AU2021106930A4 - Use of epimedium-derived flavonoid glycoside in preparation of medicine for treating melanoma - Google Patents
Use of epimedium-derived flavonoid glycoside in preparation of medicine for treating melanoma Download PDFInfo
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- AU2021106930A4 AU2021106930A4 AU2021106930A AU2021106930A AU2021106930A4 AU 2021106930 A4 AU2021106930 A4 AU 2021106930A4 AU 2021106930 A AU2021106930 A AU 2021106930A AU 2021106930 A AU2021106930 A AU 2021106930A AU 2021106930 A4 AU2021106930 A4 AU 2021106930A4
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/29—Berberidaceae (Barberry family), e.g. barberry, cohosh or mayapple
- A61K36/296—Epimedium
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- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
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Abstract
OF THE DISCLOSURE
The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the
preparation of a medicine for treating a melanoma, belonging to the technical field of biomedicines,
where the Epimedium-derived flavonoid glycoside includes an icariside I. Even a high dose of the
icariside I has a little effect on organs of mice, indicating that the icariside I is relatively safe. The
icariside I can significantly reduce a tumor volume of the mice bearing B16F10 (mouse melanoma
cells), with an effect better than an icariin. Meanwhile, the icariside I improves splenomegaly of
tumor-bearing mice, and changes a spleen level of the tumor-bearing mice to normal. In addition,
the icariside I increases the mass of a thymus in the tumor-bearing mice, and changes a thymus
level of the tumor-bearing mice to normal. Furthermore, the icariside I can restore immune organs
of the tumor-bearing mice to normal.
ABSTRACT DRAWING
Liver weight
111
Kidney weight
FIG. IA
Description
[01] The present disclosure belongs to the technical field of biomedicines, and in particular relates to use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma.
[02] A melanoma as a common clinical tumor is generally originated in the skin and mucous membranes. Observations from clinical practice have shown that the melanoma is highly-malignant and prone to distant metastasis, and is also one of the malignant tumors with the fastest-growing incidence. The melanoma is insensitive to radiotherapy and chemotherapy, and has a high drug resistance. Currently, there are only a few medicines that can clinically treat the melanoma, while these medicines have large side effects. Most patients with melanoma die within five years.
[03] Icariside I is a trace flavonoid glycoside in a Chinese herbal medicine Epimedium. At present, there are few reports on the pharmacological activity of the icariside I. Shen Jingshan et al. (CN101113157A, ISOPENTENYL FLAVONE DERIVATIVE, PREPARATION METHOD AND USE THEREOF) mentioned that an isopentenyl flavone derivative can treat or prevent sexual dysfunction and improve vasoconstriction-related diseases. Seong Park Jun et al. (CNO1316573A, COSMETIC COMPOSITION CONTAINING HYDROLYSATES OF ICARIIN) prepared anti-oxidant, anti-aging, whitening or anti-wrinkle cosmetic compositions using an icariside I. Dong Hui et al. (CN100500160C, MEDICINAL COMPOSITION CONTAINING EPIMEDIUM ACTIVE CONSTITUENT AND USE THEREOF) prepared a pharmaceutical composition for preventing and treating prostate hyperplasia by mixing an icariside I with other Epimedium ingredients. Gu Nianquan et al. (CN104825479B, ICARISIDE DERIVATIVES AS WELL AS PREPARATION METHOD AND USE THEREOF IN PROMOTING HUMAN CELLS TO GENERATE INTERFERON-GAMMA AND TREATING DISEASE) prepared a medicine using icariside derivatives, for treating infectious diseases such as tuberculosis, influenza, hepatitis B and hepatitis C, and tumors.
[04] At present, there is no specific report on the icariside I in the preparation of anti-melanoma medicines.
[05] An objective of the present disclosure is to provide use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I. The present disclosure provides a new way to use the icariside I.
[06] To achieve the above objective, the present disclosure provides the following technical solutions:
[07] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I.
[08] Preferably, the icariside I may have a purity of at least 90%.
[09] The present disclosure further provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting cell proliferation of a melanoma, where the Epimedium-derivedflavonoid glycoside includes an icariside I.
[10] The present disclosure further provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting tumor growth of a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I.
[11] The present disclosure further provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for protecting an immune organ, where the Epimedium-derived flavonoid glycoside includes an icariside I.
[12] Preferably, the immune organ may include a thymus and/or a spleen.
[13] Preferably, the medicine may have a dosage of a tablet, a capsule, a granule, a soft capsule, a dripping pill, a syrup or an injection.
[14] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I.
[15] The results of an example of the present disclosure show that: even a high dose of the icariside I has a little effect on organs of mice, indicating that the icariside I is relatively safe. The icariside I can significantly reduce a tumor volume of the mice bearing B16F10 (mouse melanoma cells), with an effect better than an icariin. Meanwhile, the icariside I improves splenomegaly of tumor-bearing mice, and changes a spleen level of the tumor-bearing mice to normal; and the icariside I increases the mass of a thymus in the tumor-bearing mice, and changes a thymus level of the tumor-bearing mice to normal. Therefore, the icariside I can restore immune organs of the tumor-bearing mice to normal.
[16] FIG. 1A illustrates an effect of different doses of icariside I on the organs of normal mice (liver weight).
[17] FIG. 1B illustrates an effect of different doses of icariside I on the organs of normal mice
(kidney weight).
[18] FIG. 1C illustrates an effect of different doses of icariside I on the organs of normal mice (spleen weight).
[19] FIG. ID illustrates an effect of different doses of icariside I on the organs of normal mice (spleen appearance).
[20] FIG 2A illustrates an inhibitory effect of icariside I on the tumors in melanoma-bearing mice (tumor volume change).
[21] FIG 2B illustrates an inhibitory effect of icariside I on the tumors in melanoma-bearing mice (tumor weight).
[22] FIG 2C illustrates an inhibitory effect of icariside I on the tumors in melanoma-bearing mice (tumor appearance).
[23] FIG. 3 illustrates an effect of icariside I on the body weight of tumor-bearing mice.
[24] FIG. 4 illustrates a comparison of the tumor inhibitory effects of icariside I and icariin (SU) on melanoma-bearing mice (tumor volume change).
[25] FIG. 5A illustrates an effect of icariside I on a thymus index of melanoma-bearing mice (compared with icariin (SU)).
[26] FIG. 5B illustrates an effect of icariside I on a spleen index of melanoma-bearing mice (compared with icariin (SU)).
[27] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I. In the present disclosure, the icariside I has a purity of preferably at least 90%. The medicine has a dosage form preferably selected from the group consisting of a tablet, a capsule, a granule, a soft capsule, a dripping pill, a syrup or an injection. The icariside I is the only active ingredient in the medicine. There is no special limitation on the content of the icariside I in the medicine. There is no special limitation on a preparation method of the medicine, and conventional preparation methods for each dosage form can be used.
[28] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting cell proliferation of a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I. In the present disclosure, the icariside I has a purity of preferably at least 90%. The medicine has a dosage form preferably selected from the group consisting of a tablet, a capsule, a granule, a soft capsule, a dripping pill, a syrup or an injection. The icariside I is the only active ingredient in the medicine. There is no special limitation on the content of the icariside I in the medicine. There is no special limitation on a preparation method of the medicine, and conventional preparation methods for each dosage form can be used.
[29] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting tumor growth of a melanoma, where the Epimedium-derived flavonoid glycoside includes an icariside I. In the present disclosure, the icariside I has a purity of preferably at least 90%. The medicine has a dosage form preferably selected from the group consisting of a tablet, a capsule, a granule, a soft capsule, a dripping pill, a syrup or an injection. The icariside I is the only active ingredient in the medicine. There is no special limitation on the content of the icariside I in the medicine. There is no special limitation on a preparation method of the medicine, and conventional preparation methods for each dosage form can be used.
[30] The present disclosure provides use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for protecting an immune organ, where the Epimedium-derived flavonoid glycoside includes an icariside I. In the present disclosure, the immune organ preferably includes a thymus and/or a spleen. The icariside I has a purity of preferably at least 90%. The medicine has a dosage form preferably selected from the group consisting of a tablet, a capsule, a granule, a soft capsule, a dripping pill, a syrup or an injection. The icariside I is the only active ingredient in the medicine. There is no special limitation on the content of the icariside I in the medicine. There is no special limitation on a preparation method of the medicine, and conventional preparation methods for each dosage form can be used.
[31] The technical solutions provided by the present disclosure will be described in detail below with reference to examples, but the examples should not be construed as limiting the claimed scope of the present disclosure.
[32] Example 1
[33] Effect of different doses of an icariside I on the organs of normal mice
[34] Totally 21 commercially-available specific pathogen free-grade (SPF-grade) C57 female mice were divided into 7 groups from groups A to G, and each group included 3 mice; the group A was given corn oil by gavage, and the groups B to G were given the icariside I by gavage at 5 mg/kg, 20 mg/kg, 80 mg/kg, 160 mg/kg, 320 mg/kg and 640 mg/kg, respectively; after 7 days of continuous administration, the mice were sacrificed to observe the organs.
[35] It can be seen from FIG. 1A to FIG.ID that, even under high-dose administration, the icariside I has no significant effect on the main organs (liver, kidney, and glands and the like) of normal mice. It indicates that the icariside I is less toxic.
[36] Example 2
[37] Experiment of an icariside I inhibiting the melanoma in mice (while conducting a comparison test of an icariin and an evaluation of effects on the immune organs of tumor-bearing mice)
[38] All tumor cell lines were self-cultivated after purchase. B16F10 (mouse melanoma cells) were adherent cells, and were cultivated in a Dulbecco's modified eagle medium (DMEM) high-glucose medium containing 10% fetal bovine serum.
[39] A tumor mouse model was constructed with the B16F10 (mouse melanoma cells). A Group A was regarded as a normal control group, with no tumor cells inoculated. Constructed tumor models were randomly divided into a total of 5 groups B to E, and labeling was conducted according to cages. The Groups A and B were given a corn oil, the group C was given 5 mg/kg of the icariside I, the group D was given 20 mg/kg of the icariside I, and the group E was given 5 mg/kg of the icariin (A was a health group, B was a control group, C was a 5 mg/kg group, D was a mg/kg group, and E was an SU- 5 mg/kg group). All groups were administered by gavage. An administration was conducted according to the above dosing schedule for 7 consecutive days, a weight of the mice was recorded every day, and a weight change curve of the mice was drawn. A long-term toxicity of the icariside I could be reflected by a weight change of the mice. A longest diameter (L) and a transverse diameter (S) of the tumor were measured every day, an approximate volume of the tumor was calculated according to a formula V=0.5xLxS 2 , and a tumor volume change curve was drawn. Melanoma-bearing mice were sacrificed on the 7th day, the thymus and spleen were removed; residual blood was drained with a filter paper, the mice were weighed (mg); and an obtained weight was divided by a maternal body weight (g), and multiplied by 10 to obtain a thymus index and a spleen index. The thymus index and the spleen index were compared between the groups C and E.
[40] It can be seen from FIG. 2A to FIG. 2C that, the icariside I can significantly inhibit the growth of melanoma in vivo. Especially in the case of a dose of 20 mg/kg, the icariside I has an inhibition rate reaching 56% compared to a tumor volume and a weight of the control group.
[41] It can be seen from FIG 3 that, the icariside I has no significant effect on the weight of the tumor-bearing mice, indicating that the icariside I is less toxic.
[42] It can be seen from FIG. 4 that, the icariside I has a desirable anti-tumor effect when administered at the same dose of 5 mg/kg for 7 days, which is 1 time better than the icariin.
[43] It can be seen from FIG. 5A to FIG. 5B that, the icariside I improves the thymus index and the spleen index when administered at the same dose of 5 mg/kg for 7 days, and ameliorates the immune function of tumor-bearing mice. At the same dose, the icariin can improve the thymus index with a worse effect than that of the icariside I; and the icariin has little effect on the spleen index.
[44] The above descriptions are merely preferred implementations of the present disclosure. It should be noted that a person of ordinary skill in the art may further make several improvements and modifications without departing from the principle of the present disclosure, but such improvements and modifications should be deemed as falling within the protection scope of the present disclosure.
Claims (5)
1. Use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for treating a melanoma, wherein the Epimedium-derived flavonoid glycoside comprises an icariside I.
2. The use according to claim 1, wherein the icariside I has a purity of at least 90%.
3. Use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting cell proliferation of a melanoma, wherein the Epimedium-derived flavonoid glycoside comprises an icariside I.
4. Use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for inhibiting tumor growth of a melanoma, wherein the Epimedium-derived flavonoid glycoside comprises an icariside I.
5. Use of an Epimedium-derived flavonoid glycoside in the preparation of a medicine for protecting an immune organ, wherein the Epimedium-derived flavonoid glycoside comprises an icariside I.
ˉ1/4ͨ 24 Aug 2021
DRAWINGS 2021106930
FIG. 1A
FIG. 1B
FIG. 1C
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FIG. 1D
FIG. 2A
FIG. 2B
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FIG. 2C
FIG. 3
FIG. 4
ˉ4/4ͨ
FIG. 5B FIG. 5A
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