CN111035643A - Application of theophylline as acrolein inhibitor - Google Patents
Application of theophylline as acrolein inhibitor Download PDFInfo
- Publication number
- CN111035643A CN111035643A CN201911242202.6A CN201911242202A CN111035643A CN 111035643 A CN111035643 A CN 111035643A CN 201911242202 A CN201911242202 A CN 201911242202A CN 111035643 A CN111035643 A CN 111035643A
- Authority
- CN
- China
- Prior art keywords
- theophylline
- acr
- acrolein
- inhibitor
- adduct
- 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.)
- Granted
Links
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 title claims abstract description 150
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 title claims abstract description 135
- 229960000278 theophylline Drugs 0.000 title claims abstract description 68
- 239000003112 inhibitor Substances 0.000 title claims abstract description 16
- 235000013305 food Nutrition 0.000 claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 9
- 230000000269 nucleophilic effect Effects 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 11
- 239000000126 substance Substances 0.000 claims description 10
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 230000002939 deleterious effect Effects 0.000 claims description 2
- 239000002075 main ingredient Substances 0.000 claims 1
- 238000004132 cross linking Methods 0.000 abstract description 5
- 229920002521 macromolecule Polymers 0.000 abstract description 5
- 238000012545 processing Methods 0.000 abstract description 4
- 238000001727 in vivo Methods 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 230000008569 process Effects 0.000 abstract description 3
- 239000002516 radical scavenger Substances 0.000 abstract 1
- 239000000047 product Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 11
- 230000005764 inhibitory process Effects 0.000 description 9
- 235000014510 cooky Nutrition 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 241001122767 Theaceae Species 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 150000002500 ions Chemical class 0.000 description 4
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 4
- 230000004962 physiological condition Effects 0.000 description 4
- 238000011160 research Methods 0.000 description 4
- HORQAOAYAYGIBM-UHFFFAOYSA-N 2,4-dinitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O HORQAOAYAYGIBM-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 239000000654 additive Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 108010068370 Glutens Proteins 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 235000009470 Theobroma cacao Nutrition 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- 229930013930 alkaloid Natural products 0.000 description 2
- 235000015895 biscuits Nutrition 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001212 derivatisation Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 235000013312 flour Nutrition 0.000 description 2
- 239000012634 fragment Substances 0.000 description 2
- 235000021312 gluten Nutrition 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000004885 tandem mass spectrometry Methods 0.000 description 2
- 238000005084 2D-nuclear magnetic resonance Methods 0.000 description 1
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 235000006468 Thea sinensis Nutrition 0.000 description 1
- 235000010724 Wisteria floribunda Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 1
- 230000000711 cancerogenic effect Effects 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 210000000748 cardiovascular system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 235000012489 doughnuts Nutrition 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 210000000750 endocrine system Anatomy 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000012020 french fries Nutrition 0.000 description 1
- -1 french fries Chemical class 0.000 description 1
- 235000021552 granulated sugar Nutrition 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007365 immunoregulation Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 238000000238 one-dimensional nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 235000017924 poor diet Nutrition 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- 238000002137 ultrasound extraction Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/03—Organic compounds
- A23L29/045—Organic compounds containing nitrogen as heteroatom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Toxicology (AREA)
- Pain & Pain Management (AREA)
- Urology & Nephrology (AREA)
- Nutrition Science (AREA)
- Hospice & Palliative Care (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Compared with the prior art, the invention discloses a new application of Theophylline (TP) as an Acrolein (ACR) inhibitor, namely the novel application of Theophylline (TP) can effectively capture ACR to control the content of ACR and prevent the ACR from reacting with nucleophilic biological macromolecules to form various harmful adduction or crosslinking products. Theophylline can be used as scavenger of ACR, and can inhibit ACR generated in vivo and in food processing process, thereby preventing harm to human body caused by various harmful adduction or crosslinking products formed by reaction of ACR and nucleophilic biological macromolecule.
Description
Technical Field
The invention discloses an application of theophylline as an acrolein inhibitor, belonging to the technical field of new application of alkaloids.
Background
Acrolein (ACR) is alpha, β -unsaturated aldehyde which is the simplest structure and is also an active carbonyl compound (RCS) with the strongest activity, ACR is listed as a precursor compound of 2 kinds of carcinogen acrylamide by international cancer research institutes of world health organization, and a plurality of researches report that accumulation of ACR in vivo can cause a plurality of diseases, such as atherosclerosis, Alzheimer disease, Parkinson disease, diabetes, cardiovascular diseases and the like.
ACR is widely distributed in human daily life and natural environment, and the main sources are divided into three types: environmental pollution, endogenous metabolism and daily diet. ACR has been reported to be present in a variety of food systems, especially foods rich in fat and carbohydrates, such as french fries, donuts, frying vegetable oils, etc., at levels between 10-11300 ug/kg. ACR is mainly produced during food processing and storage through an oil oxidation reaction, a maillard reaction, and microbial fermentation. Therefore, natural, safe and efficient substances are searched, food systems are added or corresponding health care products are developed to reduce the ACR (acrylate receptor) intake level in food, the action mechanism of the substances is researched to be a necessary means for improving the food safety, and the substances have very important practical significance and theoretical value for preventing chronic diseases caused by poor diet.
The exogenous additives for inhibiting ACR reported so far mainly include flavones, polyphenols, terpenes, vitamins, etc. The color, odor and solubility of these natural actives limit their use in food products, and their structure is unstable, long-lasting during food processing and subsequent efficacy are not significant. The application of related alkaloids in inhibiting ACR is rarely reported.
Theophylline is mainly present in tea (Camellia sinensis) and cocoa (theobroma cacao) of Theaceae, belongs to xanthine derivatives, and is one of the main active ingredients in tea. The theophylline is white crystal, is easily soluble in hot water, has colorless aqueous solution, and has stable structure. The theophylline not only has great influence on the quality of tea, but also has obvious physiological and pharmacological activity. A great deal of literature reports that theophylline has certain positive effects on the nervous system, the cardiovascular system, the digestive system, the endocrine system and the like, and in addition, theophylline also has the effects of promoting urination, enhancing the motor ability, resisting inflammation and inhibiting bacteria.
At present, the research on theophylline at home and abroad mainly focuses on the effects on the respiratory system, the anti-inflammation and the immunoregulation, and the research on the aspect of inhibiting the acrolein by the theophylline is not found.
Disclosure of Invention
The purpose of the invention is as follows: in view of the above technical problems, the present invention provides the use of theophylline as an inhibitor of theophylline (ACR) in food and pharmaceutical products.
The technical scheme is as follows: in order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides application of theophylline or an addition product thereof as an ACR inhibitor.
The theophylline is 1, 3-dimethyl xanthine contained in tea leaves, and the chemical structural formula of the theophylline is shown as follows:
preferably, the use of said theophylline or adduct thereof as an acrolein inhibitor in a food product.
Preferably, the use of said theophylline or adduct thereof for the preparation of an acrolein inhibitor in the human body. It can prevent the occurrence of chronic diseases in human body, such as tumor, Alzheimer disease, aging, atherosclerosis or inflammation caused by the addition or cross-linking of biological nucleophilic macromolecules induced by ACR.
Preferably, the addition product is a mono-or di-addition product of theophylline and acrolein.
The theophylline or addition product thereof is capable of capturing acrolein and thereby reducing the acrolein content.
The theophylline or its adduct product is capable of inhibiting the formation of various deleterious adduct or cross-linked products formed by the reaction of acrolein with nucleophilic biological macromolecules.
When in use, the inhibitor takes theophylline or an addition product thereof as the only component. Or the inhibitor is a preparation formed by compounding and using theophylline or an addition product thereof as a main component and other substances together.
When the theophylline or the additive product thereof is used for removing ACR, the theophylline or the additive product thereof can be independently added into food or medical products for use, and can also be used by being compounded with other natural or synthetic ACR scavengers, thereby achieving the purposes of reducing the ACR content and reducing the harmful substances ingested by human bodies.
The technical effects are as follows: compared with the prior art, the invention discloses a new application of theophylline, namely the theophylline can effectively control the content of ACR and avoid various irreversible harmful adduction or crosslinking products formed by further reaction with nucleophilic biological macromolecules. The theophylline can be used as an inhibitor of ACR, can remove ACR generated in vivo and in the process of food processing, further blocks the formation of harmful cross-linking products induced by ACR, and prevents the harm to human body.
Drawings
FIG. 1 shows the result of the measurement of ACR inhibitory activity of theophylline and its addition products (MA, DA) with ACR under simulated physiological conditions.
FIG. 2 shows the result of measurement of inhibition of ACR activity in cookies by theophylline and its addition products (MA, DA).
Detailed Description
The invention is further elucidated with reference to the drawings and the specific examples.
Example 1 purification and Structure Studies of the adduct of theophylline with ACR
(1) Experimental materials and instruments
45 micron silica gel filler (fuji, japan); ethyl acetate (analytical grade, Shanghai pharmaceutical group chemical Co., Ltd.).
AVANCE 400MHz nuclear magnetic resonance instrument (bruker corporation); 1290/6460 LC-MS (Agilent, USA).
(2) Experimental procedure
Reacting theophylline with ACR in a molar ratio of 1:1, performing primary purification through a silica gel column, and crystallizing to obtain an addition product MA of the theophylline and the ACR; reacting theophylline with ACR in a molar ratio of 1:3, primarily purifying by a silica gel column, and crystallizing to obtain theophylline and ACRThe bis-adduct DA of (a); analyzing the molecular weight by LC-MS; 1D-NMR1H，13C，2D-NMR1H-13CHMQC and HMBC were subjected to structural analysis.
(3) Results of the experiment
3.1 MA identification
The prepared MA is measured by LC-MS, and M/z is 237[ M + H ] in positive ion mode]+Bitheophylline M/z 181[ M + H ]]+56 (MW) in excessACR56) and 237[ M + H ] in MS/MS]+The major fragment ion peak of (a) was m/z 181, missing one ACR molecular weight group, thus indicating that TP-MA is an addition product of one molecule of ACR and theophylline.
TABLE 1 of theophylline and theophylline-ACR adduct (MA)1H NMR (400Hz) and13c NMR (100MHz) spectroscopic data (deuterated DMSO, in. delta. ppm)
As can be seen from Table 1, the hydrogen spectrum of MA is compared with theophylline, and hydrogen protons δ H4.49 t, 3.10td and 9.66d appear, as shown in the MA structure in FIG. two, the HMBC spectrum shows that the hydrogen proton δ H4.49 t is related to δ C143.18 s (C-4), 106.31s (C-5), which indicates that the hydrogen proton is H-8, and the hydrogen proton δ H3.10 td is related to δ C40.58 s (C-8), which indicates that the hydrogen proton is H-9. The MA structure is deduced by integrating the characteristics of the nuclear magnetic spectrum, and the MA is a novel compound.
3.2 DA identification
The prepared DA has M/z 275M + H in positive ion mode as determined by LC-MS]+Bitheophylline M/z 181[ M + H ]]+94(2 MW) in excessACR-MWWater (W)94) and 275[ M + H ] in MS/MS]+The major fragment ion peaks of (a) were m/z 181 and m/z 234, thus indicating that DA is the addition product of two molecules of ACR minus one molecule of water and theophylline.
TABLE 2 of theophylline and theophylline-2 ACR adduct (DA)1H NMR (400Hz) and13c NMR (100MHz) spectroscopic data (deuterated DMSO, in. delta. ppm)
According to the data in Table 2, such as DA structure, the same reasoning as in Table 1 suggests DA structure, which is a novel compound.
The chemical structural formulas of theophylline, MA and DA are as follows:
example 2 theophylline and its adduct MA/DA mimic the inhibitory activity of ACR under physiological conditions
(1) Experimental materials and instruments
MA (adduct of theophylline and ACR, HPLC, > 98%); DA (a diadduct of theophylline and ACR, HPLC, is more than or equal to 96%); theophylline (> 99%, Shanghai Aladdin Biotechnology GmbH); 2, 4-dinitrophenylhydrazine (DNPH & HCl, > 98%, Tokyo Chemical Industry); acrolein (ACR, 98% aqueous solution, analytical purity, Shandong-Xiya chemical industries, Ltd.); acetonitrile (chromatographically pure, Shanghai national drug group chemical reagent, Inc.); purified water (Hangzhou Wahaha group Co., Ltd.); both sodium dihydrogen phosphate and disodium hydrogen phosphate were analytical reagents (Shanghai pharmaceutical group chemical Co., Ltd.).
High performance liquid chromatograph: agilent Technologies 1260 (Agilent Technologies, USA); ZQTY-70 desktop shake culture tank (Shanghai Zhichu instruments Co., Ltd.); QL-861 vortex mixer (Lenbel instruments, Inc. of Haiman city, Jiangsu); KQ-300B ultrasonic cleaner (Kunshan ultrasonic instruments Co., Ltd.); PHS-3C digital pH meter (Shanghai Sanxin Meter factory); FA2104N electronic analytical balance (shanghai precision scientific instruments ltd).
(2) Experimental procedure
Preparing an ACR solution by using 0.1mol/L PBS with pH of 7.4, respectively adding 0.5mL ACR solution (2mmol/L) and 0.5mL theophylline/MA/DA solution (2mmol/L) into a 2mL centrifuge tube, replacing the theophylline/MA/DA solution with 0.5mL PBS solution as a blank, uniformly mixing by vortex, placing the mixture in a desktop shaking incubator at 37 ℃ and 220rpm, and respectively reacting for 1h, 2h, 4h, 6h and 24h in a dark place. And after the reaction is finished, adding 300 mu L of DNPH solution into 500 mu L of reaction solution, performing derivatization, detecting the content of ACR by using high performance liquid chromatography, and calculating the inhibition rate of theophylline/MA/DA on ACR under simulated physiological conditions. Three replicates of each sample were made.
(3) Results of the experiment
As can be seen from FIG. 1, under simulated physiological conditions, theophylline/MA/DA all showed ACR-inhibiting effect, and the inhibiting effect is remarkably enhanced with the time. In a short time, the inhibition effect of MA and DA on ACR is better than that of theophylline, and the inhibition effect of theophylline on ACR is better after 6 hours, and the ACR is supposed to be inhibited by the addition product generated in the system and the theophylline together.
EXAMPLE 3 Theine and adduct MA/DA inhibition of ACR Activity in cookies
(1) Experimental materials and instruments
YXP 101-2 commercial electric oven, BUD 302 mixer (Shanghai early seedling food Co., Ltd.).
(2) Experimental procedure
54g of butter is melted in a stirring cylinder each time, 0.169g of theophylline/MA/DA (the addition amount is 0.1%) is respectively added, the stirring is continued, 40g of white granulated sugar, 15g of eggs, 40g of high gluten flour and 20g of low gluten flour are sequentially added, the mixture is uniformly mixed and then is filled into a decorating bag to be extruded to a baking tray, and the initial mass of each cookie is 5 g; setting the upper fire at 180 deg.C and the lower fire at 170 deg.C, and baking for 15 min.
Accurately weighing 0.5g of crushed cookie sample, placing the crushed cookie sample in a centrifuge tube, adding 5mL of distilled water, performing vortex centrifugation, and collecting supernatant fluid 1; and continuously adding 5mL of 50% methanol aqueous solution, performing vortex mixing, performing ultrasonic extraction for 60min, centrifuging, collecting supernate 2, mixing the supernate obtained in the step 1 and the supernate obtained in the step 2, and centrifuging. Three replicates of each sample were made. And (3) taking 0.5mL of supernatant for derivatization reaction, measuring the ACR content by liquid chromatography, and calculating the inhibition rate.
(3) Results of the experiment
The cookies are biscuits with high oil content and high sugar content, and a certain amount of ACR can be generated through lipid oxidation, Maillard reaction and other ways in the high-temperature baking process. The experiment finds that the content of ACR can be reduced by adding a small amount of theophylline and the addition product MA/DA thereof into the cookie biscuits, and the addition product still has the inhibition effect on ACR and shows the continuous inhibition effect. As shown in figure 2, theophylline has the best effect of inhibiting ACR, and the inhibition rate reaches 30.9%.
Claims (8)
1. Use of theophylline or an addition product thereof as an acrolein inhibitor.
2. Use according to claim 1, wherein the theophylline or an adduct thereof is used as an acrolein inhibitor in a food product.
3. Use according to claim 1, wherein the theophylline or an adduct thereof is used in the preparation of an acrolein inhibitor in the human body.
4. Use according to claim 1, wherein the addition product is a mono-or di-addition product of theophylline and acrolein.
5. Use according to claim 1, wherein the theophylline or adduct thereof is capable of capturing acrolein and thereby reducing the acrolein content.
6. Use according to claim 1, wherein the theophylline or an adduct thereof is capable of inhibiting the formation of various deleterious adductions or cross-links by reaction of acrolein with nucleophilic biomacromolecules.
7. The use according to claim 1, wherein the inhibitor comprises theophylline or an addition product thereof as the sole component.
8. The use according to claim 1, wherein the inhibitor is a preparation comprising theophylline or an adduct thereof as a main ingredient and used in combination with other substances.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911242202.6A CN111035643B (en) | 2019-12-06 | 2019-12-06 | Application of theophylline as acrolein inhibitor |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911242202.6A CN111035643B (en) | 2019-12-06 | 2019-12-06 | Application of theophylline as acrolein inhibitor |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN111035643A true CN111035643A (en) | 2020-04-21 |
| CN111035643B CN111035643B (en) | 2021-08-31 |
Family
ID=70234824
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911242202.6A Active CN111035643B (en) | 2019-12-06 | 2019-12-06 | Application of theophylline as acrolein inhibitor |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111035643B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113648321A (en) * | 2021-07-23 | 2021-11-16 | 南京师范大学 | cyanidin-3-O-glucoside and application of addition product of cyanidin-3-O-glucoside and acrolein as acrolein inhibitor |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670579A1 (en) * | 1967-10-13 | 1971-02-25 | Degussa | SS-Theophyllino-propionaldehyde and process for its preparation |
| CN1149585A (en) * | 1996-09-06 | 1997-05-14 | 中国科学院昆明植物研究所 | Producing technology for natural theine |
-
2019
- 2019-12-06 CN CN201911242202.6A patent/CN111035643B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670579A1 (en) * | 1967-10-13 | 1971-02-25 | Degussa | SS-Theophyllino-propionaldehyde and process for its preparation |
| CN1149585A (en) * | 1996-09-06 | 1997-05-14 | 中国科学院昆明植物研究所 | Producing technology for natural theine |
Non-Patent Citations (2)
| Title |
|---|
| A. RABINOVITCH ET AL.: "Theophylline protects against diabetes in BB rats and potentiates cyclosporine protection", 《DIABETOLOGIA》 * |
| 邹悦瑜等: "食品中丙烯醛形成、危害及控制研究进展", 《食品安全质量检测学报》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113648321A (en) * | 2021-07-23 | 2021-11-16 | 南京师范大学 | cyanidin-3-O-glucoside and application of addition product of cyanidin-3-O-glucoside and acrolein as acrolein inhibitor |
| CN113648321B (en) * | 2021-07-23 | 2023-03-24 | 南京师范大学 | cyanidin-3-O-glucoside and application of addition product of cyanidin-3-O-glucoside and acrolein as acrolein inhibitor |
Also Published As
| Publication number | Publication date |
|---|---|
| CN111035643B (en) | 2021-08-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Mao et al. | Polysaccharides from Chinese Liupao dark tea and their protective effect against hyperlipidemia | |
| EP2799075A1 (en) | Maillard reaction inhibitor | |
| EP0423419A1 (en) | Inhibitive agent against activity of alpha-amylase | |
| Luo et al. | An approach for degradation of grape seed and skin proanthocyanidin polymers into oligomers by sulphurous acid | |
| JPWO2005030200A1 (en) | Autoimmune disease treatment | |
| CN111657419A (en) | Application of curcumin as acrolein inhibitor | |
| CN111035643B (en) | Application of theophylline as acrolein inhibitor | |
| JP7333815B2 (en) | COMPOSITION FOR IMPROVING LIVER FUNCTION | |
| Song et al. | Inhibitory effect on acrolein by cyanidin-3-O-glucoside and its acrolein adducts from the pigment of mynica red | |
| CN113080382B (en) | Application of cardamomin as acrolein inhibitor | |
| US11007237B2 (en) | Agent for suppressing carbohydrate breakdown and absorption | |
| EP1645557A1 (en) | Novel substance having alpha-glucosidase inhibiting activity and food containing the same | |
| CN115500495B (en) | Application of composite combination of semen Alpiniae and curcumin as acrolein inhibitor | |
| JP2008273935A (en) | Inhibitor of fat accumulation and method for suppressing fat accumulation | |
| CN115554323A (en) | Preparation method and application of novel traditional Chinese medicine composition | |
| KR101078002B1 (en) | Composition comprising galla rhois extract for prevention and treatment of obesity by means of autophagic mechanism | |
| KR102513138B1 (en) | Composition for Anti-obesity Using an Extract of Spiraea prunifolia | |
| CN115530314B (en) | Application of disodium 5 '-inosinate and disodium 5' -guanylate as acrolein inhibitor | |
| KR101509220B1 (en) | A preparation method of immune-boosting composition using fermented coffee spent | |
| JP2008013525A (en) | Naringenin derivative, glucose uptake promoter and agent for inhibiting rise in blood sugar level containing the same | |
| Lin et al. | Simultaneous scavenging capacity of Glycine and Serine for formaldehyde along with glyoxal and the cytotoxicity of the interaction product in three cell lines | |
| JP2009221158A (en) | Neutral fat-reducing agent and suppressor of body fat increase | |
| KR101466381B1 (en) | Food and pharmaceutical composition for preventing or improving obesitiy comprising specific compound isolated from Eisenia bicyclis as effective component | |
| CN104761463B (en) | D pantothenic acid sodium crystal and its production and use | |
| KR102669644B1 (en) | Composition for improving, preventing or treating fatty liver, including milk thistle extract with increased bioavailability of silymarin |
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 |