CN112107572B - Composition for inhibiting skin cell proliferation and/or resisting inflammation and application of apigenin and luteolin - Google Patents
Composition for inhibiting skin cell proliferation and/or resisting inflammation and application of apigenin and luteolin Download PDFInfo
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- CN112107572B CN112107572B CN202010342661.8A CN202010342661A CN112107572B CN 112107572 B CN112107572 B CN 112107572B CN 202010342661 A CN202010342661 A CN 202010342661A CN 112107572 B CN112107572 B CN 112107572B
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- cell proliferation
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
Abstract
Provided is a composition for inhibiting skin cell proliferation and/or anti-inflammation, comprising: apigenin (apigenin); and luteolin (luteolin), wherein a weight ratio of the apigenin to the luteolin is about 1.5-25:1, or a molar ratio of the apigenin to the luteolin is about 1.5-25: 1. The apigenin and luteolin have synergistic effect in inhibiting skin cell proliferation and/or resisting inflammation.
Description
Technical Field
The present disclosure relates to a synergistic composition containing apigenin (apigenin) and luteolin (luteolin), and more particularly, to a composition containing apigenin and luteolin for inhibiting skin cell proliferation and/or resisting inflammation, and the use of apigenin and luteolin for preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation.
Background
Skin diseases are the most common diseases worldwide, with skin-related medical expenditures of up to 25% in healthcare expenditures.
Skin diseases can be divided into four broad categories, namely dermatitis (e.g., allergic and contact), cancer (e.g., melanoma), immune diseases (e.g., psoriasis), and infectious skin diseases (e.g., bacterial, fungal and viral infections).
At present, the literature indicates that flavonoids such as apigenin (apigenin) and luteolin (luteolin) have cell proliferation inhibiting and anti-inflammatory activities, but the interaction between the two is still unclear.
Therefore, it is desired to obtain a synergistic composition containing apigenin (apigenin) and luteolin (luteolin) to provide a drug with better therapeutic effect but at a lower dosage, and to be applied in the treatment of skin diseases or inflammatory diseases.
Disclosure of Invention
The present disclosure provides a composition for inhibiting skin cell proliferation and/or anti-inflammation, comprising: apigenin (apigenin); and luteolin (luteolin), wherein a weight ratio of the apigenin to the luteolin is about 1.5-25:1, or a molar ratio of the apigenin to the luteolin is about 1.5-25: 1. Furthermore, the apigenin and the luteolin have synergistic effect on inhibiting skin cell proliferation and/or resisting inflammation.
The present disclosure also provides a use of apigenin and luteolin in preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein the weight ratio of apigenin to luteolin is about 1.5-25:1, or the molar ratio of apigenin to luteolin is about 1.5-25: 1. And, wherein the apigenin and the luteolin have synergistic effects in inhibiting skin cell proliferation and/or resisting inflammation.
The present disclosure also provides a method for inhibiting skin cell proliferation and/or inflammation, comprising administering the skin cell proliferation and/or inflammation inhibiting composition of the present disclosure to a subject in need thereof.
The present disclosure also provides a method for treating a skin disease and/or an inflammatory disease, comprising administering to a subject in need thereof the above-described composition for inhibiting skin cell proliferation and/or anti-inflammation of the present disclosure.
In order to make the aforementioned and other objects, features, and advantages of the present disclosure more comprehensible, preferred embodiments accompanied with figures are described in detail below:
detailed description of the preferred embodiments
The present disclosure may provide a composition for inhibiting skin cell proliferation and/or anti-inflammation, which may be a synergistic composition that may include, but is not limited to, apigenin (apigenin) and luteolin (luteolin).
In the composition for inhibiting skin cell proliferation and/or inflammation according to the present disclosure, apigenin and luteolin may have a synergistic effect on inhibiting skin cell proliferation, inflammation, etc., or any combination thereof, but are not limited thereto.
The term "having synergistic effect" as used in the present disclosure may mean that a combination of a plurality of components is analyzed by the CalcuSyn software for a specific physiological or medical purpose, and the Combination Index (CI) of the combination is confirmed to be less than 1 (Ting-Chao Chou; Cancer Res; 70(2) january15,2010), or that the combination of the plurality of components has better efficacy for the specific physiological or medical purpose than that of the plurality of components alone under the same total content or concentration, but is not limited thereto.
In one embodiment, in the above-mentioned composition for inhibiting skin cell proliferation and/or anti-inflammation of the present disclosure, whether apigenin and luteolin have synergistic effect on inhibiting skin cell proliferation and/or anti-inflammation is evaluated by the combination index of the combination of apigenin and luteolin.
Examples of the skin cells include, but are not limited to, keratinocytes, skin fibroblasts, and the like. In addition, the inflammation may include, but is not limited to, inflammatory reactions involving immune cells, such as macrophages, and the like.
In the above-described compositions for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure, the weight ratio of apigenin to luteolin can be about 1.5-25:1, e.g., about 1.5-20:1, about 1.5-15:1, about 1.5-12:1, about 1.5-10:1, about 2-25:1, about 2-20:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 1.9:1, about 2:1, about 3:1, about 4:1, about 4.7:1, about 5:1, about 9:1, about 9.4:1, about 10:1, about 12:1, about 15:1, about 18.8:1, about 19:1, about 20:1, about 25:1, etc. Alternatively, in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure, the weight ratio of apigenin to luteolin can be about 1.5-25:1, for example, about 1.5-20:1, about 1.5-15:1, about 1.5-12:1, about 1.5-10:1, about 2-25:1, about 2-20:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 2:1, about 3:1, about 4:1, about 5:1, about 10:1, about 12:1, about 15:1, about 20:1, about 25:1, and the like, but is not limited thereto.
In one embodiment, in the composition for inhibiting skin cell proliferation and/or inflammation of the present disclosure, apigenin and luteolin can have a synergistic effect on inhibiting skin cell proliferation. In this embodiment, the weight ratio of apigenin to luteolin in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure can be about 1.5-15:1, such as about 1.5-12:1, about 1.5-10:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 1.9:1, about 2:1, about 3:1, about 4:1, about 4.7:1, about 5:1, about 9:1, about 9.4:1, about 10:1, about 12:1, about 15:1, etc. Alternatively, in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure, the molar ratio of apigenin to luteolin can be about 1.5-15:1, such as about 1.5-12:1, about 1.5-10:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 2:1, about 3:1, about 4:1, about 5:1, about 10:1, about 12:1, about 15:1, etc., but is not limited thereto.
In another embodiment, in the composition for inhibiting skin cell proliferation and/or inflammation of the present disclosure, apigenin and luteolin can have a synergistic effect on anti-inflammation. In this embodiment, the weight ratio of apigenin to luteolin in the above-described compositions for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure can be about 1.5-25:1, e.g., about 1.5-20:1, about 1.5-15:1, about 1.5-12:1, about 1.5-10:1, about 2-25:1, about 2-20:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 1.9:1, about 2:1, about 3:1, about 4:1, about 4.7:1, about 5:1, about 9:1, about 9.4:1, about 10:1, about 12:1, about 15:1, about 18.8:1, about 19:1, about 20:1, about 25:1, etc. Alternatively, in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure, the molar ratio of apigenin to luteolin can be about 1.5-25:1, such as, but not limited to, about 1.5-20:1, about 1.5-15:1, about 1.5-12:1, about 1.5-10:1, about 2-25:1, about 2-20:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 2:1, about 3:1, about 4:1, about 5:1, about 10:1, about 12:1, about 15:1, about 20:1, about 25:1, etc.
In yet another embodiment, in the above skin cell proliferation and/or inflammation inhibiting composition of the present disclosure, apigenin and luteolin can have synergistic effects on both skin cell proliferation inhibition and inflammation resistance. In this embodiment, the weight ratio of apigenin to luteolin in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure can be about 1.5-15:1, such as about 1.5-12:1, about 1.5-10:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 1.9:1, about 2:1, about 3:1, about 4:1, about 4.7:1, about 5:1, about 9:1, about 9.4:1, about 10:1, about 12:1, about 15:1, etc. Alternatively, in the composition for inhibiting skin cell proliferation and/or resisting inflammation of the present disclosure, the molar ratio of apigenin to luteolin can be about 1.5-15:1, such as about 1.5-12:1, about 1.5-10:1, about 2-15:1, about 2-12:1, about 2-10:1, about 1.5:1, about 2:1, about 3:1, about 4:1, about 5:1, about 10:1, about 12:1, about 15:1, etc., but is not limited thereto.
In one embodiment, the composition for inhibiting skin cell proliferation and/or inflammation according to the present disclosure may further include a pharmaceutically acceptable vehicle, carrier or salt in addition to apigenin and luteolin, but is not limited thereto. In one embodiment, the total content of apigenin and luteolin in the composition for inhibiting skin cell proliferation and/or inflammation according to the present disclosure may be about 0.1-20 wt%, such as 0.2-15 wt%, 0.3-10 wt%, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%, 3 wt%, 4 wt%, 5 wt%, but is not limited thereto.
Pharmaceutically acceptable vehicles may serve as diluents, dispersants or carriers for the active ingredients. Pharmaceutically acceptable vehicles can include materials commonly used in skin care products such as water, liquid or solid emollients, silicone oils, emulsifiers, solvents, humectants, thickeners, powders, propellants and the like.
The vehicle can comprise 80-99.9 wt%, e.g., 95-99.5 wt% of the above composition and can constitute the remainder of the composition in the absence of other adjuvants.
In addition, all of the compositions described above can be made in the form of a skin paint in one embodiment, including, but not limited to, an emulsion, a cream, a gel, a spray, a lotion, a shampoo, a mousse, and the like. Generally, skin sprays can be composed of spray copolymers, such as polyvinylpyrrolidone, vinyl acetate, and the like, and can function as lotions. Skin gels are prepared in a manner similar to sprays, but are gelatinous and free of the presence of alcohol and can be adhered to the skin. Skin curtains are foams released by pressure. The skin emulsion is hydrophobic or hydrophilic emulsion, ointment, gel, emollient, spray, paint, skin conditioning water, shampoo or mousse. In addition, suitable ingredients may be added to the skin cream, such additional ingredients including petrolatum, waxes, lanolin, silicones, liposomes, vegetables, mineral oils, plasticizers, fragrances, preservatives, penetration enhancers, pH adjusters or other ingredients suitable for topical application to the skin. This additional ingredient wets the skin, stabilizes the active compound, increases the aforementioned composition-to-skin contact, thereby increasing the concentration of the topical area and controlling the release of the composition.
Also, the compositions may also include other specific skin benefit activators such as sunscreens and skin lightening agents. Vehicles may also further include adjuvants such as antioxidants, fragrances, opacifiers, preservatives, colorants, and buffers.
Pharmaceutically acceptable carriers can include, but are not limited to, solvents, dispersion media, coatings, antibacterial and antifungal agents, and isotonic and absorption delaying agents, among others, that are compatible with pharmaceutical administration. For different modes of administration, the pharmaceutical composition can be formulated into dosage forms (dosage form) using conventional methods.
Also, the pharmaceutically acceptable salts may include, but are not limited to, salts including inorganic cations, for example, alkali metal salts such as sodium, potassium or amine salts, alkaline earth metal salts such as magnesium, calcium salts, salts containing divalent or tetravalent cations such as zinc, aluminum or zirconium salts. In addition, they may be organic salts such as dicyclohexylamine salts and methyl-D-glucamine, amino acid salts such as arginine, lysine, histidine, glutamine.
Examples of the compositions for inhibiting skin cell proliferation and/or anti-inflammation disclosed herein include, but are not limited to, pharmaceutical compositions or health care compositions.
The pharmaceutical or nutraceutical compositions described in the present disclosure may be administered non-orally, via inhalation spray (inhalation spray), or by way of an implanted reservoir (implanted reservoir). Non-oral administration may include application to any area of the skin or desired area, subcutaneous (subcutaneous), intradermal (intracutaneous), intramuscular (intramusculary), intraarticular (intraarterial), intrasynovial (intracavitary), intrasternal (intrasternal), intrathecal (intraspecific), intralesional (intradivision) injection, and infusion techniques.
Oral compositions may be in the form of, but are not limited to, tablets, capsules, emulsions (emulsions), aqueous suspensions (aqueous suspensions), dispersions (dispersions), and solutions.
And topical forms of application may include, but are not limited to, ointments, creams, liquids, gels, and the like.
In a specific embodiment, the composition for inhibiting skin cell proliferation and/or anti-inflammation of the present disclosure can be a pharmaceutical composition. In this particular embodiment, the pharmaceutical composition may be in a form for topical administration, wherein the form for topical administration may include, but is not limited to, ointments, creams, liquids, gels, or the like. Also, in this particular embodiment, the pharmaceutical composition may include, but is not limited to, a pharmaceutical composition for treating a skin disorder and/or an inflammatory disorder. Examples of the pharmaceutical composition for treating skin diseases and/or inflammatory diseases include, but are not limited to, pharmaceutical compositions for treating psoriasis, pharmaceutical compositions for treating allergic or contact dermatitis, and the like.
Based on the foregoing, the present disclosure also provides a use of apigenin and luteolin in preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation. In the application of the apigenin and the luteolin in preparing the composition for inhibiting skin cell proliferation and/or resisting inflammation, the apigenin and the luteolin have a synergistic effect on inhibiting skin cell proliferation and/or resisting inflammation.
Further, for all relevant descriptions of apigenin and luteolin involved in the application of apigenin and luteolin in preparing the composition for inhibiting skin cell proliferation and/or resisting inflammation according to the present disclosure, reference can be made to the preceding description of the composition for inhibiting skin cell proliferation and/or resisting inflammation according to the present disclosure, and the description of apigenin and luteolin is not repeated herein.
In one embodiment, in the application of apigenin and luteolin in the preparation of a composition for inhibiting skin cell proliferation and/or inflammation, a pharmaceutically acceptable vehicle, carrier or salt can also be used for preparing the composition for inhibiting skin cell proliferation and/or inflammation.
For the description of the pharmaceutically acceptable vehicle, carrier or salt, reference is also made to the description in the preceding paragraphs for the composition for inhibiting skin cell proliferation and/or inflammation according to the present disclosure, and therefore, the description is not repeated here.
Furthermore, all relevant descriptions of the prepared skin cell proliferation and/or inflammation inhibiting composition in the above-mentioned application of apigenin and luteolin in preparation of the skin cell proliferation and/or inflammation inhibiting composition can be found in all the descriptions in the preceding description of the skin cell proliferation and/or inflammation inhibiting composition of the present disclosure, but not limited thereto.
In addition, based on the foregoing, the present disclosure also provides a method for inhibiting skin cell proliferation and/or anti-inflammation. The method may include, but is not limited to, administering any of the above described compositions of the present disclosure for inhibiting skin cell proliferation and/or anti-inflammation to a subject in need thereof.
Also, based on the foregoing, the present disclosure may also provide a method of treating a skin disease and/or an inflammatory disease. The method may include, but is not limited to, administering any of the above described compositions of the present disclosure for inhibiting skin cell proliferation and/or anti-inflammation to a subject in need thereof.
Skin disorders described herein may include, but are not limited to, psoriasis, allergic or contact dermatitis, and the like.
The subject of the present disclosure may include, but is not limited to, vertebrates. The above vertebrates may include, but are not limited to, fishes, amphibians, reptiles, birds, or mammals. Examples of mammals can include, but are not limited to, humans, orangutans, monkeys, cows, horses, donkeys, dogs, cats, rabbits, guinea pigs, rats, mice, and the like. In one embodiment, the subject may be a human.
Furthermore, the application of the composition in all the treatment methods of the present disclosure can be referred to the related description in the preceding paragraphs of the composition for inhibiting skin cell proliferation and/or anti-inflammation of the present disclosure, and therefore, the description thereof is omitted here for brevity.
Examples
1. Determination of the inhibition Rate of keratinocyte (HaCaT cells) proliferation
1-1. Process
Dimethyl sulfoxide (DMSO) is used as a solvent to prepare test samples with different concentrations of apigenin and luteolin. Tests were run in 9 batches, batch 1 to batch 9. There were 6 independent trials in each batch of trials.
In each independent experiment, the inhibition rate of the specific concentration of apigenin test sample and the specific concentration of luteolin test sample on the keratinocyte proliferation is determined, and the inhibition rate of the combination of the specific concentration of apigenin test sample and the specific concentration of luteolin test sample on the keratinocyte proliferation is determined. Between the independent experiments, the concentration of the apigenin test sample is different, the concentration of the luteolin test sample is also different, and the molar ratio or the weight ratio of the apigenin test sample to the luteolin test sample is the same.
Also, the molar ratio or the weight ratio of the apigenin test sample to the luteolin test sample is not the same between each batch of tests.
The experimental procedure is as follows:
will be 5X 10 3 The keratinocyte cell line of (1), HaCaT cells were seeded in a 96-well culture plate, and then placed at 37 ℃ and 5% CO 2 The number of cells at this time point (T0) was used as a reference point for cell proliferation in the incubator at overnight.
After overnight culture, the cells in the culture dish were added with the test sample (see Table 1, the cells in the control group were treated with only dimethyl sulfoxide) to co-culture for 48 hours (T48). The supernatant in the culture dish was then removed.
After removing the supernatant, 50. mu.L of MTT solution (0.5 mg/mL; Life Technologies Cat. No. M-6494) was added to the cells, and the culture plate was then placed at 37 ℃ and 5% CO 2 The culture was carried out in an incubator for 1.5 hours. Then, 150. mu.L of DMSO (J.T.Baker, Cat.No.9224-03) was added to the cells in the culture dish and shaken for 5 minutes.
Then, the absorbance at a wavelength of 570nm of each well of the culture dish was measured by a continuous wavelength microplate analyzer, and the cell proliferation inhibition rate was calculated by the following formula
Cell proliferation inhibition rate (T48 control group) 570nm -T48 test groups 570nm ) /(T48 control group 570nm -T0 control group 570nm )。
1-2. results
The cell proliferation inhibition rate of each test sample is shown in table 1 below.
TABLE 1 inhibition of cell proliferation for each sample tested
2. Measurement of inhibition ratio of inflammation (anti-inflammatory Activity)
2-1 Process
Dimethyl sulfoxide is used as a solvent to prepare test samples with different concentrations of apigenin and luteolin. Tests were run in 9 batches, batch 1 to batch 9. There were 6 independent trials in each batch of trials.
In each independent experiment, the inhibition rate of inflammation of the apigenin test sample with a specific concentration and the luteolin test sample with a specific concentration is determined, and the inhibition rate of inflammation of the combination of the apigenin test sample with a specific concentration and the luteolin test sample with a specific concentration is determined. Between the independent experiments, the concentration of the apigenin test sample is different, the concentration of the luteolin test sample is also different, and the molar ratio or the weight ratio of the apigenin test sample to the luteolin test sample is the same.
Also, the molar ratio or the weight ratio of the apigenin test sample to the luteolin test sample is not the same between each batch of tests.
Will be 5X 10 4 OfCytophaga strain, RAW264.7 cell species, was seeded in 96-well culture plates before being placed at 37 ℃ and 5% CO 2 The incubator was incubated overnight.
After overnight culture, the supernatant was removed, and Lipopolysaccharide (LPS) (50ng/mL) and a sample to be tested (see table 2, cells of the induction group were treated with lipopolysaccharide and dimethyl sulfoxide, and cells of the control group were treated with dimethyl sulfoxide only) were added to the cells to react for 24 hours.
Then, the supernatant of each well in the culture dish was transferred to a new culture dish and reacted with a Griess reagent (Promega, cat. No. g2930), and then the content of Nitric Oxide (NO) was evaluated by measuring the absorbance at a wavelength of 540nm of each well of the culture dish using a continuous wavelength microplate analyzer, and the anti-inflammatory activity was calculated by the following formula
Anti-inflammatory group (Induction group) 540nm Experimental group 540nm ) /(Induction group) 540nm Control group 540nm )。
2-2. results
The anti-inflammatory activity of each test sample is shown in table 2 below.
TABLE 2
Example 3
Evaluation of the synergistic Effect of apigenin and luteolin
In this experiment, CalcuSyn software (bios) was used to analyze the synergistic effect of apigenin and luteolin.
The Calcusyn software is a commonly used analysis software for analyzing the drug dose effect of a single drug and a plurality of drugs. Calcusyn software can be used to analyze drug-complexing interactions and automatically quantify various phenomena, such as synergy (synergism) and inhibition (inhibition). Calcusyn software is capable of processing data for individual drugs and combination drugs at either fixed-ratio or non-fixed-ratio (on-constant-ratio) and can evaluate the interaction of the combination drugs by the Combination Index (CI) calculated by the Calcusyn software (Chou and Talalay, adv. enzyme Regul.22:27-55 (1984). the formula for the combination index is as follows:
combination index of C1/IC1+ C2/IC2
C1 and C2 are the respective concentrations of the first compound and the second compound, respectively, at which 50% (or 75%, or 90%) of their activity for a particular physiological or medicinal purpose is measured when the first compound and the second compound are assayed in combination; IC1 and IC2 are the respective concentrations of the first compound and the second compound, respectively, at which 50% (or 75%, or 90%) of the activity of the first compound and the second compound for a particular physiological or medicinal purpose is achieved when the first compound and the second compound are analyzed independently.
A combination index of less than 1 indicates that the two compounds have a synergistic effect (synergistic effect) for a particular physiological or medicinal purpose, a combination index of 1 indicates that the two compounds have an additive effect (additive effect) for a particular physiological or medicinal purpose, and a combination index of greater than 1 indicates that the two compounds have an antagonistic effect (antagonistic effect) for a particular physiological or medicinal purpose (Ting-Chao Chou; Cancer Res; 70(2) January15,2010).
3-1 evaluation of synergistic Effect of apigenin and luteolin on inhibition of skin cell proliferation
3-1-1. Process
The test results of 9 batches shown in table 1 in example 1 were analyzed by Calcusyn software, respectively, to calculate respective combination indices of apigenin and luteolin in different ratios for inhibiting skin cell proliferation.
3-1-2. results
The respective combination indices of apigenin and luteolin combined in different ratios for inhibiting skin cell proliferation calculated by Calcusyn are shown in table 3 below.
TABLE 3
As can be seen from Table 3, when the molar ratio of apigenin to luteolin is 2-10:1, apigenin and luteolin have synergistic effect in inhibiting skin cell proliferation. In contrast, when the molar ratio of apigenin to luteolin is 1:1, 20:1 or 1:2-20, apigenin and luteolin do not have a synergistic effect on inhibiting skin cell proliferation and even produce an antagonistic effect.
3-2 evaluation of the synergistic Effect of apigenin and luteolin on anti-inflammation
3-2-1. Process
The test results of 9 lots shown in table 2 in example 2 were analyzed by Calcusyn software, respectively, to calculate respective combination indices of apigenin and luteolin at different ratios for anti-inflammation.
3-2-2. results
The respective combination indices of apigenin and luteolin combined in different ratios for anti-inflammation, calculated by Calcusyn, are shown in Table 4 below.
TABLE 4
As can be seen from Table 4, when the molar ratio of apigenin to luteolin is 2-20:1, apigenin and luteolin have synergistic effect on anti-inflammation. In contrast, when the molar ratio of apigenin to luteolin is 1:1 or 1:2-20, apigenin and luteolin do not have a synergistic effect on anti-inflammation and even produce an antagonistic effect.
3-3. conclusion
From the above results, it is clear that, in the inhibition of skin cell proliferation or anti-inflammatory apigenin and luteolin, apigenin and luteolin in any combination ratio do not have a synergistic effect, but the apigenin and the luteolin in a specific combination ratio have to have a synergistic effect. When the molar ratio of apigenin to luteolin is about 2-20:1, apigenin and luteolin can have synergistic effects in inhibiting skin cell proliferation and/or resisting inflammation.
Although the present invention has been described with respect to the preferred embodiments, it will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (20)
1. A composition for inhibiting skin cell proliferation and/or anti-inflammation, comprising:
apigenin; and
the content of luteolin in the raw materials of the medicine,
wherein the active ingredients of the composition for inhibiting skin cell proliferation and/or resisting inflammation comprise apigenin and luteolin, and
wherein the weight ratio of apigenin to luteolin is 1.5-25:1, or the molar ratio of apigenin to luteolin is 1.5-25:1, and wherein the apigenin and luteolin have a synergistic effect on anti-inflammation, or,
wherein the weight ratio of the apigenin to the luteolin is 1.5-15:1, or the molar ratio of the apigenin to the luteolin is 1.5-15:1, and wherein the apigenin and the luteolin have a synergistic effect on inhibiting skin cell proliferation and/or resisting inflammation.
2. The composition for inhibiting skin cell proliferation and/or inflammation according to claim 1, wherein the skin cells comprise keratinocytes or dermal fibroblasts.
3. The anti-inflammatory and/or anti-proliferative composition of claim 1, wherein the inflammation comprises an inflammatory response involving macrophages.
4. The anti-inflammatory and/or anti-proliferative composition according to claim 1, wherein the anti-inflammatory and/or proliferative composition comprises a pharmaceutical composition or a nutraceutical composition.
5. The anti-inflammatory and/or anti-proliferative composition according to claim 4, further comprising a pharmaceutically acceptable carrier or salt.
6. The composition for inhibiting skin cell proliferation and/or resisting inflammation as claimed in claim 5, wherein the total content of apigenin and luteolin is 0.1-20 wt%.
7. The skin cell proliferation and/or inflammation inhibiting composition of claim 4, wherein the skin cell proliferation and/or inflammation inhibiting composition is the pharmaceutical composition.
8. The anti-inflammatory and/or anti-proliferative composition according to claim 7, wherein the pharmaceutical composition is in a form for topical administration, wherein the form for topical administration comprises an ointment, cream, liquid or gel.
9. The anti-inflammatory and/or anti-proliferative composition according to claim 8, wherein the pharmaceutical composition comprises a pharmaceutical composition for treating a skin disease and/or an inflammatory disease.
10. The anti-inflammatory and/or anti-proliferative composition according to claim 9, wherein the pharmaceutical composition for treating skin diseases and/or inflammatory diseases comprises a pharmaceutical composition for treating psoriasis or a pharmaceutical composition for treating allergic or contact dermatitis.
11. An application of apigenin and luteolin in preparing composition for inhibiting skin cell proliferation and/or resisting inflammation,
wherein the active ingredients of the composition for inhibiting skin cell proliferation and/or resisting inflammation comprise apigenin and luteolin, and
wherein the weight ratio of apigenin to luteolin is 1.5-25:1, or the molar ratio of apigenin to luteolin is 1.5-25:1, and wherein the apigenin and luteolin have a synergistic effect on anti-inflammation, or,
wherein the weight ratio of the apigenin to the luteolin is 1.5-15:1, or the molar ratio of the apigenin to the luteolin is 1.5-15:1, and wherein the apigenin and the luteolin have a synergistic effect on inhibiting skin cell proliferation and/or resisting inflammation.
12. Use of apigenin and luteolin according to claim 11 for preparing a composition for inhibiting skin cell proliferation and/or anti-inflammation, wherein said skin cells comprise keratinocytes or dermal fibroblasts.
13. Use of apigenin and luteolin in the preparation of a composition for inhibiting skin cell proliferation and/or resisting inflammation as claimed in claim 11, wherein the inflammation comprises an inflammatory response involving macrophages.
14. The use of apigenin and luteolin according to claim 11 for preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein the composition for inhibiting skin cell proliferation and/or resisting inflammation comprises a pharmaceutical composition or a health care composition.
15. The use of apigenin and luteolin according to claim 11 for preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein a pharmaceutically acceptable carrier or salt is also used for preparing the composition for inhibiting skin cell proliferation and/or resisting inflammation.
16. The use of apigenin and luteolin in the preparation of a composition for inhibiting skin cell proliferation and/or resisting inflammation as claimed in claim 15, wherein the total content of apigenin and luteolin is 0.1-20 wt%.
17. The use of apigenin and luteolin in claim 14 for preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein the composition for inhibiting skin cell proliferation and/or resisting inflammation is the pharmaceutical composition.
18. The use of apigenin and luteolin in claim 17 for the preparation of a composition for inhibiting skin cell proliferation and/or anti-inflammation, wherein the pharmaceutical composition is in a topical dosage form, wherein the topical dosage form comprises an ointment, cream, liquid or gel.
19. The use of apigenin and luteolin according to claim 14 for preparing a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein the pharmaceutical composition comprises a pharmaceutical composition for treating a skin disease and/or an inflammatory disease.
20. The use of apigenin and luteolin in claim 19 for the preparation of a composition for inhibiting skin cell proliferation and/or resisting inflammation, wherein the pharmaceutical composition for treating skin diseases and/or inflammatory diseases comprises a pharmaceutical composition for treating psoriasis or a pharmaceutical composition for treating allergic or contact dermatitis.
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| TW108148607A TWI727584B (en) | 2019-06-20 | 2019-12-31 | Composition for inhibiting skin cell proliferation and/or anti-inflammatory and use of apigenin and luteolin in manufacture of a composition for inhibiting skin cell proliferation and/or anti-inflammatory |
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