CN114831980A - A composition containing wogonin and baicalein and its application in preparing medicine for treating colorectal cancer - Google Patents
A composition containing wogonin and baicalein and its application in preparing medicine for treating colorectal cancer Download PDFInfo
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- CN114831980A CN114831980A CN202210524940.5A CN202210524940A CN114831980A CN 114831980 A CN114831980 A CN 114831980A CN 202210524940 A CN202210524940 A CN 202210524940A CN 114831980 A CN114831980 A CN 114831980A
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- baicalein
- wogonin
- colorectal cancer
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- 239000003814 drug Substances 0.000 title claims abstract description 28
- FXNFHKRTJBSTCS-UHFFFAOYSA-N Baicalein Natural products C=1C(=O)C=2C(O)=C(O)C(O)=CC=2OC=1C1=CC=CC=C1 FXNFHKRTJBSTCS-UHFFFAOYSA-N 0.000 title claims abstract description 25
- UDFLTIRFTXWNJO-UHFFFAOYSA-N baicalein Chemical compound O1C2=CC(=O)C(O)=C(O)C2=C(O)C=C1C1=CC=CC=C1 UDFLTIRFTXWNJO-UHFFFAOYSA-N 0.000 title claims abstract description 23
- 229940015301 baicalein Drugs 0.000 title claims abstract description 23
- 206010009944 Colon cancer Diseases 0.000 title claims abstract description 21
- XLTFNNCXVBYBSX-UHFFFAOYSA-N wogonin Chemical compound COC1=C(O)C=C(O)C(C(C=2)=O)=C1OC=2C1=CC=CC=C1 XLTFNNCXVBYBSX-UHFFFAOYSA-N 0.000 title claims abstract description 21
- 208000001333 Colorectal Neoplasms Diseases 0.000 title claims abstract description 19
- HIMJIPRMECETLJ-UHFFFAOYSA-N Wogonin Natural products COc1cc(O)c(O)c2C(=O)C=C(Oc12)c3ccccc3 HIMJIPRMECETLJ-UHFFFAOYSA-N 0.000 title claims abstract description 19
- 239000000203 mixture Substances 0.000 title claims abstract description 19
- 238000002360 preparation method Methods 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000000463 material Substances 0.000 claims description 4
- 239000004480 active ingredient Substances 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000002671 adjuvant Substances 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 230000035755 proliferation Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 6
- 239000001963 growth medium Substances 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 240000004534 Scutellaria baicalensis Species 0.000 description 4
- 235000017089 Scutellaria baicalensis Nutrition 0.000 description 4
- 238000005138 cryopreservation Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000002195 synergetic effect Effects 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 3
- 238000011282 treatment Methods 0.000 description 3
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- 241000282414 Homo sapiens Species 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000002512 chemotherapy Methods 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229930003935 flavonoid Natural products 0.000 description 2
- 235000017173 flavonoids Nutrition 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 238000001959 radiotherapy Methods 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 108010019160 Pancreatin Proteins 0.000 description 1
- 230000002292 Radical scavenging effect Effects 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 230000003698 anagen phase Effects 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 238000001516 cell proliferation assay Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000036461 convulsion Effects 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 206010061428 decreased appetite Diseases 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- -1 flavonoid compound Chemical class 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 239000006481 glucose medium Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000004957 immunoregulator effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 229940055695 pancreatin Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a wogonin and baicalein composition and application thereof in preparing an anti-colorectal cancer medicament. The invention discovers that wogonin and baicalein have obvious activity of synergistically inhibiting the proliferation of colorectal cancer cells, the technical effect that 1+1 is larger than 2 which is unexpected for people is generated, and the composition of wogonin and baicalein has the prospect of developing medicaments for resisting colorectal cancer.
Description
Technical Field
The invention belongs to the field of medicines, and particularly relates to a wogonin-baicalein and baicalein composition and application thereof in preparation of an anti-colorectal cancer medicine.
Background
Colorectal cancer (CRC) is one of the most prevalent cancers worldwide, with the fourth largest cancer type worldwide. According to epidemiological data statistics, in 2020, 193 million CRC (accounting for about 10 percent and the third place), 94 ten thousand death (accounting for about 9.4 percent and the second place) are newly diagnosed worldwide, and the trend of rapid growth and youthfulness is shown, thereby seriously threatening the health of human beings. Surgical treatment remains the most effective treatment at present, but the risk of recurrence and metastasis remains. Radiotherapy and chemotherapy as adjuvant therapy of surgery can reduce local recurrence rate, but can cause adverse reactions such as emesis, enteritis, alopecia, anorexia, leukopenia, and immunity decline. Although the clinical treatment scheme of the colon cancer is continuously improved, the 5-year survival rate of the chemotherapy, the radiotherapy and other comprehensive treatments mainly based on the operation still does not exceed 40 percent.
Wogonin is one of the main active ingredients of traditional Chinese herbal medicine scutellaria baicalensis, is a flavonoid compound derived from natural plants and separated from scutellaria baicalensis roots, and has various pharmacological effects of resisting inflammation, allergy, virus, convulsion, blood vessel protection, thrombosis and tumor and the like. Baicalein (baicalein) is a flavonoid monomer compound separated from the dried root of the traditional Chinese medicine scutellaria baicalensis, is the main drug effect substance basis of scutellaria baicalensis, and is called 5,6, 7-trihydroxyflavone. Baicalein has been reported to have antiviral, antibacterial, antiallergic, radical scavenging, cancer treating and immunoregulatory functions.
At present, no research at home and abroad shows that wogonin and baicalein have synergistic anti-colorectal cancer activity, and no report that wogonin and baicalein are combined for preparing anti-colorectal cancer medicaments is reported.
Disclosure of Invention
The invention aims to provide a wogonin and baicalein composition and application thereof in preparing an anti-colorectal cancer medicament.
The above purpose of the invention is realized by the following technical scheme:
use of a composition for the preparation of a medicament against colorectal cancer, said composition consisting of wogonin and baicalein.
Preferably, the ratio of the amount of wogonin to baicalein in the composition is 1:0.5625 to 1: 18.
More preferably, the medicine takes the composition as an active ingredient for resisting colorectal cancer, and also contains pharmaceutically acceptable carriers or auxiliary materials, so as to prepare pharmaceutically acceptable dosage forms.
More preferably, the carrier or adjuvant is a solid, liquid or semi-solid.
More preferably, the dosage forms include tablets, capsules, pills, transdermal microneedle preparations and injections.
Has the advantages that:
the invention discovers that wogonin and baicalein have obvious synergistic effect in the aspect of resisting colorectal cancer, the technical effect that 1+1 is larger than 2 which is unexpected for people is generated, and the composition of wogonin and baicalein has the prospect of developing into a medicament for resisting colorectal cancer.
Detailed Description
The following examples are given to illustrate the essence of the present invention, but not to limit the scope of the present invention.
First, experimental material
Reagent: DMSO (Sigma-Aldrich, USA); penicillin-streptomycin (Hyclone, usa); 0.5% pancreatin-EDTA solution (Boshide, Wuhan doctor de bioengineering, Inc.); PBS solution (Hyclone, usa); FBS (Gibco, usa); DMEM medium (Gibco, USA), MTT (Kyoto Kayji Biotechnology Co., Ltd.).
Consumable material: 100mm cell culture dishes, cell cryopreservation tubes, 96-well plates (Corning, USA), 15ml/50ml centrifuge tubes (cantonhou jiert biofiltration gmbh).
Medicine preparation: wogonin (CAS: 632-85-9) was purchased from Chengduiesi Biotech, Inc., purity: 99 percent; baicalein (CAS: 491-67-8) was purchased from Cheng-rui-fen Biotech limited, purity: 98 percent.
Cell: human colon cancer cell HCT116 (purchased from Nanjing Kebai Biotech Co., Ltd.).
Second, Experimental methods
1. HCT116 cell culture
HCT116 cells were cultured in high-glucose medium containing 10% FBS and 1% penicillin-streptomycin and 89% DMEM.
1.1 cell recovery: taking HCT116 cells frozen in liquid nitrogen to 37 ℃ constant temperature water bath, shaking to rapidly heat and melt the cells, rapidly transferring the cells to a centrifuge tube containing 10mL of culture medium, and centrifuging the cells for 5min at 1000 rpm. The supernatant was discarded, 2mL of medium was added to resuspend the cells, the cells were transferred to a 100mm petri dish containing 8mL of medium, the cells were shaken up "8", and the mixture was placed at 37 ℃ in 5% CO 2 Culturing in a constant-temperature cell culture box.
1.2 cell passage: when the HCT116 cell healing rate was 80-90%, the medium was discarded, washed twice with PBS, and 1mL of 0.25% trypsin solution (containing EDTA) was added and digested at 37 ℃ for 1 min. When the cells are sandy and slippery, 2mL of complete culture medium is quickly added to stop digestion, the cells are gently blown, the cell suspension is collected into a 15mL centrifuge tube, and the centrifugation is carried out at 1000rpm for 5min, and then the operation is carried out in the same way as the 'cell recovery'.
1.3 cell cryopreservation: after the cells were digested and centrifuged, the supernatant was discarded, and the cells were resuspended in 1mL of cell cryopreservation solution (100. mu.L DMSO + 900. mu.L FBS), blown, mixed and transferred to a cryopreservation tube. Storing at 4 deg.C for 0.5 hr, storing at-20 deg.C for 2 hr, storing at-80 deg.C overnight, and transferring to liquid nitrogen for long-term storage.
2. MTT cell proliferation assay
Collecting HCT116 cells in logarithmic growth phase, digesting with pancreatin, collecting cells, and processing at 3 × 10 3 The density of cells/wells is inoculated in a 96-well plate, wogonin with different concentrations is given to a single wogonin group, baicalein with different concentrations is given to a single baicalein group, and the drug concentration of a combined group is set to be pairwise crossed with the above concentration; the solvent is a basal culture medium. Cells were seeded in 96-well plates followed by 5% CO 2 After the cells are cultured at 37 ℃ overnight for adherence, the blank group and the control group are replaced by fresh culture media, the administration group is replaced by fresh drug-containing culture media, and the cells are continuously placed in 5% CO 2 Incubate at 37 ℃ for 48 hours. Thereafter, 20. mu.L of 5mg/mL MTT solution was added to each well and the mixture was placed on 5% CO 2 After incubation in an incubator at 37 ℃ for 4 hours, the well solutions were aspirated, reconstituted with 150mL DMSO, and placed on a microplate shaker at 300rpm for 10 min. The absorbance of each well was measured at a wavelength of 570 nm. Cell growth inhibition (%) [1- (OD administration group-OD blank)/(OD control group-OD blank group)]×100％。
3. Evaluation index of drug synergism
The evaluation method of the drug synergy adopts a Jinzhengyun Q value method (Jinzhengyun, addition in combined medication [ J ] recognized in the field]The chinese pharmacology bulletin, 1980). I.e. Q ═ M AB /(M A +M B -M A *M B ). The numerator in the formula represents the "measured combinationUnion effect ", denominator" desired union effect ", where M is A 、M B And M AB Respectively shows the inhibition rate of the drug A, the inhibition rate of the drug B and the inhibition rate of the combination of the two drugs under the current dose. Drug synergy index Q is defined as follows: when the Q value is less than 0.85, the two drugs are considered to have antagonistic effect; when the Q value is between 0.85 and 1.15, the two medicines are considered to be independent of each other and have additive effect; when the Q value is greater than 1.15, a synergistic effect is believed to exist between the two drugs.
Third, experimental results
The results of the inhibition rate and Q value calculation of different monomers or their compositions on HCT116 cells are shown in the following table. The results show that there is a significant synergistic effect of wogonin and baicalein on the inhibitory activity of HCT116 cells.
In conclusion, the wogonin and baicalein composition has a prospect of being developed into an anti-colorectal cancer medicament.
The above-described embodiments are intended to be illustrative of the nature of the invention, but those skilled in the art will recognize that the scope of the invention is not limited to the specific embodiments.
Claims (5)
1. Use of a composition for the preparation of a medicament against colorectal cancer, said composition consisting of wogonin and baicalein.
2. Use according to claim 1, characterized in that: the ratio of the mass of wogonin to the mass of baicalein in the composition is 1: 0.28125-1: 9.
3. Use according to claim 1 or 2, characterized in that: the medicine takes the composition as an active ingredient for resisting colorectal cancer, also contains pharmaceutically acceptable carriers or auxiliary materials, and is prepared into pharmaceutically acceptable dosage forms.
4. Use according to claim 3, characterized in that: the carrier or adjuvant is solid, liquid or semisolid.
5. Use according to claim 3, characterized in that: the dosage forms include tablets, capsules, pills, transdermal microneedle preparations and injections.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210524940.5A CN114831980B (en) | 2022-05-13 | 2022-05-13 | Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210524940.5A CN114831980B (en) | 2022-05-13 | 2022-05-13 | Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114831980A true CN114831980A (en) | 2022-08-02 |
| CN114831980B CN114831980B (en) | 2024-05-28 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN202210524940.5A Active CN114831980B (en) | 2022-05-13 | 2022-05-13 | Wogonin and baicalein composition and application thereof in preparation of anti-colorectal cancer drugs |
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| Country | Link |
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| CN (1) | CN114831980B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117045639A (en) * | 2023-09-27 | 2023-11-14 | 山东益康药业股份有限公司 | Pharmaceutical composition for treating gastric cancer and application thereof |
-
2022
- 2022-05-13 CN CN202210524940.5A patent/CN114831980B/en active Active
Non-Patent Citations (2)
| Title |
|---|
| CHUNHAO YU 等: "Pretreatment of baicalin and wogonoside with glycoside hydrolase: A promising approach to enhance anticancer potential" * |
| SO-JUNG KIM 等: "Antitumor actions of baicalein and wogonin in HT-29 human colorectal cancer cells" * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117045639A (en) * | 2023-09-27 | 2023-11-14 | 山东益康药业股份有限公司 | Pharmaceutical composition for treating gastric cancer and application thereof |
| CN117045639B (en) * | 2023-09-27 | 2024-04-02 | 山东益康药业股份有限公司 | Pharmaceutical composition for treating gastric cancer and application thereof |
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| Publication number | Publication date |
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| CN114831980B (en) | 2024-05-28 |
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