CN110251543B - Application of heterophylly falsestarwort root extract in preparing natural anti-depression medicine - Google Patents
Application of heterophylly falsestarwort root extract in preparing natural anti-depression medicine Download PDFInfo
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- CN110251543B CN110251543B CN201910688554.8A CN201910688554A CN110251543B CN 110251543 B CN110251543 B CN 110251543B CN 201910688554 A CN201910688554 A CN 201910688554A CN 110251543 B CN110251543 B CN 110251543B
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- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/50—Methods involving additional extraction steps
- A61K2236/55—Liquid-liquid separation; Phase separation
Abstract
An application of a heterophylly falsestarwort root extract in preparing an antidepressant medicament is disclosed, the heterophylly falsestarwort root extract is prepared by crushing stalks of the heterophylly falsestarwort root, soaking and heating the crushed stalk in purified water, sequentially extracting obtained leachate with 95% ethanol and 75% ethanol, then extracting the leachate with petroleum ether, concentrating the extract and drying the concentrated extract. The forced swimming test and tail suspension test of mice show that the athyris variabilis extract has obvious antidepressant effect and good depression treatment effect. Through long-term mouse toxicity test observation, the medicine has no abnormality and good safety, and is expected to be developed into a new natural antidepressant medicine.
Description
Technical Field
The invention relates to a function research of a panax variegatus extract, in particular to an application of the panax variegatus extract in preparing an antidepressant natural medicine.
Background
Depression is a common psychological disorder, with many factors and an undefined etiology. Due to the rapid development of modern economy, the quality of life of people is continuously improved, the pace of life is gradually accelerated, the psychological pressure is continuously increased, the people always keep pressure in the heart, and the people are easy to suffer from depression. The main manifestations of depression are marked and sustained mood depression, and serious thoughts and behaviors of suicide.
There are data showing that depression patients are a population with a high suicide rate, and WHO data show that about 100 million suicide deaths occur each year in the world due to depression. Depression affects physical and mental health, social interaction, occupational abilities and physical activities of people to a great extent, and is mainly manifested by incapability of working, decline in working ability, marital incompatibility, paternity and the like. The depression patients not only cause pain to the patients and families, but also reduce the labor capacity of the patients and cause serious economic loss.
The existing antidepressant synthetic drugs have high price, large side effect and narrow antidepressant spectrum. The traditional Chinese medicine has the advantages of multi-component, multi-target, multi-channel, compound synergistic effect, adverse reaction and small side effect. The history of treating depression by traditional Chinese medicines is long, and researches find that a plurality of traditional Chinese medicines have the effect of resisting depression.
The heterophylly falsestarwort root (Dendropanax proteus (Champ.) Benth.) is a plant of the genus heterophylly of the family Araliaceae, is mainly distributed in places such as Fujian, Jiangxi, Hunan, Guangdong, Guangxi and the like, grows in mountain valley stream side more cloudy and humid dense forest with the altitude of 400-600 m, is characterized in that the leaves are of two or more types, the leaf shape variation is larger, the root and stem of the heterophylly falsestarwort root are used as medicines, and are common folk herbal medicines, and the plant of the genus heterophylly is a closely-related plant of famous and precious traditional Chinese medicines such as ginseng, pseudo-ginseng, acanthopanax and the like. However, there has been little research on the ginseng having the modified leaves.
Disclosure of Invention
The invention aims to provide the application of the panax variegatus extract in preparing the antidepressant natural medicine aiming at the defects of the prior art, and provides a basis for finding out the antidepressant with good effect and less adverse reaction.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows: the application of the panax variegatus extract in preparing antidepressant drugs is characterized in that the panax variegatus extract is a petroleum ether extract obtained by extracting the panax variegatus with ethanol.
The petroleum ether extract obtained after the ethanol extraction of the heterophylly falsestarwort root is obtained by taking stalks of the heterophylly falsestarwort root, crushing, adding purified water, heating, boiling and filtering, extracting the obtained leaching solution by using ethanol with the mass concentration of 90-95 percent, then extracting by using ethanol with the mass concentration of 70-75 percent, heating the extracting solution until the ethanol is volatilized and the ethanol smell is eliminated, extracting by using petroleum ether, concentrating and drying the extracting solution, and obtaining the extract.
Specifically, the petroleum ether extract of the above radix pseudostellariae extracted with ethanol is prepared by: taking and crushing the stems of the physalis pubescens, adding purified water, heating to boil, keeping the boiling for 4.5-6.1 hours, filtering, concentrating the filtrate to 1/3-1/5 of the original volume, cooling to room temperature, extracting for 2 times at 18-23 ℃ by using 90-95% ethanol with the mass concentration of 12-16 hours each time, wherein the ethanol is 1.5-2.5 times of the volume of the concentrated filtrate, extracting for 3 times by using 70-75% ethanol with the mass concentration of 12-16 hours each time, the ethanol is 1.5-2.5 times of the volume of the concentrated filtrate, combining the extracting solutions, heating the extracting solution until all the ethanol is volatilized (no alcohol smell), extracting for 2-3 times by using petroleum ether with the same volume, extracting for 4-6 hours each time, combining the extracting solutions, concentrating and drying the extracting solution to obtain dry extract, storing in a refrigerator at 4 deg.C for use.
The addition amount of the purified water is 3mL of purified water per gram of the metaphylium anisopliae powder.
The petroleum ether extract of the panax variegatus after ethanol extraction can be used as an active ingredient and is prepared into an anti-depression oral traditional Chinese medicine with auxiliary materials acceptable in pharmaceutical production.
The invention has the advantages of preparing the antidepressant medicament by using the petroleum ether extract of a single traditional Chinese medicine, along with multi-component, multi-target, multi-channel and wide antidepressant action spectrum pharmacodynamics, adverse reaction and small side effect.
Detailed Description
Materials and methods used in this experiment
1. Extracting raw materials and experimental animals
Collecting the ginseng with changeable leaves in Yuhua mountain natural area in Feng city of Jiangxi province; animals: ICR male mice, body weight 20-23g, SPF grade, certification number: SCXK (Xiang) 2018-.
2. Reagent and apparatus
Fluoxetine hydrochloride, production batch: i1508018, which is dissolved in distilled water to form a suspension before the experiment; SOP electronic balance: sartorius beijing ltd; natural product extraction device and instrumentation: chengdu Lap Instrument Co., Ltd; purifying the water; a measuring cylinder; conical flasks, etc.
Example 1 preparation of Petroleum Ether extract (hereinafter referred to as "Folius variegates extract") obtained by extracting Folius variegates with ethanol
Taking 5kg of physalis pubescens stems, crushing, adding purified water (the liquid-solid ratio is 3mL:1g), heating to boil, keeping for 5 hours, filtering, concentrating the filtrate to 1/3 of the original volume, cooling to room temperature, slowly adding ethanol with the mass concentration of 95% while stirring at the temperature of 18-23 ℃ for extraction for 2 times, wherein the ethanol is used for 14 hours each time (the ethanol is used for 2 times of the volume of the concentrated filtrate), extracting for 3 times with ethanol with the mass concentration of 70-75% (the ethanol is used for 2 times of the volume of the concentrated filtrate), extracting for 14 hours each time, and combining the extracting solutions; heating the extract until all ethanol volatilizes (no alcohol smell), adding petroleum ether with the same volume, stirring and soaking at room temperature for 5 hours, separating the upper layer petroleum ether extract, repeating for 2 times, combining the extracts, concentrating and drying the extracts to obtain 150g of thick extract which is equivalent to the extract containing 66.6g/kg of crude drug. Storing in a refrigerator at 4 deg.C for use.
Example 2 simulation of efficacy in antidepressant animals
The petroleum ether extract obtained by extracting the panax variegatus with ethanol is used for carrying out the antidepressant effect experiment of animals.
1. Forced swimming preliminary experiment of mice
Mice were randomly divided into 3 groups, a model group (solvent group, experiment without drug), a fluoxetine hydrochloride group (0.02g/kg), and a high dose treatment group of Leptospermum variegatum extract (8g/kg), 3 per group. The pre-swimming is carried out for 15 minutes before the experiment, and the formal forced swimming pre-experiment is carried out after 24 hours, namely, the mouse is placed in a 2000ml big beaker with the height of 20cm and the diameter of 14cm after the gastric lavage administration for 30 minutes, the water in the beaker is about 10cm, the water temperature is 23 +/-2 ℃, the mouse is forced to swim for 6 minutes, and the accumulation time of the mouse which is forced to swim and does not move within 4 minutes is recorded.
2. Tail suspension experiment of mice
Mice were randomly divided into 3 groups of 3 mice each, a model group (solvent group, experiment without drug), a fluoxetine hydrochloride group (0.02g/kg), and a high dose treatment group of the extract of Leptospira japonica (8 g/kg). After the mice are subjected to intragastric administration for 30 minutes, the tail end of each mouse is attached to a hook (2 cm away from the tail end) of a horizontal iron rod through a transparent adhesive tape, the head of each mouse is about 40cm away from the horizontal ground, in order to prevent mutual interference among the mice in an experiment and influence the result, the two sides of each mouse in suspension are blocked by black baffles, the tail of each test mouse is suspended for 6 minutes, and the cumulative time of the mice in suspension within 4 minutes is recorded.
3. Forced swimming test of mice
44 mice were randomly divided into 4 groups, namely a model group (solvent group, experiment without drug), a fluoxetine hydrochloride group (0.02g/kg), a low dose group (2g/kg) for the treatment of the extract of the heterophylly falsestarwort root, and a high dose group (8g/kg) for the treatment of the extract of the heterophylly falsestarwort root, 11 mice per group. The pre-swimming is carried out for 15 minutes before the experiment, and a formal forced swimming experiment is carried out after 24 hours, namely, after the mouse is subjected to gastric lavage for 30 minutes, the mouse is placed in a 2000ml big beaker with the height of 20cm and the diameter of 14cm, the water temperature of the beaker is about 10cm and 23 +/-2 ℃, the mouse is forced to swim for 6 minutes, and the accumulation time of the immobility of the mouse is tested within 4 minutes after the record.
4. Results and analysis
4.1 forced Pre-swim results in mice
The forced pre-swimming results of the mice are shown in Table 1 below, and it can be seen that the cumulative immobility time of the athroma variabilis extract treatment high dose group (8g/kg) is significantly shorter than that of the model group, and is similar to that of the fluoxetine group. The obtained extract of Leptospermum variegatum has antidepressant effect. In the preliminary experiment process, after the mouse is subjected to intragastric administration, the state is stable, the activity is natural, and no lethargy or limb convulsion toxic reaction or death occurs, which indicates that the petroleum ether extract has mild drug property.
TABLE 1 Pre-test results for forced swimming of mice
4.2 forced swimming test results of mice
The forced swimming test results of the mice with the aphanoplosis variegata extract are shown in the following table 2, and the table 2 shows that after the treatment groups are administrated, the immobility time of the mice with the positive control medicament fluoxetine hydrochloride group is reduced by 24.5s, the immobility time of the mice with the high-dose treatment group with the aphanoplosis variegata extract is reduced by 28.1s, and the drug effect is better than that of the positive control medicament; although the mice treated with the extract of the aegilops tauschii have less decrease of the immobility time than the mice treated with the extract of the aegilops tauschii in the low-dose group, the effect is obviously better than that of the mice treated with the extract of the aegilops tauschii in the model group. Therefore, the result shows that the antidepressant effect of the panax variegatus extract is close to that of the positive control medicament fluoxetine hydrochloride.
TABLE 2 forced swimming test of mice with Leptospermum heterophyllum extract
| Each test group | Dosage (g/kg) | Cumulative motionless time (S) | Dead time reduction (S) |
| Model set | — | 76.9±26.5 | |
| Fluoxetine hydrochloride group | 0.02 | 52.4±3.6** | 24.5 |
| Low dose group of extract of Leptospermum heterophyllum for treatment | 2 | 65.7±3.5* | 11.2 |
| Treatment of high dose group with Leptospermum heterophyllum extract | 8 | 48.8±4.2** | 28.1 |
Note: compared with model control group (. p < 0.05,. p < 0.01).
4.3 Tail suspension test results of mice
The results of the mouse tail suspension test are shown in the following table 3, the time for the mice in the fluoxetine hydrochloride group to suspend the tail is reduced by 31.4s, the time for the mice in the high-dose group to suspend the tail by the athyris variabilis extract disclosed by the invention is reduced by 38.9s, and the effect of the athyris variabilis extract on the low-dose group is better than that of the model group. Shows that: the high-dose group of the panax variegatus extract is remarkably faster than the fluoxetine hydrochloride group in the onset time, and the action effect is similar to or stronger than that of fluoxetine.
TABLE 3 mouse tail suspension test of Leptospermum variegatum extract with fluoxetine
| Each test group | Dosage (g/kg) | Cumulative motionless time (S) | Dead time reduction (S) |
| Model set | — | 84.5±5.5 | |
| Fluoxetine hydrochloride group | 0.02 | 53.1±3.7** | 31.4 |
| Low dose group of extract of Leptospermum heterophyllum for treatment | 2 | 66.5±3.6* | 18.0 |
| Treatment of high dose group with Leptospermum heterophyllum extract | 8 | 45.6±3.1** | 38.9 |
Note: compared with model control group (. p < 0.05,. p < 0.01).
In forced swimming tests and tail suspension tests of mice, the statistical difference with a model group shows that the athyris variabilis extract has obvious antidepressant effect and has good effect of treating depression. In long-term mouse toxicity test observation, no abnormal mouse performance, no abnormal liver and kidney slices and good safety are found, and the panax variegatus extract is expected to be developed into a novel antidepressant natural medicament.
Claims (3)
1. The application of the heterophylly falsestarwort root extract in preparing the antidepressant drug is characterized in that the heterophylly falsestarwort root extract is a petroleum ether extract obtained by extracting heterophylly falsestarwort root by using ethanol, the petroleum ether extract is obtained by taking stalks of the heterophylly falsestarwort root, crushing, adding purified water, heating, boiling and filtering, extracting an obtained leaching solution by using ethanol with the mass concentration of 90-95%, then extracting by using ethanol with the mass content of 70-75%, heating an extracting solution until the ethanol is volatilized and has no alcohol smell, extracting by using petroleum ether, concentrating and drying an extracting solution.
2. The use of claim 1, wherein the petroleum ether extract of the ethanol-extracted aegilops tauschii is obtained by taking stems of the aegilops tauschii, crushing, adding purified water, heating to boil, keeping for 4.5-6.1 hours, filtering, concentrating the filtrate 2/3-4/5, cooling to room temperature, extracting with 90-95% ethanol for 2 times at 18-23 ℃ for 12-16 hours each time, the amount of ethanol being 1.5-2.5 times of the volume of the concentrated filtrate, extracting with 70-75% ethanol for 3 times at 12-16 hours each time, the amount of ethanol being 1.5-2.5 times of the volume of the concentrated filtrate, combining the extracts, heating the extract to no ethanol taste, extracting with petroleum ether of the same volume for 2-3 times, 4-6 hours each time, mixing extractive solutions, concentrating, and drying.
3. The use of claim 1, wherein the purified water is added in an amount of 3mL per gram of the powder of the ginseng shigella sativa.
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| Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats;Amira M. Abo-youssef;《Beni-Suef University Journal of Basic and Applied Sciences》;20160615;第187-192页 * |
| 变叶树参根醋酸乙酯部位化学成分研究;李陆军等;《现代药物与临床》;20130330;第28卷(第02期);第144-146页 * |
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