Promoters of decreased 8-OHdG concentration in the jejunum, promoters of decreased malondialdehyde (MDA) concentration, promoters of increased ZIP4 concentration, and promoters of increased serum zinc concentration.

Abstract

This invention aims to provide an agent that can improve oxidative stress conditions by promoting the reduction of MDA concentration, 8-OHdG concentration, ZIP4 concentration, or serum zinc concentration in the jejunum. Specifically, it utilizes 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient and is characterized by its ability to promote the reduction of 8-OHdG concentration in the jejunum.

Description

Technical Field

[0001] This invention relates to promoters that reduce 8-OHdG concentration in the jejunum, promote MDA concentration reduction, promote ZIP4 concentration increase, and promote serum zinc concentration increase. Prior Technology

[0002] The inventors confirmed a significant increase in serum zinc concentration when type 2 diabetic patients were given oyster (Miyagioyster) soft extract fractionation (e.g., oyster meat is immersed in an extract to extract various components from the oyster meat) for 12 weeks.

[0003] However, in the mixed fractions of precipitate and clarified fractions from the soft extract of oyster meat (e.g., precipitate and clarified fractions obtained by immersing oyster meat in an extract, stirring the extract from which various components are extracted, and then precipitating), the mechanism for this result has not been elucidated because it does not contain zinc, which can significantly increase the concentration of zinc in the serum.

[0004] This study focuses on verifying the zinc absorption mechanism in the intestine and exploring its impact on the zinc absorption mechanism in the intestine of soft extract fractions from Ostrea gigas.

[0005] Zinc is absorbed in the duodenum and jejunum, but primarily in the jejunum. The intestinal zinc transporter ZIP4 is considered essential for zinc absorption.

[0006] In the past, there have been reports of increased ZIP4 levels in the intestines in zinc-deficient states. However, the inventors of this case observed an increase in ZIP4 concentration in the duodenum of rats fed a low-zinc diet, obtaining the same results as the aforementioned past reports of "increased ZIP4 levels in the intestines in zinc-deficient states".

[0007] However, a decrease in ZIP4 concentration was observed in the jejunum of rats fed a low-zinc diet. The changes in ZIP4 concentration in rats fed a zinc-deficient diet not only differed in the degree of zinc deficiency but also took into account the possible differences in the intestinal location.

[0008] On the other hand, as a very interesting report, the H2O2 concentration was significantly increased in the roots and shoots of maize lines that are susceptible to zinc deficiency, but the expression of the ZIP4 transporter gene was not increased.

[0009] On the other hand, it has been reported that the expression of the ZIP4 transporter gene is increased in the roots and shoots of maize strains grown in soils with low zinc content, and antioxidant defense has an effect on the increase in the expression of the ZIP4 transporter gene. In other words, the influence of oxidation state on the expression of the ZIP4 transport gene can be confirmed by maize roots.

[0010] In this invention, a phenomenon related to the decrease in superoxide dismutase (SOD) activity induced by a low-zinc diet, leading to a decrease in zinc concentration in the jejunum, and consequently an increase in reactive oxygen species in the rat jejunum, can be predicted. In other words, an oxidative stress state, characterized by an increase in MDA concentration in the jejunum, an increase in 8-OHdG concentration, a decrease in ZIP4 concentration, and a decrease in serum Zn concentration, can be predicted.

[0011] However, the inventors, regarding the aforementioned oxidative stress state, administered various fractions of the extract of the soft shell of the Pacific oyster, which has antioxidant properties—in other words, components extracted from the precipitated fraction, clarified fraction, or soft shell of the Pacific oyster—specifically, 3,5-dihydroxy-4-methoxybenzyl alcohol, further synthesized as 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), to the aforementioned rats. This resulted in no changes in the aforementioned oxidative stress state, or in other words, it can be verified whether the administration of 3,5-dihydroxy-4-methoxybenzyl alcohol, through the improvement of the oxidative stress state, can promote a reduction in jejunal MDA concentration, a reduction in 8-OHdG concentration, an increase in ZIP4 concentration, and an increase in serum zinc concentration. [Previous Technical Documents] [Patent Literature]

[0012] [Patent Document 1] Japanese Patent Application Publication No. 2016-042825 Summary of the Invention

[0013] [The problem solved by the invention]

[0014] This invention aims to provide a component extracted from the extract of oyster shells with antioxidant properties, specifically the components extracted from the precipitated and clarified fractions, particularly 3,5-dihydroxy-4-methoxybenzyl alcohol, and more specifically, the synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) administered to rats. The invention is intended to improve oxidative stress by promoting the reduction of MDA concentration in the jejunum, the reduction of 8-OHdG concentration, the increase of ZIP4 concentration, and the increase of serum zinc concentration. [Methods for solving the problem]

[0015] This invention is characterized by using 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient, which promotes the reduction of 8-OHdG concentration in the jejunum; or using 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat as an active ingredient, which promotes the reduction of 8-OHdG concentration in the jejunum; or using the clarified fraction of the extract obtained by stirring the extract from oyster meat as an active ingredient, which promotes the reduction of 8-OHdG concentration in the jejunum; or using the precipitate fraction obtained by stirring the extract from oyster meat and then allowing precipitation as an active ingredient. Characterized by a promoting effect on reducing 8-OHdG concentration in the jejunum, or by using synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient to promote the reduction of 8-OHdG concentration in the jejunum; or by using 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient to promote the reduction of MDA concentration in the jejunum; or by using 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat as an active ingredient to promote the reduction of MDA concentration in the jejunum; or by clarifying the extract from oyster meat after stirring. The clarified fraction of the extract, as the active ingredient, is characterized by promoting the reduction of MDA concentration in the jejunum; or the precipitate fraction obtained by stirring and then precipitating the extract from oyster meat, as the active ingredient, is characterized by promoting the reduction of MDA concentration in the jejunum; or synthetic 3,5-dihydroxy-4-methoxybenzyl alcohol, as the active ingredient, is characterized by promoting the reduction of MDA concentration in the jejunum; or 3,5-dihydroxy-4-methoxybenzyl alcohol, as the active ingredient, is characterized by promoting the increase of ZIP4 concentration in the jejunum; or 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat... The active ingredient is 3,5-dihydroxy-4-methoxybenzyl alcohol, characterized by its ability to promote an increase in ZIP4 concentration in the jejunum; or the active ingredient is the clarified fraction of the extract obtained by stirring an extract from oyster meat, characterized by its ability to promote an increase in ZIP4 concentration in the jejunum; or the active ingredient is the precipitate fraction obtained by stirring an extract from oyster meat, characterized by its ability to promote an increase in ZIP4 concentration in the jejunum; or the active ingredient is synthetically produced 3,5-dihydroxy-4-methoxybenzyl alcohol.This product is characterized by its ability to promote the increase of ZIP4 concentration in the jejunum, or by using 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient to induce an increase in serum zinc concentration; or by using 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from oyster meat as an active ingredient to induce an increase in serum zinc concentration; or by using synthetically produced 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient to induce an increase in serum zinc concentration; or by using a clarified fraction containing DHMBA from an extract obtained by stirring an extract obtained from oyster meat as an active ingredient to induce an increase in serum zinc concentration; or by using a precipitate containing DHMBA from an extract obtained by stirring an extract obtained from oyster meat as an active ingredient to induce an increase in serum zinc concentration. [Effects of the Invention]

[0016] According to the present invention, for the state of oxidative stress, by extracting various fractions of the extract of oyster shell with antioxidant properties, in other words, the components extracted from the precipitated fraction and the clarified fraction, especially 3,5-dihydroxy-4-methoxybenzyl alcohol, and further further, by administering the synthesized 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) to rats, the oxidative stress state has been shown to be improved, achieving excellent effects in promoting the reduction of MDA concentration in the jejunum, the reduction of 8-OHdG concentration, the increase of ZIP4 concentration, and the increase of serum zinc concentration. Simple Explanation of the Diagram

[0017] [Figure 1] Explanation of SOD concentration in the jejunum of standard diet and low zinc diet. [Figure 2] Explanation of 8-OHdG concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + clarified fraction group. [Figure 3] Explanation of 8-OHdG concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + precipitate fraction group. [Figure 4] Illustration of 8-OHdG concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + synthetic DHMBA group. [Figure 5] Explanation of MDA concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + clarified fraction group. [Figure 6] Illustration of ZIP4 concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + clarified fraction group. [Figure 7] Illustration of ZIP4 concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + precipitate fractionation group. [Figure 8] Illustration of ZIP4 concentration in the jejunum of standard diet, low-zinc diet, and low-zinc diet + synthetic DHMBA group. [Figure 9] An explanatory graph illustrating the correlation between MDA concentration and ZIP concentration in the standard food, low-zinc food, and low-zinc food + clarified fraction group. [Figure 10] An explanatory graph illustrating the correlation between MDA concentration and ZIP concentration in standard food, low-zinc food, and low-zinc food + precipitate fractionation groups. [Figure 11] An explanatory graph illustrating the correlation between MDA concentration and ZIP concentration in the standard diet, low-zinc diet, and low-zinc diet + synthetic DHMBA group. [Figure 12] A diagram illustrating the serum zinc concentrations of patients on a standard diet, a low-zinc diet, and a low-zinc diet plus synthetic DHMBA group. [Figure 13] An illustration of the correlation between jejunal ZIP concentration and serum zinc concentration in the standard diet, low-zinc diet, and low-zinc diet + synthetic DHMBA group. [Figure 14] An explanatory graph illustrating the correlation between jejunal ZIP concentration and serum zinc concentration in the standard diet, low-zinc diet, and low-zinc diet + clarified fraction group. [Figure 15] An explanatory graph illustrating the correlation between ZIP concentration in the jejunum and serum zinc concentration in the standard diet, low-zinc diet, and low-zinc diet + precipitate fractionation group. [Figure 16] An explanatory graph illustrating the correlation between MDA concentration in the jejunum and serum zinc concentration in the standard diet, low-zinc diet, and low-zinc diet + synthetic DHMBA group. [Figure 17] An explanatory graph illustrating the correlation between MDA concentration in the jejunum and zinc concentration in serum among the standard diet, low-zinc diet, and low-zinc diet + clarified fraction group. [Figure 18] An explanatory graph illustrating the correlation between MDA concentration in the jejunum and zinc concentration in serum among standard diet, low-zinc diet, and low-zinc diet + precipitate fractionation group. Implementation

[0018] [Types of Invention Implementation] (Example)

[0019] This invention provides a promoter that uses 3,5-dihydroxy-4-methoxybenzyl alcohol as an active ingredient to improve the oxidative stress state in the jejunum, thereby promoting the reduction of MDA concentration, the reduction of 8-OHdG concentration, the increase of ZIP4 concentration, and the increase of serum zinc concentration.

[0020] The aforementioned promoter is manufactured by immersing oyster meat in an extract, and using 3,5-dihydroxy-4-methoxybenzyl alcohol extracted from the oyster meat immersed in the extract as the active ingredient. Furthermore, 3,5-dihydroxy-4-methoxybenzyl alcohol can also be a synthetically produced form.

[0021] Then, during the manufacture of the aforementioned promoter, animal experiments were conducted to determine whether it could improve the oxidative stress state in the jejunum and achieve promotion of reduced MDA concentration, reduced 8-OHdG concentration, increased ZIP4 concentration, and increased serum zinc concentration, and these results were confirmed.

[0022] That is, when a low-zinc diet composed of the specified ingredients is ingested by the specified rats, the activity of superoxide dismutase (SOD) will decrease, the reactive oxygen species in the rat jejunum will increase, resulting in an increase in MDA concentration in the jejunum, an increase in 8-OHdG concentration, a decrease in ZIP4 concentration, and a decrease in serum Zn concentration.

[0023] In contrast, for example, oyster meat is soaked in an extract, and the 3,5-dihydroxy-4-methoxybenzyl alcohol flowing from the soaked oyster meat into the extract is added to a low-zinc diet for rats.

[0024] Furthermore, it was confirmed that the 3,5-dihydroxy-4-methoxybenzyl alcohol in the oyster meat flowing into the extract differed in quantity from the precipitate fraction and the clarified fraction precipitated after stirring the extract for a predetermined time.

[0025] However, considering the above, the determination of whether there were any changes in the concentrations of MDA, 8-OHdG, ZIP4, and serum Zn in the rat jejunum when 3,5-dihydroxy-4-methoxybenzyl alcohol, which has antioxidant properties extracted from oyster meat, was further verified when the synthesized 3,5-dihydroxy-4-methoxybenzyl alcohol (hereinafter also referred to as DHMBA) was administered to the aforementioned rats was verified.

[0026] Through this verification, excellent performance was confirmed in the manufacture of the aforementioned accelerators, and an accelerator that can effectively treat oxidative stress was manufactured.

[0027] Here is a brief overview of the animal experiments. (Experimental Methods) Male Slc / SD rats (4 weeks old) were used as experimental animals. (Grouping and Feed) The aforementioned rats were grouped as shown below, and their diet was as shown below. Here, n represents the number of rats.

[0028] Standard diet group (n=6): Free access to standard diet (Standard zinc concentration in food: 34.1 mg zinc / kg of diet) Furthermore, the standard dietary zinc concentration is set at 20 mg zinc / kg of diet to 55 mg zinc / kg of diet. (Also, the standard concentration of DHMBA in food is zero.)

[0029] Low-zinc diet group (n=6): Free access to low-zinc foods (Zinc concentration in low-zinc diet: 3.9 mg zinc / kg diet) Furthermore, as a low-zinc diet, the zinc concentration is set at 2.5 mg zinc / kg of food to 10 mg zinc / kg of food. (Also, the DHMBA concentration in low-zinc foods is zero.)

[0030] Low-zinc diet + clarified fraction group (n=6): Low-zinc diet + clarified fraction from oyster extract The zinc concentration in a low-zinc diet is as described above. Furthermore, the so-called clarified fraction of oyster extract is, for example, oyster meat immersed in an extract, and the clarified fraction of the extract from the surface side of the extract containing various components extracted from the oyster meat is taken out after stirring. Then, the DHMBA concentration of the clarified fraction was 0.96 μg / rat BW100g. Furthermore, the concentration of DHMBA in the clarified fraction was set at 0.68 μg / rat BW100g to 2.38 μg / rat BW100.

[0031] Low-zinc food + precipitate fraction group (n=6): Low-zinc food + oyster extract precipitate fraction For low-zinc diets, the zinc concentration is as described above. Then, the so-called long oyster extract precipitate fraction refers to, for example, the fraction obtained by immersing oyster meat in an extract, stirring the extract from the various components extracted from the oyster meat, and then allowing the extract to precipitate. Furthermore, although this precipitate fraction is forcibly administered orally, the zinc concentration in this fraction is 0.894 μg / day, which is negligible. Then, the DHMBA concentration of the precipitate fraction was 0.38 μg / rat BW100g. Furthermore, the concentration of DHMBA as a precipitate fraction was set at 0.1 μg / ratB.W.100g~0.5 μg / ratB.W.100g.

[0032] Low-zinc diet + synthetic DHMBA group (n=6): Low-zinc diet + synthetic DHMBA For a low-zinc diet, the zinc concentration is as described above: 3.9 mg zinc / kg diet. The term "synthetic DHMBA" refers to DHMBA that is not extracted from oyster meat, but rather produced through chemical synthesis. The concentration of this DHMBA is 7.9 mg / rat BW100g. Furthermore, the concentration of DHMBA synthesized in the generated state was set in the range of 5 mg / rat BW100g to 15 mg / rat BW100g.

[0033] (Trial Schedule) [1] Preparation period (7 days) From the time the animals were introduced to the experiment until the day before formal feeding began, they underwent preparatory feeding, which involved individual feeding (n=1 / cage) for acclimatization. During the preparatory feeding period, they were given a standard diet, and grouping was based on their weight at the end of the preparatory feeding period. [2] During the formal feeding period (7 days) From the start of the formal rearing period, the standard diet was divided into four groups: low-zinc diet, low-zinc diet + precipitate fraction, low-zinc diet + clarified fraction, and low-zinc diet + synthetic DHMBA. These groups were provided with free access to the low-zinc diet. On days 5 and 6, the standard diet and low-zinc diet groups were orally administered 0.5% methylcellulose solution. The low-zinc diet + clarified fraction group was orally administered oyster extract clarified fraction, the low-zinc diet + precipitate fraction group was orally administered oyster extract precipitate fraction, and the low-zinc diet + synthetic DHMBA group was orally administered synthetic DHMBA. The dosage for the experimental subjects was set at 0.5 mL / 100 g B.W. Then, 24 hours after administration on day 6, the experimental subjects were dissected and their organs were removed.

[0034] (Measurement Items) The concentrations of SOD, MDA, 8-OHdG, ZIP4, and zinc in the jejunum and serum were measured.

[0035] For SOD concentration SOD (superoxide dismutase) Superoxide dismutase (SOD) refers to an enzyme that has the ability to remove reactive oxygen species. SOD is abundant in the mitochondria of cells and has the function of protecting the body from oxidative stress caused by reactive oxygen species. Superoxide (SOD) can convert superoxide into hydrogen peroxide and oxygen, that is, it is an enzyme that catalyzes the reaction 2·O 2- + 2H+ → H 2O 2 + O 2. This reaction can proceed rapidly even without an enzyme, but the presence of SOD at least eliminates superoxide earlier, which is important for living organisms. In the cytoplasm of eukaryotic organisms, CuZn-SOD containing copper and zinc exists at its active site. Therefore, reducing the SOD concentration will increase oxidative stress.

[0036] For MDA concentration MDA stands for malondialdehyde. MDA is a product of lipid peroxidation and is used as a primary marker of lipid peroxidation. As an indicator of lipid peroxidation in cell or tissue samples, it can be used to assess oxidative stress. Increased MDA concentration indicates increased oxidative stress. MDA is produced by free radicals such as hydroxides (･OH). When unsaturated fatty acids are oxidized to free radicals (･OH), they become lipid peroxidation products, and ultimately, MDA is formed. If free radicals (･OH) are present in high concentrations within organs, MDA concentration will also increase. A decrease in MDA concentration indicates a reduction in ･OH.

[0037] For 8-OHdG concentration 8-OHdG refers to the substance formed by the oxidation of guanine bases into 8-hydroxy-deoxyguanine nucleoside (8-OHdG). DNA is composed of four types of bases: adenine, guanine, cytosine, and thymine. DNA is known to be damaged by reactive oxygen species (ROS), and guanine bases are oxidized to 8-OHdG. This 8-OHdG is excised from the gene during DNA repair and excreted in the urine via the bloodstream. Furthermore, 8-OHdG is a relatively stable substance; it is not metabolized or broken down in vivo and is rapidly excreted in urine. Therefore, it can sensitively reflect in vivo damage caused by ROS and can be used as an excellent biomarker. dG has the lowest redox potential among the four types of DNA bases, making it easily oxidized by reactive oxygen species. Therefore, 8-OHdG, as the main oxidation product of dG, can keenly reflect the effects of reactive oxygen species on living organisms. An increase in 8-OHdG concentration indicates an increased state of oxidative stress.

[0038] For ZIP4 concentration Zinc transporters play a crucial role in maintaining zinc homeostasis in living organisms. In the zinc absorption mechanisms of the digestive tract, the zinc transporter ZIP4 (ZIP4: ZRT, IRT-like protein 4) plays a vital role. ZIP4 is a membrane-bound protein that transports zinc from the jejunal lumen into the jejunal cells.

[0039] For serum Zn concentration Zinc is an essential mineral for humans, second only to iron in terms of its abundance in the body. It is found in large quantities in bones, muscles, skin, hair, liver, taste buds, and testes. In the body, it plays an indispensable role in the activity of over 300 types of enzymes. Deficiency can lead to a variety of symptoms, including taste abnormalities, dermatitis, hair loss, anemia, stomatitis, diarrhea, male sexual dysfunction, increased susceptibility to infections (lowered immunity), and osteoporosis. Furthermore, zinc deficiency is diagnosed in many patients with cirrhosis, diabetes, chronic inflammatory bowel disease, and chronic kidney disease.

[0040] (Results and Investigation) As shown in Figure 1, the SOD concentration in the jejunum of the low-zinc diet group (3.07 ± 0.42 U / mg) was significantly lower than that of the standard diet group (5.85 ± 0.61 U / mg). This confirms that a low-zinc diet can reduce SOD concentration. A decrease in SOD (Superoxide Dismutase) concentration can increase oxidative stress. Secondly, as shown in Figure 2, the 8-OHdG concentration in the jejunum of the low-zinc diet + clarified fraction group (7.23±0.64) was significantly lower than that of the low-zinc diet group (9.31±0.29). Furthermore, even with the low-zinc diet, no significant difference was observed in the 8-OHdG concentration between it and the standard diet, indicating that the 8-OHdG concentration was reduced to the same level as the standard diet. Therefore, this method can promote the reduction of 8-OHdG concentration of DHMBA in the clarified fractions of the low-zinc diet in the jejunum, thereby confirming the DNA antioxidant effect.

[0041] 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 is presumably due to the increase in reactive oxygen species in the jejunum, thus confirming that the intake of a low-zinc diet can induce oxidative stress. In contrast, the 8-OHdG concentration of the low-zinc diet plus precipitate fraction was significantly lower than that of the standard diet alone. Even with a low-zinc diet, no significant difference in 8-OHdG concentration was observed between it and the standard diet, indicating that the 8-OHdG concentration was reduced to the same level as the standard diet. This promotes a decrease in the 8-OHdG concentration of the precipitate fraction in the low-zinc diet plus precipitate fraction in the jejunum, thereby confirming its DNA antioxidant effect.

[0042] As shown in Figure 4, the 8-OHdG concentration of the low-zinc diet plus the synthetic DHMBA group (7.81±0.49) was significantly lower than that of the low-zinc diet group (9.31±0.29). Furthermore, even with the low-zinc diet, no significant difference was observed in the 8-OHdG concentration between it and the standard diet, indicating that the 8-OHdG concentration was reduced to the same level as the standard diet. Therefore, this confirms the DNA antioxidant effect of promoting the reduction of 8-OHdG concentration in synthetic DHMBA fractions from low-zinc diets in the jejunum.

[0043] As shown in Figure 5, the MDA concentration in the jejunum of the low-zinc diet group (6.67 ± 0.47 mg / g) was significantly higher than that of the standard diet group (4.53 ± 0.26 mg / g). This confirms the increase in reactive oxygen species (oxidative stress) caused by the decreased SOD concentration due to the low-zinc diet.

[0044] In contrast, the MDA concentration of the low-zinc diet plus clarified fraction was significantly lower than that of the low-zinc diet alone. Furthermore, even with a low-zinc diet, no significant difference in MDA concentration was observed between it and the standard diet; the MDA concentration decreased to the same level as the standard diet. This confirms the antioxidant effect of DHMBA unsaturated fatty acids in the clarified fraction of the low-zinc diet plus clarified fraction in the jejunum.

[0045] As shown in Figure 6, the ZIP4 concentration of the low-zinc diet plus clarified fraction group (7.41±0.44 pg / mg) was significantly higher than that of the low-zinc diet group (4.38±0.33 pg / mg). Furthermore, even with the low-zinc diet, no significant difference was observed in ZIP4 concentration between it and the standard diet; the ZIP4 concentration increased to the same level as the standard diet. This confirms the promoting effect of increased ZIP4 concentration in DHMBA, a clarified fraction from the low-zinc food + clarified fraction group.

[0046] Secondly, as shown in Figure 7, the ZIP4 concentration in the low-zinc diet group (4.38±0.33 pg / mg) was significantly lower than that in the standard diet group (8.89±0.71 pg / mg). In contrast, the ZIP4 concentration of the low-zinc diet plus the precipitate fraction group (6.76 ± 0.67 pg / mg) was significantly higher than that of the low-zinc diet group (4.38 ± 0.33 pg / mg). Furthermore, even with the low-zinc diet, no significant difference was observed in ZIP4 concentration between it and the standard diet; the ZIP4 concentration increased to the same level as the standard diet. This confirms the promoting effect of increased ZIP4 concentration from the low-zinc diet plus the precipitate fraction group.

[0047] As shown in Figure 8, the ZIP4 concentration of the low-zinc diet + synthetic DHMBA fraction group (6.44±0.76 pg / mg) was significantly higher than that of the low-zinc diet group (4.38±0.33 pg / mg). Therefore, this confirms the promoting effect of increased ZIP4 concentration in the synthesis of DHMBA by a low-zinc diet combined with the synthesis of DHMBA groups.

[0048] Figure 9 shows the correlation between MDA concentration and ZIP4 concentration in the jejunum. As shown in Figure 9, it was confirmed that the increase in reactive oxygen species (MDA) in the jejunum induced by the intake of a low-zinc diet led to a decrease in the induced ZIP4 value. At the same time, for the low-zinc diet + clarified fraction group, it was confirmed that the decrease in reactive oxygen species (MDA) in the jejunum induced by the intake of DHMBA, a clarified fraction with antioxidant function, led to an increase in the induced ZIP4 value.

[0049] As shown in Figure 10, the increase in reactive oxygen species (MDA) in the jejunum induced by the intake of a low-zinc diet leads to a decrease in the induced ZIP4 value. Secondly, for the low-zinc diet + precipitate fraction group, it was confirmed that the decrease in reactive oxygen species in the jejunum due to the intake of antioxidants (the decrease in MDA) caused an increase in the induced ZIP4 value.

[0050] Figure 11 confirms that the increase in reactive oxygen species (ROS) in the jejunum induced by the intake of a low-zinc diet (increase in MDA) leads to a decrease in the induced ZIP4 value. It also confirms that the increase in ROS in the jejunum induced by the intake of a low-zinc diet (increase in MDA) leads to a decrease in the induced ZIP4 value. Furthermore, for the low-zinc diet + synthetic DHMBA fraction group, it is confirmed that the decrease in ROS in the jejunum (decrease in MDA) induced by the intake of DHMBA fractions with antioxidant functions leads to an increase in the induced ZIP4 value.

[0051] As shown in Figures 9, 10, and 11 above, it can be confirmed that there is a close correlation between the concentration of MDA and the concentration of ZIP4 in the jejunum. That is, as mentioned above, the report indicates that ZIP4 does not increase in the roots and shoots of corn under oxidative stress, but can be increased through antioxidant defense.

[0052] However, this invention further confirms that, in the jejunum of mammals such as rats, although oxidative stress reduces the zinc transporter ZIP4, it can increase ZIP4 by administering DHMB, an antioxidant, to eliminate reactive oxygen species (reducing MDA).

[0053] Figure 12 shows the changes in serum zinc concentration in a standard diet group, a low-zinc diet group, and a low-zinc diet group plus a synthetic DHMBA diet group. The zinc content in the synthetic DHMBA fraction was zero. Then, the zinc intake was the same when the diet was low in zinc and when the diet was low in zinc plus synthetic DHMBA.

[0054] However, even with the same zinc intake, the serum zinc concentration in the low-zinc diet plus synthetic DHMBA diet group was significantly higher than that in the low-zinc diet group. This indicates that synthetic DHMBA, a fraction of synthetic DHMBA, can increase zinc absorption. As shown in Figure 12, DHMBA was confirmed to be a functional component associated with increasing serum zinc concentration under oxidative stress.

[0055] Secondly, Figure 13 shows the correlation between ZIP4 concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet + synthetic DHMBA fraction group. Figure 14 shows the correlation between ZIP4 concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet + clarified fraction group. Figure 15 shows the correlation between ZIP4 concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet + precipitated fraction group.

[0056] Secondly, as shown in Figure 13, the correlation between ZIP4 concentration in the jejunum and serum zinc concentration indicates that for the three groups of standard diet, low-zinc diet, and low-zinc diet plus synthetic DHMBA fractions, an increase in serum zinc concentration is accompanied by an increase in ZIP4 in the jejunum. However, it was confirmed that even in a low-zinc diet with synthetic DHMBA fractions, the administration of synthetic DHMBA fractions could lead to an increase in serum zinc concentration, accompanied by an increase in ZIP4 in the jejunum.

[0057] Furthermore, as shown in Figure 14, the correlation between ZIP4 concentration in the jejunum and serum zinc concentration shows that for the three groups of standard diet, low-zinc diet, and low-zinc diet + clarified fraction, an increase in serum zinc concentration is observed along with an increase in ZIP4 in the jejunum. However, it was confirmed that in the low-zinc diet + clarified fraction group, the administration of DHMBA by the clarified fraction could lead to an increase in serum zinc concentration, accompanied by an increase in ZIP4 in the jejunum.

[0058] Figure 15 shows the correlation between ZIP4 concentration in the jejunum and serum zinc concentration. For the three groups of standard diet, low-zinc diet, and low-zinc diet + precipitate fraction, the increase in serum zinc concentration is accompanied by the increase in ZIP4 in the jejunum. However, it was confirmed that in the low-zinc diet + precipitate fraction group, the administration of DHMBA by the precipitate fraction could lead to an increase in serum zinc concentration accompanied by an increase in ZIP4 in the jejunum.

[0059] Figure 16 shows the correlation between MDA concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet group plus synthetic DHMBA fraction. Figure 17 shows the correlation between MDA concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet group plus clarified fraction. Figure 18 shows the correlation between MDA concentration in the jejunum and serum zinc concentration in the standard diet group, the low-zinc diet group, and the low-zinc diet + precipitate fraction group. Figures 16, 17, and 18 above confirm that there is a significant inverse correlation between MDA concentration in the jejunum and serum zinc concentration.

[0060] Figure 16 confirms that a low-zinc diet combined with synthetic DHMBA intake leads to an increase in serum zinc concentration due to a decrease in MDA concentration in the jejunum (a decrease in free radical hydroxyl radicals). This phenomenon can be inferred from Figures 13-15 that the decrease in reactive oxygen species in the jejunum (a decrease in MDA in the jejunum) increases ZIP4 concentration, which in turn increases the zinc supply to the serum.

[0061] Figure 17 confirms that for low-zinc diets with clarified fractions, the decrease in MDA concentration in the jejunum due to DHMBA intake via clarified fractions can lead to an increase in serum zinc concentration.

[0062] Figure 18 confirms that for low-zinc diets with precipitated fractions, the decrease in MDA concentration in the jejunum due to DHMBA uptake via precipitated fractions can lead to an increase in serum zinc concentration.

[0063] As shown in Figures 17 and 18, and as can be confirmed in Figures 13 to 15, it can be inferred that the reduction of reactive oxygen species in the jejunum (the reduction of MDA in the jejunum) can increase the concentration of ZIP4, and the reduction of MDA concentration in the jejunum can increase the zinc supply to the serum.

Claims

1. Use of 3,5-dihydroxy-4-methoxybenzyl alcohol in the manufacture of a ZIP4 concentration-increasing promoter that can adjust the SOD concentration in the jejunum.

2. Use of 3,5-dihydroxy-4-methoxybenzyl alcohol for manufacturing a serum zinc concentration-increasing inducer that can adjust the concentration of SOD in the jejunum.

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