CN115990151A - Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy - Google Patents
Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy Download PDFInfo
- Publication number
- CN115990151A CN115990151A CN202211481248.5A CN202211481248A CN115990151A CN 115990151 A CN115990151 A CN 115990151A CN 202211481248 A CN202211481248 A CN 202211481248A CN 115990151 A CN115990151 A CN 115990151A
- Authority
- CN
- China
- Prior art keywords
- parkin
- autophagy
- pink
- oxidative stress
- mitochondrial
- 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.)
- Pending
Links
Images
Classifications
-
- 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
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy, and relates to the technical field of biological medicines. The invention discovers that the vanillic acid can regulate and control the pathway mediated by the PINK-1/Parkin, activate the mitochondrial autophagy, improve the oxidative stress damage of cells, and provide a way for researching or treating related diseases caused by abnormal pathway of the PINK-1/Parkin and/or abnormal autophagy of the mitochondria.
Description
Technical Field
The invention relates to the technical field of biological medicines, in particular to an application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy.
Background
As the social rhythm gradually increases, the incidence of cardiovascular diseases steadily decreases year by year, but the total number of patients increases year by year, and cardiovascular diseases still remain serious clinical and public health problems. In recent years, although the standardized treatment of cardiovascular diseases improves the life quality and prognosis of heart failure patients, how to further reduce the death rate and readmission rate of cardiovascular diseases, improve the life quality of cardiovascular disease patients, reduce the social and economic burden, and the medical community is urgently needed to continue to explore and study. Oxidative stress is involved in the occurrence and development of a variety of cardiovascular diseases in clinical and experimental settings, and is caused by reactive oxygen species generation and endogenous antioxidant defense disorders. Too high a concentration of Reactive Oxygen Species (ROS) can lead to cellular dysfunction, protein and lipid peroxidation, DNA damage, and irreversible cell damage and death. Active oxygen production in the myocardium is mainly produced by mitochondria, NADPH oxidase, xanthine oxidase and unconjugated Nitric Oxide Synthase (NOS), and under pathological conditions, the electron transfer chain of mitochondria induces the formation of a large number of superoxide, which has been demonstrated in current research to cause myocardial cell injury or more serious myocardial injury after acute myocardial infarction.
Research on the molecular mechanism of the protective effect of compounds on oxidative stress injury to provide more compounds capable of improving myocardial oxidative stress injury is one of the problems to be solved urgently.
In view of this, the present invention has been made.
Disclosure of Invention
The invention aims to provide application of vanilloid in improving related diseases by regulating PINK-1 and Parkin to activate mitochondrial autophagy.
The invention is realized in the following way:
in a first aspect, embodiments of the present invention provide the use of vanillic acid in the preparation of a product for treating or ameliorating a related disorder caused by an abnormality of the PINK-1/Parkin pathway.
In a second aspect, embodiments of the present invention provide the use of vanillic acid for the manufacture of a product for the treatment or amelioration of a disease associated with abnormal autophagy of mitochondria.
In a third aspect, embodiments of the present invention provide a method of preparing vanillic acid for improving H 2 O 2 Products of apoptosis of induced oxidative stress damaged cellsIs used in the field of applications.
The invention has the following beneficial effects:
the invention discovers that the vanillic acid can regulate and control the pathway mediated by the PINK-1/Parkin, activate the mitochondrial autophagy, improve the oxidative stress damage of cells, and provide a way for researching or treating related diseases caused by abnormal pathway of the PINK-1/Parkin and/or abnormal autophagy of the mitochondria.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings that are needed in the embodiments will be briefly described below, it being understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and other related drawings may be obtained according to these drawings without inventive effort for a person skilled in the art.
FIG. 1 shows VA toxicity improvement H 2 O 2 Induced cardiomyocyte apoptosis; the cardiomyocytes were cultured in a medium containing VA 50. Mu.M, 100. Mu.M, 200. Mu.M, 600. Mu. M H 2 O 2 Treating H9c2 cardiomyocytes for 3H; (A) VA is toxic to myocardial cells; (B) Protective effect of different concentrations of VA on myocardial cells damaged by oxidative stress; (C) apoptosis rate; (D) lactate dehydrogenase content of the cell supernatant; (E) apoptosis level; * Vs M<0.01，****vs M<0.001，ns vs M＞0.05；
FIG. 2 shows the improvement of mitochondrial respiration function and morphology of oxidative stress damaged cardiomyocytes by VA; cardiomyocytes were cultured in a medium containing VA at 50. Mu.M, 100. Mu.M, 200. Mu.M, 600. Mu.MH was used 2 O 2 Treating H9c2 cardiomyocytes for 3H; (A) (B) (C) (D) (E) VA can improve the effects of oxidative stress on mitochondrial respiration function, residual respiration, ATP production, proton leakage and basal respiration of myocardial cells; (F) (G) VA helps to maintain mitochondrial morphology and number; (H) (I) VA improves the decline in mitochondrial membrane potential in oxidative stress damaged H9C2 cells; * Vs M P<0.01，****vs M P<0.001，ns vs M P>0.05，#vs Ctrl P<0.05，##vs Ctrl P<0.01，#vs Ctrl P<0.001，#vs Ctrl P<0.0001；
FIG. 3 shows that VA improves oxidative stress injury H9C2 intracellular redox levels (C) (D) intracellular ROS levels are detected using flow cytometry; (a) VA reduces intracellular MDA levels; (B) VA increases intracellular SOD levels; all data are expressed as mean ± SEM of 3 independent experiments; #vs Ctrl P <0.05; * vs M P <0.05, # vs M P < 0.01, # vs M P < 0.001, # vs Ctrl P < 0.0001;
FIG. 4 shows that VA can increase H by modulating PINK-1/Parkin/LC3 activated autophagy to reduce myocardial oxidative damage (A) (B) VA 2 O 2 Autophagy flow damaging cardiomyocytes, VA activation autophagy function was inhibited following administration of 3-MA inhibitors; (C) (D) (E) (F) (G) VA increases H 2 O 2 The expression level of PINK-1 and Parkin of damaged myocardial cells is increased, the expression of P62 is increased, the ratio of LC3-II to LC3-I is increased, and after the 3-MA mitochondrial autophagy inhibitor is used, VA cannot influence the expression level of PINK, parkin, P and LC3, and autophagy flow is influenced; * Vs M P<0.01，****vs M P<0.001，ns vs M P>0.05，#vs Ctrl P<0.05，##vs Ctrl P<0.01，#vs Ctrl P<0.001，#vs Ctrl P<0.0001。
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below. The specific conditions are not noted in the examples and are carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
The embodiment of the invention provides application of vanilloid in preparing a product for treating or improving related diseases caused by abnormal PINK-1/Parkin pathway.
PINK-1/Parkin mediated mitochondrial autophagy is one of the mitochondrial autophagy pathways. When mitochondria are damaged, PINK-1 can accumulate in large numbers in the inner membrane of the online granulocyte, followed by activation of the fusion protein mitotic fusion protein 2 (Mfn-2) at the mitochondrial surface. PINK-1 promotes recruitment of Parkin and ubiquitinates protein molecules of the inner mitochondrial membrane, thereby generating a target recognized by autophagy-adapted protein p62, which mediates interactions with microtubule-associated protein 1 light chain 3 (LC 3), which is involved in the elongation of phagocytic membranes. As a result, mitochondria are encapsulated by phagosomes, forming autophagosomes in which the mitochondria are digested. Silencing of PINK-1 and Parkin in cardiomyocytes inhibits mitochondrial autophagy, resulting in decreased mitochondrial membrane potential, influenced metabolism, and decreased cardiac function.
The inventors of the present application used H 2 O 2 Inducing myocardial cells to establish an in vitro myocardial oxidative stress model, observing the influence of Vanillic Acid (VA) on myocardial cell oxidative stress and mitochondrial energy metabolism, and discussing the relation between VA and Parkin in myocardial oxidative stress. As a result, it was found that VA improved H 2 O 2 The induced myocardial oxidative stress injury can up-regulate the expression of Parkin, activate the autophagy of mitochondria, maintain the quality of mitochondria, improve the energy metabolism of mitochondria and reduce the apoptosis. VA vs H after use of 3-MA mitochondrial autophagy inhibitor 2 O 2 The oxidative stress protection effect of the induced myocardial cells is lost, the quality of the cell suction mitochondria is reduced, and the energy metabolism cannot be recovered. Therefore, VA can activate mitochondrial autophagy, maintain mitochondrial quality, relieve myocardial cell oxidative stress injury by regulating and controlling a Parkin/P62 pathway, and is a candidate compound for improving myocardial oxidative stress injury. Activation of mitochondrial autophagy by modulating PINK-1/Parkin/p62 to protect against oxidative stress damage may be a potential target for VA treatment of CVD.
"treatment" herein is the manner in which beneficial or desired results (including clinical results) are obtained. For the purposes of the present invention, beneficial or desired clinical results include, but are not limited to, at least one of the following: reducing symptoms caused by the disease, reducing the extent of the disease, stabilizing the disease (e.g., preventing or delaying exacerbation of the disease), preventing or delaying the spread of the disease (e.g., metastasis), preventing or delaying the occurrence or recurrence of the disease, delaying or slowing the progression of the disease, ameliorating the disease state, providing (partial or complete) remission of the disease, reducing the dosage of one or more other drugs required to treat the disease, increasing quality of life, and/or prolonging survival. Also encompassed by "treatment" is a reduction in the pathological consequences of a disease (e.g., cancer).
In some embodiments, the abnormality of the PINK-1/Parkin pathway comprises a decrease (or inhibition) in the amount of expression of PINK-1 and/or Parkin. The expression level of the PINK-1 and/or the Parkin comprises the expression level of the PINK-1 and/or the Parkin protein and/or the expression level of mRNA. Specifically, the expression level of PINK-1 and/or Parkin in myocardial cells is included.
In some embodiments, the related disease comprises: decreased autophagy flux due to abnormality of the PINK-1/Parkin pathway, thereby causing diseases.
In some embodiments, the product includes any one of a reagent, a kit, and a medicament.
In another aspect, embodiments of the present invention also provide the use of vanillic acid in the manufacture of a product for treating or ameliorating a related disorder caused by an abnormal autophagy of mitochondria.
In some embodiments, the abnormal mitochondrial autophagy refers to a decrease in mitochondrial autophagy flux.
In some embodiments, the mitochondrial autophagy abnormality comprises: at least one of an increase in p26 level and a decrease in LC3-II/LC3-I ratio. The increase in p26 levels specifically includes an increase in p26 protein levels and/or an increase in mRNa levels. The LC3-II/LC3-I ratio includes the ratio of the level of LC3-II protein to the level of LC3-I protein in the cell.
In some embodiments, the mitochondrial autophagy abnormality comprises a factor of H 2 O 2 Reduced mitochondrial autophagy flux resulting from induced oxidative stress injury.
In some embodiments, the product includes any one of a reagent, a kit, and a medicament.
In addition, the embodiment of the invention also provides the preparation of the vanillic acid for improving H 2 O 2 Use of an induced oxidative stress to damage the products of apoptosis of cells.
In some embodiments, the oxidative stress damaged cells comprise oxidative stress damaged H9C2 cardiomyocytes.
The features and capabilities of the present invention are described in further detail below in connection with the examples.
Example 1
1. Method of
1.1 grouping: the cells of each group are respectively divided into a Ctrl group, an M group, a VA-50 mu M group, a VA-100 mu M group and a VA-200 mu M group; the immunoblotting analysis experiments are respectively a Ctrl group, an M group, a VA group, a VA+3-MA group and a 3-MA group.
1.2 cell Activity assay: H9C2 cardiomyocytes were grown at 1X 10 4 Density of wells/wells were seeded into 96-well plates with 100. Mu.L of complete medium per well and attached overnight at 37 ℃. Afterwards, each well is divided into Ctrl, M, 50 mu M, 100 mu M, 200 mu M and LMKL groups, and the concentrations of vanillic acid are respectively corresponding to the 50 mu M, 100 mu M and 200 mu M groups; the concentration of the LMKL group drug is Lian Mei particles 400 mug/mL.
1.3 immunoblot analysis
Cells were cultured in 6-well plates, washed twice with PBS, and total protein was extracted by adding lysate. Equal amounts of proteins were separated using electrophoresis and then transferred to PVDF membrane (Millipore), blocked with 5% skim milk, and incubated with primary anti-Parkin, LC3, BCL-2, caspase, bax, gadph antibodies at 4 ℃. Protein levels were normalized to the density of Gadph.
1.3 flow cytometry
Cells were cultured in 6-well plates, cells were digested with EDTA-free pancreatin and washed twice with PBS to collect cells. Apoptosis was detected by cytometry using Fluo-4 calcium fluorescent probes, or FITC, ROS, JC-1 staining. Cells were collected, washed twice with PBS, incubated in ROS probes for 30 min, and cellular ROS was detected by cell flow.
1.4 laser confocal
Cells were seeded into the middle glass well portion of copolymer Jiao Min, 200 μl of complete medium per dish, 4000 cells. Placing at 37deg.C, 5% CO 2 The incubator was allowed to adhere overnight. After cell attachment, each group was dosed.
After 24h of administration, 200. Mu.L of 600. Mu.M hydrogen peroxide was added to each group, and incubated in an incubator for 3h. After 3h, the dishes were removed and the Ctrl group was given an equal amount of basal medium, the liquid in each dish was aspirated and washed 2 times with PBS. Mito-Tracker Green (C1048 Beyotime, china) was prepared as a 1mM stock solution, 1. Mu.L of Mito-Tracker Green stock solution was added to 5mL of basal medium, vortexed away from light for 30s, and 1mL of the prepared staining solution was added to each confocal dish. Incubate in incubator for 20min. After incubation, the dishes were rinsed 1 time with PBS, and 1mL of basal medium was added to each dish and placed on ice in the dark for use. And (5) loading the confocal microscope.
1.5 mitochondrial energy metabolism
Experiment first day: seaHorse XFE24 cell plates were opened, 1 million cells per well, 500. Mu.L of complete medium, with A1, B4, C3, D6 as background wells, and no cells were seeded. The cells were incubated overnight at 37℃in an incubator. The following day of the experiment: the well plate medium was aspirated and dosed. Taking out probe card, and at 37deg.C, without CO 2 One sensor probe plate was hydrated overnight with SeaHorse XF calibrator in an incubator, and 500. Mu.L of calibrator was added to each well. Experiments were designed in Wave software. Preparing a detection liquid: the test solution was prepared by supplementing SeaHorse XF DMEM or RPMI medium with an additive. XF medium at pH 7.4 and XF additives were placed in a cell culture ultra clean bench. Compound stock and working solution were prepared: three tube compounds of oligomycin (blue cap), FCCP (Huang Gai) and rotenone/antimycin a (red cap) were configured. Each tube of reagent was resuspended in the volume indicated in table 1 with the prepared assay solution.
Table 1: concentration of each drug
| Compounds of formula (I) | Volume of detection solution | Concentration of stock solution |
| Oligomycin | 630μL | 100μmol/L |
| FCCP | 720μL | 100μmol/L |
| Rotenone | 540μL | 50μmol/L |
1.6 statistical analysis
Data were analyzed using GraphPadPrism software 9.0 and expressed as mean ± SEM. Statistical significance was determined using one-way analysis of variance (ANOVA) followed by multiple comparisons using Tukey test. P <0.05 is considered statistically significant.
2. Results
2.1 VA can improve H 2 O 2 The induced oxidative stress damages the apoptosis of cardiomyocytes.
Using 600 mu M H 2 O 2 And (5) inducing H9C2 myocardial cells to establish an oxidative stress model. The VA concentration is below 5000 mu M, so that the cell proliferation is not obviously affected, the survival rate of the VA medium-high dose group and the survival rate of the Lianmei granule group are obviously improved compared with the survival rate of the model group, and the Lactic Dehydrogenase (LDH) VA concentration group and the Lianmei granule group are obviously reduced. The early apoptosis and late apoptosis rates of cells were significantly reduced in the VA and Lian Mei groups. See fig. 1.
2.2 VA can improve mitochondrial respiration and mitochondrial morphology in oxidative stress damaged cardiomyocytes.
After administration and modeling, the mitochondrial pressure of H9C2 cardiomyocytes was measured using Agilent Seahorse, see FIG. 2, and as a result, VA was found to significantly improve mitochondrial respiration in oxidative stress injured cardiomyocytes, increase residual respiratory capacity, improve cellular mitochondrial ATP production, increase cellular proton leakage, and improve cellular basal respiration. The improvement of mitochondrial morphology of cells in VA, high dose and LMKL groups was evident compared to model groups.
2.3VA improves the level of oxidative stress related products in H9C2 cardiomyocytes with oxidative stress injury.
Research shows that after oxidative stress injury, a great amount of ROS can be produced, and normal functions of cells are damaged, so that autophagy and energy metabolism of the cells are affected. In this example, the effect of VA on intracellular redox related material levels was explored, see figure 3. The results indicate that VA can reduce intracellular ROS levels, reduce oxidation product MDA levels, and increase intracellular antioxidant enzyme SOD levels.
2.4VA activates mitochondrial autophagy by modulating PINK-1/Parkin/P62.
See FIG. 4, H 2 O 2 The induced oxidative stress injury H9C2 myocardial cell autophagy flux is reduced, VA can up regulate the expression amount of PINK-1 and Parkin, and autophagy is activated. To further confirm whether VA can affect autophagy flow in cells by modulating PINK-1 and Parkin, the mitochondrial autophagy inhibitor 3-MA was used. It was found that the autophagy flow level of cardiomyocytes decreased, the LC-II/LC-I ratio decreased and P62 accumulation increased.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (10)
1. Use of vanillic acid for the preparation of a product for the treatment or amelioration of a related disorder caused by abnormal PINK-1/Parkin pathway.
2. The use according to claim 1, wherein said abnormal pathway of PINK-1/Parkin comprises reduced expression of PINK-1 and/or Parkin.
3. The use according to claim 2, wherein the related diseases comprise: decreased autophagy flux due to abnormality of the PINK-1/Parkin pathway, thereby causing diseases.
4. The use according to claim 2, wherein the product comprises any one of a reagent, a kit and a medicament.
5. Use of vanillic acid for the preparation of a product for the treatment or amelioration of a related disorder caused by abnormal autophagy of mitochondria.
6. The use according to claim 5, wherein said abnormal mitochondrial autophagy is a decrease in mitochondrial autophagy flux.
7. The use of claim 6, wherein the abnormal mitochondrial autophagy comprises: at least one of an increase in p26 level and a decrease in LC3-II/LC3-I ratio.
8. The use of claim 6, wherein said mitochondrial autophagy abnormality comprises the inhibition of the autophagy by H 2 O 2 Reduced mitochondrial autophagy flux resulting from induced oxidative stress injury.
9. The use according to any one of claims 5 to 8, wherein the product comprises any one of a reagent, a kit and a medicament.
10. Vanillin preparation for improving H 2 O 2 Use of an induced oxidative stress to damage apoptosis of cells;
preferably, the oxidative stress damaged cells comprise oxidative stress damaged H9C2 cardiomyocytes.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211481248.5A CN115990151A (en) | 2022-11-24 | 2022-11-24 | Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211481248.5A CN115990151A (en) | 2022-11-24 | 2022-11-24 | Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115990151A true CN115990151A (en) | 2023-04-21 |
Family
ID=85989609
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211481248.5A Pending CN115990151A (en) | 2022-11-24 | 2022-11-24 | Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115990151A (en) |
-
2022
- 2022-11-24 CN CN202211481248.5A patent/CN115990151A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Cao et al. | Curcumin ameliorates oxidative stress-induced intestinal barrier injury and mitochondrial damage by promoting Parkin dependent mitophagy through AMPK-TFEB signal pathway | |
| Liao et al. | Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies | |
| Xuan et al. | Astaxanthin blocks preeclampsia progression by suppressing oxidative stress and inflammation | |
| Chiu et al. | Synergistic antitumor effects of radiation and proteasome inhibitor treatment in pancreatic cancer through the induction of autophagy and the downregulation of TRAF6 | |
| Hou et al. | Prussian blue nanozyme promotes the survival rate of skin flaps by maintaining a normal microenvironment | |
| Kim et al. | The aqueous extract of Prunella vulgaris suppresses cell invasion and migration in human liver cancer cells by attenuating matrix metalloproteinases | |
| Chang et al. | Valproic acid sensitizes human glioma cells to gefitinib‐induced autophagy | |
| Wang et al. | Astragaloside IV protects retinal pigment epithelial cells from apoptosis by upregulating miR‑128 expression in diabetic rats | |
| Wang et al. | Selenium deficiency induces apoptosis and necroptosis through ROS/MAPK signal in human uterine smooth muscle cells | |
| Ye et al. | Ononin shows anticancer activity against laryngeal cancer via the inhibition of ERK/JNK/p38 signaling pathway | |
| Kovács et al. | Olaparib: a clinically applied PARP inhibitor protects from experimental Crohn’s disease and maintains barrier integrity by improving bioenergetics through rescuing glycolysis in colonic epithelial cells | |
| Wu et al. | Resveratrol inhibits proliferation of myometrial and leiomyoma cells and decreases extracellular matrix-associated protein expression | |
| Cheung et al. | Lectin from Agaricus bisporus inhibited S phase cell population and Akt phosphorylation in human RPE cells | |
| Wang et al. | Silencing MR-1 protects against myocardial injury induced by chronic intermittent hypoxia by targeting Nrf2 through antioxidant stress and anti-inflammation pathways | |
| US20220211728A1 (en) | Alkyl-tpp compounds for mitochondria targeting and anti-cancer treatments | |
| Shan et al. | Effect of Tripterygium wilfordii polyglycoside on experimental prostatitis caused by Ureaplasma urealyticum in rats | |
| CN115990151A (en) | Application of vanillic acid in improving related diseases by regulating and controlling PINK-1 and Parkin to activate mitochondrial autophagy | |
| Wan et al. | Dot1l aggravates keratitis induced by herpes simplex virus type 1 in mice via p38 MAPK-mediated oxidative stress | |
| CN106928229A (en) | The purposes of couroupitine A and its derivative in hIDO2 inhibitor is prepared | |
| CN110075303A (en) | Na+-H+Exchange the method that pump inhibitor combination with cisplatin promotees ovarian carcinoma drug-resistant cell apoptosis | |
| CN112245587B (en) | Pharmaceutical composition containing NAD and cholinesterase inhibitors and application thereof | |
| AU2020386436A1 (en) | Compounds, compositions, and methods for treating ischemia-reperfusion injury and/or lung injury | |
| Jiang et al. | Construction of lycetin nanocarriers and its effect on the proliferation and apoptosis of hepatocellular carcinoma cells by regulating nuclear factor E2 related factor/antioxidant response element pathway | |
| Yan et al. | Diisopropylamine dichloroacetate alleviates liver fibrosis through inhibiting activation and proliferation of hepatic stellate cells | |
| CN105969725B (en) | The purposes of fructus lycii red pigment |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |