CN107488204A - Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives - Google Patents
Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives Download PDFInfo
- Publication number
- CN107488204A CN107488204A CN201710708593.0A CN201710708593A CN107488204A CN 107488204 A CN107488204 A CN 107488204A CN 201710708593 A CN201710708593 A CN 201710708593A CN 107488204 A CN107488204 A CN 107488204A
- Authority
- CN
- China
- Prior art keywords
- glucopyranosyls
- hydroxyl
- configurations
- ocotillol
- work
- 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
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
Abstract
The invention belongs to tetracyclic triterpenoid and its applied technical field, more particularly to a kind of dammarane type ginsenoside (member) and its ocotillol type derivatives, or the purposes of their pharmaceutically acceptable salts, hydrate and solvate in terms of anti-inflammatory.Through In vitro cell experiment, such compound has good anti-inflammatory activity, therefore can be used for preparing anti-inflammatory drug.
Description
Technical field
The invention belongs to tetracyclic triterpenoid and its applied technical field, and in particular to a kind of dammarane type ginseng soap
The antiphlogistic use of glycosides (member) and its ocotillol type derivatives, or their pharmaceutically acceptable salts, hydrate and solvent close
Purposes of the thing in terms of anti-inflammatory
Background technology
The pathogenesis of many chronic diseases is directed to inflammation, such as rheumatoid arthritis, cancer, therefore suppresses anticusp
The generation of disease molecule turns into prevention or treats the important target spot of various diseases.Nitric oxide (NO) is that a kind of important inflammation is situated between
Matter, it is to be prevalent in the cell messenger factor as in macrophage, myocyte, the medium various kinds of cell of endothelial cell, and energy
Enough influence many physiology or pathologic process.NO has both sides effect in inflammatory process, first, endogenic NO is to inflammation
Disease reaction is inhibited；Second, in the inflammation later stage, iNOS, which can be induced, produces a large amount of NO, and the cytotoxicity pair of NO mediations
Inflammation has facilitation.
The inflammation treatment thing used at present is mostly synthetic drug such as brufen, antihistaminic, steroids, but these medicines
Only temporarily alleviate inflammation and with the side effect such as hypersensitivity and immune system degeneration.Now traditional synthesis class resists
Scorching medicine has been difficult to satisfy social needs, and natural drug turns into the focus of the world of medicine's concern.Ginseng is used in existing over thousands of year in China
Medicine history, there is multi-efficiencies such as " intelligence development, calming the nerves, anti-aging ", ginsenoside is its main active substances, according to the knot of sapogenin
Structure is different, can be divided into dammarane type saponin(e, ocotillol types saponin(e and oleanane glycoside.Research finds that ginsenoside has
There are antagonism morphine, prevention senile dementia, protection cardiovascular and cerebrovascular and other effects.
The content of the invention
It is an object of the present invention to provide a kind of dammarane type ginsenoside (member) and its ocotillol types derivative or
Person their pharmaceutically acceptable salts, the purposes of hydrate and solvate in terms of anti-inflammatory.
The purpose of the present invention is realized by following technical scheme：
In a first aspect, the present invention relates to the antiphlogistic use of a kind of dammarane type ginsenoside (member), the knot of the compound
Structure is as shown in logical formula (I)：
Compound shown in logical formula (I) is as shown in table 1：
Table 1, compound 1-5
Second aspect, the antiphlogistic use of the ocotillol type derivatives of above-mentioned dammarane type ginsenoside (member), describedization
The structure of compound such as formula (IIa) and (IIb) are shown：
Compound shown in formula (IIa) is as shown in table 2：
Table 2, compound 6-17
Compound shown in formula (IIb) is as shown in table 3：
Table 3, compound 18-27
Also, such ocotillol type derivative has anti-inflammatory activity.
The third aspect, above-claimed cpd, i.e., dammarane type ginsenoside (member) and its ocotillol types derivative or it
The application of pharmaceutically acceptable salt, hydrate and solvate in anti-inflammatory drug is prepared.We survey with Griess methods
A kind of dammarane type ginsenoside (member) and its ocotillol types derivative have been tried to LPS inducing mouse macrophages RAW
The inhibitory action of 264.7 release inflammatory mediator nitric oxides (NO).As a result show, such dammarane type ginsenoside (member) and its
Ocotillol type derivatives have the function that good anti-inflammatory, and therefore, above-claimed cpd is used to prepare the use in anti-inflammatory drug
On the way.
Embodiment
Below in conjunction with specific embodiment, the invention will be further described.It should be understood that following examples are merely to illustrate this
Invention is not for restriction the scope of the present invention.
The experimental method of unreceipted actual conditions in the following example, generally according to normal condition, or the bar that manufacturer provides
Part is carried out.
Embodiment：The anti-inflammatory activity of dammarane type ginsenoside (member) and its ocotillol type derivatives is screened.
1 material
Tetracyclic triterpenes ginsenoside：Reference literature method (Ma Shuangang, Jiang Yongtao, Song Shaojiang, wait Acta Pharmaceutica Sinicas, and 40
(2005)924-930；Dan Shujun, Cong Dengli, Song Changchun, wait Chinese Pharmaceutical Journals, 35 (2000):82-84；Monarch's Wu Yan ginsengs
Composition Study [D] the Changchun of saponin(e-Re alkaline degradation products:Jilin University；2008.；The bright protopanaxatriols type secondary people of Zang Hui
Join preparation method research [D] the Changchun of saponin(e and sapogenin:Jilin University；2016.；Stem and leaves of American ginseng glycol group soaps are won in will
Composition Study [D] the Changchun of thuja acid catabolite:Jilin University；2009.) it is prepared for dammarane type ginsenoside；Reference literature
(Yang J,YuX,Cai XX,etal.Chem.Res.Chin.Univ.,32(2016):35-40) method, it is prepared for such and reaches
The ocotillol type derivatives of agate alkane type ginsenoside.The structure of above compound is through NMR and HRMS spectrum confirmations.
The culture mediums of RPMI 1640, hyclone：Hyclone companies of the U.S..RAW264.7 mouse macrophages：Chinese section
Institute's Shanghai cell bank.Griess reagent As, Griess reagents B：Yantai Sai Ersi Bioisystech Co., Ltd.MTT：Sigma is public
Department.
2 methods：
(1) taken the logarithm the mouse macrophage RAW264.7 in growth period, and 1 × 10 is diluted to RPMI 1640 culture mediums6
Individual/ml concentration, then it is inoculated in 96 orifice plates, 200 μ L/ holes.It is placed in the CO of constant-humidity constant-temperature2One hour in incubator.
(2) medicine and LPS solution to be tested is prepared
Medicine to be measured is dissolved with cell culture level DMSO respectively, the storage stoste that concentration is 50mM is made into, stoste is used
Cell culture level DMSO sesquialters are diluted to 6.25 μ Μ, i.e. administration concentration is 50,25,12.5,6.25 μM.
0.036g LPS are weighed, is added in 90mL Milli-Q water, is produced 0.4mg/mL solution, pipette this solution 10mL simultaneously
30mL Milli-Q water is added, produces 100 μ g/mL LPS solution 40mL, filtration sterilization.
(3) cell is divided into three groups：Blank group, LPS groups, administration group, every group of three parallel multiple holes.Blank group adds cell
Cultivate the μ L/ holes of level DMSO 0.4；LPS groups add DMSO0.4 μ L/ holes and the μ L/ holes of LPS 2 (final concentration of 1 μ g/mL)；Administration group
Per hole, (initial concentration of medicine is respectively that 50 μM of sesquialters are diluted to the μ L of medicine to be measured 0.4 of the addition μ L of LPS 2 and various concentrations
6.25 μ Μ, i.e. administration concentration are 50,25,12.5,6.25 μM).
(4) after cell administration, culture plate is placed in CO224h is cultivated in incubator, 100 μ L cell supernatants are drawn per hole
It is transferred in new ELISA Plate.
(5) take Griess reagent As, each 5mL of Griess reagents B to mix in equal volume, produce Griess reagent working solutions 10mL.
(6) the μ L of Griess reagents working solution 100 are added per hole, are placed in shaking reaction 10min on shaking table.
(7) using the light absorption value under ELIASA measure 540nm.
(8) respectively with the NaNO that concentration is 1,10,20,50 μM2Solution draws concentration-light absorption value standard curve.Then root
According to NaNO2Solution standard curve calculates the cell supernatant Nitrite (NO of RAW 264.72 -) concentration, and calculate drug
The inhibiting rate that thing discharges to NO.
(9) formula is as follows：
NO inhibiting rates (%)=([NO2 -]LPS-[NO2 -]Administration group)/([NO2 -]LPS-[NO2 -]Blank) × 100%
3 results
Extracorporeal anti-inflammatory Activity Results of the compound 1-5 of table 4 to RAW264.7
In table 4, _:Low concentration has cytotoxicity, a:100 μM have cytotoxicity.
It can be seen that compound 1-5 is respectively provided with anti-inflammatory by a kind of dammarane type ginsenoside 1-5 of table 4 anti-inflammatory activity result
Activity, especially compound 2,4,5 have significant anti-inflammatory activity.
Extracorporeal anti-inflammatory activity of the compound 6-27 of table 5 to the cells of RAW 264.7
In table 5, _:Low concentration has cytotoxicity, a:100 μM have cytotoxicity.
It can be seen by the anti-inflammatory activity result of the ocotillol type derivatives 6-27 of a kind of dammarane type ginsenoside in table 5
Go out, compound 6-27, which is respectively provided with anti-inflammatory activity, especially compound 6,7,8,18,19,23, has significant anti-inflammatory activity, and table
Reveal certain stereo disparity.
Claims (6)
1. a kind of dammarane type ginsenoside (member), it is characterised in that the structure of compound is as shown in formula I：
Wherein：
* asymmetric C atoms, R are represented1Selected from hydroxyl, or β-D- glucopyranosyls；R2Selected from hydrogen, either hydroxyl or β-
D- glucopyranosyls；And the dammarane type ginsenoside has anti-inflammatory activity.
2. according to the compound or pharmaceutically acceptable salt thereof described in claims 1, it is characterised in that：Work as R2For hydrogen, R1Selected from hydroxyl,
β-D- glucopyranosyls, then * is R configurations；Work as R1For hydroxyl, R2For β-D- glucopyranosyls, then * is R configurations；Work as R1For
Hydroxyl, R2For hydroxyl, then * is selected from R or S configurations.
3. a kind of dammarane type ginsenoside (member) or its pharmaceutically acceptable salt, hydrate described in claim 2 and
The purposes of solvate, it is characterised in that prepare the purposes of anti-inflammatory drug.
4. a kind of ocotillol type derivatives of dammarane type ginsenoside (member), it is characterised in that the structure of compound is as led to
Shown in Formula II a and IIb：
Wherein：
* asymmetric C atoms, R are represented1And R3Selected from hydroxyl, β-D- glucopyranosyls, β-D- glucopyranosyls-(1 → 2)-
β-D- glucopyranosyls；R2And R4Selected from hydrogen, hydroxyl, β-D- glucopyranosyls, α-L- rhamnopyranosyls-(1 → 2)-β-
D- glucopyranosyls；And the ocotillol types derivative has anti-inflammatory activity.
5. the compound or pharmaceutically acceptable salt thereof according to claim 4, it is characterised in that：Work as R2For hydrogen when, R1Selected from hydroxyl,
β-D- glucopyranosyls, β-D- glucopyranosyls-(1 → 2)-β-D- glucopyranosyls, then * be selected from R configurations or S structures
Type；Work as R1For hydroxyl when, R2Selected from hydroxyl, β-D- glucopyranosyls, α-L- rhamnopyranosyls-(1 → 2)-β-D- pyrans Portugal
Grape glycosyl, then * be selected from R configurations or S configurations；
Work as R4During selected from hydrogen, R3Selected from hydroxyl, β-D- glucopyranosyls, β-D- glucopyranosyls-(1 → 2)-β-D- pyrans
Glucosyl group, then * be selected from R configurations or S configurations；Work as R3For hydroxyl, R4For β-D- glucopyranosyls-(1 → 2)-β-D- pyrans Portugal
During grape glycosyl, then * is selected from S configurations；Work as R3Selected from hydroxyl, R4Selected from hydroxyl, β-D- glucopyranosyls, β-D- glucopyranoses
Base-(1 → 2)-β-D- glucopyranosyls, then * be selected from R configurations or S configurations.
6. the ocotillol types derivative or their pharmacy of a kind of dammarane type ginsenoside (member) described in claim 5
The purposes of upper acceptable salt, hydrate and solvate, it is characterised in that the purposes in anti-inflammatory drug is prepared.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710708593.0A CN107488204A (en) | 2017-08-17 | 2017-08-17 | Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710708593.0A CN107488204A (en) | 2017-08-17 | 2017-08-17 | Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN107488204A true CN107488204A (en) | 2017-12-19 |
Family
ID=60645420
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710708593.0A Pending CN107488204A (en) | 2017-08-17 | 2017-08-17 | Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN107488204A (en) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320575A (en) * | 2018-04-22 | 2019-02-12 | 吉林大学 | Pseudo-ginsenoside 12- ketone-PF11 and extracting method and its medical usage |
| CN109705183A (en) * | 2019-03-02 | 2019-05-03 | 中国科学院昆明植物研究所 | Smelly seven secondary metabolites and its pharmaceutical composition and preparation method and its application |
| CN109776647A (en) * | 2019-02-14 | 2019-05-21 | 烟台大学 | Pyxinol esterification derivative with anti-inflammatory activity and its preparation method and application |
| CN110452278A (en) * | 2019-01-29 | 2019-11-15 | 中国科学院昆明植物研究所 | Smelly seven secondary metabolites and preparation method thereof and its application in pharmacy |
| WO2020036310A1 (en) * | 2018-08-13 | 2020-02-20 | ㈜아모레퍼시픽 | Antioxidant composition comprising novel ginsenoside |
| CN112654631A (en) * | 2018-08-13 | 2021-04-13 | 株式会社爱茉莉太平洋 | Novel ginsenoside and anti-inflammatory composition containing same |
| CN112638929B (en) * | 2018-08-13 | 2023-07-21 | 株式会社爱茉莉太平洋 | Antioxidant composition comprising novel ginsenoside |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1212966A (en) * | 1997-09-26 | 1999-04-07 | 中国人民解放军军事医学科学院放射医学研究所 | Usage of steroi saponin for preventing and curing senile dementia and new steroid saponin |
| KR20150019636A (en) * | 2013-08-14 | 2015-02-25 | 주식회사 엘지생활건강 | Composition for skin cell regeneration, anti-wrinkle, antioxidant, anti-imflamation, and skin whitening |
-
2017
- 2017-08-17 CN CN201710708593.0A patent/CN107488204A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1212966A (en) * | 1997-09-26 | 1999-04-07 | 中国人民解放军军事医学科学院放射医学研究所 | Usage of steroi saponin for preventing and curing senile dementia and new steroid saponin |
| KR20150019636A (en) * | 2013-08-14 | 2015-02-25 | 주식회사 엘지생활건강 | Composition for skin cell regeneration, anti-wrinkle, antioxidant, anti-imflamation, and skin whitening |
Non-Patent Citations (3)
| Title |
|---|
| JIE YANG ET AL: ""Semisynthesis and bioactive evaluation of oxidized products from 20(S)-ginsenoside Rg3, Rh2, protopanaxadiol (PPD) and their 20(R)-epimers as cytotoxic agents"", 《STEROIDS》 * |
| RENZENG SHEN ET AL: ""Synthesis of Ocotillol-Type Ginsenosides"", 《JOURNAL OF ORGANIC CHEMISTRY》 * |
| WOO-YONG CHOI ET AL: ""Anti-inflammatory, antioxidative and matrix metalloproteinase inhibitory properties of 20(R)-ginsenoside Rh2 in cultured macrophages and keratinocytes"", 《JOURNAL OF PHARMACY AND PHARMACOLOGY》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109320575A (en) * | 2018-04-22 | 2019-02-12 | 吉林大学 | Pseudo-ginsenoside 12- ketone-PF11 and extracting method and its medical usage |
| CN109320575B (en) * | 2018-04-22 | 2021-02-12 | 吉林大学 | Pseudo-ginsenoside 12-ketone-PF 11, extraction method and medical application thereof |
| WO2020036310A1 (en) * | 2018-08-13 | 2020-02-20 | ㈜아모레퍼시픽 | Antioxidant composition comprising novel ginsenoside |
| CN112654631A (en) * | 2018-08-13 | 2021-04-13 | 株式会社爱茉莉太平洋 | Novel ginsenoside and anti-inflammatory composition containing same |
| CN112638929B (en) * | 2018-08-13 | 2023-07-21 | 株式会社爱茉莉太平洋 | Antioxidant composition comprising novel ginsenoside |
| CN112654631B (en) * | 2018-08-13 | 2023-09-19 | 株式会社爱茉莉太平洋 | Novel ginsenoside and anti-inflammatory composition containing same |
| CN110452278A (en) * | 2019-01-29 | 2019-11-15 | 中国科学院昆明植物研究所 | Smelly seven secondary metabolites and preparation method thereof and its application in pharmacy |
| CN109776647A (en) * | 2019-02-14 | 2019-05-21 | 烟台大学 | Pyxinol esterification derivative with anti-inflammatory activity and its preparation method and application |
| CN109705183A (en) * | 2019-03-02 | 2019-05-03 | 中国科学院昆明植物研究所 | Smelly seven secondary metabolites and its pharmaceutical composition and preparation method and its application |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN107488204A (en) | Dammarane type ginsenoside（Member）And its antiphlogistic use of ocotillol type derivatives | |
| Devi | Withaferin A: a new radiosensitizer from the Indian medicinal plant Withania somnifera | |
| Chen et al. | Antitumor activity of Annona squamosa seed oil | |
| US7524824B2 (en) | Composition comprising Xanthoceras sorbifolia extracts, compounds isolated from same, methods for preparing same and uses thereof | |
| CN106496171B (en) | Polycyclic polyisocyanate pentenyl phloroglucinol derivatives compound, preparation method and application with anti-tumor activity | |
| Xiao et al. | Ethno-medicinal study of Artemisia ordosica Krasch.(traditional Chinese/Mongolian medicine) extracts for the treatment of allergic rhinitis and nasosinusitis | |
| CN102311475B (en) | New compound separated from Ganoderma lucidum, preparation method thereof and medicinal purpose thereof | |
| Choi et al. | Effects of 4′, 7-dimethoxyflavanone on cell cycle arrest and apoptosis in human breast cancer MCF-7 cells | |
| CN101880306B (en) | Stauntonia brachyanthera Hand-Mazz saponins components as well as preparation method and application thereof | |
| CN105198943B (en) | A kind of entitled tea hill how glycosides A acylated flavonoids glucosides and its preparation method and application | |
| CN102267891B (en) | Novel triterpenoid compound and preparation method thereof | |
| CN114642670B (en) | Application of triptolide derivative in preparing medicament for treating tumor drug resistance and pharmaceutical composition for treating tumor drug resistance | |
| Xie et al. | Anti-proliferative effects of cucurmosin on human hepatoma HepG2 cells | |
| Lee et al. | Saponins from Solanum torvum and S. macaonense with their cytotoxic and anti-allergic effects | |
| CN109705183B (en) | Clerodendrum cyrtonema metabolite, pharmaceutical composition thereof, preparation method and application thereof | |
| CN102702215B (en) | Compound mangostenone F, preparation method and application in preparation of antitumor drugs thereof | |
| CN103908493B (en) | The preparation method and its pharmaceutical applications of a kind of semen strychni total alkaloids | |
| Chen et al. | Co-assemblies based on natural Hemslecin A and β-sitosterol as a new sight for synergistic anti-gastric cancer efficacy in TCM | |
| CN104693121A (en) | Pyrazol compounds with anti-senile dementia activity as well as preparation method and application of pyrazol compounds | |
| KR101021975B1 (en) | A composition for enhancing the radiotherapy of cancer | |
| CN103588782B (en) | Resina garciniae alkyd and preparation method thereof and in application pharmaceutically | |
| Ji et al. | The present research situation of Crinum asiaticum alkaloids active ingredient | |
| Alqahtani et al. | Pancreatic Cancer Management by Pentacyclic Triterpenes | |
| CN103588783B (en) | Table Resina garciniae alkyd and preparation method thereof and in application pharmaceutically | |
| CN104262126A (en) | Preparation method of incanone and application of incanone in preparing anti-leukemia medicament |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20171219 |
|
| RJ01 | Rejection of invention patent application after publication |