CN108685885A - Medical composition and its use containing schizandrin A - Google Patents
Medical composition and its use containing schizandrin A Download PDFInfo
- Publication number
- CN108685885A CN108685885A CN201810749178.4A CN201810749178A CN108685885A CN 108685885 A CN108685885 A CN 108685885A CN 201810749178 A CN201810749178 A CN 201810749178A CN 108685885 A CN108685885 A CN 108685885A
- Authority
- CN
- China
- Prior art keywords
- schizandrin
- platelet
- platelet aggregation
- blood
- aggregation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- JEJFTTRHGBKKEI-OKILXGFUSA-N deoxyschizandrin Chemical compound C1[C@H](C)[C@H](C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC JEJFTTRHGBKKEI-OKILXGFUSA-N 0.000 title claims abstract description 25
- JEJFTTRHGBKKEI-UHFFFAOYSA-N deoxyschizandrin Natural products C1C(C)C(C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC JEJFTTRHGBKKEI-UHFFFAOYSA-N 0.000 title claims abstract description 25
- FYSHYFPJBONYCQ-UHFFFAOYSA-N schisanhenol Natural products C1C(C)C(C)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2O FYSHYFPJBONYCQ-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 239000000203 mixture Substances 0.000 title description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 claims abstract description 26
- 239000003814 drug Substances 0.000 claims abstract description 14
- 208000007536 Thrombosis Diseases 0.000 claims abstract description 10
- 229940079593 drug Drugs 0.000 claims abstract description 8
- 230000002776 aggregation Effects 0.000 claims description 6
- 238000004220 aggregation Methods 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 230000002785 anti-thrombosis Effects 0.000 claims description 3
- 208000031169 hemorrhagic disease Diseases 0.000 claims description 2
- 208000014759 blood platelet disease Diseases 0.000 claims 1
- 239000000178 monomer Substances 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 5
- 230000006698 induction Effects 0.000 abstract description 3
- 210000001772 blood platelet Anatomy 0.000 description 17
- 238000012360 testing method Methods 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical group CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 235000008422 Schisandra chinensis Nutrition 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- YEFOAORQXAOVJQ-RZFZLAGVSA-N schisandrol a Chemical compound C1[C@H](C)[C@@](C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-RZFZLAGVSA-N 0.000 description 4
- 241000283977 Oryctolagus Species 0.000 description 3
- 240000006079 Schisandra chinensis Species 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000005622 photoelectricity Effects 0.000 description 3
- YEFOAORQXAOVJQ-UHFFFAOYSA-N wuweizischun A Natural products C1C(C)C(C)(O)CC2=CC(OC)=C(OC)C(OC)=C2C2=C1C=C(OC)C(OC)=C2OC YEFOAORQXAOVJQ-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 210000003038 endothelium Anatomy 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 229930193195 schizandrin Natural products 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 108091008803 APLNR Proteins 0.000 description 1
- 206010003178 Arterial thrombosis Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000037260 Atherosclerotic Plaque Diseases 0.000 description 1
- 102000015081 Blood Coagulation Factors Human genes 0.000 description 1
- 108010039209 Blood Coagulation Factors Proteins 0.000 description 1
- 241000208365 Celastraceae Species 0.000 description 1
- 206010008132 Cerebral thrombosis Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 1
- 241000218377 Magnoliaceae Species 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 102000007466 Purinergic P2 Receptors Human genes 0.000 description 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 1
- 241000736075 Schisandra Species 0.000 description 1
- 235000000336 Solanum dulcamara Nutrition 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 229940127217 antithrombotic drug Drugs 0.000 description 1
- 230000007214 atherothrombosis Effects 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 239000003114 blood coagulation factor Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000000875 corresponding effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- 210000001501 megacaryocyte Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000010118 platelet activation Effects 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000019640 taste Nutrition 0.000 description 1
- 238000002834 transmittance Methods 0.000 description 1
- 238000004879 turbidimetry Methods 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
- A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
- A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
A kind of traditional Chinese medicine monomer schizandrin A, the traditional Chinese medicine monomer have the rush platelet aggregation for inhibiting ADP inductions.Basic research of the schizandrin A in thrombosis is using as a kind of drug of novel platelet aggregation-against.
Description
Technical field
The present invention relates to the medical composition and its uses containing traditional Chinese medicine monomer schizandrin A, have and ADP is inhibited to lure
Lead the effect of platelet aggregation.
Background technology
Schisandra chinensis is the dry mature fruit of perennial fallen leaves liana magnoliaceae schisandra section Schizandra, sweet,
It is sour, pungent, bitter, salty bittersweet, therefore claim Schisandra chinensis.Lignanoids is as most important active constituent in Schisandra chinensis, including the five tastes
Sub- A prime, deoxyschizandrin etc..It is very extensive to the research of schizandrin A pharmacological action, it is related to digestive system, cardiovascular system
The various aspects such as system, central nervous system, reproductive system and urinary system.And it can be with the new work(of platelet aggregation-against for it
Can, it is not found so far.Platelet aggregation is the important link that thrombus and thrombotic diseases are formed.Blood platelet is haemocyte
In one kind, but its essence is not cell, be get off from the megacaryocyte cytoplasm crack releasing of marrow maturation have biology living
The cast of property.Blood platelet does not have nucleus, small volume, and the service life is in the discoid of two-sided dimpling probably at 7 to 14 days.
In a very long time, blood platelet is all counted as the non-functional cell fragment in blood.After have numerous studies discovery, blood small
Plate can be activated under the action of certain stimulants, and various changes occur:Deformation, adherency, aggregation and release reaction.Blood platelet
These changes can successively occur, or occur with various combination, or individually occur, and the reparation and physiological for participating in body vessel stop
Blood, and and atherothrombosis, cerebral thrombosis disease, metastases, the diseases such as inflammatory reaction it is closely related.Blood
Platelet, which activates, and the blood vessel endothelium of damage participates in atherosclerosis plaque forming simultaneously causes atheromatous plaque unstable, and platelet activation is still again
The major reason of perfusion injury.Body under normal circumstances when, blood platelet is in quiescent condition, is not susceptible to activate;And work as machine
When damage or inflammation occur for body vessel endothelium, blood platelet, which activates, to be occurred to assemble and then starts coagulation process.Blood platelet mistake
Degree activation can then form thrombus.So, the drug for inhibiting platelet aggregation is explored, and is thrombotic disease and its correlation
Disease finds corresponding action target spot and is of great significance.
Invention content
The inventor of the present application discovered that a kind of traditional Chinese medicine monomer schizandrin A.It belongs to a kind of inhibition platelet aggregation and blood
Bolt forms peptide, it would be desirable to inhibit the rush platelet aggregation of ADP.Wherein, ADP by activate platelet membrane on adp receptor,
The activity for inhibiting ATP enzyme makes blood platelet expose a variety of effects such as phospholipid surface and causes platelet aggregation.ADP is body blood coagulation
Natural component in system, is even more important for intrinsic coagulation.
The present invention provides a kind of pharmaceutical composition for treating hemorrhagic disease, it is characterised in that:The pharmaceutical composition includes
Schizandrin A.
The present invention also provides the purposes that a kind of schizandrin A is used to prepare drug, and the wherein drug can be by acting on APJ
Receptor is treated by the disease caused by platelet aggregation or thrombosis;Or prevent platelet aggregation or antithrombotic.
Present invention finds the physiologic function of schizandrin A, itself to platelet aggregation without effect.
Present invention finds the physiologic function of schizandrin A, the rabbit platelet aggregation that ADP can be inhibited to induce.
The present invention relates to a kind of schizandrin As;It is related to its new function research for inhibiting new zealand rabbit platelet aggregation.Hair
Existing schizandrin A can inhibit the new zealand rabbit platelet aggregation that ADP is induced.The invention also discloses schizandrin As in thrombus
Basic research in being formed is using as a kind of novel antithrombotic drug.
In testing in vitro, the gradient of concentration is 0.001mol/L, 0.01mol/L, 0.1mol/L, 1.0 μm of ol/L, preferably
For 1.0 μm of ol/L.
The advantageous effects of the present invention
1, traditional Chinese medicine monomer schizandrin A of the invention can be treated by acting on apj receptor by platelet aggregation or thrombus
Form caused disease;Or therefore prevention platelet aggregation or antithrombotic can be used for preparing drug.
Description of the drawings:
Fig. 1 be schizandrin A itself individually on platelet aggregation without influence
(Mean+SEM, n=4, ns vs control;ns vs DMSO group).
Fig. 2 is the platelet aggregation that schizandrin A inhibits ADP inductions
(ADP at 5 μM of together with deoxyschizandrin for 5min, mean+SEM, n=5, ns
vs control;***p<0.001vs DMSO group;ns vs ADP;###p<0.001vs ADP+DMSO group).
Specific implementation mode
Embodiment 1 measures influence of the schizandrin A to platelet aggregation
It is small that blood is measured with platelet aggregation coagulation factor analyzer (LG-PABER-I types, Beijing Steellex Scientific Instrument Company)
Plate aggregation rate.This instrument tests platelet aggregation using photoelectric turbidimetry:Use platelet poor plasma (platelet poor
Plasma, PPP) it is used as substrate, it is measured using Platelet-rich plasm (platelet rich plasma, PRP).In magnetic
Under the stirring of power pearl, derivant is added in PRP, blood platelet is assembled, and the light transmittance of PRP increases or turbidity reduction.By light
The variation of turbidity is converted to the variation of electric signal, to calculate the aggregation rate of blood platelet.
Aggregation rate=(measurement voltage value-PPP photoelectricity voltages value)/(PRP photoelectricity voltage value-PPP photoelectricity voltages value) *
100%.
1. measuring influence of the schizandrin A of various concentration (0.001,0.01,0.1,1 μm of ol/L) to platelet aggregation
Arterial blood drawing in new zealand rabbit ear is then centrifuged for sodium citrate anti-freezing, is first centrifuged 10min with 800r/min, is taken
Supernatant obtains PRP, then centrifuges 10min with 3000r/min, and supernatant is taken to obtain PPP.Accurately it is added 300 μ l's in test cup
PPP is put into TCH test channel, presses after PPP keys carry out substrate measurement and takes out.In another test cup, the accurate PRP that 300 μ l are added,
At 37 DEG C after pre-temperature 1min, using adding pearl device that 1 test pearl is added in the test cup, after starting test, divide in three seconds
Not Jia Ru the schizandrin A of various concentration (0.001,0.01,0.1,1 μm of ol/L) test 5min, the maximum for recording blood platelet is poly-
Collection rate (referring to Fig. 1).
2. the schizandrin A for measuring various concentration (1,0.1 0.01,0.001 μm of ol/L) inhibits the rabbit blood of ADP inductions small
Plate is assembled
PPP is acquired, PRP is same as above, and schizandrin A is added in PRP and is incubated 5 minutes, the survey for having mixed up baseline is placed into
It tries in area, test pearl is added, be rapidly added after starting test or ADP is tested five minutes, recorded the maximum aggregation rate of blood platelet, see
Examine inhibiting effect of the test result detection schizandrin A to platelet aggregation (referring to Fig. 2).
In conclusion the traditional Chinese medicine monomer of the present invention has effects that ideal platelet aggregation-against and thrombosis, it can
It is used to prepare relevant drug.
Claims (2)
1. a kind of pharmaceutical composition for treating hemorrhagic disease, it is characterised in that:The pharmaceutical composition includes schizandrin A.
2. schizandrin A is used to prepare the purposes of drug, wherein the drug can be treated by acting on apj receptor by blood platelet
Disease caused by aggregation or thrombosis;Or prevent platelet aggregation or antithrombotic.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710569204 | 2017-07-11 | ||
| CN2017105692040 | 2017-07-11 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108685885A true CN108685885A (en) | 2018-10-23 |
| CN108685885B CN108685885B (en) | 2023-11-17 |
Family
ID=63851512
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810749178.4A Active CN108685885B (en) | 2017-07-11 | 2018-07-10 | Pharmaceutical composition containing schizandrin A and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108685885B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1970001A (en) * | 2005-11-22 | 2007-05-30 | 黄振华 | Pharmaceutical composition comprising kurarinone, magnolia vine fruit and ginseng for treating hepatitis |
| CN102188486A (en) * | 2011-05-10 | 2011-09-21 | 王智森 | Pharmaceutical composition for preventing and treating fatty liver and preparation method thereof |
| CN105456481A (en) * | 2015-12-07 | 2016-04-06 | 中山大学 | Application of fructus schisandrae sphenantherae extract in preparation of liver regeneration medicine |
-
2018
- 2018-07-10 CN CN201810749178.4A patent/CN108685885B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1970001A (en) * | 2005-11-22 | 2007-05-30 | 黄振华 | Pharmaceutical composition comprising kurarinone, magnolia vine fruit and ginseng for treating hepatitis |
| CN102188486A (en) * | 2011-05-10 | 2011-09-21 | 王智森 | Pharmaceutical composition for preventing and treating fatty liver and preparation method thereof |
| CN105456481A (en) * | 2015-12-07 | 2016-04-06 | 中山大学 | Application of fructus schisandrae sphenantherae extract in preparation of liver regeneration medicine |
Non-Patent Citations (2)
| Title |
|---|
| 罗旭灵: "中国优秀硕士学位论文全文数据库医药卫生科技辑" * |
| 陈恩瑜等: "RP-HPLC 法同时测定补肾益脑胶囊中五味子醇甲、五味子甲素和五味子乙素的含量" * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108685885B (en) | 2023-11-17 |
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