the progression of osteoporosis. In this study, a group of peptides, referred as P3, was identified from the enzymolysis of soybean protein isolates, and its biological functions were investigated. The results showed that MC3T3-E1 cell cycle progression from G0/G1 to S phase was accelerated by P3 treatment. MC3T3-E1 cell proliferation was enhanced by P3 via ERK1/2 activation. Importantly, P3 treatment abolished the antiproliferative effect of FAC on MC3T3-E1 cell. In addition, P3 treatment increased the expression of ALP, COL-1, OCN, consequently promoting the differentiation and mineralization of MC3T3-E1 cells via activation of p38 MAPK pathway. Consequently, P3 treatment was able to reverse the inhibitory effect of FAC on osteoblasts differentiation and mineralization. Our findings suggest P3, as a dietary supplement, has a potential therapeutic function to attenuate the adverse effects of FAC on bone metabolism and to prevent osteoporosis progression.

Complete chloroplast genome sequence of Acacia crassicarpa (Fabaceae).

Acacia crassicarpa (Fabaceae), a nitrogen-fixing tree species, is critically important for coastal protection in southeast China. In this study, we report the complete chloroplast genome sequence of A. crassicarpa, with a length of 176,493 bp. It contains a pair of inverted repeats (IR 39,851 bp), a large single-copy region (LSC 91,869 bp), and a small single-copy region (SSC 4,922 bp). The complete genome comprises 138 genes, including 93 protein-coding genes, 37 tRNA, and 8 rRNA genes. Our phylogenetic analysis reveals that A. crassicarpa is closely related to A. podalyriifolia and A. dealbata.

Soybean-derived gma-miR159a alleviates colon tumorigenesis by suppressing TCF7/MYC in mice.

Previous reports have shown that plant-derived microRNAs (miRNAs) regulate mammalian gene expression through dietary intake. Our prior study found that gma-miR159a, which is abundant in soybean, significantly inhibited the proliferation of colon cancer cells. In the current study, dietary gma-miR159a was utilized to study its anti-colon cancer function in azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon cancer mice. Under processing conditions, gma-miR159a exhibited excellent stability in cooked soybean. In vitro, gma-miR159a suppressed the expression of the oncogene MYC downstream of the Wnt signaling pathway by targeting the TCF7 gene, significantly inhibiting the growth of colon cancer cells. The in vivo experiments showed that gma-miR159a and soybean RNA (total RNA extracted from soybean) significantly reduced tumor growth in AOM/DSS-induced colon cancer mice by gavage. This effect disappeared when anti-miR159a was present. In addition, gma-miR159a and soybean RNA significantly attenuated inflammation in colon cancer mice. These results showed that long-term dietary intake of soybean-derived gma-miR159a effectively prevented the occurrence of colon cancer and colitis, which provides novel evidence for the prevention function of soybean.

Neuroprotective Effects of ZiBuPiYin Recipe on db/db Mice via PI3K-Akt Signaling Pathway by Activating Grb2.

Background: Diabetes-associated cognitive decline (DACD) is one of the nervous system dysfunctions induced by diabetes mellitus with cognitive impairment as the major symptom. In a previous preliminary proteomic study, we found that endoplasmic reticulum processing and PI3K-Akt signaling pathway might be impaired in DACD pathogenesis. In addition, growth factor receptor-bound protein 2 might be a crucial protein as a molecular target of the neuroprotective effects of ZiBuPiYin recipe (ZBPYR). Methods: In this study, 6-8 weeks aged db/db mice were treated with excipients or ZBPYR for 6 weeks. Body weight and RBG were recorded weekly. Oral glucose tolerance and insulin tolerance tests were used to assess insulin sensitivity. Morris water maze (MWM) tests were used to assess memory function. The expression of Grb2, Gab2, Akt, and GSK3ß in mouse hippocampus and cerebral cortex were analyzed by Western blotting. Results: ZBPYR not only significantly reduced RGB and improved glucose tolerance and insulin resistance, but also improved spatial cognition in DACD mice. The expression of Grb2 and Gab2 in hippocampus and cerebral cortex of db/db mice was upregulated after treated with ZBPYR, and then affected the PI3K/Akt signaling pathway, and inhibited GSK3ß overactivity. Conclusions: This study showed that ZBPYR could enhance the memory and learning ability of db/db mice. Such neuroprotective effect might be related to the activation of Grb2-PI3K/Akt signaling which might provide a novel therapeutic target for the clinical treatment of DACD.

Niazirin from Moringa oleifera Lam. attenuates high glucose-induced oxidative stress through PKCζ/Nox4 pathway.

BACKGROUND: Diabetic complications-coronary atherosclerosis is closely related to the increased reactive oxygen species (ROS) induced by hyperglycemia. ROS are reported to induce the abnormal proliferation of vascular smooth muscle cells (VSMCs) under high glucose conditions. Leaf and seed extracts from Moringa oleifera are found to exhibit antioxidant activity. However, few studies are evaluating the antioxidant activities of chemical compounds isolated from the M. oleifera especially in cardiovascular field. PURPOSE: The aim of this study is to explore the antioxidative effect during hyperglycemia of niazirin from M. oleifera. STUDY DESIGN: A cell model was applied. METHODS: After the taking the in vitro antioxidant experiment including ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS) assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Cell viability was carried out using high glucose-induced VSMCs model. ROS production was tested by 2',7'-dichlorofluorescein diacetate (DCF-DA) assay. The protein kinase C zeta (PKCζ) and NADPH oxidase 4 (Nox 4) expression in vitro and in vivo were measured by western blot analysis. RESULTS: Niazirin showed good free radical scavenging activity. Niazirin significantly attenuated the proliferation of high glucose-induced VSMCs. Furthermore, it could decrease the ROS and malondialdehyde (MDA) productions, while increased total antioxidant capacity (T-AOC), superoxide dismutase (SOD) as well as glutathione peroxidase (GPx) levels in high glucose-induced VSMCs and streptozotocin-induced mice. In addition, niazirin could eliminate the high glucose-induced PKCζ activation, indicated by Thr410 phosphorylation and inhibition of the Nox4 protein expression in vitro and in vivo. CONCLUSION: Niazirin from M. oleifera exhibited notably antioxidant activities and could be utilized as a potential natural antioxidant in preventing diabetic atherosclerosis.

Wheat germ-derived peptide ADWGGPLPH abolishes high glucose-induced oxidative stress via modulation of the PKCζ/AMPK/NOX4 pathway.

This study explores the antioxidative effect of a specific wheat germ-derived peptide on high glucose-induced oxidative stress in vascular smooth muscle cells (VSMCs) and the underlying mechanisms. The peptide ADWGGPLPH was identified by LC-MS/MS. The effects of this peptide on the production of ROS and the expression of oxidative stress signaling proteins in VSMCs were determined. STZ-induced mice were utilized to confirm the anti-oxidative and anti-diabetic cardiovascular disease effects of this peptide in vivo. The results showed that ADWGGPLPH significantly prevented high glucose-induced cell proliferation, decreased intracellular ROS generation, stimulated AMPK activity, inhibited the PKCζ, AKT and Erk1/2 phosphorylation, and suppressed NOX4 protein expression. In addition, ADWGGPLPH enhanced the antioxidant abilities and attenuated inflammatory cytokine generation in STZ-induced diabetic mice. Therefore, ADWGGPLPH prevents high glucose-induced oxidative stress in VSMCs by modulating the PKCζ/AMPK/NOX4 pathway.