CN110237079B - Application of radix stemonae alkaloid analogue - Google Patents
Application of radix stemonae alkaloid analogue Download PDFInfo
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- CN110237079B CN110237079B CN201910583877.0A CN201910583877A CN110237079B CN 110237079 B CN110237079 B CN 110237079B CN 201910583877 A CN201910583877 A CN 201910583877A CN 110237079 B CN110237079 B CN 110237079B
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- 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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Abstract
The invention belongs to the technical field of medicines, and discloses application of an alkaloid analog of radix stemonae. The stemona alkaloid analogue is used for inhibiting the generation of nitric oxide induced by LPS (lipopolysaccharide); the stemona alkaloid analogue is used for preparing a medicine for inhibiting inflammatory reaction induced by endogenous or exogenous substances; the stemona alkaloid analogue is used for preparing a medicament for treating or preventing chronic inflammatory diseases. An antiinflammatory medicine is radix Stemonae alkaloid analog with structural formula
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to application of an alkaloid analog of radix stemonae.
Background
The inflammatory response is a repair mechanism for the body to maintain homeostasis in response to injury and infection. However, the occurrence of inflammation is accompanied by the occurrence of side reactions, and in particular, persistent inflammation progresses to chronic inflammation. The chronic inflammation is related to the occurrence and development of autoimmune diseases, cancer, neurodegenerative diseases, cardiovascular diseases, metabolic diseases and the like. Chinese use of herbal medicines to control inflammation began as early as 4000 years ago. Natural products and their derivatives have become the main source of anti-inflammatory drugs.
The radix Stemonae alkaloid is an alkaloid separated from radix Stemonae, has a unique structure, is a main active component of the traditional Chinese medicine, and has the pharmacological effects of killing insects, resisting bacteria, relieving cough, reducing phlegm, relieving asthma, resisting tumors and the like. The documents report that the radix stemonae-containing traditional Chinese medicine, the radix stemonae extract and the radix stemonae alkaloid have anti-inflammatory activity. The stemona alkaloid has rich structure, is favorable for synthesizing anti-inflammatory drugs with various structures by a medicinal chemical means, finds an anti-inflammatory lead compound with a novel structure and develops the anti-inflammatory drug with a unique action mechanism. However, no stemona alkaloid monomeric compound with anti-inflammatory activity is found at present.
Disclosure of Invention
In view of the above technical problems, the present invention aims to provide an application of stemona alkaloid analogs in the inhibition of inflammatory reactions, and provide an anti-inflammatory agent of stemona alkaloid analogs.
In order to solve the technical problems, the invention adopts the following technical scheme:
application of stemona alkaloid analogue, wherein the structural formula of the stemona alkaloid analogue is shown in the specification
Is applied to the preparation of anti-inflammatory drugs.
Further, the stemona alkaloid analogue is used for inhibiting the generation of nitric oxide induced by LPS (lipopolysaccharide). Experimental studies showed that the stemona alkaloid analogue concentration-dependently inhibited LPS-induced nitric oxide production in RAW246.7 cells.
Further, the sessile stemona alkaloid analogue is subjected to safety evaluation. Experimental research shows that the stemona alkaloid analogue has no toxicity to RAW246.7 cells.
Further, the stemona alkaloid analogue is used for inhibiting inflammatory reaction induced by endogenous or exogenous substances, and the stemona alkaloid analogue is used for preparing a medicament for treating or preventing chronic inflammatory diseases. The inflammatory reaction induced by the endogenous substance refers to an inflammatory reaction caused by inflammatory factors in a body, and the inflammatory reaction induced by the exogenous substance refers to an inflammatory reaction induced by viruses or bacteria.
An antiinflammatory medicine is radix Stemonae alkaloid analog with structural formula
Compared with the prior art, the invention has the following beneficial effects:
the stemona alkaloid analogue is a stemona alkaloid monomeric compound with anti-inflammatory activity. The stemona alkaloid analog is used for preparing the anti-inflammatory drug, and more medication options are provided for preventing and treating chronic inflammatory diseases.
Drawings
FIG. 1 is a diagram illustrating the establishment of an anti-inflammatory activity assay employed in the present invention;
FIG. 2 is an anti-inflammatory activity assay of stemonine analogs of the present invention;
FIG. 3 is a cytotoxicity assay of stemonine analogs of the invention.
Detailed Description
The technical solutions of the present invention will be further described in detail and fully with reference to the accompanying drawings and specific embodiments, 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.
The structural formula of the stemona alkaloid analogue is shown in the specification
The stemona alkaloid analogue is used for inhibiting the generation of nitric oxide induced by LPS (lipopolysaccharide); the stemona alkaloid analogue is used for preparing a medicine for inhibiting inflammatory reaction induced by endogenous or exogenous substances; the stemona alkaloid analogue is used for preparing a medicament for treating or preventing chronic inflammatory diseases. The inflammatory reaction induced by the endogenous substance refers to an inflammatory reaction caused by inflammatory factors in a body, and the inflammatory reaction induced by the exogenous substance refers to an inflammatory reaction induced by viruses or bacteria. The chronic inflammatory diseases include chronic gastritis, chronic enteritis, etc.
An antiinflammatory medicine is radix Stemonae alkaloid analog with structural formula
The application verification analysis of the stemona alkaloid analogue is as follows:
1. the invention relates to the establishment of an analysis system for the anti-inflammatory activity of stemona alkaloid analogue
The rise in nitric oxide in the macrophage RAW246.7 induced by Lipopolysaccharide (LPS) was used to assess the inflammatory response. RAW246.7 cells were cultured in 1640 medium at 37 ℃ with 5% CO2After the confluence degree of the cells reaches 90%, the cells are digested by pancreatin to prepare cell suspension. The cells were seeded at a density of 15000 cells/well in 96-well plates at 100. mu.L/well and cultured for 24 h. mu.L of 1640 medium containing LPS (10, 5, 1, 0.1, 0. mu.g/mL) was added thereto, the culture was continued, and after 24, 36, and 48 hours of culture, 50. mu.L of the supernatant medium was taken and the production of nitric oxide was measured using a Nitric Oxide (NO) detection kit. As shown in FIG. 1, it was demonstrated that the maximum amount of nitric oxide production was induced after LPS treatment of 5. mu.g/mL for 36 hours on RAW246.7 cells.
2. Evaluation of anti-inflammatory Activity of Stemona alkaloid analogs of the invention
The stemona alkaloid analogue and the anti-inflammatory positive compound BAY 11-7082 are respectively dissolved by DMSO to prepare 100mM of stemona alkaloid analogue mother liquor and BAY 11-7082 respectively, and experiments are divided into a stemona alkaloid analogue administration group, a BAY 11-7082 administration group and a blank group. Radix Stemonae alkaloid analogue administration group, adding 100 μ L1640 culture medium containing radix Stemonae alkaloid analogue (final concentration 50, 25, 12.5, 6.25, 3.125, 1.5625, 0 μ M) and LPS (5 μ g/mL); BAY 11-7082 group to which 100. mu.L of 1640 medium containing BAY 11-7082 compound (final concentration 50, 25, 12.5, 6.25, 3.125, 1.5625, 0. mu.M) and LPS (5. mu.g/mL) was added; blank, add 100 μ L1640 medium. And continuously culturing for 36h, and measuring the content of NO. The evaluation results are shown in fig. 2, the stemonine analog concentration-dependently inhibits the LPS-induced production of nitric oxide in RAW246.7 cells, and the inhibition effect is stronger than that of the positive compound BAY 11-7082. The stemona alkaloid has anti-inflammatory activity, and the activity is superior to BAY 11-7082.
3. Cytotoxicity assays
Detecting cytotoxicity by SRB method based on protein content determinationThe number of cells is determined. Cells in logarithmic growth phase, trypsinized, and adjusted to 3-7X 10 cell density with fresh medium4one/mL, 100. mu.L/well in 96-well plates, 5.0% CO at 37.0 ℃2And culturing overnight in an incubator with saturated humidity to allow the cells to adhere to the wall. The experiment is divided into a stemona alkaloid analogue administration group and a BAY 11-7082 administration group. Radix Stemonae alkaloid analogue administration group, adding 100 μ L1640 culture medium containing radix Stemonae alkaloid analogue (final concentration 50, 25, 12.5, 6.25, 3.125, 1.5625, 0 μ M); BAY 11-7082 group was administered, 100. mu.L of 1640 medium containing BAY 11-7082 (final concentration 50, 25, 12.5, 6.25, 3.125, 1.5625, 0. mu.M) was added. The culture was continued for 72h, the cell culture medium was discarded, 100. mu.L of pre-cooled 10% (Wt/Vol) trichloroacetic acid (TCA) was gently added, and the mixture was allowed to stand at 4 ℃ for at least 1 h. The TCA fixative was removed, washed five times with slow flowing water, the remaining water was removed with absorbent paper, 100. mu.L of SRB staining solution was added gently and incubated at room temperature for 15-30 min. The SRB staining solution was removed and unbound dye was removed by five washes with 1% glacial acetic acid solution. Drying at room temperature, adding 100 μ L10 mM Tris (pH 10.0) solution, and detecting OD with microplate reader after the dye is completely dissolved570nm. The results are shown in fig. 3, the stemonine analog does not affect the survival rate of RAW246.7 cells, while the positive compound BAY 11-7082 reduces the survival rate of RAW246.7 cells. The stemona alkaloid analogue has no cytotoxicity and is superior to BAY 11-7082 in safety.
Although the present invention has been described in detail with reference to the foregoing embodiments, it will be apparent to those skilled in the art that various changes in the embodiments and/or modifications of the invention can be made, and equivalents and modifications of some features of the invention can be made without departing from the spirit and scope of the invention.
Claims (4)
1. The application of the stemona alkaloid analogue is characterized in that: the structural formula of the stemona alkaloid analogue is shown in the specification
Is applied to the preparation of anti-inflammatory drugs.
2. The application of the stemona alkaloid analogue as claimed in claim 1, wherein: the stemona alkaloid analogue is used for inhibiting the generation of nitrogen monoxide induced by LPS (lipopolysaccharide).
3. The application of the stemona alkaloid analogue as claimed in claim 1, wherein: the stemona alkaloid analogue is used for inhibiting inflammatory reaction induced by endogenous or exogenous substances.
4. The application of the stemona alkaloid analogue as claimed in claim 1, wherein: the stemona alkaloid analogue is used for preparing a medicament for treating or preventing chronic inflammatory diseases.
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| CN111297871A (en) * | 2020-04-07 | 2020-06-19 | 山西大学 | Application of radix stemonae alkaloid analogue |
| CN113842437A (en) * | 2021-11-02 | 2021-12-28 | 美益添生物医药(武汉)有限公司 | Application of radix stemonae in preparing product for inhibiting intestinal flora proliferation |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1350512A1 (en) * | 2002-04-03 | 2003-10-08 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Combinations of epinastine, belladonna and pseudoephedrine as new pharmaceutical formulations |
| CN105232539A (en) * | 2015-10-16 | 2016-01-13 | 辽宁中医药大学 | Application of two purslane-derived alkaloids to preparation of anti-inflammatory medicines or healthcare products |
| CN108864123A (en) * | 2018-07-11 | 2018-11-23 | 山西大学 | A kind of synthetic method of Stemona alkaloids |
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| US20090181078A1 (en) * | 2006-09-26 | 2009-07-16 | Infectious Disease Research Institute | Vaccine composition containing synthetic adjuvant |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1350512A1 (en) * | 2002-04-03 | 2003-10-08 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Combinations of epinastine, belladonna and pseudoephedrine as new pharmaceutical formulations |
| CN105232539A (en) * | 2015-10-16 | 2016-01-13 | 辽宁中医药大学 | Application of two purslane-derived alkaloids to preparation of anti-inflammatory medicines or healthcare products |
| CN108864123A (en) * | 2018-07-11 | 2018-11-23 | 山西大学 | A kind of synthetic method of Stemona alkaloids |
Non-Patent Citations (2)
| Title |
|---|
| "(±)-Parvistemonine A的全合成";马开庆等;《有机化学》;20190308;参见2095页表1 * |
| "百部抗炎成分筛选";金伶佳等;《中国中医药现代远程教育》;20150731;第13卷(第13期);参见摘要 * |
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