CN111419862A - Application of rhizoma paridis saponin in preparation of STAT3 inhibitor - Google Patents
Application of rhizoma paridis saponin in preparation of STAT3 inhibitor Download PDFInfo
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- CN111419862A CN111419862A CN202010153650.5A CN202010153650A CN111419862A CN 111419862 A CN111419862 A CN 111419862A CN 202010153650 A CN202010153650 A CN 202010153650A CN 111419862 A CN111419862 A CN 111419862A
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- China
- Prior art keywords
- saponin
- stat3
- diseases
- paris polyphylla
- rhizoma paridis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- 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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Abstract
The invention discloses application of paridis saponin in preparation of an STAT3 inhibitor, and experiments prove that the paridis saponin is an antagonist of STAT3, has good activity of inhibiting a STAT3 signal channel, is used as an active ingredient to prepare a medicament based on inhibition of a STAT3 signal as a target, and is used for treating diseases related to continuous activation of the STAT3 signal channel, wherein the diseases related to continuous activation of the STAT3 signal channel comprise autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, nerve and nerve degenerative diseases, cardiovascular diseases, allergic reactions, asthma Alzheimer's disease and cancers. The invention discloses that the paris polyphylla saponin is an antagonist of STAT3, and the paris polyphylla saponin is a natural small molecular compound, and has the advantages of wide source, mature extraction process, low development cost, controllable toxicity and the like.
Description
Technical Field
The invention belongs to the field of medicine preparation, and particularly relates to application of paris polyphylla saponin in preparation of a STAT3 inhibitor.
Background
The traditional Chinese medicine Paris polyphylla is dried rhizome of Paris polyphylla Smith var.yunnanensis (Franch.) hand-Mazz or Paris polyphylla Smith var.chinensis (Franch.) Hara of the family Liliaceae, has the effects of clearing heat and releasing toxin, relieving swelling and pain and cooling liver and arresting convulsion, is used for treating symptoms such as furuncle swelling, sore throat, venomous snake bite, traumatic injury and cold wind convulsion, and has the effects of stopping bleeding, eliminating phlegm, inhibiting bacteria, relieving pain and calming, resisting pregnancy and killing sperms, resisting cytotoxin and the like through modern pharmacological actions. Paris polyphylla saponin (RPS) has broad-spectrum antitumor activity, and mainly comprises diosgenin and pennogenin, wherein the diosgenin accounts for most of them. Paris saponin II belongs to diosgenin, and has multiple anticancer activities. For example, the paris polyphylla saponin II can inhibit the growth of lung cancer of a T739 mouse and also can inhibit the growth of HepG2 cells, mainly by inducing the cells to generate apoptosis and S-phase retardation. Paris saponin II can also promote apoptosis of ovarian cancer cells to play an anti-cancer role by inhibiting angiogenesis and increasing activity of Bax, cytochrome C, Caspase-3 and Caspase-9 in cytoplasm, and can also inhibit a NF-kB signal pathway.
Signal Transducer and Activator of Transcription (STAT), a unique family of proteins that bind to DNA. STAT is highly expressed in a variety of human malignant tumor tissues and cell lines, while there is little or no activation of STAT in normal tissues. STAT activation is currently detectable in both squamous cell carcinoma of the head and forepart, breast cancer, autohemangiopathy/lymphoma, lung cancer, renal cell therapy, and in both Mongolian, melanoma, pancreatic and ovarian carcinomas. Particularly STAT 3. It is considered that the gene may be an oncogene, and the abnormality of the signal transduction pathway involved in the gene may play an important role in the invasion and metastasis of tumors. Blocking the oncogene STAT3 signaling pathway in tumor cells can play a role in treating tumors.
However, at present, no report on the application of the paris polyphylla saponin in the preparation of the STAT3 inhibitor exists.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides application of paris polyphylla saponin in preparing STAT3 inhibitors.
The technical scheme of the invention is summarized as follows:
use of paridis saponin in preparing STAT3 inhibitor is provided.
Preferably, the rhizoma paridis saponin is rhizoma paridis saponin II, rhizoma paridis saponin I, rhizoma paridis saponin H, rhizoma paridis saponin VII, β -1, 2-glucosylcysteine dioscin, 2-deoxyglucosylcysteine dioscin or rhamnose β -1, 2-glucosylcysteine dioscin.
Most preferably, the paris polyphylla saponin is paris polyphylla saponin II.
The invention has the advantages that:
the experiment proves that the paris polyphylla saponin is an antagonist of STAT3, has good activity of inhibiting a STAT3 signal channel, is used as an active ingredient to prepare a medicament based on inhibiting a STAT3 signal and treat diseases related to the continuous activation of the STAT3 signal channel, wherein the diseases related to the continuous activation of the STAT3 signal channel comprise autoimmune diseases, inflammatory diseases, bone diseases, metabolic diseases, nerve and nerve degenerative diseases, cardiovascular diseases, allergic reactions, asthma Alzheimer's disease and cancers. The invention discloses that the paris polyphylla saponin is an antagonist of STAT3, and the paris polyphylla saponin is a natural small molecular compound, and has the advantages of wide source, mature extraction process, low development cost, controllable toxicity and the like.
Drawings
FIG. 1 shows the results of in vitro anti-tumor activity assay of paridis saponin, wherein a is a Bel-7402 cell survival rate assay, and b is a HepG2 cell survival rate assay.
FIG. 2 shows STAT3 protein expression level of the yamogenin in inhibiting liver cancer cell HepG 2.
Detailed Description
The present invention will be further illustrated by the following specific examples.
Example 1
Rhizoma paridis saponin II (RPSII), Rhizoma Paridis Saponin I (RPSI), Rhizoma Paridis Saponin H (RPSH), rhizoma paridis saponin VII (RPS VII), β -1, 2-glucosyl dioscin (P81E), 2-deoxyglucosyl dioscin (P51E), rhamnose β -1, 2-glucosyl dioscin (P80E)
Rhizoma paridis saponin I:
the molecular formula is C44H70O16The molecular weight is 855.02, and the white crystal powder can be dissolved in organic solvent such as methanol, ethanol, DMSO, etc., and is derived from rhizome of Paris yunnanensis Franch of Liliaceae. CAS number: 50773-41-6, structural formula is shown in formula I:
rhizoma paridis saponin II:
the molecular formula is C44H70O17, the molecular weight is 877.02, white crystal powder can be dissolved in organic solvents such as methanol and DMSO, and can be easily dissolved in water; is derived from rhizome of Paris yunnanensis Franch, belonging to Liliaceae. CAS number: 76296-72-5, structural formula as shown in formula II:
rhizoma paridis saponin H:
the molecular formula is C44H70O17, the molecular weight is 871.02, the white crystal powder can be dissolved in organic solvents such as methanol, ethanol, DMSO, etc., and is derived from rhizome of Paris yunnanensis Franch of family Liliaceae. CAS number: 81917-50-2, the structural formula is shown in formula III:
rhizoma paridis saponin VII:
the molecular formula is C51H84O22The molecular weight is 1049.2, white crystal powder can be dissolved in organic solvents such as methanol and DMSO, and can also be easily dissolved in water; is derived from rhizome of Paris yunnanensis Franch of Liliaceae. CAS number: 76296-75-8, structural formula is shown in formula IV:
rhamnose β -1, 2-glucose dioscin (P80E):
the molecular formula is C38H60O14The molecular weight is 740.8, and the white crystal powder is soluble in organic solvents such as methanol and DMSO, and also soluble in water. CAS number: 145385-66-6, the structural formula is shown in formula V:
β -1, 2-glucose dioscin (P81E):
the molecular formula is C45H72O17The molecular weight is 884, and the white crystal powder can be dissolved in organic solvents such as methanol and DMSO, and can be easily dissolved in water. The structural formula is shown as formula VI:
2-deoxyglucosamine dioscin (P51E):
the molecular weight is 486, white crystal powder, can be dissolved in organic solvents such as methanol, DMSO, and the like, and can also be easily dissolved in water; is derived from rhizome of Paris yunnanensis Franch of Liliaceae. CAS number: 32685-93-1, the structural formula is shown in formula VII:
example 2
Method for testing antitumor activity
1. In vitro antitumor Activity test
1.1 cell lines and culture
The hepatoma cell line HepG2 cell line, which is an adherent cell, was cultured in a DMEM medium containing 10% inactivated fetal calf serum, 100U/m L penicillin, and 100. mu.g/m L streptomycin at 37 ℃ with 5% CO2Culturing in incubator under saturated humidity condition, and subculturing for 3-4 days.
1.2 determination of antitumor Activity of drugs (Paris Saponin I, Paris Saponin II, Paris Saponin VII)
MTT method, wherein cells in logarithmic growth phase are digested with pancreatin, and then prepared into a concentration of 3 × 10 using the medium used in step 1.1 as a solvent5The method comprises the steps of inoculating cell suspension of each m L to a 96-well enzyme label plate, adding 200 mu L to each well, changing to a serum-free state after 24 hours, adding DMEM culture medium containing 100U/m L penicillin and 100 mu g/m L streptomycin to enable cells to synchronously grow, adding fresh culture solution containing drugs (DMSO is used as a solvent) with different concentrations and corresponding solvent (DMSO) controls on the third day, adding 200 mu L to each well, setting 5 dosage groups of tested drugs, arranging 8 parallel wells in each group, adding 0.5mg/m L MTT 100 mu L freshly prepared by serum-free phenol-free DMEM culture solution to each well after 24 hours of culture at 37 ℃, continuing to culture for 4 hours, adding 100 mu L DMSO to each well to dissolve MTT formazan particles, uniformly mixing by using a micro-oscillator, measuring an optical density value (OD) on an enzyme label reader, repeating the experiment for three times, and taking an average value.
And (3) replacing the hepatoma cell line HepG2 cell line with the hepatoma cell line Bel-7402 cell line, replacing the DMEM culture medium with the 1640 culture medium, repeating the experiment for three times in the same step 1.2, and taking an average value.
The inhibition ratio was calculated from the OD value of the control group of tumor cells treated with a solvent control, and the inhibition ratio was calculated as [ (control OD value-experimental OD value)/control OD ] × 100, from which IC50 (half inhibition ratio) was obtained.
The results (see FIG. 1, where a is a Bel-7402 cell viability assay and b is a HepG2 cell viability assay) show that: the paris polyphylla saponin I, the paris polyphylla saponin II and the paris polyphylla saponin VII can obviously inhibit the activity of liver cancer cells.
2. Paris saponin targeting STAT3 protein
By software: the small molecule target protein prediction is carried out by SwissTargetPrediction, the software analyzes the protein possibly acted by the compound through the analysis of a chemical structural formula, and the analysis result shows that a plurality of paridis saponins can be combined with STAT3 protein.
3. Paris polyphylla saponin inhibition STAT3 protein expression
After the cell HepG2 cell strain is treated for 24 hours by using different concentrations of the paris polyphylla saponin (DMSO is used as a solvent), cell whole protein is extracted, and the change of the STAT3 protein level is detected by using an immunoblotting experiment.
The results show that: paris saponin inhibited STAT3 protein expression (FIG. 2).
Three conclusions
Experiments prove that the paris polyphylla saponin I, the paris polyphylla saponin II and the paris polyphylla saponin VII have high anti-liver cancer activity;
paris saponin II, Paris saponin I, Paris saponin H, Paris saponin VII, β -1, 2-glucose dioscin, 2-deoxyglucosamine dioscin, and rhamnose β -1, 2-glucose dioscin inhibit STAT3 protein expression.
Claims (3)
1. Use of paridis saponin in preparing STAT3 inhibitor is provided.
2. The use of claim 1, wherein the rhizoma paridis saponin is rhizoma paridis saponin II, rhizoma paridis saponin I, rhizoma paridis saponin H, rhizoma paridis saponin VII, β -1, 2-glucosylceragenin, 2-deoxyglucosylceragenin or rhamnose β -1, 2-glucosylceragenin.
3. The use according to claim 2, wherein the polyphyllin is polyphyllin II.
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