CN110101710A - The purposes of Verbascoside and/or purplestem privet leaf glycosides A in medicine preparation - Google Patents
The purposes of Verbascoside and/or purplestem privet leaf glycosides A in medicine preparation Download PDFInfo
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Abstract
The invention discloses a kind of purposes of Verbascoside and/or purplestem privet leaf glycosides A in preparation treatment of vascular endothelial cell inflammatory damage drug.The present invention has the advantages that Verbascoside and/or purplestem privet leaf glycosides A have the vascular endothelial cell vigor that can improve CVF induced damage; and there is significant inhibiting effect to inflammation mediators; the effect for reducing adhesion factor level has the effects that significantly to protect to the damage of LPS induction HMEC cell.Verbascoside and/or purplestem privet leaf glycosides A can be used for the preparation of related drugs, have great importance to exploitation related drugs.
Description
Technical field
The present invention relates to a kind of Verbascoside and/or the new medicine use of purplestem privet leaf glycosides A, especially Verbascosides and/or purple
Application of the stem Ligustrum lucidum Ait A in preparation treatment of vascular endothelial cell inflammatory damage drug.
Background technique
Vascular endothelial cell (VEC) is one layer of selective permeable barrier being covered between vascular wall and blood flow, energy
The substance of synthesis and regulation of secretion Coagulation-fibrinolysis, the factor for adjusting antiotasis and cell factor etc., in blood vessel shape
At (EndemannDH, the etal.Endothelialdysfunction.JAm of playing an important role in, wound healing and inflammatory reaction
SocNephrol.2004,15 (8): being the pith for resisting exotic invasive first layer barrier 1983-92.).When it is sensed
When external irritant, a variety of factors are synthesized and release, to adjust and play such as hemostasis, cell growth, vessel retraction and diastole, inflammation
The functions such as disease process.In inflammatory process, the phenotype of endothelial cell is activated, further discharge von Willebrand factor,
Selectin, proinflammatory cytokine and adhesion molecule etc., the vasopermeability of plasma protein increase, proinflammatory cytokine, chemotactic because
Sublist adjusts adhesion molecule to increase, vascular endothelial cell is broken function point analysis stable state up to rising.In proinflammatory factor and other thorns
Under the long term for swashing factor, vascular endothelial cell will appear inflammatory damage, and showing as inflammatory factor includes intercellular adhesion point
Son (ICAM-1), blood vessel endothelium adhesion molecule (VCAM-1), palatelet-selectin (P-selectin), E-Selectin (E-
Selectin), the release of interleukins IL-6 etc..Vascular endothelial cell damage results in Dysfunction of vascular endothlial cells,
The a variety of and closely related metabolic disorder of vascular function (JamwalS., etal., endotheliumdysfunction:
aconservativetargetinmetab olicdisorders.Inflamm.Res.2018.).At present, VEC it is impaired by
It is considered as that a variety of diseases such as wound, shock, infection, cardiovascular disease, tumour and acute lung injury and syndrome occur, development is total to
Same pathologic basis.
Thus, vascular endothelial cell is protected, is that prevention and treatment are a variety of closely related with Dysfunction of vascular endothlial cells
One important channel of disease.
Finding from natural products, there is vascular endothelial cell damage to have the molecule of protective effect, be prepare for treat with
The important channel of vascular endothelial cell damage associated disease drug.Traditional Chinese medicine by multiple target point, multipath, with anti-oxidation stress,
Adjust rouge, anti-inflammatory etc. intervention vessel endothelial injuries significant effect.What is such as had found from Chinese medicine has improvement blood vessel endothelium thin
(Wang Shufeng etc., ligustrazine is to type 2 diabetic patient's vascular endothelial cell for the ligustrazine of born of the same parents' function and prevention and treatment diabetic angiopathy
The research of effect, clinical medicine practice, 2009,18 (5): 340-341.), Puerarin (TengY, etal., Protectiveef
Fectofpueracinondiabeticretinophathyinrats, MolBiolRep, 2009,36 (5): 1129-1133),
(Luo Xianling etc., ginseng sapoglycoside Rg 3 express the lower retinal endothelial cell proliferation of high sugar and ICAM-1 to ginseng sapoglycoside Rg 3
Influence, international ophthalmology magazine, 2009,9 (10): 1865-1867.), (Liu Ping etc., polysaccharides is to diabetes rat for polysaccharides
The influence of kidney PKC-bII and IV expression of collagen, Chinese Medicine pharmaceutical journal, 2008,28 (13): 1544-1547.), hexichol
Ethylene glycosides (Li Cairong etc., Stibene-glucoside to the adjustment effect of diabetes rat blood lipid and inflammatory factor, when treasure's traditional Chinese medical science traditional Chinese medicines it is miscellaneous
Will, 2010,21 (9): 2243-2244.), tanshinone IIA the protective effect of blood vessel endothelium is presented under high sugared factor induction
(effect of the .ATP such as Hu Haiyan sensitive potassium channel in tanshinone IIA confrontation high glucose induction function of vascular endothelium damage, China are old
Year learns magazine, 2015,35 (1): 174-176.) etc., there is the asiatic acid (Zhu Lihua of protective effect to acute renal injury in mice
Deng, influence and mechanism of the asiatic acid pretreatment to pyemia acute renal injury in mice, Shandong medicine, 2017,57 (30): 10-
And the chlorogenic acid of Human Umbilical Vein Endothelial Cells inflammatory damage protective effect (Sun Qianyun etc., the inflammation based on blood vessel endothelium inflammatory damage 13.)
Venereal disease disease protective agents and its application, CN108635345A) etc..
Small-leaf Kuding tea is that the southwests such as Sichuan, Yunnan, Guizhou are commonly expected on behalf of the tea, derives from Oleaceae Ligustrum
The leaf of plant Ligustrum robust (Ligustrum robustum).Small-leaf Kuding tea has reducing blood lipid, blood pressure lowering and other effects, therefrom
The effective component being separated to is phenylethanoid glycoside, have the pharmacological actions such as anti-oxidant, immunological regulation, reducing blood lipid (He Zhendan,
The new opplication of phenyl propanoid total glycoside, Chinese invention patent, patent No. CN101357145B), representative ingredient is Verbascoside
(Acteoside) and purplestem privet leaf glycosides A (Ligupurpu rosideA) (He Zhendan, Liu Yuqing, Yang Chongren.Zhaotong County, Yunnan produces bitter
The glycocide ingredient of fourth tea, Yunnan plant research, 1992,14 (3): 328-336.) (attached drawing 1), wherein Verbascoside has anti-suppression
Strongly fragrant (Gao Li, Yan Ming, Huo Shixia, purposes of the acteoside in preparation antidepressant, Chinese invention patent, application number
20160390189.9), antianxiety (Gao Li, Yan Ming, Huo Shixia, acteoside are preparing the purposes in anxiolytic drugs, in
State's patent of invention, application number 201611145131.4), anti-senile dementia (Yan Ming, Huo Shixia, Gao Li, Peng Xiaoming, Yi Huang, class leaf
Purposes of the cimicifugoside in preparation prevention and treatment Alzheimer disease drugs, Chinese invention patent, application number 201210240638.3),
(go to the field rich department, Tanaka's profit department, Dan Shaojie, and village's well is promoted, hyperlipemia prophylactic and therapeutic agent, Chinese invention patent, application for reducing blood lipid
Number 200810089320), lipase inhibits (Wu Xu oak, He Zhendan, Wu Haiqiang, a kind of lipase inhibitor and its extracting method
With application, Chinese invention patent, application number 201510704758.8) the effects of, but they are being based on vascular endothelial cell inflammatory
Damage prevents and treats the purposes in relevant drug, has no and has been reported that.
Summary of the invention
The object of the present invention is to provide Verbascosides and/or purplestem privet leaf glycosides A in preparation treatment of vascular endothelial cell inflammatory
New application in damage medicine.
The application of Verbascoside and/or purplestem privet leaf glycosides A in preparation treatment of vascular endothelial cell inflammatory damage drug.
In application above-mentioned, the vascular endothelial cell inflammatory damage includes acute lung injury, pyemia, injury of kidney, moves
Pulse atherosclerosis and diabetic vascular complications.
The preparation method of Verbascoside of the present invention, purplestem privet leaf glycosides A, is with Ligustrum robust (Ligustrum
Robustum), privet (Ligustrum japonica), Herba Cistanches (Cistanche deserticola) He Guanhua meat
One or more of desert cistanche (Cistanche tubulosa) etc. and other raw materials for containing both compounds use existing
What technology was extracted.
The molecular structural formula of Verbascoside of the present invention is as follows:
The molecular structural formula of purplestem privet leaf glycosides A of the present invention is as follows:
Beneficial effects of the present invention
Experimental result shows that Verbascoside and/or purplestem privet leaf glycosides A have the blood vessel endothelium that can improve CVF induced damage thin
Born of the same parents' vigor, and there is significant inhibiting effect to inflammation mediators, the effect of adhesion factor level is reduced, LPS is induced
The damage of HMEC cell has the effects that significantly to protect.Verbascoside and/or purplestem privet leaf glycosides A can be used for the system of related drugs
It is standby, have great importance to exploitation related drugs.
Detailed description of the invention
Attached drawing 1: the chemical structural formula of Verbascoside (acteoside) and purplestem privet leaf glycosides A (Ligupurpuroside A)；
Attached drawing 2: the influence of Verbascoside and purplestem privet leaf glycosides A to the vascular endothelial cell vigor of CVF induced damage；
Attached drawing 3: the vascular endothelial cell inflammation adhesion factor ICAM- of Verbascoside and purplestem privet leaf glycosides A to CVF induced damage
1 influence；
Attached drawing 4: the vascular endothelial cell inflammation adhesion factor VCAM- of Verbascoside and purplestem privet leaf glycosides A to CVF induced damage
1 influence；
Attached drawing 5: the shadow of Verbascoside and purplestem privet leaf glycosides A to the vascular endothelial cell inflammation E-selectin of CVF induced damage
It rings；
Attached drawing 6: the shadow of Verbascoside and purplestem privet leaf glycosides A to the vascular endothelial cell inflammation TNF-α factor of CVF induced damage
It rings；
Attached drawing 7: the vascular endothelial cell inflammation medium IL-6 factor of Verbascoside and purplestem privet leaf glycosides A to CVF induced damage
Influence；
Attached drawing 8: Verbascoside and purplestem privet leaf glycosides A are to NF- κ Bp65 phosphorylation in the vascular endothelial cell of CVF induced damage
The influence of effect；
Attached drawing 9: the influence of Verbascoside and purplestem privet leaf glycosides A to the vascular endothelial cell vigor of LPS induced damage；
Attached drawing 10: the influence of Verbascoside and purplestem privet leaf glycosides A to the vascular endothelial cell vigor of Ox-LDL induced damage；
Attached drawing 11: Verbascoside and purplestem privet leaf glycosides A to ICAM-1, P-selectin in mice with acute lung injury serum,
TNF-α, influence (1, Verbascoside of the parameters such as IL-6；2, purplestem privet leaf glycosides A；3, total glycosides TGR)；
Attached drawing 12: Verbascoside and purplestem privet leaf glycosides A are to ICAM-1, P- in mice with acute lung injury BALF supernatant
Selectin, TNF-α, influence (1, Verbascoside of the parameters such as IL-6；2, purplestem privet leaf glycosides A；3, total glycosides TGR)；
Attached drawing 13: Verbascoside and purplestem privet leaf glycosides A mice with acute lung injury are administered the shadow that front and back pathologic is sliced
It rings: normal group (A), model group (B), positive control PDTC group (C), Verbascoside group (D), purplestem privet leaf glycosides A group (E) and total glycosides
TGR group (F)；
Attached drawing 14: the shadow of Verbascoside and purplestem privet leaf glycosides A to BUN, Cr level in LPS induction acute kidney injury mice serum
Ring (1, Verbascoside；2, purplestem privet leaf glycosides A；3, total glycosides TGR).
Specific embodiment
Below with reference to embodiment, the present invention is further illustrated, but is not intended as the foundation limited the present invention.
The embodiment of the present invention
Embodiment 1
The preparation of Verbascoside, purplestem privet leaf glycosides A
Small-leaf Kuding tea (Ligustrum robustum) dried leaf 10kg, after crushing, with 95% ethyl alcohol extract (25L ×
2), merge extracting solution twice, be concentrated under reduced pressure, obtain medicinal extract.Medicinal extract is scattered in 5L water, filtering, pretreated AB-8 on filtrate
Large pore resin absorption column is first eluted with water until wash water color is shallower, then with 50% ethanol elution, 3 column volumes, collects
50% ethanol eluate is concentrated under reduced pressure, and obtains total glycosides rich in benzyl carbinol glycosides.Total glycosides is taken, using high-speed counter-current extraction-chromatography
(HSCCC) method is separated, and extraction eluent is ethyl acetate-n-butanol-water (5:2:5), and upper phase is as stationary phase, lower phase
As mobile phase, first separation can respectively obtain Verbascoside, purplestem privet leaf glycosides A, HPLC detection, and purity is respectively 95.2% He
97.5%.
Embodiment 2
The preparation of extract (total glycosides) containing Verbascoside and purplestem privet leaf glycosides A
Small-leaf Kuding tea (Ligustrum robustum) dried leaf 10kg, after crushing, with 95% ethyl alcohol extract (25L ×
2), merge extracting solution twice, be concentrated under reduced pressure, obtain medicinal extract.Medicinal extract is scattered in 5L water, filtering, pretreated AB-8 on filtrate
Large pore resin absorption column is first eluted with water until wash water color is shallower, then with 50% ethanol elution, 3 column volumes, collects
50% ethanol eluate is concentrated under reduced pressure, and obtains total glycosides (TGR) rich in Verbascoside and purplestem privet leaf glycosides A.With homemade Verbascoside
With purplestem privet leaf glycosides A sterling as standard items, HPLC external standard method content, in total glycosides (TGR) Acteoside and
The content of Ligupurpuroside A is respectively 37.2% and 31.0%.
Experimental example:
1. the Nnti-cobratoxin factor (CVF) the induction of vascular endothelial cellular damage pharmacology of Verbascoside and purplestem privet leaf glycosides A are real
It tests
1.1 Verbascosides, purplestem privet leaf glycosides A compound stimulate CAC the influence of cell viability after HMEC:
[Li Chaosheng, Sun Qianyun, three kinds of chemical small molecules cause Adhesion Molecules on Endothelial Cells to complement bypass-activation to reference literature
The intervention and Mechanism Study Chinese Pharmacological Bulletin of expression, 2015,31 (10): 1421-6.] method, first by normal human serum
(NHS) and after CVF mixing, 37 DEG C of water-bath 30min are put into, CVF activation product (CAC) of NHS are prepared into, then by people's capilary
Endothelial cell (HMEC) is with 1 × 105cells·well-196 porocyte culture plates are inoculated in, supernatant, administration group are abandoned in culture afterwards for 24 hours
Be separately added into 20 μ L various concentration samples, 20 μ L physiological saline are added in Normal group and model group, after cultivating 2h, model group and
60 μ L CAC are added in administration group, and each hole cultivating system total volume is 200 μ L, after continuing culture for 24 hours, detect every group using mtt assay
Cell survival rate.
Fig. 2 is the results show that Verbascoside, purplestem privet leaf glycosides A cause cellular damage to have protection to due to CAC stimulation HMEC respectively
Effect, can improve cell viability, and show apparent dose-effect relationship significantly.
1.2 Verbascosides, purplestem privet leaf glycosides A compound stimulate the intracellular adhesion factor and inflammatory factor after HMEC to CAC
It influences:
It influences in experiment after culture for 24 hours, to take supernatant after identical method grouping, be centrifuged, sample by cell viability in 1.1
Product packing after, be put into -80 DEG C freeze it is spare.According to kit illustrate measure ICAM-1, VCAM-1, E-selectin, IL-6,
IL-1 and TNF-α.
If Fig. 3-Fig. 7 is shown, after CAC stimulates HMEC, intracellular adhesion factor ICAM-1, VCAM-1, selectin E-
Selectin and inflammatory factor IL-6, TNF-α all significantly raise, and after giving Verbascoside, purplestem privet leaf glycosides A, can significantly lower
These inflammatory factors are horizontal, illustrate that the inflammatory reaction in vascular endothelial cell can be reduced, to reach cytoprotection.
1.3 Verbascosides, purplestem privet leaf glycosides A compound stimulate CAC the influence of cell inner expression NF- κ B after HMEC:
It takes 1 μ L recombinant plasmid (1ng) to be added in 100 μ L competence DH5 α suspensions, mixes, after ice-water bath 30min, 42 DEG C
Water-bath 90s takes out, then ice-water bath 3min, and 900 μ L LB culture mediums are then added, is placed in 37 DEG C of shaken cultivation 45min, takes bacterium solution
100 μ L are spread evenly across in screening flat board, are set 37 DEG C of overnight incubations, are chosen and expanded with white colony, and by specification extracts matter
Grain.HMEC cell is with 1 × 105Cellswell-1 is inoculated in 96 orifice plates, and supernatant is abandoned in culture afterwards for 24 hours, is cultivated with serum-free 1640
Base is washed 2 times, and 90 μ L, 1640 culture medium containing serum is then added, is turned by Lipofecter lipofectamine specification
Dye.It is specific as follows: NF- κ B expression plasmid and internal reference plasmid and liposome reagent are mixed with 1640 culture medium of serum-free RPMI
Even, (20-25) DEG C is incubated for 20min.Then 10 μ L of the transfection cocktail is added in every hole, removes supernatant, medicine group after transfecting 20h
It is separately added into sample, Normal group and model group are added physiological saline, and 37 DEG C, 5%CO230 μ L are abandoned after being incubated for 2h in incubator
Supernatant is added 30 μ L CAC, makes each 100 μ L of hole cultivating system total volume, while the incubation object that CVF and INHS is arranged is opposed
According to continuing to cultivate 4h and detect fluorescence intensity by double luciferase report gene detection kit specifications, be obtained by calculation each
The opposite Transcription Activity In Nuclei of group.
Such as Fig. 8, the result shows that, after CAC stimulates HMEC, the relatively core transcriptional level of intracellular NF- κ B is improved, and shows its inflammation
Disease reaction occurs, and Verbascoside is added, after purplestem privet leaf glycosides A, and Human Umbilical Vein Endothelial Cells are because of NF- κ B caused by complement bypass-activation product
P65 phosphorylation all shows the reduction of certain inhibiting effect (P < 0.05) NF- κ B relatively core transcriptional level, and explanation can pass through
NF- kB pathway inhibits inflammatory reaction degree.
The above experimental result shows that Verbascoside, purplestem privet leaf glycosides A can improve the vascular endothelial cell of CVF induced damage
Vigor, and there is significant inhibiting effect to inflammation mediators, adhesion factor level is reduced, illustrates that this two compound can be protected
Vascular endothelial cell inflammatory damage is protected, while prompting may be related with NF- κ B access adjusting.
The inflammatory damage of vascular endothelial cell caused by complement system excessive activation is the common pathological characters of a variety of diseases,
Such as pyemia, acute lung injury, injury of kidney and atherosclerosis, diabetic complication inflammatory injury are all and blood vessel
Endothelial cell damage has close association.Inflammatory reaction is reduced, vascular endothelial cell damage is protected, is the important prevention and treatment of these diseases
Method.The above experimental result prompt, Verbascoside and purplestem privet leaf glycosides A can be used for the preparation of related drugs, to exploitation related drugs
Have great importance.
2. the anti-LPS induction of vascular endothelial cellular damage pharmacological evaluation of Verbascoside and purplestem privet leaf glycosides A
HMEC is pressed 1 × 105A cell mL-1Density be inoculated on 96 orifice plates, set 37 DEG C, 5%CO2It is incubated in incubator
It educates, after culture for 24 hours, changes serum-free RPMI-1640 culture solution and continue to be incubated for for 24 hours, cell is divided into Normal group and LPS is damaged
Group.Normal group: 1640 culture medium of serum-free is added；LPS damage group: the final concentration of 300mgL containing LPS is added-1Without blood
Clear 1640 culture medium, each concentration set 5 parallel holes, and action time 12,24,48h, experiment is repeated 4 times.Mtt assay detection is thin
Born of the same parents' survival rate.After HMEC fusion growth is at single layer, 0.1molL-1PBS rinse 2 times, with 0.25% trypsin digestion point
From with 1 × 105A cell mL-196 orifice plates are inoculated in, are randomly divided into blank control group, model group (LPS), medicine group, each
Concentration is all provided with 5 multiple holes, and experiment is repeated 4 times.It cultivates for 24 hours in 1640 complete mediums containing 10% fetal calf serum, then uses
RPMI1640 containing serum-free continues culture for 24 hours.After being previously added the drug culture cell of above-mentioned final concentration for 24 hours, LPS is added
Model group and each medicine group, LPS stimulate cell 48h, MTT to measure cell viability.
Such as Fig. 9 the results show that comparing with model group, Verbascoside, purplestem privet leaf glycosides A molecule are to LPS induction HMEC cell
Damage has significant protective effect.
3. the anti-Ox-LDL induction of vascular endothelial cellular damage pharmacological evaluation of Verbascoside and purplestem privet leaf glycosides A
The preparation of Ox-LDL: the LDL prepared in advance is put into bag filter, and the CuSO that concentration is 10 μm of ol/L is added4, put
It sets in 4 DEG C of environment for 24 hours to be dialysed and be oxidized to Ox-LDL.After placing for 24 hours, it is anti-to terminate that the EDTA of 100 μm of ol/L is added
It answers, and after heat sterilization, is placed under 4 DEG C of environment and saves backup.Blank control group, model group, low dose are divided into this experiment
Amount group, middle dose group, 5 groups of high dose group.The culture medium of control group is+5% serum of routine DMEM liquid, and the culture medium of other groups is
Conventional+5% serum+100mg/LQx-LDL of DMEM liquid is simultaneously carried out under the conditions of randomization, by the culture cell inoculation after grouping in
24 orifice plates carry out Experiment intervention processing after cell grows to 90% fusion.Five set carries out culture for 24 hours, mtt assay inspection
Survey cell viability.
Such as Figure 10 the results show that after Ox-LDL is handled, model group vascular endothelial cell existence activity is significantly lower than blank
Control group, low, middle and high dose groups vascular endothelial cell existence activity are above model group, and vascular endothelial cell existence activity
It increases and increases with saponin concentrations.
4. the resisting acute lung injury pharmacological evaluation of Verbascoside and purplestem privet leaf glycosides A
Using the CVF specific Immune Complexes Activating Complement alternative route of 35 μ g/kg of tail vein injection, inducing mouse acute lung injury
(Sun Qianyun etc., based on the inflammatory conditions protective agents of blood vessel endothelium inflammatory damage and its application, CN108635345A).It sets up
Blank control group (0.2%CMCNa control), model group, positive drug control group (pyrrolidines disulfide group formates, PDTC group),
High dose group (300mg/kg), low dose group (100mg/kg), totally 5 groups, every group 12, gastric infusion.Each group mouse prevent to
Medicine 7 days, after the 7th day administration 1h, then give CVF induction acute inflammation.Eyeball is plucked after 1h takes blood centrifugation to prepare serum, packing
It is frozen in -80 DEG C；De- neck execution mouse progress bronchoalveolar lavage after blood is taken to obtain BAL fluid (BALF), BALF
Take supernatant to dispense, -80 DEG C freeze it is spare.After taking right lung to weigh, superior lobe of right lung is placed in -80 DEG C and is frozen, measured for MPO,
Specific method is carried out according to kit specification.Middle lobe of right lung claims weight in wet base, then with 70 DEG C of baking 48h to constant weight, according to formula:
(weight in wet base-dry weight)/weight in wet base 100% calculates moisture content of lung.Inferior lobe of right lung is placed in 10% formalin fixed, row pathological section
It checks.Take -80 DEG C of mice serums frozen, BALF supernatant testing index ICAM-1, P-selectin, TNF-α, IL-6 etc..
In this experiment, instrument medicine of the CVF as specific activating complement alternative pathway, by specifically mouse being activated to mend
Body alternative pathway, leads to acute lung injury.ALI mouse lung tissue index of correlation and normal group compare, BALF cell number and MPO
Content significantly increases.It is compared with model group, after positive controls and administration group treatment, can substantially reduce BALF cell number
Mesh reduces MPO content.Hou Ge group moisture content of lung is administered without significant change, as shown in table 1.
The influence of 1 Verbascoside of table and purplestem privet leaf glycosides A to acute lung injury model mouse lung tissue index of correlation
#: it compares, P < 0.01, *: being compared with model group, P < 0.01 with normal group.(n=8, M ± SD)
And inflammation index testing result such as Figure 11 and Figure 12 are shown, Verbascoside and/or purplestem privet leaf glycosides A are to alternative route spy
The inflammation index that the chmice acute injury of lungs of anisotropic activator is shown have significant improvement result, especially significantly improve with
Blood vessel inner skin cell function closely related ICAM-1, P-selectin etc. indexs.Illustrate Verbascoside and/or purplestem privet leaf glycosides A
The damage of vascular endothelial cell can be improved in vivo.Meanwhile pathological section is the results show that normal organization is normal, rare inflammation
Property cellular infiltration；The visible interstitial lung of model group is broadening, and alveolar is slightly expanded, universal visible inflammatory cell infiltration, and Verbascoside and/
Or the inflammatory cell infiltration of purplestem privet leaf glycosides A administration group and positive drug PDTC group is substantially reduced, as shown in Fig. 13.
It is known in acute lung injury, pyemia, ischemical reperfusion injury, burning (wound) wound, systemic inflammatory response syndrome, sugar
It urinates in the diseases such as disease, complement bypass-activation leads to that endothelial cell is inflamed reaction and damage is that above-mentioned many related diseases are levyd disease
In important general character mechanism.Based on other symptom and acute lung injury above-mentioned aspect general character pathologic basis, Verbascoside and/or
Purplestem privet leaf glycosides A can be applied equally to the prevention and treatment of these related symptom.
5. Verbascoside and the anti-LPS of purplestem privet leaf glycosides A induce injury of kidney pharmacological evaluation
The BALB/C mice that weight is 18-22g is randomly divided into 6 groups, every group 10, respectively blank control group, model
Group (LPS 10mgKg-1), positive controls (dexamethasone 5mgKg-1), administration group (200mgKg-1) (contain Verbascoside
Group, purplestem privet leaf glycosides A group, total glycosides TGR group).Give drug treatment within 3 hours before LPS modeling, 3 hours after modeling, 6 hours again
It gives positive control drug and drug is treated, eyeball takes blood after treatment 3 hours.It is small that the Mouse whole blood of taking-up is stored at room temperature 2
Shi Hou, 3500rpm are centrifuged 15min, and 200 μ L of supernatant is taken to detect blood urea nitrogen relevant to injury of kidney using blood biochemistry analyzer
(BUN) and creatinine (Cr) is horizontal.
In the kidney troubles such as acute glomerulonephritis, pyelonephritis, kidney failure, impaired renal function causes urea in serum equal
It increases.Experimental result such as Figure 14 is shown, is compared with blank group, and in model group mice serum, serum urea nitrogen and creatinine level are aobvious
It writes and increases, administration group all reduces serum urea nitrogen and creatinine level to varying degrees, illustrates Verbascoside and/or purple stem female
Loyal glycosides A has therapeutic effect to the LPS acute kidney injury induced.
The present invention provides Verbascosides and/or purplestem privet leaf glycosides A compound to prepare anti-vascular endothelial cell inflammatory damage
Application in drug.This kind of compound may mitigate vascular endothelial cell by adjusting the number of ways such as NF- κ B signal access
Inflammatory reaction plays a protective role to vascular endothelial cell inflammatory damage.Verbascoside and/or purplestem privet leaf glycosides of the present invention
A belongs to first public preparing the application in anti-vascular endothelial cell inflammatory damage drug, and raw material sources are abundant, preparation side
Method is mature, in acute lung injury relevant to vascular endothelial cell damage, injury of kidney, pyemia, atherosclerosis and glycosuria
There is good application value in the exploitation of the protective agents such as sick vascular complication.
Claims (6)
1. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation treatment of vascular endothelial cell inflammatory damage drug.
2. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation prevention and treatment acute lung injury drug.
3. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation prevention and treatment medication for treating pyemia.
4. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation prevention and treatment injury of kidney drug.
5. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation prevention and treatment atherosclerosis drug.
6. the application of Verbascoside and/or purplestem privet leaf glycosides A in preparation prevention and treatment diabetic vascular complications drug.
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Cited By (1)
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| CN109513008A (en) * | 2019-01-16 | 2019-03-26 | 温州医科大学 | A kind of pharmaceutical composition and preparation method thereof for treating idiopathic interstitial pneumonia |
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| CN104688749A (en) * | 2015-03-27 | 2015-06-10 | 高南南 | Ligustrum phenethyl alcohol glycoside composition for treating obesity and application thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109513008A (en) * | 2019-01-16 | 2019-03-26 | 温州医科大学 | A kind of pharmaceutical composition and preparation method thereof for treating idiopathic interstitial pneumonia |
| CN109513008B (en) * | 2019-01-16 | 2021-03-23 | 温州医科大学 | Pharmaceutical composition for treating idiopathic interstitial pneumonia and preparation method thereof |
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Application publication date: 20190809 |