Application of water-soluble tomato concentrate in preparation of composition capable of regulating biological rhythm

Abstract

The invention relates to application of a water-soluble tomato concentrate in preparation of a composition capable of regulating biological rhythm. Researches find that the water-soluble tomato concentrate can improve the expression of a core gene Per2 of a biological rhythm and other rhythm core genes including Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora, can obviously increase the amplitude of the biological rhythm, and can prevent and / or improve sleep disorders, so that the water-soluble tomato concentrate can play a good role in improving sleep quality or regulating the biological rhythm, and can be used for preparing a health-care product. The composition can be used for preparing the composition for regulating the biological rhythm or improving the sleep quality.

Description

Technical Field

[0001] The present application relates to the field of biomedicine and food technology, and in particular to the application of a water-soluble tomato concentrate in preparing a composition capable of regulating biological rhythms. Background Art

[0002] Sleep problems are one of the most concerned health issues in today's society. Sleep disorders directly affect body functions, accelerate aging, damage brain cognition, affect emotional health, and may lead to the occurrence of a variety of diseases including metabolic diseases and cardiovascular diseases. Sleep is mainly regulated by two key driving factors, biological rhythms and sleep-wake homeostasis. Biological rhythms refer to the physiological and behavioral changes that occur in organisms according to certain rules within a day or a year, mainly including circadian rhythms, monthly rhythms, seasonal rhythms, etc. Among them, the biological rhythm that regulates sleep is mainly the circadian rhythm. The circadian rhythm senses the periodic changes in light and converts signals into sleep regulation through the secretion of melatonin, changes in body temperature and changes in some metabolic activities.

[0003] Circadian rhythm is essentially a mechanism by which a group of biological clock genes of autonomous oscillating transcription-translation negative feedback loop (TTL) regulate the body's life activities. The core TTL's positive molecules mainly include Clock and Bmal1, and the negative molecules mainly include Cry and Per. The fluctuation of circadian rhythm can be represented by the circadian rhythm curve, which has three basic parameters like the sine curve: period, phase and amplitude. The amplitude is half of the difference between the peak value and the trough value in the rhythm curve fluctuation, which is used to characterize the magnitude of the change in the circadian rhythm. Studies have shown that the amplitude of the circadian rhythm is a key factor affecting sleep. The weakening of the circadian rhythm amplitude may lead to shallower sleep depth and poorer sleep quality, that is, lead to maintenance sleep disorders.

[0004] The causal relationship between circadian rhythm disorders and sleep disorders is bidirectional. A reduction in the amplitude of circadian rhythm can lead to sleep disorders, while irregular sleep time or frequent changes in circadian sleep time can lead to a further decrease in the amplitude of circadian rhythm, further aggravating circadian rhythm disorders and causing long-term sleep disorders.

[0005] In recent years, with the acceleration of the pace of society, many industries have long-term business trips, frequent jet lag, day and night shift work, irregular eating, and irregular rest, which lead to circadian rhythm disorders. Circadian rhythm disorders can cause a series of sleep disorders or sleep disorder-related diseases, such as long sleep latency, long non-rapid eye movement sleep latency (specifically manifested as short deep sleep time), sleep fragmentation, and sleep-related anxiety / depression-like behaviors.

[0006] The research of Lu Yue et al. (Nutrition Journal, Vol. 45, No. 2, 2023) shows that enhancing the amplitude of circadian rhythm genes can improve circadian rhythm disorders and improve sleep quality. Perturbation of Per2 expression levels is a core component of the circadian rhythm system. Increasing the expression of Per2 rhythm genes and enhancing the amplitude of Per2 expression can increase the oscillation amplitude of the circadian rhythm. et al. ( A study published in the Journal of Clinical Oncology (Volume 11, Issue 2, 2016) showed that melatonin supplementation can induce increased expression of Per2 in the human body and regulate circadian rhythms, thereby preventing and / or treating circadian rhythm disorders, as well as preventing and / or treating sleep disorders.

[0007] Provis Natural Products Co., Ltd. has developed water-soluble tomato concentrate (WSTC), known as "natural aspirin", which has a very strong function of inhibiting platelet aggregation and has no adverse reactions such as gastrointestinal bleeding. It is expected to have very good application prospects in the prevention and treatment of cerebral thrombosis. In 2009, EFSA (European Food Safety Authority) approved the health claim research on "water-soluble tomato concentrate helps maintain normal platelet aggregation and contributes to healthy blood flow" for the first time. This health research claim has been approved. Multiple test results have confirmed that water-soluble tomato concentrate contains naturally occurring antiplatelet compounds, which can inhibit the platelet activity of healthy people after ingestion, reduce platelet aggregation, thereby keeping the blood in a fluid and low coagulation state, prevent the formation of microaggregates in the circulatory system, and prevent platelets from adhering to the blood vessel wall or fatty plaques, thereby maintaining healthy blood circulation. At the same time, platelet function is not completely inhibited and is maintained at an appropriate level, so that platelets can aggregate when blood vessels are damaged, but will not disrupt the necessary coagulation process after injury. Water-soluble tomato concentrate has been used as a nutritional supplement in Europe in the form of FRUITFLOW ® Brand sales.

[0008] In addition, other studies have found that the water-soluble tomato concentrate has the effects of reducing hair loss, treating cerebral ischemia-reperfusion injury, and improving memory, but there are no reports on its effects on regulating biological rhythms. Summary of the invention

[0009] A first aspect of the present application provides use of a water-soluble tomato concentrate in preparing a composition having the function of regulating biological rhythm.

[0010] In some embodiments, regulating biological rhythm includes preventing and / or improving circadian rhythm disorders.

[0011] In some embodiments, the prevention and / or improvement of circadian rhythm disorders includes increasing circadian rhythm amplitude.

[0012] In some embodiments, the prevention and / or improvement of circadian rhythm disorders includes increasing the circadian rhythm amplitude by enhancing the expression of rhythm-related proteins, and the rhythm-related proteins include one or more of Per2, Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora.

[0013] In some embodiments, the prevention and / or improvement of circadian rhythm disorders includes preventing and / or improving sleep disorders.

[0014] In some embodiments, the prevention and / or improvement of sleep disorders includes one or more of shortening sleep latency, prolonging sleep duration, and alleviating anxiety or depression-like behaviors related to sleep.

[0015] In some embodiments, the prevention and / or improvement of sleep disorders includes improving sleep disorders associated with jet lag, shift work or age.

[0016] In some embodiments, the composition is a health food or a medicine.

[0017] In some of the embodiments, the composition further contains auxiliary materials or additives acceptable in health food or medicine.

[0018] In some embodiments, the dosage form of the health food or medicine is tablets, pills, granules, powders, capsules, liquid preparations or gels.

[0019] Studies have shown that water-soluble tomato concentrate can increase the expression of the core gene Per2 of the biological rhythm and several other core rhythm genes, including Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora, and can significantly increase the amplitude of the biological rhythm, prevent and / or improve sleep disorders. Therefore, it can play a good role in improving sleep quality or regulating biological rhythms, and can be used to prepare compositions that have the function of regulating biological rhythms or improving sleep quality, such as medicines or health foods. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The behavior trajectory of zebrafish in each group in the zebrafish behavior experiment in the embodiment (5min);

[0021] Figure 2 The moving distance statistics (mean ± sem) of each group of zebrafish in the zebrafish behavior experiment in the embodiment;

[0022] Figure 3 The effect of different concentrations of water-soluble tomato concentrate on the expression of the rhythmic core gene Per2 in the example;

[0023] Figure 4 The effects of different concentrations of water-soluble tomato concentrate on the biorhythm curve in the examples;

[0024] Figure 5 The figure shows the effects of different concentrations of water-soluble tomato concentrate on the expression of eight rhythmic genes (Per2, Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora) in the examples. DETAILED DESCRIPTION

[0025] The following is a further detailed description of the use of the water-soluble tomato concentrate of the present application in the preparation of a medicine or health food having the function of regulating biological rhythms in conjunction with specific examples. The present application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the present application more thoroughly and comprehensively understood.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application belongs. The terms used herein in the specification of this application are only for the purpose of describing specific embodiments and are not intended to limit this application.

[0027] The optional scope of the terms "and / or", "or / and", and "and / or" used in this article includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, said any and all combinations include any combination of any two related listed items, any more related listed items, or all related listed items.

[0028] As used herein, "one or more" refers to any one, any two, or any two or more of the listed items.

[0029] In this application, "the first aspect", "the second aspect", etc. are only used for descriptive purposes and cannot be understood as indicating or implying relative importance or quantity, nor can they be understood as implicitly indicating the importance or quantity of the indicated technical features. Moreover, "the first", "the second", etc. only serve the purpose of non-exhaustive enumeration and description, and it should be understood that they do not constitute a closed limitation on quantity.

[0030] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0031] In this application, when it comes to numerical ranges, unless otherwise specified, the above numerical ranges are deemed to be continuous and include the minimum and maximum values ​​of the range, as well as each value between such minimum and maximum values. Further, when a range refers to an integer, each integer between the minimum and maximum values ​​of the range is included. In addition, when multiple ranges are provided to describe features or characteristics, the ranges can be merged. In other words, unless otherwise specified, all ranges disclosed herein should be understood to include any and all subranges included therein.

[0032] The percentage contents involved in this application, unless otherwise specified, refer to mass percentage for solid-liquid mixing and solid-solid mixing, and refer to volume percentage for liquid-liquid mixing.

[0033] The percentage concentrations mentioned in this application, unless otherwise specified, refer to the final concentration, which refers to the percentage of the added component in the system after the addition of the component.

[0034] The temperature parameters in this application, unless otherwise specified, allow for both constant temperature treatment and treatment within a certain temperature range. The constant temperature treatment allows the temperature to fluctuate within the accuracy range of instrument control.

[0035] The room temperature in this application generally refers to 4°C~30°C, preferably 20±5°C.

[0036] It will be appreciated that in the art, "water-soluble tomato extract" and "water-soluble tomato concentrate" have the same meaning.

[0037] Sleep is mainly regulated by two key driving factors, biological rhythm and sleep-wake homeostasis. It is currently believed that some metabolic molecules including adenosine and intracellular biochemical processes such as protein phosphorylation mediate the increase in sleep pressure during wakefulness, and adenosine is considered to be an important source of our sleepiness. However, during the study, it was found that the simple application of adenosine did not improve sleep quality, while the application of water-soluble tomato concentrate was able to achieve a better effect of regulating biological rhythms and improving sleep quality.

[0038] Based on this, some examples of the present application provide the use of a water-soluble tomato concentrate in preparing a composition having the function of regulating biological rhythm.

[0039] Water-soluble tomato concentrate is an extract derived from tomatoes. It is mainly obtained by separating water-soluble components from tomatoes through physical methods (centrifugation, filtration, etc.), and then concentrating and desugaring to obtain water-soluble components. Its main characteristic components are nucleoside compounds, flavonoid compounds and phenolic acid compounds. At present, water-soluble tomato concentrate is managed as a common food in Europe, the United States and my country.

[0040] Water-soluble tomato concentrate (WSTC) is mainly composed of heat-stable water-soluble compounds derived from tomatoes, which are the main bioactive ingredients. The main bioactive ingredients in the water-soluble tomato concentrate may come from the pulp of tomato fruits and / or the juice around tomato fruit seeds, and then the solid insoluble components, fat-soluble components and water-soluble sugars from the above sources are further removed, and then concentrated and dried to obtain the water-soluble tomato concentrate. The water-soluble compounds in WSTC include nucleoside compounds, flavonoid compounds and phenolic acid compounds. The nucleoside compounds can be nucleoside compounds themselves or nucleotides formed by phosphorylation, and the nucleoside compounds may include at least one of uridine, cytidine, adenosine and guanosine; the nucleoside compounds are further preferably at least one of adenosine, adenosine-3'-monophosphate and adenosine-5'-monophosphate. The flavonoid compound may be a flavonoid compound itself or a glycosylation product thereof, and the flavonoid compound may be selected from at least one of myricetin, luteolin, kaempferol, and naringenin; the flavonoid compound is further preferably at least one of quercetin-3-O-glucoside, naringin, and rutin. The phenolic acid compound may be a phenolic acid compound itself or a glycosylation product thereof, wherein the phenolic acid compound may be cinnamic acid or a derivative thereof, such as at least one of p-coumaric acid, caffeic acid, coumaric acid, ferulic acid, and sinapic acid; wherein the phenolic acid compound may be benzoic acid or a derivative thereof, such as at least one of p-hydroxybenzoic acid, chlorogenic acid, gallic acid, vanillic acid, and syringic acid. It is understood that the bioactive components in WSTC are not limited to one or more of the above-mentioned types of substances, and may also contain other substance components.

[0041] In addition, the water-soluble tomato concentrate of the present application is lycopene-free or substantially lycopene-free. The water-soluble tomato concentrate is substantially free of water-insoluble particulate matter.

[0042] Additionally, the water-soluble tomato concentrate can be formulated with food or pharmaceutically acceptable excipients to improve its commercial attributes, including improved delivery, shelf life and taste.

[0043] The water-soluble tomato concentrate described in the present application can be purchased from Provis Natural Products Co., Ltd. or its authorized sales agency. WO 99 / 55350, WO 2010 / 049707 and CN102271697 also disclose methods for preparing the water-soluble tomato concentrate that can be used in the present application. Therefore, the water-soluble tomato concentrate used in the present application can also be prepared by itself according to WO 99 / 55350, WO 2010 / 049707 or CN102271697. If prepared by itself according to the methods described in WO 99 / 55350, WO 2010 / 049707 or CN102271697, it should be ensured that the ingredients of the prepared water-soluble tomato concentrate meet the above requirements. For example, it can be prepared according to the method of CN102271697. Figure 2 and Figure 4 The process described is a preferred method for producing a water-soluble tomato concentrate.

[0044] Without limitation, the water-soluble tomato concentrate described in the present application can be prepared by the following method, and the effect of regulating biorhythm of the present application can be achieved. The preparation method of the water-soluble tomato concentrate comprises the following steps:

[0045] (a) preparing an initial mixture of tomato homogenate;

[0046] (b) separating the water-soluble component from the initial mixture, the separation temperature being no higher than 60° C.;

[0047] (c) filtering and concentrating the water-soluble components, wherein the concentration temperature is not higher than 60°C.

[0048] In some examples, the temperature of the initial mixture in step (a) is not higher than 35°C.

[0049] In some examples, the pH of the initial mixture in step (a) does not exceed 5.5.

[0050] In some examples, the browning index of the initial mixture does not exceed 0.4 AU at 4% solids, wherein the browning index is defined as the absorbance of the soluble fraction at 420 nm.

[0051] In some examples, in step (b), water-insoluble solids with a particle size greater than 500 μm are separated and removed from mixture A to obtain a water-soluble component.

[0052] In some examples, the separation in step (b) includes at least one of centrifugal separation and natural sedimentation separation, and the water-soluble component is the supernatant obtained after separation.

[0053] In some examples, in step (c), the filtration is performed using a filter membrane. Without limitation, the pore size of the filter membrane used for filtration is no greater than 1 μm, specifically 0.2 μm.

[0054] In some of the examples, the concentration in step (c) can be carried out by membrane filtration concentration, low temperature evaporation concentration, freeze drying concentration or spray drying concentration.

[0055] In some examples, in the step (c), before filtering, the step further includes removing free sugars from the water-soluble components.

[0056] In some examples, regulating biological rhythms includes preventing and / or ameliorating circadian rhythm disorders.

[0057] In some examples, the prevention and / or improvement of circadian rhythm disorders includes increasing circadian rhythm amplitude.

[0058] In some of these examples, the prevention and / or improvement of circadian rhythm disorders includes increasing the circadian rhythm amplitude by enhancing the expression of rhythm-related proteins, and the rhythm-related proteins include one or more of Per2, Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora.

[0059] In some examples, the prevention and / or improvement of circadian rhythm disorders includes preventing and / or improving sleep disorders.

[0060] It is understandable that the causal relationship between circadian rhythm disorder and sleep disorder is bidirectional. The reduction of circadian rhythm amplitude will lead to sleep disorder, while irregular sleep time or frequent changes in circadian sleep time will further reduce the amplitude of circadian rhythm, further aggravate circadian rhythm disorder, and then make sleep disorder exist for a long time. Water-soluble tomato concentrate can prevent and / or improve circadian rhythm disorder and sleep disorder at the same time, and achieve good effects of improving sleep quality and regulating biological rhythm.

[0061] In some of these examples, the prevention and / or improvement of sleep disorders includes one or more of shortening sleep latency, prolonging sleep duration, and alleviating anxiety or depression-like behaviors related to sleep.

[0062] In some examples, the preventing and / or improving sleep disorders includes improving sleep disorders associated with jet lag, shift work, or age.

[0063] In some examples, the composition is a health food or a medicine.

[0064] In some of the examples, the composition further contains excipients or additives acceptable in health food or medicine.

[0065] In some of these examples, the health food or medicine is in the form of tablets, pills, granules, powders, capsules, liquid preparations or gels.

[0066] Without limitation, the drug may also include one or more of melatonin, γ-aminobutyric acid and NMN.

[0067] Without limitation, the health food may also include one or more of passion fruit extract, lemon balm extract, valerian extract, tangerine peel extract, citrus extract, spearmint extract, rosemary extract, astragalus extract, green tea extract, Bacopa monnieri extract, cinnamon extract, hops extract, Ganoderma lucidum extract, Magnolia officinalis extract, licorice extract, Cornus officinalis extract, Citrus aurantium extract, black cohosh extract, Pueraria root extract, Ziziphus jujuba seed extract, Gastrodia elata extract, Polygonum cuspidatum extract, Cordyceps militaris extract, and St. John's wort extract.

[0068] For experimental parameters not specified in the following specific embodiments, reference is made to the instructions given in the present application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to experimental conditions recommended by manufacturers.

[0069] The raw materials and reagents involved in the following specific examples can be obtained from commercial sources, or can be prepared by those skilled in the art according to known methods.

[0070] The water-soluble tomato concentrate used in the examples of this application was purchased from Provis Natural Products Co., Ltd., which is FRUITFLOW ® Brand sales.

[0071] Example

[0072] This example provides research on the efficacy of water-soluble tomato concentrate in regulating biological rhythm and promoting sleep.

[0073] 1. Experimental cell lines and experimental animals

[0074] The mouse MEF cells used in the experiment were from the Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences.

[0075] Zebrafish were raised in 28°C fish water (water quality: 200 mg instant sea salt was added to 1 L of reverse osmosis water, conductivity was 450-550 μS / cm, pH was 6.5-8.5, and hardness was 50-100 mg / L CaCO3), provided by the Zebrafish Center of Guangzhou Shanhai Biotechnology Co., Ltd. Wild-type AB strain zebrafish were bred in natural pairs, and zebrafish aged 5 days after fertilization (5 dpf) were selected for efficacy research.

[0076] 2. Instruments, consumables and reagents

[0077] Dissecting microscope (SZX7, OLYMPUS, Japan); CCD camera (VertA1, Shanghai Tusen Vision Technology Co., Ltd., China); behavior analyzer (zebra Lab 3.11, ViewPoint, France); precision electronic balance (CP214, OHAUS, USA); 6-well plate (Nest Biotech, China); 96-well plate (Nest Biotech, China).

[0078] 3. Detection method

[0079] 3.1. Zebrafish model to evaluate the sleep-promoting effects of test substances

[0080] 5 dpf wild-type AB strain zebrafish were randomly selected in a 96-well plate, with one fish per well. Water-soluble tomato concentrate (1 mg / mL, containing 9.4 μg / mg adenosine) and an equal amount of adenosine (9.4 μg / mL) were administered, and a blank control group was set up at the same time. Each group was set up with 10-36 wells, and the volume of each well was 100 μL. After 24 h of treatment at 28 ℃, the 96-well plate was placed in a zebrafish behavior analyzer, and the light and dark conditions were set to 14 hours of light and 10 hours of darkness. The behavior trajectory of zebrafish was continuously recorded for 48 hours under the zebrafish behavior analyzer. The data captured by the zebrafish behavior analyzer were first analyzed using the analysis software provided by the system (Ethovision10.0 software, Noldus Information Technology). The data were obtained using a 10-minute time interval, and the movement distance was used as the quantitative basis. The data of 10-36 zebrafish fry (N=10-36) for each drug were obtained at a total of 48 hours with a 10-minute time interval. The generated data were expressed as mean ± standard deviation. The sleep-promoting effect of the test substance was determined based on the total movement distance of the zebrafish under the treatment conditions of each group.

[0081] 3.1. Evaluation of the regulatory effects of water-soluble tomato concentrate on biological rhythms using Per2-labeled cell lines

[0082] 1) The pGL3-Per2:Luc plasmid was transfected into MEF cells by Lipofectamine 3000. On the second day, the cells were digested and the cell suspension was evenly spread in a 96-well plate at a concentration of 5000 / well and cultured in a cell culture incubator. After one day of culture, six concentration gradient culture solutions of water-soluble tomato concentrate (0, 0.2, 1, 5, 25, 100 μg / mL) were prepared. The culture solution in the 96-well plate was removed, and 100 μL of the culture solution with water-soluble tomato concentrate was added and placed in the incubator. After 24 hours of culture, the culture solution in the 96-well plate was removed and 100 μL of ONE-Glo (Promega) was added. The luciferase luminescence detection was performed by microplate reader to analyze the effect of different concentrations of the test substance on the expression of Per2.

[0083] 2) The pGL3-Per2:Luc plasmid was transfected into MEF cells by Lipofectamine 3000. On the second day, the cells were digested and counted, and the cell suspension was evenly spread in a 35mm plate at a concentration of 200,000 / well and cultured in a cell culture incubator. On the second day, the cells were treated with 100nM dexamethasone for 1 hour to synchronize the cells, and then replaced with different concentrations of culture medium containing water-soluble tomato concentrate (0, 5, 25, 100μg / mL). Then, the 32-channel LumiCycle fluorescence recording system was used to record and analyze the effects of the samples on the biological rhythm period and amplitude in real time.

[0084] 3) The pGL3-Per2:Luc plasmid was transfected into primary neurons by Lipofectamine 3000. The cells were digested and counted on the second day. The cell suspension was evenly spread in a 35 mm plate at a concentration of 200,000 / well and cultured in a cell culture incubator. On the second day, the cells were treated with 100 nM dexamethasone for 1 hour to synchronize the cells, and then the culture medium was changed to a medium containing water-soluble tomato concentrate (25 μg / mL). After 24 hours of culture, the total RNA of the cells was extracted, and the effect of water-soluble tomato concentrate on the expression of 8 core rhythmic genes (Bmal1, Clock, Per1, Per2, Cry1, Cry2, Rora and Rev-Erba) was detected by q-PCR.

[0085] 4. Judgment criteria

[0086] In the zebrafish behavioral experiment, the total movement distance of the sample group was significantly lower than that of the blank control group, and the difference was statistically significant at p < 0.05, indicating that the sample has the effect of promoting sleep.

[0087] In the Per2 expression experiment, when the sample group was compared with the blank group, the difference was statistically significant when p < 0.05. If the Per2 expression level in the sample group was statistically different from that in the blank group, it indicated that the sample had the effect of regulating biological rhythms.

[0088] In the real-time expression analysis of Per2, the influence of the sample on the rhythm in terms of amplitude, phase and period is determined based on the expression curve graph, where the difference between the peak and the trough represents the amplitude, the time span between two peaks or troughs represents the period, and the difference in the time of occurrence of the peak and trough represents the phase.

[0089] In the analysis of the expression of rhythmic core genes, when the sample group was compared with the blank group, the difference was statistically significant when p < 0.05. If the expression of rhythmic genes in the sample group was statistically different from that in the blank group, it indicated that the sample had the effect of regulating biological rhythms.

[0090] 5. Test results

[0091] In zebrafish behavioral experiments, the behavioral trajectories (see Figure 1 ) and statistical movement distance (see Figure 2 , Table 1), it can be seen that the total movement distance of the water-soluble tomato concentrate is lower than that of the blank control group, indicating that the water-soluble tomato concentrate has the effect of promoting sleep; and the same amount of adenosine contained in the water-soluble tomato concentrate cannot reduce the movement distance of zebrafish, and does not have the effect of promoting sleep.

[0092] Table 1

[0093]

[0094] In cell experiments, water-soluble tomato concentrate significantly increased the expression of the rhythm core gene Per2 compared with the blank control group (see Figure 3 ), and p < 0.05 was statistically significant (Table 2); and according to the real-time monitoring of Per2 gene expression, the luciferase activity of Per2 gene fusion was used to reflect the intracellular biological rhythm curve. Figure 4 From the biorhythm curve shown, it can be observed that the water-soluble tomato concentrate significantly increased the rhythm amplitude, and the peak was significantly higher than that of the control group.

[0095] Water-soluble tomato concentrate also significantly enhanced the expression of several other rhythmic core genes, including Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora, with p<0.05 being statistically significant (see Figure 5 ); indicating that water-soluble tomato concentrate has the effect of regulating biological rhythms by enhancing the amplitude.

[0096] Table 2

[0097]

[0098] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0099] The above-described embodiments only express several implementation methods of the present application, which is convenient for understanding the technical solution of the present application in detail, but it cannot be understood as limiting the scope of protection of the patent application. It should be pointed out that for ordinary technicians in this field, without departing from the concept of the present application, several modifications and improvements can be made, which all belong to the scope of protection of the present application. It should be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent of this application shall be based on the content of the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. Use of water-soluble tomato concentrate in preparing a composition for regulating biological rhythm.

2. The use according to claim 1, characterized in that: The regulating biological rhythm includes preventing and / or improving circadian rhythm disorders.

3. The use according to claim 2, characterized in that: The prevention and / or improvement of circadian rhythm disorders includes increasing the circadian rhythm amplitude.

4. The use according to claim 3, characterized in that: The prevention and / or improvement of circadian rhythm disorders includes increasing the circadian rhythm amplitude by enhancing the expression of rhythm-related proteins, and the rhythm-related proteins include one or more of Per2, Bmal1, Clock1, Cry1, Cry2, Per1, Rev-erba and Rora.

5. The use according to claim 2, characterized in that: The prevention and / or improvement of circadian rhythm disorders includes the prevention and / or improvement of sleep disorders.

6. The use according to claim 5, characterized in that: The prevention and / or improvement of sleep disorders includes one or more of shortening sleep latency, prolonging sleep duration, and alleviating anxiety or depression-like behaviors associated with sleep.

7. The use according to claim 5, characterized in that: The prevention and / or improvement of sleep disorders includes improving sleep disorders associated with jet lag, shift work or age.

8. The use according to claim 1, characterized in that: The composition is a health food or a medicine.

9. The use according to claim 8, characterized in that: The composition also contains auxiliary materials or additives acceptable in health food or medicine.

10. The use according to claim 8, characterized in that: The dosage form of the health food or medicine is tablets, pills, granules, powders, capsules, liquid preparations or gels.

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