CN108096246B - Application of quercetin and aconitine in preparation of medicine for treating cervical cancer and medicine for treating cervical cancer - Google Patents
Application of quercetin and aconitine in preparation of medicine for treating cervical cancer and medicine for treating cervical cancer Download PDFInfo
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- CN108096246B CN108096246B CN201711276446.7A CN201711276446A CN108096246B CN 108096246 B CN108096246 B CN 108096246B CN 201711276446 A CN201711276446 A CN 201711276446A CN 108096246 B CN108096246 B CN 108096246B
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- quercetin
- aconitine
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- 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
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
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- 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
Abstract
The invention relates to the field of medicines, in particular to an application of quercetin and aconitine in preparation of a medicine for treating cervical cancer. The invention analyzes the interaction of the quercetin and the aconitine when being used together, and finds that the two medicines have synergistic effect in a wide effect range when being simultaneously applied. The combination of quercetin and aconitine in the treatment of human cervical cancer is prompted, so that the dosage of quercetin and aconitine can be reduced, the effect of treating cervical cancer can be improved, and the pain of patients can be relieved.
Description
Technical Field
The invention relates to the field of medicines, in particular to an application of quercetin and aconitine in preparation of a medicine for treating cervical cancer.
Background
Cervical cancer is one of the most common gynecological malignancies, and is not sensitive to most anticancer drugs so far, with an effective rate of chemotherapy of no more than 15%. It is becoming more urgent to find effective low-or non-toxic drugs for treating cervical cancer.
Quercetin is a typical representative of flavonoids, is a flavonoid distributed most widely in the plant kingdom, has the effects of resisting oxidation, resisting bacteria, diminishing inflammation, protecting liver and kidney, cardiovascular and cerebrovascular systems, stopping diarrhea and the like.
Disclosure of Invention
The invention aims to provide application of combined medication of quercetin and aconitine in a medicament for treating human cervical carcinoma.
According to a specific embodiment of the present invention, the present invention provides the use of quercetin in combination with aconitine for the preparation of a medicament for the treatment of cervical cancer.
According to the specific embodiment of the invention, the invention provides the application of the combination of quercetin and aconitine in preparing the medicine for treating cervical cancer, wherein the dosage ratio of the quercetin to the aconitine is 1: 1.
According to a specific embodiment of the present invention, there is provided a medicament for treating cervical cancer, comprising quercetin and aconitine.
According to a specific embodiment of the present invention, the drug for treating cervical cancer comprises 1:1 quercetin and aconitine.
According to the specific embodiment of the invention, the experimental result of the combined application of quercetin and aconitine on the proliferation of human cervical carcinoma He L a cells shows that the half-inhibitory concentration of the quercetin on the human cervical carcinoma He L a cells is 55.99 +/-1.21 mu g/m L when the quercetin is used alone, the half-inhibitory concentration of the aconitine on the human cervical carcinoma He L a cells is 71.89 +/-0.98 mu g/m L when the aconitine is used alone, and the half-inhibitory concentration of the He L a cells is 44.08 +/-0.68 mu g/m L when the quercetin and the aconitine are used together.
The invention analyzes the interaction of the quercetin and the aconitine when being used together, and finds that the two medicines have synergistic effect in a wide effect range when being simultaneously applied. The combination of quercetin and aconitine in the treatment of human cervical cancer is prompted, so that the dosage of quercetin and aconitine can be reduced, the effect of treating cervical cancer can be improved, and the pain of patients can be relieved.
Drawings
FIG. 1 shows the inhibition of the growth of human cervical carcinoma He L a cells by quercetin, wherein C is a positive control drug camptothecin and has a concentration of 10 μ g/m L.
FIG. 2 shows the inhibition of human cervical carcinoma He L a cell growth by aconitine, wherein C is positive control drug camptothecin, and the concentration is 10 μ g/m L.
FIG. 3 shows the inhibition of human cervical carcinoma He L a cell growth by the combined administration of quercetin and aconitine, wherein C is a positive control drug camptothecin with a concentration of 10 μ g/m L.
FIG. 4 shows the median effect method for determining the combination of quercetin and aconitine.
Detailed Description
The present invention is further illustrated by the following specific examples, which are intended to be illustrative, not limiting and are not intended to limit the scope of the invention.
The reagents used in the present invention are conventional reagents, unless otherwise specified; the method used is a conventional method unless otherwise specified.
Quercetin and aconitine were purchased from the Chinese food and drug testing institute.
Example 1 combination of Quercetin and Aconitine inhibits He L a cell proliferation
First, MTT method for detecting cell proliferation
Detecting cell proliferation by tetramethylazoazolium salt colorimetric method (MTT method), inoculating cells in logarithmic growth phase into 96-well culture plate at 100 μ L/well at 37 deg.C and 5% CO2Culturing in incubator for 24 hr, adding medicine with different concentrations, quercetin with final concentration of 1.56, 3.12, 6.25, 12.5, 25, 50, 100 μ g/m L, aconitine with final concentration of 1.56, 3.12, 6.25, 12.5, 25, 50, 100 μ g/m L, and two medicines with concentration ratio of 1:1, and MTT (5mg/m L) 10 μ L, and culturing for 48 hr, discarding culture solution, adding MTT (5mg/m L) 10 μ g/m L, and adding other medicines with different concentrationsCulturing for 4h, discarding the supernatant, adding dimethyl sulfoxide 100 μ L into each well, shaking for 10min in dark to dissolve MTT crystal, measuring absorbance A of each well by selecting 490nm wavelength, and calculating proliferation inhibition rate of cells by the following formula.
Percent inhibition of cell proliferation (1-mean of experimental group a/mean of control group a) × 100% (1)
The results are shown in fig. 1, fig. 2 and fig. 3, when quercetin and aconitine are used singly or in combination, the effect of inhibiting the He L a cells of human cervical carcinoma is gradually enhanced along with the increase of the drug concentration, namely, the drug concentration is in direct proportion to the effect.
II, judging the influence of the combined application of quercetin and aconitine on the proliferation of human cervical carcinoma He L a cells by a meso-position effect method
The median effect method was used to determine the combined effect of the two drugs. The method firstly needs to draw dose-effect curves when the two medicines are applied independently and jointly, and calculates the concentrations of the two medicines which are used independently and jointly at different inhibition rates according to a medium-effect equation, wherein the formula is as follows:
D＝Dm[fa/(1-fa)]1/m(2)
wherein D is the drug concentration, Dm is the intermediate dose, fa is the cell proliferation inhibition rate, m is the slope, and the Combination Index (CI) of the two drugs is calculated as
(Dx)1And (Dx)2The concentration required to produce x% inhibition of cell proliferation for the two drugs alone, (D)1And (D)2The concentrations required for each to produce the same x% inhibition of cell proliferation for the two drugs used in combination α ═ 1 when the interaction of the two drugs is non-repulsive, and α ═ 0. (Dx) when the interaction of the two drugs is repulsive1And (Dx)2Can be obtained according to the formula (2) and (D)1And (D)2Can be obtained according to the following formula according to the fixed proportion (P/Q) adopted when the two medicines are used together:
(D)1＝(Dx)1，2×P/(P+Q) (4)
(D)2＝(Dx)1，2×Q/(P+Q) (5)
in formula (Dx)1，2The concentration required to produce an inhibition rate of x% cell proliferation when the two drugs are used in combination can be determined according to equation (2).
If the CI value obtained according to the formula (3) is less than 1, the combined action of the two medicines is considered as a synergistic effect; if CI > 1, the two drugs are considered to exhibit antagonism; if CI is 1, the combined effect of the two drugs is considered to be additive. The obtained data are all input into Excel software for analysis and processing.
The results are shown in Table 1, the effect of the combination of quercetin and aconitine on the growth inhibition of human cervical carcinoma He L a cells is better than that of a single medicine, the effective concentration of the two medicines after the combination can be respectively calculated according to the combination ratio (1:1), the effective concentration of the quercetin is 22.04 mug/m L, the effective concentration is reduced by 60.63% compared with that of the single medicine, the aconitine is 22.04 mug/m L, and the effective concentration is reduced by 69.34% compared with that of the single medicine.
TABLE 1 mean concentration (. mu.g/m L) and slope for the single and combined use of the two drugs
The results are shown in fig. 4, and it can be seen from the dose-response graph of the two drugs that when fa is 0.6 and CI is 1, the two drugs interact as an additive in the effect. When the two medicines are in small dose (less than IC)60) When used together, the composition shows synergistic effect (CI is less than 1); and large doses of both drugs (greater than IC)60) When used in combination, the compound shows antagonism (CI is more than 1).
Claims (1)
1. Application of quercetin and aconitine in preparation of medicine for treating cervical cancer is provided, wherein the dosage ratio of quercetin to aconitine is 1: 1.
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Inventor after: Li Xiumei Inventor after: Yang Peilong Inventor after: Zhang Tongcun Inventor after: Shi Dongdong Inventor after: Liu Jing Inventor after: Wen Zhiguo Inventor after: Niu Canfang Inventor before: Yang Peilong Inventor before: Li Xiumei Inventor before: Zhang Tongcun Inventor before: Shi Dongdong Inventor before: Liu Jing Inventor before: Wen Zhiguo Inventor before: Niu Canfang |
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