CN113116912A - Application of apiose-removed platycodin D in preparation of medicine for preventing and/or treating liver cancer - Google Patents

Application of apiose-removed platycodin D in preparation of medicine for preventing and/or treating liver cancer Download PDF

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CN113116912A
CN113116912A CN202110630314.XA CN202110630314A CN113116912A CN 113116912 A CN113116912 A CN 113116912A CN 202110630314 A CN202110630314 A CN 202110630314A CN 113116912 A CN113116912 A CN 113116912A
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platycodin
apiose
liver cancer
growth
human
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李一权
韩继成
房金波
朱羿龙
白冰
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Jilin Kaibo Biotechnology Co ltd
Changchun University of Chinese Medicine
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Jilin Kaibo Biotechnology Co ltd
Changchun University of Chinese Medicine
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A61K31/7034Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
    • A61K31/704Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents

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Abstract

An application of apiose-removed platycodin D in preparing a medicine for preventing and/or treating liver cancer relates to the field of anticancer medicines. According to the invention, the in vitro CCK-8 anticancer activity evaluation discovers that the apiose-removed platycodin D has a remarkable inhibition effect on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7, the IC50 values for inhibiting the growth of the 3 cell strains are respectively 26.99 +/-0.753 mu M, 19.03 +/-0.733 mu M and 26.70 +/-0.753 mu M, and the apiose-removed platycodin D has a very strong inhibition activity on the human liver cancer cell strains. The apiose-removed platycodin D has small growth inhibition effect on human normal liver cells THLE-2 and shows obvious selective inhibition effect. The apiose-removed platycodin D shows good anti-liver cancer activity, can be used for preparing anti-liver cancer drugs and has good development and application prospects.

Description

Application of apiose-removed platycodin D in preparation of medicine for preventing and/or treating liver cancer
Technical Field
The invention relates to the technical field of anti-cancer drugs, in particular to application of apiose-removed platycodin D in preparation of a drug for preventing and/or treating liver cancer.
Background
Tumors are classified into benign tumors and malignant tumors according to their general pathological forms, differentiation maturity, growth modes and degree of harm to human beings. Among them, benign tumors are called tumors, and malignant tumors are called cancers. Cancer is generally understood to mean virtually all malignant tumors. Cancer refers to a local mass formed by local tissue cell proliferation abnormality under the influence of various pathogenic factors, and is a space occupying lesion. Cancer is one of the most harmful diseases to human life health, and a large number of people die of cancer every year.
Research and development of anticancer drugs are always hot research in the pharmaceutical field. At present, the existing anticancer drugs generally have the following types. 1. Anticancer by chemotherapeutic drugs such as cyclophosphamide, daunorubicin, doxorubicin, mitoxantrone, methotrexate, vincristine, vindesine, etoposide, teniposide, etc. 2. Anticancer therapy is carried out by targeted drugs, which are generally: gefitinib, erlotinib, afatinib, herceptin monoclonal antibody, lapatinib and the like. 3. Can also be used for treating diseases with traditional Chinese medicines, such as Ci shu capsule, detoxicating and benefiting lung capsule, etc. 74 percent of the anticancer drugs are natural products or derivatives thereof, for example, paclitaxel and the derivatives thereof are the anticancer drugs with better clinical application effect at present. Therefore, the search for anticancer compounds from natural products is of great significance.
The apigenin-removed platycodin D is a novel saponin compound extracted from platycodon grandiflorum (Xu BJ, et al. in vitro inhibiting effect Of tribenoidal saponin from Platycodi Radix on supercritical lipase [ J ]. Archives Of pharmaceutical Research,2005,28(2): 180-. At present, the disclosed applications of the apiose-removed platycodin D mainly comprise: protection against inflammatory cholestatic liver injury (Kim T-W, et al. protective effect Of the aqueous extract from the root Of plant grandiflora on cholestisis-induced fatty in microorganisms (vol 50, pg 1473,2012) [ J ]. Pharmaceutical Biology,2016,54(1): 187), Antioxidant (Jeon S-H, et al. effective Of the cosmetic Content And Antioxidant Activities Of the plant grandiflora radiation by treating Length [ J ]. Korea Journal Of the medical Science,2015,23(5): 363), anti-Hepatitis C Virus (Kim J-W, sample J. fatty in tissue, pancreas grandiflora [ III ] inhibition Of fatty acid B kinase, fatty acid B kinase [ III ] III, fatty acid B [ III ] III, IV [ III ] III, IV ] III, IV, III, IV, III, IV, III, 2005,28(2):180-185.). The application of the apiose-removed platycodin D in the anticancer field is not reported yet.
Disclosure of Invention
The invention aims to provide a new application of apiose-removed platycodin D, and particularly relates to an application of apiose-removed platycodin D in preparation of a medicine for preventing and/or treating liver cancer.
The technical scheme adopted by the invention for solving the technical problem is as follows:
the invention relates to application of apiose-removed platycodin D in preparation of a medicine for preventing and/or treating liver cancer.
In a preferred embodiment, the concentration of the apiose-removed platycodin D is 1 to 100 μ M.
In a preferred embodiment, the structural formula of the apiose platycodin D is shown as follows:
Figure BDA0003103426300000031
in a preferred embodiment, the IC50 values of the apiose-removed platycodin D on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7 are respectively as follows: 26.99 + -0.753 μ M, 19.03 + -0.733 μ M, and 26.70 + -0.753 μ M.
In a preferred embodiment, the apigenin-D plays an anti-liver cancer activity by inhibiting the growth of human liver cancer cell lines HepG-2, HCCLM3 and HuH-7.
In a preferred embodiment, the apigenin-D has no inhibition effect on the growth of human normal liver cells THLE-2.
In a preferred embodiment, the apigenin D has a selective inhibitory effect on tumor cells.
The invention has the beneficial effects that:
according to the invention, the in vitro CCK-8 anticancer activity evaluation discovers that the apiose-removed platycodin D has a remarkable inhibition effect on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7, the IC50 values for inhibiting the growth of the 3 cell strains are respectively 26.99 +/-0.753 mu M, 19.03 +/-0.733 mu M and 26.70 +/-0.753 mu M, and the apiose-removed platycodin D has a very strong inhibition activity on the human liver cancer cell strains. The apiose-removed platycodin D has small growth inhibition effect on human normal liver cells THLE-2 and shows obvious selective inhibition effect. The apiose-removed platycodin D shows good anti-liver cancer activity, can be used for preparing anti-liver cancer drugs and has good development and application prospects.
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FIG. 1 shows the results of the growth inhibition of the compound apiose platycodin D on the human hepatoma cell line HepG-2 evaluated by the CCK-8 method in example 1.
FIG. 2 shows the results of the growth inhibition of the compound apiose platycodin D on human liver cancer cell line HCCLM3 evaluated by the CCK-8 method in example 1.
FIG. 3 shows the results of the growth inhibition of the compound apiose platycodin D on human hepatoma cell line HuH-7 evaluated by the CCK-8 method in example 1.
FIG. 4 shows the results of the CCK-8 method used in example 1 to evaluate the growth inhibitory effect of the compound of apiose platycodin D on human normal liver cells THLE-2.
Detailed Description
The invention relates to application of apiose-removed platycodin D in preparation of a medicine for preventing and/or treating liver cancer.
Preferably, the concentration of the apiose-removed platycodin D is 1-100 mu M.
Preferably, the structural formula of the apiose-removed platycodin D is as follows:
Figure BDA0003103426300000041
preferably, the IC50 values of the apiose-removed platycodin D on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7 are respectively as follows: 26.99 + -0.753 μ M, 19.03 + -0.733 μ M, and 26.70 + -0.753 μ M.
Preferably, the apiose-removed platycodin D plays an anti-liver cancer activity by inhibiting the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7.
Preferably, the apiose-removed platycodin D has no inhibition effect on the growth of the normal human liver cells THLE-2.
Preferably, the apiose-removed platycodin D has the selective inhibition effect on tumor cells.
The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Material sources are as follows:
the apiose-removed platycodin D is purchased from Dorper scientific development Co.
Human hepatoma cell line HepG-2 was purchased from Chengdu-Mi-Prie-method science and technology development, Inc.
The human liver cancer cell strain HCCLM3 is purchased from the institute of Biotechnology, Chuanglian and Union of Beijing.
The human hepatoma cell strain HuH-7 was purchased from the institute of Biotechnology, Chuangna, Beijing.
Human normal hepatocytes THLE-2 were purchased from the institute of Biotechnology, Beijing, Ministry of invasiveness and Biotechnology.
Example 1 evaluation of growth inhibitory Effect of the Compound Desenanthes platycodin D on human hepatoma cell lines by CCK-8 method
The method comprises the following steps: human hepatoma cell line He in logarithmic growth phase of digestionpG-2, HCCLM3 and HuH-7. Counting and adjusting cell concentration to 1X 10 with complete cell culture broth5One cell/ml, 100. mu.l/well in 96-well cell culture plates (i.e., 1X 10)4One/well), after the cells adhere to the wall (about 24 h), the culture solution is aspirated and washed 2 times with Hank's solution. The test was divided into a blank control group and a drug-treated group. The blank control group is replaced by DMEM medium containing 10% fetal bovine serum; the drug treatment groups replaced medium containing apigenin D at concentrations of 100. mu.M, 50. mu.M, 20. mu.M, 10. mu.M, 5. mu.M and 1. mu.M. Human normal hepatocytes THLE-2 were treated in the same manner. After culturing for 48h, absorbing and removing the culture solution in the holes, adding 100 mul/hole CCK-8 dye solution (evenly mixing the CCK-8 dye solution and the culture medium according to the volume ratio of 1:9 of the CCK-8 dye solution to the culture medium to prepare working solution), continuously placing the working solution in an incubator for culturing for 2h, measuring the light absorption value (the wavelength is 490nm) by using a microplate reader (products of TECAN company), calculating the survival condition of cells according to the light absorption value, and arranging 6 repeat holes for each treatment. The kill rate was calculated as follows:
percent killing (%) (control well a value-experimental well a value)/control well a value
As a result: as shown in figures 1-3, apiose-removed platycodin D has a remarkable inhibiting effect on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7. The IC50 values of the apiose-removed platycodin D for inhibiting the growth of human hepatoma cells HepG-2, HCCLM3 and HuH-7 are respectively as follows: 26.99 + -0.753 μ M, 19.03 + -0.733 μ M, and 26.70 + -0.753 μ M; and has small inhibition effect on human normal liver cells THLE-2, as shown in figure 4, the platycodin D without apiose has selective inhibition effect on tumor cells.
And (4) conclusion: the experiments prove that the apiose-removed platycodin D has good inhibition effect on the growth of human liver cancer cell strains HepG-2, HCCLM3 and HuH-7. Therefore, the apiose-removed platycodin D has the liver cancer resisting activity and can be applied to preparing liver cancer resisting medicines.
Finally, it should be noted that: the above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: it is to be understood that modifications may be made to the technical solutions described in the foregoing embodiments, or equivalents may be substituted for some of the technical features thereof, but such modifications or substitutions do not depart from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims (7)

1. Application of platycodin D without apiose in preparing medicine for preventing and/or treating liver cancer is provided.
2. The use as claimed in claim 1, wherein the concentration of said apigenin D is 1-100 μ M.
3. The use as claimed in claim 1, wherein the structural formula of the apiose platycodin D is as follows:
Figure FDA0003103426290000011
4. the use as claimed in claim 1, wherein the apigenin-D has IC50 values for growth of human hepatoma cell lines HepG-2, HCCLM3 and HuH-7, respectively: 26.99 + -0.753 μ M, 19.03 + -0.733 μ M, and 26.70 + -0.753 μ M.
5. The use as claimed in claim 1, wherein the apigenin-D exerts anti-hepatoma activity by inhibiting the growth of the human hepatoma cell lines HepG-2, HCCLM3 and HuH-7.
6. The use as claimed in claim 1, wherein the apigenin D is not inhibitory to the growth of human normal liver cells THLE-2.
7. The use as claimed in claim 1, wherein the apigenin D has a selective inhibitory effect on tumour cells.
CN202110630314.XA 2021-06-07 2021-06-07 Application of apiose-removed platycodin D in preparation of medicine for preventing and/or treating liver cancer Pending CN113116912A (en)

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Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101240005A (en) * 2007-10-29 2008-08-13 吉林农业大学 Method for preparing platycodin D from balloon-flower root and application thereof in anti-cancer medicament
CN102264378A (en) * 2009-01-23 2011-11-30 B&C生物制药株式会社 Pharmaceutical composition for preventing or treating hepatitis c, comprising the roots extract of platycodon grandiflorum or platycodon grandiflorum saponin components
KR20120117197A (en) * 2011-04-14 2012-10-24 삼척시 Immune and anticancer activities enhanced composition containing the platycodon grandiflorum fraction from the platycodon grandiflorum roots with high purity platycosides
CN104873563A (en) * 2015-04-29 2015-09-02 吉林农业大学 Preparation method of platycodon root stem leaf saponin and application of platycodon root stem leaf saponin in preparing anti-tumor medicines and health-care products
CN111394266A (en) * 2019-12-03 2020-07-10 延边大学 Preparation method and application of apiose-removed platycodin D
KR102204452B1 (en) * 2020-07-01 2021-01-15 한국수목원관리원 Method for producing rare saponins using saponins derived from platycodon grandiflorum

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101240005A (en) * 2007-10-29 2008-08-13 吉林农业大学 Method for preparing platycodin D from balloon-flower root and application thereof in anti-cancer medicament
CN102264378A (en) * 2009-01-23 2011-11-30 B&C生物制药株式会社 Pharmaceutical composition for preventing or treating hepatitis c, comprising the roots extract of platycodon grandiflorum or platycodon grandiflorum saponin components
KR20120117197A (en) * 2011-04-14 2012-10-24 삼척시 Immune and anticancer activities enhanced composition containing the platycodon grandiflorum fraction from the platycodon grandiflorum roots with high purity platycosides
CN104873563A (en) * 2015-04-29 2015-09-02 吉林农业大学 Preparation method of platycodon root stem leaf saponin and application of platycodon root stem leaf saponin in preparing anti-tumor medicines and health-care products
CN111394266A (en) * 2019-12-03 2020-07-10 延边大学 Preparation method and application of apiose-removed platycodin D
KR102204452B1 (en) * 2020-07-01 2021-01-15 한국수목원관리원 Method for producing rare saponins using saponins derived from platycodon grandiflorum

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
K J LEE,等: "Isolation of a new saponin and cytotoxic effect of saponins from the root of Platycodon grandiflorum on human tumor cell lines", 《PLANTA MED》 *
LI-JUAN XIU,等: "Anticancer effects of traditional Chinese herbs with phlegm-eliminating properties – An overview", 《J ETHNOPHARMACOL》 *
YEON HEE CHOI,等: "Antiproliferative Effects of Saponins from the Roots of Platycodon grandiflorum on Cultured Human Tumor Cells", 《J NAT PROD》 *

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Application publication date: 20210716