CN109180484B - 2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof - Google Patents
2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof Download PDFInfo
- Publication number
- CN109180484B CN109180484B CN201810940470.4A CN201810940470A CN109180484B CN 109180484 B CN109180484 B CN 109180484B CN 201810940470 A CN201810940470 A CN 201810940470A CN 109180484 B CN109180484 B CN 109180484B
- Authority
- CN
- China
- Prior art keywords
- noni
- ethyl acetate
- ferment
- mixed solvent
- column chromatography
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Endocrinology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to the technical field of natural medicinal chemistry, in particular to a 2, 4-disubstituted phenol derivative compound extracted from noni ferment, a preparation method thereof and application thereof in preparing hypoglycemic drugs. The phenol derivative compound provided by the invention has a novel structure, has a good treatment effect on reducing blood sugar, is natural in source and small in side effect; meanwhile, the preparation method has the advantages of simple process, low cost and wide raw material source.
Description
Technical Field
The invention relates to the technical field of natural pharmaceutical chemistry, in particular to a 2, 4-disubstituted phenol derivative compound extracted from noni ferment, and an extraction method and application thereof.
Background
Diabetes mellitus is a chronic disease characterized by elevated blood sugar associated with abnormal insulin production and action. With the development of socioeconomic in China, the change of dietary structure and the continuous improvement of living standard of people, the prevalence rate of diabetes is on the rapid rising trend, and the total number of diabetes patients in the world is more than 1.2 hundred million people at present. The current situation of diabetes in China is very severe, the incidence rate is as high as 9.6%, and the situation becomes the country with the fastest increase of the number of people suffering from diabetes worldwide. The prevalence of diabetes in our country has increased since decades, and the prevalence of diabetes in people 25 to 64 years in our country is 2.5% by national diabetes epidemiological investigation in 1995. The Chinese disease prevention and control center between 8 months 2010 and 12 months 2010 and Shanghai medical college of transportation university jointly carry out diabetes investigation on 98658 people living in 18 years and above all over China, and the investigation result shows that the prevalence rate of diabetes of the 18 years and above all over China is 9.65% in 2010. At present, the number of people with diabetes among adults 18 years old and older in China reaches 9240 ten thousands, and the people are the first in the world, meanwhile, the disease condition of diabetes of teenagers in China is not optimistic, and the diabetes prevention and treatment becomes one of the most major public health problems in China. Hyperglycemia occurring in the long term of diabetes results in chronic damage to, and dysfunction of, various tissues, particularly the eyes, kidneys, heart, blood vessels, nerves.
The existing hypoglycemic drugs are not abundant enough, and often have drug resistance after long-term administration, and a large number of patients have to select injection insulin therapy with higher cost and higher risk due to the drug resistance, so that a new hypoglycemic drug with good effect is urgently needed to be further developed.
Noni (Noni) is the fruit of morinda citrifolia. Shrubs to small trees, 1-5 meters high; the stem is straight and the branch is close to the quadrangular shape. The leaves are alternately opposite, and are long round, oval or oval, 12-25 cm long, tapered or sharp at both ends, generally glossy, hairless and complete. Noni ferment has effects of lowering blood pressure, regulating blood lipid, improving osteoporosis and auditory ability, relieving fatigue, improving memory, repairing wound, and expelling parasites. Through literature search, the application of noni ferment and the extract thereof in reducing blood sugar is not reported at present.
Disclosure of Invention
The first objective of the present invention is to provide a 2, 4-disubstituted phenol derivative compound extracted from noni ferment, which has the following structure:
the second purpose of the invention is to provide an extraction method of the compound, which comprises the following steps:
(1) fermenting noni fruits to obtain noni ferment;
(2) extracting noni ferment with ethyl acetate;
(3) concentrating the extractive solution, and performing column chromatography, thin layer chromatography and gel column chromatography to obtain the above compound.
Preferably, the preparation method of the noni ferment is as follows:
a. cleaning the skin of mature noni fruits by using a brush, and cutting into slices with the thickness of 1-5 mm;
b. mixing noni fruits according to the proportion of white granulated sugar: and (3) noni fruits: putting water in a clean fermentation container in a ratio of 1: 2-4: 8-20, and leaving 20-30% of space in the fermentation container for fermentation;
c. fermenting in shade for three months, wherein the first month is that the fermentation container is opened or shaken every day, and filtering after three months to obtain noni ferment.
Preferably, the volume ratio of the noni ferment to the ethyl acetate in the step (2) is 1: 1 to 5.
Preferably, the extract liquid in the step (3) is concentrated to 1/20-1/100 of the original volume.
Preferably, the column chromatography conditions in step (3) are as follows: and filling a column chromatographic column with 300-mesh silica gel, and taking an ethyl acetate-petroleum ether mixed solvent with the ethyl acetate volume percentage of 10-20% as an eluent.
Preferably, the thin layer chromatography conditions in step (3) are specifically as follows: the developing solvent is ethyl acetate-petroleum ether mixed solvent with 10-20% of ethyl acetate volume percentage, or petroleum ether-acetone mixed solvent with 4:1 volume ratio, or chloroform-acetone mixed solvent with 10:1 volume ratio.
Preferably, the gel column chromatography conditions in step (3) are as follows: the gel is Sephadex LH-20, and a chloroform-methanol mixed solvent with the chloroform volume percentage of 20-40% is used as an eluent.
A third aspect of the present invention is to improve the use of the above compounds for the preparation of a medicament for the treatment of hypoglycemia.
The invention has the beneficial effects that: the 2, 4-disubstituted phenol derivative compound provided by the invention is novel in structure, has a good treatment effect on reducing blood sugar, is natural in source and has small side effect; meanwhile, the preparation method has the advantages of simple process, low cost and wide raw material source.
Detailed Description
The technical solutions of the present invention are described below by way of specific examples, but the scope of the present invention is not limited thereto.
Example 1
(1) Preparation of noni enzyme
a. Cleaning the skin of mature noni fruits by using a brush, and cutting into slices with the thickness of 1-5 mm;
b. mixing noni fruits according to the proportion of white granulated sugar: and (3) noni fruits: putting water in a ratio of 1:2:20 into a clean fermentation container, and leaving 20-30% of space in the fermentation container for fermentation;
c. fermenting in shade for three months, wherein the first month is that the fermentation container is opened or shaken every day, and filtering after three months to obtain noni ferment.
(2) Extraction of
Extracting the obtained noni ferment twice by using ethyl acetate, wherein the using amount of the ethyl acetate is 2.5 times of the volume of the noni ferment to be extracted each time, and collecting extract liquor;
(3) separation of
Concentrating the extract obtained in the step (2) to 1/50 of the original volume, and sequentially carrying out column chromatography, thin layer chromatography and gel column chromatography; the column chromatography conditions were: the chromatographic column is a 300-mesh silica gel column, an ethyl acetate-petroleum ether mixed solvent with 20% ethyl acetate volume percentage is used as an eluent, and the eluent is collected, concentrated and enters thin-layer chromatography; the thin layer chromatography conditions were: collecting the product point with the largest area on the thin-layer chromatography by taking an ethyl acetate-petroleum ether mixed solvent with 25 percent of ethyl acetate volume percentage as a developing solvent; the gel column chromatography conditions are as follows: the gel is Sephadex LH-20, a chloroform-methanol mixed solvent with the chloroform volume percentage of 40 percent is used as an eluent, and the eluent is collected and concentrated to obtain the target compound.
Example 2
(1) Preparation of noni enzyme
a. Cleaning the skin of mature noni fruits by using a brush, and cutting into slices with the thickness of 1-5 mm;
b. mixing noni fruits according to the proportion of white granulated sugar: and (3) noni fruits: putting water in a ratio of 1:4:8 into a clean fermentation container, and leaving 20-30% of space in the fermentation container for fermentation;
c. fermenting in shade for three months, wherein the first month is that the fermentation container is opened or shaken every day, and filtering after three months to obtain noni ferment.
(2) Extraction of
Extracting the obtained noni ferment twice by using ethyl acetate, wherein the using amount of the ethyl acetate is 1/2 of the volume of the noni ferment to be extracted each time, and collecting extract liquor;
(3) separation of
Concentrating the extract obtained in the step (2) to 1/100 of the original volume, and sequentially carrying out column chromatography, thin layer chromatography and gel column chromatography; the column chromatography conditions were: the chromatographic column is a 300-mesh silica gel column, an ethyl acetate-petroleum ether mixed solvent with 10% ethyl acetate volume percentage is used as an eluent, and the eluent is collected, concentrated and enters thin-layer chromatography; the thin layer chromatography conditions were: collecting the product point with the largest area on the thin-layer chromatography by taking an ethyl acetate-petroleum ether mixed solvent with the ethyl acetate volume percentage of 10% as a developing agent; the gel column chromatography conditions are as follows: using a chloroform-methanol mixed solvent with the chloroform volume percentage of 20 percent as an eluent, collecting the eluent and concentrating to obtain the target compound.
Example 3
The physicochemical properties, hydrogen spectrum and mass spectrum detection data of the target compound are as follows:
the target compound is colorless crystal, is easily dissolved in methanol and DMSO, and is black and dark spot under an ultraviolet lamp of 254 nm. HRESI-MS [ m/z 263.0, calculated 240.10]The molecular weight of the compound is 240, and the molecular formula is C12H16O5The unsaturation degree is 5.1H NMR(400MHz in CD3OD) and13C NMR(100MHz in CD3OD) are shown in the table.
Example 4
The target compound was subjected to an α -glucosidase inhibitory activity test:
the target compounds were prepared into stock solutions of 0.6, 0.3, 0.15mg/mL with PBS (phosphate buffered saline).
Preparing an enzyme solution with the concentration of 2U and a substrate PNPG with the concentration of 2.5mmol/L for standby
The experimental steps are as follows: adding 58 μ l of 0.1M PBS buffer into a 96-well plate; mu.l of diluted compound (4 groups, 3 groups and 1 group as a control) was added to the mixed solution, 10. mu.l of the prepared enzyme solution was added to the control group, 0.01M PBS buffer solution was added to the control group, 20. mu.l of substrate PNPG was added after mixing, a blank control was set, 20. mu.l of DMSO was added, and the other operations were the same as above. Mixing, placing in 37 deg.C constant temperature incubator for 15min, taking out, adding 150 μ l stop solution (Na)2CO3Solution) and the absorbance is measured by a microplate reader with acarbose as a standard control.
Judging the influence of the 2, 4-disubstituted phenol derivative compounds in the noni ferment on the alpha-glucosidase by the inhibition rate of the alpha-glucosidase, calculating the inhibition rate (inhibition rate) (monomer compound group OD value-control group OD value/control group OD value) multiplied by 100 percent according to the following formula, and calculating IC (integrated circuit) by the inhibition rate50The values, experimental results are shown in table 1.
TABLE 1 phenol derivative compounds of noni ferment alpha-glucosidase inhibitory activity IC50Value of
The experimental result shows that the inhibiting activity of the target compound on alpha-glucosidase is higher than that of a reference product acarbose.
In light of the foregoing description of the preferred embodiment of the present invention, many modifications and variations will be apparent to those skilled in the art without departing from the spirit and scope of the invention. The technical scope of the present invention is not limited to the content of the specification, and must be determined according to the scope of the claims.
Claims (4)
1. A2, 4-disubstituted phenol derivative compound extracted from noni ferment has the following structure:
2. a method for extracting a compound according to claim 1, comprising the steps of:
(1) fermenting noni fruits to obtain noni ferment;
(2) extracting noni ferment with ethyl acetate; the volume ratio of the noni ferment to the ethyl acetate is 1: 1-5;
(3) concentrating the extractive solution, and performing column chromatography, thin layer chromatography and gel column chromatography to obtain the above compound;
the column chromatography conditions in the step (3) are as follows: filling a column chromatographic column with 300-mesh silica gel, and taking an ethyl acetate-petroleum ether mixed solvent with 10-20% of ethyl acetate by volume as an eluent;
the thin layer chromatography conditions in the step (3) are as follows: taking an ethyl acetate-petroleum ether mixed solvent with the volume percentage of 10-20% of ethyl acetate as a developing solvent, or taking a petroleum ether-acetone mixed solvent with the volume ratio of 4:1 as a developing solvent, or taking a chloroform-acetone mixed solvent with the volume ratio of 10:1 as a developing solvent;
the gel column chromatography conditions in the step (3) are as follows: using chloroform-methanol mixed solvent with 20-40% of chloroform volume percentage as eluent.
3. The method for extracting the compound according to claim 2, wherein the specific preparation method in the step (1) is as follows:
a. cleaning the skin of mature noni fruits by using a brush, and cutting into slices with the thickness of 1-5 mm;
b. mixing noni fruits according to the proportion of white granulated sugar: and (3) noni fruits: putting water in a clean fermentation container in a ratio of 1: 2-4: 8-20, and leaving 20-30% of space in the fermentation container for fermentation;
c. fermenting in shade for three months, wherein the first month is that the fermentation container is opened or shaken every day, and filtering after three months to obtain noni ferment.
4. Use of the 2, 4-disubstituted phenol derivatives according to claim 1 for the preparation of a medicament for lowering blood sugar.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810940470.4A CN109180484B (en) | 2018-08-17 | 2018-08-17 | 2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810940470.4A CN109180484B (en) | 2018-08-17 | 2018-08-17 | 2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN109180484A CN109180484A (en) | 2019-01-11 |
| CN109180484B true CN109180484B (en) | 2021-04-20 |
Family
ID=64918191
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810940470.4A Active CN109180484B (en) | 2018-08-17 | 2018-08-17 | 2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN109180484B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112645950B (en) * | 2020-12-28 | 2021-12-28 | 海南师范大学 | Indole alkaloid compound in noni ferment as well as preparation method and application thereof |
| CN116063262B (en) * | 2021-10-29 | 2024-02-20 | 海南师范大学 | Kojic acid compound in noni fruits and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003020296A1 (en) * | 2001-08-31 | 2003-03-13 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | INHIBITION OF ANGIOGENESIS AND DESTRUCTION OF ANGIOGENIC VESSELS WITH EXTRACTS OF NONI JUICE $i(MORINDA CITRIFOLIA) |
| CN104374854A (en) * | 2014-08-21 | 2015-02-25 | 中国食品发酵工业研究院 | Method for simultaneously detecting content of multiple phenolic acids in Noni juice by HPLC (high performance liquid chromatography) wavelength switching technology |
-
2018
- 2018-08-17 CN CN201810940470.4A patent/CN109180484B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003020296A1 (en) * | 2001-08-31 | 2003-03-13 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | INHIBITION OF ANGIOGENESIS AND DESTRUCTION OF ANGIOGENIC VESSELS WITH EXTRACTS OF NONI JUICE $i(MORINDA CITRIFOLIA) |
| CN104374854A (en) * | 2014-08-21 | 2015-02-25 | 中国食品发酵工业研究院 | Method for simultaneously detecting content of multiple phenolic acids in Noni juice by HPLC (high performance liquid chromatography) wavelength switching technology |
Non-Patent Citations (3)
| Title |
|---|
| "Novel Oxooxepane Derivatives and New Phorbic Acid Derivative from Paederia scandens";Y. W. Chin et al.;《Bull. Korean Chem. Soc.》;20130220;第34卷(第2期);第683-685页 * |
| "诺丽叶降血压、降血糖和抗氧化活性的研究";张伟敏等;《食品研究与开发》;20131031;第34卷(第19期);第66-70页 * |
| "诺丽的化学成分及药理活性研究进展";晏永球等;《中草药》;20170531;第48卷(第9期);第1888-1905页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN109180484A (en) | 2019-01-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109180484B (en) | 2, 4-disubstituted phenol derivative compounds extracted from noni ferment, and extraction method and application thereof | |
| CN103435580A (en) | Lingzhiol A and application of lingzhiol A in drug production and foods | |
| CN110615821A (en) | Mulberry extract, extraction and separation method and application thereof | |
| CN109053530B (en) | Pyrrole derivative compound in noni ferment and preparation method and application thereof | |
| CN102911222A (en) | Extraction method of aucubin and application of aucubin | |
| CN109053451B (en) | Phenol derivative compound extracted from noni ferment, and extraction method and application thereof | |
| CN106220701A (en) | triterpene compound and preparation method and application thereof | |
| CN101220100A (en) | Separation and purification method for squash polyoses and use of obtained component | |
| CN113968916B (en) | Extraction method and application of phlebopus portentosus polysaccharide | |
| CN108379404A (en) | A kind of extraction purification technology of neural cell injury repair medicine | |
| CN104910291B (en) | A kind of jackfruit leaf polyose and its preparation method and application | |
| CN112645913B (en) | P-diphenyl compound and preparation method and application thereof | |
| CN107513092B (en) | Malonyl ginsenoside Rb1Preparation method and medical application thereof | |
| CN111440186B (en) | Coumarin norisoflavone compound extracted from small horse blebs and having liver protecting effect, and preparation method and application thereof | |
| CN110143989B (en) | Ellagitannins alpha-glucosidase inhibitor and preparation method thereof | |
| CN108403980B (en) | Hypoglycemic plant extract effective part and preparation method and application thereof | |
| CN103585226B (en) | A kind of preparation method of Herba Elephantopi Mollis extract and application thereof | |
| CN108853184B (en) | Cyclocarya paliurus and lithocarpus polystachyus rehd extract composition | |
| CN107986968B (en) | dicaffeoyl succinyl methyl ester quininic acid compound, preparation method and application | |
| CN112641816A (en) | Composition containing jerusalem artichoke extract and application of composition in type II diabetes mellitus and complications | |
| CN111812252B (en) | Screening and separating method for hypoglycemic functional compounds in plants | |
| CN101332220A (en) | Preparation method of extracting and separating potato vine polysaccharide from natural plant sweet potato vine | |
| CN100434088C (en) | Intravenous administration preparation extracted from marsdenia tenacissima stem | |
| CN110559307A (en) | albizzia julibrissin new lignan compound and new application thereof | |
| CN110227080A (en) | application of mannoglucuronosyl poly (oligo) saccharide and derivative thereof in preparing medicament for treating and/or preventing type 2 diabetes |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |