CN109096350B - Thioether compound in moringa seed and its application - Google Patents

Thioether compound in moringa seed and its application Download PDF

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CN109096350B
CN109096350B CN201810206480.5A CN201810206480A CN109096350B CN 109096350 B CN109096350 B CN 109096350B CN 201810206480 A CN201810206480 A CN 201810206480A CN 109096350 B CN109096350 B CN 109096350B
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thioether
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叶文才
范春林
王英
刘辉
李满妹
刘俊珊
黄晓君
张晓琦
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
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    • C07—ORGANIC CHEMISTRY
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    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/10—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C323/11—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
    • C07C323/16—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and singly-bound oxygen atoms bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton containing six-membered aromatic rings
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    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
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    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
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    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
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Abstract

The invention relates to 4 new disulfide and trithioether compounds extracted and separated from moringa seeds and application of the disulfide compounds in preparing medicaments for treating diabetes, depression and senile dementia, and experiments show that the compounds have better effects of reducing blood sugar, depression and senile dementia. The thioether compound has the characteristics of clear activity mechanism, low toxicity, safety and the like, and has wide application prospect.

Description

Thioether compound in moringa seed and its application
Technical Field
The invention relates to a thioether compound separated from moringa seeds and application thereof in preparing medicaments for treating diabetes, depression and senile dementia.
Background information
Moringaoleeifera L am is a Moringaceae plant, namely a perennial tropical deciduous arbor, originally produced in arid and semiarid regions of tropical and southern subtropics, and is widely distributed in tropical marine climatic regions such as Africa, Arab, southeast Asia and Pacific island (Anwar F, et al. Phytothermres, 2007,21(1): 17-25). after 60 years of the last century, large-area planting (Dongnan, Hainan, Guangdong, Guangxi, etc.) in China has been carried out (Cantonese Elegano. 2008,17(9): 39-41.) Moringa oleifera is a fast-growing arbor, which can blossom out after 6 months of planting, and roots, stems, leaves, flowers and seeds of the Moringa oleifera can all use medicinal (Chinese plant journal, 1984:34(1): 6). The Moringaceae, Moringaolifera contains phenols and glycosides, flavonoids, glycosides, polysaccharides and polysaccharides, and other medicinal ingredients for relieving pain, and for liver disease, and protecting liver and liver diseases (23. the same) has been reported as pharmacological activities of liver disease-relieving pain and liver disease.
The invention discovers a series of thioether compounds from moringa seeds, wherein the thioether compounds comprise 5 new compounds, and the thioether compounds are discovered to have the effects of treating diabetes, resisting depression and senile dementia for the first time through research.
Disclosure of Invention
The invention relates to a thioether compound separated from moringa seeds and application thereof in preparing medicaments for treating diabetes, depression and senile dementia.
The chemical general formula of the thioether compound and the derivative thereof is as follows:
Figure GDA0002521084470000021
wherein R is1、R2Is hydrogen or a sugar radical; n is 1, 2 or 3, and the ether group is preferably monosulfide, disulfide, trisulfide or the like; the glycosyl is preferably six-carbon (glucose, mannose, rhamnose) pyranose, and six-carbon furanose, and the acylated saccharide is preferably six-carbon (glucose, mannose, rhamnose) pyranose, and six-carbon furanose. Or an acyl sugar (acetyl, propionyl, benzoyl). Preferred substituents and names of compounds according to the invention are shown in table 1.
TABLE 1 thioether substituent and name
Figure GDA0002521084470000022
Figure GDA0002521084470000031
When the compound of the present invention is used as a medicament, it may be used as it is or in the form of a pharmaceutical composition. Comprises at least one compound of formula (I) as an active ingredient in combination with one or more pharmaceutically acceptable carriers and excipients which are non-toxic and inert to humans.
The carriers and excipients used are one or more of solid, semi-solid and liquid diluents, fillers and pharmaceutical adjuvants. The pharmaceutical composition of the invention is prepared into various dosage forms, such as liquid preparations (suspension, syrup, oral liquid or injection, and the like), solid preparations (tablets, capsules or granules, and the like), sprays, and the like by adopting a method accepted in the pharmaceutical field. The above medicine can be administered by oral administration, sublingual administration, or injection (intravenous injection, intramuscular injection, subcutaneous injection, etc.).
Description of the drawings:
FIG. 1 is an ESI-MS diagram of Compound 1;
FIG. 2 is a NMR spectrum of Compound 1;
FIG. 3 is a NMR carbon spectrum of Compound 1;
FIG. 4 is an ESI-MS plot of Compound 2;
FIG. 5 is a NMR spectrum of Compound 2;
FIG. 6 is a NMR carbon spectrum of Compound 2;
FIG. 7 is an ESI-MS diagram of Compound 3;
FIG. 8 is a NMR spectrum of Compound 3;
FIG. 9 is a NMR carbon spectrum of Compound 3;
FIG. 10 is an ESI-MS plot of Compound 4;
FIG. 11 is a NMR spectrum of Compound 4;
figure 12 is the nmr carbon spectrum of compound 4.
Detailed Description
The invention will be more readily understood by reference to the following examples, which are given to illustrate the invention, but are not intended to limit the scope thereof.
EXAMPLE 1 isolation and Structure characterization of novel Compounds
Pulverizing Moringa seed 5kg, percolating with 55% ethanol 10 times the weight of Moringa seed twice for 24 hr each time, mixing extractive solutions, concentrating, filtering, adsorbing the filtrate with D101 macroporous resin column, eluting with water and 10% ethanol sequentially to remove impurities, eluting with 80% ethanol 50L, recovering 80% ethanol eluate, concentrating, drying under reduced pressure to obtain total extract, subjecting 150g of total extract to silica gel column chromatography, gradient eluting with petroleum ether-ethyl acetate system (volume ratio of petroleum ether to ethyl acetate from 100:0 to 1:1), recovering solvent from each gradient, mixing to obtain fraction Fr.1-Fr.10. Fr.2(28g) by ODS column chromatography (reverse octadecyl bonded silica gel), gradient eluting with methanol-water system (volume ratio of methanol to water from 2:8 to 1:0) to obtain 6 fractions, subjecting Fr.3a-Fr.3f, wherein Fr.3c (1.3g) is prepared HP L C, gradient eluting with 30% methanol-water as mobile phase, preparing 3 (3 g) compound (3: 24% ODS) and preparing methanol-13.26 g) from Fr.3 g, and recovering solvent from Fr.3 a-10. C (volume ratio of methanol) as mobile phase chromatography (8: 1: 1.10. Fr.3 g) to obtain HP 3g) by HP 3. C.26. C, and HP 3. C (gradient eluting with water) as mobile phase chromatography, and methanol-10. 5.10. C, and 10. C (gradient) as mobile phase chromatography, preparing compound (mobile phase) from 5. by HP).
Compound 1 is a yellow amorphous powder with the chemical formula:
Figure GDA0002521084470000051
the spectral data are as follows: ESI-MSm/z 569.1531[ M-H ]]-. ESI-MS is shown in FIG. 1.1H-NMR(CD3OD): 7.18(2H, d, J ═ 8.5Hz, H-2, and H-6), 7.02(1H, d, J ═ 8.5Hz, H-3, and H-5), 5.42(1H, d, J ═ 1.5Hz, H-1 '), 3.99(1H, m, H-2'), 3.83(1H, dd, J ═ 9.3,3.5Hz, H-3 '), 3.60(1H, m, H-5'), 3.56(2H, d, J ═ 5.9Hz, H-7), 3.45(1H, t, J ═ 9.3Hz, H-4 '), 1.18(3H, d, J ═ 6.2Hz, H-6'). The hydrogen nuclear magnetic resonance spectrum is shown in FIG. 2.13C-NMR(CD3OD): 157.2(C-4), 132.6(C-1), 131.7(C-2 and C-6), 117.4(C-3 and C-5), 99.7(C-1 '), 73.8 (C-4'), 72.2(C-2 '), 72.0 (C-3'), 70.6(C-5 '), 43.3(C-7), 18.0 (C-6'). The NMR spectrum is shown in FIG. 3. The above data indicate that compound 1 is a highly symmetric phenolic glycoside containing disulfide.
Hydrolyzing compound 1 with acid to obtain aglycone and sugar part, performing derivatization reaction on sugar, comparing with standard sugar derivative by HP L C liquid phase analysis, and identifying sugar is L-rhamnose, and C-3-C-5 conjugated with rhamnose13C chemical shift value identifies the glycosyl as α -L-rhamnosyl。
Based on the above information, compound 1 was identified as S, S' -bis [ (4-O- α -L-rhamnosyl) benzyl ] -disulfide as a new compound.
Compound 2 is a yellow amorphous powder with the chemical formula:
Figure GDA0002521084470000052
the spectral data are as follows: ESI-MSm/z 601.1252[ M-H ]]-. ESI-MS is shown in FIG. 4.1H-NMR(CD3OD): 7.24(2H, d, J ═ 8.5Hz, H-2, and H-6), 7.02(1H, d, J ═ 8.5Hz, H-3, and H-5), 5.41(1H, d, J ═ 1.5Hz, H-1 '), 3.98(1H, m, H-2'), 3.97(2H, d, J ═ 5.9Hz, H-7), 3.83(1H, dd, J ═ 9.3,3.5Hz, H-3 '), 3.61(1H, m, H-5'), 3.44(1H, t, J ═ 9.3Hz, H-4 '), 1.20(3H, d, J ═ 6.2Hz, H-6'). The hydrogen nuclear magnetic resonance spectrum is shown in FIG. 5.13C-NMR(CD3OD): 157.3(C-4), 131.7(C-2 and C-6), 117.5(C-3 and C-5), 99.8(C-1 '), 73.8 (C-4'), 72.2(C-2 '), 72.0 (C-3'), 70.6(C-5 '), 43.3(C-7), 18.0 (C-6'). The NMR spectrum is shown in FIG. 6. The above data indicate that compound 2 is a highly symmetric phenolic glycoside containing trisulfide.
Hydrolyzing compound 2 with acid to obtain aglycone and sugar part, performing derivatization reaction on sugar, comparing with standard sugar derivative by HP L C liquid phase analysis, and identifying sugar is L-rhamnose, and C-3-C-5 conjugated with rhamnose13C chemical shift values identify the glycosyl as α -L-rhamnosyl.
Combining the above information, compound 2 was identified as S, S "-bis [ (4-O- α -L-rhamnosyl) benzyl ] -trisulfide as a new compound.
Compound 3 is a yellow amorphous powder with the chemical formula:
Figure GDA0002521084470000061
the spectral data are as follows: ESI-MSm/z 423.0904[ M-H ]]-. ESI-MS is shown in FIG. 7.1H-NMR(CD3OD)：7.19(2H,d,J ═ 8.5Hz, H-2, and H-6), 7.06(2H, d, J ═ 8.5Hz, H-2 ', and H-6'), 7.02(1H, d, J ═ 8.5Hz, H-3, and H-5), 6.72(1H, d, J ═ 8.5Hz, H-3 ', and H-5'), 5.42(1H, d, J ═ 1.5Hz, H-1 "), 3.99(1H, m, H-2"), 3.84(1H, dd, J ═ 9.5,3.5Hz, H-3 "), 3.62(1H, m, H-5"), 3.59(2H, s, H-7), 3.53(2H, s, H-8), 3.44(1H, t, J ═ 9.5, H-4 ", 3.5Hz, H-6 ″), 3.6H-5 ″, and H-6 ″. The hydrogen nuclear magnetic resonance spectrum is shown in FIG. 8.13C-NMR(CD3OD): 158.0(C-4 '), 157.2(C-4), 132.7(C-1), 131.7 (C-2' and C-6 '), 131.6(C-2 and C-6), 117.5 (C-3' and C-5 '), 129.5 (C-1'), 116.2(C-3 and C-5), 99.8(C-1 '), 73.8 (C-4'), 72.2(C-2 '), 72.0 (C-3'), 70.6(C-5 '), 43.7(C-8), 43.4(C-7), 18.0 (C-6'). The NMR spectrum is shown in FIG. 9. The above data indicate that compound 3 is a disulfide-containing phenolic glycoside compound.
Hydrolyzing compound 3 with acid to obtain aglycone and sugar part, performing derivatization reaction on sugar, comparing with standard sugar derivative by HP L C liquid phase analysis, and identifying sugar is L-rhamnose, and C-3-C-5 conjugated with rhamnose13C chemical shift values identify the glycosyl as α -L-rhamnosyl.
Based on the above information, compound 3 was identified as S- [ (4-O- α -L-rhamnosyl) benzyl ] -S '- (4' -hydroxybenzyl) -disulfide as a new compound.
Compound 4 is a yellow amorphous powder with the chemical formula:
Figure GDA0002521084470000071
the spectral data are as follows: ESI-MSm/z 455.0663[ M-H ]]-. ESI-MS is shown in FIG. 10.1H-NMR(CD3OD): 7.24(2H, d, J ═ 8.5Hz, H-2, and H-6), 7.11(2H, d, J ═ 8.5Hz, H-2 ', and H-6'), 7.03(1H, d, J ═ 8.5Hz, H-3, and H-5), 6.72(1H, d, J ═ 8.5Hz, H-3 ', and H-5'), 5.40(1H, d, J ═ 1.5Hz, H-1 "), 3.99(2H, s, H-7),3.98(1H, m, H-2"), 3.94(2H, s, H-8), 3.83(1H, dd, J ═ 9.5,3.5Hz, H-3 ", 3.61(1H, m, H-5"), 3.44 "(1H, t ″, t ═ 4, H-5", 3.6H-5 ", 1H-4, H-5", 3.6 ", J ″, 6H, H-5", and H-5 ". The hydrogen nuclear magnetic resonance spectrum is shown in FIG. 11.13C-NMR(CD3OD): 158.1(C-4), 157.3(C-4 '), 131.8(C-1), 131.8(C-2 and C-6), 131.7 (C-2' and C-6 '), 117.6(C-3 and C-5), 117.5 (C-3' and C-5 '), 128.7 (C-1'), 99.8(C-1 '), 73.8 (C-4'), 72.2(C-2 '), 72.0 (C-3'), 70.6(C-5 '), 43.7(C-8), 43.4(C-7), 18.0 (C-6'). The nuclear magnetic resonance carbon spectrum is shown in FIG. 12. The above data indicate that compound 4 is a trisulfide containing phenolic glycoside compound.
Hydrolyzing compound 4 with acid to obtain aglycone and sugar part, performing derivatization reaction on sugar, comparing with standard sugar derivative by HP L C liquid phase analysis, and identifying sugar is L-rhamnose, and C-3-C-5 conjugated with rhamnose13C chemical shift values identify the glycosyl as α -L-rhamnosyl.
Based on the above information, compound 4 was identified as S- [ (4-O- α -L-rhamnosyl) benzyl ] -S "- (4' -hydroxybenzyl) -trisulfide, a new compound.
EXAMPLE 2 injection
Taking 10 parts by weight of the compound or the derivative thereof obtained in the example 1, 8.5 parts by weight of sodium chloride and 1000 parts by weight of water for injection, mixing and dissolving, stirring, adding 2 parts by weight of activated carbon, stirring for 30min, filtering the solution through a microporous filter membrane (0.22 mu m), subpackaging in 5ml of ampoule, sterilizing, checking to be qualified and preparing into 50mg of water injection per ampoule. Other examination items should meet the requirements under the injection item of pharmacopoeia of the people's republic of China (2015 edition).
EXAMPLE 3 lyophilized powder for injection
Taking 10 parts by weight of the compound or the derivative thereof obtained in the example 1, dissolving the compound or the derivative thereof in 1000 parts by weight of 1% mannitol injection water, adding 5 parts by weight of activated carbon, stirring for 20min, filtering the solution through a microporous filter membrane (0.22 mu m) to obtain a clear solution, subpackaging the clear solution in 10ml penicillin bottles with 2ml each, and freeze-drying to prepare freeze-dried powder injection containing 20mg each. Other examination items should meet the requirements under the injection item of pharmacopoeia of the people's republic of China (2015 edition).
EXAMPLE 4 tablets
Taking 20 parts by weight of the compound or the derivative thereof obtained in the example 1, 30 parts by weight of starch as a filling agent, 5 parts by weight of hydroxypropyl methyl cellulose as a binding agent and 10 parts by weight of microcrystalline cellulose as a disintegrating agent; and 0.5 part of magnesium stearate is selected as a lubricant, mixed, added with a proper amount of 50% ethanol for granulation, dried and tabletted to obtain the tablet. Other examination items should meet the requirements under the item of tablets in pharmacopoeia of the people's republic of China (2015 edition).
Example 5 hypoglycemic Activity of thioether Compounds in Moringa seed
(1) Principle of experiment
A mouse diabetes model induced by High Fat Diet (HFD) and Streptozotocin (STZ) is adopted, different compounds are respectively used for intragastric administration, the influence of the novel thioether compounds on the blood sugar and the body weight of a diabetic mouse is observed, and the effect of the compounds on treating diabetes is evaluated.
(2) Experimental Material
Kunming mice; 1-4 of a new moringa seed thioether compound; streptozotocin; lard oil; blood glucose test paper and glucometer; sodium citrate buffer (pH 4.4); a glove; a mouse box; and (4) distilled water.
(3) Experiment grouping
Thioether new compound experimental group; normal group (distilled water); model set (HFD + STZ).
(4) Preparation and treatment of the model
3 male Kunming mice are placed in a cage, the room temperature is 22 +/-3 ℃, the relative humidity is 60 +/-10%, the illumination is carried out for 12 hours every day, and the mice can be freely eaten and drunk. After 1 week of adaptive feeding, randomized into groups of 10: normal group was fed with normal diet, high-fat diet diabetes (HFD + STZ) group was fed with high-fat diet, and after 3 weeks, mice were fasted for 12 hours without water deprivation, (HFD + STZ) mice and STZ solution were administered with intraperitoneal injection of 100mg/kg, and normal group mice were intraperitoneally injected with citric acid-sodium citrate buffer at the same dose. After the STZ injection, the mice were kept on the same diet, and the mice were kept on the same diet. The tail vein blood was taken one or two weeks after administration and was checked with a glucometer. 10 mice with common feed are normal groups, and 60 mice with successfully molded diabetes are randomly divided into 6 groups. The administration was according to the following groups: 20mg/kg of thioether new compound group in the moringa seeds and 0.3-0.4 ml/day of distilled water in a model group and a normal group are administrated in a stomach-irrigation mode for 1 time per day.
(5) Detailed Experimental procedures
Observing the conditions of ingestion, drinking, body quality, mental state, hair color and the like after administration for 1 and 2 weeks; respectively measuring: blood sugar level and body weight.
(6) Results of the experiment
① general case observation
After the model is made, the mice have the symptoms of polydipsia, polyphagia, polyuria, weight loss, slow response, disorder and dull fur and the like, the symptoms of all groups of mice are improved to different degrees after the administration of the thioether new compound in the moringa seeds, the response is more flexible, and the fur is flat and glossy.
② influence of thioether novel compounds in moringa seeds on blood sugar content of HFD + STZ diabetic mice
From the results (table 2) it can be seen that: the average blood sugar of the diabetes mice induced by HFD + STZ is obviously increased and has a significant difference compared with the normal group (P < 0.001). Compared with the mouse model group, the thioether new compound group in the moringa seeds has the advantages that the blood sugar is obviously reduced (P <0.05, P <0.01 and P < 0.001). The results show that the thioether new compounds in the moringa seeds can reduce the blood sugar of diabetic mice.
TABLE 2 Effect of thioether Compounds in Moringa seed on blood glucose levels in HFD + STZ diabetic mice ((S))
Figure GDA0002521084470000101
n＝10)
Figure GDA0002521084470000102
###P<0.001, model group vs blank group; p<0.05，**P<0.01，***P<0.001, administration group vs model group
③ Effect of thioether New Compounds in Moringa seed on the body weight of HFD + STZ diabetic mice the results (Table 3) show that the body weight of mice in the diabetic model group is significantly increased (P <0.01, P <0.001) compared with the body weight of mice in the normal group, and the body weight of thioether New compounds is significantly decreased (P <0.05, P <0.01) compared with the model group.
TABLE 3 Effect of thioether Compounds in Moringa seed on weight in diabetic mice: (
Figure GDA0002521084470000103
n＝10)
Figure GDA0002521084470000104
##P<0.01，###P<0.001, a v s normal group of an administration group; p<0.05，**P<0.01, administration group vs model group.
Example 6 antidepressant Activity of thioether Compounds in Moringa seed
(1) Principle of experiment
The Forced Swimming Test (FST) system is mainly used for research of antidepressant, sedative and analgesic drugs. By placing the experimental animal in a confined environment (such as water) where the animal struggles to struggle to try to escape and fail to escape, a non-avoidable stressed environment is provided in which the animal exhibits a typical "immobility" after a period of experimentation, reflecting a condition known as "behavioral despair", and a series of parameters are recorded during the process in which the animal in the environment develops the desired immobility. The immobility time of the mouse is an index for judging the action of the depression drug, and the shorter the immobility time is, the stronger the antidepressant action is. Mouse Tail Suspension Test (TST): is a classic method for rapidly evaluating the drug effects of antidepressant drugs, stimulants and sedatives. The principle is that the mouse tries to escape after hanging the tail but cannot escape, so that struggle is abandoned and the special depression immobility state is entered, the animal immobility time is recorded in the experimental process to reflect the depression state, and antidepressant drugs and exciting drugs can obviously shorten and change the state.
(2) Experimental Material
C57B L/6 mouse, thioether new compound in moringa seed, fluoxetine hydrochloride, glove, mouse box, deionized water, organic glass water jar, camera, and No. 12 mouse stomach-filling needle.
(3) Experiment grouping
Experimental group of new compounds of moringa seed thioether: 10 per group, 20 mg/kg; group of positive drugs (fluoxetine hydrochloride): 10, 20 mg/kg; blank group: 10 pieces of deionized water were given.
(4) Detailed Experimental procedures
Forced swimming experiment: mice were taken, fasted and kept without water for 12h, and transferred to the laboratory 1h before the experiment to adapt to the environment. After the gavage for 1h, the mice are respectively placed in glass jar water for swimming, the first 2min is taken as adaptation time, and the cumulative time of floating and immobility of the mice stopping swimming within 4min is recorded. The administration group is administered at 9-10 am every day for 6 days, and on 7 th day, before administration, fasting is advanced for 1h, after intragastric administration for 1h, the mice are respectively placed in glass jar for swimming, the first 2min is taken as adaptation time, and the cumulative time of floating and standing which stops swimming within 4min after administration is recorded.
Tail suspension test: 1h after the last administration, fixing the part of the tail of the mouse, which is 2cm away from the root, on a self-made tail suspension bracket, enabling the head of the mouse to be in an inverted hanging state about 5cm away from the table top, and separating the two sides of each animal by using plates to shield the sight of the animals so as not to interfere with each other. The cumulative immobility time of each group of animals within 5min after tail suspension within 6min was observed.
(5) The experimental results are as follows:
① compared with the model group, the thioether new compounds in the moringa seeds can obviously shorten the cumulative immobility time in forced swimming (P <0.05, P <0.01), and the results are shown in Table 4.
TABLE 4 Effect of thioether Compounds in Moringa seed on forced swimming of mice ((S))
Figure GDA0002521084470000121
n＝10)
Figure GDA0002521084470000122
P <0.05, P <0.01, administration group vs blank group
② compared with the model group, the thioether new compounds in the moringa seeds can obviously shorten the cumulative immobility time of tail-suspended mice (P <0.05), and the results are shown in Table 5.
TABLE 5 Effect of thioether Compounds in Moringa seed on mouse Tail suspension experiment ((S))
Figure GDA0002521084470000123
n＝10)
Figure GDA0002521084470000124
P <0.05, administration group vs blank group
(6) And (4) experimental conclusion:
experimental results show that the thioether compounds in the moringa seeds prepared by the invention can shorten the immobility time of mice in forced swimming experiments and tail suspension experiments. Shows that: the thioether compound prepared by the moringa seed through a certain extraction and separation method has a good anti-depression effect, and can be used for preparing and developing an anti-depression preparation.
Example 7 anti-senile dementia Activity of thioether Compounds in Moringa seed
(1) Principle of experiment
The A β deposition is one of the most typical pathological features of senile dementia, and has a key role in the occurrence and development process of senile dementia, the accuracy rate of senile dementia diagnosis according to the A β deposition condition can reach 80%, and the study shows that the A β deposition in the brain can reach 80%40And A β42The Morris water maze test is a classic method for evaluating space learning and memory ability and an objective index for evaluating the replication result of a dementia animal model, in recent years, the dementia animal model becomes an important means for researching senile dementia, and SD rats are adopted to prepare A β1-42A dementia model is injected into a brain chamber, a thioether new compound and normal saline are respectively given to moringa seeds, and the improvement condition of the thioether compound in the moringa seeds on the learning and memory ability of senile dementia rats is evaluated through a Morris water maze experiment.
(2) Experimental Material
SPF SD male rat, thioether new compound in moringa seed, and amyloid protein fragment (A β)1-42) (ii) a DW-5 rat brain stereotaxic instrument; WMT-100Morris water fanA palace video analysis system; a glove; a mouse box; deionized water; an organic glass water tank; a camera; and (5) performing gastric lavage.
(3) Experiment grouping
Control group (saline), model group (condensed state A β)1-42) And the new thioether compounds in the moringa seeds are 10 in each group.
(4) Dosage and frequency of administration
The thioether new compound experimental group in the moringa seeds is 20mg/kg, and is administrated in an intragastric manner 1 time a day for 7 days continuously.
(5) Detailed Experimental procedures
① model preparation comprises anesthetizing SD rat with 10% urethane, fixing skull, positioning in 3.4mm behind bregma, 2.0mm left and right of midline of brain, and injecting 5 μ L condensed A β at 2.7mm depth below skull surface1-42The model A β control group was injected with isotonic saline at equal volume and the Morris water maze behavioural test was performed 1 week after molding.
② Morris water maze behavioural test, selecting a quiet, dark light and constant temperature environment for testing, properly pasting different figures on the wall of a laboratory to help an animal to determine the direction, filling a bucket with clear water to a preset height (about 40cm) before the test, adding a proper amount of white pigment to enable the water to be opaque milky liquid, heating the water to 25 ℃, placing a platform in the center of a fourth quadrant at about 1.5cm below the water surface, and keeping the platform position unchanged in the whole test process, positioning a sailing test, wherein the positioning sailing test lasts for four days, placing the platform in the center of a second quadrant, allowing the rat to enter water from the four surfaces of the pool wall in sequence, recording the time for the rat to find the platform in 120s, namely, an escape latency (E L), if the rat does not find the platform in 120s, the escape latency is 120s, guiding the rat to get on the platform, keeping the rat on the platform for 15s, making the rat as an escape point, calculating the average value of the number of the rat in each group of memory platforms, calculating the average value of the number of the rat escape latency of the rat in the search time, and recording the average number of the rat in the rat escape latency of the rat search space after the rat search, wherein the rat search process, the rat is recorded 6335.
(6) Results of the experiment
As shown in Table 6, in the localization navigation test, the mean escape latency of thioether compounds in moringa seeds is remarkably shortened (P <0.05) compared with that of a model group. In the space search test, compared with the model group, the number of cross-platform times and the distance of the thioether compound group in the moringa seeds are obviously improved (P <0.05 and P <0.01) (Table 7). The above results show that: the thioether compounds in Moringa seed have effect in improving dysmnesia of rats with senile dementia.
TABLE 6 thioether pairs in Moringa seed A β1-42Effect of induced Alzheimer's disease on escape latency in rats: (
Figure GDA0002521084470000151
n＝10)
Figure GDA0002521084470000152
#P<0.05，##P<0.01, model group vs control group; p<0.05 administration group vs model group
TABLE 7 thioether pairs in Moringa seed A β1-42Effect of induced Alzheimer's disease rat spatial search experiment (1)
Figure GDA0002521084470000153
n＝10)
Figure GDA0002521084470000154
##P<0.01, model group vs control group; p<0.05，**P<0.01 administration group v s model group

Claims (2)

1. The thioether compound in the moringa seed is characterized by being selected from disulfide or trithioether compounds, and having the following specific structure:
Figure FDA0002503841150000011
2. the use of thioether compounds from moringa seeds as claimed in claim 1 for the manufacture of a medicament for the treatment of diabetes, antidepressant and anti-senile dementia.
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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101143192A (en) * 2006-04-07 2008-03-19 中央研究院 Therapeutic gastrodia extracts
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* Cited by examiner, † Cited by third party
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CN101426763A (en) * 2000-10-11 2009-05-06 埃斯佩里安医疗公司 Sulfide and disulfide compounds and compositions for cholesterol management and related uses

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101948416A (en) * 2003-08-20 2011-01-19 维尔斯达医疗公司 The compound that is used for the treatment of metabolism disorder
CN101143192A (en) * 2006-04-07 2008-03-19 中央研究院 Therapeutic gastrodia extracts

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
Chemical fingerprint and metabolic profile analysis of ethyl acetatefraction of Gastrodia elata by ultra performance liquidchromatography/quadrupole-time of flight mass spectrometry;Chunlan Tang et al.，;《Journal of Chromatography B》;20151117;第1011卷;第233–239页 *
Studies on the Decomposition of Sinalbin part Ⅰ. The Decomposition Products of Sinalbin;Shunro KAWAKISHI et al.，;《Agricultural and Biological Chemistry》;20140909;第30卷(第7期);第688-692页 *
Synthesis of S-Linked Glycosyl Amino Acids in Aqueous Solution with Unprotected Carbohydrates;Scott B. Cohen et al.,;《ORGANIC LETTERS》;20010110;第3卷(第3期);第405-407页 *
辣木的化学成分研究;刘长倩 等，;《安徽农业科学》;20161231;第44卷(第5期);第142-144页 *

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