CN106727492A - A kind of application of polymethoxyflavone on the medicine for preparing treatment cutaneous papilloma - Google Patents
A kind of application of polymethoxyflavone on the medicine for preparing treatment cutaneous papilloma Download PDFInfo
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Abstract
The present invention relates to polymethoxyflavone treatment cutaneous papilloma.The active ingredient of the invention includes the polymethoxyflavones such as 5,7,3 ', 4 ' tetramethoxy flavones, 5,7,3 ', 4 ', 5 ' pentamethoxyl flavones and 5,6,7,3 ', 4 ', 5 ' hexa methoxy flavones.Cutaneous papilloma is formed with dimethylbenzanthracene and three (2 picolyl) amine induction ICR mouse, compared with induction group, respectively with 5 μm the 5 of ol/L concentration, 7,3 ', 4 ' tetramethoxy flavones, 5,7,3 ', 4 ', 5 ' pentamethoxyl flavones or 5,6,7,3 ', after the treatment of 4 ', 5 ' hexa methoxy flavones, mouse skin tumour quantity reduces 24.2%, 42.5% and 54.2% respectively.
Description
Technical field
The present invention relates to a kind of application of polymethoxyflavone on the medicine for preparing treatment cutaneous papilloma.
Background technology
In defense mechanism, appropriate inflammatory response with activated immune system, and can start immune and inflammatory response in vivo,
Remove the injury of exotic.It is eliminated when exotic and after tissue repairing, acute inflammation is to stop；If exotic cannot be removed completely
Entirely, immune system is not complete or releases signal transmission imbalance of inflammation effect etc., will form chronic inflammation reaction, normal cell or
Destroying for the free radical that tissue is produced by inflammation or immunocyte, causes the excessive diastole of blood vessel, necrosis, produces carcinogenicity
Influence, wherein comprising the structural modification for causing DNA base mutation and protein, influenceing cell membrane function or causing intracellular protein
The function of matter or enzyme is lost.Inflammatory cell start to transform to tumour cell and constantly hyperplasia [Allavena, P., Garlanda,
C.,Borrello,M.G.,Sica,A.,and Mantovani,A.(2008)Pathways connecting
inflammation and cancer.Curr.Opin.Genet.Dev.,18,3-10.]。
Chemical carcinogenesis is typically in the presence of compound, and induced tumor is formed.Early in nineteen forty-seven, Bernblum and
The result of study of Shubik just confirms, in murine skin surface partial smearing chemical carcinogenesis medicine, can make corresponding site skin shape
Into Papillary Tumors [Berenblum, I.and Shubik, P. (1949) The persistence of latent tumour
cells induced in the mouse's skin by a single application of 9:10-dimethyl-1:
2-benzanthracene.Br.J.Cancer,3,384-386.].This processing method can shorten long-term carcinogenicity testing when
Between, can help to understand carcinogenic substance in tumour generation and development with the dynamic of clear view to tumour growth during smearing
Different phase, mechanism of action [Mueller, M.M. (2006) Inflammation in development are formed to tumour
epithelial skin tumours:old stories and new ideas.Eur.J.Cancer,42,735-744.]。
The chemical carcinogens that chemical carcinogenesis is more often used include dimethylbenzanthracene (7,12-dimethylbenzanthraene,
) and three (2- picolyls) amine (12-O-Tetradecanoyl-phorbol 13-Acetate, TPA) DMBA.It is many as one kind
The aromatic hydrocarbon base class pluripotency carcinogenic substance of ring, DMBA enters in organism after skin absorption, and many sites that can induce DNA are dashed forward
Become, influence a series of expression of oncogenes and tumor suppressor gene, the canceration of active cell.In the partial smearing TPA meetings of mouse skin
The increase of oxyradical is caused, causes the phenomenon of oxidative pressure rising and local inflammation.TPA will cause intracellular anti-oxidant system
System is unbalance, tumor tissues is maintained the microenvironment of inflammation, promotes cell that canceration occurs.In inflammatory response, the oxygen of induction type one
Change nitrogen synthase (inducible nitric oxide synthase, iNOS) and its product nitric oxide (Nitrogen
Monoxide, NO) content be higher than normal structure, DNA damage, the repair ability of destruction misreplication DNA can be caused, cause
Expressed protein changes, and it is lost original function with activity；NO have promote angiogenesis, leucocyte it is glutinous
Attached, infiltration and the transfer of tumour cell.Existing much researchs are confirmed, in different chronic inflammation diseases and malignant tumor tissue
In, all NO with high level.Extracellular, NO is extremely unstable, and nitrite is just converted into after several seconds, generally all passes through
The content of nitrite is determined to detect content [Moncada, S., Palmer, R.M., the and Higgs, E.A. of intracellular NO
(1991)Nitric oxide:physiology,pathophysiology,and
pharmacology.Pharmacol.Rev.,43,109-142.].COX-2 (cyclooxygenase, COX-2) be by
Prostaglandin synthesizes, and the synthesis of COX-2 is subject to tumor necrosis factor-alpha (tumor necrosis factor alpha, TNF-
α), interleukin-1 ' beta ' (interleukin-1 β, IL-1 β) and EGF (Epidermal growth factor,
EGF induction), in inflammatory response period, the expression of COX-2 can increase vasopermeability, lifting white blood cell and immunocyte
Chemotaxis, expands scope [Tsujii, M., Kawano, S., Tsuji, S., Sawaoka, H., Hori, M., the and of inflammatory response
DuBois,R.N.(1998)Cyclooxygenase regulates angiogenesis induced by colon
cancer cells.Cell,93,705-716.]；Separately there is research to point out, before DMBA and TPA treatment, with iNOS and COX-2
After inhibitor pretreatment of mice skin, DMBA and the TPA Tumor incidence for being induced and the number for forming tumour can be substantially reduced
Amount [Chun, K.S., Cha, H.H., Shin, J.W., Na, H.K., Park, K.K., Chung, W.Y., and Surh, Y.J.
(2004)Nitric oxide induces expression of cyclooxygenase-2 in mouse skin
through activation of NF-kappaB.Carcinogenesis,25,445-454.].So, from the induction of inflammation
During tumour is developed into, iNOS and COX-2 play an important role.
Cutaneous papilloma is formed after epithelial tissue hyperplasia due to epidermis nipple spline structure.Cutaneous papilloma
The incidence of disease show increase year by year and rejuvenation trend, because the sick risk factor is more, the cause of disease is complicated, definite pathogenesis
It is still unclear.On clinical treatment, cutaneous papilloma have easy canceration turn into cutaneum carcinoma, operative treatment after easily recurrence,
The features such as multiple and generation disorganization.At present, the research report both at home and abroad in terms of cutaneous papilloma treatment is relative
It is less, the generation of the disease how is effectively controlled, therapeutic effect is improved, the recurrence and canceration of tumour are prevented, with very important
Meaning.
In recent years, numerous results of study confirms that the natural materials for partly being extracted from plant are swollen with stronger prevention
The activity of tumor cell growth.Polymethoxyflavone belongs to flavone compound, has content higher in orange peel.It is such
More than two methoxy substitution bases are connected on the C6-C3-C6 skeletons of compound, have preferable biology sharp because polarity is relatively low
With rate.Existing result of study shows that polymethoxyflavone class material has bioactivity [the Middleton E of anti-inflammatory
Jr,Kandaswami,C.,and Theoharides,T.C.(2000)The effects of plant flavonoids on
ma mmalian cells:implications for inflammation,heart disease,and
cancer.Pharmacol.Rev.,52,673-751.Manthey,J.A.,Grohmann,K.,and Guthrie,N.
(2001)Biological properties of citrus flavonoids pertaining to cancer and
inflammation.Curr.Med.Chem.,8,135-153.].Many researchs confirm that polymethoxyflavone has and not by first
It is the similar activity of base flavones, such as anticancer, antiviral, and bioavailability is higher than the flavones not being methylated
[Nielsen,S.E.,Breinholt,V.,Cornett,C.,and Dragsted,L.O.(2000)
Biotransformation of the citrus flavone tangeretin in rats.Identification of
metabolites with intact flavane nucleus.Food Chem.Toxicol.,38,739-746.].This hair
Bright used polymethoxyflavone compound is following three kinds：5,7,3 ', 4 '-tetramethoxy flavones (3 ', 4 ', 5,7-
Tetramethoxy flavone, 4-PMF), 5,7,3 ', 4 ', 5 '-pentamethoxyl flavones (5,7,3 ', 4 ', 5 '-
Pentamethoxy flavones, 5-PMF) and 5,6,7,3 ', 4 ', 5 '-hexa methoxy flavones (5,6,7,3 ', 4 ', 5 '-
Hexamethoxy flavone, 6-PMF), three belongs to polymethoxyflavone, and 4-PMF is moon tangerine (Murraya
Paniculata) one of with polymethoxyflavone main in black ginger (Kaempferia parviflora), these plants carry
Take thing and have been shown to have the bioactivity such as anti-inflammatory, antitumor and anti-oxidant [Kinoshita, T.and Shimada, M.
(2002)Isolation and structure elucidation of a new prenylcoumarin from
Murraya paniculata var.omphalocarpa(Rutaceae).Chem.Pharm.Bull.(Tokyo),50,118-
120.Yenjai,C.,Prasanphen,K.,Daodee,S.,Wongpanich,V.,and Kittakoop,P.(2004)
Bioactive flavonoids from Kaempferia parviflora.Fitoterapia,75,89-92.].This patent
It is application of the polymethoxyflavone on treatment cutaneous papilloma is prepared, reaches the purpose for the treatment of cutaneous papilloma.
The content of the invention
There is easy canceration for cutaneum carcinoma, postoperative easy recurrence, multiple growth for most skin emulsus knurl and group is also easy to produce
The characteristics of knitting destruction, the answering on the medicine for preparing treatment cutaneous papilloma the invention provides a kind of polymethoxyflavone
With.By cell experiment and zoopery, it is found that such compound has obvious action effect to cutaneous papilloma.
Described many methyl flavones include being connected to the flavones that more than two methoxies replace base on all C6-C3-C6 skeletons,
Including 4-PMF (structural formula is shown in Fig. 1), 5-PMF (structural formula is shown in Fig. 1) and 6-PMF (structural formula is shown in Fig. 1).
The preparation of chemical reagent：
DMBA：Accurately weigh 1.2815mg DMBA, with 200 μ L acetone solutions after, the DMBA for being configured to 1 μm of ol/mL is molten
Liquid, it is now with the current.
TPA：5mg TPA accurately are weighed, with the TPA stock solutions that 100nmol/200 μ L are configured to after 200 μ L acetone solutions,
Using preceding 5nmol/200 μ L are diluted to acetone.
4-PMF、5-PMF、6-PMF：0.0342g 4-PMF, 0.0372g 5-PMF, 0.0402g6-PMF accurately are weighed, point
After not with 200 μ L acetone solutions, be configured to 100 μm of storing solutions of ol/200 μ L, using it is preceding with acetone be diluted to required for it is dense
Degree.The concentration of the polymethoxyflavone is 2.5-40 μm of ol/L.
Application method of the polymethoxyflavone of the present invention to the growth inhibition effects of mouse macrophage RAW 264.7
For：By cell culture in the streptomysin of the penicillin containing 100U/ml and 100 μ g/ml, the DMEM culture mediums of 10% hyclone
In, cultivation temperature is 37 DEG C, and gas concentration lwevel is under conditions of 5%, when cell growth is full to 8 points, to be trained in DMEM respectively
Support lipopolysaccharides (Lipopolysaccharides, LPS) and final concentration of 2.5-10 μ that base adds final concentration of 100ng/mL
Mol/L after culture 24h, collects the supernatant of cell culture fluid with the polymethoxyflavone of acetone solution, determines nitrite and contains
Amount.
Polymethoxyflavone of the present invention makes to chemical induction ICR mouse skin papilloma growth inhibition effects
It is with method：ICR mouse are randomly assigned to each cage by 6/cage, two cages are one group (i.e. one group has 12), are divided into
It is induction group, control group, 5 μm of ol/200 μ L 4-PMF treatment groups, 5 μm of ol/200 μ L 5-PMF treatment groups and 5 μm of ol/200 μ L
6-PMF treatment groups.After adapting to raise one week, ICR mouse backs are rejected into one piece of area about near tail position with small-sized razor
2cm2The hair in region.It is 1 μm of DMBA of ol/mL reject hair position to smear 200 μ L concentration, again in same area after 2 days
Smear the DMBA of 200 μ L same concentrations.After DMBA processes a week, hair position is being rejected, induction group continues per week
Smeared 2 times with the TPA of 5nmol/200 μ L concentration；The acetone that control group continues 200 μ L per week is smeared 2 times；4-PMF treatment
It is that 5 μm of 4-PMF of ol/200 μ L are smeared 2 times that group continues 200 μ L concentration per week；5-PMF treatment groups are persistently per week to use 200
μ L concentration is that 5 μm of 5-PMF of ol/200 μ L are smeared 2 times；It is 5 μm of ol/200 that 6-PMF treatment groups continue 200 μ L concentration per week
The 6-PMF of μ L is smeared 2 times, and after the 2nd DMBA treatment, all groups are persistently processed 20 weeks again.Record with diameter greater than 1mm weekly simultaneously
Persistently there is 2 tumour quantity more than week, and measure tumor size.Mouse, statistics tumour quantity, tumour hair are put to death after 20 weeks
Raw rate (%) and tumor size.
The device have the advantages that：
Selected polymethoxyflavone in the present invention, can extract separation from plant, belong to natural plant chemical combination
Thing, wide material sources, it is also possible to directly from Reagent Company's purchase.Compared with induction group, respectively with 4-PMF, 5- of 5mol/L concentration
After PMF or 6-PMF treatment, mouse skin tumour quantity reduces 24.2%, 42.5% and 54.2% respectively.Test result indicate that,
Polymethoxyflavone is notable to the therapeutic effect of cutaneous papilloma.The present invention can instruct the new cutaneous papilloma of exploitation to treat
Method, for Future Development provides new direction and strategy using polymethoxyflavone class compound.
Brief description of the drawings
Fig. 1 is the molecular structure of 4-PMF, 5-PMF and 6-PMF.
Fig. 2 is that the LPS and various concentrations polymethoxyflavone of the cells of RAW 264.7 100ng/ml process culture after 24h
The content of base nitrite.
Fig. 3 is the expression of iNOS and COX-2 in different groups of ICR mouse back skins.
Fig. 4 is the expression of DNMT1 and DNMT3b in different groups of ICR mouse back skins.
Fig. 5 is the expression of GPR55 in different groups of ICR mouse back skins.
Fig. 6 is the expression of p38 and p-p38 in different groups of ICR mouse back skins.
Fig. 7 is the expression of p-PI3K and p-Akt in different groups of ICR mouse back skins.
Fig. 8 is the effect of the ICR mouse skin tumour quantity that polymethoxyflavone is induced DMBA/TPA.
Fig. 9 is different groups of ICR mouse skin tumor inducing percentage.
Figure 10 is the inhibitory action of the ICR mouse skin tumours that polymethoxyflavone is induced DMBA/TPA.
Specific embodiment
Influence of the polymethoxyflavone of embodiment 1 to the content of nitrite of mouse macrophage RAW 264.7
The cell cultivated is mouse macrophage RAW 264.7, and culture medium is DMEM culture mediums, containing final concentration of
The streptomysin of the penicillin of 100U/ml and 100 μ g/ml, the hyclone that volume ratio is 10%, cultivation temperature are 37 DEG C, dioxy
It is 5% to change concentration of carbon.Mouse macrophage RAW 264.7 is cultivated in 24 porocyte culture plates, when cell growth is full to 8 points
Afterwards, add lipopolysaccharides (Lipopolysaccharides, LPS) and the end of final concentration of 100ng/mL dense in different holes respectively
Spend for 2.5 μm of ol/L, 5 μm of ol/L, 10 μm of ol/L, 20 μm of ol/L, 40 μm of ol/L 4-PMF, 5-PMF or 6-PMF, continue to cultivate
After 24 hours, take respectively in medium supernatant to 96 orifice plates of the above-mentioned each treatment of 100 μ L, this examination in 100 μ L lattice is added per hole
After agent (aqueous solution containing 1% sulfanilamide (SN) and 0.1% hydrochloride naphthodiamide) is well mixed, under wavelength 570nm, examined with ELIASA
Survey light absorption value.Light absorption value testing result as shown in Fig. 2 compared with induction group, the NO contents of 4-PMF treatment groups reduce 3.39~
16.42%, inhibition is compared with induction group and there was no significant difference；In concentration 2.5,5 and 10M, 5-PMF treatment groups have bright
The aobvious effect for suppressing NO synthesis, NO contents reduce 30.96%, 40.38% and 35.75% respectively；Concentration is 2.5,5,10,20 and
The 6-PMF of 40M is respectively 0.11%, 24.60%, 31.12%, 45.38% and 45.76% to the inhibiting rate that NO synthesizes, and presents
Dose-dependent phenomenon, and there is significant difference compared with induction group.Learn from the above, polymethoxyflavone has suppression
The ability of NO synthesis processed, and with the increase of methoxyl group quantity, its suppression is more obvious, it is optimal with 6-PMF rejection abilities.
Influence of the polymethoxyflavone of embodiment 2 to DMBA/TPA induction ICR mouse skins papilloma growths
Experiment is purchased from Le Sike biotech inc with ICR mouse, is randomly assigned to each cage by 6/cage
Son, two cages are one group (i.e. one group has 12), are divided into induction group, control group, 5 μm of ol/200 μ L 4-PMF treatment groups, 5 μ
Mol/200 μ L 5-PMF treatment groups and 5 μm of ol/200 μ L 6-PMF treatment groups.Feeding environment keeps 25 DEG C of constant temperature, daily illumination
12 hours/dark 12 hours, bedding and padding and drinking water were changed weekly 2 times.After adapting to raise one week, with blade by ICR mouse backs
One piece of area is rejected near tail position be about 2cm2Hair.It is 1 μm of ol/mL reject hair position to smear 200 μ L concentration
DMBA, after 2 days again same area smear 200 μ L same concentrations DMBA.After DMBA processes a week, hair is being rejected
Hair position, each group presses following processing method continuous processing 20 weeks：Induction group continues the TPA of use 5nmol/200 μ L concentration per week
Smear 2 times；The acetone that control group continues 200 μ L per week is smeared 2 times；4-PMF treatment groups continue per week with 200 μ L concentration
For 5 μm of 4-PMF of ol/200 μ L are smeared 2 times, after 4-PMF being painted with every time 30 minutes, 5nmol/200 μ L are smeared in same area
TPA；It is that 5 μm of 5-PMF of ol/200 μ L are smeared 2 times that 5-PMF treatment groups continue 200 μ L concentration per week, and 5- is painted with every time
After PMF 30 minutes, the TPA of 5nmol/200 μ L is smeared in same area；6-PMF treatment groups continue per week with 200 μ L concentration
For 5 μm of 6-PMF of ol/200 μ L are smeared 2 times, after 6-PMF being painted with every time 30 minutes, 5nmol/200 μ L are smeared in same area
TPA.Experiment is whole to be eaten with single water that steams using the standard feed that can sterilize for experimental animal.Record with diameter greater than 1mm weekly simultaneously
Persistently in the presence of 2 week above tumour quantity and measure tumor size.After 20 weeks, locate after last time TPA is processed 24 hours
Dead mouse, statistics tumour quantity, Tumor incidence (%) and tumor size (Fig. 3, Fig. 4, Figure 10).
Cosmetic variation：Persistently after 20 weeks, the back of every mouse of induction group has papilloma to generate to treatment TPA；Control
Group does not have tumour then；Pre-process in the group of PMFs, 4-PMF, 5-PMF and 6-PMF treatment group have suppression tumour quantity
With the phenomenon (Fig. 3, Fig. 4, Figure 10) of size.
Tumour growth situation：After testing 20 weeks, statistics such as Fig. 3, Fig. 4 of each group mouse tumor quantity and incidence.
After induction group mouse persistently smears TPA to the 7th weeks in experimentation, that is, papillomatous generation is begun with, to after the 20th week, often
Mouse tumour quantity average out to 21, Tumor incidence is up to absolutely；Control group is then until experiment end in 20 weeks does not all have
Papilloma is formed, the tumor inducing pattern for showing the experiment is to set up；Every mouse tumor quantity of 4-PMFs groups is average
It it is 12.0, Tumor incidence is 92%；Every mouse tumor quantity average out to 9.1 of 5-PMF groups, Tumor incidence is
83%；Every mouse tumor quantity average out to 4.7 of 6-PMF groups, Tumor incidence is 100%.
Tumour quantity and size distribution：Induction group ICR mouse skin tumor sizes are：1-3mm3Have 7.8 ± 3.8；
3-5mm3Have 3.0 ± 1.1；≧5mm3Have 10.3 ± 6.9.4-PMF groups tumor size is 1-3mm3Have 6.4 ± 2.4
；3-5mm3Have 2.2 ± 2.2；≧5mm3Have 3.5 ± 3.8.5-PMF groups tumor size is 1-3mm3Have 5.4 ±
4.3；3-5mm3Have 0.8 ± 1.0；≧5mm3Have 2.9 ± 3.3.6-PMF groups tumor size is 1-3mm3Have 2.1
± 2.0；3-5mm3Have 0.8 ± 1.0；≧5mm3Have 1.8 ± 2.0.
Learn from the above, after being processed with 4-PMF, 5-PMF or 6-PMF that concentration is 5 μm of ol/L, experiment mice it is swollen
Knurl quantity is significantly reduced, and compared with induction group, 24.2%, 42.5% and 54.2% is reduced respectively.Accordingly, our inferences, with
The increase of PMFs methoxyl group quantity, the tumour quantity, the effect of size caused by PMF suppression DMBA/TPA are more obvious, and
Statistical conspicuousness is reached, but cannot be improved for Tumor incidence, its reason is probably because PMFs cannot suppress the
Gene mutation in one week DMBA Induction Process, then, smearing TPA persistently stimulates the skin histology, oxidative pressure gradually to increase, most
Papillomatous generation cannot be suppressed eventually.
Influence of the polymethoxyflavone of embodiment 3 to DMBA/TPA induction ICR murine genes expression
Mouse is processed as described in Example 2, and the skin for the treatment of site after death, is collected by place.Skin histology is cut into tiny
Fragment after, according to every 20mg skin histologies add 150-250 μ L lysates (NaCl, 1mmol/L's containing 150mmol/L
The PMSF of the leupeptin of EDTA, 1g/mL, the aprotinin of 1g/mL, the pepsin inhibitor of 1g/mL and 1mmol/L)
Ratio add Tissue lysates, with glass homogenizer be homogenized to fully cracking after, 10,000rpm centrifugation 5 minutes, take supernatant.
It is concentration titer with 2mg/mL BSA solution, the light absorption value at 595nm, protein concentration in conversion sample is determined with ELIASA.
After protein is through polyacrylamide gel electrophoresis, transferring film, with reference to primary antibody, secondary antibody, testing goal Protein G PR55, phospho-
The change of p38, phospho-PI3K, phospho-Akt, DNMT1, DNMT3b, iNOS and COX-2 expression.Each sample
It is repeated 3 times, experimental result is represented with average value ± standard deviation, and analyzes the difference between each group, when p value is less than 0.05
Represent that statistically there is significant difference.
Experimental result shows that compared with control group, the protein expression amount of GPR55 substantially increases induction group, shows GPR55
Participate in TPA and lure that mouse skin produces the process of lesion into；In polymethoxyflavone pretreated group, with 5-PMF groups and 6-PMF groups
Suppression is the most obvious, and wherein the inhibition of 5-PMF is better than 6-PMF (Fig. 5).It follows that polymethoxyflavone can lead to
Cross reduction TPA and be led to the effect of GPR55 in skin, and then reach the generation of the phenomenons such as dephlogistication.In induction group mouse skin
Phospho-p38 expressing quantities be significantly higher than control group, and in 4-PMF, 5-PMF and 6-PMF treatment group, TPA inductions
The expressional function of phospho-p38 all receives certain suppression, and the wherein inhibitory activity of 5-PMF treatment groups is most strong (Fig. 6)；This
Outward, phospho-PI3K the and phospho-Akt expressions of induction group are significantly increased compared with control group, 4-PMF, 5-
PMF is significantly reduced with the expression of phospho-PI3K, phospho-Akt of 6-PMF treatment groups compared with control group, wherein
Again with the inhibitory action of 5-PMF and 6-PMF treatment groups the most substantially (Fig. 7)；As shown in Figure 8, two important DNA of induction group
Transmethylase：DNMT1 and DNMT3b are not activated, and the DNMT1 and DNMT3b of polymethoxyflavone treatment group are expressed
Level has increase, and, to the expression highest of DNMT1, the expression of the DNMT3b of 6-PMF treatment groups is most for 5-PMF treatment groups
It is high.Two results of summary are it may be speculated that polymethoxyflavone can be adjusted by regulating and controlling the expression of DNMT1 and DNMT3b
The transcriptional activity of iNOS.It follows that the expression that PMFs suppresses inflammatory factor may be by regulation and control phospho-p38MAPK on the way
Footpath and PI3K/Akt approach, are transferred in nucleus and transcribe out downstream iNOS and COX-2 (Fig. 9), Jin Erda to suppress NF- κ B
To the effect for suppressing inflammatory response.
Bio-toxicity evaluation of the polymethoxyflavone of embodiment 4 to ICR mouse
Mouse is processed as described in Example 2, after putting to death mouse, weighs body weight, the liver,spleen,kidney weight of each group ICR mouse
Amount, blood is gathered in Culling heart blood mode, and after room temperature places 1h, 4 DEG C of 3000rpm are centrifuged 10min, collect serum, are stored in -80
In DEG C refrigerator.Liver function biochemical index is detected with automatic clinical chemistry analyzer：Aspartic acid transaminase (aspartate
Aminotransferase, AST), alanine aminotransferase (alanine aminotransferase, ALT), triglyceride
(triglyceride, TG) and T-CHOL (total cholesterol, T-cho), testing result is shown in Table 1.From testing result
As can be seen that not existing significant sex differernce between two groups of data, polymethoxyflavone does not show bio-toxicity to ICR mouse.
Bio-toxicity evaluation of the polymethoxyflavone of table 1 to ICR mouse
| Group | Liver/body weight | Kidney/body weight | Spleen/body weight | GOT(Unit/L) | GPT(Unit/L) | TG(mg/dl) | T-cho(mg/dl) |
| Induction group | 3.91±0.25 | 0.85±0.07 | 0.25±0.03 | 93.4±9.7 | 23.2±4.8 | 113.7±28.9 | 78.9±4.2 |
| 4-PMF treatment groups | 3.95±0.35 | 0.89±0.02 | 0.23±0.04 | 93.6±7.2 | 24.1±4.9 | 112.4±28.9 | 76.5±4.1 |
| 5-PMF treatment groups | 3.92±0.28 | 0.83±0.07 | 0.24±0.03 | 93.1±8.1 | 22.5±3.6 | 114.3±15.6 | 76.2±3.6 |
| 6-PMF treatment groups | 3.99±0.31 | 0.88±0.04 | 0.26±0.05 | 94.1±6.3 | 24.9±5.2 | 113.1±20.3 | 79.3±4.7 |
Claims (5)
1. application of a kind of polymethoxyflavone on the medicine for preparing treatment cutaneous papilloma.
2. the application described in claim 1, it is characterised in that polymethoxyflavone include 5,7,3 ', 4 '-tetramethoxy flavones,
5,7,3 ', 4 ', 5 '-pentamethoxyl flavones and 5,6,7,3 ', in 4 ', 5 '-hexa methoxy flavones any one, two kinds or many
Kind.
3. the application described in claim 2, it is characterised in that polymethoxyflavone is on the medicine for the treatment of skin Ru Tou Zhuan liu
Using.
4. the application described in claim 3, it is characterised in that the tumour for being suppressed is dimethylbenzanthracene and three (2- pyridine first
Base) cutaneous papilloma that is formed of amine induction ICR mouse.
5. the application described in claim 3, it is characterised in that the concentration of described polymethoxyflavone is 2.5 μm of ol/L-
40μmol/L。
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| CN201611199889.6A CN106727492A (en) | 2016-12-22 | 2016-12-22 | A kind of application of polymethoxyflavone on the medicine for preparing treatment cutaneous papilloma |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US20030216481A1 (en) * | 2002-04-30 | 2003-11-20 | Unigen Pharmaceuticals, Inc. | Formulation of a mixture of Free-B-ring flavonoids and flavans as a therapeutic agent |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030216481A1 (en) * | 2002-04-30 | 2003-11-20 | Unigen Pharmaceuticals, Inc. | Formulation of a mixture of Free-B-ring flavonoids and flavans as a therapeutic agent |
Non-Patent Citations (5)
| Title |
|---|
| A. LAKSHMI, S. SUBRAMANIAN: "Chemotherapeutic effect of tangeretin, a polymethoxylated flavone studied in 7, 12-dimethylbenz(a)anthracene induced mammary carcinoma in experimental rats", 《BIOCHIMIE》 * |
| AKIRA MURAKAMI: "Inhibitory Effect of Citrus Nobiletin on Phorbol Ester-induced Skin Inflammation,", 《CANCER RESEARCH》 * |
| JUN WU ET AL.,: "The anti-inflammatory activity of several flavonoids isolated from Murraya paniculata on murine macrophage cell line and gastric epithelial cell (GES-1)", 《PHARMACEUTICAL BIOLOGY》 * |
| LARISSA G. FAQUETI ET AL.,: "Antinociceptive and anti-inflammatory activities of standardized extract of polymethoxyflavones from Ageratum conyzoides", 《JOURNAL OF ETHNOPHARMACOLOGY》 * |
| NIANHAN MA ET AL.,: "5-Demethyltangeretin is more potent than tangeretin in inhibiting dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin tumorigenesis", 《JOURNAL OR FUNCTIONAL FOODS》 * |
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