CN105878231A - Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs - Google Patents
Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs Download PDFInfo
- Publication number
- CN105878231A CN105878231A CN201510036805.6A CN201510036805A CN105878231A CN 105878231 A CN105878231 A CN 105878231A CN 201510036805 A CN201510036805 A CN 201510036805A CN 105878231 A CN105878231 A CN 105878231A
- Authority
- CN
- China
- Prior art keywords
- hiv
- cell
- quercetin
- puerarin
- people
- 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
Abstract
The invention belongs to the field of medicine, and relates to an application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs. The compounds have been applied to clinical tests (phase I or II); based upon tests, the compounds disclosed by the invention have a function of inducing activation of HIV latent cells; the compounds, when used in a mode of combining with a PKC activator Prostratin and a histone deacetylase inhibitor VPA, have a synergistic effect; and the compounds are relatively low in cytotoxicity within an effective concentration, and the compounds can be used for preparing the anti-HIV-latency therapeutic drugs; therefore, a new way is provided to radically cure Aids.
Description
Technical field
The invention belongs to field of medicaments, relate to flavone compound and preparing the medicine that AntiHIV1 RT activity is hidden
In purposes.
Background technology
Research discloses acquired immune deficiency syndrome (AIDS) i.e. acquired immune deficiency syndrome (AIDS), is a kind of by HIV
The serious infectious disease that poison (human immunodeficiency virus, HIV) causes.Virus
Main infection also destroys in human immune system most importantLymphocyte, causes immune function
Defect, resistance reduces, finally dead due to various opportunistic infection.HIV examines in clinic in 1981
It is found in Duan, along with the viral and molecular biology research of course of infection and medicine are ground by the mankind
That sends out constantly brings forth new ideas, and the treatment of acquired immune deficiency syndrome (AIDS) has had the development advanced by leaps and bounds.Anti-Retrovirus
Therapy (High Active Antiretroviral Therapy, HAART) can successfully by
Patient's peripheral blood virus quantity controls, at Clinical detection (less than 50 copies/mL) below horizontal, to significantly improve
The survival rate of patient and life quality (1. Yeni, P.G.et al.Treatment for adult HIV
infection:2004recommendations of the International AIDS Society-USA
Panel.JAMA.2004,292:251-65。②Blankson,J.N.et al.The challenge
of viral reservoirs in HIV-1infection.Annu Rev Med.2002,53:557-93)
People once placed hope on by the fully erased internal HIV of HAART, thus reached thoroughly to cure AIDS's
Purpose.But the most subsequently it was verified that once stop Drug therapy, virus load can rebound again
Level (Ho, D.D.Toward HIV eradication or remission:the tasks before treatment
Ahead.Science, 1998.280:1866 1867.).Research display, HIV is difficult in vivo
The major reason being completely removed is to there is latent virus storage vault in patient body.This latent virus stores up
Warehousing is mainly remembered CD4+T cell and in initial infection activation by the dormancy of long-term latent infection
CD4+T cell is converted into memory T cell and constitutes after being infected by HIV-1, latent cells is when non-irriate
Do not express viral gene, thus body immune system or antiretroviral drugs effect can be escaped
(Chun,T.W.and Fauci,A.S.Latent reservoirs of HIV:obstacles to
the eradication of virus.Proc Natl Acad Sci U S A,1999.
96:10958-61.).Although infected individuals carries latent infected cells negligible amounts, but attenuation rate is such
Slow, to such an extent as to be intended within the individual survival phase only it thoroughly be removed, at least at present by HAART treatment
For be impossible.Therefore, the tranquillization CD4+T cell of HIV latent infection is to constitute body inner virus
The major part of bunker (reservoir), is also that current clinical treatment can not thoroughly remove HIV simultaneously
Huge obstacle [Finzi, D.et al.Latent infection of CD4+T cells provides
a mechanism for life long persistence of HIV-1,even in patients on
effective combination therapy.Nature Med.1999,5,512–517].At present
The HIV-1 provirus hidden by various micromolecular compound reactivation, reaches to subtract in combination with HAART
Few latent virus storage vault even removes the therapy of HIV-1, is referred to as immune activation therapy
(Immunoactivation therapy, IAT), this therapy has become the main plan for the treatment of acquired immune deficiency syndrome (AIDS)
Slightly (Prins, J.M.et al.Immuno-activation with anti-CD3and recombinant
human IL-2in HIV-1-infected patients on potent antiretroviral
Therapy.AIDS, 1999.13,2405-10.), also the removing for virus storage vault opens newly
Thinking.
Be currently used for activating the hide medicine in storehouse of HIV-1 and be broadly divided into following several: (1) cell because of
Son and chemotactic factor: such as TNFa (TNF-a)；(2) histon deacetylase (HDAC) suppression
Agent: such as SAHA and VPA；(3) histone methylated transferase inhibitor: such as BIX01294；(4)
DNA methylation inhibitors: mainly 5-Aza and its derivant；(5) Protein kinase C
Activator: such as prostratin and bryostatin-1；(6) forward transcriptional elongation factor activator:
Such as HMBA and JQ1 (S)；(7) other unnamed material: such as disulfiram.(Xing,S.and
Siliciano,R.F.Targeting HIV latency:pharmacologic strategies
toward eradication,Drug Discov Today,2013.18,541-51)；Above-mentioned induction
Agent is combined in clinically achieved with preliminary efficacy with Effective Anti adverse transference record virus therapy respectively, but still suffers from
That such as activation efficiency is the highest or the problem such as toxic and side effects, having so there is a need in the art for developing more safety
Imitate activates medicine or seeks to work in coordination with the medicine of use.
Quercetin (Quercetin) is a kind of flavone compound extracted from plant, and chemistry is entitled
3,3', 4', 5,7-pentahydroxyflavone (2-(3,4-Dihydroxyphenyl)-3,5,7-trihydroxy
-4H-1-benzopyran-4-one 3,3′,4′,5,6-Pentahydroxyflavone Quercetin
-3-O-rhamnoside), research shows that it has multiple pharmacological effect, and treatment toxicity is relatively easy to control.
It is approved by the fda in the United States for I, I I clinical trial phase at present.(①Beneficial Effects of
Quercetin in Chronic Obstructive Pulmonary Disease(COPD)-Full Text
View-Cl inicalTrial s.gov。②Effect of Quercetin in Prevention and
Treatment of Oral Mucositis-Full Text View-Cl inicalTrials.gov)。
Puerarin (Puerarin) falls within flavone compound, has been proved to multiple pharmacological effect,
Have been applied to II clinical trial phase (1. Puerarin Effects on Alcohol Drinking at present
-Study Results-ClinicalTrials.gov。②The Effect of Puerarin
Injection on Carotid Intima-Media Thickness in Patients With
Rheumatoid Arthritis-Full Text View-ClinicalTrials.gov)。
But, up to now, there is not yet about Quercetin (Quercetin) and puerarin (Puerarin)
There is AntiHIV1 RT activity hide the report of therapeutical effect.
Summary of the invention
It is an object of the invention to provide the chemicals for the treatment of of hiding for AntiHIV1 RT activity.It is specifically related to flavonoid
Compound purposes in preparing the medicine that AntiHIV1 RT activity is hidden, particularly relates to the flavonoid of the present invention
Compound activates HIV latent infected cells, and finally removes described latent virus.
In order to confirm whether described chemicals makes its latent virus again swash HIV latent infected cells
Living and act on, technical scheme is as described below.
Used by the present invention, main agents material is as follows:
The HIV latent infected cells model that the present invention selects is built by this laboratory, and this cell is with carrying
The HIV-1 pseudovirus (pNL4-3-EGFP) of green fluorescent protein (EGFP) reporter gene infects people's T lymph
Cell Jurkat strain, is obtained by cell sorting and expresses that GFP is positive and negative cells group, and this HIV hides sense
Dye model has obtained Chinese patent mandate (Zhu Huanzhang, Xin Qingting；Liu Shaohui；Tang Lisha；Yu Long, a kind of screening
The T cell of activating dormant infection HIV-1 compound and preparation method, the patent No.: ZL200810038851.X).
This cell model biological characteristics is to integrate to have inhibition of HIV pseudogene, but viral gene is not expressed, and (gene sinks
Silent)；Green fluorescent protein owing to feature can be observed on living cells, thus, green fluorescent protein is as this mould
The reporter gene of type, the labelling i.e. whether being activated as latent infected cells.
Flavone compound of the present invention includes: Quercetin (quercetin) and puerarin
(Puerarin), deriving from SIGMA, article No. is respectively Sigma Q4951 and Sigma P5555,
All it is dissolved in DMSO (purchased from SIGMA), stores concentration 100mM.
In the present invention, described HIV latent infected cells is selected from: people's mononuclearcell, human macrophage,
People's CD4T lymphocyte, people's mastocyte, people's dendritic cell, people's folliculus sample dendritic cell, artificial blood
CFU-GM, people's natural killer cell, human neure or oligodendroglia, etc..
In the present invention, flavone compound medicine is combined with inverase has activation removing latent virus
And finally scavenging action.
In the present invention, described flavone compound has a following structural formula of compound:
In the present invention, described inverase is:
(1) efabirenz: 1. zidovudine zidovudine (AZT or ZDV)；
2. didanosine didanosine (ddl, Videx)；3. zalcitabine Zalcitabine (ddc)；④
Stavudine Stavudine (d4T)；5. lamivudine Lamivudine (3TC)；6. Abacavir
abacavir(1592U89Ziagen)；
(2) non-nucleoside reverse transcriptase inhibitor (NNRTI): 1. nevirapine nevirapine；②
Delavirdine delavird；3. efavirenz efavirene；
(3) protease inhibitor: 1. Saquinavir saguinavir；2. indinavir indinavir；
3. ritonavir ritonavir；4. viracept see nelfinaivr nelfinavirr；5. amprenavir amprenavir.
The present invention is realized by following technical scheme:
(1) HIV is hidden induced activation efficiency by the variable concentrations of Quercetin and Puerarin medicine
Impact test
The present invention is with the drug treating HIV latent infected cells model that concentration is 5 μMs-40 μMs, at medicine
After reason 3 days, by examining the fluorescence microscope of reporter gene green fluorescent protein and flow cytometry
Survey, analyze the activation efficiency of HIV latent infected cells, thus obtain pharmaceutically-active dose-effect relationship；
Result shows, along with the rising of Quercetin and Puerarin compound concentration, in cell model
The cell number expressing green fluorescence increases；HIV latent infected cells is after Quercetin (20 μMs) processes
The cell proportion of the green fluorescence positive reaches up to 13.7%；Puerarin fluorescent positive thin when 20 μMs of concentration
Born of the same parents' cell proportion reaches 9.7%.Do not add the HIV latent infected cells that derivant processes, the cell of its fluorescent positive
Ratio only has and activates less than 2% background；Result shows, it is right that Quercetin and Puerarin compound has
The activation of HIV latent infected cells, it preferably activates concentration is 20 μMs, and has dose-effect relationship；
(2) action time of Quercetin and Puerarin medicine HIV is hidden induced activation efficiency
Impact test
HIV latent infected cells models are processed with 20 μMs of drug level, 1 day after drug treating, 2
My god, 3 days, in 4 day time, by the fluorescence microscope of reporter gene green fluorescent protein and streaming
Cell art detects, and analyzes the activation efficiency of HIV latent infected cells, thus obtains pharmaceutically-active time effect
Relation；
Result shows, Quercetin and Puerarin processes HIV latent infected cells model respectively, with
Time of extends, and the positive cell number of green fluorescence gradually increases, and Quercetin hides sense processing HIV
The cell proportion that after dye cell model 72h, green fluorescence is positive reaches the highest by 13%, and Puerarin is processing HIV
The cell proportion that after latent infected cells model 72h, green fluorescence is positive reaches the highest by 10%；Show that two medicines have
Time-effect relationship；
(3) toxic action of cell is tested by Quercetin and Puerarin
With the drug treating HIV latent infected cells of variable concentrations, pass through in the 72h after drug treating
The proliferation activity of CCK-8 method detection cell, calculates the medicine half toxic concentration (CC50) to cell,
Thus obtain the medicine toxic action to cell；
Result shows, the half toxic concentration of human normal cell line is divided by Quercetin and Puerarin medicine
Not Wei CC50=160 μM and CC50=120 μM, i.e. Quercetin concentration be 160 μMs process cell time,
Have 50% be processed cell display toxicity, Puerarin concentration be 120 μMs process cell time, have 50% quilt
Processing cell display toxicity, CC50 is the highest, and its cytotoxicity is the lowest；Thus, this result shows Quercetin
With Puerarinza in valid density relatively low to cytotoxicity, lay a good foundation for clinical practice；
(4) Quercetin and Puerarin and PKC activator Prostratin and histone deacetylase
Change the test of enzyme inhibitor valproic acid (VPA) synergistic activation
The most just the same based on each HIV latent infected cells state, thus, the HIV mechanism of hiding is
Different；In order to maximize activation HIV latent infected cells and reduce toxicity, to Quercetin in the present invention
Carry out detection with the synergistic activation of Puerarin Yu PKC activator Prostratin and VPA to analyze；
Result shows, each medicine or Combined Treatment HIV latent infected cells are after 72 hours, to report base
Because of the Flow cytometry of green fluorescent protein, the cell proportion of its green fluorescence positive is respectively
Quercetin (14.3%), Prostratin (22.6%), VPA (11.4%)；Quercetin+Prostratin
(63.1%), Quercetin+VPA (44%)；Puerarin (10.2%), Puerarin+Prostratin
(53.8%), Puerarin++VPA (34.4%)；Do not add medicine (Mock) group (2%)；Result table
Bright, either Quercetin with Prostratin or be combined with VPA medicine process cell, its active cell
After efficiency all processes than two medicines, gfp positive cell proportional summation is high, and equally, Puerarin also obtains
Similar results, illustrates, Quercetin and Puerarin and PKC activator Prostratin and VPA have
Synergistic activation.
The experimental result of the present invention and experimental data, demonstrate that Quercetin and Puerarin not only has height
Induced activation effect, and relatively low to cytotoxicity；Go with PKC activator Prostratin and histone
Acetylase inhibitor VPA is used in combination, and has co-induction activation.Thus, described flavonoid
Compound can be used for preparing the medicine that AntiHIV1 RT activity is hidden, described Quercetin and Puerarin
To activate for HIV latent infection virus induction and final removing will provide a new way and means.
Accompanying drawing explanation
Fig. 1 is that HIV is hidden induced activation efficiency by the obstructed concentration of Quercetin and Puerarin compound
Impact, wherein, medicine final concentration is respectively 5 μMs, 10 μMs, 20 μMs, 40 μMs；Process cell 72 little
Flow cytometry, analysis of fluorescence cell proportion is carried out time after.
Fig. 2 is induced activation efficiency of hiding HIV the action time of Quercetin and Puerarin compound
Impact, which show, at final concentration of 20 μMs of drug treating cell 24h, after 48h, 72h, 96h,
Flow cytometry fluorecyte proportion.
Fig. 3 is the Quercetin and the Puerarin toxic action to cell, which show, with final concentration
Being 5 μMs, 10 μMs, 20 μMs, 40 μMs, 80 μMs, Quercetin and Puerarin of 160 μMs processes HIV
Latent infected cells model, the activity of CCK-8 method detection cell.
Fig. 4 shows that Quercetin and Puerarin and PKC activator Prostratin and histone go
Acetylase inhibitor valproic acid (VPA) synergistic activation.
Detailed description of the invention
The activity of embodiment 1.Quercetin and Puerarin compound HIV is hidden induced activation effect
The impact of rate
By 2 × 10E4, every hole cell, C11 cell seeding is added 100ul contain in 96 orifice plates, every hole
1640 culture medium (Gibco) of 10%FBS (Gibco).After 24 hours, add the Quercetin of variable concentrations
And Puerarin, make final concentration be respectively 5 μMs, 10 μMs, 20 μMs, 40 μMs.Each concentration at least 3
Multiple hole, each experiment is repeated 3 times, and drug treating cell is after 72 hours, observation of cell under fluorescence microscope
GFP expression, and collect cell and carry out Flow cytometry, analysis of fluorescence cell proportion；
Result shows, along with the rising of Quercetin and Puerarin compound concentration, in cell model
The cell number expressing green fluorescence increases, and all reaches the highest at 20 μMs；HIV latent infected cells warp
The cell proportion that after Quercetin (20 μMs) process, green fluorescence is positive reaches up to 13.7%；Puerarin exists
During 20 μMs of concentration, the cell ratio of fluorescent positive reaches 9.7%；Do not add the HIV latent infection that derivant processes
Cell, the cell proportion of its fluorescent positive only has and activates less than 2% background；Result point out, Quercetin and
Puerarin compound all has the activation to HIV latent infected cells, and it preferably activates concentration range
For 5-40 μM, and there is dose-effect relationship.
Induction of hiding HIV the action time of embodiment 2.Quercetin and Puerarin compound swashs
The impact of active rate
By 2 × 10E4, every hole C11 cell seeding in 96 orifice plates, every hole adds 100ul containing 10%FBS
(Gibco) 1640 culture medium (Gibco), after 24 hours, add the MGCD0103 of final concentration of 200nM
And MS275.At drug treating cell 24h, after 48h, 72h, 96h, observation of cell under fluorescence microscope
GFP expression, and collect cell and carry out Flow cytometry, analysis of fluorescence cell proportion, each
The multiple hole of Shi Xiangdian at least 3, each experiment is repeated 3 times, and com-parison and analysis induced activation induced activation kinetics is special
Point；
Result shows, Quercetin and Puerarin processes HIV latent infected cells model respectively, with
Time of extends, and the positive cell number of green fluorescence gradually increases, and Quercetin hides sense processing HIV
The cell proportion that after dye cell model 72h, green fluorescence is positive reaches the highest by 13%, and Puerarin is processing HIV
The cell proportion that after latent infected cells model 72h, green fluorescence is positive reaches the highest by 10%, shows that two medicines have
Time-effect relationship.
Embodiment 3.Quercetin and the Puerarin toxic action to cell
By 2 × 10E4, every hole C11 cell seeding in 96 orifice plates, every hole adds 100ul containing 10%FBS
(Gibco) 1640 culture medium (Gibco).After 24 hours, it is separately added into the Quercetin of variable concentrations
And Puerarin, make final concentration be respectively 5 μMs, 10 μMs, 20 μMs, 40 μMs, 80 μMs, 160 μMs.Each dense
Spending at least 3 multiple holes, each experiment is repeated 3 times, and drug treating cell, after 72 hours, adds in every hole
CCK-8 reagent 10 μ L (purchased from Dojindo), cell culture medium hatches 0.5-4h, 450nm in microplate reader
Place surveys OD value, calculates CC50=(experimental group OD value/matched group OD value) X100%；
Result shows, the half toxic concentration of human normal cell line is divided by Quercetin and Puerarin medicine
Not Wei CC50=160 μM and CC50=120 μM, CC50 is the highest, and its cytotoxicity is the lowest, thus, result table
Bright in normal Valid concentration Quercetin and Puerarin relatively low to cytotoxicity, for clinical practice
Lay a good foundation.
Embodiment 4.Quercetin and Puerarin with PKC activator Prostratin and histone are gone
The synergistic activation of acetylase inhibitor valproic acid (VPA)
By 2 × 10E4, every hole cell, C11 cell seeding is added 100ul contain in 96 orifice plates, every hole
1640 culture medium (Gibco) of 10%FBS (Gibco), after 24 hours, being separately added into concentration is 20 μMs
Quercetin and Puerarin, and Quercetin and Puerarin is respectively with 200nM's
The VPA Combined Treatment of Prostratin or 2mM, the multiple hole of each concentration at least 3, each experiment repeats 3
Secondary, drug treating cell is after 72 hours, observation of cell GFP expression under fluorescence microscope, and collects
Cell carries out Flow cytometry, analysis of fluorescence cell proportion；
Result shows, each medicine or Combined Treatment HIV latent infected cells are after 72 hours, to report base
Because of the Flow cytometry of green fluorescent protein, the cell proportion of its green fluorescence positive is respectively as follows:
Quercetin (14.3%), Prostratin (22.6%), VPA (11.4%)；Quercetin+Prostratin
(63.1%), Quercetin+VPA (44%)；Puerarin (10.2%), Puerarin+Prostratin
(53.8%), Puerarin++VPA (34.4%)；Do not add medicine (Mock) group (2%)；Result table
Bright, either Quercetin with Prostratin or be combined with VPA medicine process cell, its active cell
After efficiency all processes than two medicines, gfp positive cell proportional summation is high, and equally, Puerarin also obtains
Similar results, illustrates, Quercetin and Puerarin and PKC activator Prostratin and histone
Deacetylase inhibitor VPA has synergistic activation.
Claims (6)
1. flavone compound purposes in preparing the medicine that AntiHIV1 RT activity is hidden,
Described flavone compound selected from Quercetin (quercetin) or puerarin (Puerarin),
Described structural formula of compound is:
2. the purposes as described in claim 1, it is characterised in that described flavone compound activates HIV
Latent infected cells, and finally remove described latent virus.
3. the purposes as described in claim 1 or 2, it is characterised in that described flavone compound with
Inverase combines activation, removes latent virus.
4. the purposes as described in claim 1, it is characterised in that described HIV latent infected cells choosing
From people's mononuclearcell, human macrophage, people's CD4T lymphocyte, people's mastocyte, people's dendron is thin
Born of the same parents, people's folliculus sample dendritic cell, hematopoietic progenitor cells, people's natural killer cell, human neure or few prominent
Neurogliocyte.
5. the purposes as described in claim 1, it is characterised in that described inverase is selected from:
(1) efabirenz, or (2) non-nucleoside reverse transcriptase inhibitor,
Or (3) protease inhibitor.
6. the purposes as described in claim 5, it is characterised in that in described inverase:
(1) efabirenz is selected from 1. zidovudine zidovudine, 2. red promise
Pungent didanosine, 3. zalcitabine Zalcitabine, 4. stavudine Stavudine, 5. rummy
Husband determines Lamivudine, or 6. Abacavir abacavir；
(2) non-nucleoside reverse transcriptase inhibitor is selected from 1. nevirapine nevirapine, 2. dilazep
Wei pyridine delavird, or 3. efavirenz efavirene；
(3) protease inhibitor is selected from 1. Saquinavir saguinavir, 2. indinavir
Indinavir, 3. ritonavir ritonavir, 4. viracept see nelfinaivr nelfinavirr or 5. amprenavir
amprenavir。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510036805.6A CN105878231A (en) | 2015-01-26 | 2015-01-26 | Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510036805.6A CN105878231A (en) | 2015-01-26 | 2015-01-26 | Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105878231A true CN105878231A (en) | 2016-08-24 |
Family
ID=56999184
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510036805.6A Pending CN105878231A (en) | 2015-01-26 | 2015-01-26 | Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105878231A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113880898A (en) * | 2020-10-30 | 2022-01-04 | 杭州拉林智能科技有限公司 | Flavonoid glycoside-organic amine antimicrobial agent double-salt compound and preparation method and application thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013182662A1 (en) * | 2012-06-06 | 2013-12-12 | Bionor Immuno As | Vaccine |
-
2015
- 2015-01-26 CN CN201510036805.6A patent/CN105878231A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2013182662A1 (en) * | 2012-06-06 | 2013-12-12 | Bionor Immuno As | Vaccine |
Non-Patent Citations (3)
| Title |
|---|
| KI MO KIM等: "Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: A possible pathway through the induction of heme oxygenase-1 expression", 《TOXICOLOGY AND APPLIED PHARMACOLOGY》 * |
| 王晓建 等: "天然产物中槲皮素类化合物的抗HIV作用研究", 《中国实验方剂学杂志》 * |
| 王晓建 等: "槲皮素类化合物抗HIV的研究进展", 《中国中医药远程现代教育》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113880898A (en) * | 2020-10-30 | 2022-01-04 | 杭州拉林智能科技有限公司 | Flavonoid glycoside-organic amine antimicrobial agent double-salt compound and preparation method and application thereof |
| WO2022089600A1 (en) * | 2020-10-30 | 2022-05-05 | 杭州拉林智能科技有限公司 | Flavonoid glycoside-organic amine antimicrobial agent double salt compound, preparation method therefor and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Yildirim et al. | Antiviral activity of hatay propolis against replication of herpes simplex virus type 1 and type 2 | |
| Sun et al. | Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats | |
| CN103237546B (en) | The antiviral compound that contains azide | |
| CN106265679A (en) | Bromine domain protein inhibitor is preparing the purposes that anti-HIV-1 is hidden in medicine | |
| Serkedjieva | Antiviral activity of the red marine alga Ceramium rubrum | |
| Rawat et al. | Neutrophils at the crossroads of acute viral infections and severity | |
| CN105418410A (en) | Emodin derivatives and application thereof in preparation of anti-HIV-1 medicines | |
| Chen et al. | Ganoderic acid Me induces G1 arrest in wild-type p53 human tumor cells while G1/S transition arrest in p53-null cells | |
| CN104069106A (en) | Application of benzamide compound in preparation of medicine for activating latent human immunodeficiency virus | |
| CN105878231A (en) | Application of flavonoid compounds in preparing anti-HIV-latency therapeutic drugs | |
| CN112704072A (en) | Application of wood frog antibacterial peptide in preparation of medicine for resisting novel coronavirus SARS-CoV-2 | |
| CN102000081A (en) | Application of phenylamine acid compound in preparing anti-HIV latent medicament | |
| Sun et al. | Effects of AZT and RNA-protein complex (FA-2-b-β) extracted from Liang Jin mushroom on apoptosis of gastric cancer cells | |
| AU2015352041A1 (en) | Titled extracts of Cynara scolymus and uses thereof | |
| CN105055387A (en) | Applications of taurine in preparing medicines for resisting viruses | |
| Feng et al. | Compound C17 inhibits the lung metastasis of breast cancer. | |
| CN105267211B (en) | Aspochalasin classes compound prepare AntiHIV1 RT activity hide drug and treat AIDS-treating medicine in application | |
| RU2597150C2 (en) | Antiviral compound of multiple action, its composition and method of treating viral diseases | |
| CN108635346B (en) | 3,3 '-(3,4- dichloro benzylidene)-bis- -4 hydroxy coumarins are used to prepare the application of rabies cytotoxic drug | |
| CN102068452A (en) | Antiviral medicinal composition | |
| CN105381024A (en) | Pharmaceutical composition for treating chicken coccidiosis and preparation method thereof | |
| CN102000048B (en) | Application of 4-dimethyl amino nitrogen-5-hydroxy-formyl-hexyl amine for preparing anti-human immunodeficiency virus (HIV) latent medicine | |
| Yuniarti et al. | The potentiation effect of Bawang Dayak (Sisyrinchium palmifolium L.) extract on T47D cell growth inhibition after 5-fluorouracil treatment | |
| Golovacheva et al. | The Effect of Drugs with α-Glutamyl–Tryptophan for Cytokine Secretion and Level of Surface Molecule ICAM-1 In Vitro | |
| CN113712984B (en) | Application of PNPT 1-based small molecule inhibitor combination in preparation of antiviral drugs |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160824 |
|
| RJ01 | Rejection of invention patent application after publication |