CN109078049A - The antidepression application of benzyl carbinol glycosides substance based on Herba Cistanches - Google Patents
The antidepression application of benzyl carbinol glycosides substance based on Herba Cistanches Download PDFInfo
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- CN109078049A CN109078049A CN201811182856.XA CN201811182856A CN109078049A CN 109078049 A CN109078049 A CN 109078049A CN 201811182856 A CN201811182856 A CN 201811182856A CN 109078049 A CN109078049 A CN 109078049A
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- herba cistanches
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Classifications
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/64—Orobanchaceae (Broom-rape family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Abstract
Benzyl carbinol glycoside extract in cistanche extract or Herba Cistanches is used to prepare the depressed drug for treating male mammal by a kind of antidepression application of the benzyl carbinol glycosides substance based on Herba Cistanches；The cistanche extracts, by the way that Herba Cistanches medicinal material powder is obtained concentrate after liquid reflux is extracted, the most active component isolated through macroporous adsorbent resin column chromatography afterwards.The present invention has preferable antidepressant effect by the active principle prepared using Desert Herba Cistanches and Cistanche tubulosa through certain extraction separation method, can be applied to prepare and develop antidepression preparation.
Description
Technical field
The present invention relates to a kind of technology of biomedicine field, specifically a kind of benzyl carbinol glycoside based on Herba Cistanches
The antidepression application of substance.
Background technique
The reason of modern pathological research shows since the pathogenesis of depression is complex, induction have it is very much, for
The drug of certain single link is often difficult to obtain satisfactory effect.Currently, the synthesis class drug for treating depression is mainly single
Amine oxidase inhibitor, tricyclic antidepressant and serotonin reuptake inhibitor.Although synthesis class antidepressants have
Certain effect, but the drawbacks such as its generally existing antidepression spectrum is narrow, drug resistance, toxic side effect are big.For example, the depression of about 12-15%
Disease patient state of an illness after taking the antidepressant based on " monoamine neurotransmitter hypothesis " design is not improved, and is generated such as
Many toxic side effects such as gastrointestinal reaction, sex dysfunction, headache, insomnia and fash.Therefore, domestic and international researcher is in antidepression
In terms of the exploitation of medicine, the development and application of more safe and efficient and Small side effects natural drugs is increasingly paid close attention to.It is reported that
Nearly all antidepressants can cause the adverse reaction of sex dysfunction, and nearly 36% patients with depression is antidepression efficacy-enhancing ingredient
The sex dysfunction risen is considered as a kind of unacceptable adverse reaction, to seriously affect drug compliance.For facing at present
On bed the treatment means of depression and existing drug there are the drawbacks of, development efficacy is good, side effect lesser treatment depression
Chinese medicine or natural drug especially have antidepression curative effect and can improve the drug of sex dysfunction, be of great significance and answer
Use prospect.
After searching and discovering the prior art, Wei Zhenzhen is " Herba Cistanches benzyl carbinol glycosides are to large and small mouse climacteric model
Influence " in observation Herba Cistanches benzyl carbinol glycosides are small to climacteric, influence of rat and perimenopausal depression mouse model, and visit
Therapeutic effect and feature of the Herba Cistanches benzyl carbinol glycosides to perimenopausal syndrome are begged for, but the model that the document uses is excision female
The perimenopausal syndrome depression model of mouse ovarian combination chronic stimulation duplication, limitation is that investigation object is climacteric
Because of the depressed animal model of the female of decrease in estrogen induction.Open source literature there is no to record the suppression of male mammal at present
Medicinal application in terms of strongly fragrant disease.
Summary of the invention
The present invention is complicated for prior art extraction process and is related to the organic reagents such as the acetone that a variety of human bodies can not be eaten,
The antidepression application for proposing a kind of benzyl carbinol glycosides substance based on Herba Cistanches, can be applied to preparation treatment depression drug or
Health care product and preparation process is simple, is not related to toxic hazardous solvent.
The present invention is achieved by the following technical solutions:
The antidepression application for the benzyl carbinol glycosides substance based on Herba Cistanches that the present invention relates to a kind of, i.e., extract cistanche
Benzyl carbinol glycoside extract in object or Herba Cistanches is used to prepare antidepressant, more particularly, to prepares the male lactation for the treatment of
The depressed drug of class animal.
The drug, including but not limited to granule, tablet, capsule, patch or ointment.
The extract, by the way that Herba Cistanches medicinal material powder is obtained concentrate after liquid reflux is extracted, most afterwards through big
The benzyl carbinol glycosides effective kind part that macroporous adsorbent resin column chromatography for separation obtains.
The Herba Cistanches medicinal material powder, including Desert Herba Cistanches and/or Cistanche tubulosa medicinal material powder.
The liquid reflux extraction refers to: by Desert Herba Cistanches and/or Cistanche tubulosa medicinal material powder with 8-16 times of weight
Water or amount of alcohol be greater than 0 and less than or equal to 95% water-ethanol liquid refluxing extraction three times, 1-2 hours each, three layers of gauze mistake
Filter merges medical fluid three times, is condensed into Desert Herba Cistanches and/or Cistanche tubulosa concentrate.
The macroporous adsorbent resin column chromatography refers to: concentrate being separated with macroporous adsorbent resin column chromatography, first uses water
Elution obtains water elution position, then the ethanol for being 40% with content elutes, and each position is concentrated, after freeze-drying, obtains water position
With 40% alcohol elution.
The active component refers to: 40% alcohol elution of Desert Herba Cistanches and/or Cistanche tubulosa, antidepression
Effect is more significant, the drug or the application in terms of health care product which may be directly applied to preparation treatment depression.
Technical effect
Compared with prior art, present invention can apply to prepare the drug for the treatment of depression or health care product and preparation process letter
It is single, it is not related to toxic hazardous solvent.
Detailed description of the invention
Fig. 1 is that each administration group of 2 Herba Cistanches of embodiment influences schematic diagram to Tail suspension test；
In figure: P < 0.001 * P < 0.05, * * P < 0.01, * * *, compared with blank group, n=15, Mean ± SEM；
Fig. 2 is that each administration group of 2 Herba Cistanches of embodiment influences schematic diagram to mouse forced swimming test；
In figure: P < 0.001 * P < 0.05, * * P < 0.01, * * *, compared with blank group, n=15, Mean ± SEM；
Fig. 3 is that each administration group of 2 Herba Cistanches of embodiment influences schematic diagram to mouse spacious field experimental activity total distance
In figure: n=15, Mean ± SEM；
Fig. 4 is that 3 Cistanche tubulosa extract of embodiment is motionless to chronic unpredictable cause depression rat model forced swimming
The influence schematic diagram of time；
In figure: #P < 0.05, compared with model group, n=8, Mean ± SEM；
Fig. 5 is 3 Cistanche tubulosa extract of embodiment to chronic unpredictable cause depression rat model sucrose preference function
Influence schematic diagram；
In figure: P < 0.05 *, compared with blank group；#P < 0.05, compared with model group, n=8, Mean ± SEM；
Fig. 6 is 3 Cistanche tubulosa extract of embodiment to chronic unpredictable cause depression rat model spacious field experimental activity
The influence schematic diagram of total distance；
In figure: P < 0.01 * *, compared with blank group；#P < 0.05, compared with model group, n=8, Mean ± SEM；
Fig. 7 is 3 Cistanche tubulosa extract of embodiment to chronic unpredictable cause depression rat model new environment feed suppression
The influence schematic diagram of time processed；
In figure: P < 0.05 *, compared with blank group；#P < 0.05, compared with model group, n=8, Mean ± SEM；
Fig. 8 is 4 Cistanche tubulosa extract UPLC-Q-TOF-MS total ion current figure of embodiment；
Fig. 9 is the structure of echinacoside, acteoside, different acteoside in 4 Cistanche tubulosa extract of embodiment
Formula and cleavage of mass spectrum fragment.
Specific embodiment
Embodiment 1
The preparation process at Herba Cistanches and its each position is as follows
By Desert Herba Cistanches or Cistanche tubulosa pulverizing medicinal materials, medicinal material powder is obtained；Then by medicinal material powder with 10 times of weight
Three times, 2 hours every time, three layers of filtered through gauze merged medical fluid three times to 70% ethanol refluxing extraction, were concentrated under reduced pressure into concentrate.
Concentrate is separated with macroporous adsorbent resin column chromatography, is first eluted with water, water elution position, then the ethyl alcohol for being 40% with content are obtained
Liquid elution, is concentrated each position, after freeze-drying, obtains water position and 40% alcohol elution.
Embodiment 2
Desert Herba Cistanches and Cistanche tubulosa and its each position are to mouse behavioral despair model antidepression pharmacodynamic study.
Select mouse behavioral despair model (Tail suspension test, mouse forced swimming test) evaluation Desert Herba Cistanches and pipe
Flower herba cistanches alcohol extract and its antidepressant effect at different elution positions.
Experimental animal: male ICR mouse, 135, weight 18g-20g.
Experimental group:
Test 1 group: blank group
Test 2 groups: 15mg/kg Prozac (positive drug)
Test 3 groups: 15mg/kg imipramine (positive drug)
Test 4 groups: 2181mg/kg Desert Herba Cistanches alcohol extract
Test the Desert Herba Cistanches alcohol extract water elution position 5 groups: 1112mg/kg
Test 6 groups: 917mg/kg Desert Herba Cistanches alcohol extract, 40% alcohol elution
Test 7 groups: 1555mg/kg Cistanche tubulosa alcohol extract
Test the Cistanche tubulosa alcohol extract water elution position 8 groups: 456mg/kg
Test 9 groups: 792mg/kg Cistanche tubulosa alcohol extract, 40% alcohol elution
Experimental method: taking healthy male cleaning grade ICR mouse 135, is randomly divided into 9 groups, and every group 15, by Shanghai traffic
University's Experimental Animal Center is responsible for buying from Shanghai Slac Experimental Animal Co., Ltd..Mouse adapts to after a week, by each
Group dosage gastric infusion, blank group stomach-filling physiological saline, 1 time a day, successive administration 7 days.
(1) tail-suspention test
It the 8th day after mouse administration, will be adjacent at the about 1cm of Mouse Tail-tip position with medical proof fabric, the other end is attached to outstanding tail dress
It sets on cross bar, the suspension time is 6min, and mouse adds up the dead time in 4min after statistics.
(2) forced swim test
The 9th day after mouse administration, mouse is put into 23-25 DEG C of water temperature of 5L beaker respectively, prevent mouse hind leg from leaning on
Bottom supports body.Swimming time is 6min, and mouse adds up the dead time in 4min after statistics.
(3) spacious field is tested
The 10th day after mouse administration, mouse is put in spacious field case, activity total distance in every mouse 5min is recorded, center
Regional activity distance.
Experimental result:
Tail suspension test result
As seen from Figure 1, after successive administration 7 days, compared to the blank group, Desert Herba Cistanches alcohol extract group, pipe flower meat desert
Rong's alcohol extract group, Cistanche tubulosa water position group, 40% ethyl alcohol position group of Cistanche tubulosa, imipramine positive controls can
Substantially reduce dead time of the mouse in tail-suspention test.
Mouse forced swimming test result
As seen from Figure 2, after successive administration 7 days, Desert Herba Cistanches alcohol extract group, Desert Herba Cistanches water position group, famine
Unconcerned 40% ethyl alcohol position group of Herba Cistanches, Cistanche tubulosa alcohol extract group, 40% ethyl alcohol position group of Cistanche tubulosa, Prozac are positive
Control group, imipramine positive controls are compared to the blank group compared with can substantially reduce mouse in forced swim test not
The dynamic time.
Mouse spacious field experimental result
As a result as shown in figure 3, after successive administration 7 days, all administration groups compared to the blank group, mouse spacious field experiment in from
Hair activity there are no significant difference, indicates all administration groups and will not influence the autonomic activities ability of mouse.
Conclusion
This experimental study proves, Desert Herba Cistanches alcohol extract, Cistanche tubulosa alcohol extract, 40% ethyl alcohol portion of Cistanche tubulosa
Position can substantially reduce the dead time in mouse tail suspension and forced swim test after successive administration 7 days, show certain
Antidepression ability；Spacious field is experiments have shown that Desert Herba Cistanches alcohol extract, Cistanche tubulosa alcohol extract, 40% second of Cistanche tubulosa simultaneously
Alcohol position will not influence the autonomic activities ability of mouse.
Embodiment 3
Pharmacodynamic study of the Cistanche tubulosa extract part to depression rat model caused by chronic unpredictable stimulation
Depression model caused by the unpredictable stimulation of rat chronic is established, tested using forced swim test, sucrose preference,
The antidepression of 40% alcohol elution of Cistanche tubulosa alcohol extract alcohol extract is evaluated in spacious field experiment, new environment feed Inhibition test
Effect.
Experimental animal: male SD rat, 40, weight 180g-220g.
Experimental group:
Test 1 group: blank group
Test 2 groups: model group
Test 3 groups: 10mg/kg Prozac (positive drug)
Test 4 groups: 400mg/kg Cistanche tubulosa alcohol extract, 40% alcohol elution high dose group
Test 5 groups: 200mg/kg Cistanche tubulosa alcohol extract, 40% alcohol elution low dose group
Experimental method: taking healthy male cleaning grade SD rat 180-220g totally 40, is randomly divided into 5 groups, and every group 8, by
Shanghai Communications University's Experimental Animal Center is responsible for buying from Beijing Vital River Experimental Animals Technology Co., Ltd..Rat adapts to one
Zhou Hou carries out sucrose water drinking-water horizontal checkout by the sucrose water consumption training of 72h.Sucrose water consumption is trained for experiment and starts
When two bottles of identical 1% (v/v) sucrose waters are placed on cage, replacing wherein one bottle of sucrose water afterwards for 24 hours is pure water, then
After taking away another bottle of sucrose water afterwards for 24 hours.After 14h fasting for solids and liquids, single mouse single cage is raised, and one bottle of 75mL water and one bottle are placed on cage
75mL sucrose water carries out sucrose water drinking-water horizontal checkout 1h, rejects unqualified rat, consumes even group-division by sucrose level.It is empty
White group of 4, every cage, is raised under mutually isolated environment with other group rats, as required bio-occlusion and feed and drinking-water,
Any stimulation is not received.Every 4, cage of remaining group, the gastric infusion before stress stimulation 1h.Other than blank group does not give any stimulation,
Other groups receive 9 kinds of stimulations, and every kind of stimulation is used 2-3 times, and homologous stimulus discontinuously occurs, and keeps its unpredictable.
9 kinds of specific stimulations be 20-20KHz white noise 1-2h and stroboscopic illumination stay overnight 12h, fasting for 24 hours, prohibit water for 24 hours, limit
Movable 1-2h and all night illumination 12h, folder tail 1min, wet environment are for 24 hours, forced swimming 5min, 45 ° of inclinations are raised, concussion is rocked
30min.Every kind of stimulation is random to be carried out, and a kind of daily stimulation continues 28 days.During stress stimulation, in addition to fasting for solids and liquids and sugarcane
Outside syrup horizontal checkout, free diet drinking-water.
Evaluation method:
(1) forced swim test: rat carries out forced swimming test in modeling third day, test the previous day, rat is put
Enter diameter 20cm, high 40cm, adapts to 15min in the circular non-opaque resin barrel of depth of water 15cm.It is after 1h is administered, each group is big after for 24 hours
Mouse is put into respectively in above-mentioned forcing device, camera shooting record swimming process.Swimming time is 6min, and rat is accumulative in 4min after statistics
Dead time.
(2) sucrose preference is tested: 1 day after the last administration, carrying out the experiment of sucrose preference.14h fasting for solids and liquids before testing, divides cage
Orphan supports, while giving 2 bottles of water, and 1 bottle is pure water, and 1 bottle is that (volume of every bottle of water is 150mL to 1% sucrose water, gives preceding title
Weight).All water bottles are removed after 1h, are weighed.Calculate sucrose preference experiment index (the sucrose water amount of drinking/sucrose water+normal water drink
With total amount).
(3) spacious field is tested: the 3rd day after the last administration, carrying out spacious field experiment.Rat is put in spacious field case, records every
Activity total distance in rat 5min.
(4) new environment feed inhibits the time: the 5th day after the last administration, carrying out new environment feed and inhibits time experiment.It will be big
It is respectively 50cm that mouse, which is put into length, width and height, and the experimental box of 40cm, 40cm, morse is placed on blank sheet of paper in bottom center.Before experiment
For 24 hours, record rat 5min is interior since the time interval fed into experimental box for fasting.
Experimental result:
Forced swim test result
As seen from Figure 4, after successive administration 3 days, compared with model group, 40% ethyl alcohol position low dosage of Cistanche tubulosa
Group can substantially reduce dead time of the rat in forced swim test, and it is exhausted during forced swimming can to improve rat
Prestige behavior has positive therapeutic effect.
Sucrose preference experimental result
As seen from Figure 5, rat is after undergoing chronic unpredictable stimulation in 28 days, the sucrose preference of model group rats
Index is significantly lower than blank group rat, shows that chronic unpredictable stimulation causes depression rat model to be successfully established.Prozac is made
It is compared for positive drug with model group and is a significant increase the sucrose preference function of rat, further prove chronic unpredictable thorn
Swash the validity for causing depression rat model to judge antidepression pharmacodynamic index.Compared to model group, 40% ethyl alcohol of Cistanche tubulosa
Position high dose group can significantly improve the sucrose preference function of rat, indicate that chronic long gives Cistanche tubulosa 40% ethyl alcohol
Position shows good antidepressant effect.
Spacious field experimental result
As shown in fig. 6, rat is after undergoing chronic unpredictable stimulation in 28 days, and compared to the blank group, model group rats
Activity distance significantly shortens, and shows that depression rat model is successfully established.Prozac is compared significantly as positive drug with model group
The activity total distance for increasing rat further proves that the model judges the validity of antidepression pharmacodynamic index.Compared to mould
Type group, 40% ethyl alcohol position high dose group of Cistanche tubulosa and low dose group, can significantly extend the activity total distance of rat,
Indicate that chronic long gives 40% ethyl alcohol position of Cistanche tubulosa and shows good antidepressant effect.
New environment feed inhibits time experimental result
As seen from Figure 7, rat is after undergoing chronic unpredictable stimulation in 28 days, compared to the blank group, model group
The feed of rat inhibits the time significantly to extend, and shows that depression rat model is successfully established.Prozac is as positive drug, although and mould
Type group inhibits the time compared to feed is reduced, but simultaneously there was no significant difference.Compared to model group, 40% ethyl alcohol portion of Cistanche tubulosa
Position high dose group, the then feed that can significantly shorten new environment inhibit the time, indicate that chronic long gives Cistanche tubulosa 40%
Ethyl alcohol position shows good antidepressant effect.
Conclusion
This experimental study proves that 40% ethyl alcohol position of Cistanche tubulosa can significantly shorten chronic unpredictable stimulation and cause suppression
The forced swimming dead time of strongly fragrant rat model, sucrose preference function is significantly improved, the significant activity extended in spacious field experiment is total
Distance, and the feed for significantly shortening new environment inhibits the time, shows good antidepression ability.
In view of above-mentioned effect experiment as a result, cistanche extract and its benzyl carbinol glycoside active site in the present invention have
There is significant antidepressant activity, therefore cistanche extract and its benzyl carbinol glycoside active site can be used for preparing antidepressant
Or health care product.
Embodiment 4
The present embodiment the following steps are included: by embodiment 3 be made 40% alcohol elution of Cistanche tubulosa alcohol extract into
Row UPLC-Q-TOF-MS analysis, total ion current figure are shown in Fig. 8.Using MassLynx mass spectral analysis software, Cistanche tubulosa alcohol is analyzed
40% alcohol elution compound peaks of extract alcohol extract, and compare standard quality spectrum information, it is thus identified that 3 ingredients are shown in Table 1,
It is echinacoside, acteoside, different acteoside respectively.Its chemical structural formula and cleavage of mass spectrum rule are shown in Fig. 9.
1 Cistanche tubulosa alcohol extract of table, 40% alcohol elution UPLC-Q-TOF-MS information
In conclusion this method is based on mouse behavioral despair model and the unpredictable depression model of rat chronic is imitated
Fruit demonstration illustrates that cistanche extract and benzyl carbinol glycoside active site have and significantly improves male depression rat depression
Symptom.
Above-mentioned specific implementation can by those skilled in the art under the premise of without departing substantially from the principle of the invention and objective with difference
Mode carry out local directed complete set to it, protection scope of the present invention is subject to claims and not by above-mentioned specific implementation institute
Limit, each implementation within its scope is by the constraint of the present invention.
Claims (7)
1. a kind of antidepression application of the benzyl carbinol glycosides substance based on Herba Cistanches, which is characterized in that by cistanche extract
Or the benzyl carbinol glycoside extract in Herba Cistanches is used to prepare the depressed drug for treating male mammal；The Herba Cistanches are extracted
Object, by the way that Herba Cistanches medicinal material powder is obtained concentrate after liquid reflux is extracted, most afterwards through macroporous adsorbent resin column chromatography point
From obtained active component.
2. application according to claim 1, characterized in that the drug, form use granule, tablet, capsule
Agent, patch or ointment.
3. application according to claim 1, characterized in that the Herba Cistanches medicinal material powder refers to: Desert Herba Cistanches and/or
Cistanche tubulosa medicinal material powder.
4. application according to claim 1, characterized in that the described liquid reflux extraction refers to: by Desert Herba Cistanches and/
Or water-ethanol liquid of the Cistanche tubulosa medicinal material powder with the water or amount of alcohol of 8-16 times of weight greater than 0 and less than or equal to 95% flows back
It extracts three times, 1-2 hours each, three layers of filtered through gauze merge medical fluid three times, are condensed into Desert Herba Cistanches and/or pipe flower meat desert
Rong's concentrate.
5. application according to claim 1, characterized in that the macroporous adsorbent resin column chromatography refers to: by concentrate
It is separated with macroporous adsorbent resin column chromatography, is first eluted with water, obtain water elution position, then the ethanol for being 40% with content elutes,
Each position is concentrated, after freeze-drying, obtains water position and 40% alcohol elution.
6. application according to claim 1, characterized in that the active component refers to: Desert Herba Cistanches and/or pipe flower
40% alcohol elution of Herba Cistanches, antidepressant effect is more significant, can be applied to prepare the drug for treating depression.
7. according to application described in any of the above-described claim, characterized in that the cistanche extracts include: Echinacea purpurea
Glycosides, acteoside and different acteoside.
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| CN109106760B (en) * | 2018-09-29 | 2021-03-23 | 辽宁中医药大学 | New use of cistanche phenylethanoid glycosides in improving sleep and application thereof |
| CN109223734B (en) * | 2018-10-17 | 2020-07-28 | 山东省药学科学院 | New application of hydroxytyrosol and derivatives thereof in preparation of anti-depression products |
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