8-OHdG concentration reduction accelerator or malondialdehyde (MDA) concentration reduction accelerator or ZIP4 concentration increase accelerator or serum zinc concentration increase accelerator for jejunum

Abstract

[Problem] The purpose of the present invention is to provide a jejunum MDA concentration decrease-promoting agent, 8-OHdG concentration decrease-promoting agent, ZIP4 concentration increase-promoting agent, or serum zinc concentration increase-promoting agent so as to be able to promote a jejunum MDA concentration decrease, a jejunum 8-OHdG concentration decrease, a jejunum ZIP4 concentration increase, and a jejunum serum zinc concentration increase, and to provide a jejunum MDA concentration decrease-promoting agent, a jejunum 8-OHdG concentration decrease-promoting agent, a jejunum ZIP4 concentration increase-promoting agent, and a jejunum serum zinc concentration increase-promoting agent. The oxidative stress state is improved. [Solution] The present invention has, as an active ingredient, 3, 5-dihydroxy-4-methoxybenzyl alcohol (3, 5-dihydroxy-4-methoxybenzyl alcohol), and has an 8-OHdG concentration reduction promoting effect that reduces the 8-OHdG concentration in the jejunum.

Description

Technical Field

[0001] The present invention relates to an agent for promoting a decrease in 8-OHdG concentration in the jejunum, an agent for promoting a decrease in MDA concentration, an agent for promoting an increase in ZIP4 concentration, and an agent for promoting an increase in serum zinc concentration. Background Art

[0002] The inventors have confirmed that when an oyster mollusk extract fraction (eg, oyster meat is soaked in an extract solution and fractions of various components are extracted from the oyster meat) is administered to type 2 diabetic patients for, for example, 12 weeks, the serum zinc concentration is significantly increased.

[0003] However, a mixed fraction of a precipitate fraction and a supernatant fraction of an oyster soft body extract (for example, a precipitate fraction obtained by soaking oyster meat in an extracting solution, stirring the extracting solution to extract various components from the oyster meat, and then precipitating and a supernatant fraction of the supernatant) does not contain zinc to such an extent that the zinc concentration in serum is significantly increased, and therefore the mechanism of this result is puzzling.

[0004] Therefore, the zinc absorption mechanism in the intestine was taken as the focus of verification, and the effect of oyster soft body extract fraction on the zinc absorption mechanism in the intestine was explored.

[0005] Zinc is absorbed in the duodenum and jejunum, but mainly in the jejunum. Studies have shown that zinc transporter ZIP4 in the intestine plays an important role in zinc absorption.

[0006] There have been reports that the expression of ZIP4 in the intestine increases under zinc deficiency. However, the present inventors observed an increase in the concentration of ZIP4 in the duodenum of rats fed a low-zinc diet, and were able to obtain the same result as the above-mentioned previous reports that "the expression of ZIP4 in the intestine increases under zinc deficiency".

[0007] However, a decrease in ZIP4 concentration was observed in the jejunum of rats fed a low-zinc diet. It is believed that the change in ZIP4 expression in rats fed a zinc-deficient diet is not only due to the difference in the degree of zinc deficiency, but also may be caused by the difference in intestinal location.

[0008] On the one hand, an intriguing report showed that H2O2 concentrations increased dramatically in roots and shoots of maize lines sensitive to zinc deficiency, without increasing the expression of the ZIP4 transporter gene.

[0009] On the other hand, it was reported that the expression of ZIP4 transporter gene was increased in roots and shoots of maize lines tolerant to cultivation in soils with low zinc content, and that antioxidant defense affected the increase in the expression of ZIP4 transporter gene.

[0010] That is, it was confirmed that the expression of the ZIP4 transporter gene in maize roots is affected by the oxidative state.

[0011] In the present invention, it is predicted that the decrease in superoxide dismutase (SOD) activity induced by the decrease in zinc concentration in the jejunum due to low zinc diet feeding will lead to an increase in reactive oxygen species in the jejunum of rats and phenomena related thereto. That is, it is predicted that there will be a situation in which an oxidative stress state shown by an increase in MDA concentration in the jejunum, an increase in 8-OHdG, a decrease in ZIP4 concentration, and a decrease in serum Zn concentration will occur.

[0012] Furthermore, the present inventors verified the following with respect to the above-mentioned oxidative stress state, namely, by feeding each fraction of the oyster mollusk extract fraction having an antioxidant effect, namely, a sediment fraction, a supernatant fraction, and a component extracted from the oyster mollusk, particularly 3,5-dihydroxy-4-methoxybenzyl alcohol, and further synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) to the above-mentioned rats, to verify whether the above-mentioned oxidative stress state would be changed in any way. In other words, by feeding 3,5-dihydroxy-4-methoxybenzyl alcohol, it was verified whether the decrease in the MDA concentration in the jejunum, the decrease in the 8-OHdG concentration, the increase in the ZIP4 concentration, and the increase in the serum zinc concentration could be promoted by improving the oxidative stress state.

[0013] Prior art literature

[0014] Patent Literature

[0015] Patent Document 1: Japanese Patent Application Publication No. 2016-042825 Summary of the invention

[0016] Problem that the invention aims to solve

[0017] The present inventors aim to provide a proven MDA concentration reduction promoter, 8-OHdG concentration reduction promoter, ZIP4 concentration increase promoter, and serum zinc concentration increase promoter for the jejunum, which can promote the reduction of MDA concentration, the reduction of 8-OHdG concentration, or the increase of ZIP4 concentration and the increase of serum zinc concentration in the jejunum, and improve the oxidative stress state. The above-mentioned verification is to verify the oxidative stress state by feeding each fraction of the oyster mollusk extract fraction having an antioxidant effect, that is, the components extracted from the sediment fraction and the supernatant fraction, especially 3,5-dihydroxy-4-methoxybenzyl alcohol, and then synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) to rats.

[0018] Solutions for solving problems

[0019] The present invention is characterized in that 3,5-dihydroxy-4-methoxybenzyl alcohol is used as an active ingredient and has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum.

[0020] or,

[0021] The invention is characterized in that it contains 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat as an active ingredient and has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum.

[0022] or,

[0023] The invention is characterized in that the extract obtained from oyster meat is stirred and the supernatant extract is taken out as an active ingredient, and the extract has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum,

[0024] or,

[0025] The invention is characterized in that the precipitate fraction obtained by stirring an extract obtained from oyster meat and then precipitating the extract is used as an active ingredient, and has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum.

[0026] or,

[0027] The invention is characterized in that it contains synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum.

[0028] or,

[0029] The invention is characterized in that it contains 3,5-dihydroxy-4-methoxybenzylalcohol as an active ingredient and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

[0030] or,

[0031] The invention is characterized in that it contains 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat as an active ingredient and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

[0032] or,

[0033] The invention is characterized in that the extract obtained from oyster meat is stirred and the supernatant fraction obtained after taking out the supernatant extract is used as an effective ingredient, and the extract has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

[0034] or,

[0035] The invention is characterized in that the extract obtained from oyster meat is stirred and precipitated with a precipitate fraction as an active ingredient, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

[0036] or,

[0037] The invention is characterized in that it contains synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

[0038] or,

[0039] The invention is characterized in that it contains 3,5-dihydroxy-4-methoxybenzylalcohol as an active ingredient and has a ZIP4 concentration-increasing promoting effect of increasing the ZIP4 concentration in the jejunum.

[0040] or,

[0041] The invention is characterized in that the active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

[0042] or,

[0043] The invention is characterized in that the extract obtained from oyster meat is stirred and the supernatant fraction obtained after taking out the supernatant extract is used as an active ingredient, and the extract has a ZIP4 concentration-increasing promoting effect of increasing the ZIP4 concentration in the jejunum,

[0044] or,

[0045] The invention is characterized in that the extract obtained from oyster meat is stirred and precipitated with a precipitate fraction as an active ingredient, and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

[0046] or,

[0047] The invention is characterized in that it contains synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

[0048] or,

[0049] The invention is characterized in that 3,5-dihydroxy-4-methoxybenzylalcohol is used as an active ingredient, and has the effect of inducing an increase in the zinc concentration in serum.

[0050] or,

[0051] The invention is characterized in that the active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, which has the effect of inducing an increase in the zinc concentration in serum.

[0052] or,

[0053] The invention is characterized in that it uses synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and has the effect of inducing an increase in the zinc concentration in serum.

[0054] or,

[0055] The invention is characterized in that the supernatant fraction containing DHMBA obtained by stirring the extract extracted from oyster meat and taking out the supernatant extract is used as an active ingredient, and has the effect of inducing an increase in the zinc concentration in serum.

[0056] or,

[0057] The invention is characterized in that a precipitate fraction containing DHMBA obtained by stirring an extract obtained from oyster meat and precipitating the precipitate fraction is used as an effective ingredient, and has an effect of inducing an increase in the zinc concentration in serum.

[0058] Effects of the Invention

[0059] According to the present invention, the proven excellent effect of improving the oxidative stress state, promoting the decrease of MDA concentration in the jejunum, the decrease of 8-OHdG concentration or the increase of ZIP4 concentration and the increase of serum zinc concentration is produced, and the above-mentioned verification is carried out by feeding the components extracted from each fraction of the oyster mollusk extract fraction having an antioxidant effect, namely, the sediment fraction and the supernatant fraction, especially 3,5-dihydroxy-4-methoxybenzylalcohol, and then synthetic 3,5-dihydroxy-4-methoxybenzylalcohol (DHMBA) to rats. BRIEF DESCRIPTION OF THE DRAWINGS

[0060] FIG. 1 is a graph illustrating the SOD concentration in the jejunum of subjects on a standard diet and a low-zinc diet.

[0061] FIG. 2 is a graph illustrating the 8-OHdG concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0062] FIG. 3 is a graph illustrating the 8-OHdG concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet+precipitate fraction groups.

[0063] FIG. 4 is a graph illustrating the 8-OHdG concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0064] FIG. 5 is a graph illustrating the MDA concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0065] FIG. 6 is a graph illustrating the ZIP4 concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0066] FIG. 7 is a graph illustrating the ZIP4 concentration in the jejunum of the standard diet, low zinc diet, and low zinc diet+precipitate fraction groups.

[0067] FIG. 8 is a graph illustrating the concentration of ZIP4 in the jejunum of the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0068] FIG. 9 is an explanatory diagram illustrating the correlation between the MDA concentration and the ZIP concentration in the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0069] FIG. 10 is an explanatory diagram illustrating the correlation between the MDA concentration and the ZIP concentration in the standard diet, low zinc diet, and low zinc diet+precipitate fraction groups.

[0070] FIG. 11 is an explanatory graph showing the correlation between the MDA concentration and the ZIP concentration in the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0071] FIG. 12 is an explanatory graph showing serum zinc concentrations in the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0072] FIG. 13 is an explanatory graph showing the correlation between the jejunal ZIP concentration and the serum zinc concentration in the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0073] FIG. 14 is an explanatory graph showing the correlation between the ZIP concentration in the jejunum and the zinc concentration in the serum in the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0074] FIG. 15 is an explanatory graph showing the correlation between the jejunum ZIP concentration and the serum zinc concentration in the standard diet, low zinc diet, and low zinc diet+precipitate fraction groups.

[0075] FIG. 16 is an explanatory graph showing the correlation between the jejunal MDA concentration and the serum zinc concentration in the standard diet, low zinc diet, and low zinc diet + synthetic DHMBA groups.

[0076] FIG. 17 is an explanatory graph showing the correlation between the MDA concentration in the jejunum and the zinc concentration in the serum in the standard diet, low zinc diet, and low zinc diet+supernatant fraction groups.

[0077] FIG. 18 is an explanatory graph showing the correlation between the MDA concentration in the jejunum and the zinc concentration in the serum in the standard diet, low zinc diet, and low zinc diet+precipitate fraction groups. DETAILED DESCRIPTION

[0078] (Example)

[0079] The present invention uses 3,5-dihydroxy-4-methoxybenzylalcohol as an active ingredient to manufacture a promoter, and provides the above-mentioned various promoters after manufacture. The promoter promotes the improvement of the oxidative stress state in the jejunum, promotes the reduction of MDA concentration, the reduction of 8-OHdG concentration, the increase of ZIP4 concentration and the increase of serum zinc concentration.

[0080] The accelerator is produced by soaking oyster meat in an extract solution, and using 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from the oyster meat soaked in the extract solution as an active ingredient. 3,5-dihydroxy-4-methoxybenzyl alcohol may also be a synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol.

[0081] Furthermore, when the above-mentioned promoter was produced, an animal experiment was conducted to confirm whether it could improve the oxidative stress state, promote the decrease of MDA concentration, decrease of 8-OHdG concentration, increase of ZIP4 concentration, and increase of serum zinc concentration.

[0082] That is, when the specified rats are fed a low-zinc diet composed of specified ingredients, the activity of superoxide dismutase (SOD) will decrease, and the reactive oxygen species in the jejunum of the rats will increase, leading to an increase in the MDA concentration in the jejunum, an increase in the 8-OHdG concentration, a decrease in the ZIP4 concentration, and a decrease in the serum zinc concentration, etc.

[0083] On the other hand, for example, oyster meat is soaked in an extract, 3,5-dihydroxy-4-methoxybenzyl alcohol that flows out from the soaked oyster meat into the extract is taken out, and added to a low-zinc diet as a rat diet.

[0084] Furthermore, it was confirmed that the amount of 3,5-dihydroxy-4-methoxybenzyl alcohol in the oyster meat flowing out from the above-mentioned extract was different in the precipitate fraction obtained by stirring the above-mentioned extract and precipitating it after a predetermined period of time and the supernatant fraction of the supernatant.

[0085] Therefore, in view of the above situation, if 3,5-dihydroxy-4-methoxybenzyl alcohol (3,5-dihydroxy-4-methoxybenzyl alcohol) extracted from oyster meat and synthesized 3,5-dihydroxy-4-methoxybenzyl alcohol (hereinafter also referred to as DHMBA) with antioxidant effects are fed to the above rats, it can be verified and understood how the concentrations of MDA, 8-OHdG, ZIP4 in the rat jejunum and serum Zn change.

[0086] Through this verification, it was confirmed that each of the above-mentioned promoters has excellent efficacy during production, and that promoters that can effectively cope with oxidative stress can be produced and provided.

[0087] Here, an overview of animal experiments is described.

[0088] (Experimental Method)

[0089] As experimental animals, Slc / SD male rats (4 weeks old) were used.

[0090] (Grouping and baiting)

[0091] The rats were divided into groups as follows and fed with the following food.

[0092] Where n represents the number of rats.

[0093] Standard diet group (n=6): free intake of standard diet

[0094] (Zinc concentration in standard diet: 34.1 mg zinc / kg diet)

[0095] Again, the zinc concentration in the standard diet was assumed to be 20 mg zinc / kg diet to ~55 mg zinc / kg diet).

[0096] (Again, the DHMBA concentration in a standard diet is zero).

[0097] Low zinc diet group (n=6): free intake of low zinc diet

[0098] (Zinc concentration in low zinc diet: 3.9 mg zinc / kg diet).

[0099] Again, the zinc concentration in the low zinc diet was assumed to be 2.5 mg zinc / kg diet to 10 mg zinc / kg diet).

[0100] (Also, the DHMBA concentration in a low-zinc diet is zero).

[0101] Low zinc diet + supernatant fraction group (n=6): low zinc diet + oyster extract supernatant fraction

[0102] The zinc concentration of the low zinc diet was as described above.

[0103] The oyster extract supernatant fraction refers to a fraction obtained by, for example, soaking oyster meat in an extracting solution, stirring the extracting solution to extract various components from the oyster meat, and then taking out a supernatant extract on the surface side.

[0104] The DHMBA concentration of the supernatant fraction was 0.96 μg / rat BW100 g.

[0105] Furthermore, it is assumed that the DHMBA concentration of the supernatant fraction is 0.68 μg / rat B.W.100 g to 2.38 μg / rat B.W.100 g.

[0106] Low zinc diet + precipitate fraction group (n=6): low zinc diet + oyster extract precipitate fraction The zinc concentration of the low zinc diet was as described above.

[0107] The oyster extract precipitate fraction is, for example, a fraction obtained by soaking oyster meat in an extract solution, stirring the extract solution to extract various components from the oyster meat, and then taking out the precipitated extract. In addition, although the precipitate fraction was administered orally by forced oral administration, the zinc concentration in the fraction was 0.894 μg / day, which is considered to be a negligible zinc content.

[0108] The DHMBA concentration in the precipitate fraction was 0.38 μg / rat BW100g.

[0109] Furthermore, it is assumed that the DHMBA concentration of the precipitate fraction is 0.1 μg / rat BW100g to 0.5 μg / rat BW100g).

[0110] Low zinc diet + synthetic DHMBA group (n = 6): Low zinc diet + synthetic DHMBA

[0111] The zinc concentration of the low zinc diet was as described above, zinc concentration: 3.9 mg zinc / kg diet.

[0112] Synthetic DHMBA refers to DHMBA that is not extracted from oyster meat but is produced by chemical synthesis. The concentration of this DHMBA is 7.9 μg / rat BW100g.

[0113] In addition, it is assumed that the DHMBA concentration of the synthetic DHMBA is in the range of 5 mg / rat BW100 g to 15 mg / rat BW100 g according to the state of production.

[0114] (Test Schedule)

[0115] [1] Preparatory feeding period (7 days)

[0116] The test animals were acclimated by individual housing (n=1 / cage) from the day before the start of the main breeding period. The animals were fed a standard diet during the preparatory breeding period, and the body weight on the last day of the preparatory breeding was considered when grouping.

[0117] [2] Main feeding period (7 days)

[0118] From the start day of main feeding, the standard diet group was fed with a standard diet, and the low zinc diet group, low zinc diet + precipitate fraction group, low zinc diet + supernatant fraction group, and low zinc diet + synthetic DHMBA group were fed with a low zinc diet in a free intake manner. On the 5th and 6th days, the standard diet group and the low zinc diet group were orally fed with a 0.5% methylcellulose solution, the low zinc diet + precipitate fraction group was orally fed with an oyster extract supernatant fraction, the low zinc diet + precipitate fraction group was orally fed with an oyster extract precipitate fraction, and the low zinc diet + synthetic DHMBA group was orally fed with synthetic DHMBA. The feeding amount of the test subjects was 0.5 mL / 100 g BW. In addition, the test subjects were dissected 24 hours after feeding on the 6th day to remove the organs.

[0119] (Measurement Items)

[0120] The concentrations of SOD, MDA, 8-OHdG, ZIP4 in the jejunum and serum zinc were measured.

[0121] About SOD concentration

[0122] The so-called SOD (superoxide dismutase) is an enzyme that has the ability to remove reactive oxygen species. SOD exists in large quantities in the mitochondria within cells and has the function of protecting the body from oxidative stress caused by reactive oxygen species.

[0123] SOD is a catalytic reaction 2·O2 - +2H + →H2O2+O2 enzyme, which can convert superoxide into hydrogen peroxide and oxygen. The existence of SOD shows that it is very important for organisms to remove superoxide as quickly as possible, although this reaction would have been very fast without the enzyme. CuZn-SOD exists in the cytoplasm of eukaryotic organisms, and its active center contains copper and zinc.

[0124] Therefore, when the SOD (superoxide dismutase) concentration decreases, the oxidative stress state will be aggravated.

[0125] About MDA concentration

[0126] MDA is malondialdehyde. MDA is one of the decomposition products of lipid peroxidation and is used as a major marker of lipid peroxidation. It can be used as an indicator of lipid peroxidation in cell and tissue samples to verify the state of oxidative stress. An increase in MDA concentration indicates an increase in the state of oxidative stress.

[0127] MDA is produced by hydroxyl radicals (·OH) and the like. When unsaturated fatty acids are oxidized by hydroxyl radicals (·OH) and the like, they become lipid peroxidation decomposition products, and then the final product becomes MDA. If the concentration of hydroxyl radicals (·OH) and the like in the organs is high, the MDA concentration will increase. A decrease in the MDA concentration means a decrease in ·OH.

[0128] About 8-OHdG concentration

[0129] 8-OHdG is a substance in which guanine base is oxidized to 8-hydroxydeoxyguanosine (8-OHdG). DNA is composed of four bases: adenine, guanine, cytosine, and thymine. It is well known that DNA can be damaged by oxidation due to reactive oxygen species, and guanine bases can be oxidized to 8-OHdG. This 8-OHdG is cut off from the main body of the gene during the repair process of gene DNA and excreted into the urine through the blood. In addition, 8-OHdG is a relatively stable substance that is not metabolized or decomposed in the body, but is rapidly excreted from the urine. Therefore, it is used as an excellent biomarker that can sensitively reflect biological damage caused by reactive oxygen species.

[0130] Among the four DNA bases, dG has the lowest redox potential and is therefore easily oxidized by reactive oxygen species.

[0131] Therefore, 8-OHdG, as the main oxidation product of dG, can sensitively reflect the impact of reactive oxygen species on organisms. The increase in 8-0HdG concentration indicates an aggravated oxidative stress state.

[0132] Concentration of ZIP4

[0133] Zinc transporters have the function of maintaining zinc balance in the body. In the zinc absorption mechanism of the digestive tract, the zinc transporter ZIP4 (ZIP4: ZRT, IRT-like protein 4) plays a role.

[0134] ZIP4 is a transmembrane protein that transports zinc from the jejunal lumen to jejunal enterocytes.

[0135] Serum zinc concentration

[0136] Zinc is an essential mineral for the human body. Its content in the body is second only to iron. It is found in large quantities in bones, muscles, skin, hair, liver, taste buds and testicles. The role of zinc in the body is essential for the activity of more than 300 enzymes. Zinc deficiency can lead to a variety of symptoms, including abnormal taste, dermatitis, hair loss, anemia, stomatitis, diarrhea, male sexual dysfunction, susceptibility to infection (decreased immunity) and osteoporosis. In addition, many patients with cirrhosis, diabetes, chronic inflammatory bowel disease and chronic kidney disease have been found to have zinc deficiency.

[0137] (Results and Investigation)

[0138] As shown in Figure 1, the SOD concentration in the jejunum of the low-zinc diet group was 3.07±0.42U / mg, which was significantly lower than that of the standard diet group (5.85±0.61U / mg). This confirms that the intake of a low-zinc diet leads to a decrease in SOD concentration. If the SOD (superoxide dismutase) concentration decreases, the oxidative stress state will be aggravated.

[0139] Next, as shown in Figure 2, the 8-OHdG concentration in the jejunum of the low zinc diet + supernatant fraction group was 7.23 ± 0.64, which was significantly lower than the 8-OHdG concentration of the low zinc diet group (9.31 ± 0.29). In addition, despite the intake of the low zinc diet, there was no significant difference in 8-OHdG concentration between the standard diet and the low zinc diet, and the 8-OHdG concentration dropped to the same level as the standard diet.

[0140] Therefore, this promoted the decrease in 8-OHdG concentration in the supernatant fraction of the low zinc diet + supernatant fraction group in the jejunum by DHMBA, thereby confirming the DNA antioxidant effect.

[0141] As shown in Figure 3, the concentration of 8-OHdG in the jejunum of the low-zinc diet group was 9.31±0.29 ng / g, which was significantly higher than that of the standard diet group (6.82±0.56 ng / g). This may be due to the increase in reactive oxygen species in the jejunum, thus confirming that the intake of a low-zinc diet induced oxidative stress.

[0142] In contrast, the 8-OHdG concentration in the low zinc diet + precipitate fraction group was significantly lower than that in the low zinc diet group, or despite the intake of a low zinc diet, there was no significant difference between the 8-OHdG concentration and the standard diet, and the 8-OHdG concentration dropped to the same level as the standard diet. This promoted the decrease in 8-OHdG concentration in the jejunum caused by the precipitate fraction in the low zinc diet + precipitate fraction group, thereby confirming the DNA antioxidant effect,

[0143] As shown in Figure 4, the 8-OHdG concentration of 7.81±0.49 in the low zinc diet + synthetic DHMBA group was significantly lower than that of 9.31±-0.29 in the low zinc diet group. Despite the intake of a low zinc diet, there was no significant difference in 8-OHdG concentration between the group and the standard diet, and the 8-OHdG concentration dropped to the same level as the standard diet.

[0144] Therefore, since the decrease in 8-OHdG concentration caused by synthetic DHMBA in the low zinc diet + synthetic DHMBA fraction group in the jejunum was promoted, the DNA antioxidant effect was confirmed.

[0145] As shown in Figure 5, the MDA concentration in the jejunum of the low zinc diet group was 6.67±0.47 mg / g, which was significantly higher than that of the standard diet group (4.53±0.26 mg / g). This confirmed that the decrease in SOD concentration caused by the intake of a low zinc diet led to an increase in reactive oxygen species (oxidative stress).

[0146] In contrast, the MDA concentration of the low zinc diet + supernatant fraction group was significantly lower than that of the low zinc diet group, or there was no significant difference between the MDA concentration and the standard diet despite the intake of the low zinc diet, and the MDA concentration dropped to the same level as the standard diet. Thus, the antioxidant effect of DHMBA on unsaturated fatty acids in the supernatant fraction of the low zinc diet + supernatant fraction group in the jejunum was confirmed.

[0147] As shown in Figure 6, the ZIP4 concentration of the low zinc diet + supernatant fraction group was 7.41±0.44 pg / mg, which was significantly higher than the ZIP4 concentration of the low zinc diet group, 4.38±0.33 pg / mg. In addition, despite the intake of the low zinc diet, there was no significant difference in ZIP4 concentration between the standard diet and the low zinc diet, and the ZIP4 concentration increased to the same level as the standard diet.

[0148] Thus, the ZIP4 concentration-increasing promoting effect was confirmed by DHMBA of the supernatant fraction in the low zinc diet+supernatant fraction group.

[0149] Secondly, as shown in Figure 7 , the ZIP4 concentration of 4.38±0.33 pg / mg in the low zinc diet group was significantly lower than that of 8.89±0.71 pg / mg in the standard diet group.

[0150] In contrast, the ZIP4 concentration of the low zinc diet + precipitate fraction group was 6.76±0.67pg / mg, which was significantly higher than the ZIP4 concentration of the low zinc diet group, 4.38±0.33pg / mg. In addition, despite the intake of the low zinc diet, there was no significant difference in ZIP4 concentration between the standard diet and the standard diet, and the ZIP4 concentration increased to the same level as the standard diet. Based on this, the low zinc diet + precipitate fraction group confirmed the effect of promoting the increase in ZIP4 concentration.

[0151] Next, as shown in FIG8 , the ZIP4 concentration of the low zinc diet group + synthetic DHMBA fraction group, 6.44±0.76 pg / mg, was significantly higher than the ZIP4 concentration of the low zinc diet group, 4.38±0.33 pg / mg.

[0152] Therefore, the promoting effect of synthetic DHMBA on the increase in ZIP4 concentration in the low zinc diet + synthetic DHMBA group was confirmed.

[0153] FIG. 9 is a graph showing the correlation between the MDA concentration and the ZIP4 concentration in the jejunum.

[0154] As shown in Figure 9, it was confirmed that the increase in the amount of reactive oxygen in the jejunum (increase in MDA) induced by the intake of a low-zinc diet induced a decrease in the ZIP4 value, and at the same time, in the low-zinc diet + supernatant fraction group, the intake of DHMBA, a supernatant fraction with antioxidant function, induced an increase in the ZIP4 value accompanied by a decrease in the amount of reactive oxygen in the jejunum (decrease in MDA).

[0155] As shown in FIG. 10 , the increase in the amount of reactive oxygen species in the jejunum (increase in MDA) induced by the intake of a low-zinc diet also induced a decrease in the ZIP4 value.

[0156] Next, it was confirmed that in the low zinc diet + precipitate fraction group, an increase in the ZIP4 value was induced along with a decrease in the amount of active oxygen in the jejunum (reduction in MDA) due to the intake of food having an antioxidant function.

[0157] According to Figure 11, it can be confirmed that the increase in the amount of reactive oxygen in the jejunum (increase in MDA) induced by the intake of a low zinc diet also induced a decrease in the ZIP4 value. At the same time, it can be confirmed that the increase in the amount of active oxygen in the jejunum (increase in MDA) induced by the intake of a low zinc diet also induced a decrease in the ZIP4 value. At the same time, it can be confirmed that in the low zinc diet + synthetic DHMBA fraction group, the intake of DHMBA, a synthetic DHMBA fraction with antioxidant function, also induced an increase in the ZIP4 value accompanied by a decrease in the amount of reactive oxygen in the jejunum (decrease in MDA).

[0158] As shown in FIGS. 9 , 10 , and 11 , it was confirmed that there was a close correlation between the MDA concentration and the ZIP4 concentration in the jejunum.

[0159] That is, as described above, only in the roots and shoots of maize, ZIP4 is not increased by oxidative stress, but it has been reported that ZIP4 is increased by antioxidant defense.

[0160] Therefore, according to the present invention, it was confirmed that in the jejunum of rats, which are mammals, the zinc transporter ZIP4 decreases due to oxidative stress, but increases with the removal of active oxygen (reduction of MDA) by administration of DHMB, which is an antioxidant.

[0161] FIG. 12 verifies the changes in serum zinc concentration in the standard diet group, the low zinc diet group, and the low zinc diet + synthetic DHMBA diet group.

[0162] The synthetic DHMBA fraction contains zero zinc. Furthermore, the zinc intake was the same in the low zinc diet group and the low zinc diet + synthetic DHMBA group.

[0163] However, even with the same amount of zinc intake, the serum zinc concentration in the low zinc diet + synthetic DHMBA diet group was significantly higher than that in the low zinc diet group, indicating that the synthetic DHMBA in the synthetic DHMBA fraction increased the amount of zinc absorption.

[0164] Therefore, as shown in FIG12 , the functional components involved in DHMBA increasing the serum zinc concentration under oxidative stress were confirmed.

[0165] Next, Figure 13 examines the correlation between the ZIP4 concentration in the jejunum and the serum zinc concentration in the standard diet group, the low zinc diet group, and the low zinc diet + synthetic DHMBA fraction group; Figure 14 examines the correlation between the ZIP4 concentration in the jejunum and the serum zinc concentration in the standard diet group, the low zinc diet group, and the low zinc diet + supernatant fraction group; Figure 15 examines the correlation between the ZIP4 concentration in the jejunum and the serum zinc concentration in the standard diet group, the low zinc diet group, and the low zinc diet + sediment fraction group.

[0166] Next, as shown in the correlation between the jejunal ZIP4 concentration and the serum zinc concentration in FIG13 , in the three groups of the standard diet group, the low zinc diet group, and the low zinc diet + synthetic DHMBA fraction group, the serum zinc concentration increased with the increase in jejunal ZIP4.

[0167] However, in the low-zinc diet + synthetic DHMBA fraction group, it was confirmed that the serum zinc concentration increased along with the increase of ZIP4 in the jejunum by administration of synthetic DHMBA to the synthetic DHMBA fraction group.

[0168] Furthermore, as shown in the correlation between the ZIP4 concentration in the jejunum and the zinc concentration in the serum in FIG14 , in the three groups of the standard diet group, the low zinc diet group, and the low zinc diet + supernatant fraction group, the serum zinc concentration increased along with the increase in ZIP4 in the jejunum.

[0169] However, it was confirmed that in the low-zinc diet + supernatant fraction group, the administration of DHMBA contained in the supernatant fraction increased the serum zinc concentration along with the increase of ZIP4 in the jejunum.

[0170] As shown in the correlation between the ZIP4 concentration in the jejunum and the serum zinc concentration in FIG15 , in the three groups of the standard diet group, the low zinc diet group, and the low zinc diet group+precipitate fraction group, the serum zinc concentration increased with the increase of ZIP4 in the jejunum.

[0171] However, it was confirmed that in the low-zinc diet + sediment fraction group, the serum zinc concentration increased along with the increase of ZIP4 in the jejunum due to the administration of DHMBA contained in the sediment fraction.

[0172] Figure 16 examines the correlation between the MDA concentration in the jejunum and the zinc concentration in the serum in the standard diet group, the low zinc diet group, and the low zinc diet + synthetic DHMBA fraction group. Figure 17 examines the correlation between the MDA concentration in the jejunum and the zinc concentration in the serum in the standard diet group, the low zinc diet group, and the low zinc diet + supernatant fraction group.

[0173] Figure 18 examines the correlation between the MDA concentration in the jejunum and the zinc concentration in the serum in the standard diet group, the low zinc diet group, and the low zinc diet + precipitated fraction group. Based on the above Figures 16, 17 and 18, it is believed that there is a significant inverse correlation between the MDA concentration in the jejunum and the zinc concentration in the serum.

[0174] According to Figure 16, it can be confirmed that in the low zinc diet group + synthetic DHMBA group, the zinc concentration in the serum also increased with the decrease in the MDA concentration in the jejunum caused by the intake of synthetic DHMBA. This phenomenon is believed to be due to the increase in ZIP4 concentration due to the decrease in active oxygen in the jejunum (decrease in MDA in the jejunum), as confirmed in Figures 13 to 15, which is accompanied by a decrease in the MDA concentration in the jejunum, which is believed to increase the zinc supply in the serum.

[0175] According to FIG. 17 , in the low-zinc diet + supernatant fraction group, it was confirmed that the serum zinc concentration increased along with the decrease in the MDA concentration in the jejunum due to the ingestion of DHMBA as the supernatant fraction.

[0176] In the low zinc diet + precipitate fraction group in FIG. 18 , it was confirmed that the serum zinc concentration increased along with the decrease in the MDA concentration in the jejunum due to the ingestion of DHMBA of the precipitate fraction.

[0177] As shown in FIGS. 17 , 18 and 16 , as confirmed in FIGS. 13 to 15 , the concentration of ZIP4 increased due to the decrease in active oxygen in the jejunum (decrease in MDA in the jejunum), which is considered to mean that the decrease in the jejunum MDA concentration increased the supply of zinc in the serum.

Claims

1. An agent for promoting reduction of 8-OHdG concentration in the jejunum, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol, and has an 8-OHdG concentration-lowering promoting effect, which reduces the 8-OHdG concentration in the jejunum.

2. An agent for promoting the reduction of 8-OHdG concentration in the jejunum, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, and has an 8-OHdG concentration-lowering promoting effect that reduces the 8-OHdG concentration in the jejunum.

3. An agent for promoting reduction of 8-OHdG concentration in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and the supernatant extract is taken out, and the supernatant fraction is used as an active ingredient, and has an 8-OHdG concentration-lowering promoting effect of lowering the 8-OHdG concentration in the jejunum.

4. An agent for promoting the reduction of 8-OHdG concentration in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and precipitated with a precipitate fraction as an active ingredient, and has an 8-OHdG concentration-lowering promoting effect that reduces the 8-OHdG concentration in the jejunum.

5. An agent for promoting the reduction of 8-OHdG concentration in the jejunum, characterized in that: The active ingredient is synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol, and has an 8-OHdG concentration-lowering promoting effect, which reduces the 8-OHdG concentration in the jejunum.

6. A jejunal MDA concentration reduction promoter, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

7. An agent for promoting reduction of MDA concentration in the jejunum, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

8. An agent for promoting reduction of MDA concentration in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and the supernatant extract is taken out, and the supernatant fraction is used as an active ingredient, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

9. An agent for promoting reduction of MDA concentration in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and precipitated with a precipitate fraction as an active ingredient, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

10. An agent for promoting reduction of MDA concentration in the jejunum, characterized in that: The active ingredient is synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol, and has an MDA concentration-lowering promoting effect of lowering the MDA concentration in the jejunum.

11. A ZIP4 concentration-increasing promoter in the jejunum, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol, and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

12. A ZIP4 concentration-increasing promoter in the jejunum, characterized in that: The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

13. A ZIP4 concentration-increasing promoter in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and the supernatant extract is taken out, and the supernatant fraction is used as an active ingredient, which has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

14. A ZIP4 concentration-increasing promoter in the jejunum, characterized in that: The extract obtained from oyster meat is stirred and precipitated with a precipitate fraction as an active ingredient, which has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

15. A ZIP4 concentration-increasing promoter in the jejunum, characterized in that: The active ingredient is synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol, and has a ZIP4 concentration-increasing promoting effect that increases the ZIP4 concentration in the jejunum.

16. An inducer for increasing zinc concentration in serum, characterized in that The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol, which has the effect of inducing an increase in serum zinc concentration.

17. An inducer for increasing zinc concentration in serum, characterized in that The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat, which has the effect of inducing an increase in serum zinc concentration.

18. An inducer for increasing zinc concentration in serum, characterized in that The active ingredient is synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol, which has the effect of inducing an increase in serum zinc concentration.

19. An inducer for increasing zinc concentration in serum, characterized in that The extract obtained from oyster meat is stirred and the supernatant extract is taken out. The supernatant fraction containing DHMBA is used as an active ingredient and has an effect of inducing an increase in the zinc concentration in serum.

20. An inducer for increasing zinc concentration in serum, characterized in that The precipitate fraction containing DHMBA obtained by stirring and precipitating an extract obtained from oyster meat has the effect of inducing an increase in serum zinc concentration.

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