WO2013097665A1 - Saponin derivative and use thereof - Google Patents

Abstract

A saponin derivative, the structure thereof is as represented by formula (I). Animal experimentation proves that the saponin derivative is provided with significant antidepressant pharmacological activity, can be used as an active ingredient to be prepared into a medicament, food, or healthcare product, and, either separately or in conjunction with other substances, can be used for preventing and treating depression.

Description

 Saponin derivatives and uses thereof

 The present invention relates to a saponin derivative, and more particularly to a furane-type saponin derivative, and the use of the derivative in the prevention and treatment of depression.

Dragon

 Zhimu (also known as rabbit oil grass, wearing dragon) is the dry rhizome of Anemarrhena asphodeloides. According to the "Plants", it is bitter and cold, and it has the effect of nourishing yin and reducing fire, moistening and drying the intestines, and benefiting the urine.

The main chemical components of Chinese herbal medicines are saponins, dibenzopyrones, polysaccharides and lignins, such as: timosaponin A- I, A- IK A-III, A-IV, B-I, Β-Π和口 B-III, wherein the structure of timosaponin-Α and A-IV is unknown. And amemarsaponin A2, ie, Marcos saponin-3-0-pD-glucopyranosyl ( 1 → 2 ) -β-D-pyridinium galactoside B (marlogenin-3-0-PD -glucopyranosy ( 1 ^→ 2) -β-D-galactopyranoside B) Degalactose (desgalactotigonin) F-deglucoside (F-gitonin) and smilageninoside. In addition, it contains anemarone A/B/C/D, cis-hinokiresinol, monomethyl-cis-hinokiresinol, oxidized-cis- Phenolic resin phenol (oxy- cis-himokiresinol), 2,6,4'-trihydroxy-4-methoxybenzophenone (2,6,4'-trihydroxy-4-methoxy benzophenone) p-hydroxybenzene P-hydroxyphenyl crotonic acid, pentacosyl vinyl ester β-sitosterol, mangiferin nicotinic acid, nicotinamide (p-hydroxyphenyl crotonic acid) Nicotinamide) and pantothenic acid.

 Anthraquinone saponin- Π has an improved effect on learning and memory impairment caused by cerebral ischemia (Neuroscience letter., 2007, 421, 147-151 timosaponin-ΠΙ mainly inhibits acetylcholinesterase and inhibits the expression of inflammatory factors. It has a mitigating effect on memory loss (Pharmacol. Biochem. Be., 2009, 93, 121-127).

 Many studies have shown that these substances contained in Zhimu have therapeutic effects on various diseases, such as: Total timosaponin can be used to treat myocardial ischemia (CN1682873A), mainly known as timosaponin-ΠΙ and B-II. Ingredients made from ingredients have also been used to treat thrombotic diseases (WO 2011/026259). Anthraquinone saponin-ΠΙ can induce apoptosis in human cervical cancer cells, and has been shown to have colon and rectal cancer effects in both in vivo and in vitro experiments (Cancer Res., 2008, 68, 10229-10237), and has inhibitory blood vessels. A significant effect of endothelial cell proliferation has therapeutic effects in the treatment of diseases such as tumors and rheumatoid arthritis (CN102030812A).

Recent studies have also shown that Zhimu total soap has antidepressant effects in various depression models, which may be related to the enhancement of noradrenergic and serotonergic nervous system (New Chinese Medicine and Clinical Pharmacology, 2007, 18, 29) . It was confirmed by animal experiments that the saponins contained in Zhimu had a certain effect on experimental depression in mice, which could affect the activity of dopamine and monoamine oxidase in the brain of mice, and make the saponins have antidepressant activity (Biol. Pharm. Bull., 2006, 29, 2304-2306). I Jia et al. found that timosaponin B-II has antidepressant activity, and its mechanism may be related to enhancing the effects of 5-HT and DA nervous system in the brain (CN101214253A; Journal of Pharmaceutical Practice, 2010, 28, 283-287) ).

 Chinese medicine believes that depression is often caused by excessive anxiety, and the heart and the spleen are sick. The treatment should be based on tranquillity, nourishing the blood and nourishing yin. Therefore, in most prescriptions for the treatment of depression in Chinese medicine, Zhimu is also a commonly used Chinese herbal medicine. The most commonly used antidepressants in clinical practice include tricyclic and tetracyclic antidepressants, monoamine oxidase inhibitors, selective 5-HT reuptake inhibitors (SSRIs), atypical antidepressants, and lithium salts.

 In recent years, the most widely used SSRI drug, fluoxetine, has many adverse reactions, such as: systemic or local allergies, gastrointestinal dysfunction, etc. (China Modern Applied Pharmacy, 2008, 25, 763-765; China New Drug Journal, 2001, 10, 20; Journal of Practical Medicine, 2004, 20, 318-319). Studies have shown that the use of fluoxetine in young children may increase suicidal tendencies, and there are reports that fluoxetine may cause increased violent tendencies and congenital cardiovascular birth defects.

 Sertraline, a SSRI drug, is an antidepressant brand drug with a large prescription in the United States, but it is easy to cause sinus tachycardia and ST-T changes in China (Chinese Journal of New Drugs and Clinical Medicine, 2002, 21, 711) -713) Adverse reactions, which may cause manic episodes or metastasis to some extent during the treatment of depressive episodes (Forensic Psychiatry, 2004, 31, 104).

 Although venlafaxine and clomipramine are as easy to tolerate, about one-third of the patients will develop nausea, especially in the weeks when the drug is started. Adverse reactions caused by venlafaxine have been found to have malignant syndrome, induced mania, purpura, hallucinations, sudden hallucinations, withdrawal syndrome, 5-HT syndrome, chest tightness, dizziness, hypotension, menopause, and eyes Increased pressure, etc., have a higher rate of conversion in children (Journal of Clinical Psychiatry, 2002, 12, 382).

 According to World Health Organization experts, the total social burden of depression will rise to the top of all disease burdens by 2020, and the active molecules contained in drugs used to treat depression activity are mainly obtained by chemical synthesis. Most of them have problems of toxic side effects, narrow anti-depression spectrum and high price. Only 2% of the patients with depression currently treated in our country have potential harm to families and society. Therefore, it is particularly necessary to develop safe, effective and inexpensive antidepressant innovative drugs.

 Traditional Chinese medicine and natural medicine are one of the important sources of innovative drug research and development. In recent years, international and domestic research and development of natural drugs with antidepressant effects such as St. John's wort have achieved a series of results (Chinese Modern Chinese Medicine, 2009, 11, 6-9; Chinese patent medicine, 2006, 28, 713-716; Guangdong Medicine, 2005, 859-860; Journal of Nanjing University of Traditional Chinese Medicine, 2001, 17, 294-298; Journal of Pharmaceutical Sciences, 2003, 19, 426-428; Journal of Pharmaceutical Practice, 2004, 22, 104-105; Pharm. Biol ., 2006, 44, 503-510). However, no new Chinese medicines for treating depression have been listed, and there are few reports on the relationship between chemical structure and pharmacodynamic mechanisms. Summary of the invention

 SUMMARY OF THE INVENTION An object of the present invention is to provide a saponin derivative which has an antidepressant pharmacological action and can be used as an active ingredient for the preparation of a medicament for the treatment and prevention of depression.

Another object of the present invention is to provide a furane-type saponin derivative having an antidepressant pharmacological action, It can be used as an active ingredient in the preparation of a medicament for the treatment and prevention of depression.

 Still another object of the present invention is to provide a furazan-type saponin derivative obtained from timosaponin Β-ΠΙ or from a medicinal material of the medicinal material, which has an antidepressant pharmacological action.

 A further object of the present invention is to provide a composition for the manufacture of a medicament, a food and a health supplement using the provided saponin derivative as an active ingredient, alone or in combination with other substances, for the prevention and treatment of depression.

 The term "saponin derivative" as used in the present invention means a saponin derivative and a pharmaceutically acceptable salt thereof, such as: but not limited to hydrochloride, sulfate, carbonate, hydrogencarbonate, acetate, Potassium salts, sodium salts, calcium salts, magnesium salts, barium salts, manganese salts, zinc salts, iron salts and quaternary ammonium salts.

 The term "furane-type saponin derivative" as used in the present invention means a furane-type saponin derivative and a pharmaceutically acceptable salt thereof, such as: but not limited to hydrochloride, sulfate, carbonate, hydrogencarbonate Salt, acetate, potassium salt, sodium salt, calcium salt, magnesium salt, barium salt, manganese salt, zinc salt, iron salt and quaternary ammonium salt.

 The term "furane-type saponin derivative obtained from the Chinese medicinal material known as the mother" refers to a compound of the derivative with various inorganic acids, inorganic bases, organic acids or organic bases, including Chinese herbal medicines. In the process of preparing a furazan-type saponin derivative from Zhimu, a furane-type saponin derivative and a direct or indirect precursor compound thereof (such as: timosaponin-oxime) and a preparation system thereof The pharmaceutically acceptable salts of the various reagents used are, for example, hydrochlorides, sulfates, carbonates, bicarbonates, acetates, sodium salts, potassium salts or quaternary ammonium salts.

 The "Chinese herbal medicine known as the mother" refers to various parts of the Anemarrhena asphodeloides, such as roots, stems, pages and fruits, because the most targets can be obtained from the roots of the plant. A saponin derivative, and thus the present invention prefers its dried rhizome. Whether the selection and processing of these medicinal herbs conforms to the processing technology and standards of Chinese medicinal materials shall not limit the present invention.

 The term "depression" as used in the present invention is a mood disorder, which is a syndrome characterized by a significant and persistent low mood. The so-called depression refers to clinical major depression (Chinese Journal of Experimental Traditional Chinese Medicine, 2005, 11, 46; Journal of Pharmaceutical Practice, 2008, 26, 282). Patients with depression are often accompanied by anxiety symptoms, which can aggravate the development of depression (China Clinical Rehabilitation, 2006, 10, 58). The episode of depression is dominated by low mood, which is not commensurate with its situation. It can be from sullen and unhappy to grief and even stupor. In severe cases, psychotic symptoms such as hallucinations and delusions may occur. The anxiety and motility agitation in some cases is significant. The diagnostic criteria are also dominated by low mood, accompanied by at least four of the following: (1) loss of interest, no sense of pleasure; (2) lack of energy or fatigue; (3) psychomotor retardation or agitation;

(4) Self-evaluation is too low, self-blame, or guilty; (5) Lenovo's difficulty or conscious thinking decline; (6) Repeated thoughts of wanting to die or suicidal, self-injury; (7) Sleep disorders, Such as insomnia, early waking, or excessive sleep;

(8) decreased appetite or significant weight loss; and (9) loss of libido. The impaired social function and the pain or adverse consequences for me are serious criteria for the development of the disease. From the point of view of the disease, the patient met the symptom criteria and the severe standard for at least 2 weeks; there may be some schizophrenic symptoms, but it does not meet the diagnosis of schizophrenia. If it meets the symptom criteria of schizophrenia, meet the criteria for depressive episodes at least 2 weeks after the mitotic symptoms are alleviated (Chinese Classification and Diagnostic Criteria for Mental Disorders [M], Jinan: Shandong Science and Technology Press, 2001, 28-35).

The term "anti-depression" as used in the present invention refers to a subject which can treat, improve or cure the symptoms of a patient suffering from depression. In order to improve the patient's condition to return to normal.

 The "Forced Swimming Test (FST)" or "forced swimming animal model of depression" referred to in the present invention means that a laboratory animal (e.g., a mouse) is placed in a confined environment (e.g., in water). ), animals struggled in this environment and tried to escape and could not escape, thus providing an unavoidable oppressive environment. After a period of experimentation, the animals showed a typical "immobility state". In fact, the animals gave up and escaped. Hope, reflecting a series of parameters called "behavior desperate state", recording the desperate state of the animal in the environment. The system uses the camera to record the experimental process and track the image with the corresponding software to reduce the human operation and the data is objective. The animal model of forced swimming is a reliable experimental model for studying the pharmacology of human depression and its pathogenesis, screening and observing antidepressant drugs. Its main feature is the high specificity of drug action. The experiment can be very good. Antidepressants are distinguished from strong anti-anxiety and anti-anxiety drugs, and the effects of most antidepressants are significantly associated with clinical potency (Arch. Int. Pharmacodyn. Ther., 1977, 229, 327-336; Neurosei. Biobehav. Rev., 1995, 19, 377-395).

 The "Tail Suspension Test (TST)" referred to in the present invention is a classic and rapid method for evaluating the efficacy of antidepressants. The principle is to use the mouse to suspend the tail and attempt to escape, but can not escape, thus giving up the struggle and entering the unique state of depression and immobility. During the experiment, the animal is not moved to reflect the depression state, and the antidepressant can significantly shorten its change. status.

 The term "organism", "animal" or "patient" as used in the present invention refers to humans, wild animals and livestock (Livestocks are wild animals that are not artificially domesticated in a natural state. Livestock is a human word for providing food sources) Animals such as: but not limited to dogs, cats, rats, rats, hamsters, pigs, rabbits, cows, buffalo, bulls, sheep, goats, geese, chickens, etc. Treating "patients", "animals" or " The organism "preferres to mammals, especially humans.

 The term "prevention" as used in the present invention refers to various means or measures for preventing the occurrence or development of a disease, including medical, physical or chemical means, to prevent and reduce various diseases before the disease is not recognized by clinical standards. The occurrence or development of symptoms.

 The term "treatment" as used in the present invention means to prevent or reduce the occurrence or development of a disease, and to inhibit, suppress, alleviate, ameliorate, slow down, stop, delay or reverse the progression or aggravation of the disease course. / or various indicators of disease, disorder, or pathology at the time of administration include alleviating or reducing symptoms or complications, or curing or eliminating a disease, disorder, or condition.

 The term "food" as used in the present invention refers to a single compound or composition comprising various saponin derivatives provided by the present invention to be made edible. The production and manufacture of such a single compound or composition should be in accordance with relevant food safety standards, but such food safety standards must not limit the invention.

 The term "health product" as used in the present invention means that a plurality of saponin derivatives provided by the present invention are formulated into an edible single compound or composition for administration to a patient for the purpose of preventing and treating diseases. It belongs to the food of the present invention, but its production, manufacture and sale should also comply with various relevant requirements, standards and specifications.

The term "drug" as used in the present invention means a single compound which can be used for preventing or treating a certain disease, a composition formed of a plurality of compounds, a Chinese medicinal material and an extract thereof, or a composition containing a single compound as a main active ingredient. Or Formulation also refers to a composition or formulation comprising a plurality of compounds as active ingredients. "Drug" should be understood to mean not only the products approved and approved for production by the administrative agencies established by the laws of a country, but also the inclusion of a single compound as the active ingredient in order to obtain approval and approval of production. Various forms of matter. "Formation" is understood to be obtained by means of chemical synthesis, biotransformation or purchase.

 The term "formulation" as used in the present invention means a dosage form containing a drug delivery of an isoflavone compound of the present invention, such as, but not limited to, an aqueous solution injection, a powder injection, a pill, a powder, a tablet, a patch. , suppositories, emulsions, creams, gels, granules, capsules, aerosols, sprays, powders, sustained release agents and controlled release agents. These pharmaceutical excipients may be conventionally used in various preparations, such as, but not limited to, isotonic agents, buffers, flavoring agents, excipients, fillers, binders, disintegrators, lubricants, and the like. Or may be selected for use in accordance with the substance, such as: emulsifiers, solubilizers, bacteriostatic agents, analgesics and antioxidants, etc., such excipients can effectively improve the stability of the compounds contained in the composition And solubility or changing the release rate and absorption rate of the compound, etc., thereby improving the metabolism of the compound of the present invention in the living body, thereby enhancing the administration effect. In addition, excipients such as: sustained release, controlled release, and pulsed administration, such as: but not limited to, gelatin, albumin, chitosan, may also be used for specific purposes or modes of administration. , Polyether and polyester polymer materials, such as: but not limited to, polyethylene glycol, polyurethane, polycarbonate and copolymers thereof. The main manifestations of "good for administration" are: However, it is not limited to improving the therapeutic effect, improving bioavailability, reducing toxic side effects, and improving patient compliance.

The term "effective therapeutic dose" as used in the present invention refers to an amount which can alleviate various pathologically significant symptoms using the compound of the present invention as an active ingredient, and the amount given is generally determined according to the body weight of the living body, such as: 0.05mg/kg-50mg/kg _o According to the actual situation of the organism and its condition, the amount used and the number of times used can also be adjusted, for example, the total amount of 0.05-0.5mg/kg, 0.6_lmg/kg is given twice a day or more. , l_10mg/kg, l l_25mg/kg, 26_40mg/kg or 41_50mg/kg. Depending on the dosage form of the drug, the amount to be given will also vary, such as: 10 mg/kg for regular tablets and lower for slow release formulations. The specific dose of the body saponin derivative of the present invention needs to be determined depending on the specific circumstances, such as the manner of administration, the route of administration, the state of the patient at the time of administration, and the pathological condition at the time of treatment.

The "base compound" referred to in the present invention is a compound obtained by substituting "hydrogen" for all variable substituents of the structural formula of the compound. For example, a compound obtained by simultaneously replacing "hydrogen" with the substituents F, R ₂ and R ₃ in the structure of the following formula I is a basic compound.

 The term "substituent" as used in the present invention refers to a general term for one or more inorganic or organic groups which substitute a hydrogen atom at a specific position on a base compound, and may be an atom, a molecule, an ion, a compound, a polymer or the like.

 The "halogen" referred to in the present invention includes fluorine, chlorine, bromine and iodine, and is applied as a substituent to the base compound in a combination of _F, -Cl, -Br and -I.

The "sulfate group" referred to in the present invention is _OS0 ₃ H, _OS0 ₃ Na, _OS0 ₃ K and _OS0 ₃ NH ₄ .

The "phosphate group" referred to in the present invention is -OPO(HO) ₂ , and a pharmaceutically acceptable salt formed by hydrogen substitution thereon.

The "trifluoroacetate group" referred to in the present invention is _OCOCF ₃ .

The "substituted amino group" referred to in the present invention is an ammonia in which hydrogen on the amino group is partially or completely substituted by a C1-C3 saturated alkane. Base, such as: but not limited to methylamino and dimethylamino.

 The "C1-C3 saturated alkane" referred to in the present invention is a linear or branched alkane having 1-3 carbon atoms. Wherein, the letter C represents a carbon atom, and the subsequent number is a positive integer, such as: 1, 2 or 3, etc., indicating the number of carbon atoms contained in the group, such as: methane, ethane, and propane.

 The term "sugar", also known as "sugar", is a basic organic substance in chemical or biochemistry. It is a polyhydroxy (more than 2) aldehyde, polyhydroxyketone composed of C, H and 0 elements. (greater than 2) and an organic compound capable of hydrolyzing to form a polyhydroxy aldehyde or a polyhydroxy ketone. According to its molecular structure, it can be divided into "monosaccharide", "disaccharide" and "polysaccharide". An organic compound formed by condensation of a plurality of monosaccharide molecules via a glycosidic bond, also known as a "sugar chain." The present invention preferably employs a monosaccharide or a disaccharide as a substituent for the base compound.

 The term "monosaccharide" as used in the present invention refers to an organic compound composed of C, H and 0 elements, and is also a basic unit constituting other saccharide substances, generally a polyhydroxy group having 3 to 6 carbon atoms. An organic substance of an aldehyde or a polyhydroxyketone. Preference is given to polyhydroxy aldehydes or polyhydroxy ketones having 5 or 6 carbon atoms, also known as "pentoses" and "hexoses" such as: but not limited to ribose, xylose, arabinose, glucose, mannose, galactose, Allosterose, fructose, sorbose, tagatose, gulose, idose, tarotose, allose and altrose. In the monosaccharide structure of the present invention, the 0 element may be partially or completely replaced by the S element.

 The term "disaccharide" as used in the present invention means an organic compound composed of C, H and 0 elements, and is generally formed by linking two monosaccharide molecules by condensation and dehydration to form glycosidic bonds. Well known disaccharides such as: sucrose, lactose, cellobiose, trehalose and maltose. Glycosidic bonds formed between monosaccharide molecules such as: but not limited to α-1,1-, α-1,2-, α-1,3-, α-1,4-, β-1,4- and Several glycosidic bond forms such as α-1,6-. In the disaccharide structure of the present invention,

The 0 element can be partially or completely replaced by the S element.

 The term "polysaccharide" as used in the present invention also includes oligosaccharide, which means C,

An organic compound composed of H and 0 elements is generally a linear or branched polymer in which three or more monosaccharide molecules are linked by condensation and dehydration to form glycosidic bonds. Preferred are linear or branched polymers in which 3-15 monosaccharide molecules are linked by glycosidic bonds. Well-known polysaccharides such as: gentiotriose, melezitose, artichrin, mullein, stachyose and raffin Wait. The glycosidic bonds formed between the monosaccharide molecules are as follows: but not limited to several glycosidic bond forms such as α-1,4-, β-1,4- and α-1,6-. In the polysaccharide structure of the present invention, the 0 element may be partially or completely replaced by the S element.

 The "C1-C6 alcohol" referred to in the present invention is a linear or branched saturated or unsaturated hydrocarbon substituted with one or more hydroxy groups. Wherein, the letter C represents a carbon atom, and the subsequent digits are positive integers, such as: 1, 2, 3, 4 or 5, etc., indicating the number of carbon atoms contained in the group, such as: methanol, ethanol, propanol, isopropyl Alcohol and n-butanol.

The present invention provides a saponin derivative, specifically a furane-type saponin derivative, which has the structure shown in Formula I. Wherein, a substituent represented by a group selected from -OH, -SH, halogen and a C1-C3 saturated alkane-substituted amino group; R ₂ represents a substituent selected from -OH, -SH, A halogen, a sulfate group, a phosphate group, a trifluoroacetic acid group, a C1-C3 saturated alkane-substituted amino group, a sugar linked by an 0-glycosidic bond, and a group of a sugar linked by an S-glycosidic bond.

The present invention provides another saponin derivative having the structure shown in Formula I, wherein a substituent is selected from a group selected from the group consisting of -OH, -SH, halogen and a C1-C3 saturated alkane substituted amino group. R ₂ represents a substituent selected from -0H, -SH, halogen, sulfate group, phosphate group, trifluoroacetic acid group, C1-C3 saturated alkane-substituted amino group, single unit linked by 0-glycosidic bond A group of sugars and monosaccharides linked by S-glycosidic bonds.

The present invention provides another saponin derivative having the structure shown in formula I, wherein a substituent is selected from -OH or -SH; and R ₂ represents a substituent selected from -OH and _SH. a halogen, a sulfate group, a phosphate group, a trifluoroacetic acid group, a C1-C3 saturated alkane-substituted amino group, a monosaccharide linked by an O-glycosidic bond, and a group of a monosaccharide linked by an S-glycosidic bond.

The present invention provides another saponin derivative having the structure shown in formula II, wherein R ₂ represents a substituent selected from the group consisting of -OH, -SH, halogen, sulfate group, phosphate group, trifluoroacetic acid A group substituted with a C1-C3 saturated alkane, a group of a monosaccharide through a 0-glycosidic bond.

 The present invention provides a saponin derivative having the structure shown in the formula III-I.

Another saponin derivative provided by the present invention has a structure as shown by the formula ΠΙ-Π. ΠΙ - Π

 The various body saponin derivatives provided by the present invention can be obtained by various methods, such as dissolving timosaponin-III or timosaponin-saponin in a solvent, adding various necessary reagents, The reaction is carried out under the protection of an inert gas such as, but not limited to, nitrogen, hydrogen or helium. After completion of the reaction, the reaction is terminated with a quencher such as trimethylamine, triethylamine, sodium hydrogencarbonate or sodium thiosulfate. The obtained product is separated by column chromatography using silica gel, alumina, ODS or macroporous resin, and the solvent used for separation is as follows: but not limited to tetrahydrofuran, petroleum ether, ethyl acetate, DMF, pyridine, dichloromethane, ethanol, One or more of methanol or water.

The invention provides a relatively straightforward method for obtaining various saponin derivatives of the present invention, which is obtained by hydrolyzing and separating the timosaponin-indole as a raw material, and the specific method thereof is as follows: according to the weight fraction of the timosaponin Β-ΠΙ Solvent (solvent can be 10v / _V % -100W _V % Cl-C6 alcohol aqueous solution and other common organic solvent aqueous solution, or water added cosolvent, such as: surfactant) Volume ratio 1: 0.2-10, will be known The saponin ΠΙ-ΠΙ is dissolved in a container, and the inorganic acid is added in a volume ratio of 1:1 by weight of the timosaponin to the mineral acid (such as hydrochloric acid and sulfuric acid), and the reaction is carried out at 60 ° C -100 ° C. After 1-10 hours, the reaction is stopped, and the reaction solution is neutralized to pH6_8 by adding an appropriate amount of alkali solution (such as sodium hydrogencarbonate and sodium hydroxide), and the ratio of the weight fraction of the timosaponin to the n-butanol is 1: The mixture was extracted 1 to 3 times, and the n-butanol extraction portion was combined, and the solvent was recovered under reduced pressure to give a solid. The solid is dissolved in a common organic solvent (such as acetonitrile and methanol, etc.), and the main chromatographic peak is separated and collected by an analytical, semi-preparative or preparative HPLC or open ODS column, and the solution containing the target product of the present invention is recovered by a solvent. A yellowish or white product is obtained, which is a furazan-type saponin derivative of the invention.

 Various saponin derivatives, pharmaceutically acceptable salts or combinations thereof provided by the present invention can be obtained by various direct or indirect methods. Those skilled in the art can foresee that the timosaponin B-III (for example, CN101307090A) can be firstly extracted from the mother or its extract, and the various furans provided by the present invention can be indirectly obtained by the acid hydrolysis method disclosed above. The saponin derivative, for example, is hydrolyzed from the timosaponin ΠΙ-ΠΙ obtained from the Chinese medicinal material, and the furan-type saponin derivative represented by the formula I is obtained by separation. In addition, the target derivatives of the present invention can also be obtained by the timosaponin-saponin, and other methods such as: organic synthesis, extraction from biological metabolites, separation and purification, chemical total synthesis, and biocatalysis and conversion. These derivatives are also available. The various preparation methods exemplified in the present invention should be understood as necessary disclosures for carrying out the technical solutions of the present invention. Those skilled in the art can obtain the saponin derivatives of the present invention according to the teachings of textbooks and experimental manuals, as well as through necessary experiments, and the methods for obtaining saponin derivatives described herein are not intended to limit the present invention.

The various saponin derivatives provided by the present invention can be used as the sole or main active ingredient for preparing a medicament for preventing or treating a viral disease, or together with other one or more chemicals or drugs having an antidepressant effect. To the organism. These chemicals are, for example, but not limited to the extract of the mother-in-law, the total saponins of the timosaponin and its hydrolysate, the timosaponin Π-Π and its hydrolysate, the timosaponin saponins, the timosaponin Β-ΠΙ and their Hydrolysates, tricyclic and tetracyclic antidepressants, monoamine oxidase inhibitors, selective 5-HT reuptake inhibitors (SSRI), atypical antidepressants, and lithium salts. The term "administered to an organism together" means that the various saponin derivatives of the present invention are administered alone or in combination with one or more other compounds or drugs having antidepressant effects, such as: but not limited to Oral (Oral), nasal (Nasal), buccal, transdermal, Pulmonal, vaginal, subcutaneous or intravenous; or The other one or more chemical substances or drugs having antidepressant effects are respectively administered to the organism through various administration routes, such as: but not limited to, the immediate release oral preparation is combined with the sustained release release implant preparation.

 The forced swimming test and the tail suspension test prove that the effective therapeutic dose of the furan-type saponin derivative of the formula I of the present invention is administered to the living organism, thereby improving or eliminating the depressive symptoms of the living body. Thus, the furazan-type saponin derivative provided by the present invention has remarkable antidepressant activity, and is used as an active ingredient to prepare medicines, foods, and health care products for use in the prevention and treatment of depression.

 The present invention provides a pharmaceutical composition comprising the various furanosyl saponin derivatives provided as an active ingredient for the prevention and treatment of depression.

 The present invention provides a food product comprising the various furanosyl saponin derivatives provided as an active ingredient for preventing and treating depression.

 The present invention provides a health care product comprising the various furanosyl saponin derivatives provided as an active ingredient for the prevention and treatment of depression.

 The beneficial effects achieved by the technical solution of the invention:

 The furazan-type saponin derivative of the formula I of the present invention, particularly a furan-type saponin derivative having a structural conformation as shown by the formulas III-I and III-II, has significant antidepressant pharmacological activity and can be used as an activity Ingredients are made into medicines, foods and health supplements, either alone or in combination with other substances for the prevention and treatment of depression. DRAWINGS

Figure 1 is a formula III-I 1H NMR if (400MHz, Pyr-t ₅ );

Figure 2 is a formula III-I ¹³ C-NMR spectrum and DEPT135 spectrum (100MHz, Pyr-t ₅ );

Figure 3 is a HMBC spectrum of formula III-II (Pyr-t ₅ );

Figure 4 is a formula III-II ROESY spectrum (Pyr-t ₅ );

 Figure 5 is a HMBC correlation diagram of the formula III-II, which represents the hydrogen-carbon remote correlation;

 Figure 6 is a diagram showing the ROESY correlation of the formula III-II. In the figure, "一→" represents the hydrogen-related NOE correlation. detailed description

The technical solution of the present invention will be described in detail below with reference to the accompanying drawings. The embodiments of the present invention are only used to illustrate the technology of the present invention. The present invention has been described in detail with reference to the preferred embodiments thereof, and those skilled in the art should understand that the invention may be modified or substituted without departing from the spirit and scope of the invention. The scope should be covered by the scope of the claims of the invention.

 The reagents used in the present invention were purchased from Sigma-Aldrich if not explicitly indicated.

 1 2 Preparation of a furazan-type saponin monosaccharide derivative using timosaponin Β-ΠΙ as a reaction starting material, the specific steps are as follows:

(1) Dissolving 0.05 mol of timosaponin-indene in 300 ml of a methanol solution (water or 30 v/v% ethanol solution or lw/v% tween solution) in a volume ratio of 10 v/v%, and adding 0.5 ml of lml. Concentrated sulfuric acid, reacted at 80 ° C -150 ° C for 1 hour - 6 hours.

 (2) The above reaction solution was adjusted with sodium hydroxide to pH = 6-7.

 (3) The solution obtained by neutralizing the extraction step (2) with 900 ml to 1200 ml of n-butanol is carried out, and the extract is concentrated under reduced pressure to dryness.

(4) The solid was dissolved in water, and the saponin was adsorbed on the ODS column, and then eluted with 40 _v / _v %-60 W _V % methanol to collect the eluate.

(5) The solution was recovered under reduced pressure, and evaporated to give a furan-saponin monosaccharide derivative 2 (NMR: see Table 1 for details). Example 2 Preparation of a furan-type saponin derivative

(1) Dissolve 0.05 mol of timosaponin-indene in 300 mL of 10% by volume methanol solution (water or 30% ethanol solution or 1% Tween solution), add 2 mL_4 mL of concentrated hydrochloric acid, 80_15 (TC reaction for 1 hour) ~ 6 hours.

 (2) The above reaction solution was adjusted with sodium hydroxide to pH = 6-7.

 (3) The extraction step is carried out in three steps of 900 mL to 1200 mL of n-butanol. (2) The solution obtained after neutralization is concentrated under reduced pressure to dryness.

(4) The above solid was dissolved in water, and the saponin was adsorbed on the ODS column, and then eluted with 40 W _V % to 60 W _V % methanol to collect the eluate.

 (5) The solution was recovered under reduced pressure and evaporated to dryness to give the saponin monosaccharide derivative 2 (NMR: see Table 1 for details).

 3 T1 2

 The furazolidin-type saponin monosaccharide derivative is prepared by using timosaponin Β-ΠΙ as a reaction starting material, and the specific steps are as follows:

(1) O.lmol of timosaponin Β-ΠΙ was dissolved in 600 ml of a methanol solution having a volume ratio of 1 (% by weight), and 3 O of 5 Oml of concentrated hydrochloric acid was added thereto, and the mixture was reacted at 80 ° C - 100 ° C for 2 hours.

 (2) Adjust to pH=6_7 with sodium hydroxide.

(3) The solution obtained after the neutralization step (2) was extracted with 1.8 L-2.4 L of n-butanol in three steps, and the extract was concentrated under reduced pressure to dryness. (4) The solid was dissolved in water, and the saponin was adsorbed on the ODS column, and then eluted with 40 _v / _v %-60 W _V % methanol to collect the eluate.

 (5) The solution was recovered under reduced pressure, and evaporated to dryness to obtain the aglycone 3 of the parent saponin Β-ΠΙ (NMR: 30.63 (1-C); 27.14 (2-C); 66.07 (3-C); 34.41 (4) -C); 37.04(5-C); 26.97(6-C); 28.65(7-C); 35.27(8-C); 40.02(9-C); 35.57(10-C); 21.38(11- C); 40.15(12-C); 43.88(13-C); 54.83(14-C); 31.39(15-C); 84.59(16-C); 64.68(17-C); 14.45(18-C );26.26(19-C); 103.59(20-C); 11.83(21-C); 152.38(22-C); 34.41(23-C); 23.62(24-C); 33.68(25-C) 68.76 (26-C); 17.16 (27-C)).

(6) Dissolve 0.05 mol of aglycone B-III aglycon and 0.05 mol-0.07 mol of reagent Tl in dichloromethane, reduce the temperature to -20 ° C -0 ° C under nitrogen protection, and add 0.91 m to 1.4 ml CF. ₃ S0 ₃ Si(CH ₃ ) ₃ , the reaction was stopped after 40 minutes and 1 hour.

 (7) The reaction was quenched by the addition of triethylamine, and the solvent was evaporated to dryness.

(8) The precipitate is added to 200 mL of CH ₂ Cl ₂ -MeOH (2: Ι, ν/v) solution, and then added with 50 ml of 1 mol/L_1.5 mol/L sodium methoxide methanol solution, reacted for 3-5 hours, and evaporated to dryness.

(9) The above solid was dissolved in water, and the saponin was adsorbed on the ODS column, and then eluted with 40 _v / _v %-60 W _V % methanol to collect the eluate. The solution is recovered under reduced pressure and evaporated to dryness to give the saponin monosaccharide derivative 2.

 Example 4 Preparation of furan-type saponin iodine derivatives

 3 4 The alkaloid saponin prepared in Example 3 is a reaction starting material, and a furan-type saponin iodine derivative is obtained. The specific steps are as follows:

 (1) Dissolving 0.05 mol of saponin aglycone obtained in the step (5) of Example 3 and 0.05 mol of sodium iodide in 150 ml of 200 ml of 2-butanone, and reacting at 25 ° C - 50 ° C for 1 hour - 3 hour.

 (2) After the reaction is completed, the reaction solution is poured into 1.25 L - 2 L of water, filtered, and washed twice with water.

 (3) The filter cake was dried and recrystallized from methanol.

(4) Filtration, drying the product, that is, the furan-type saponin iodine derivative 4 (NMR: 30.60 (1-C); 27.27 (2-C); 66.05 (3-C); 37.37 (4-C); 40.68(5-C); 27.22(6-C); 29.64(7-C); 34.92(8-C); 40.02(9-C); 35.57(10-C); 21.38(11-C); 40.15 (12-C); 43.88(13-C); 54.83(14-C); 31.39(15-C); 84.59(16-C); 64.68(17-C); 14.45(18-C); 24.26( 19-C); 103.59(20-C); 11.83(21-C); 152.38(22-C); 17.14(23-C); 32.62(24-C); 35.82(25-C); 32.87(26 -C); 20.23(27-C) ).

 The aglycone 3 of the timosaponin Β-ΠΙ obtained in Example 3 is used as a reaction starting material to prepare a furan-type saponin brominated derivative. The specific steps are as follows:

(1) Dissolving 0.05 mol of the saponin obtained in the step (5) of Example 3 in 250 ml-300 ml of CH ₂ Cl ₂ , and adding 25 ml of 30 ml of boron trifluoride-diethyl ether complex reagent (CAS: 109-63- 7), adding 0.05 mol-0.1 mol of acetic anhydride dropwise, reacting at 20 ° C - 60 ° C for 30 minutes _1 hours, washing the reaction solution with 1 L of a saturated NaCl aqueous solution, washing the reaction solution with 750 ml_l of water, separating the organic phase, using Na ₂ S0 _{4 was} dried; the organic phase was filtered, the filtrate was evaporated, and the product was purified by silica gel column chromatography.

(2) The product obtained in the step (1) is dissolved in a solution of 250 ml-300 ml of tetrahydrofuran, and 0.05 mol-0.1 mol of NBS and 0.005 mol of .01 mol (Ph) ₃ P are added, and the reaction is carried out at room temperature for 5 hours to 7 hours.

(3) The reaction solution was filtered, spin solvent was evaporated under reduced _{pressure, A200mLCH 2 Cl 2 -MeOH (2} : l, v / v) solution was extracted by adding 1 mol / L- 1.5mol / L sodium methoxide in methanol 50ml_ 100ml, The reaction is carried out at 20 ° C _ 50 ° C for 5 hours - 8 hours.

(4) Distillation under reduced pressure, concentration reaction, and recrystallization from a mixture of ethanol and ethyl acetate to give the final product furazane saponin bromo derivative 7 (NMR: 31.52 (1-C); 26.44 (2-C) ; 33.85(3-C); 38.32(4-C); 40.68(5-C); 27.22(6-C); 29.64(7-C); 34.92(8-C); 40.02(9-C); 35.57(10-C); 21.38(11-C); 40.15(12-C);

43.88(13-C); 54.83(14-C); 31.39(15-C); 84.59(16-C); 64.68(17-C); 14.45(18-C);

24.26(19-C); 103.59(20-C); 11.83(21-C); 152.38(22-C); 34.41(23-C); 23.63(24-C); 35.43(25-C); 68.07 (26-C); 17.04 (27-C)).

 The aglycone 3 of the timosaponin prepared in Example 3 is a reaction starting material, and a furan-type saponin phosphate derivative is obtained. The specific steps are as follows:

 (1) 0.05 mol of the saponin aglycone obtained in the step (5) in Example 3 was dissolved in 200 ml of tetrahydrofuran, and the temperature was lowered to -50 ° C to 20 ° C, and 0.25 mol-0.3 mol of pyrophosphorus was gradually added thereto. The acid chloride is kept at the same temperature for 1 hour to 3 hours.

(2) Dilute the reaction solution with water, raise the temperature to about 40 ° C -60 ° C, add a certain amount of Na ₂ C0 ₃ to the bubble free release, stir the reaction at 25 ° C -35 ° C for 0.5 hour - 1.5 hours, filter , layering, the lower aqueous solution was steamed at 50 ° C until no obvious bubbles. Hydrochloric acid was added thereto, and pH = 1 - 2 was adjusted to precipitate a white precipitate.

 (3) The precipitate was filtered, and the precipitate was washed three times with acid, and dried to obtain the product furanosyl saponin derivative 8 (NMR: 30.60 (1-C); 27.27 (2-C); 66.05 (3-C) 37.37(4-C); 40.68(5-C); 27.22(6-C); 29.64(7-C);

34.92(8-C); 40.02(9-C); 35.57(10-C); 21.38(11-C); 40.15(12-C); 43.88(13-C); 54.83(14-C); 31.39 (15-C); 84.59 (16-C); 64.68 (17-C); 14.45 (18-C); 24.26 (19-C); 103.59 (20-C); 11.83 (21-C); 152.38 ( 22-C); 33.43 (23-C); 24.12 (24-C); 34.82 (25-C); 71.13 (26-C); 16.21 (27-C)).

 Example 7 Preparation of a furan-type saponin sulfate derivative

Generational derivatives, the specific steps are as follows:

(1) 0.05 mol of the saponin obtained in the step (5) of Example 3 was dissolved in 300 mL of DMF, and subjected to nitrogen gas protection, and the temperature was lowered to -15 ° C to 0 ° C. 0.05 mol H).lmol of Et ₃ N*SO ₃ and 0.4 mol of H.6 mol of p-toluenesulfonic acid were added to the reaction solution for 3 hours to 5 hours.

 (2) 0.05 mol of 0.07 mol of triethylamine was added, followed by the addition of methanol to the volume ratio of 1:1. Stirring is continued for 3 hours to 5 hours; the temperature is raised to 20 ° C to 30 ° C, stirring is continued, and stirring is carried out for 2 hours to 4 hours.

 (3) The solvent was dissolved in vacuo, and the above solid was dissolved with water, and the saponin was adsorbed on an ODS column, and then eluted with 4 (?%_7 (%% methanol).

 (4) The solution was recovered under reduced pressure and evaporated to dryness to give a solid.

 (5) Dissolve the solid with 50 ml of 60 ml of a 1 mol/L NaOH solution, heat to 40 ° C - 70 ° C, and stir for 1 hour - 3 hours.

 (6) Evaporating the solvent, recrystallizing from acetone, and filtering to give the product saponin saponin derivative derivative 9 (NMR: 30.60 (1-C); 27.27 (2-C); 66.05 (3-C); 37.37(4-C); 40.68(5-C); 27.22(6-C); 29.64(7-C); 34.92(8-C); 40.02(9-C); 35.57(10-C); 21.38 (11-C); 40.15(12-C); 43.88(13-C); 54.83(14-C); 31.39(15-C); 84.59(16-C); 64.68(17-C); 14.45( 18-C); 24.26(19-C); 103.59(20-C); 11.83(21-C); 152.38(22-C); 33.43(23-C); 24.12(24-C); 32.82(25 -C); 84.13(26-C); 17.41(27-C)).

 10 11

 The aglycone 3 of the timosaponin Β-ΠΙ obtained in Example 3 is used as a reaction starting material to prepare a furazan-type saponin trifluoroacetic acid-substituted derivative. The specific steps are as follows:

(1) Dissolving 0.05 mol of the saponin aglycone obtained in the step (5) of Example 3 in 250 ml of CH ₂ Cl ₂ , adding 50 m of 60 ml of a boron trifluoride-diethyl ether complexing reagent, and adding 0.1 mol-0.13 of acetic anhydride. Mol, reaction at 20 ° C - 40 ° C for 1 hour - 2 hours, wash the reaction solution with 1 L of saturated aqueous NaCl solution, wash the reaction solution with 750 ml of water, separate the organic phase, and dry with Na ₂ SO ₄ ; The filtrate was dried, and the product was purified by silica gel column chromatography, eluting with petroleum ether and ethyl acetate.

(2) Dissolving the product in (1) in 250 ml of CH ₂ Cl ₂ , cooling to -40 ° C - 15 ° C, adding 0.075 mol of O.lmol of trifluoroacetyl trifluoromethanesulfonate (TFAT), the reaction 2 hours - 4 hours.

(3) After the reaction is completed, the reaction is quenched by the addition of sodium hydrogencarbonate, stirring is continued for 30 minutes to 1 hour, the temperature is raised to 20 ° C to 30 ° C, and stirring is continued for 30 minutes to 1 hour. 3/:i O S9i/-8l£ s99/-6oiAV

 ()()(κ()()()30ζ6£0ΐ36ΐ9Γ inch ζ38ΐ inch inch ΐ3ΐ89 inch 939ΐ6 inch 83ΐ6£ΐ£5Α55------·...·

 (()(()39ζ£Γ inch 3ΐ inch 3ζΐ8ΐ3⁄4ΝΑ3⁄4ΝΑ---- ..

S3⁄4 ^sEE^^^ Aqueous solution. Liebermann-Burchard and Morish react positively, demonstrating that the compound is an timosaponin. [a] ² _D ^e = -66.0 (c 0.05 mg/ml, pyridine ).

HR-ESI-MS (positive ion mode) showed [M+Na]+ w/z 601.3713 (calculated as C ₃₃ H ₅₆ 0 ₉ Na: 601.3711 ), and its molecular formula was determined to be C ₃₃ H ₅₅ 0 ₈ .

The NMR spectrum suggests that the structure contains one molecule of glucose. In the hydrogen spectrum (1H-MNR, see Figure 1), δ 4.87 (d, J = 7.7 Hz) is the glucose-end matrix sub-signal, which is determined to be the configuration. A comprehensive analysis of ¹³ C-NMR spectra and DEPT spectra (see Figure 2) confirmed the presence of four methyl carbon signals, 12 methylene carbon signals, and 13 methine carbon signals in the carbon signal on 26 aglycones. 4 quarter carbon signals. The carbon and hydrogen spectra of the aglycon moiety of the compound are similar to those of the timosaponin B3, indicating that it has a similar nucleus to the timosaponin B3. In the HMBC spectrum (see Figure 3), H21 is remotely related to C20 and C22, indicating that the position of the double bond is consistent with the timosaponin B3. In addition, the 4.87 (Η-Γ) glucose end stromal is remotely related to 75.22 (C-26), and the position of glycosidation is determined, that is, glucose is linked to 26-OH to form a glycoside. The relative stereo configuration is determined by the ROESY spectrum (see Figure 4), that is, the H-5 proton is associated with the presence of NOE in the H-19 proton, and the A and B rings are determined to be in the cis configuration. Other NMR data and correlations are shown in Table 1, Figure 5 and Figure 6. This compound has not been reported in the literature and is a new compound named timosaponin Bill -4 (or simply ΒΠΙ -4).

NMR data of the derivatives of formula III-II

 Type III- II

 No.

 <3⁄4 (J in Hz) Sc

 1 1.89 (m) 30.64

 2 1.94 (m), 1.33 (m) 27.14

 3 4.42 (m) 66.07

 4 1.63 (m), 1.55 (m) 34.41

 5 2.17 (m) 37.04

 6 1.34 (m), 1.18 (m) 26.97

 7 1.76 (m), 1.59 (m) 28.65

 8 1.52 (m) 35.27

 9 1.80 (m) 40.12

 10 - 35.57

 11 1.79 (m), 1.40 (m) 21.38

 12 1.39 (m), 1.27 (m) 40.15

 13 - 43.88

 14 1.49 (m) 54.82

 15 1.89 (m), 1.51 (m) 31.39

 16 4.88 (m) 84.59

 17 2.55 (d, 10.1) 64.68

 18 0.75 (s) 14.45

 19 1.05 (s) 24.26

 20 - 103.59

 21 1.67 (s) 11.83

 22 - 152.38

 23 1.56 (m) 34.41

 24 2.23 (m), 1.04 (m) 23.62

 25 1.63 (m) 33.68

 26 4.11 (dd, 5.7, 9.2), 3.52 (dd, 6.9, 9.2) 75.22

 27 1.08 (m) 17.16

 1 ' 4.87 (m, 7.7) 105.19

 2' 4.07 (m) 75.21

 3' 4.28 (m) 78.53

 4' 4.28 (m) 71.68

 5' 4.00 (m) 78.60

 6' 4.59 (m), 4.43 (m) 62.82

 Example 11 Verification of antidepressant activity

 Both FST and TST behavioral despair models are sensitive to most antidepressants, simple and fast, and are widely used in the screening of such drugs. This example is also prepared by using this model for Example 1 - Example 9. The antidepressant pharmacological effects of the derivatives were verified.

Male ICR mice, weighing (20 ± 2 ) g, were purchased from the Experimental Animal Center of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, free access to drinking water, room temperature (23 ± 2) V, and natural light. All mice were randomly divided into 10/cage, and the experiment was started after 3 days of adaptation in the word culture environment. Fasting for 12 hours before the experiment, drinking water was free. The specific administration method is: blank control Group one group, give an equal volume of normal saline.

 FST verification experiment

 1) Specific operation: Continuous administration for 6 days, and testing 1 hour after the last administration. First, the autonomous activity of the mice was measured by the open field method, and the mice were individually placed in a cylindrical glass jar, timed for 4 minutes, and the number of lifting arms within 2 minutes after recording was recorded. The mice were then individually placed in a cylindrical glass jar 20 cm high and 14 cm in diameter with a water depth of 10 cm and a water temperature of 23-25 °C. After the mice were in water for 6 minutes, the cumulative immobility time within 4 minutes after recording (determination of immobility criteria: the mice stopped struggling in the water, or floating, only small limb movements to keep the head floating on the water). Each group of mice was operated in parallel.

 2) Experimental data processing: The experimental results are expressed as mean ± standard error (x ± SE ). Statistical analysis was performed using the t test to determine whether it was significant. First, the t-test was performed on the indicators of autonomic activity, and 1> > 0.05 indicated that the autonomous post-movement of the mice had no effect, so as to avoid the interference of the central stimulant. Then, the t-test was performed on the forced swimming test index. The blank control group and the high-middle and low-dose three groups were compared to determine whether there is antidepressant effect and the relationship between the antidepressant effect intensity and the dose.

 TST verification experiment

 1) Specific operation: Continuous administration for 6 days, and testing 1 hour after the last administration. First, the autonomous activity of the mice was measured by the open field method, and the mice were individually placed in a cylindrical glass jar, timed for 4 minutes, and the number of lifting arms within 2 minutes after recording was recorded. Then use the tape to stick the mouse tail to the horizontal bar at 2cm from the tip of the tail. The plate is isolated from the animal's line of sight. The horizontal bar is about 25cm away from the ground. The mouse is about 10cm away from the ground, and the time is 6min. At the time of the movement, each group of mice was operated in parallel.

 2) Experimental data processing: The experimental results are expressed as mean ± standard error (x ± SE ). Statistical analysis was performed using the t test to determine whether it was significant. First, the t-test was performed on the indicators of autonomic activity, and 1> > 0.05 indicated that the autonomous post-movement of the mice had no effect, so as to avoid the interference of the central stimulant. Then, the t-test was performed on the experimental indicators of the suspension tail. The blank control group was compared with the high- and low-dose three groups to determine whether there was antidepressant effect and the relationship between the antidepressant effect intensity and the dose.

The effects of the derivatives prepared by the present invention against depression were verified by animal experiments. The results and data are shown in Tables 2 and 3. Mice were given 10 mg/Kg of various compounds by intraperitoneal injection, and a blank control group (physiological saline) was additionally provided. There were no significant differences in the t-test of the indicators of spontaneous activity in mice, indicating that these compounds had no effect on the autonomic activity of mice. The t test was performed on the immobility time of the forced swimming and tail suspension test of the mice. The results showed that the various derivatives prepared in Example 1 - Example 9 can significantly shorten the forced swimming and the suspension of the mouse. Time, suggesting that they have significant antidepressant activity. Effect of intraperitoneal administration on forced swimming time in ICR mice

 Immobility time ±SE (average dose (mg/Kg) number of animals (only)

 Value, sec) Physiological saline 0.1 ml/10 g 10 190.00 soil 7.85 Example 1 (Compound 2) 10 10 86.60 Soil 8.76** Example 2 (Compound 2) 10 10 89.67 ± 10.72* Example 3 (Compound 2) 10 10 103.50 soil 6.59* Example 4 (Compound 4) 10 10 105.72 Soil 8.25* Example 5 (Compound 7) 10 10 110.65 Soil 9.59* Example 6 (Compound 8) 10 10 111.58 Soil 10.26* Example 7 (Compound 9) 10 10 116.38 Soil 8.96* Example 8 (Compound 11) 10 10 109.28 Soil 10.35* Example 9 (Compound 12) 10 10 1071 Soil 10.25* indicates P<0.05; "**" indicates P<0.01.

 Table 3 Effect of intraperitoneal administration on the time of suspension of ICR mice

 Immobility time ±SE (average dose (mg/Kg) number of animals (only)

 Value, sec) Physiological saline 0.1 ml/10 g 10 119.90 soil 5.65 Example 1 (Compound 2) 10 10 42.30 Soil 6.28** Example 2 (Compound 2) 10 10 43.26 Soil 10.62* Example 3 (Compound 2) 10 10 53.34 Soil 10.34* Example 4 (Compound 4) 10 10 57.28 Soil 9.98* Example 5 (Compound 7) 10 10 59.26 Soil 10.09* Example 6 (Compound 8) 10 10 52.58 ± 11.27* Example 7 (Compound 9) 10 10 61.36 soil 9.81* Example 8 (Compound 11) 10 10 54.98 ± 7.98** Example 9 (Compound 12) 10 10 59.76 Soil 10.34*

*,, means P<0.05; "**,, means P<0.01.

Claims

Claim WO 2013/097665 PCT/CN2012/087265

1 . A formula I

Wherein the substituent is selected from the group consisting of -OH, _SH, halogen and a C1-C3 saturated alkane substituted amino group; the substituent R _{2 is} selected from the group consisting of -OH, -SH, halogen, sulfate group, phosphate group, three A fluoroacetic acid group, a C1-C3 saturated alkane-substituted amino group, a sugar linked by an O-glycosidic bond, and a sugar linked by an S-glycosidic bond.

 2. A saponin derivative as shown in formula III-I,

Formula III-I.

 The furan-type saponin derivative according to claim 2, wherein the conformation of the formula III-I is represented by the formula III-II.

Type III- II

 The furane-type saponin derivative according to any one of claims 1 to 3, which is produced from timosaponin Β-ΠΙ or timosaponin Β-saponin. .

The furane-type saponin derivative according to any one of claims 1 to 3, which is obtained from an imaginary parent or an extract thereof. Claim

 WO 2013/097665 PCT/CN2012/087265

 The furane-type saponin derivative according to any one of claims 1 to 3 as an active ingredient for the preparation of a medicament, a food or a health supplement for preventing and treating depression.

 An antidepressant administration method, which comprises administering a therapeutically effective amount of a furan-type saponin derivative according to any one of claims 1 to 3.

 The antidepressant administration method according to claim 7, wherein the effective therapeutic dose is a total amount of 0.05 mg/kg to 50 mg/kg of the furazan-type saponin derivative per day.

 A composition for antidepressant, wherein the active ingredient comprises the furan-type saponin derivative according to any one of claims 1 to 3 as an active ingredient.

 The pharmaceutical composition for antidepressant according to claim 9, which comprises a therapeutically effective amount of the saponin derivative to a patient suffering from depression.