CN102652757A - Application of health-care drinking liquid containing deep seawater in preparation of medicaments or health-care products for preventing or treating metabolic syndrome - Google Patents
Application of health-care drinking liquid containing deep seawater in preparation of medicaments or health-care products for preventing or treating metabolic syndrome Download PDFInfo
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Abstract
The invention provides application of health-care drinking liquid containing deep seawater in preparation of medicaments or health-care products for preventing or treating metabolic syndrome. The health-care drinking liquid comprises liquid A and liquid B, wherein the liquid A is fresh water; and the liquid B is high-concentration concentrate obtained by reduced pressure concentration of concentrated water separated from the deep seawater through a reverse osmosis device, and the hardness range of the liquid B is 200 to 1000ppm. The health-care drinking liquid can regulate the insulin signaling channel in vitro level and improve the resistance of insulin so as to prevent the metabolic syndrome. The health-care drinking liquid prepared from the deep seawater has the advantages of rich resources, easiness in industrialization and the like, and has broad market and application prospect on the aspect of preventing and treating the metabolic syndrome.
Description
Technical field
The invention belongs to the marine biotechnology field, relate to the comprehensive utilization of deep seawater, be specifically related to a kind of healht-care liquid that contains deep seawater in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product.
Background technology
Metabolic syndrome is one group and assembles morbidity with central obesity, hyperglycemia (diabetes or IGR), hyperlipidemia and hypertension etc.; Have a strong impact on the clinical syndrome of body health; Appearing as clinical characters with multiple metabolic disease merging, is the combination of one group of risk factor that in metabolism, is mutually related.In recent years, along with economy develops rapidly, life and diet style westernization, the prevalence of metabolic syndrome raises.Metabolic syndrome day by day becomes China, especially the important public health problem in big and medium-sized cities.Research shows that insulin resistant (IR) is the pathogenesis basis of metabolic syndrome, and insulin resistant has become a research focus of medical domain in recent years.
Insulin resistant is meant that a certain amount of insulin combines the artifact effect to be lower than normally with its specific receptor; Be the effect that the insulin of physiological concentration does not reach expection, mainly show as insulin and suppress liver and discharge the ability of glucose and promote surrounding tissue (mainly being skeletal muscle and fat) to absorb and utilize the ability drop of glucose.
Liver is the critical organ of insulin resistant.The liver insulin resistant is meant that mainly insulin suppresses the ability drop of liver glucose output.Glycogen output mainly is made up of glyconeogenesis and glycogenolysis two parts.Glyconeogenesis is meant synthesis of glucose such as nonsugar such as lactic acid, 1-propenol-3, glucogenic amino acid, glycerol; Glycogenolysis is meant that employing the glycogen that is stored in the liver provides glucose.Liver is kept generation and the output and sugared absorption, utilization and the storage in feed back of the endogenous sugar under the empty stomach state as the main target organ of insulin action.In recent years liver insulin resistant Study on Mechanism has been become focus.
The IRS-2/PI3K signal is the main signal transduction pathway of insulin at liver performance physiological effect.After the feed of animal or human's class, go into the Insulin receptor INSR (InsR) that blood acts on the liver plasma membrane surface by the insulin that the beta Cell of islet secretion produces, the tyrosine site autophosphorylation that is located at intracytoplasmic β subunit activates.Activated Insulin receptor INSR activates after making IRS (IRS-2) tyrosine site phosphorylation; And then activation phosphatidylinositols 3 kinases (PI3K); PI3K after the activation can catalysis 4; 5-diphosphonic acid phosphatidylinositols (PIP2) generates triphosphoric acid phosphatidylinositols (PIP3); It is as second message,second messenger's activated protein kinase B (Akt), and activatory Akt participates in the metabolism regulating action of performance insulin through following approach: (1) plays an important role through the transposition of glucose transporter GLUT4 vesicle in the pair cell.Under insulin stimulating, GLUT4 vesicle pond in the cell moves to cell membrane, merges with film then, the GLUT4 molecule is fixed on the cell membrane, thus the effect of performance transhipment glucose; (2) promote glycogen synthetic through glycogen synthase kinase-3 (GSK-3).GSK-3 is the physiology substrate of first found PKB/Akt, and PI3K, PDK, Akt and GSK3 have formed insulin and regulated an important branch road in the synthetic signal cascade of the glycogen system.The isomer GSK3 α of the GSK3 of two kinds of forms and the aminoterminal of GSK3 β all contain the phosphorylation site of Akt, and insulin promotes glycogen synthetic through phosphorylation and inactivation GSK3; (3) expression and the glyconeogenesis of inhibition glyconeogenesis gene G-6-Pase (G6Pase) and PCK (PEPCK), final blood sugar lowering.
Insulin receptor INSR signal transduction defective is the main cause that IR takes place, and the key of normal insulin signaling conduction is the tyrosine phosphorylation process on the various kinase proteins.In most insulin resistants; The tyrosine phosphorylation of Insulin receptor INSR is normal basically; The key position that insulin resistant takes place is IRS; IRS-1, the IRS-2 main signal protein after as InsR wherein, the reduction of its gene expression, the minimizing of protein expression and phosphorylation obstacle all can cause its activation to PI3K obviously to descend, and have hindered the conduction of insulin signaling pathway downstream signal thus and cause IR.
The energy metabolism dysequilibrium is the major reason that IR takes place.The activated protein kinase of adenosine phosphate (AMP) (AMPK) signal path is the key link of regulating the cellular energy state, change that can perception cellular energy metabolism state, and keep cellular energy demand balance through influencing the metabolic a plurality of links of cellular material.Activate after the AMPK phosphorylation, active A MPK activates the multiple target molecule in its downstream, closes metabolic pathway of synthesizing thereby reach, and opens the effect of catabolic pathway.At skeletal muscle, glucose uptake and fatty acid oxidation are increased, and promote mitochondrial biosynthesis; At liver, suppress the synthetic of glucose and lipid, promote lipid oxidation; In fatty tissue, reduced lipid decomposition and lipid and generated.Otherwise when AMPK dephosphorylation inactivation, the body anabolism is occupied an leading position, lipid within endothelial cells, the synthetic increase of glycogen.Under the normal physiological state, its downstream signal pathway of activated AMPK regulation and control increases the reaction to insulin of transposition and the enhances skeletal flesh of GLUT4 on the one hand, and motion and metformin improve the type 2 diabetes mellitus patient through this approach exactly; On the other hand; Active A MPK can suppress Hydroxymethylglutaryl list acyl coenzyme A reductase (HMGCR), acetyl-CoA carboxylase lipid synthase activities such as (ACC); Reduce the expression of conjugated protein (SREBP)-lc of sterin regulating element and FAS E.C. 2.3.1.85 (FAS); Thereby the inhibition lipogenesis increases the fatty acid oxidation approach simultaneously, reduces liver inner lipid content.In addition, behind the AMPK pathway activation, downstream can be through strengthening mitochondrial function, promoting mitochondrion propagation to promote the energy utilization.Therefore, the damage of AMPK approach can cause body IR and lipid dystopy deposition.
Oxidative stress is that insulin resistant takes place and a major reason that develops.Secular hyperglycemia, hyperlipidemia can cause mitochondrion to produce a large amount of reactive oxygen specieses (ROS); The generation of a large amount of ROS and accumulate in tissue; As can not be removed by in-house antioxidant system, will pass through the activation of systems such as IKK, NF-κ B, p38MAKP, JNK/SAPK, the signal path in interference cell Insulin receptor INSR signal transduction and downstream such as Akt; Insulin receptor INSR and receptor substrate phosphorylation finally cause insulin resistant.
Mineral element plays a significant role in the generation of IR, evolution.Find that through experiment magnesium deficiency is relevant with the activity reduction of insulin receptor tyrosine kinase like Su á res etc.; Chromium can be expressed and influence content of insulin, increases Insulin receptor INSR quantity, improves beta Cell of islet sensitivity, strengthens and take the photograph and activate insulin receptor tyrosine kinase in the adhesion, enhancing insulin of insulin and increase insulin sensitivity through regulating insulin gene; Zinc, selenium then can through the oxidation resistance that improves body accelerate free radical removing and inhibited oxidation stress, thereby improve insulin resistant.
Deep seawater typically refer to solar radiation less than, can not carry out photosynthesis, the sea water below about 200m degree of depth.Deep seawater is in the ocean of no sunlight entering does not have photosphere, and away from influence and pollution from the mankind, land and atmospheric chemical substance.Research shows that deep seawater has following main feature: (1) low temperature homeostasis-do not receive solar radiation, and changeable unlike the sea surface coolant-temperature gage, deep seawater is temperature-resistant all the year round, is constant at about 5 ℃; (2) the abundant and stability of mineral element-with sea surface water ratio; Deep seawater is rich in 92 kinds of mineral elements such as the necessary calcium of human body, magnesium, potassium, sodium, ferrum, copper, lithium, molybdenum, manganese, zinc, germanium, iodine, phosphorus, fluorine, selenium, trivalent chromium, silicate ion, has contained the required element kind of human body metabolism.Except its content is abundant; Because these water flow in the bathypelagic of " no photosphere " with the very long time; Ectocine with taking place, not receiving in unglazed cooperation, and therefore the composition of contained mineral element is very stable, has ideally solved the requirement that total balance of the body is absorbed various required mineral elements; (3) aseptic spatter property-the be in deep water of ocean " no photosphere " except away from the influence of human modern civilization and do not receive the pollution of land, Atmospheric Chemistry material, pathogenic bacteria, itself does not have the condition that generates antibacterials such as pathogen yet.Therefore, deep seawater is the water of the aseptic nature that cleans very much; (4) deep seawater water quality is alkalescence.
Owing to have above characteristics, deep seawater is receiving attracting attention of common people as a kind of new natural resources.Deep seawater is rich in various mineral and trace element, and it has good improvement effect to insulin resistant and metabolic syndrome in theory.China marine site is broad, and the coastline is very long, and marine resources are abundant, but does not still have the research of deep seawater Application and Development aspect; And China's water scarcity, water is seriously polluted, and the bathypelagic water resource of exploitation China has crucial meaning.
China marine site is broad, and the coastline is very long, and marine resources are abundant, but does not still have the research of deep seawater Application and Development aspect; And China's water scarcity, water is seriously polluted, and the bathypelagic water resource of exploitation China has crucial meaning.
Summary of the invention
, water in short supply day by day to present China water resource pollutes and is on the rise and the rapid hot issue such as risings of metabolic syndrome sickness rate, the invention provides a kind of healht-care liquid that contains deep seawater in the preparation prevention or treat the medicine of metabolic syndrome or the application in the health product.
For realizing the foregoing invention purpose, the present invention adopts following technical proposals to be achieved:
A kind of healht-care liquid that contains deep seawater is in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; Said healht-care liquid comprises A liquid and B liquid, and said A liquid is fresh water, and said B liquid makes through following steps: deep seawater is isolated dense water section behind reverse osmosis unit; Dense water section is carried out concentrating under reduced pressure; Make its volume be concentrated into the 0.67-3.33% of original volume, remove by filter the sodium chloride of separating out then, the height concentrated solution that obtains is B liquid; The hardness of said healht-care liquid is at 200-1000ppm, and said deep seawater is below the 500m of sea level and the sea water after desalting processing.
Further improvement to technique scheme: magnesium in the said healht-care liquid: calcium: potassium: the concentration ratio of sodium element is 2.5-3.5: 0.45-1: 0.3-1: 0.3-1.5, do not contain Organic substance, and water quality is alkalescence.
Further improvement to technique scheme: said magnesium: calcium: the ratio of greater inequality of the concentration of potassium is 3: 1: 1.
Further improvement to technique scheme: the water quality of said healht-care liquid is alkalescence, the pH value 7.5 ± 0.3 of 25 ℃ of mensuration.
Further improvement to technique scheme: the beneficial element content in the said healht-care liquid is: zinc 0.0325-16.4 μ g/L; Selenium 0.0395-0.712 μ g/L; Chromium 0.104-4.54 μ g/L; Manganese 0.156-5.52 μ g/L.
Further improvement to technique scheme: the harmful element content in the said healht-care liquid is: lead＜5 μ g/L; Hydrargyrum＜0.5 μ g/L; Arsenic＜5 μ g/L; Cadmium＜1 μ g/L.
Further improvement to technique scheme: said deep seawater is taken from apart from beyond the 20km of coastline.
Further improvement to technique scheme: said fresh water sources Yu Haiyang deep water is isolated fresh water after the reverse osmosis unit circulation.
Further improvement to technique scheme: it is the healht-care liquid of 600-1000ppm that diet is selected hardness for use to the less metabolic syndrome patient of the picked-up of mineral, is the healht-care liquid of 200-400ppm otherwise select hardness.
Compared with prior art, advantage of the present invention and good effect are:
The healht-care liquid that contains deep seawater provided by the invention is rich in healthy trace elements with household magnesium, calcium, vanadium, chromium, manganese, zinc, selenium; And poisonous trace element hydrargyrum is very low with plumbous content; The present invention shows that through biotic experiment this healht-care liquid does not have toxicity on cellular level, safe; And can promote the synthetic of glycogen, thereby reduce glycogen output; Can improve insulin resistant through the lipid route of synthesis that activates in the AMPK inhibition liver; Can also improve insulin resistant through the oxidation resistance of enhancing body.Significantly regulate insulin signaling pathway through these approach, metabolic diseases such as metabolic syndrome are had prevention and therapeutical effect preferably.
The specific embodiment
Below in conjunction with the specific embodiment technical scheme of the present invention is done further detailed explanation.
Embodiment 1
One, the preparation of healht-care liquid
The method for preparing of healht-care liquid according to the invention is following:
1) bathypelagic water pretreatment: will take from apart from beyond the 20km of coastline; Sea level 500m puts into water tank with dark deep seawater, adopts filter to filter, and removes phytoplankton and microorganism in the sea water; And, further remove Organic substance through the active carbon filter filtration.
2) fresh water and dense separated form water: the deep seawater that obtains after the pretreatment is divided into the fresh water part through high-pressure pump entering reverse osmosis unit with deep seawater, and (fresh water part water quality is identical with pure water, or water quality is near pure water with dense water section; The concentration of various zwitterions is near 2 times of various ion concentrations in the former sea water in the dense water section), isolated fresh water partly is that A liquid gets into the fresh water water tank, isolated dense water section gets into dense water water tank.The technological parameter of reverse osmosis unit is: 4MPa, power 1.5KW, aquifer yield 1T/d are pressed in running.
3) dense water takes off the sodium processing: the dense water section in the dense water water tank is carried out concentrating under reduced pressure; Make its volume be concentrated into the 0.67-3.33% of original volume; Remove by filter the sodium chloride of separating out then; Obtain highly spissated concentrated solution and be B liquid, magnesium in the said concentrated solution: calcium: potassium: the concentration ratio of sodium element is 2.5-3.5: 0.45-1: 0.3-1: 0.3-1.5, and said magnesium, calcium, potassium, the content concn unit of sodium element in concentrated solution are mg/L.Trace element chromium wherein, zinc, selenium, the concentration of manganese etc. and cycles of concentration are the multiple proportions relation.
Perhaps, also can adopt the selectivity electrodialysis to reverse osmosis after isolated dense water section take off sodium and handle, electrodialysis plant adopts 1 valency cation selective to see through film, cavity block adopts the conventional ion exchange membrane.All aniones all can see through cavity block in electrodialytic process, and only univalent cation sees through anode membrane, and the polyvalent cation that takes off in the sodium dense water afterwards is close with the concentration in the former dense water.
4) healht-care liquid fill: will pass through fresh water A liquid that the step 1) reverse osmosis unit comes out and the resulting B liquid of step 3) can according to demand mixed the healht-care liquid of different hardness, said hardness is with CaCO
3Cubage (GB 5749-2006 drinking water sanitary standard), hardness=Ca (ppm)) * 2.5+Mg (ppm) * 4.1 its computing formula is:, through high temperature sterilize, packing gets final product.
Adopt inductively coupled plasma mass spectrum (ICP-MS) that the inorganic element content in the healht-care liquid is measured: with hardness is that 1000 healht-care liquid is example, and wherein several kinds of main mine materials and micronutrient levels are: magnesium: 200-224mg/L; Calcium: 33-67mg/L; Potassium: 20-67mg/L; Sodium: 20-100mg/L (content of sodium is low more good more); Zinc: 0.0325-16.4 μ g/L; Selenium: 0.0395-0.712 μ g/L; Chromium: 0.104-4.54 μ g/L; Manganese 0.156-5.52 μ g/L, lead＜5 μ g/L; Hydrargyrum＜0.5 μ g/L; Arsenic＜5 μ g/L; Cadmium＜1 μ g/L.
Healht-care liquid mineral under the 200-1000 hardness according to the invention and micronutrient levels are directly proportional with its hardness.Magnesium in the said healht-care liquid: calcium: potassium: the concentration ratio of sodium element is 2.5-3.5: 0.45-1: 0.3-1: 0.3-1.5, is rich in healthy trace elements with household zinc, selenium, chromium; Manganese, poisonous trace element lead, hydrargyrum, arsenic; Cadmium content is lower, do not contain Organic substance, and water quality is alkalescence.
Said healthy trace elements with household content is following: zinc: 0.0325-16.4 μ g/L; Selenium: 0.0395-0.712 μ g/L; Chromium: 0.104-4.54 μ g/L; Manganese 0.156-5.52 μ g/L.
Said poisonous micronutrient levels is following: lead＜5 μ g/L; Hydrargyrum＜0.5 μ g/L; Arsenic＜5 μ g/L; Cadmium＜1 μ g/L.
Use pH meter that its pH value is measured (25 ℃), the result shows healht-care liquid pH value in 7.5 ± 0.3 scopes, and water quality is alkalescence.
Two, healht-care liquid is to the improvement effect and the mechanism of insulin signaling pathway and insulin resistant
1, experimental technique
1) cell culture: human liver cancer cell HepG2 cell, cell culture medium are low sugar DMEM (5.5mmol/L) culture medium that contains 10% hyclone, and culture environment is 37 ℃, 5%CO
2, went down to posterity once in 1: 3 ratio in per 3 days.
2) healht-care liquid is to the cytotoxicity of HepG2 cell: collect the logarithmic (log) phase cell, the adjustment concentration of cell suspension is inoculated in 96 orifice plates, 10000 cells in every hole.37 ℃, 5%CO
2Cultivate, treat that cell degree of converging reaches at 70% o'clock, be changed to the DMEM that does not contain serum, hunger is spent the night, and adds the healht-care liquid of different hardness as shown in table 1 then, and each concentration is established 6 parallel holes.Continue to cultivate 24h, every hole adds freshly prepared 20 μ L MTT (5mg/mL), continues to cultivate 4h.Sop up supernatant then, every hole adds 150 μ L DMSO, low-speed oscillation 10min, and abundant dissolving crystallized thing is surveyed the OD value with enzyme-linked immunosorbent assay instrument at 570-630nm, and the record result calculates the cell inhibiting rate.
3) foundation of insulin resistant HepG2 (IR-HepG2) cell model and administration are handled: the HepG2 cell of the trophophase of taking the logarithm; DMEM culture fluid with containing 10%FBS is made into the individual cells suspension; According to requirement of experiment; By cell density is that 1.0 * 106cell/mL is inoculated in the culture plate of different apertures, and 37 ℃ of incubators are hatched under 5% carbon dioxide conditions.Treat cell degree of converging to 70%, be changed to the DMEM culture fluid hunger that does not contain serum and spend the night that the serum-free medium that is changed to low sugar (5.5mmol/L) or high sugar (30mmol/L) then continues to hatch 24h.The HepG2 cell of in low sugar culture-medium, hatching is the blank cell, and the HepG2 cell of in high glucose medium, hatching is the IR-HepG2 cell.When setting up insulin resistant model, give the healht-care liquid of different hardness, observe the preventive effect of healht-care liquid insulin resistant.When detecting the insulin signaling pathway correlative protein expression, before the harvesting, 100nM insulin stimulating 10min.
4) healht-care liquid is to the influence of IR-HepG2 cell sugar output: behind the drug incubation 24h; With sugar-free DMEM culture medium washed cell 3 times; Add glucose output culture medium (sugar-free that contains 2mM Sodium Pyruvate and 20mM sodium lactate does not have phenol red DMEM) then and continue to hatch 16h, wherein last 3h adds the 1nM insulin.After hatching end, get supernatant and measure glucose content, BCA method mensuration protein content after lower floor's lysis in the plate.
5) healht-care liquid is to the influence of IR-HepG2 cell glycogen content: behind the drug incubation 24h, the PBS washed cell adds the culture medium that contains 1n M insulin and continues to hatch 3h, discards culture fluid; Pre-cooling PBS washes 2 times, and cell is scraped and got, 12000r/min, 4 ℃ of centrifugal 15min; Abandon supernatant, add 0.5mL 30%KOH in the cell precipitation, put 100 ℃ of water-bath 20min, take out 10 μ L and measure protein content with the BCA method; All the other add the 1.5mL dehydrated alcohol, spend the night, and the centrifugal 15min of 4000r/min abandons supernatant; Add distilled water 0.5mL in the deposition, add 1mL 0.2% anthrone (the 0.2g anthrone is dissolved in 100mL 98% sulphuric acid) subsequently, 100 ℃ of water-bath 20min.ELIASA detects 620nm wavelength OD value, and the glucose solution of cofabrication 100,50,25,12.5,6.25,3.125 and 1.56 μ g/mL is done sugared concentration standard curve.
6) healht-care liquid is to the influence of IR-HepG2 cytolipin content: behind the drug incubation 24h, absorb remaining culture liq, ice PBS washes 2 times; Add 100 μ L cell pyrolysis liquids, piping and druming was evenly incubated in the frozen water 30 minutes; Constantly scrape during this time and smear, lysate is fully contacted with cell with cell; Lysate is transferred in the 1.5mL ep pipe low temperature ultrasonication 10s; 12000rpm, 15min, 4 ℃ are centrifugal ,-20 ℃ of freezing preservations, the cytolysate that takes a morsel is measured protein content with the BCA method, and all the other are used to detect intracellular lipid content.Measure the content of cell inner cholesterol and triglyceride respectively: unit calculates with every milligram of protein content (μ g/mg protein).
7) healht-care liquid is to the influence of ROS content in the IR-HepG2 cell born of the same parents: use the active oxygen detection kit to measure ROS content in the born of the same parents.According to the description operation, behind the drug effect 24h, the trypsinization harvesting; PBS washes 3 times, is resuspended in 10 μ M 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA); Hatch 30min for 37 ℃ then; ROS content in the fluorescent spectrophotometer assay born of the same parents, excitation wavelength 488nm, emission wavelength 525nm.
8) western blot detects healht-care liquid to the expression of GAP-associated protein GAPs such as insulin signaling pathway, AMPK signal path and JNK signal path and the influence of phosphorylation degree: cell pyrolysis liquid is with BCA method mensuration protein concentration; Appearance on the equivalent; 10% separation gel SDS-PAGE; Change film 1h; Add IRS-2, pIRS-2 (Tyr612), Akt, pAkt (Ser473), GSK-3, G6Pase, AMPK, pAMPK, pHMGCR, pACC, SREBP-1 behind the 5%BSA sealing 2h, reach anti-working solutions such as JNK, pJNK, actin, 4 ℃ of shaken over night.After one anti-the hatching, TBST washes film, adds two anti-working solutions of the horseradish peroxidase-labeled of dilution in 1: 5000, and room temperature is shaken 1h, the ECL colour developing.
9) statistical procedures: data all represent that with mean ± standard deviation
group difference adopts the t method of inspection to carry out.
2, experimental result
1) healht-care liquid is to the influence of HepG2 cell proliferation: can be found out that by table 1 the healht-care liquid of different hardness does not have influence basically to the propagation of HepG2 cell, therefore can be used for next step experiment.
Table 1: healht-care liquid is to the influence of HepG2 cell proliferation
2) healht-care liquid is to the influence of IR-HepG2 cell sugar output and glycogen content: it is the important special disease of insulin resistant that glycogen output increases, and glycogen is exported and is made up of glyconeogenesis and glycogenolysis two parts.Can be learnt that by table 2 model group cell sugar output significantly increases, glycogen content then significantly reduces, and explains that high sugar processing makes hepatocyte that insulin resistant take place; And the processing of healht-care liquid can make the sugared output of IR-HepG2 cell significantly reduce, and glycogen content significantly increases, and explains that healht-care liquid can promote the synthetic of glycogen, thereby reduces glycogen output.
Table 2: healht-care liquid is to the influence of IR-HepG2 cell sugar output and glycogen content
Annotate: contrast with blank control group:
#P＜0.05,
##P＜0.01; Contrast with model group:
*P＜0.05,
*P＜0.01
3) healht-care liquid influence that IR-HepG2 cell IRS-2/PI3K signal related protein is expressed: Western blot result shows; As shown in table 3; Behind the high concentration glucose effect 24h; The expressing quantity of IRS-2 is constant basically, but the phosphorylation degree of IRS-2, Akt, GSK-3 significantly reduces, and the expression of G6Pase then significantly increases.Healht-care liquid then can dose dependent ground promotes the phosphorylation of IRS-2, Akt, GSK-3, suppresses the expression of G6Pase.Infer that healht-care liquid suppresses glyconeogenesis through this signal path, promote glycogen synthetic, thereby reduce glycogen output improvement insulin resistant, specificity activates the IRS-2/PI3K signal path and is likely that healht-care liquid improves the target spot of insulin resistant.
Table 3: the influence that healht-care liquid is expressed IR-HepG2 cell IRS-2/PI3K signal related protein
Annotate: contrast with blank control group:
#P＜0.05,
##P＜0.01; Contrast with model group:
*P＜0.05,
*P＜0.01
4) healht-care liquid is to the influence of IR-HepG2 cell born of the same parents inner lipid content: as shown in table 4, behind the high concentration glucose effect 24h, model group cell born of the same parents inner lipid content is significantly higher than blank control group, and the high sugar of prompting is handled and induced HepG2 lipid within endothelial cells deposition; Lipid content obviously reduces after 24 hours and process healht-care liquid is handled.
Table 4: healht-care liquid is to the influence of IR-HepG2 cell born of the same parents inner lipid content
Annotate: contrast with blank control group:
#P＜0.05,
##P＜0.01; Contrast with model group:
*P＜0.05,
*P＜0.01
5) healht-care liquid influence that IR-HepG2 cell AMPK signal related protein is expressed: western blot detects and finds that the AMPK phosphorylation level reduces in the model group cell; Corresponding with it is the phosphorylation degree reduction of synthetic rate-limiting enzyme HMGCR of cholesterol and fatty acid and ACC; The expression of SREBP-1 increases; And through after the healht-care water treatment, the AMPK activity significantly increases, and the phosphorylation of HMGCR and ACC strengthens simultaneously; SREBP-1 expresses then corresponding reduction; The synthetic minimizing of lipids such as triglyceride and cholesterol in the final hepatocyte, insulin resistant improves, and these results show: health-care drinking-water can improve insulin resistant through the lipid route of synthesis that activates in the AMPK inhibition liver.
Table 5: the influence that healht-care liquid is expressed IR-HepG2 cell AMPK signal related protein
Annotate: contrast with blank control group:
#P＜0.05,
##P＜0.01; Contrast with model group:
*P＜0.05,
*P＜0.01
6) healht-care liquid to the IR-HepG2 cellular oxidation stress influence: as shown in table 6; High sugar is handled the phosphorylation degree that has significantly increased interior ROS content of born of the same parents and JNK; The activity of important antioxidase GSH-Px then significantly reduces in the body; Explain that redox equilibrium is seriously lacked of proper care in the model group cell, produced oxidative stress.After healht-care liquid was handled 24h, the phosphorylation degree of ROS content and JNK significantly reduced, and the activity of GSH-Px also obviously increases simultaneously, explains that this healht-care liquid can improve insulin resistant through the oxidation resistance of enhancing body.
Table 6: healht-care liquid to the IR-HepG2 cellular oxidation stress influence
Annotate: contrast with blank control group:
#P＜0.05,
##P＜0.01; Contrast with model group:
*P＜0.05,
*P＜0.01
This experimental result shows that this healht-care liquid can improve insulin signaling pathway preferably in external level, suppresses the excessively synthetic and oxidative stress of glyconeogenesis, lipid, effectively improves insulin resistant.This healht-care liquid can be used as the prevention that a kind of natural drink is used for insulin resistant and metabolic syndrome; The healht-care liquid that metabolic syndrome patient can select corresponding hardness according to oneself health and dietary habit; If diet is less to the picked-up of mineral; Can select the healht-care liquid (600-1000ppm) of high rigidity for use, otherwise select healht-care liquid (200-400ppm) than soft.
This healht-care liquid derives from deep seawater, has aboundresources, is easy to industrialization, and safe advantages of higher, aspect the preventing and treating of hyperlipemia, has vast market and application prospect.The present invention will be the higher value application of deep seawater offer reference meaning and enlightenment.
Above embodiment is only in order to explaining technical scheme of the present invention, but not limits it; Although the present invention has been carried out detailed explanation with reference to previous embodiment, for the person of ordinary skill of the art, still can make amendment to the technical scheme that previous embodiment is put down in writing, perhaps the technological special disease of part wherein is equal to replacement; And these modifications or replacement do not make the essence of relevant art scheme break away from the spirit and the scope of the present invention's technical scheme required for protection.
Claims (9)
1. a healht-care liquid that contains deep seawater is in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; Said healht-care liquid comprises A liquid and B liquid, and said A liquid is fresh water, and said B liquid makes through following steps: deep seawater is isolated dense water section behind reverse osmosis unit; Dense water section is carried out concentrating under reduced pressure; Make its volume be concentrated into the 0.67-3.33% of original volume, remove by filter the sodium chloride of separating out then, the height concentrated solution that obtains is B liquid; The hardness of said healht-care liquid is at 200-1000 ppm, and said deep seawater is below the 500m of sea level and the sea water after desalting processing.
2. a kind of healht-care liquid that contains deep seawater according to claim 1 is in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; It is characterized in that magnesium in the said healht-care liquid: calcium: potassium: the concentration ratio of sodium element is 2.5-3.5:0.45-1:0.3-1:0.3-1.5; Do not contain Organic substance, and water quality is alkalescence.
3. a kind of healht-care liquid that contains deep seawater according to claim 2 is characterized in that said magnesium: calcium in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product: the ratio of greater inequality of the concentration of potassium is 3:1:1.
4. a kind of healht-care liquid that contains deep seawater according to claim 2 is in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; The water quality that it is characterized in that said healht-care liquid is alkalescence, the pH value 7.5 ± 0.3 of 25 ℃ of mensuration.
5. a kind of healht-care liquid that contains deep seawater according to claim 1 is characterized in that the beneficial element content in the said healht-care liquid is: zinc 0.0325-16.4 μ g/L in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; Selenium 0.0395-0.712 μ g/L; Chromium 0.104-4.54 μ g/L; Manganese 0.156-5.52 μ g/L.
6. a kind of healht-care liquid that contains deep seawater according to claim 1 is characterized in that the harmful element content in the said healht-care liquid is: plumbous < 5 μ g/>L in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; Hydrargyrum < 0. 5 μ g/>L; Arsenic < 5 μ g/>L; Cadmium < 1 μ g/>L.
7. a kind of healht-care liquid that contains deep seawater according to claim 1 is characterized in that in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product said deep seawater is taken from apart from beyond the 20km of coastline.
8. a kind of healht-care liquid that contains deep seawater according to claim 1 is characterized in that said fresh water sources Yu Haiyang deep water isolated fresh water after the reverse osmosis unit circulation in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product.
9. a kind of healht-care liquid that contains deep seawater according to claim 1 is in preparation prevention or the medicine of treatment metabolic syndrome or the application in the health product; It is characterized in that it is the healht-care liquid of 600-1000 ppm that diet is selected hardness for use to the less metabolism syndrome patient of the picked-up of mineral, is the healht-care liquid of 200-400 ppm otherwise select hardness.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106211749A (en) * | 2014-03-31 | 2016-12-07 | 株式会社阿丽浱欧 | Comprise the functional drinks of the mineral water of the high rigidity made from salty subsoil water or deep seawater |
| CN108095111A (en) * | 2017-12-17 | 2018-06-01 | 广州此壹海洋资源开发有限公司 | Alimentation composition comprising deep sea water minerals and the effect in postpartum lactagogue |
| CN109602764A (en) * | 2018-05-14 | 2019-04-12 | 山东中医药大学 | A kind of application of health promoting liquid in preparation prevention and treatment Alzheimer disease drugs |
| CN111184737A (en) * | 2020-02-28 | 2020-05-22 | 山东中医药大学 | Application of fucoidan and deep seawater in prevention and treatment of diabetes cognitive impairment |
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| TWI585046B (en) * | 2016-08-26 | 2017-06-01 | A mixture of high magnesium content concentrate and high magnesium content of drinking water |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106211749A (en) * | 2014-03-31 | 2016-12-07 | 株式会社阿丽浱欧 | Comprise the functional drinks of the mineral water of the high rigidity made from salty subsoil water or deep seawater |
| CN108095111A (en) * | 2017-12-17 | 2018-06-01 | 广州此壹海洋资源开发有限公司 | Alimentation composition comprising deep sea water minerals and the effect in postpartum lactagogue |
| CN108095111B (en) * | 2017-12-17 | 2021-06-18 | 锦上花医疗健康科技发展(广东)有限公司 | Nutritional composition containing deep seawater minerals and its application in promoting lactation after delivery |
| CN109602764A (en) * | 2018-05-14 | 2019-04-12 | 山东中医药大学 | A kind of application of health promoting liquid in preparation prevention and treatment Alzheimer disease drugs |
| CN111184737A (en) * | 2020-02-28 | 2020-05-22 | 山东中医药大学 | Application of fucoidan and deep seawater in prevention and treatment of diabetes cognitive impairment |
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