CN104161767A

CN104161767A - Flavonoids compound, preparation method and application thereof

Info

Publication number: CN104161767A
Application number: CN201410323110.1A
Authority: CN
Inventors: 郭澄; 万丽丽; 李斌
Original assignee: Shanghai Sixth Peoples Hospital
Current assignee: Shanghai Sixth Peoples Hospital
Priority date: 2014-07-08
Filing date: 2014-07-08
Publication date: 2014-11-26

Abstract

The invention provides a flavonoids compound, a preparation method and an application of the flavonoids compound in medicine for prevention and treatment of cachexia. The compound has a structure shown in a structural formula (I) as follows. The provided flavonoids compound can be used for preparing the medicine for treating human and animal cachexia, and cachexia relative to a plurality of diseases can be treated, lowered body weight due to skeletal muscle atrophy and fat degradation atrophy can be effectively alleviated, tumour burden can be obviously mitigated, protein degradation is inhibited, and cytokine TNF-a and IL-6 level can be increased.

Description

A kind of flavone compound and its preparation method and application

Technical field

The present invention relates to a kind of flavone compound and its preparation method and application, relate in particular to a kind of for prevention, treat cachectic flavone compound, and its preparation method and application.

Background technology

Cachexia is the many organs syndrome taking weight loss, amyotrophy and fatty tissue consumption as feature, often occur together in various chronic diseases, as tumor, tuberculosis, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure, infectious disease and acquired immune deficiency syndrome, its carrying out property loses weight and muscular tissue atrophy can not be reversed by conventional nutritional support, causes carrying out property body function obstacle; Clinical manifestation is anorexia, lose weight, anemia and amyotrophy, and these cause Quality of Life of Patients to decline and the existence time limit significantly shortens, and have intervened the normal therapeutic process of disease.Epidemiological study shows cachexia, and in tumor colony, sickness rate is more than 40%, and wherein the solid tumor sickness rate such as gastroenteric tumor, breast carcinoma, pulmonary carcinoma, carcinoma of prostate, cancer of pancreas is higher, and late incidence is even up to 80%; In acquired immunity syndrome patient, sickness rate is about 35%, Patients with Chronic Obstructive Pulmonary Disease sickness rate approximately 20%, patients with renal failure sickness rate 40%, arthritic's sickness rate approximately 10%, patients with heart failure sickness rate approximately 20%.The sickness rate that cachexia is high and fatality rate receive much concern its clinical treatment drug research.

Tumor cachexia be a kind of can not reverse by conventional nutritional support treatment follow or do not follow multifactor syndrome lipopenic, the minimizing of carrying out property skeletal muscle, although the best mode for the treatment of cancer cachexia is treated malignant tumor exactly, the treatment of most of cancers still can not obtain satisfied curative effect.The cachectic pathogeny of tumor is not yet completely clear and definite at present, it is generally acknowledged that cachectic generation is relevant to patient's energy Deficiency of Intake, consumption increase, intermediate supersession disorder, cytokine increase etc.; There is theory and mainly contain cytokine theory, muscle mass theory, protein ubiquitination degradation theory, fat acid decomposition theory etc. in it, the change of patient's sense of taste, appetite depression, hypothalamic function are bad, the machine-processed easily anorexia such as abnormal of appetite stimulator, cause energy Deficiency of Intake.Patient is in the Chronic consumptions evolutions such as tumor simultaneously, a large amount of glucoses are degraded with glycolysis form, lactic acid increases, and the sensitivity decline of tumor patient insulin beta cell receptor to glucose, and so vicious cycle causes the poor efficiency utilization of a large amount of energy expenditures and glucose; The conversion ratio of glycerol and fatty acid increases, and the body of becoming thin can not be oxidized endogenous fatty acid or blood fat with normal speed, in the time of glucose infusion, can not suppress fatty decomposition; Protein in body synthesis rate declines, and albuminolysis increases, and causes rest energy expenditure to increase.The intermediate material that metabolism disorder simultaneously produces is affected as lactic acid etc. causes patient physiological function.The immunomodulating of the early stage participation such as cytokine TNF-α, IL-1, IL-6, INF-r body to tumor cell, but along with the progress of the tumor course of disease, these substances produce significant appetite inhibiting effect, cause the uncomfortable reaction of serious body, and TNF-α, INF-γ etc. and albumen, steatolysis are relevant, it can suppress lipoprotein lipase activity, activates the protein catabolism approach such as Ubiquitin-proteasome path and causes proteolysis, causes the decomposition of muscle and fatty tissue.Therefore, increase appetite, muscle and body weight aspect have been concentrated on for treatment of cachexia.Mainly contain two schemes for treatment of cachexia at present, the one, by the medicine that improves anorexia, increase appetite, for example progestogens medicine is as medroxyprogesterone, megestrol, the part stomach flesh of growth hormone endogenous receptor is starved element, and novel melanocortin receptor agonists etc. increase cachexia patient's food-intake; The 2nd, the medicine of the signal transduction path that the inflammatory mediator that muscle quantities is lost for reducing, minimizing causes muscle consumption and blocking-up muscle consume, the such as medicine of the anti-inflammatory factor and monoclonal antibody, Thalidomide, Embrel TNF-α and IL-6 monoclonal antibody, polyunsaturated fatty acid, beta 2 receptor agonist formoterol, NSAID (non-steroidal anti-inflammatory drug) class indomethacin, celecoxib etc.; But said medicine or because lower curative effect and larger side reaction, has limited its extensive use.

Do not develop at present and be applied to the cachectic natural drug of clinical treatment.Society of Oncology of U.S. nursing branch recommends the medicine of clinical practice to only have progestin preparation and Donisolone, and this two classes medicine, as medroxyprogesterone, dexamethasone etc. are only improved the effect of appetite, do not put on weight and suppresses skeletal muscle; And other as protein stimulatory synthetics, Thalidomide, the Pei Tuoxi film etc. still not exemplary application in clinical; In natural drug, be not applied to the cachectic medicine of clinical treatment yet.

Flavone compound claims again bioflavonoids, previously refer to taking basic parent nucleus as 2-phenyl chromone compounds (structural formula X represents), now make a general reference two phenyl ring with phenolic hydroxyl group interconnect the compounds forming general name by three carbon atoms of central authorities, it is extensively present in each position of plant, and flavone belongs to the one of flavone compound.Replacing flavone can extract or be obtained through chemical modification by extract from Chinese medicine, because it has antioxidation, antiinflammatory, antitumor isoreactivity, cachexia to adenocarcinoma of colon induction has significant mitigation, can prevent and treat or alleviate the caused anorexia of cachexia, weight loss and muscle consumption.

In body, experiment showed, that flavone compound modifies weight loss and the loss of appetite that can effectively suppress after certain position due to malignant tumor induction cachexia, improve weight and muscle treatment, alleviate apositia; Chinese patent CN03115624.X discloses 3,7,3 ', 4 '-replace chromocor compound in the application of preparing in the medicine for the treatment of cancer cachexia, find 3,7,3 ', 4 '-replacing chromocor compound can obviously suppress the cytokines such as mouse macrophage secreting tumor necrosis factor, interleukin-1 and-6, and experimental cancer cachexia is had to obvious therapeutical effect.Flavone compound is developed as the cachectic medicine for the treatment of by this result of study support.

Summary of the invention

The invention provides a kind of flavone compound (flavonoids), and preparation method thereof and application in prevention, treatment cachexia medicine.

A first aspect of the present invention is to provide a kind of flavone compound, and the effective ingredient of described medicine is 3,5,6,7,3 ', 4 '-replacement flavone, and its structural formula represents with (I):

Wherein:

R1, R2, R3 are selected from carbochain, the NR of H, hydroxyl, C1-C22 ₁₁r ₁₂, wherein, R ₁₁, R ₁₂respectively independently selected from H and the group that can eliminate at people or mammal internal metabolism;

R4 is for having the group of structural formula (II):

R5, R6 are carbochain, the NR of cyano group, hydroxyl, carboxyl, C1-C22 ₁₁r ₁₂, wherein, R ₁₁, R ₁₂respectively independently selected from H and the group that can eliminate at people or mammal internal metabolism.

Wherein, the carbochain of described C1-C22 is selected from aliphatic group branching or straight chain or ring-type, saturated or undersaturated, aryl radical, aliphatic group substituted aroma alkyl, aryl radical substituted fatty hydrocarbon base, main chain containing containing heteroatomic carbocyclic ring on heteroatomic carbochain, ring skeleton.

Described hetero atom can be to be selected from any one or a few in N, O, S, P, B.

Described heteroatomic quantity can be 1-3, more preferably 1-2.

More preferably, the carbochain that the carbochain of described C1-C22 is C1-C15, the more preferably carbochain of C1-C12.

The carbochain of described C1-C22 can be to be selected from any one or a few in alkyl, aromatic radical substituted alkyl, aromatic radical, alky-substituted aromatic base, alkoxyalkyl, phenoxyalkyl, alkyl substituted benzene oxygen base alkyl, alkyl amino alkyl.

In foregoing of the present invention, the carbochain of C1-C22 can be: methyl, ethyl, propyl group, isopropyl, normal-butyl, isobutyl group, the tert-butyl group, n-pentyl, n-hexyl, n-heptyl, n-octyl, n-nonyl, positive decyl, methoxyl group, ethyoxyl, methoxy, methoxy ethyl, ethoxyl methyl, ethoxyethyl group, phenoxymethyl, phenyl, benzyl, phenethyl, aminomethyl phenyl, furyl, pyridine radicals, pyrrole radicals, pyranose, pyrazinyl, thienyl, indyl, quinolyl, imidazole radicals, piperidyl, carbazyl, purine radicals, thiazolyl, pyrimidine radicals, oxazolyl, benzofuranyl, benzothiazolyl, cyclopropyl, cyclopenta, cyclohexyl, fluorenyl, azepine fluorenyl etc.

In foregoing of the present invention, described halogen atom can be any one in Cl, Br, I, F, more preferably any one in Cl, Br, I, more preferably any one in Cl, Br, more preferably Cl.

In foregoing of the present invention, described " group that can eliminate at people or mammal internal metabolism " can be selected from: any one or a few in triazole and derivant thereof, and as phenyl substituted 1,2,4-triazole, BTA, amino substituted 1,2,4-triazole etc.

Second aspect present invention is to provide one and treats and/or prevents cachectic medicine, and described medicine comprises any one or a few in the flavone compound, pharmaceutically acceptable salt, its prodrug of the structure shown in (I) that has structural formula.

Wherein:

R4 is for having the group of structural formula (II):

Wherein, described flavone compound can be to be selected from any one or a few in flavone (flavone), isoflavone (isoflavone), flavonol (flavonol) and isoflavone alcohol (chalcone).

Wherein, described medicine can be pharmaceutically acceptable any dosage form, as any one or a few in solution, emulsion, suspension, freeze dried powder, pill, tablet, granule, powder.

Wherein, described medicine can also be any one or a few in slow releasing agent, controlled release agent, targeting preparation.

In a kind of preferred embodiment of second aspect present invention, described medicine can also comprise that at least one can be used for treating and/or preventing cachectic extra active component.

Wherein, described extra active component can be any one or a few in Chinese medicine extract, synthetic drug, biological product.

Wherein, described extra active component can be to mix with described flavone compound, pharmaceutically acceptable salt or its prodrug, or separate existence.

In a kind of preferred embodiment of second aspect present invention, described medicine can also comprise pharmaceutically acceptable adjuvant.

Wherein, described adjuvant can be to be selected from any one or a few in excipient (comprise solid carrier, paste carrier, liquid flux any one or a few), antiseptic, lubricant, antioxidant, emulsifying agent, suspending agent, binding agent, stabilizing agent, cosolvent, dispersant, buffer agent, pH value regulator, antifreezing agent, correctives, disintegrating agent, filler, coloring agent.

Wherein, described cachexia can be any one or a few in cancer cachexia, Tuberculous cachexia, diabetic cachexia, hematopathy-relevant cachexia, endocrinopathy-relevant cachexia, chronic obstructive pulmonary disease-relevant cachexia, chronic kidney disease-relevant cachexia, heart failure-relevant cachexia, infectious disease-relevant cachexia or acquired immune deficiency syndrome-relevant cachexia.

Third aspect present invention is to provide a kind of preparation method of above-mentioned flavone compound.

Described flavone compound can taking Labiatae, Rosaceae, Compositae and fabaceous one or more as raw material, extract.

Wherein, the source of described flavone compound is preferably: taking materials such as the leaf of Flos Camelliae Japonicae sinensin, Cortex Pini, Semen Vitis viniferae, Semen Ginkgo, Silybum marianum Gaertn as raw material, extract, obtain comprising to have the flavone compound shown in structural formula (I):

Wherein:

R4 is for having the group of structural formula (II):

Wherein, described extraction solvent can be any one or a few in water extraction, alcohol extraction, supercritical carbon dioxide extraction, and is preferably alcohol extraction.

Wherein, described alcohol can be any one or a few in methanol, ethanol, isopropyl alcohol, butanols or its aqueous solution, and as ethanol water, volumetric concentration is preferably 80-99%, more preferably 85-97%, more preferably 90-95%.

Wherein, described alcohol extraction is preferably under reflux conditions and carries out.

In a kind of preferred embodiment of preparation method described in third aspect present invention, gained flavone compound carries out chemical modification and obtains the flavone compound described in first aspect present invention.

Flavone compound provided by the present invention, the cachectic medicine that can be used as treating people, animal, treats the cachexia relevant to various diseases.Can effectively slow down skeletal muscle atrophy and fat acid decomposition atrophy and cause body weight and muscle to alleviate, be mainly the inflammatory factor discharging by suppressing tumor and host, and then inhibition body inflammatory reacts and works.

Brief description of the drawings

Fig. 1 is the diet of the embodiment of the present invention 1 flavone compound to cachexia animal pattern and the intervention effect contrast of body weight;

Fig. 2 is the contrast of the main organs of the embodiment of the present invention 1 flavone compound to cachexia animal pattern and muscle, fat weight, and wherein Fig. 2 a, 2b, 2c, 2d are respectively heart, kidney, gastrocnemius and epididymal adipose tissues weight;

Fig. 3 is the effect of the serum cytokines of the embodiment of the present invention 1 flavone compound to cachexia animal pattern, and Fig. 3 a is the level of blood serum tumor TNF-α, and Fig. 3 b is the level of blood serum tumor IL-6;

Fig. 4 is the muscular tissue effect of the embodiment of the present invention 1 flavone compound to cachexia animal pattern, and Fig. 4 a, 4b, 4c, 4d are respectively the muscular tissue of matched group, model group, H-F group, H-L group mice;

Fig. 5 is the contrast of the gastrocnemius muscular tissue atrophy specific proteins effect of the embodiment of the present invention 1 flavone compound to cachexia animal pattern.

Detailed description of the invention

Embodiment 1

Flavone compound in the present embodiment (being called FD-1 in the present embodiment) molecular structure is as shown in (III):

FD-1 described in the present embodiment is purchased from Nantong Fei Yu Co., Ltd, HPLC purity >98%.

Material: the FD-1 purchasing in the present embodiment, HPLC purity >98%, accurately take respectively 15mg and 5mg FD-1, be settled in 100mL phosphate buffer (PBS), obtain two kinds of storing solutions (being designated as respectively F-H, F-L) that concentration is respectively 150ppm and 50ppm, it is biological company limited that mice TNG-α and IL-6 cytokine test kit reach section purchased from Shenzhen, and in experiment, other organic reagent is conventional commercially available prod.

Animal: clean level male and healthy balb/c mice, 18～22g, credit number: SCXK (Shanghai) 2008-0016, purchased from Shanghai western pul-Bi Kai laboratory animal company limited, in 26 DEG C of constant-temperature purification ventilation SPF level Animal Houses, raise, freely ingest and drink water, each 12 hours of illumination time, before experiment, raising one week to conform.According to the requirement of laboratory animal working specification, subcutaneous in animal right fore back upper place with the fragment of trocar inoculation CT26 colon cancer glandular epithelium tumor, animal ad lib and drinking-water, carry out decrement method mensuration to food-intake.

After being weighed, 48 balb/c healthy male mices are divided at random 4 groups, 12 every group;

Matched group: (D0) every right side of mice back subcutaneous injection PBS0.2ml the 0th day time, D1 starts every mouse peritoneal injection PBS0.2ml, injects continuously 15 days;

Every right side of mice back subcutaneous injection CT26 tumor cell 2 × 10 model group: D0 days time ⁶(0.2ml), D1 starts every mouse peritoneal injection PBS0.2ml, injects continuously 15 days;

F-H group: every right side of mice back subcutaneous injection CT26 tumor cell 2 × 10 when D0 ⁶(0.2ml), D1 starts every mouse peritoneal injection pastille PBS0.2ml (150mg/kg), injects continuously 15 days;

F-L group: every right side of mice back subcutaneous injection CT26 tumor cell 2 × 10 when D0 ⁶(0.2ml), D1 starts every mouse peritoneal injection PBS0.2ml (50mg/kg), injects continuously 15 days.

The 16th day time, respectively organize mice and pluck eyeball and get blood, then de-cervical vertebra is put to death mice, gets flesh before tumor, liver, the heart, spleen, lung, kidney, bilateral gastrocnemius, bilateral tibial, bilateral epididymal adipose tissues is weighed; Blood preparation, putting to death in 2 hours in centrifugal 20 minutes of 4 DEG C of 3000rpm, is carefully drawn supernatant and is loaded in EP pipe, and-80 DEG C of preservations, thaw when cytokine to be detected; Every group of three mice gastrocnemiuss are fixing in 10% formalin, preserve to be checked in all the other gastrocnemius liquid nitrogen.

prevention cachexia mice anorexia and weight loss

After animal injection tumor, next day, grouping gave medicine and placebo treatment, start to be designated as D0 from subcutaneous implantation tumor, 0th, 1,3,5,7,9,11,13,16 natural gift another names are measured each group of Mouse Weight, the 5th, 7,9,11,13,16 days diet total amounts of each group mice, and calculating the each group of mice average amount of food of 11st～16 days, analysis result is shown in Fig. 1.

Structure: as shown in Figure 1, since the 9th day, model group mice diet starts to decline, and mice diet accumulative total intake after FD-1 intervenes obviously than model group many (see Fig. 1 a), and 11-16 days average dietary intakes of mice after FD-1 intervenes also showed increased (see Fig. 1 b); FD-1 intervention group weight loss is compared with model group evening, (see Fig. 1 c), the 16th day matched group body weight and FD-1 intervention group were compared with baseline values all without declining, and model group declines and exceedes 10% and (see Fig. 1 d).

# represents that relatively there were significant differences (P<0.05) with model group;

※ represents that relatively there were significant differences (P<0.05) with normal group.

prevention cachexia mouse muscle, fat weight alleviate

Undertaken 15 days by described administering mode, within the 16th day, whole fasting water 4h posterior orbits are got blood, and cervical vertebra is put to death mice, get Mouse Liver, the heart, spleen, lung, kidney and gastrocnemius, tibialis anterior, epididymal adipose tissues, tumor body is weighed; Every group of 3 routine gastrocnemiuss are fixed by 10% neutral formalin, and remaining muscular tissue packs in liquid nitrogen and is stored in-80 DEG C.

Main organs and muscle, fat weight measurement result in table 1 the present embodiment 1

Parameter	Matched group	Model group	F-H group	F-L group
					Liver weight/mg	993.9±34.43	102.21±55.87	1144.9±33.21	1085.4±46.44
Cardiac weight/mg	126.7±6.5	84.6±4.93 ^※	108.6±6.05 ^#	106.9±4.68 ^#
					Spleen weight/mg	110.7±5.61	247.8±13.62 ^※	246.3±13.36 ^※	237.6±13.84 ^※
Lung weight/mg	137.3±32.2	129±5.21	129.3±2.85	137.6±4.83
					Kidney weight/mg	343.7±9.5	283.9±11.24 ^※	320.3±5.81 ^#	325.1±9.66 ^#
Gastrocnemius/mg	252.3±8.18	178.1±2.76 ^※	232.8±4.89 ^#	228.8±8.16 ^#
					Tibialis/mg	114.5±6.24	81.5±4.42 ^※	90.6±5.54 ^※	91.1±3.18 ^※
Epididymal adipose tissues/mg	428.8±16.17	104.2±7.14 ^※	198.4±11.43 ^※#	179.0±16.73 ^※#
					Tumor weight/mg	----	4214±296.9	3663.3±315.35	2655.4±397.80 ^#

Table 1 and Fig. 2 are known, the quality such as the internal organs such as heart, kidney of lotus tumor treated animal and gastrocnemius, epididymal adipose tissues are compared with control animals, both have significant difference, and after FD-1 pharmaceutical intervention, the described internal organs of lotus tumor treated animal and muscle, fat obviously increase than the animal of intervening without FD-1, illustrate that FD-1 slows down cachexia and causes weight loss mainly by reducing skeletal muscle (gastrocnemius and tibialis anterior are representative) atrophy and fat acid decomposition atrophy.

the anti-cachexia mouse cytokine of FD-1 rises

High dose FD-1 treatment cachexia Mouse Weight alleviates after off-test, mice is condemned to death, research Cytokine of Serum TNF-α and IL-6 level, after blood specimen collection, 4 DEG C of standing 2h wait rear 3000r/min, 4 DEG C of centrifugal 20min, liquid-transfering gun draw supernatant be stored in-80 DEG C to be detected, adopt ELISA test kit to detect, research Cytokine of Serum TNF-a and IL-6 level, the results are shown in Figure 3.

Fig. 3 shows that tumor-bearing mice is after FD-1 pharmaceutical intervention, its serum tumor necrosis factor-alpha (TNF-α) declines to some extent compared with model group, the content of IL-6 also has obvious reduction, illustrates that FD-1 can suppress cytokine TNF-a due to tumor chronic stimulation and the rising of IL-6.Existing document shows, in cachexia process, lean tissue mass of collective Quality Down is mainly because the nuclear factor due to cytokine-kappaB raises, and then activates ubiquitin protein degeneration system, protein in body is decomposed and accelerate, cause negative nitrogen balance, amyotrophy and weight loss.

# represents that relatively there were significant differences (P<0.05) with model group

the anti-cachexia mouse muscle degraded of FD-1

Muscular tissue after 10% formalin solution is fixing, paraffin embedding, the section of being cut into 3～5 μ m, HE dyeing, then pathology expert uses optical microscope read tablet and result is judged, picks out representative pathological picture for every group.

By mice gastrocnemius muscular tissue transverse section through after HE dyeing, at the micro-Microscopic observation of light microscopic.As shown in Figure 4, pathological examination results shows, baicalin can obviously suppress the dissolving of muscular tissue.Fig. 4 a is normal group, and Fig. 4 b is model group, and Fig. 4 c is F-H intervention group, and Fig. 4 d is F-L intervention group; As we can see from the figure F-H intervention group approach normal, and model group muscle fiber obscurity boundary, disorder, muscle degraded.

the atrophy of the anti-cachexia mouse muscle of FD-1

Adopt western blot to detect the expression of muscular tissue specificity ubiquitin enzyme E3MURF-1 and Atrogin-1: (1) muscular tissue protein extraction and quantitatively: after muscular tissue is thawed, to weigh, use glass homogenizer homogenate on ice after adding the ratio of 200ml lysate to add in 20mg tissue; Centrifugal 5 minutes of 12000rpm, 4 DEG C, get supernatant; Adopt BCA protein quantification standard measure.(2) electrophoresis: extract albumen and mix in the ratio of 4:1 with 5 × albumen sample-loading buffer, loading after 100 DEG C of Denatured proteins, applied sample amount is 30 μ g, constant voltage electrophoresis, upper strata glue 60V, the glue 120V of lower floor.(3) transferring film: the gel after electrophoresis finishes is switched to suitable size, put into and be soaked with pvdf membrane, in the transferring film buffer of filter paper and sponge, after sponge, filter paper, gel, pvdf membrane, filter paper, sponge are put in alignment in transfer folder successively in order, clip and fill it up with electricity and turn liquid; Turn 90min with 100V constant voltage electricity; (4) take out pvdf membrane, with after TBST rinsing, at confining liquid room temperature sealing 1h; (5) primary antibodie is hatched: dilute respectively the anti-Atrogin-1 antibody of rabbit (1:500), the anti-GAPDH antibody of the anti-MURF-1 antibody of rabbit (1:1000) rabbit (1:5000) with confining liquid dilution, after 4 DEG C of overnight incubation, TBST washes film; (6) two anti-hatching: with confining liquid dilution HRP labelling goat-anti rabbit two anti-(1:5000), after incubated at room 1h, T BST washes film; (7) on imager, detect after adding ECL chemiluminescence agent.Carry out ribbon density analysis with ImageJ, destination protein band and internal reference protein band density ratio are quantitative values, carry out statistical analysis.

Fig. 5 shows, after FD-1 therapeutic intervention, the expression of amyotrophy specific proteins Atrogin-1 and MURF-1 obviously declines compared with model group, there are some researches show, by suppressing MuRF1 in ubiquitin protein degeneration system, may so that Profilin degraded.

※ represents that relatively there were significant differences (P<0.05) with normal group

Above specific embodiments of the invention be have been described in detail, but it is just as example, the present invention is not restricted to specific embodiment described above.To those skilled in the art, any equivalent modifications that the present invention is carried out and alternative also all among category of the present invention.Therefore, equalization conversion and the amendment done without departing from the spirit and scope of the invention, all should contain within the scope of the invention.

Claims

1. treat and/or prevent a cachectic medicine, it is characterized in that, described medicine comprises any one or a few in the flavone compound, pharmaceutically acceptable salt, its prodrug of the structure shown in (I) that has structural formula:

Wherein:

R4 is for having the group of structural formula (II):

2. medicine according to claim 1, it is characterized in that, the carbochain of described C1-C22 is selected from aliphatic group branching or straight chain or ring-type, saturated or undersaturated, aryl radical, aliphatic group substituted aroma alkyl, aryl radical substituted fatty hydrocarbon base, main chain containing containing heteroatomic carbocyclic ring on heteroatomic carbochain, ring skeleton.

3. medicine according to claim 1, is characterized in that, described flavone compound is selected from any one or a few in flavone, isoflavone, flavonol and isoflavone alcohol.

4. medicine according to claim 1, is characterized in that, also comprises at least one extra active component.

5. medicine according to claim 1, is characterized in that, also comprises pharmaceutically acceptable adjuvant.

6. flavone compound treats and/or prevents the application in the medicine of cancer cachexia in preparation, it is characterized in that, described flavone compound structural formula is (I):

Wherein:

R4 is for having the group of structural formula (II):

7. flavone compound treats and/or prevents the application in the cachectic medicine of Tuberculous in preparation, it is characterized in that, described flavone compound structural formula is (I):

Wherein:

R1, R2, R3 are selected from carbochain carbochain, the NR of H, hydroxyl, C1-C22 ₁₁r ₁₂, wherein, R ₁₁, R ₁₂respectively independently selected from H and the group that can eliminate at people or mammal internal metabolism;

R4 is for having the group of structural formula (II):

8. flavone compound treats and/or prevents the application in the cachectic medicine of diabetic in preparation, it is characterized in that, described flavone compound structural formula is (I):

Wherein:

R4 is for having the group of structural formula (II):

9. flavone compound treats and/or prevents the application in the relevant cachectic medicine of hematopathy in preparation, it is characterized in that, described flavone compound structural formula is (I):

Wherein:

R4 is for having the group of structural formula (II):

10. flavone compound treats and/or prevents the application in the relevant cachectic medicine of infectious disease in preparation, it is characterized in that, described flavone compound structural formula is (I):

Wherein:

R4 is for having the group of structural formula (II):