CN103012543A - 3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid with anti-inflammatory action and preparation method of 3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid. - Google Patents
3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid with anti-inflammatory action and preparation method of 3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid. Download PDFInfo
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Abstract
The invention discloses lupane-type triterpene 3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid with an anti-inflammatory action and a preparation method of lupane-type triterpene 3 alpha,11 alpha-dihydroxy-23-formyl-lupin-20(29)-alkene-28-acid. The compound has the good anti-inflammatory action. The preparation method has simple steps; the extraction efficiency is high; a scheme design does not influence a product structure; a separating effect is good; and the product purity is high.
Description
Technical field
The invention belongs to biomedicine field, relate to a kind of lupine alkane type triterpenoid with anti-inflammatory action and preparation method thereof, more specifically, relate to lupine alkane type triterpenoid 3 α with following formula I, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-application of 28-acid in the disease medicament that causes for the preparation of inflammatory mediator.
Formula I
Background technology
HMGB1 is the Chromatin nonhistone protein of a class rich content in the eukaryotic cell nuclear, plays very important regulating and controlling effect as a kind of DBP of examining at aspects such as the structure kernel function of stabilized DNA and genetic transcriptions.But the immunocyte active secretion HMGB1 that is stimulated is to the extracellular, and the apoptotic cell of necrosis, damaged cell and some type also can passive release HMGB1.Extracellular HMGB1 can induce with the inflammation medium mutually as a kind of short inflammatory factor, and this medium inflammatory reaction longer duration occurs late period.Participate in the pathology generating process of the inflammation such as Sepsis, endotoxemia.Because HMGB1 is inflammatory mediator in a kind of late period, its window phase is more much longer than the window phase of the targeted therapies of other cytokine, the operability of anti-inflammatory measure in clinical practice for HMGB1 is stronger, HMGB1 has become important target in present inflammatory and the infectious diseases study on prevention, with country great new drug formulating important solution such as malignant tumour, cardiovascular and cerebrovascular diseases, diabetes, autoimmune disorder, the resistance pathogenic bacterial infection, the major disease of 10 classes such as disease of viral infection (kind) serious harm people ' s health is directly related, and the screening of anti-HMGB1 medicine has great importance.
TNF-α, IL-1 β and HMGB1 can induce mutually, and the inhibition that TNF-α, IL-1 β are secreted can reduce it theoretically to the stimulation of cell, and then suppress the secretion of HMGB1, thereby play good antiphlogistic effects.
Traditional Chinese medicine and natural drug have become the source of original new drug research and development, and the medicine that therefrom searching activity is high, side effect is low or guide's material carry out original new drug research the unrivaled advantage of synthetic drugs.Triterpene and glycoside thereof are most important and the most active secondary metabolic product of research, have good biological activity and pharmacological action, especially show good prospect at anti-inflammatory, immunomodulatory and the aspect such as antitumor.But the systematic study about the anti-HMGB1 activity of lupine alkane type triterpenoid has no other reports except the correlative study of CN 100591334 C Acankoreanogenia As.The anti-inflammatory activity of research lupine alkyl-type triterpenoids, the restraining effect of particularly HMGB 1 being secreted, the original new drug problem that need to solve solving national great innovation, exploitation is used for the treatment of medicine or the prodrug of hepatitis gravis and rheumatosis etc., and tool is of great significance.
In addition, because the concentration that reactive monomer exists is extremely low, how to improve extraction efficiency in natural drug, improving product purity is the technical problem that those skilled in the art need to be resolved hurrily.
Summary of the invention
The object of the present invention is to provide a kind of lupine alkyl-type triterpenoids 3 α with anti-inflammatory action, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid and preparation method thereof.
Compound of the present invention can be used as a kind of application of more effective, safer anti-inflammatory activity composition in the illnesss such as hepatitis gravis, liver failure, rheumatosis, pyemia, endotoxemia, resistance pathogenic bacterial infection, disease of viral infection.
One aspect of the present invention relates to a kind of lupine alkane type triterpenoid with anti-inflammatory action, and it has the chemical structure suc as formula I:
Formula I
The present invention also relates to lupine alkane type triterpenoid 3 α on the other hand, the application of 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid in the disease medicament that preparation treatment inflammatory mediator causes.
Application described above, wherein said inflammatory mediator include but not limited to high mobility group protein-1 (HMGB1), tumor necrosis factor-alpha (TNF-α) or interleukin 1 (IL-1).
Application described above, wherein said disease includes but not limited to pyemia, endotoxemia, liver failure, rheumatosis or hepatitis gravis.
Application described above, wherein said disease include but not limited to ischemic, wound or the burn of noninfectious disease.
Application described above, wherein said disease also comprises other complication, for example hepatogenic encephalopathy, hepatorenal syndrome or hemorrhage.
Application described above, wherein, if necessary, comprise or do not comprise other anti-inflammatory activity component in the described medicine, further, can be used as main activity (mass percent in all activeconstituentss is greater than 50%) composition or unique activeconstituents.
3 α of formula I of the present invention, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid are present in the leaf of studies on plants of Acanthopanax Miq. in Araliaceae, particularly acanthopanax gracilistylus.Can prepare by extracting to separate.For example, the present invention prepares 3 α of formula I by the following method, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid:
The acanthopanax gracilistylus leaf is extracted with flash extracter, and methyl alcohol (perhaps ethanol) is solvent, extracts 1～3 time at 30～80 ℃; Behind the reclaim under reduced pressure alcohol, carry out skimming treatment with the sherwood oil reflux after merging; Extracting solution after the degreasing reclaims methyl alcohol and obtains extract; The extract that obtains with the ethanol gradient elution of 30%-100%, is collected 60%～100% ethanol part through macroporous resin, and Recycled ethanol after merging is dried to dried cream; Dried cream is mixed thoroughly with silica gel, pass through silica gel column chromatography, with chloroform by volume: methyl alcohol: water is 22-28: 1: 0,18-22: 1: 0,9-11: 1: 0,8-10: 1: 0.1 gradient elution, wherein, 18-22: part was used respectively by volume chloroform again in 1: 0: methyl alcohol: water is 18-22: 1: 0,8-12: 1: 0.1 elutriant, carry out the silica gel column chromatography gradient elution, collect 18-22: 1: 0 part, remove solvent, through the ODS reversed phase column chromatography, with 7-9: 2 methyl alcohol: the water mixed solution wash-out obtains formula I compound behind the condensing crystal.
The present invention finds, 3 α of formula I, 11 alpha-dihydroxy-s-cell growth did not have impact substantially when 23-aldehyde radical-lupine-20 (29)-alkene-28-acid was lower than 50 μ mol/L in concentration, do not have a cytotoxicity, in this safe concentration scope, the formula I of different concns all can significantly reduce LPS and stimulate lower RAW264.7 scavenger cell strain TNF-α and the secretion of IL-1 β, HMGB1, and effect is remarkable, and presents dose-dependence.It is suppressed the machine-processed Primary Study of HMGB1 and find, can reduce HMGB1 and discharge, but not affect the HMGB1 total amount, do not change the steady-state level of HMGB1 in RAW 264.7 nucleus.
In the present invention, if without specified otherwise, when there are contradiction in compound title and structural formula, be as the criterion with structural formula
Description of drawings
Fig. 1: EZ4U cell proliferation and cytotoxicity analysis kit measurement formula I cell toxicant result
(each figure post is after different concns formula I intervenes, 460nm detect draw respectively organize OD value mean value (n=3),
*P＜0.05 is vs blank group respectively, shows that drug target has remarkably influenced in this concentration cell growth)
Fig. 2: ELISA detects TNF-alpha levels in the basic supernatant of different concns formula I intervention group RAW 264.7 trainings
(the figure post is after formula I intervenes, the concentration mean value (n=3) that is calculated by typical curve,
*P＜0.05 is vs LPS blank group respectively, shows that drug target has remarkably influenced to suppressing TNF-α secretion)
Fig. 3: ELISA detects the basic supernatant IL-1 β level of different concns formula I intervention group RAW 264.7 trainings
(the figure post is after formula I intervenes 6h, the concentration mean value (n=3) that is calculated by typical curve,
*P＜0.05 is vs LPS blank group respectively, shows that drug target has remarkably influenced to suppressing IL-1 β secretion)
Fig. 4: formula I stimulates the impact of RAW264.7 HMGB1 secretion on LPS
(each data is respectively to organize HMGB1 gray scale and LPS group percentage ratio relatively among the figure,
*P＜0.05vs LPS+, the I-group shows that secretion has remarkably influenced to this concentration on HMGB1)
Fig. 5: RAW 264.7 total protein of cell Western-blotting detect HMGB1
Embodiment
Embodiment 1: preparation lupine alkane type triterpenoid 3 α, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid
With acanthopanax gracilistylus leaf 1000g, extract with flash extracter, methyl alcohol (perhaps ethanol) is solvent, extracts 1～3 time at 30～80 ℃. behind the reclaim under reduced pressure alcohol, carry out skimming treatment with the sherwood oil reflux after merging; Extracting solution after the degreasing reclaims methyl alcohol and obtains extract; The extract that obtains with the ethanol gradient elution of 30%-100%, is collected 60%～100% ethanol part through macroporous resin, and Recycled ethanol after merging is dried to dried cream.Dried cream is mixed thoroughly with silica gel, pass through silica gel column chromatography, with chloroform by volume: methyl alcohol: water is 25: 1: 0,20: 1: 0,10: 1: 0,9: 1: 0.1 gradient elutions, wherein, part was used by volume chloroform again in 20: 1: 0: methyl alcohol: water is 20: 1, (proportionlity is not very clear) carried out the silica gel column chromatography gradient elution in 10: 1, collect 20: 1 parts, remove solvent, through the ODS reversed phase column chromatography, with methyl alcohol: water (8: 2) wash-out, concentrated solution obtains formula I compound after using alcohol crystal, yield 0.13%, and purity HPLC detects more than 99%.
After testing, formula I compound: M.F.:C
30H
46O
5Mp:189～191 ℃.
Table 1 formula I compound
1H-NMR and
13C-NMR data (pyridine-d
5, δ ppm)
Annotate (s: unimodal; Brs: wide unimodal; M: multiplet; *: signal is overlapping, and its peak type and J value be difficult the resolution)
Its spectral data is respectively such as table 1, therefore confirm that its structural formula is suc as formula shown in the I, but called after 3 α, 11 α-dihydroxy-23-oxo-lup-20 (29)-en-28-oic acid (3 α, 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid).
Embodiment 2: the cytotoxicity of drug target
Formula I compound final concentration is to carry out the EZ4U cytotoxicity analysis in 10,20,30,40,50,60,70,80,100, the 120 μ mol/L scopes.Cultured RAW 264.7 cells with trysinization after, add the DMEM contain 10%FCS and be made into 1 * 10
4Individual/the mL single cell suspension, be inoculated in 96 orifice plates about 1000 cells in every hole.5%CO
2Constant incubator is cultivated 8h under 37 ℃ of conditions of saturated humidity, then, changes fresh training base 200 μ L, by gradient concentration drug target is added respectively in 96 orifice plates and (answers the hole, n=3), and set up blank.Behind the 48h, every hole adds substrate solution 20 μ L, continues to hatch 4h, stops cultivating concussion 10mins.Select 460nm wavelength colorimetric, measure each hole absorbance at enzyme-linked immunosorbent assay instrument.
EZ4U cell proliferation and cytotoxicity analysis test kit detect finds when concentration is higher cell to be had certain toxic action, just influential to the growth of RAW 264.7 cells greater than 50 μ M the time, the results are shown in shown in Figure 1.
Embodiment 3: on the impact of RAW 264.7TNF-α
Drug intervention: after having cultivated RAW 264.7 cells, use trysinization, add the DMEM nutrient solution that contains 10%FCS and be made into 4 * 10
6Individual/the mL single cell suspension, be inoculated in 12 orifice plates every hole about 1 * 10
6Individual cell, adherent after, at once change anteserum-less substrate OPTI-MEM I, every hole 1mL according to EZ4U result, selects the formula I compound of different concns to intervene, adding final concentration after one hour is the LPS of 100ng/mL, 5%CO
2Constant incubator is cultivated under 37 ℃ of conditions of saturated humidity, sets up simultaneously blank group, positive controls.
After intervening 6h, adopt the ELISA method to detect TNF-alpha levels in the cell culture fluid, undertaken by mouse TNF-α ELISA test kit operation instructions.In the coated enzyme plate of TNF-alpha monoclonal antibodies, standard orifice adds 100 μ L by the standard solution of test kit dilution, sample well, control punch add respectively after the 50 μ L drug intervention respectively organize cell culture fluid and by the control sample solution of operation instruction dilution and all add 50 μ L standard substance diluents, all the other each holes all add 50 μ L biotinylated Ms TNF-α Biotin Conjugate solution except the spectrum blank well, mixing, shrouding, incubated at room 90mins, wash plate 5 times, except blank well, every hole adds the peppery 0 peroxidase labelling Streptavidin working fluid of 100 μ L, shrouding, incubated at room 30mins washes plate 4 times, add developer 100 μ L/ holes, lucifuge incubated at room 30mins.Add stop buffer 100 μ L/ holes, behind the mixing at once on microplate reader 450nm measure absorbancy, the adding standard substance dilution buffer liquid dilution of excessive concentration, the drawing standard curve is read each samples contg by the typical curve equation.
ELISA detects the basic supernatant of RAW 264.7 trainings and finds that formula I compound can reduce the secretion of TNF-α, and in the experimental concentration scope, is dose dependent.Concrete outcome is seen Fig. 2.
Embodiment 4: on the impact of RAW 264.7IL-1 β
Drug intervention is with embodiment 2.
After compound is intervened 6h, adopt the ELISA method to detect IL-1 β level in the cell culture fluid, undertaken by mouse IL-1 β ELISA test kit operation instructions.In the coated enzyme plate of IL-1 β monoclonal antibody, except the spectrum blank well, all the other each holes all add 50 μ L incubation buffer and 50 μ L standard diluents, standard orifice adds 50 μ L by the standard solution of test kit dilution, sample well, control punch adds respectively the control sample solution of respectively organizing cell culture fluid and diluting by operation instruction after the 50 μ L drug intervention, all the other each holes all add 50 μ L biotinylated Ms IL-1 β Biotin Conjugate solution except the spectrum blank well, pat the panel edges mixing, shrouding is hatched 90mins for 37 ℃, carefully suck solution, wash plate 5 times, except blank well, every hole adds 100 μ L horseradish peroxidase-labeled Streptavidin working fluids, shrouding, incubated at room 30mins washes plate 4 times, adds developer 100 μ L/ holes, it is blue that color becomes, lucifuge incubated at room 30mins.Add stop buffer 100 μ L/ holes, behind the mixing at once on microplate reader 450nm measure absorbancy, the adding standard substance dilution buffer liquid dilution of excessive concentration, the drawing standard curve is read each samples contg by the typical curve equation.
ELISA detects the basic supernatant of RAW 264.7 trainings and finds that formula I compound can reduce the secretion of IL-1 β, reaches 66.7% at 50 μ mol/L inhibiting rates, is dose-dependence in the experimental concentration scope.Concrete outcome is seen Fig. 3.
Embodiment 5: on the impact of RAW 264.7HMGB1 secretion
Drug intervention is with embodiment 2.
Behind the drug intervention 8h, in the Centricon YM-10 ultra-fine filter that absorption cell culture fluid supernatant 400 μ L adding Millipore company produces (prewetting with distilled water), 4 ℃, the centrifugal 10mins of 12000 * g, and then draw 400 μ L and join in this ultra-fine filter, 4 ℃, the centrifugal 15mins of 12000 * g.At last, be inverted ultra-fine filter, the centrifugal 2mins of 1000 * g carefully washes the albumen that concentrates with the PBS of 0.1M ice bath from ultra-fine filter, guarantee that its final volume is 40 μ L, and it is stand-by that the sample after concentrating is put-70 ℃ of preservations.
Draw concentrating sample 25 μ L, the total protein sample 15 μ g that slowly thaw on ice and add water to 25 μ L, add respectively 5 μ L sample-loading buffers.100 ℃ of heating 10mins make protein denaturation.12%SDS-PAGE100V constant voltage electrophoresis 1.5h.After electrophoresis finishes, ordinary method transferring film 1h.After the transferring film, 37 ℃ of sealings of confining liquid 1h; Hatch primary antibodie (rabbit anti-human (mouse) the HMGB1 polyclonal antibody that BD company produces 1: 1000), spend the night for 4 ℃; PBST washing pvdf membrane 10mins * 4 times; Normal temperature two anti-(1: 5000) is hatched 1h, PBST washing 10mins * 4 time; Carry out the specificity band by Ecl Western Blot detection kit explanation at last and show, development, photographic fixing, develop a film.
Behind the scanning egative film, carry out photodensitometry with Quantity One software, observe each medicine to the impact of HMGB1 secretion.
When formula I reaches 50 μ mol/L in concentration, 8.2% the when concentration of HMGB1 only has or not drug intervention in the supernatant, in the scope less than 50 μ mol/L concentration, be dose dependent.Concrete outcome is seen Fig. 4.
Embodiment 6: anti-HMGB1 compound effects Mechanism Study
Drug intervention is with embodiment 2.
Behind the drug intervention 8h, after cold PBS washing 3-4 time, add 100 μ L cell pyrolysis liquid (50mmol/L Tris, 150mmol/L NaCl, 0.1%SDS, 0.02% sodium azide, 1%NonidetP-40, facing the time spent, to add final concentration be 1mmol/L PMSF) put lysing cell 30mins on ice, collecting cell.The peak power impulse ultrasound is pulverized 30s, and 12000g, 4 ℃ of centrifugal 30mins remove cell debris, get supernatant liquor, presses the explanation of BCA test kit and measures protein concentration, and it is stand-by that sample is put-70 ℃ of preservations.
The mensuration of protein concentration is undertaken by BCA protein content detection kit operation instructions.In brief, prepare 96 hole enzyme plates, add standard solution by the test kit requirement, the every hole of sample well adds albumen supernatant liquor and the 16 μ L deionized waters that 4 μ L extract, and each hole adds 200 μ LBCA working fluids, vibration 30s, 37 ℃ of lower placement 30mins, colorimetric estimation under 562nm.Draw typical curve by the standard substance hole, sample contains metering-orifice as reference take 0, draws protein concentration from typical curve.
Draw the total protein sample 15 μ g that slowly thaw on ice and add water to 25 μ L, add respectively 5 μ L sample-loading buffers.100 ℃ of heating 10mins make protein denaturation.12%SDS-PAGE100V constant voltage electrophoresis 1.5h.After electrophoresis finishes, ordinary method transferring film 1h.After the transferring film, 37 ℃ of sealings of confining liquid 1h; Hatch primary antibodie (rabbit anti-human (mouse) the HMGB1 polyclonal antibody that BD company produces 1: 1000), spend the night for 4 ℃; PBST washing pvdf membrane 10mins * 4 times; Normal temperature two anti-(1: 5000) is hatched 1h, PBST washing 10mins * 4 time; Carry out the specificity band by Ecl WesternBlot detection kit explanation at last and show, development, photographic fixing, develop a film.
Behind the aobvious band of pvdf membrane HMGB1, with behind the antibody strip buffer 15mins * 2 times, wash 15mins * 3 time with TBST again, show with the special band of Western-blotting method with confidential reference items β-actin again, then compare with the HMGB1 band, observe whether the HMGB1 protein content changes in the born of the same parents.
HMGB1 content behind the intervention 8h in the total protein does not significantly change, and this formula I compound can reduce HMGB1 and discharge, but does not affect the HMGB1 total amount, does not change the steady-state level of the interior HMGB1 of RAW264.7 nucleus, the results are shown in Figure 5.Its effect is consistent with the effect of the Nicotine of having reported, Acankoreanogenia A etc.
Above embodiment shows and has described ultimate principle of the present invention and principal character and advantage of the present invention.The technician of the industry should understand; the present invention is not restricted to the described embodiments; that describes in above-described embodiment and the specification sheets just illustrates principle of the present invention; rather than limit the scope of the invention by any way; without departing from the scope of the invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope.
Claims (8)
1. formula I compound with anti-inflammatory action:
Formula I.
2. method for preparing the described formula I compound of claim 1, it comprises the steps:
(1) sudden strain of a muscle formula is extracted: the acanthopanax gracilistylus leaf is extracted with flash extracter, and methyl alcohol and/or ethanol are solvent, extract 1～3 time at 30～80 ℃. get medicinal extract after merging behind the reclaim under reduced pressure alcohol;
(2) degreasing: step (1) medicinal extract carries out skimming treatment with sherwood oil;
(3) extract: medicinal extract extracts 1～3 time at 30～80 ℃ with methyl alcohol again after step (2) degreasing, and extracting solution reclaims methyl alcohol and obtains extract; (4) separate: the extract that obtains with the ethanol gradient elution of 30%-100%, is collected 60%～100% ethanol part through macroporous resin, and Recycled ethanol after merging is dried to dried cream; Dried cream is mixed thoroughly with silica gel, pass through silica gel column chromatography, with chloroform by volume: methyl alcohol: water is 22-28: 1: 0,18-22: 1: 0,9-11: 1: 0,8-10: 1: 0.1 gradient elution, wherein, 18-22: part was used by volume chloroform again in 1: 0: methyl alcohol: water is 18-22: 1: 0.1,8-12: 1: 0.3, carry out the silica gel column chromatography gradient elution, collect 18-22: 1: 0 part, remove solvent, through the ODS reversed phase column chromatography, with 7-9: 2 methyl alcohol: the water mixed solution wash-out obtains formula I compound behind the condensing crystal.
3. method according to claim 2, comprising the step to the product recrystallizing and refining, recrystallization solvent is selected from ethanol, methyl alcohol, a kind of in the chloroform or their arbitrary combination.
4. lupine alkane type triterpenoid 3 α of formula I, the application of 11 alpha-dihydroxy-s-23-aldehyde radical-lupine-20 (29)-alkene-28-acid in the disease medicament that preparation treatment inflammatory mediator causes
Formula I.
5. application according to claim 4 is characterized in that described inflammatory mediator includes but not limited to high mobility group protein 1 (HMGB1), tumor necrosis factor-alpha (TNF-α) or interleukin 1 (IL-1).
6. according to claim 4 or 5 described application, wherein said disease is selected from pyemia, endotoxemia, liver failure, rheumatosis or the hepatitis gravis of infectious diseases.
7. according to claim 4 or 5 described application, wherein said disease is selected from ischemic, wound or the burn of noninfectious disease.
8. according to claim 4 or 5 described application, wherein said disease is selected from hepatogenic encephalopathy, hepatorenal syndrome or the hemorrhage of complication class.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109734767A (en) * | 2018-11-04 | 2019-05-10 | 长沙博海生物科技有限公司 | A kind of new lupin alkane type triterpenoid acanthopanax gracilistylus aglycon S and preparation method thereof |
| CN111419852A (en) * | 2020-05-21 | 2020-07-17 | 湖南中医药大学 | Application of 3 α, 11 α -dihydroxy-lupin-20 (29) -alkene-28-acid in preparation of hypoglycemic drugs |
-
2012
- 2012-12-25 CN CN201210566064.9A patent/CN103012543B/en not_active Expired - Fee Related
Non-Patent Citations (2)
| Title |
|---|
| ZOU QIN-PENG ET.AL.: "Lupane-triterpenoids from the methanol extracts of leaves of Acanthopanax gracilistylus W.W. Smith", 《兰州大学学报（自然科学版）》 * |
| 钱士辉 等: "细柱五加枝叶提取物的抗肿瘤和抗血管生成活性", 《中药材》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109734767A (en) * | 2018-11-04 | 2019-05-10 | 长沙博海生物科技有限公司 | A kind of new lupin alkane type triterpenoid acanthopanax gracilistylus aglycon S and preparation method thereof |
| CN111419852A (en) * | 2020-05-21 | 2020-07-17 | 湖南中医药大学 | Application of 3 α, 11 α -dihydroxy-lupin-20 (29) -alkene-28-acid in preparation of hypoglycemic drugs |
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