CN102935083A - Application of phenylethanoid glycoside monomer compounds - Google Patents
Application of phenylethanoid glycoside monomer compounds Download PDFInfo
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- CN102935083A CN102935083A CN2012105015911A CN201210501591A CN102935083A CN 102935083 A CN102935083 A CN 102935083A CN 2012105015911 A CN2012105015911 A CN 2012105015911A CN 201210501591 A CN201210501591 A CN 201210501591A CN 102935083 A CN102935083 A CN 102935083A
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Abstract
The invention relates to the field of traditional Chinese medicine, and discloses application of phenethyl alcohol glycoside monomer compounds savatiside E and savatiside A in preparing a medicine for preventing and treating myocardial ischemia and hypoxia. According to the invention, the ability of the savatiside E and savatiside A in clearing oxygen radicals is measured by a DPPH method, and the result indicates that the oxygen radicals can be cleared in a dose-dependent mode. The H2O2 and Na2S2O3-caused myocardial cell damage model is adopted to detect the influence on survival rate of the H2O2 and Na2S2O3-caused rat myocardial cell oxidative damage, and the result indicates that the survival rate of myocardial cells can be improved in a dose-dependent mode to suppress peroxidation damage. Moreover, the in-vivo experiments also indicate that the savatiside E and savatiside A can reduce the area of the coronary artery ligation-caused rat myocardial infarction.
Description
Technical field
The present invention relates to field of medicaments, relate to specifically the application of phenethyl alcohol glycosides monomeric compound, especially phenethyl alcohol glycosides monomeric compound savatiside E and the savatiside A application in preparation prevention and treatment myocardial ischemia ischemia diseases medicine.
Background technology
Herba monochasmatis, English name: Antlerpilose grass, be the herb of Scrophulariaceae Herba monochasmatis platymiscium MIAOMAO Herba monochasmatis (Monochasma savatieri Franch), plant is high 15～40 centimetres, all by silvery white close fine hair.Stem is thin and hard, is the shape branch of growing thickly.Leaf is verticillate, intensive to life or SANYE, the internode cripetura; The base portion leaf is flakey, long 3～5 millimeters; Upper leaf is narrow lanceolar, long 1～2 centimetre, and wide 1～3 millimeter, full edge, tip is point gradually, and base portion is narrow, stockless.Hua Dan is born in axil, and every flower has 2 pieces of linear squamellas, and is born in the calyx tube base portion; The calyx tubular, 5～7 millimeters of cylinder ministers, top 4 is split, and sliver and calyx tube are closely isometric, help 9～10; The corolla pale red, lip, long 2～2.5 centimetres.The upper lip pocketed is crooked, and 2 split, the blunt circle of sliver, and lower lip 3 splits, and middle sliver is longer, and there are 2 hooks in throat; Stamen 4, the last two; The ovary oval, style is elongated.The capsule Long Circle, tip is sharp-pointed, and tool 4 longitudinal furrows are wrapped in the calyx; Seed is yellow, and majority is tiny, flat ellipse.4～May of florescence.The Herba monochasmatis another name Radix Pulsatillae, thousandweight tower, hoary hair's hair etc. are distributed in the ground such as Jiangsu, Zhejiang, Jiangxi, Fujian, Taiwan, Hunan, Guangdong, economize widely distributed at Jiangxi, China, all have from reaching north in the south, often be born in hillside area without shade, the weeds or sylvan life, summer, autumn gather, using fresh herb or dry.
Herba monochasmatis bitter in the mouth, cool in nature has heat-clearing and toxic substances removing, cooling blood for hemostasis, the effects such as wind-expelling pain-stopping, and tcm clinical practice is usually used in flu, chronic bronchitis, hemoptysis is spitted blood, and has blood in stool pneumonia, gingivitis, pulpitis, acute mastitis, carbuncle, oral aphthae in children, the treatment of the diseases such as rheumatic arthritis.Chinese patent medicine kind " scorching peaceful granule " namely is take Herba monochasmatis as principal agent, and carries out compatibility with Herba Hedyotidis Diffusae, Herba Commelinae, has heat-clearing and toxic substances removing, and the effects such as anti-inflammtory anti-dysentery are used for the treatment of upper respiratory infection, tonsillitis, and urinary tract infection etc., clinical efficacy is definite.
The relevant report of the chemical constitution study of Herba monochasmatis is less at present; existing bibliographical information Herba monochasmatis comprises that iridoids, phenolic acids are (such as 4; 5-O-dicaffeoyl-quinic acid, 3,5-O-dicaffeoyl-quinic acid, chlorogenic acid etc.), the chemical constituent such as flavonoid, triterpenes, organic acid.These chlorogenic acids in the Herba monochasmatis, sesquiterpene lactones constituents, Flavonoid substances have the widely pharmacologically active such as antiinflammatory, sterilization according to the literature, can be used for the treatment of chronic tracheitis.Application number is in the Chinese patent of 201110459715.X, disclose the phenylethanoid glycoside in the Herba monochasmatis and had in the prevention of cardiovascular disease and the new purposes aspect the treatment, yet specifically which phenethyl alcohol glycoside monomer effect is not clear.
Most of cardiovascular disease is all relevant with ischemia, anoxia.The pathophysiological basis of myocardial ischemia ischemia is that the blood oxygen supply of cardiac muscle is unbalance, stops up or spasm because coronary atherosclerosis causes coronary stricture, makes cardiac muscle can not get enough blood oxygen, causes myocardial cell aging, impaired, and cardiac trigger is sick.And for example myocardial infarction is owing to coronary occlusion, blood flow interruption cause the caused myocardial necrosis of ischemia that cardiac muscle is serious and lasting.Ischemia, anoxia and cardiovascular disease reciprocal causation become the direct killer who affects life.Therefore, provide the new application of phenethyl alcohol glycoside monomer in preparation prevention and treatment myocardial ischemia ischemia diseases medicine, significant to the control of myocardial ischemia ischemia diseases.
Summary of the invention
The invention provides the new application of phenethyl alcohol glycosides monomeric compound, i.e. phenethyl alcohol glycosides monomeric compound savatiside E and the savatiside A application in preparation prevention and treatment myocardial ischemia ischemia diseases medicine.
The present patent application people adopts the method for Natural Medicine Chemistry, extracts and 2 kinds of new phenethyl alcohol glycosides monomeric compounds of isolation identification from Herba monochasmatis etc., has structure shown in the formula I,
Wherein, R is methyl or hydrogen.
In one embodiment; R is methyl; be that described phenethyl alcohol glycosides monomeric compound has structure shown in the formula II; its chemistry (R)-1 by name " O-2-(3; the 4-hydroxy phenyl)-2-hydroxy ethoxy-O-α-L-rhamanopyranosyl-(1 " ' → 2 ")-(6 " O-Resina Ferulae acyl group)-β-D-Glucose glycosides ((R)-1 "-O-2-(3; 4-dihydroxyphenyl)-2-hydroxyethoxy-O-α-L-rhamnopyranosyl-(1 " ' → 2 ")-(6 " O-feruloyl)-β-D-glucopyranoside); called after savatiside E
In one embodiment; R is hydrogen; be that described phenethyl alcohol glycosides monomeric compound has structure shown in the formula III; its chemistry (R)-1 by name " O-2-(3; the 4-hydroxy phenyl)-2-hydroxy ethoxy-O-α-L-rhamanopyranosyl-(1 " ' → 2 ")-(6 " the O-coffee acyl)-β-D-Glucose glycosides ((R)-1 "-O-2-(3; 4-dihydroxyphenyl)-2-hydroxyethoxy-O-α-L-rhamnopyranosyl-(1 " ' → 2 ")-(6 " O-caffeoyl)-β-D-glucopyranoside); called after savatiside A
Excessive free radical causes a series of biologicallies in body, the destruction that causes histiocyte, subcellular fraction and molecular structure, and expand gradually and cause function damage along with destroying level, causing cardiovascular disease, cancer and old and feeble etc., it is the pathologic basis that consists of a lot of diseases.Oxygen-derived free radicals also is the principal element that causes Damage of Myocardial Ischemia.Therefore, the present invention at first adopts the DPPH method to measure phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A to the removing ability of oxygen-derived free radicals.The result shows that phenethyl alcohol glycosides monomeric compound savatiside E can dose-dependent mode remove oxygen-derived free radicals in 3.125 μ g/mL-100 μ g/mL scopes, and wherein the oxygen radical removing rate is 85.05% when 100 μ g/mL.Phenethyl alcohol glycosides monomeric compound savatiside A also can dose-dependent mode remove oxygen-derived free radicals in 3.125 μ g/mL-100 μ g/mL scopes, the oxygen radical removing rate is 82.77% when 100 μ g/mL.Show that phenethyl alcohol glycosides monomeric compound savatiside E of the present invention and savatiside A have the effect of removing oxygen-derived free radicals, therefore the invention provides phenethyl alcohol glycosides monomeric compound savatiside E and the savatiside A application in the preparation oxygen free radical scavenger.
H
2O
2Be a kind of strong oxidizer, can form hydroxy radical, cause the rat myocardial cell oxidative damage.H
2O
2Causing the myocardial cell injury model is classical cell model in the myocardial ischemia-anoxemia damage.The present invention adopts H
2O
2Cause the myocardial cell injury model, detected described phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A to H
2O
2Cause the impact of rat myocardial cell oxidative damage survival rate.The result shows, described phenethyl alcohol glycosides monomeric compound savatiside E can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Phenethyl alcohol glycosides monomeric compound savatiside A also can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Show that phenethyl alcohol glycosides monomeric compound savatiside E and savatisideA all can resist H
2O
2Cause the rat myocardial cell damage, suppress H
2O
2The myocardial cell oxidative damage that causes.
Therefore the invention provides phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A at preparation H
2O
2Cause the application in the myocardial cell oxidative damage inhibitor.
Na
2S
2O
35H
2O is a kind of oxygen scavenger, and it can remove rapidly the oxygen that incorporates in the culture medium, can't the damaging cells film, and therefore, the present invention adopts Na
2S
2O
35H
2O induces the chemical hypoxic model, has detected described phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A to Na
2S
2O
3Cause the impact of rat myocardial cell oxidative damage survival rate.The result shows, described phenethyl alcohol glycosides monomeric compound savatiside E can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Phenethyl alcohol glycosides monomeric compound savatiside A also can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Show that phenethyl alcohol glycosides monomeric compound savatiside E and savatisideA all can resist Na
2S
2O
3Cause the rat myocardial cell damage, suppress Na
2S
2O
3The myocardial cell oxidative damage that causes.
Therefore the invention provides phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A at preparation Na
2S
2O
3Cause the application in the myocardial cell oxidative damage inhibitor.
The most basic prophylactico-therapeutic measures of myocardial ischemia ischemia diseases is to improve the blood confession, reduces the oxygen consumption, by remove or the antagonism harmful substance to the harmful effect of cardiac muscle to protect cardiac muscle.Oxygen-derived free radicals plays a crucial role in the pathogenesis of myocardial ischemia-anoxemia damage.Can produce a large amount of oxygen-derived free radicals during ischemia/reperfusion, oxygen-derived free radicals can cause lipid peroxidation, destroys cell membrane, and intracellular calcium overload causes myocardial cell injury, causes cardiac disorder and causes arrhythmia.H
2O
2Being the intermediate product of vivo oxidation metabolism, is again a kind of active oxygen simultaneously, excessive H
2O
2Can cause myocardial cell injury.Na
2S
2O
35H
2O is a kind of oxygen scavenger, excessive Na
2S
2O
3Also can cause myocardial cell injury.The above results shows that phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A have the effect of removing oxygen-derived free radicals simultaneously to H
2O
2And Na
2S
2O
3The rat myocardial cell anoxia-induced apoptosis that causes has protective effect, can obviously improve the myocardial cell form, suppresses peroxide injury, can reach the purpose of prevention and treatment myocardial ischemia ischemia diseases.
In addition; the present invention adopts the SD rat; following coronary artery occlusion causes the acute myocardial ischemia anoxia model, finds that phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A all can reduce myocardial infarction area, have protective effect to the myocardial ischemia in rats anoxia.Show that phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A have protective effect to the acute myocardial ischemia anoxia.
Therefore the invention provides phenethyl alcohol glycosides monomeric compound savatiside E and the savatiside A application in preparation prevention or treatment myocardial ischemia ischemia diseases medicine.Wherein, described myocardial ischemia ischemia diseases is coronary heart disease or angina pectoris.
Phenethyl alcohol glycosides monomeric compound savatiside E of the present invention and savatisideA prepare behind AB-8 resin, NM100 resin, polyamide and DAC post (dynamic axial post) purification after the MIAOMAO Herba monochasmatis extracts successively.
The present invention also provides the pharmaceutical preparation of a kind of prevention or treatment myocardial ischemia ischemia diseases, by the phenethyl alcohol glycosides monomeric compound savatiside E of effective dose or/and savatiside A and pharmaceutically acceptable adjuvant form.Those skilled in the art can be with described phenethyl alcohol glycosides monomeric compound savatiside E or/and savatiside A directly or indirectly adds pharmaceutically acceptable various adjuvants commonly used required when preparing different dosage form, such as disintegrating agent, lubricant, emulsifying agent, binding agent etc., with the conventional medicine formulation method, make common formulations such as oral liquid, capsule, varnish, cataplasma, spray, injection, granule, tablet, pill, powder or drop pill.The suitable mode administration of described preparation in can be in the following manner: in oral, spraying suction, rectally, nasal-cavity administration, vagina administration, topical, parenterai administration such as subcutaneous, vein, muscle, intraperitoneal, the sheath, in the ventricle, in the breastbone or intracranial injection or input, or by a kind of reservoir medication of outer planting, wherein preferred oral, intramuscular injection, intraperitoneal or intravenous application method.
Using dosage and the using method of the preparation of prevention of the present invention or treatment myocardial ischemia ischemia diseases depend on factors, comprise activity intensity, Time of Administration, metabolic rate, the course of disease order of severity and diagnosis and treatment doctor's the subjective judgment of patient's age, body weight, sex, natural health situation, nutriture, chemical compound.Those skilled in the art can easily determine using dosage and using method according to above-mentioned factor.
Description of drawings
Fig. 1 shows the chromatogram of the savatiside E that embodiment 1 makes;
Fig. 2 shows the chromatogram of the savatiside A that embodiment 2 makes.
The specific embodiment
The embodiment of the invention discloses phenethyl alcohol glycosides monomeric compound savatiside E and the savatiside A application in preparation prevention and treatment myocardial ischemia ischemia diseases medicine.Those skilled in the art can use for reference this paper content, suitably improve technological parameter and realize.Special needs to be pointed out is that all similarly replace and change apparent to those skilled in the art, they all are deemed to be included in the present invention.Application of the present invention is described by preferred embodiment, and the related personnel obviously can change or suitably change and combination application as herein described within not breaking away from content of the present invention, spirit and scope, realizes and use the technology of the present invention.
In order further to understand the present invention, the present invention is described in detail below in conjunction with embodiment.HPLC liquid phase chromatogram condition wherein: instrument: Agilent 1260 chromatograph of liquid; Chromatographic column: Kromasil C
18Column (4.6mm * 250i.d.; AKZONOBEL); Flow velocity 1.0mL/min, λ=330nm; Mobile phase: 0-35min methanol: water (0.1% formic acid)=35:65,35-45min methanol: water (0.1% formic acid)=90:10; Sample preparation: sample 1mg is dissolved in the 1mL methanol, shakes up to get final product.
The preparation of embodiment 1, savatiside E
(1) medicinal material extract
Herba monochasmatis medical material 50kg is cut into the segment of 1-2cm, 15 times of water gaging heating and refluxing extraction three times, each 2 hours.Merge extractive liquid,, 70 ℃ are evaporated to 50L(relative density 1.15-1.18), adding 95% ethanol 250L, the limit adds, and stir on the limit, and hold over night is got supernatant, and 70 ℃ are evaporated to 50L again.
(2) AB-8 resin purification
Resin demand: quality of medicinal material/resin quality=1:1;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:10 of resin bed;
Get the AB-8 resin 50kg that handles well, the diameter of packing into is in the rustless steel chromatography post of 30cm, and washing is stand-by.Extracting solution loading twice, static adsorption 12h.Wash first 4BV with water, wash 3BV with 60% ethanol again, wash 2BV with 90% ethanol, collect 50% ethanol position, reclaim solvent and get extractum 1000g.
(3) NM100 resin purification
Resin demand: quality of medicinal material/resin quality=1:0.5;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:10 of resin bed;
Get the NM100 resin 25kg that handles well, the diameter of packing into is in the rustless steel chromatography post of 20cm, and washing is stand-by.Get the extractum 25L water dissolution at AB-8 resin 50% ethanol position, loading twice, static adsorption 12h.Use first 25% methanol 4BV, wash 4BV with 50% methanol again, wash 2BV with 90% methanol, collect 50% methanol position, reclaim solvent and get extractum 800g.
(4) polyamide purifying
Polyamide consumption: quality of medicinal material/polyamide quality=1:0.1;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:5 of post bed;
Get the polyamide 10kg that handles well, the diameter of packing into is in the glass chromatography column of 10cm, and washing is stand-by.Get the extractum 10L water dissolution at NM100 resin 50% methanol position, loading.Use first 10% methanol 4BV, wash 4BV with 50% methanol again, wash 2BV with 90% methanol, collect 50% methanol position, reclaim solvent and get extractum 500g.
(5) DAC post (dynamic axial post) purification
ODS particle diameter: 3-5um;
ODS aperture: 5nm;
ODS filler: 3kg;
Each applied sample amount: 10g;
Elution speed: 30mL/min;
Mobile phase: 30% methanol, detect wavelength: 254nm.
Get the extractum 10L water dissolution at polyamide purifying 50% methanol position, loading according to the appearance time at first large peak, is collected this part eluent, 70 ℃ of rotating thin film vacuum concentration, lyophilizing and get final product.Make altogether Savatiside E and amount to 50g.The HPLC-UV testing result is seen Fig. 1, and purity is greater than 90%.
The preparation of embodiment 2, savatiside A
(1) medicinal material extract
Herba monochasmatis medical material 50kg is cut into the segment of 1-2cm, 15 times of water gaging heating and refluxing extraction three times, each 2 hours.Merge extractive liquid,, 70 ℃ are evaporated to 50L(relative density 1.15-1.18), adding 95% ethanol 250L, the limit adds, and stir on the limit, and hold over night is got supernatant, and 70 ℃ are evaporated to 50L again.
(2) AB-8 resin purification
Resin demand: quality of medicinal material/resin quality=1:1;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:10 of resin bed;
Get the AB-8 resin 50kg that handles well, the diameter of packing into is in the rustless steel chromatography post of 30cm, and washing is stand-by.Extracting solution loading twice, static adsorption 12h.Wash first 4BV with water, wash 3BV with 60% ethanol again, wash 2BV with 90% ethanol, collect 50% ethanol position, reclaim solvent and get extractum 1000g.
(3) NM100 resin purification
Resin demand: quality of medicinal material/resin quality=1:0.5;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:10 of resin bed;
Get the NM100 resin 25kg that handles well, the diameter of packing into is in the rustless steel chromatography post of 20cm, and washing is stand-by.Get the extractum 25L water dissolution at AB-8 resin 50% ethanol position, loading twice, static adsorption 12h.Use first 25% methanol 4BV, wash 4BV with 50% methanol again, wash 2BV with 90% methanol, collect 50% methanol position, reclaim solvent and get extractum 800g.
(4) polyamide purifying
Polyamide consumption: quality of medicinal material/polyamide quality=1:0.1;
Loading speed: 1mL/min.cm
2
Elution speed: 2-3mL/min.cm
2
The blade diameter length ratio 1:5 of post bed;
Get the polyamide 10kg that handles well, the diameter of packing into is in the glass chromatography column of 10cm, and washing is stand-by.Get the extractum 10L water dissolution at NM100 resin 50% methanol position, loading.Use first 10% methanol 4BV, wash 4BV with 50% methanol again, wash 2BV with 90% methanol, collect 50% methanol position, reclaim solvent and get extractum 500g.
(5) DAC post (dynamic axial post) purification
ODS particle diameter: 3-5um;
ODS aperture: 5nm;
ODS filler: 3kg;
Each applied sample amount: 10g;
Elution speed: 30mL/min;
Mobile phase: 30% methanol, detect wavelength: 254nm.
Get the extractum 10L water dissolution at polyamide purifying 50% methanol position, loading according to the appearance time at second large peak, is collected this part eluent, 70 ℃ of rotating thin film vacuum concentration, lyophilizing and get final product.Make altogether Savatiside A and amount to 200g.The HPLC-UV testing result is seen Fig. 2, and purity is greater than 90%.
Embodiment 3, DPPH method are measured the phenethyl alcohol glycosides monomeric compound to the removing ability of free radical
With the savatiside A of the savatiside E of embodiment 1 preparation and embodiment 2 preparations respectively adding distil water be made into the 1mg/mL sample solution, then doubling dilution becomes 100 μ g/mL, 50 μ g/mL, 25 μ g/mL, 12.5 μ g/mL, 6.25 μ g/mL and 3.125 μ g/mL and six concentration for subsequent use respectively.Simultaneously with vitamin E (VE) solution of 100 μ g/mL as positive control.
Get respectively the sample solution 100 μ L of above-mentioned variable concentrations in 96 hole ELISA Plate, each concentration is done three parallel holes, then adds respectively the DPPH test solution of 100 μ L1mM, and concussion 30s measures each hole light absorption value (Ap) under 37 ℃ and 517nm wavelength.The blank of measuring simultaneously the sample solution do not add DPPH absorbs light value (Ac) and adds DPPH but do not add the sample solution light absorption value (A max) of (replacing sample with 100 μ L methanol), experiment repetition three times.By the clearance rate of following formula calculating oxygen-derived free radicals,
Free radical scavenging activity (%)=[1-(Ap-Ac)/A max] * 100% statistical result sees Table 1.
Table 1 free radical scavenging activity
By Fig. 1 result as seen, the savatiside E of embodiment 1 preparation can dose-dependent mode remove oxygen-derived free radicals in 3.125 μ g/mL-100 μ g/mL scopes, and wherein the oxygen radical removing rate is 85.05% when 100 μ g/mL.Measure as stated above the savatiside A of embodiment 2 preparations to the removing ability of free radical, the result shows, the savatiside A of embodiment 2 preparations also can dose-dependent mode remove oxygen-derived free radicals, and the oxygen radical removing rate is 82.77% when 100 μ g/mL.
Embodiment 4, phenethyl alcohol glycosides monomeric compound are to H
2O
2Cause the impact of rat myocardial cell oxidative damage survival rate
With the savatiside A of the savatiside E of embodiment 1 preparation and embodiment 2 preparations respectively adding distil water be made into the 1mg/mL sample solution, then doubling dilution becomes 100 μ g/mL, 50 μ g/mL, 25 μ g/mL, 12.5 μ g/mL, 6.25 μ g/mL and 3.125 μ g/mL and six concentration for subsequent use respectively.Simultaneously with vitamin E (VE) solution of 100 μ g/mL as positive control.
Get rat myocardial cell (H
9C
2C
2-D is purchased from Chinese Academy of Sciences's cell bank), adjusting cell concentration is 1 * 10
5Individual/mL, be inoculated in 96 orifice plates every hole 100 μ L, 37 ℃, 5%CO
2After cultivating 24h in the incubator, random packet is tested.Experiment is divided into blank group, positive controls (vitamin E, 500 μ M), phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A variable concentrations group.Add phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A or culture medium after 12 hours, add H
2O
2(final concentration is 200 μ M, face with configuration, need lucifuge) modeling, behind the modeling 24h, the MTT that every hole adds 10 μ L 5mg/mL cultivates 4h, and supernatant inclines, the DMSO that adds 100 μ L, jolting 10min, the absorbance (OD490nm) with full-automatic microplate reader mensuration 490nm place is used for quantitative cell survival rate.
MTT is a kind of blue class dyestuff of tetramethyl azo azoles that can accept the H atom, and commodity are called tetrazolium bromide, are called for short MTT.Succinate dehydrogenase in the living cells mitochondrion can make ectogenic MTT be reduced to the bluish violet crystal of slightly solubility and be deposited in the cell, and dead cell is without this function.This bluish violet crystal can be dissolved by DMSO, and a larger absworption peak is arranged at the 570nm place, can measure its absorbance value (OD on microplate reader
570nm), this value can reflect living cells quantity and activity, OD indirectly
570nmThe value reduction shows that living cells quantity reduces, and cytoactive descends.
Calculate cell survival rate by following formula,
Cell survival rate %=experimental group OD570nm/ normal group OD570nm * 100% statistical result sees Table 2.
Table 2 phenethyl alcohol glycosides monomeric compound savatisideE and savatisideA are to H
2O
2The experiment of myocardial cell oxidative damage
Annotate: * P＜0.05, * * P＜0.01 is with the model group ratio.
By table 2 result as seen, H
2O
2Can obviously reduce cell survival rate, cell adds H
2O
2After 24 hours, cell survival rate is 61.23%.And the phenethyl alcohol glycosides monomeric compound savatisideE of embodiment 1 preparation can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 25 μ g/mL, 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Measure as stated above the phenethyl alcohol glycosides monomeric compound savatiside A of embodiment 2 preparations to the impact of myocardial cell survival rate, the phenethyl alcohol glycosides monomeric compound savatiside A that the result shows embodiment 2 preparation also can dose-dependent raising myocardial cell survival rate, when 25 μ g/mL, 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Show that phenethyl alcohol glycosides monomeric compound savatiside E and savatisideA can resist H
2O
2Cause the rat myocardial cell damage.
Embodiment 5, phenethyl alcohol glycosides monomeric compound are to Na
2S
2O
3Cause the impact of rat myocardial cell oxidative damage survival rate
With the savatiside A of the savatiside E of embodiment 1 preparation and embodiment 2 preparations respectively adding distil water be made into the 1mg/mL sample solution, then doubling dilution becomes 100 μ g/mL, 50 μ g/mL, 25 μ g/mL, 12.5 μ g/mL, 6.25 μ g/mL and 3.125 μ g/mL and six concentration for subsequent use respectively.Simultaneously with vitamin E (VE) solution of 100 μ g/mL as positive control.
Get rat myocardial cell (H
9C
2C
2-D is purchased from Chinese Academy of Sciences's cell bank), adjusting cell concentration is 1 * 10
5Individual/mL, be inoculated in 96 orifice plates every hole 100 μ L, 37 ℃, 5%CO
2After cultivating 24h in the incubator, random packet is tested.Experiment is divided into blank group, positive controls (vitamin E, 500 μ M), phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A variable concentrations group.Add phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A or culture medium after 12 hours, add Na
2S
2O
3(final concentration is 200 μ M, face with configuration, need lucifuge) modeling, behind the modeling 24h, the MTT that every hole adds 10 μ L 5mg/mL cultivates 4h, supernatant inclines, the DMSO that adds 100 μ L, jolting 10min is with the absorbance (OD490nm) at full-automatic microplate reader mensuration 490nm place, calculate cell survival rate by following formula
Cell survival rate %=experimental group OD570nm/ normal group OD570nm * 100%
Statistical result sees Table 3.
Table 3 phenethyl alcohol glycosides monomeric compound savatisideE and savatisideA are to Na
2S
2O
3The experiment of myocardial cell oxidative damage
Annotate: * P＜0.05, * * P＜0.01 is with the model group ratio.
By table 3 result as seen, Na
2S
2O
3Can obviously reduce cell survival rate, cell adds Na
2S
2O
3After 24 hours, cell survival rate is 60.24%.And the phenethyl alcohol glycosides monomeric compound savatiside E of embodiment 1 preparation can dose dependent in the scope of 3.125 μ g/mL-100 μ g/mL raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Measure as stated above the phenethyl alcohol glycosides monomeric compound savatiside A of embodiment 2 preparations to the impact of myocardial cell survival rate, the phenethyl alcohol glycosides monomeric compound that the result shows embodiment 2 preparation also can dose-dependent raising myocardial cell survival rate, when 50 μ g/mL and 100 μ g/mL concentration, its survival rate has been compared significant difference with model group.Show that phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A can resist Na
2S
2O
3Cause the rat myocardial cell damage.
Embodiment 6, phenethyl alcohol glycosides monomeric compound are to the protective effect of Acute Myocardial Ischemia in Rats damage due to the coronary ligation
Get 80 of SD rats, male and female half and half are divided into 8 groups at random, sham operated rats, model group and phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A various dose group (15mg/kg, 30mg/kg, 60mg/kg) group, 10 every group.Phenethyl alcohol glycosides monomeric compound savatiside E and savatiside A various dose group all give the savatiside E of embodiment 1 preparation and the savatiside A of embodiment 2 preparations by the body weight gavage, sham operated rats, model group gavage give the distilled water of equivalent, once a day, continuous 7 days.About last administration 45min, lumbar injection pentobarbital sodium anesthetized rat, dorsal position is fixed, and measures the front electrocardiogram of operation, do transverse incision through breastbone and cut off skin, separating muscle takes out heart from intercostal, the following coronary artery occlusion left anterior descending branch is extruded air in the thoracic cavity, sews up rapidly and closes breast.Postoperative 24h, the pentobarbital sodium anesthetized rat is got blood, and it is dirty to core, and puts-20 ℃ of freezing 20min, and being cut into thickness is the 4-5 sheet of 2mm, puts into 1%TTC solution and dyes, and measures myocardial infarction area, the results are shown in Table 4.
Acute Myocardial Ischemia in Rats experimental result due to table 4 coronary ligation
Annotate: * P＜0.05, * * P＜0.01, * * P＜0.001 and model group ratio
By table 4 result as seen, behind the model group coronary ligation 24h, infarct size about 33.12 ± 4.14%, gastric infusion phenethyl alcohol glycosides monomeric compound savatiside E(30mg/kg, 60mg/kg) the remarkable capable of reducing myocardial infarction area of energy, myocardial infarction area is 21.02 ± 2.17% when 60mg/kg dosage, compares with model group, and significant difference is arranged.Phenethyl alcohol glycosides monomeric compound savatiside A(30mg/kg, 60mg/g) also remarkable capable of reducing myocardial infarction area, myocardial infarction area is 20.14 ± 3.05% when 60mg/kg dosage, has compared significant difference with model group.
The explanation of above embodiment just is used for helping to understand application of the present invention and core concept thereof.Should be pointed out that for those skilled in the art, under the prerequisite that does not break away from the principle of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of claim of the present invention.
Claims (7)
1. the application of chemical compound shown in the formula I in preparation prevention and treatment myocardial ischemia ischemia diseases medicine,
Wherein, R is methyl or hydrogen.
2. according to claim 1 described application is characterized in that, described myocardial ischemia ischemia diseases is coronary heart disease or angina pectoris.
3. the application of chemical compound shown in the formula I in the preparation oxygen free radical scavenger,
Wherein, R is methyl or hydrogen.
4. chemical compound shown in the formula I is at preparation H
2O
2Cause the application in the myocardial cell oxidative damage inhibitor,
Wherein, R is methyl or hydrogen.
5. chemical compound shown in the formula I is at preparation Na
2S
2O
4Cause the application in the myocardial cell oxidative damage inhibitor,
Wherein, R is methyl or hydrogen.
6. a pharmaceutical preparation that prevents or treat the myocardial ischemia ischemia diseases is characterized in that, formed by chemical compound shown in the formula I of effective dose and pharmaceutically acceptable adjuvant,
Wherein, R is methyl or hydrogen.
7. according to claim 6 described pharmaceutical preparation is characterized in that, described pharmaceutical preparation is oral liquid, capsule, varnish, cataplasma, spray, injection, granule, tablet, pill, powder or drop pill.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104922138A (en) * | 2015-06-04 | 2015-09-23 | 苏州大学 | Novel use of phenylethanoid glycoside compound Savatiside A |
| CN105541932A (en) * | 2016-01-25 | 2016-05-04 | 南阳师范学院 | Phenethyl alcohol glycoside compound extracted from common cephalanoplos herb and application |
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|---|---|---|---|---|
| CN102488779A (en) * | 2011-12-31 | 2012-06-13 | 苏州大学 | Application of extract of Antlerpilose grass |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102488779A (en) * | 2011-12-31 | 2012-06-13 | 苏州大学 | Application of extract of Antlerpilose grass |
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| LI，M ET.AL.: "《phenylethanoid glycosides from monochasma savatieri and their anticomplement activity through the classical pathway》", 《PLANTA MED.》, vol. 78, no. 12, 29 June 2012 (2012-06-29), pages 1381 - 1386 * |
| 吴培培 等: "《苯乙醇苷类化合物的研究进展》", 《医药导报》, vol. 30, no. 10, 31 October 2011 (2011-10-31), pages 1316 - 1318 * |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104922138A (en) * | 2015-06-04 | 2015-09-23 | 苏州大学 | Novel use of phenylethanoid glycoside compound Savatiside A |
| CN105541932A (en) * | 2016-01-25 | 2016-05-04 | 南阳师范学院 | Phenethyl alcohol glycoside compound extracted from common cephalanoplos herb and application |
| CN105541932B (en) * | 2016-01-25 | 2017-12-15 | 南阳师范学院 | Benzyl carbinol glycoside compound extracted from field thistle and its production and use |
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