CN114404404A - Application of tetracyclic diterpenoid compounds in preparation of medicines for treating and/or preventing mesangial proliferative glomerulonephritis and medicines - Google Patents
Application of tetracyclic diterpenoid compounds in preparation of medicines for treating and/or preventing mesangial proliferative glomerulonephritis and medicines Download PDFInfo
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- -1 tetracyclic diterpenoid compounds Chemical class 0.000 title claims abstract description 31
- 239000003814 drug Substances 0.000 title claims abstract description 26
- 229930002348 tetracyclic diterpenoid Natural products 0.000 title claims abstract description 20
- 201000008265 mesangial proliferative glomerulonephritis Diseases 0.000 title claims abstract description 19
- 229940079593 drug Drugs 0.000 title description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- 125000002252 acyl group Chemical group 0.000 claims abstract description 6
- 125000004423 acyloxy group Chemical group 0.000 claims abstract description 6
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 6
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 239000001257 hydrogen Substances 0.000 claims abstract description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 5
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims abstract description 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 4
- 125000005035 acylthio group Chemical group 0.000 claims abstract description 4
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- ABLZXFCXXLZCGV-UHFFFAOYSA-N phosphonic acid group Chemical group P(O)(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 4
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 3
- 150000001408 amides Chemical class 0.000 claims abstract description 3
- 150000003839 salts Chemical class 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- 229940049920 malate Drugs 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- 229940095064 tartrate Drugs 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 239000003981 vehicle Substances 0.000 claims description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 claims description 2
- 229910021653 sulphate ion Inorganic materials 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 125000002389 tetracyclic diterpenoid group Chemical group 0.000 claims 1
- 210000003584 mesangial cell Anatomy 0.000 abstract description 11
- 230000006907 apoptotic process Effects 0.000 abstract description 10
- 230000035755 proliferation Effects 0.000 abstract description 6
- 230000002159 abnormal effect Effects 0.000 abstract description 4
- 125000000626 sulfinic acid group Chemical group 0.000 abstract description 2
- 125000000542 sulfonic acid group Chemical group 0.000 abstract description 2
- 210000004027 cell Anatomy 0.000 description 22
- 230000000052 comparative effect Effects 0.000 description 21
- SDHTXBWLVGWJFT-XKCURVIJSA-N oridonin Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12[C@@H](O)CCC(C)(C)[C@H]1[C@H](O)[C@@]3(O)OC2 SDHTXBWLVGWJFT-XKCURVIJSA-N 0.000 description 8
- CAQAFLRZJHXSIS-UHFFFAOYSA-N oridonin Natural products CC1(C)C=CC(O)C23COC(O)(C(O)C12)C45C(O)C(CCC34)C(=C)C5=O CAQAFLRZJHXSIS-UHFFFAOYSA-N 0.000 description 8
- 238000012360 testing method Methods 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 238000000684 flow cytometry Methods 0.000 description 4
- 231100000433 cytotoxic Toxicity 0.000 description 3
- 230000001472 cytotoxic effect Effects 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 231100000331 toxic Toxicity 0.000 description 3
- 230000002588 toxic effect Effects 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 238000010166 immunofluorescence Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 150000004197 tetracyclic diterpenoid derivatives Chemical class 0.000 description 2
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 230000010190 G1 phase Effects 0.000 description 1
- 208000022461 Glomerular disease Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 206010029164 Nephrotic syndrome Diseases 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000022131 cell cycle Effects 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 238000004624 confocal microscopy Methods 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 231100000852 glomerular disease Toxicity 0.000 description 1
- 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 1
- 229960004866 mycophenolate mofetil Drugs 0.000 description 1
- 230000004987 nonapoptotic effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
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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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medical treatment, in particular to application of a tetracyclic diterpenoid compound in preparing a medicament for treating and/or preventing mesangial proliferative glomerulonephritis, wherein the tetracyclic diterpenoid compound has a structure shown in a formula (I); r1、R2、R3Each independently selected from one or two of hydrogen, hydroxyl, halogen, C1-C8 alkyl or C3-C8 cycloalkyl, C1-C8 alkoxy, C1-C8 acyloxy, C1-C8 acyl, amino, C1-C8 alkylamino, C1-C8 amide, C2-C8 alkyl imide, nitro, mercapto, alkylthio, acylthio, phosphoryloxy, sulfonyloxy, sulfinoyloxy, amidino, guanidino, carboxyl, phosphonic acid group, sulfonic acid group, sulfinic acid group and cyano. The compoundCan specifically inhibit the abnormal proliferation of mesangial cells and induce the apoptosis of mesangial cells, and is particularly suitable for treating and/or preventing mesangial proliferative glomerulonephritis.
Description
Technical Field
The invention relates to the technical field of medical treatment, in particular to application of a tetracyclic diterpenoid compound in preparing a medicine for treating and/or preventing mesangial proliferative glomerulonephritis and a medicine.
Background
Mesangial proliferative glomerulonephritis (MesPGN) is a glomerular disease which is characterized by the diffuse proliferation of mesangial cells and the expansion of mesangial matrixes in different degrees and takes nephrotic syndrome as a main clinical expression. MesPGN accounts for about 60% of cases of primary glomerulonephritis in China, and is the main cause of chronic kidney disease and uremia. However, the etiology and pathogenesis of MesPGN are not completely clear at present, and clinical specific drugs are lacked, so that only glucocorticoids (such as prednisone and the like) and cytotoxic drugs (such as cyclophosphamide and mycophenolate mofetil and the like) with large toxic and side effects can be adopted for symptomatic treatment.
Disclosure of Invention
The invention aims to solve the problems of large toxic and side effects and low specificity of the existing medicines for treating mesangial proliferative glomerulonephritis, and provides application of a tetracyclic diterpenoid compound in preparing medicines for treating and/or preventing mesangial proliferative glomerulonephritis and medicines.
In order to achieve the above objects, one aspect of the present invention provides a tetracyclic diterpenoid compound for use in the preparation of a medicament for treating and/or preventing mesangial proliferative glomerulonephritis; the tetracyclic diterpenoid compound has a structure shown in a formula (I):
wherein R is1、R2、R3Each independently selected from hydrogen, hydroxyl, halogen, C1-C8 alkyl or C3-C8 cycloalkyl, C1-C8 alkoxy, C1-C8 acyloxy, C1-C8 acyl, amino, C1-C8 alkylamino, C1-C8 acylamino, C2-C8 alkyl imido, nitro, sulfhydryl, hydrocarbon sulfhydryl sulfenylOne of an acylthio group, a phosphoryloxy group, a sulfonyloxy group, a sulfinyloxy group, an amidino group, a guanidino group, a carboxyl group, a phosphonic acid group, a sulfonic acid group, a sulfinic acid group and a cyano group.
According to a second aspect of the present invention, there is provided a medicament, said medicament being a tetracyclic diterpenoid or a pharmaceutically acceptable salt thereof.
The tetracyclic diterpenoid compound or the pharmaceutically acceptable salt thereof provided by the invention is particularly suitable for preparing a medicament for treating and/or preventing mesangial proliferative glomerulonephritis, can specifically inhibit abnormal proliferation of mesangial cells and induce mesangial cell apoptosis, and is particularly suitable for treating and/or preventing mesangial proliferative glomerulonephritis.
Drawings
FIG. 1 is a diagram showing the fluorescence of immunofluorescence confocal images of example 2 and comparative example 1 of the present invention;
FIG. 2 is a graph showing the results of apoptosis in flow cytometry in example 2 of the present invention and comparative examples 2-3.
Detailed Description
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
According to a first aspect of the invention, the invention provides a use of the tetracyclic diterpenoid compound in the preparation of a medicament for treating and/or preventing mesangial proliferative glomerulonephritis; the tetracyclic diterpenoid compound has a structure shown in a formula (I):
wherein R is1、R2、R3Each independently selected from one of hydrogen, hydroxyl, halogen, C1-C8 alkyl or C3-C8 cycloalkyl, C1-C8 alkoxy, C1-C8 acyloxy, C1-C8 acyl, amino, C1-C8 alkylamino, C1-C8 amide, C2-C8 alkyl imide, nitro, mercapto, alkylthio, acylthio, phosphoryloxy, sulfonyloxy, sulfinoyloxy, amidino, guanidino, carboxyl, phosphonic acid, sulfonic acid, sulfinic acid and cyano. The tetracyclic diterpenoid compound or the pharmaceutically acceptable salt thereof can specifically inhibit the abnormal proliferation of mesangial cells and induce the apoptosis of the mesangial cells, and is particularly suitable for treating and/or preventing mesangial proliferative glomerulonephritis.
According to a preferred embodiment of the invention, R1、R2、R3Each independently selected from one of C1-C3 alkyl, C1-C3 alkoxy, C1-C3 acyloxy, C1-C3 acyl, C1-C3 alkylamino, C1-C3 acylamino or C2-C3 alkyl acylamino.
According to a preferred embodiment of the invention, R1、R2、R3Each independently selected from R1、R2、 R3Each independently selected from C1-C3 alkyl or C1-C3 alkoxy.
According to a preferred embodiment of the invention, R1、R2、R3Each independently selected from one of methyl, ethyl, methoxy or ethoxy.
According to a preferred embodiment of the invention, R1、R2、R3Each independently selected from one of hydrogen, hydroxyl, halogen or carboxyl.
According to a preferred embodiment of the invention, the halogen is selected from fluorine or chlorine.
According to a preferred embodiment of the invention, R1、R2、R3All are hydroxyl, and the tetracyclic diterpenoid compound is oridonin. Oridonin or a pharmaceutically acceptable salt thereof,can specifically induce mesangial cell apoptosis, efficiently inhibit abnormal proliferation of mesangial cells, effectively relieve and treat mesangial proliferative glomerulonephritis, and greatly reduce harm of glucocorticoid and cytotoxic drugs to patients, and oridonin can be extracted from natural herbaceous plants with sufficient source, has small toxic and side effects on human bodies and low cost, is suitable for large-scale promotion, and can greatly reduce harm of glucocorticoid and cytotoxic drugs to mesangial proliferative glomerulonephritis patients.
In a second aspect, the invention provides a medicament comprising the tetracyclic diterpenoid compound or a pharmaceutically acceptable salt thereof.
According to a preferred embodiment of the invention, the medicament further comprises one or more of a pharmaceutically acceptable carrier, excipient, diluent, adjuvant and vehicle.
According to a preferred embodiment of the present invention, the pharmaceutically acceptable salt of the tetracyclic diterpenoid is selected from one or more of hydrochloride, hydrobromide, mesylate, sulfate, fumarate, tartrate, maleate, malate and citrate; preferably one or more of hydrochloride, sulphate, fumarate, tartrate, maleate, malate and citrate.
In the present invention, carriers, excipients, diluents, adjuvants and vehicles are not particularly limited, and pharmaceutically commonly used substances may be used, and will not be described in detail.
The present invention will be described in detail below by way of examples.
Examples 1 to 3
Preparing a 100mM solution by using a DMSO solvent, and then diluting the solution to be 1mM by using a serum-free medium II; rat mesangial cells cultured with 25% fetal bovine serum were allowed to act for 24 hours at the concentrations shown in Table 1.
Comparative example 1
Comparative example 1 rat mesangial cells were treated with an equal amount of phosphate buffer as in example 1.
TABLE 1
Example 1 | Example 2 | Example 3 | Comparative example 1 | |
Oridonin concentration (μ M) | 10 | 15 | 20 | 0 |
Test example 1
And (5) observing cell morphology.
The cells of examples 1-3 began to change in cell morphology 6h after oridonin administration: the cell volume is gradually reduced, the cell is solidified and contracted into a round shape, and the wall-sticking capability is reduced to the growth of the cell after the cell is separated from the wall. The cells of comparative example 1 grew well.
Test example 2
MTT test: the absorbance values of the cells in examples 1-3 and comparative example 1 were measured using the method specified in the EPOCH microplate reader, and the wavelength of the measurement was 570 nm. The experimental data are shown in table 2.
TABLE 2
Example 1 | Example 2 | Example 3 | Comparative example 1 | |
Absorbance value of 570nm | 0.42 | 0.12 | 0.06 | 0.48 |
Table 2 the results show that: compared with comparative example 1, the proliferation rate of the cells is obviously reduced after the oridonin is given to act on rat mesenteric cells in examples 1 to 3.
Comparative example 2
The difference from example 2 is that the same amount of phosphate buffer was used instead of the oridonin-DMSO solution treated rat mesenteric cells.
Comparative example 3
The difference from example 2 is that 15% fetal bovine serum was used to culture and the oridonin-DMSO solution-treated rat mesenteric cells were replaced with an equal amount of phosphate buffer.
Test example 3
Example 2 and comparative examples 2-3 were tested according to the flow cytometry protocol and the effect of the drug on cell cycle and apoptosis was observed. The results are shown in Table 3.
TABLE 3
Example 2 | Comparative example 2 | Comparative example 3 | |
Stage G0/G1 | 64.93%±6.69% | 44.3%±7.8% | 40.23%±7.83% |
Stage G2/M | 9.57%±5.83% | 27.33%±10.52% | 21.02%±8.58% |
The results in Table 3 show that the cells of example 2 were mostly blocked in the G1 phase (40% for comparative example 3G1 cells, 65% for example 2G1 cells, P < 0.05).
Test example 4
The green and red fluorescence of the cells were photographed for example 2 and comparative example 2, respectively, according to the method prescribed by immunofluorescence confocal microscopy. The results of the experiment are shown in FIG. 1.
FIG. 1 shows that only a small amount of cells in comparative example 2 show green fluorescence, while the fluorescence of example 2 is enhanced, and intracellular red fluorescence with obvious late apoptosis can be seen, which indicates that a large amount of apoptotic bodies can be detected by the cells under the action of oridonin.
Test example 5
The cells in example 4 and comparative examples 2 to 3 were examined for the proportion of apoptosis according to the flow cytometry requirements. The results of the experiment are shown in FIG. 2.
As can be seen from the flow cytometry apoptosis results of example 2 of the present invention and comparative examples 2-3 in FIG. 2, the apoptosis rates of comparative examples 2, 3 and 4 were 6.63% + -6.90%, 5.03% + -2.64%, and 62.43% + -4.01, respectively, indicating that the cells of example 4 were apoptotic after 24 hours of treatment with oridonin, while the cells of comparative examples 2 and 3 were almost non-apoptotic.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (10)
1. An application of a tetracyclic diterpenoid compound in preparing a medicament for treating and/or preventing mesangial proliferative glomerulonephritis, wherein the tetracyclic diterpenoid compound has a structure shown in a formula (I):
wherein R is1、R2、R3Each independently selected from one of hydrogen, hydroxyl, halogen, C1-C8 alkyl or C3-C8 cycloalkyl, C1-C8 alkoxy, C1-C8 acyloxy, C1-C8 acyl, amino, C1-C8 alkylamino, C1-C8 amide, C2-C8 alkyl imide, nitro, mercapto, alkylthio, acylthio, phosphoryloxy, sulfonyloxy, sulfinoyloxy, amidino, guanidino, carboxyl, phosphonic acid, sulfonic acid, sulfinic acid and cyano.
2. Use according to claim 1, wherein R1、R2、R3Each independently selected from C1-C3 alkyl, C1-C3 alkoxy, C1-C3 acyloxy, C1-C3 acyl, C1One of alkylamino of C3, amido of C1-C3 or alkyl imido of C2-C3.
3. Use according to claim 1 or 2, wherein R1、R2、R3Each independently selected from R1、R2、R3Each independently selected from C1-C3 alkyl or C1-C3 alkoxy.
4. Use according to claim 1 or 2, wherein R1、R2、R3Each independently selected from methyl, ethyl, methoxy or ethoxy.
5. Use according to claim 1 or 2, wherein R1、R2、R3Each independently selected from hydrogen, hydroxy, halogen or carboxy.
6. Use according to claim 5, wherein the halogen is selected from fluorine or chlorine.
7. Use according to claim 5, wherein R1、R2、R3Are all hydroxyl groups.
8. A medicament comprising the tetracyclic diterpenoid compound or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 7.
9. The medicament of claim 8, further comprising one or more of a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, and vehicle.
10. The medicament according to claim 8 or 9, wherein the pharmaceutically acceptable salts of the tetracyclic diterpenoids are selected from one or more of hydrochloride, hydrobromide, mesylate, sulfate, fumarate, tartrate, maleate, malate and citrate; preferably one or more of hydrochloride, sulphate, fumarate, tartrate, maleate, malate and citrate.
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Citations (2)
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US20150297598A1 (en) * | 2012-11-27 | 2015-10-22 | Beth Israel Deaconess Medical Center, Inc. | Methods for treating renal disease |
JP2018131429A (en) * | 2017-02-14 | 2018-08-23 | 拓己 佐藤 | Use of organic acid as method to enhance effect of nrf2 activator |
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US20150297598A1 (en) * | 2012-11-27 | 2015-10-22 | Beth Israel Deaconess Medical Center, Inc. | Methods for treating renal disease |
JP2018131429A (en) * | 2017-02-14 | 2018-08-23 | 拓己 佐藤 | Use of organic acid as method to enhance effect of nrf2 activator |
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