Research on the Nursing Effect of Glycolipids on Acne Skin

Glycolipids are lipid compounds,which are a type of amphiphilic molecules containing glycosyl ligands.This experiment studied the efficacy of glycolipids on acne skin care from the aspects of antibacterial,anti-inflammatory,anti-allergic,oil-control,soothing and repair.Research results show that glycolipids have excellent antibacterial properties against P.acnes;when the dosage of glycolipids reaches 10μg/mL,the inhibition rate of glycolipids on lipid synthesis in SZ95 cells can reach 20%;glycolipids can induce LPS induction RAW264.7 cells have the inhibitory effect on the release of inflammatory factors IL-6 and NO;when the glycolipids concentration is 15 mg/mL,the inhibition rate of glycolipids on hyaluronidase reaches 45.8%;when the glycolipids concentration is 25μg/mL,the inhibition rate on calcium ion concentration reaches 45.3%;glycolipids have a significant promoting effect on wound healing.Furthermore,human efficacy evaluation shows that glycolipids products have comprehensive care effects on acne skin.This study will help further promote the application of glycolipids in cosmetic products,especially in skin care products for acne skin.

Hypoglycemic mechanism of Tegillarca granosa polysaccharides on type 2 diabetic mice by altering gut microbiota and regulating the PI3K-akt signaling pathwaye

Type 2 diabetes mellitus(T2DM)is a complex metabolic disease threatening human health.We investigated the effects of Tegillarca granosa polysaccharide(TGP)and determined its potential mechanisms in a mouse model of T2DM established through a high-fat diet and streptozotocin.TGP(5.1×10^(3) Da)was composed of mannose,glucosamine,rhamnose,glucuronic acid,galactosamine,glucose,galactose,xylose,and fucose.It could significantly alleviate weight loss,reduce fasting blood glucose levels,reverse dyslipidemia,reduce liver damage from oxidative stress,and improve insulin sensitivity.RT-PCR and Western blotting indicated that TGP could activate the phosphatidylinositol-3-kinase/protein kinase B signaling pathway to regulate disorders in glucolipid metabolism and improve insulin resistance.TGP increased the abundance of Allobaculum,Akkermansia,and Bifidobacterium,restored the microbiota abundance in the intestinal tracts of mice with T2DM,and promoted short-chain fatty acid production.This study provides new insights into the antidiabetic effects of TGP and highlights its potential as a natural hypoglycemic nutraceutical.

Simple glycolipids of microbes:Chemistry,biological activity and metabolic engineering

Glycosylated lipids(GLs)are added-value lipid derivatives of great potential.Besides their interesting surface activities that qualify many of them to act as excellent ecological detergents,they have diverse biological activities with promising biomedical and cosmeceutical applications.Glycolipids,especially those of microbial origin,have interesting antimicrobial,anticancer,antiparasitic as well as immunomodulatory activities.Nonetheless,GLs are hardly accessing the market because of their high cost of production.We believe that experience of metabolic engineering(ME)of microbial lipids for biofuel production can now be harnessed towards a successful synthesis of microbial GLs for biomedical and other applications.This review presents chemical groups of bacterial and fungal GLs,their biological activities,their general biosynthetic pathways and an insight on ME strategies for their production.

Tilapia Head Glycolipid Alleviates Indomethacin-Induced Gastric Ulcer via Regulating Oxidative Stress and Inflammation Through COX/PGE2 Signaling Pathway in Adult Rats

The aim of this experiment was to investigate the ameliorative effect and molecular mechanism of tilapia head glycolipid(TH-GL)on indomethacin(IDM)-induced gastric ulcer in male Sprague Dawley(SD)rats.The gastric ulcer model was established by oral administration of 30mgkg^(-1) IDM after 7 days of TH-GL or omeprazole(OME)administration in rats.Then the macroscopic gastric injury symptoms,gastric mucosa protective factor cyclooxygenase 1(COX-1),cyclooxygenase 2(COX-2),prostaglandin E_(2)(PGE_(2)),the levels of oxidative stress,and inflammatory cytokine expression levels in the rats were analyzed.The experimental results showed that multiple ulcers appeared on the gastric surface of the rats in the model group.Compared to the model group,TH-GL significantly alleviated gastric ulcers and reduced the gastric damage index in rats.In addition,TH-GL significantly promoted the expression of constitutive enzyme COX-1 while inhibited the expression of inducible enzyme COX-2,and make PGE2 maintain at normal levels.TH-GL also inhibited oxidative stress and inflammatory responses,increased superoxide dismutase(SOD)activity and glutathione(GSH)content,decreased the level of malondialdehyde(MDA)and the content of pro-inflammatory factor.In conclusion,these results suggested that TH-GL could maintain the expression levels of COX-1 and PGE2 while inhibit the expression of COX-2 in the gastric of rat and then prevent IDM-induced gastric ulcer,which may be related to the regulation of oxidative stress and inflammatory response.Therefore,TH-GL might be a new option for the prevention of gastric diseases induced by IDM.

Role of cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon genes pathway in diabetes and its complications

Diabetes mellitus(DM)is one of the major causes of mortality worldwide,with inflammation being an important factor in its onset and development.This review summarizes the specific mechanisms of the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING)pathway in mediating inflammatory responses.Furthermore,it compre-hensively presents related research progress and the subsequent involvement of this pathway in the pathogenesis of early-stage DM,diabetic gastroenteropathy,diabetic cardiomyopathy,non-alcoholic fatty liver disease,and other complic-ations.Additionally,the role of cGAS-STING in autonomic dysfunction and intes-tinal dysregulation,which can lead to digestive complications,has been discuss-ed.Altogether,this study provides a comprehensive analysis of the research advances regarding the cGAS-STING pathway-targeted therapeutic agents and the prospects for their application in the precision treatment of DM.

Polymorphism of Kdo-Based Glycolipids:The Elaborately Determined Stable and Dynamic Bicelles

Understanding how the diversity of glycolipids,including how their chemical structures and composition affect their biological functions,is a remarkable fundamental challenge.In this work,we employed a rare monosaccharide,3-deoxy-Dmanno-2-octulosonic acid(Kdo)to build a simple and biomimetic model to understand the diversity of glycolipids from the viewpoint of supramolecular chemistry.Kdo was chosen not only because its unusual 8-carbon acidic carbohydrate backbone is very different from common hexoses,but also because of its key structural role in lipopolysaccharides and prevalence in bacteria,plant life,and algae.It was found that although both of the two Kdo-lipids S-Kdo and Kdo-S derived from the same carbohydrate backbone and gave bicelles as their self-assembled morphology,experimental results revealed that the self-assembly showed pathway complexity.Bicelle is the thermodynamic product of S-Kdo,while for Kdo-S,the bicelle is only a kinetically trapped state,which finally transforms to a ribbon.Molecular simulation clearly revealed the different packing of Kdo-lipids in the bicelles with different contribution from hydrogen bonds and electrostatic interactions.

Gangliosides in nervous system development,regeneration,and pathologies

Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal membranes.According to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different ganglio-series.Hundreds of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous system.While GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous system.Mutations in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological impairment.Changes in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’s.In this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.

Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus

BACKGROUND Gestational diabetes mellitus(GDM)can lead to excessive pregnancy weight gain(PWG),abnormal glucolipid metabolism,and delayed lactation.Therefore,it is necessary to provide appropriate and effective interventions for pregnant women with GDM.AIM To clarify the effects of individualized nutrition interventions on PWG,glucolipid metabolism,and lactation in pregnant women with GDM.METHODS The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Provinceand Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022,including 200 who received routine in-terventions[control(Con)group]and 210 who received individualized nutrition interventions[research(Res)group].Data on PWG,glucolipid metabolism[total cholesterol,(TC);triglycerides(TGs);fasting blood glucose(FPG);glycosylated hemoglobin(HbA1c)],lactation time,perinatal complications(cesarean section,premature rupture of membranes,postpartum hemorrhage,and pregnancy-induced hypertension),and neonatal adverse events(premature infants,fetal macrosomia,hypo-glycemia,and respiratory distress syndrome)were collected for comparative analysis.RESULTS The data revealed markedly lower PWG in the Res group vs the Con group,as well as markedly reduced TG,TC,FPG and HbA1c levels after the intervention that were lower than those in the Con group.In addition,obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group.CONCLUSION Individualized nutrition interventions can reduce PWG in pregnant women with GDM,improve their glucolipid metabolism,and promote early lactation,which deserves clinical promotion.

Research progress of artesunate in diabetes and its complications

Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabetic complications.These diseases have become the main causes of disability and death in diabetic patients.Artesunate is well known as an antimalarial drug for controlling malaria symptoms.Current studies have shown that artesunate improves diabetes and its complications by protecting islet cells,improving glucose and lipid metabolism,anti-inflammatory and immune regulation.Based on the research status in recent years,this paper focuses on the mechanism of artesunate in diabetes and its complications,to provide a theoretical basis for future diabetes research.

The Synthesis of Glycoglycerolipids

A convenient synthetic route was developed for the synthesis of the novel glycolipids: 1, 2-di-O-acyl-3-O-(2-acylamide-2-deoxy-a-D-glucopyranosyl)-sn-glycerols. 10 new compounds of glycolipids with different acyl groups were obtained.

Structure modifications based on KRN7000 and their SARs in activating NKT cells

α-Galactosylceramides, which can be recognized by natural killer T （NKT） cells, are now attracting more and more attention due to their therapeutic potential in cancer, infection and autoimmune diseases. Advances have been achieved in discovering compounds with better activities and efforts have been made to understand the structure-activity relationships （SARs） of these NKT cell ligands. In this review, we discuss the structure modifications based on KRN7000, the principal glycolipid used in the study of NKT cell stimulation, and the SARs based on these modified structures.

Human sperm motility stimulating activity of a sulfono glycolipid isolated from Sri Lankan marine red alga Gelidiella acerosa

Aim: To evaluate the sperm motility stimulating activity of a sulfono glycolipid (S-ACT-1) isolated from Gelidiellaacerosa, a Sfi Lankan marine red algae. Methods: S-ACT-I, a white amorphous powder was separated from morepolar fractions of the hexane soluble of 1:1 CH_2Cl_2/MeOH extract and subjected to ~1H, ^(13)C NMR and IR Spectroscopyafter reverse phase HPLC for identification. Effects of S-ACT-1 on human sperm motility was assessed in vitro at 10,100 and 1000μg/mL concentrations at 37℃ for 0, 5, 15, 30 and 60 min. Results: S-ACT-1 was identified as aglycolipid sulfate. The lower dose increased the sperm motility slightly, whilst the medium dose significantly increasedthe motility (P < 0.05) from 5 min of incubation reaching a peak at 15 min and the stimulant effect was sustainedthroughout the experimental period. Furthermore, the medium dose rendered 80% of the immotile viable sperm motile.In contrast, the highest dose impaired the sperm motility. The sperm stimulating activity of S-ACT-1 was dose-depen-dent and had a bell-shaped dose response curve for all the 5 incubation periods. Conclusion: S-ACT-1 of Gelidiellaacerosa is a Sulfono glycolipid. S-ACT-1 has a potent sperm motility stimulating activity in vitro and has the potentialto be developed into a sperm stimulant. (Asian J Androl 2001 Mar; 3: 27-31)

Nitrogen Source Affects Glycolipid Production and Lipid Accumulation in the Phytopathogen Fungus <i>Ustilago maydis</i>

When cultured in medium limited of nitrogen sources, the phytopathogen Ustilago maydis produces two amphipathic glycolipids: Ustilagic acid (UA) and Mannosylerythritol lipid (MEL), which in addition to the hydrophilic moiety, contain dior tri-hydroxylated C16 fatty acids (UA), or C8 and C16 saturated fatty acids (MEL). We compared the growth and morphology of cells in YPD and in minimum media containing glucose and nitrogen sources such as nitrate or urea and those deprived of nitrogen. Nitrogen-starved cells showed a dramatic accumulation of internal lipids identified as lipid droplets when stained with the hydrophobic probe BODIPY;these lipid droplets were enriched in unsaturated fatty acids. Fatty acids in YPD or medium containing nitrate as nitrogen source showed a combination of saturated/unsaturated lipids, but when urea was the nitrogen source, cells only contained saturated fatty acids. The glycolipid profiles produced in the presence or absence of nitrogen showed preferences towards the production of one kind of glycolipid: cells in media containing nitrate or urea produced different proportions of UA/MEL, but under nitrogen starvation cells contained only UA. The emulsification capacity of the glycolipids produced in media with or without nitrogen was similar (72% - 76%). HPLC of the glycolipids allowed the separation of fractions with different emulsifying characteristics. Our results indicate that U. maydis accumulates lipid droplets when deprived of nitrogen source and confirm that UA is not under nitrogen control, but rather that MEL and lipid droplets are produced and oppositely regulated by nitrogen.

Callus Cultures Of Beans Infected With Virus As A Model For Testing Antiviral Compaunds

In the work,bean callus raised from a leaves of Bean common mosaic virus infected bean plant was obtained and adapted for the testing of antiviral activity of liposomal glycan-glycolipid complexes.Ganoderma adspersum glucans and Pseudomonas spec.rhamnolipids were constituents of liposomal compaunds.It has been shown that under the long-term cultivation(up to 3 months)in the presence of a liposomal preparation containing(10-100 mg/l),the virus is eliminated from the tissue.This is evidenced by the absence of 391 bp sequence amplification product established by RT-PCR in the callus tissue,cultured on a medium containing the liposomal complex.The proposed model system is analogous to plant tumors and has obvious advantages over similar systems in vivo,since the callus growth is controlled and independent of environmental factors.

Effect of insulin and metformin on methylation and glycolipid metabolism of peroxisome proliferator-activated receptor γcoactivator-1A of rat offspring with gestational diabetes mellitus

Objective:To discuss the effect of insulin and metformin on amethylation and glycolipid metabolism of peroxisome proliferator-activated receptor γ coactivator-1A(PPARGC1A) of rat offspring with gestational diabetes mellitus(GDM).Methods:A total of 45 pregnant rats received the intraperitoneal injection of streptozotocin to establish the pregnant rat model of GDM.A total of 21 pregnant rats with GDM were randomly divided into three groups,with 7ruts in each group,namely the insulin group,metformin group and control group.Rats in the insulin group received the abdominal subcutaneous injection of 1 mL/kg recombinant insulin glargine at 18:00 every day.Rats in the metformin group received the intragastric infusion of metformin hydrochloride at 18:00 every day,with the first dose of 300 mg/kg.The doses of two groups were adjusted every 3 d to maintain the blood glucose level at 2.65-7.62 mmol/L.Rats in the control group received the intragastric infusion of 1 mL normal saline at 18:00 every day.After the natural delivery of pregnant rats.10 offspring rats were randomly selected from each group.At birth,4 wk and 8 wk after the birth of offspring rats,the weight of offspring rats was measured.The blood glucose level of offspring rats was measured at 4wk and 8 wk,while the level of serum insulin,triglyceride and leptin was measured at 8 wk.Results:The weight of offspring rats at birth in the insulin group and metformin group was significantly lower than the one in the control group(P<0.05),and there was no significant difference at 4 wk and 8 wk among three groups(P>0.05).The fasting blood glucose and random blood glucose in the insulin group and metformin group at 4 wk and 8 wk were all significantly lower than ones in the control group(P<0.05);there was no significant difference between the insulin group and metformin group(P>0.05).The expression of PPARGC1 A mRNA in the insulin group and metformin group was significantly higher and the methylation level of PPARGC1 A was significantly lower than the one in the control group(P<0.05),but there was no significant difference between the insulin group and metformin group(P>0.05).Insulin and leptin at 8 wk in the insulin group and metformin group were significantly higher,while triglyceride was significantly lower than the one in the control group(P<0.05);triglyceride level of rats in the insulin group was significantly higher than the one in the metformin group(P<0.05).There was no significant difference in insulin and leptin level of offspring rats between the insulin group and metformin group(P>0.05).Conclusions:GDM can induce the methylation of PPARGC1 A of offspring rats to reduce the expression of PPARGC1 A mRNA and then cause the disorder of glycolipid metabolism when the offspring rats grow up;the insulin or metformin in the treatment of pregnant rats with GDM can reduce the methylation level of PPARGC1 A and thus improve the abnormal glycolipid metabolism of offspring rats.

Effects of Sodium Thiosulfate on the Occurrence of a Novel Glycolipid in Cyanobacterium Synechocystis sp. PCC 6803 Cells Grown in the Presence of Glucose

A novel lipid occurred when cyanobacterium Synechocystis sp. PCC 6803 cells were grown in BG-11 medium with glucose applied. This lipid was determined to be a glycolipid, designated glycolipid-x (Glyco-x), by staining with alpha-naphthol and concentrated sulfuric acid. The occurrence of Glyco-x accompanies the disappearance of other lipids, especially DGDG. Glyco-x can also be observed in cells grown in BG-11 medium with the application of other carbon sources: fructose, maltose and lactose. Sodium thiosulfate, an effective scavenger of reactive oxygen intermediates, showed strong capability to inhibit glucose-induced occurrence of Glyco-x. In the presence of 0.3% sodium thiosulfate, Glyco-x could only be detected in cells grown in BG-11 medium with 100 mmol/L glucose applied in late-exponential phase. These results suggest that reactive oxygen species might be involved in the occurrence of Glyco-x in cyanobacterium Synechocystis sp. PCC 6803 cells grown in the presence of glucose.

SURFACE MODIFICATION OF PHOSPHOLIPID LIPOSOMES BY INCORPORATION OF GLYCOLIPID

Two single-chain glycolipids, octadecyl-β-D-glucopyranoside(1) and 2-octadecanamido-2-deoxy-D-glucopyranose(2) were synthesized and their dispersing properties in water were studied. Incorporation of 1 into the phospholipid liposomes could inhibit the aggregation of liposomes and improve the molecular packing in the bilayer membranes.

Relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease

Objective: To study the relationship between serum osteocalcin level and glucose and lipid metabolism in patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease. Methods: The clinical data of 180 type 2 diabetes mellitus patients in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, China from February 2017 to January 2018 were retrospectively analyzed, including 90 cases of nonalcoholic fatty liver disease patients (group A) and 90 cases of nonalcoholic fatty liver disease-free patients (group B), meanwhile another 100 healthy subjects were selected as the control group. Then various indexes were compared between groups, including serum osteocalcin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), prothrombin activity (PTA), fasting blood glucose (FBG), glycated hemoglobin (HbA1c), triglyceride (TG), total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting insulin (FINS), fasting C peptide (FCP), HOMA insulin resistance index (HOMA-IR), HOMA β-cell function (HOMA-β). Results: The serum osteocalcin and PTA in group A were significantly lower than those in group B and the control group (P<0.05). ALT, AST, and ALP were significantly higher than those in group B and the control group (P<0.05). The FBG and HbA1c in group A were significantly higher than those in group B and the control group (P<0.05). The TG, TC, LDL, and HDL of group A and group B were significantly higher than those of the control group (P<0.05). The FINS, FCP, and HOMA-IR in group A were significantly higher than those in group B and the control group (P<0.05). HOMA-βwas significantly lower than group B and the control group (P<0.05). Pearson correlation analysis showed that the serum osteocalcin was not correlated with ALT, AST, ALP, PTA, HbA1c, TG, TC, LDL, HDL and FINS (P>0.05), but negatively correlated with FBG and HOMA-IR (P<0.05), and positively correlated with FCP and HOMA-β (P<0.05). With serum osteocalcin as the dependent variable, and ALT, AST, ALP, PTA, FBG, HbA1c, TG, TC, LDL, HDL, FINS, FCP, HOMA-IR and HOMA-β as independent variables, multiple stepwise regression analysis showed that the FBG, HOMA-IR and HOMA-β were independent risk factors for osteocalcin. Conclusions: Patients with type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease have lower serum osteocalcin level, which is susceptible to FBG, HOMA-IR, HOMA-β, and other factors.

Efficacy of Huoxue Qianyang Qutan Recipe on essential hypertension:A randomized,double-blind,placebo-controlled trial

Background:Hypertension,a prevalent disease,is a significant risk factor for coronary heart disease.Huoxue Qianyang Qutan Recipe (HQQR),a traditional Chinese herbal remedy,has been used for treating hypertension over several years.Objective:This study assesses HQQR’s efficacy for controlling blood pressure among patients with hypertension related to blood stasis,yang hyperactivity and phlegm.Design,setting,participants and interventions:A randomized controlled trial was conducted at the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine,Shanghai University of Traditional Chinese Medicine,China,from July 2020 to June 2022.Major components of HQQR were identified using thin-layer chromatography and high-performance liquid chromatography.Participants aged18–80 years,exhibiting traditional Chinese medicine syndromes of blood stasis,yang hyperactivity or phlegm,along with grades 1 or 2 hypertension,were randomly categorized into two groups.The intervention group was given HQQR granules alongside conventional hypertension treatment,while the control group was given placebo granules in addition to conventional treatment for 12 weeks.Main outcome measures:The primary outcome was clinic blood pressure,whereas secondary outcomes included metabolic indices (e.g.,homeostasis model assessment of insulin resistance[HOMA-IR],total cholesterol[TC],low-density lipoprotein cholesterol and triglyceride),target organ damage indices (left ventricular mass index and urinary albumin creatinine ratio[UACR]) and inflammation indices(interleukin-6[IL-6]and high-sensitivity C-reactive protein[hs-CRP]).Results:HQQR’s primary components were identified as salvianolic acid B,emodin and ferulic acid.Of the 216 participants (108 in each group),compared to the control,the intervention group exhibited significant improvements (P<0.001) in clinic systolic blood pressure ([136.24±7.63]vs[130.06±8.50]mmHg),clinic diastolic blood pressure ([84.34±8.72]vs[80.46±6.05]mmHg),home systolic blood pressure([131.64±8.74]vs[122.36±8.45]mmHg) and home diastolic blood pressure ([78.47±9.53]vs[71.79±6.82]mm Hg).HQQR demonstrated a reduction in ambulatory blood pressure (24-hour systolic blood pressure:[133.75±10.49]vs[132.46±8.84]mmHg and 24-hour diastolic blood pressure:[84.12±8.01]vs[82.11±7.45]mmHg) and an improvement in HOMA-IR ([4.09±1.72]vs[3.98±1.44]),TC ([4.66±1.47]vs[3.75±1.81]mmol/L) and UACR (75.94[5.12,401.12]vs 45.61[4.26,234.26]).Moreover,HQQR demonstrated a decrease in hs-CRP (1.46[0.10,10.53]vs 0.57[0.12,3.99]mg/L) and IL-6 (6.69[2.00,29.74]vs 5.27[2.00,9.73]pg/mL),with no reported side effects (P<0.001).Conclusion:This study highlights the therapeutic potential of HQQR use in ameliorating blood pressure,glycolipid metabolism,and inflammation in patients with hypertension.

Mechanisms of Dangua Fang(丹瓜方)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics

OBJECTIVE:To explore the mechanism of Dangua Fang(丹瓜方,DGR)in multi-target and multi-method regulation of glycolipid metabolism based on phosphoproteomics.METHODS:Sprague-Dawley rats with normal glucose levels were randomly divided into three groups,including a conventional diet control group(Group A),high-fat-highsugar diet model group(Group B),and DGR group(Group C,high-fat-high-sugar diet containing 20.5 g DGR).After 10 weeks of intervention,the fasting blood glucose(FBG),2 h blood glucose[PBG;using the oral glucose tolerance test(OGTT)],hemoglobin A1c(HbA1c),plasma total cholesterol(TC),and triglycerides(TG)were tested,and the livers of rats were removed to calculate the liver index.Then,hepatic portal TG were tested using the Gross permanent optimization-participatiory action planning enzymatic method and phosphoproteomics was performed using liquid chromatography with tandem mass spectrometry(LC-MS/MS)analysis followed by database search and bioinformatics analysis.Finally,cell experiments were used to verify the results of phosphoproteomics.Phosphorylated mitogen-activated protein kinase kinase kinase kinase 4(MAP4k4)and phosphorylated adducin 1(ADD1)were detected using western blotting.RESULTS:DGR effectively reduced PBG,TG,and the liver index(P<0.05),and significantly decreased HbA1c,TC,and hepatic portal TG(P<0.01),showed significant hematoxylin and eosin(HE)staining,red oil O staining,and Masson staining of liver tissue.The total spectrum was 805334,matched spectrum was 260471,accounting for accounting 32.3%,peptides were 19995,modified peptides were 14671,identified proteins were 4601,quantifiable proteins were 4417,identified sites were 15749,and quantified sites were 14659.Based on the threshold of expression fold change(>1.2),DGR upregulated the modification of 228 phosphorylation sites involving 204 corresponding function proteins,and downregulated the modification of 358 phosphorylation sites involving 358 corresponding function proteins,which included correcting 75 phosphorylation sites involving 64 corresponding function proteins relating to glycolipid metabolism.Therefore,DGR improved biological tissue processes,including information storage and processing,cellular processes and signaling,and metabolism.The metabolic functions regulated by DGR mainly include energy production and conversion,carbohydrate transport and metabolism,lipid transport and metabolism,inorganic ion transport and metabolism,secondary metabolite biosynthesis,transport,and catabolism.In vitro phosphorylation validation based on cell experiments showed that the change trends in the phosphorylation level of MAP4k4 and ADD1 were consistent with that of previous phosphoproteomics studies.CONCLUSION:DGR extensively corrects the modification of phosphorylation sites to improve corresponding glycolipid metabolism-related protein expression in rats with glycolipid metabolism disorders,thereby regulating glycolipid metabolism through a multi-target and multi-method process.