CN114163373A - Amide alkaloid for treating depression and application thereof - Google Patents
Amide alkaloid for treating depression and application thereof Download PDFInfo
- Publication number
- CN114163373A CN114163373A CN202111462730.XA CN202111462730A CN114163373A CN 114163373 A CN114163373 A CN 114163373A CN 202111462730 A CN202111462730 A CN 202111462730A CN 114163373 A CN114163373 A CN 114163373A
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- CN
- China
- Prior art keywords
- acid
- depression
- pharmaceutically acceptable
- acceptable salt
- amide alkaloid
- Prior art date
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- -1 Amide alkaloid Chemical class 0.000 title claims abstract description 22
- 229930013930 alkaloid Natural products 0.000 title claims abstract description 18
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- 230000001430 anti-depressive effect Effects 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 15
- 229940005513 antidepressants Drugs 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/36—Oxygen or sulfur atoms
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to an amide alkaloid for treating depression and application thereof. The invention separates compounds from petroleum ether extraction parts of ethanol extract of piper sarmentosum by means of silica gel column chromatography and the like, and identifies and obtains a new compound amide alkaloid, the structure of which is shown as formula I:
Description
Technical Field
The invention relates to the technical field of medicines, in particular to an amide alkaloid with antidepressant activity and application thereof in preparing a medicine for treating depression.
Background
Depression (MDD) is a serious mood disorder, mainly characterized by low mood, anhedonia, anxiety, despair, insomnia, reaction retardation, and is one of the most common mental diseases. The incidence of depression has increased year by year, and it has been reported that the incidence of depression is about 20% worldwide. By 2015, statistically, approximately 3.22 million people worldwide suffer from depression (4.4% of the world's total population), placing a serious burden on patients and society. According to the world health organization predictions, Depression becomes the top disease burden of the global ranking by 2030 (Mata DA, Ramos MA, Bansal N, et al. Presence of Depression and Depression Symptoms environmental Physicians: A Systematic Review and Metal-analysis. the Journal of the American Medical Association,2015,314(22): 2373-. In our country, depression is now the second Disease to rank among the overall Burden of Disease (Yang G, Wang Y, Zeng Y, et al. Rapid health transfer in China, 1990-2010: details from the Global Burden of Disease Study 2010.Lancet,2013, 381(9882): 1987-2015.). Therefore, the prevention and treatment of depression is becoming more and more important as one of the problems that public health needs to be solved in the 21 st century.
Modern medicine considers that depression has a plurality of pathogenic factors and complex pathogenesis, the specific pathogenesis of the depression is still not clear up to now, and various hypotheses exist. Representative theories include the monoamine neurotransmitter hypothesis, the hypothalamic-pituitary-adrenal-axis (HPA) dysfunction hypothesis, the brain-derived neurotrophic factor (BDNF) deficiency hypothesis, the gut-brain axis disorder, the inflammatory cytokine, and the neuroplasticity hypothesis of depression. Most of the current anti-depression drugs used clinically are developed based on these hypotheses, and a monoamine drug system is the mainstream. Drugs based on monoamine neurotransmitters can be broadly classified into: the first generation of antidepressant drugs Tricyclic (TCAs) and monoamine oxidase inhibitors (MAOIs), the second generation of antidepressant drug selective 5-hydroxytryptamine (5-HT) reuptake inhibitors (SSRIs) and 5-HT antagonists and reuptake inhibitors (serotonist and reuptake inhibitors, SARIs), the third generation of antidepressant drug selective 5-NE and norepinephrine (norepinephrine) reuptake inhibitors (selective and norepinephrine reuptake inhibitors, SSRIs), NE and 5-SNSNHT specific antagonists (noradrenaline-antagonists, Nassages), NE and dopamine (dopamine) reuptake inhibitors (NDDA) and receptor agonists (NDD-2), the antidepressant drugs of the first generation of antidepressant drugs Tricyclic (TCAs) and monoamine oxidase inhibitors (MAOIs), the antidepressant drugs of the second generation of antidepressant drugs (selective 5-hydroxytryptake and reuptake inhibitors (SSRIs), the antidepressant drugs of the melanoidin reuptake and melatonin receptor antagonists of the melanoidin receptor (NDDA-receptor antagonist, NDDA-reuptake 2), de Bodinat C, Delagrange P, et al, aggregate, mechanism of action and pharmacological profile in relation to antibiotic permeability properties, British Journal of pharmacy, 2014,171(15): 3604-. In addition, a great deal of clinical and basic research reports in recent years are recorded, and the ketamine is praised as a new hope for developing antidepressant medicaments in the future. Ketamine is a non-selective N-methyl-D-aspartate receptor (NMDAR) Antagonist that produces a rapid and durable antidepressant effect (Zarate CA, Singh JB, Carlson PJ, et al. a random Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major depression. apparatuses of General Psychiatry,2006, 63 (8)). However, because the depression has a multi-factor, multi-link and multi-target pathogenesis, the western medicine with a single action mechanism not only has a difficult satisfactory curative effect, but also has serious toxic and side effects. For example, SSRIs widely used in clinic at present have unsatisfactory Clinical curative effect, the effective rate is less than 50%, 2/3 patients need to change the drug for multiple times to achieve better curative effect (Trivedi MH, Rush AJ, Wisnewski SR, et al, evaluation of outer With Clinical practice for compressing used-Based Care in STAR D: Clinical practice. American Journal of Clinical practice, 2006,163 (28-40)), and have slow onset, large adverse reaction, easy recurrence and high price (Cipriani A, Zhou X, Del GC, et al. Ketamine has the advantages of quick action, but causes mental symptoms such as hallucination and behavior separation of patients, and has addiction (Ketamine is a novel drug, commonly called K powder), so that the Ketamine is limited to be well popularized and used clinically (Baier P, Zigman D, Baier J.on the Safety and Benefits of processed oral Injections of Ketame For suppression. biological Psychiatry,2012, 72(4): e 11-2). Just because of the urgent needs of the current market and the various defects of western medicines, more and more students aim at traditional Chinese medicines and national medicines (zhangjia, handsome, liuhuan, etc. new anti-depression traditional Chinese medicine research and development, journal of traditional Chinese medicine, 2017,42(01): 29-33.). The traditional Chinese medicine has unique advantages in treating depression due to the characteristics of multiple components, multiple targets, multiple effects, less adverse reactions, strong synergistic effect, overall regulation, mild effect and the like. Therefore, the novel high-efficiency low-toxicity antidepressant is developed from the traditional Chinese medicine, and the action mechanism, the involved signal path, protein, gene and the like of the antidepressant are clarified, so that the antidepressant has important significance for preventing and treating the depression.
The HPA axis is an interacting neuroendocrine unit composed of the hypothalamus, pituitary and adrenal gland. A number of studies have shown that the HPA axis plays an important role in the pathophysiology of emotional and cognitive disorders (Bao AM, Swaab DF. the human hypo-thramus in mood disorders: the HPA axis in the center. IBRO Rep.2018,6:45-53.) and that hyperactivity of the HPA axis Is considered to be a major pathogenesis of depression (Juuruna MF, Bocarova M, Agustin B, et al. Atypical depression and non-polymorphic depression: HPA axi a biomarkerA systematic view. J Affect Disord,2018,233: 45-67) and Is also a prominent feature of depressed patients. The hypothalamus in the HPA axis secretes Corticotropin Releasing Hormone (CRH), CRH acts on the pituitary to stimulate the pituitary to secrete Adrenocorticotropin (ACTH), ACTH acts on the adrenal gland to promote the synthesis of cortisol (the rodent is corticosterone, CORT), and CORT is combined with Glucocorticoid Receptor (GR) to regulate the function of the HPA axis through negative feedback (Wang, Liu Rong, Rojie, etc.). The increased CORT content in serum and brain and excessive secretion of CRH in hypothalamus are important features of HPA axial hyperfunction. In a human or an animal in a stress or depression state, the HPA axis function is over-activated to generate a large amount of CORT, the CORT is mainly combined with GR and a Mineralocorticoid Receptor (MR), the balance of the MR/GR plays a key role in the stress response, and the stress injury diseases such as depression and the like are easily caused due to the imbalance of the MR/GR ratio in the stress state. MR contains enzymes that metabolize CORT, which stabilizes CORT concentrations from becoming too high. GR is activated only when CORT is in high concentration, and after combination, the GR acts on the HPA axis through negative feedback of CRH (inhibiting hypothalamic secretion) so as to reduce CORT concentration (high culmination, Jinweidong, research progress of the relation between antidepressant drugs and the function of the HPA axis of depression, medical guidance, 2017,36(06): 659-. Activation of GR also leads to apoptosis of hippocampal neurons, where high concentrations of CORT act simultaneously with GR in a stressed state, inducing their degenerative changes. In this damaged state, the down-regulation of GR number and function leads to a decrease in the negative feedback action of the HPA axis, leading to a failure to alleviate hyperactivity and to the formation of a vicious circle, thus aggravating the symptoms of depression (Sousa N, Cerqueira JJ, Almeida OFX. Corticosidic receptors and neuroplasticity. brain Research Reviews,2008, 57(2): 561) 570.). Antidepressants can alleviate HPA axial hyperfunction to some extent, up-regulate GR levels, enhance CRH gene expression, reduce CORT concentrations, and alleviate mood disorders (Mou Z, Huang Q, Chu SF, et al. anti-expression effects of GINSENOSIDE Rg1via regulation of HPA and HPG axis. biomedicine & Pharmacotherapy,2017,92: 962-. HPA function is also restored to normal when a depression patient or animal is subjected to effective treatment or self-recovery (Raone A, Cassanelli A, Scheggi S, et al. depression-therapy-assistance modifiers, request to chronic stress in an experimental model of depression in neuroscience,2007,146(4): 1734) -1742.). Therefore, the HPA axis has become a hot spot of research in recent years as an important target for depression and anti-depression drugs.
Piper sarmentosum Roxb is a plant in the genus of pepper of the family of Piperaceae, and can be used in medicine, and has the following functions: it can be used for treating malaria, tinea pedis, toothache, and hemorrhoid. The research on the antidepressant effect and the chemical components of the piper sarmentosum is researched at the earlier stage of the subject group, the piper sarmentosum is found to have the antidepressant effect for the first time, the antidepressant effect mechanism of the piper sarmentosum is primarily researched, the antidepressant effect of the piper sarmentosum is found to be related to HPA axis, BDNF, CREB and ERK, the chemical components of the piper sarmentosum are researched, and a new compound piperotine M is obtained by separation:
however, there are no reports of the compound of the present application, piperlotine N, and its antidepressant action.
Disclosure of Invention
The invention aims to provide a novel compound for treating depression and application thereof, aiming at the defects in the prior art.
In a first aspect, the invention provides an amide alkaloid for treating depression, wherein the amide alkaloid has a structure shown in formula I:
in a second aspect, the invention provides pharmaceutically acceptable salts of amide alkaloids of formula I.
As a specific embodiment of the present invention, the pharmaceutically acceptable salt is an organic acid salt or an inorganic acid salt.
As one specific example thereof, the inorganic acid is hydrochloric acid, sulfuric acid, phosphoric acid, diphosphonic acid, hydrobromic acid, or nitric acid; the organic acid is acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, lactic acid, p-toluenesulfonic acid, salicylic acid, oxalic acid, tannic acid, citric acid, trifluoroacetic acid, malic acid or benzene sulfonate.
In a third aspect, the present invention provides a pharmaceutical composition comprising an amide alkaloid of formula I or a pharmaceutically acceptable salt thereof, and a conventional pharmaceutical carrier.
In a fourth aspect, the invention provides an application of the amide alkaloid or the pharmaceutically acceptable salt thereof in preparing an antidepressant drug.
The compound of formula I of the present invention can be obtained by chemical synthesis or extraction from plants, and preferably, is extracted and separated from Piper sarmentosum Roxb.
A compound of formula I or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising the same, may be administered to a patient by a variety of routes of administration, including, but not limited to, oral, transdermal, intramuscular, subcutaneous, and intravenous injections.
When a compound of formula I or a pharmaceutically acceptable salt thereof is formulated, it can be prepared in any dosage form that is effective for the active ingredient to reach the body, including: tablets, sugar-coated tablets, film-coated tablets, enteric-coated tablets, capsules, hard capsules, soft capsules, oral liquids, buccal agents, granules, pills, powders, ointments, pellets, suspensions, powders, solutions, injections, suppositories, ointments, plasters, creams, sprays, drops, patches and the like; oral dosage forms are preferred, such as: capsule, tablet, oral liquid, granule, pill, powder, pellet, and unguent.
In addition to the main active ingredient, the drug formed by the compound of the formula I or the pharmaceutically acceptable salt thereof can also contain a small amount of minor ingredients which do not affect the active ingredient and/or pharmaceutically acceptable carriers, auxiliary materials necessary for various preparations and the like. For example, when the drug is in an oral dosage form, it may contain conventional excipients such as binders, fillers, diluents, tabletting agents, lubricants, disintegrants, coloring agents, flavoring agents and wetting agents, and the tablets may be coated if necessary. Suitable fillers include cellulose, mannitol, lactose and other similar fillers; suitable disintegrants include starch, polyvinylpyrrolidone and starch derivatives, such as sodium starch glycolate; suitable lubricants include, for example, magnesium stearate; suitable pharmaceutically acceptable wetting agents include sodium lauryl sulphate.
The term "pharmaceutically acceptable salt" herein refers to a salt of the compound with a pharmaceutically acceptable inorganic or organic acid, including but not limited to: hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid; such organic acids include, but are not limited to: formic acid, acetic acid, propionic acid, succinic acid, 1, 5-naphthalenedisulfonic acid, sulfinic acid, oxalic acid, tartaric acid, lactic acid, salicylic acid, benzoic acid, valeric acid, diethylacetic acid, malonic acid, succinic acid, fumaric acid, pimelic acid, adipic acid, maleic acid, malic acid, sulfamic acid, phenylpropionic acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinic acid, methanesulfonic acid, p-toluenesulfonic acid, citric acid, and amino acids; by "pharmaceutically acceptable" is meant a material that is suitable for use in humans without undue adverse side effects (such as toxicity, irritation, and allergic response), i.e., at a reasonable benefit/risk ratio.
The invention has the advantages that:
(1) the invention provides a novel amide alkaloid with antidepressant activity shown as a formula I, and widens the range of medicaments for treating depression.
(2) The compound shown in the formula I has a remarkable protection effect on PC12 cells damaged by CORT, and shows that the compound has remarkable antidepressant activity.
(3) The compound shown in the formula I can obviously reduce the immobility time of mice in a forced swimming test of the mice, shows good antidepressant activity, is expected to be used as an active ingredient for preparing the medicament for treating depression, and has wide application prospect.
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are only for illustrating the present invention and are not intended to limit the scope of the present invention. The experimental procedures, in which specific conditions are not noted in the following examples, are generally carried out according to conventional conditions or according to conditions recommended by the manufacturers.
EXAMPLE 1 preparation of piperlotine N
The sarmentosum bunge medicinal material is dried, crushed and sieved (40 meshes). Extracting with 12 times volume of 80% ethanol under reflux for 3 times, each time for 1.5 hr, collecting extractive solution, and drying under reduced pressure to obtain caulis et folium Piperis Hancei extract. Mixing the extract with water to obtain suspension, and extracting with petroleum ether for 5 times. Collecting the extractive solution, concentrating, and drying to obtain petroleum ether fraction of caulis et folium Piperis Hancei extract. Taking a sarmentosum petroleum ether extraction part sample, mixing the sample with 100-200 meshes of silica gel (1: 1-1.5), separating by column chromatography silica gel (200-300 meshes), and performing gradient elution by using a petroleum ether-ethyl acetate system according to the ratio of 20:1, 10:1, 5:1, 2:1 and 1: 1. After checking by TLC, 7 fractions (Frs.1-7) were combined. Wherein Fr.6 is subjected to silica gel column chromatography, mobile phase petroleum ether-ethyl acetate (20:1, 10:1, 5:1, 1:5) system elution is carried out to obtain Fr.6A-Fr.6F, and Fr.6E is subjected to Sephadex LH-20 gel purification (mobile phase is dichloromethane-methanol with 1: 1) to obtain the compound shown in formula I, namely amide alkaloid piperlotine N. Excimer ion peak M/z 262.1080 [ M + H ] of high resolution mass spectrum]+Calculated value of 262.1079, inferred molecular formula of C14H15NO4With 8 unsaturations. Of piperoting N1H and13the C NMR values are given in Table 1.
TABLE 1 of piperlotine N1HNMR and13CNMR nuclear magnetic data
Record in CDCl3,600MHz for 1H,δin ppm,J in Hz.
Example 2: protective effects of pirerlotine N on corticosterone-induced PC12 cell injury
The CCK-8 method is adopted to detect the protective effect of the separated compound on PC12 cell damage induced by high-concentration CORT, so as to detect the antidepressant activity of the piperotine N. PC12 cells in logarithmic growth phase were diluted to 2X 105One cell/mL, 100. mu.L per well in a 96-well plate, 5% CO at 37 ℃2And culturing in an incubator for 24h to ensure that the cells are completely attached to the wall. Then according toThe packets are processed differently: adding DMEM culture solution containing 10% fetal calf serum into the control group without other treatment; CORT injury model group, adding the injury model group containing CORT 5 × 10-4Complete culture medium of mol/L; the administration group is added after diluting the compound stock solution to corresponding concentration by using a culture medium containing 1% fetal calf serum, and the compound stock solution is added after pre-administration for 24h and contains 5 × 10-4And treating for 24 hours by mol/L CORT complete culture medium. And arranging 6 multiple wells in each group, adding 10 mu L of CCK-8 solution into each well after treatment, arranging a blank control, incubating at 37 ℃ for 90min, measuring absorbance A under the wavelength of 450nm of an enzyme labeling instrument, and calculating the cell survival rate. The results are shown in table 2, and finally we found that the compound of piperotine N can significantly increase the cell survival rate (compared with CORT model group, P is less than 0.05), which indicates that the piperotine N has significant protective effect on CORT-induced PC12 cell damage. Thus, piperotine N is likely to be an active compound in piper sarmentosum which exerts antidepressant effects.
Table 2 protective Effect of Compounds on CORT-induced PC12 cell injury
Comparison with corticosterone group:*P＜0.05
example 3: effect of Piperlotine N on immobility time of mice in forced swimming test
A Forced Swim Test (FST) model of a mouse is established to evaluate the antidepressant activity of the piperatin N. 50 male ICR mice were weighed and recorded, and the mice were randomly divided into 5 groups of 10 mice per group by weight. The grouping is as follows: blank control group (given the same volume of distilled water); group of positive drugs (20mg/kg fluoxetine); the low, medium and high dose groups of pirerlotine N (administered with 10,20,40mg/kg of pirerlotine N, respectively). The administration was continued for 7 days by gavage, and 1 hour after the 7 th administration, the mice were placed in a transparent cylindrical container 30cm high and 15cm in diameter and filled with water (water depth 12cm, water temperature 24-26 ℃ C., to ensure that the mice did not touch the bottom of the container), and allowed to swim in water. The testing time is 6min, the first 2min is adaptation time, the swimming behavior and the immobility behavior of the mouse are evaluated in the later 4min time period, and the accumulated time of the immobility behavior of the mouse is recorded. By immobility behavior is meant: the mouse stops struggling in water and is in a floating state, and no other movement behaviors except that the head is kept floating above the water surface and the nostrils are exposed out of the water surface to cause only small limb movements in order to avoid submerging in the water. The results are shown in Table 3.
TABLE 3 Effect of Piperlotine N on immobility time of mice in forced swimming test
Comparison with blank group:*P＜0.05，**P＜0.01
the results show that the piperotine N has certain curative effect on treating the depression. The effective dose is 20 mg/kg.
In summary, the following steps: the amide alkaloid piperlotine N has a remarkable protection effect on PC12 cell injury induced by corticosterone, has an effect of reducing the immobility time of a mouse in a forced swimming test of the mouse, and has a remarkable anti-depression curative effect. Can be used as an active ingredient for preparing the medicine for treating depression, and has wide application prospect.
Finally, it should be pointed out here that: the above is only a part of the preferred embodiments of the present invention, and should not be construed as limiting the scope of the present invention, and the insubstantial modifications and adaptations of the present invention by those skilled in the art based on the above description are intended to be covered by the present invention.
Claims (6)
1. An amide alkaloid for treating depression, wherein the structure of the amide alkaloid is shown as formula I:
2. a pharmaceutically acceptable salt of the amide alkaloid of claim 1.
3. The pharmaceutically acceptable salt according to claim 2, wherein the pharmaceutically acceptable salt is an organic acid salt or an inorganic acid salt.
4. The pharmaceutically acceptable salt according to claim 3, wherein the inorganic acid is hydrochloric acid, sulfuric acid, phosphoric acid, diphosphoric acid, hydrobromic acid, or nitric acid; the organic acid is acetic acid, maleic acid, fumaric acid, tartaric acid, succinic acid, lactic acid, p-toluenesulfonic acid, salicylic acid, oxalic acid, tannic acid, citric acid, trifluoroacetic acid, malic acid or benzene sulfonate.
5. A pharmaceutical composition comprising an amide alkaloid according to claim 1 or a pharmaceutically acceptable salt according to any one of claims 2 to 4, together with a conventional pharmaceutical carrier.
6. Use of an amide alkaloid according to claim 1 or a pharmaceutically acceptable salt according to any one of claims 2 to 4 for the manufacture of an antidepressant.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090093513A1 (en) * | 2007-10-09 | 2009-04-09 | Hamann Mark T | Method to Use Compositions Having Antidepressant Anxiolytic and Other Neurological Activity and Compositions of Matter |
| CN102070597A (en) * | 2010-12-21 | 2011-05-25 | 广西大学 | Amide alkaloid and preparation method thereof |
| US20140121242A1 (en) * | 2011-06-27 | 2014-05-01 | Tasly Pharmaceutical Group Co., Ltd. | Substituted cinnamamide derivative, preparation method and use thereof |
| CN104771451A (en) * | 2015-04-24 | 2015-07-15 | 中国人民解放军第二军医大学 | Traditional Chinese medicine extract with antidepressant effect and application thereof |
| CN105085308A (en) * | 2015-08-07 | 2015-11-25 | 天津中医药大学 | Calamus amide compound as well as preparation method and application of calamus amide compound |
-
2021
- 2021-12-02 CN CN202111462730.XA patent/CN114163373A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090093513A1 (en) * | 2007-10-09 | 2009-04-09 | Hamann Mark T | Method to Use Compositions Having Antidepressant Anxiolytic and Other Neurological Activity and Compositions of Matter |
| CN102070597A (en) * | 2010-12-21 | 2011-05-25 | 广西大学 | Amide alkaloid and preparation method thereof |
| US20140121242A1 (en) * | 2011-06-27 | 2014-05-01 | Tasly Pharmaceutical Group Co., Ltd. | Substituted cinnamamide derivative, preparation method and use thereof |
| CN104771451A (en) * | 2015-04-24 | 2015-07-15 | 中国人民解放军第二军医大学 | Traditional Chinese medicine extract with antidepressant effect and application thereof |
| CN105085308A (en) * | 2015-08-07 | 2015-11-25 | 天津中医药大学 | Calamus amide compound as well as preparation method and application of calamus amide compound |
Non-Patent Citations (7)
| Title |
|---|
| QING LI等: "Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity", 《JOURNAL OF ETHNOPHARMACOLOGY》, vol. 199, pages 9 - 19, XP018527302 * |
| THANAKORN DAMSUD等: "Three new phenylpropanoyl amides from the leaves of Piper sarmentosum and their a-glucosidase inhibitory activities", 《PHYTOCHEMISTRY LETTERS》, vol. 6, no. 3, pages 350 - 354 * |
| 刘方芳: "假蒟的化学成分及抗真菌活性研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 12, pages 057 - 75 * |
| 周斯仪等: "假蒟植物化学成分及其生物活性的研究进展", 《农产品加工》, no. 1, pages 65 - 68 * |
| 李清: "假蒟的抗抑郁作用和化学成分研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》, no. 6, pages 057 - 69 * |
| 李清等: "假蒟化学成分的研究", 《中成药》, vol. 42, no. 7, pages 1799 - 1802 * |
| 董文燊等: "正交试验法优选假蒟中总生物碱的提取工艺", 《实用药物与临床》, vol. 22, no. 7, pages 750 - 753 * |
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