CN119454895A - Composition for preventing and treating alcoholic liver damage and application thereof - Google Patents
Composition for preventing and treating alcoholic liver damage and application thereof Download PDFInfo
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- CN119454895A CN119454895A CN202510046119.0A CN202510046119A CN119454895A CN 119454895 A CN119454895 A CN 119454895A CN 202510046119 A CN202510046119 A CN 202510046119A CN 119454895 A CN119454895 A CN 119454895A
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- peptide
- liver
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- alcoholic liver
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Abstract
The invention relates to a composition for preventing and treating alcoholic liver injury and application thereof, wherein the composition mainly comprises the following active ingredients: wheat peptide, turtle peptide and radix puerariae powder. According to the invention, zebra fish is taken as a model organism, an alcoholic liver injury model is established by ethanol exposure treatment induction, 2 kinds of active peptides (wheat peptide and turtle peptide) and 1 kind of plant extract (kudzu root powder) are obtained by screening from 6 kinds of bioactive peptides and 5 kinds of plant extract through means of apparent histomorphology observation, biochemical index detection, gene expression analysis and the like, and the anti-alcohol liver protection effect of the compound is developed and explored from intestinal microbiology and non-targeted metabonomics layers. Research shows that the compound intervention obviously improves the liver swelling induced by alcohol, and has synergistic effect in preventing liver cell injury (improving ALDH activity) and oxidative injury (improving SOD activity) caused by alcohol.
Description
Technical Field
The invention belongs to a composition, and particularly relates to a composition for preventing and treating alcoholic liver injury and application thereof.
Background
Alcoholic liver disease (Alcoholic LIVER DISEASE, ALD) is becoming a worldwide problem for chronic liver disease, the pathogenesis of which involves multiple pathways of alcohol metabolism, oxidative damage, and lipid metabolism. Because special drugs for treating ALD have not been developed, and the existing treatment approaches may have larger toxic and side effects, development and research of safe and efficient natural functional active substances such as bioactive peptides and plant extracts are gradually and widely focused, and related compound products are developed in the market. However, existing studies lack the search for a synergistic effect between these food function factors.
The study of the anti-alcohol effect of the corn enzymolysis product opens the way of exploring the liver protection effect of the bioactive peptide. To date, liver protection peptides have been studied for different protein sources. Yu et al studied the protective effect of the maize germ flour albumin peptide fraction (APF 4) on acute alcoholic liver injury in mice. The results show that APF4 at a dose of 800 mg/kg/bw significantly promoted alcohol metabolism in the mouse model, and was specifically characterized by significantly reduced blood alcohol concentration, CYP2E1, glutamic-pyruvic transaminase (ALT), glutamic-oxaloacetic transaminase (AST), TG and MDA levels, and significantly increased acetaldehyde dehydrogenase (ALDH), SOD and GSH levels. In another study, also modeled on mouse alcoholic liver disease, wang et al found that oyster peptides significantly up-regulated Nrf-2, heme oxygenase-1 (HO-1) and quinone oxidoreductase 1 (NQO 1) in terms of gene expression levels, while significantly reduced the gene expression levels of NF- κ B, TNF- α, IL-6, and therefore speculated that the possible liver protection mechanism of oyster peptides was by enhancing antioxidant capacity in vivo and inhibiting the occurrence of inflammatory responses. In addition to traditional experimental research, emerging technological means such as molecular docking have become an important technology in the field of computer-aided drug research. Molecular docking is a method of drug design by the characteristics of the receptor and the manner of interaction between the receptor and the drug molecule, primarily studying the intermolecular interactions and predicting its binding pattern and affinity. Wang et al isolated liver protecting peptide from pig liver, simulated its binding site with ADH by molecular docking means, and analyzed the product with peptide sequence Asp-Thr-Leu-Pro-His-Pro-Thr-Ala-Pro (NTLPHPTAP) with minimum energy (-0.88 kcal/mol) required for binding with ADH, i.e. with optimal ADH activating activity, which is helpful for promoting ethanol metabolism, scavenging free radicals, and improving alcoholic liver disease. Ren et al indicated that purification and identification of the most potent antioxidant active peptides YP-4 and LP-4 from freshwater mussel significantly improved the viability of ethanol-induced injured LO2 cells. Both peptides significantly reduced ROS levels and effectively inhibited the decline in mitochondrial membrane potential. YP-4 and LP-4 were found to have potential inhibitory activity on CYP2E1 by molecular docking, thereby reducing ethanol-induced oxidative stress.
The flavone is two benzene ring series compounds with phenolic hydroxyl groups, which are formed by connecting central three carbon atoms, and the basic parent nucleus is 2-phenyl chromone. Flavonoids have been the focus of drug research and development due to their diverse physiological activities and low biotoxicity. Puerarin (Puerarin) is also called puerarin, and is isoflavone derivative separated from radix Puerariae. Xu et al studied the differences in metabolites associated with alcohol exposure and puerarin action based on UPLC-MS/MS means. Metabonomics analysis showed that alcohol resulted in abnormal expression of 82 metabolites, involving 18 metabolic pathways and modules in total, including apoptosis, necrotic apoptosis, nucleotides and fatty acid metabolism. Puerarin reverses 7 metabolites associated with necrotic apoptosis and the sphingolipid metabolic pathway. Semen Hoveniae (Hoveniae) is dried mature seed of Hoveniae Thunnb, and contains abundant flavonoid components. Qiau et al fed Sprague-Dawley rats with Lieber-DeCarli diet containing alcohol or isocalogenic maltodextrin established a model of chronic alcoholic liver injury, and evaluated the effect of hovenia dulcis thunb extract (SHE) on improving liver injury and intestinal flora disorder through intestinal-hepatic axis level. Biochemical and histopathological analysis showed that SHE significantly reduced ethanol-induced liver lipid deposition and inflammatory response. SHE upregulates the expression of zonulin ZO-1 and occludin in the gut by inhibiting the TLR4 pathway and its downstream inflammatory mediators, and significantly reverses the ethanol-induced changes in gut microbiota, reducing the production of gut-derived endotoxins. Silymarin (SILYMARIN) is a natural flavonoid lignan compound. Tvrd ý et al hypothesize that silymarin may prevent alcoholic liver injury by inhibiting ADH, so the zinc chelating activity of pure silymarin flavone lignin was tested. Among the six flavone lignin tested, the 2, 3-dehydroderivatives (2, 3-dehydrosilybin and 2, 3-dehydrosilymarin) significantly sequester zinc ions and block the action of ADH, whether zinc ions are present or not. Thus 2, 3-dehydrosilybin may have a biologically relevant inhibitory effect on ADH and glutamate dehydrogenase.
A large number of researches show that both the food-borne bioactive peptide and the plant extract have good effect of preventing alcoholic liver injury. However, most of the existing researches only prove the anti-alcoholic and alcoholic liver injury protection effects of food functional factors independently, the difference in the functions of the food functional factors is not seen in the comparison researches, and the market lacks anti-alcoholic compound health food with clear synergistic effect.
Disclosure of Invention
Aiming at the problems existing in the prior art, the invention aims to provide a composition for preventing and treating alcoholic liver injury and application thereof. The method is realized by the following technical scheme:
a composition for preventing and treating alcoholic liver injury mainly comprises the following active ingredients of wheat peptide, turtle peptide and kudzuvine root powder.
Further, the mass percentage of each active ingredient in the composition is 16.7-66.6% of wheat peptide, 16.7-66.6% of turtle peptide and 16.7-66.6% of kudzuvine root powder.
Further, the mass percentage of each active ingredient in the composition is 16.7% of wheat peptide, 66.6% of turtle peptide and 16.7% of kudzuvine root powder.
The application of the composition in preparing health food or medicine for preventing and treating alcoholic liver injury.
Further, the health food is a functional food prepared from the composition and an edible carrier.
Further, the medicine is prepared from the composition and a pharmaceutically acceptable carrier.
The invention is researched by compounding the screened active peptide and plant extract and developing the anti-alcohol and liver-protecting effects of the compound from the intestinal microbiology and non-targeting metabonomics layers. Research shows that the compound intervention obviously improves the liver swelling induced by alcohol, and has synergistic effect in preventing liver cell injury (improving ALDH activity) and oxidative injury (improving SOD activity) caused by alcohol.
Drawings
FIG. 1 shows apparent histological observations of acute alcoholic liver disease of young zebra fish (100 x, A, control; B, model; C, corn peptide; D, wheat peptide; E, turtle peptide; F, first-order soybean peptide; G, third-order soybean peptide; H, sea cucumber peptide; I, kudzuvine root powder; J, hovenia dulcis thunb; K, silymarin; L, globe artichoke; M, curcumin; N, liver area. The difference in terms of different lowercase is significant (p < 0.05));
FIG. 2 is a graph showing the effect of bioactive peptides and plant extracts on hepatocyte damage (A, AST viability change; B, ALDH viability change);
FIG. 3 is the effect of bioactive peptides and plant extracts on acute alcoholic liver oxidative damage (A, SOD activity change; B, MDA activity change);
FIG. 4 is an effect of bioactive peptides and plant extracts on acute alcoholic liver lipid metabolism;
FIG. 5 shows the apparent histomorphology of acute alcoholic liver of young fish of the zebra fish (100 x, A, control group; B, model group; C, wheat peptide; D, turtle peptide; E, kudzuvine root powder; F, scheme one; G, scheme two; H, scheme three; I, scheme four; J, scheme five; K, scheme six; L, scheme seven; M, liver area);
FIG. 6 is the effect of the compound on acute alcoholic liver cell injury in young zebra fish (A, AST activity change; B, ALDH activity change);
FIG. 7 is the effect of the compound on acute alcohol liver oxidative damage of young zebra fish (A, SOD activity change; B, MDA activity change);
FIG. 8 is an effect of the complex on acute alcohol liver lipid metabolism in young zebra fish;
FIG. 9 is a complex recipe composite score case;
FIG. 10 shows the effect of the complex on the expression level of alcohol metabolism gene (A, expression level of cyp2y3 gene; B, expression level of cyp3A65 gene);
FIG. 11 is the effect of the complex on the expression level of lipid metabolism genes (A, acc1; B, fasn; C, hmgcra; D, hmgcrb);
FIG. 12 shows the effect of the complex on the expression level of oxidative damage genes (A, atf6; B, chop; C, gadd 45. Alpha. A).
Detailed Description
The invention is further described below with reference to the drawings.
1. Feeding and breeding of zebra fish
According to the breeding method of the zebra fish, the temperature is between 27.5 and 28.5 ℃ in brief, the illumination period is 14:10 (illumination is 14 h and darkness is 10 h), artificial sea salt is added to the breeding water in an amount of about 400 mg and NaHCO 3 is added to the breeding water in an amount of about 10 mg per liter of reverse osmosis water, the conductivity of the water body is between 450 and 550 mu S/cm, the pH is between 6.8 and 7.5, and the total hardness (calculated by CaCO 3) is between 50 and 100 mg/L. The feed is fed once in the morning and evening at regular time and quantity every day, and the fresh hatched brine shrimp and the solid fish feed are fed alternately. Mating behavior of zebra fish requires biological clock control of photoperiod, which stresses into mating spawning state at the beginning of each photoperiod. The zebra fish male fish and the zebra fish female fish are placed in a mating jar in a ratio of 2:1 at night before mating, and the male fish and the female fish are separated by a partition board. And (5) after the secondary sunlight period starts, the partition plate is removed, so that male and female fishes naturally mate and spawn. The fish eggs are collected and placed in a culture dish containing embryo culture solution, developed in a biochemical incubator at a constant temperature of 28 ℃, observed every day, and dead eggs are removed in time to replace fresh embryo culture solution.
2. Selection of modeling alcohol concentration of acute alcohol liver of juvenile zebra fish
The liver is completely formed when the zebra fish embryo develops to 96 hpf, and in order to avoid the influence of feeding on metabolism, the application utilizes the juvenile fish with 5dpf to establish an acute alcoholic liver model and carry out subsequent experiments. When the embryo grows to 5dpf, 540 juvenile fish with normal liver development are selected in time, and randomly divided into a control group, a 1.0% alcohol treatment group, a 1.5% alcohol treatment group, a 2.0% alcohol treatment group, a 2.5% alcohol treatment group and a 3.0% alcohol treatment group, and the juvenile fish are placed in a six-hole cell culture plate, 30 juvenile fish per hole and three parallel holes. The control group is cultured with embryo culture solution, the alcohol treatment group is cultured with embryo culture solution containing alcohol with corresponding concentration, and the culture is carried out under the condition of 28 ℃ and the illumination period of 14:10 for 48 h. And (5) observing and recording death conditions of the juvenile fish at a plurality of time points such as 6 th, 12 th, 24 th, 36 th and 48 h th, timely removing the dead fish and calculating survival rate.
3. Alcohol treatment and active substance intervention for juvenile zebra fish
Randomly selecting young fish of 5dpf zebra fish, dividing into control group, model group and active substance intervention group, wherein the intervention group is subdivided into 6 bioactive peptide groups including corn peptide, wheat peptide, turtle peptide, primary soybean peptide, tertiary soybean peptide and sea cucumber peptide, and 5 plant extract groups including radix Puerariae powder, semen Hoveniae powder, water-soluble silymarin, globe artichoke and curcumin. All group zebra fish were placed in six well cell culture plates, 30 per well, three wells in parallel. The control group was incubated with embryo culture medium, the model group was incubated with embryo culture medium containing 350 mM ethanol (2% ethanol solution), the intervention group was incubated with embryo culture medium containing 350 mM ethanol and 5 μg/mL active substance, and 48 h was incubated at 28℃under a light cycle of 14:10.
4. Apparent histomorphology observation of liver of young zebra fish
Selecting Tg zebra fish juvenile fish, anaesthetizing the juvenile fish with 0.02% of tricaine for 10-20 s, laterally fixing the juvenile fish in 4% of sodium carboxymethyl cellulose, and photographing under the conditions of fluorescent microscope bright field and fluorescent light. The relative liver areas of the livers of the individual groups of young zebra fish were quantified by ImageJ software.
5. Alcohol treatment and compound intervention for juvenile zebra fish
Selecting young fish of 5dpf zebra fish randomly, dividing into a control group, a model group and an active substance intervention group, and selecting wheat peptide, turtle peptide and radix puerariae powder for a compound experiment according to a preliminary screening result. The intervention group is subdivided into 3 single active substance intervention groups, namely wheat peptide, turtle peptide, kudzuvine root powder and 7 compound intervention groups. The compounding scheme was designed by Minitab Statistical software, and the details are shown in table 1. All group zebra fish were placed in six well cell culture plates, 30 per well, three wells in parallel. The control group was incubated with embryo culture medium, the model group was incubated with embryo culture medium containing 350 mM ethanol (2% ethanol solution), the intervention group was incubated with embryo culture medium containing 350 mM ethanol and 5 μg/mL active substance, and 48 h was incubated at 28℃under a light cycle of 14:10. Wherein the peptide and radix Puerariae powder are derived from Hangzhou Kangyuan food technology Co.
TABLE 1 design of complex formulation
6. Analysis of synergistic action of Living active peptide and plant extract
The synergy of the combined drug is analyzed by adopting drug interaction coefficients (Drug interaction coefficient, CDI), and the calculation formula is as follows:
①
N AB is the ratio of the parameters of the bioactive peptide and plant extract compound action group to the model group, and N A or N B is the ratio of the independent intervention group to the model group of the corresponding parameters. If CDI <1, this indicates that there is a synergistic effect between the drugs, if cdi=1, this indicates that there is an additive effect between the drugs, and if CDI >1, this indicates that there is an antagonistic effect between the drugs.
7. Biochemical analysis of juvenile zebra fish
The method comprises the steps of selecting AB zebra fish juvenile fish, and determining relevant biochemical indexes according to the specification steps of a kit, wherein the relevant biochemical indexes comprise hepatocyte injury (AST and ALDH), oxidative injury (SOD and MDA) and lipid metabolism (TG).
8. Data processing
The chemistry experiments were repeated 3 times and the results were analyzed for statistics and significance using GRAPHPAD PRISM 9.5.5 software and plotted. The two sets of data are compared by adopting independent sample T test, and the multiple sets of data are compared by adopting single factor analysis of variance and Tukey's test for multiple comparison analysis. The fuzzy comprehensive evaluation matrix operation is calculated by MATLAB2023 b. Experimental data are expressed as Mean ± standard error (Mean ± SEM). With p <0.05 being a statistically significant difference, p <0.05, p <0.01, p <0.001, p <0.0001.
Analysis results
1. Influence of bioactive peptide and plant extract on apparent histomorphology of acute alcoholic liver of juvenile zebra fish
The protective effect of bioactive peptide and plant extract on alcohol-induced liver injury can be intuitively and rapidly compared by directly observing the apparent morphology of liver, and the result is shown in figure 1. Compared with a control group, the liver of the model group is obviously swelled, and the acute alcoholic liver injury model of the zebra fish after 2% alcohol exposure treatment is presumed to be successfully established, so that lipid droplets are accumulated in the liver. The liver area calculation (N in fig. 1) shows that the model group has a significant increase in liver area (p < 0.05) compared to the control group. The wheat peptide group, the soft-shelled turtle peptide group and the kudzuvine root powder group significantly improve the liver area enlargement induced by 2% alcohol exposure (p < 0.05) compared with the model group. Compared with the model group, the rest bioactive peptides and plant extracts have the trend of inhibiting the increase of liver area, but are not obvious, so that the bioactive peptides and plant extracts also have a certain protective effect on the liver enlargement induced by 2% alcohol.
2. Influence of bioactive peptide and plant extract on acute alcoholic liver cell injury of juvenile zebra fish
The content of AST in normal liver cells is low, when liver cells are damaged, the permeability of cell membranes is increased, and the concentration of AST in cytoplasm is increased due to the release of AST, so that the change of AST value can be used as an index for judging the damage of liver cells. ALDH is widely found in a variety of animals, plants and microorganisms. The main function is to oxidize acetaldehyde into acetic acid, which plays an important role in alcohol metabolism. The present application measured the two indices related to hepatocyte damage, and the results are shown in FIG. 2. The AST activity of the model group was significantly increased (p < 0.001) and the ALDH activity was significantly decreased (p < 0.0001) compared to the control group, and it was confirmed that the zebra fish acute alcoholic liver injury model was successfully established. The majority of active peptides and plant extracts in the intervention group showed repair ability to damaged hepatocytes under the influence of alcohol, wherein the top three ranks of significantly decreasing the activity of AST compared to the model group were wheat peptide group, kudzuvine root powder group and artichoke group (a, p <0.0001 in fig. 2), respectively, the activity of wheat peptide group AST was decreased by 48.8%, while the top three ranks of increasing the activity of ALDH were turtle peptide group, maize peptide group and kudzuvine root powder group (B, p <0.05 in fig. 2), respectively, the ALDH activity of turtle peptide group was 1.62 times that of the model group. According to the overall trend, the effect of the active peptide and the plant extract on reducing the activity of AST is more similar, and the effect of the active peptide on improving the activity of ALDH is better than that of the plant extract.
3. Influence of bioactive peptide and plant extract on acute alcoholic liver oxidation injury of juvenile zebra fish
SOD plays a vital role in oxidation and antioxidation balance of organisms, and can remove superoxide anion free radicals (O 2-•. Cndot.) and protect cells from damage. The activity of SOD indirectly reflects the capability of the organism to remove oxygen free radicals. Oxygen radicals produced by the body attack polyunsaturated fatty acids in the biofilm, causing lipid peroxidation and thus formation of lipid peroxides such as aldehyde (MDA), ketone, hydroxyl, carbonyl, hydroperoxy or endoperoxy groups, and new oxygen radicals. In addition, oxygen radicals can cause cell damage through the breakdown products of lipid hydroperoxides. Therefore, the MDA content can be used as an index for reflecting the peroxidation degree of the lipid in the organism, and indirectly reflects the cell damage degree. The two oxidative damage related indexes were measured in this study, and the results are shown in fig. 3. Compared with a control group, the SOD activity of the model group is obviously reduced, and the MDA content is obviously increased, so that the success of the establishment of the zebra fish acute alcohol liver injury model is further proved. The majority of active peptides and plant extracts of the intervention group show the capability of preventing and repairing oxidative damage of organisms under the influence of alcohol, wherein the top three ranks of increasing SOD activity compared with the model group are respectively a sea cucumber peptide group, a kudzuvine root powder group and a silymarin group (A in figure 3), the SOD activity of the sea cucumber peptide group is 1.21 times that of the model group, the SOD activity of the kudzuvine root powder group and the silymarin group is also more than 1.15 times that of the model group, the top three ranks of reducing MDA content are respectively a wheat peptide group, a curcumin group and a kudzuvine root powder group (B in figure 3, p is less than 0.0001), and the MDA contents of the wheat peptide group and the curcumin group are respectively 65.9 percent and 64.1 percent of the model group. The plant extract has better effect on improving SOD activity and reducing MDA content than active peptide.
4. Influence of bioactive peptide and plant extract on acute alcoholic liver lipid metabolism of juvenile zebra fish
TG is a risk factor for cardiovascular disease. Short-term high volume drinking or long-term drinking can lead to symptoms of hyperglycemia and high triglycerides in the human body. The application determines the TG content of the zebra fish after the action of the active peptide and the plant extract in the acute alcoholic liver injury model, and the result is shown in figure 4. Compared with the control group, the TG content of the model group is obviously increased (p is less than 0.01), and the model group is consistent with the detection results of other biochemical indexes, so that the success of the establishment of the acute alcoholic liver model of the zebra fish is strongly proved. In the intervention group, the first three ranks for reducing the TG content are respectively a kudzuvine root powder group, a soft-shelled turtle peptide group and a sea cucumber peptide group, compared with the model group, the liver TG content is obviously reduced (p is less than 0.01), and the TG content of the kudzuvine root powder group is reduced by 30.2%. The effect of the active peptide and the plant extract on reducing the TG content is relatively similar.
5. Influence of compound on apparent histomorphology of acute alcoholic liver of juvenile zebra fish
The observation of the direct photographing of Tg zebra fish under a fluorescence microscope is shown in fig. 5. The liver area calculation result (M in figure 5) shows that the individual intervention groups of the wheat peptide, the turtle peptide and the kudzuvine root powder obviously show the prevention effect on acute alcoholic liver injury (p < 0.05), the liver area approaches to a control group, compared with a model group, the scheme I and the scheme II obviously prevent the liver area from being enlarged (p < 0.05) induced by 2% alcohol exposure, and the liver area after the other compound formula acts shows the trend of being reduced, but does not obviously show that the compound formula also has the effect of reversing alcoholic liver injury to a certain extent.
6. Influence of compound on acute alcoholic liver cell injury of juvenile zebra fish
The present application measured two indices related to hepatocyte damage, AST and ALDH, and the results are shown in FIG. 6. The two, three, five and six protocols significantly reduced the AST viability of the hepatocytes treated with 2% alcohol exposure (a, p <0.05 in fig. 6), with the AST viability of the two and three protocols reduced by approximately 30%, with the remaining protocols other than the three protocol exhibiting a trend of increasing ALDH viability after action, with the protocol one having a significant difference compared to the model group (B, p <0.05 in fig. 6), ALDH viability being 1.38 times that of the model group.
7. Influence of compound on acute alcoholic liver oxidation injury of juvenile zebra fish
The present application measured two oxidative damage related indicators, SOD and MDA, and the results are shown in FIG. 7. The SOD activity of the fourth scheme is 1.17 times that of the model group, the SOD activity of the 2% alcohol exposure treatment is obviously improved (A, p <0.05 in figure 7), the rest of the compound schemes show the trend of improving the SOD activity, but the SOD activity is not obviously improved, all the schemes obviously reduce the MDA content (B, p <0.05 in figure 7), the MDA content of the fifth scheme is reduced by 52.5% compared with the model group, and the compound effect of the wheat peptide, the turtle peptide and the kudzuvine root powder has obvious effect on reducing the MDA content in the acute alcoholic liver injury model of the juvenile fish of the zebra fish.
8. Influence of compound on acute alcoholic liver lipid metabolism of juvenile zebra fish
The present application measured the content of TG, a lipid metabolism related index, and the results are shown in fig. 8. The seven compounding schemes obviously reduce the TG content (p < 0.05) of 2% alcohol exposure treatment, wherein the TG content of the scheme II and the scheme IV is respectively reduced by 52.6% and 45.1% compared with a model group, and the influence effect of the compounding scheme acting group on the TG content is superior to that of an active substance independent intervention group in terms of overall trend, so that the compound combination of wheat peptide, turtle peptide and kudzuvine root powder possibly has a certain synergistic effect in regulating lipid metabolism.
9. Fuzzy comprehensive evaluation (FSE) and synergy (CDI) analysis
According to the morphological observation of the apparent tissues and the measurement results of related biochemical indexes, the conclusion can be obtained that the compound product of the wheat peptide, the turtle peptide and the kudzuvine root powder has a certain prevention effect on acute alcoholic liver injury. To quantify the composite score of each compounding scheme, the biochemical index data is analyzed and calculated by a fuzzy comprehensive evaluation (FSE) method. All data are normalized, the result is shown in table 2, and then the weight vector omega= (0.1690,0.1870,0.1824,0.2051,0.2565) is obtained by calculating the entropy weight. And finally, calculating a comprehensive score, wherein the result is shown in fig. 9, the comprehensive score of the scheme six is 0.6098, which is higher than that of other schemes, and the liver area increase caused by 2% alcohol treatment is obviously prevented in the apparent histomorphology observation result (p < 0.05), so that the follow-up action mechanism exploration and the chronic alcoholic liver injury research experiment are confirmed to be carried out according to the proportion of 16.7% of wheat peptide, 66.6% of turtle peptide and 16.7% of kudzu root powder.
TABLE 2 Biochemical index data normalization
The CDI values of five biochemical indicators of each compound formulation were calculated according to formula ①, and the results are shown in table 3. Seven compounding schemes of AST activity CDI >1 show that the compounded products of the wheat peptide, the turtle peptide and the kudzuvine root powder have no synergistic effect in reducing the alcohol-induced increase of AST activity. ALDH and SOD viability CDI of all the compounding regimens <1, with ALDH viability cdi=0.422657 and SOD viability cdi= 0.747854 of regimen six, with significant synergy. In terms of MDA and TG content, the synergistic trend of the anti-hangover and liver-protecting effects of the schemes is different, and the MDA and TG content CDI <1 of the scheme I shows that the compound scheme has a synergistic effect in improving the two indexes. The method also has a third scheme of synergistic effect on reducing MDA content, and a second scheme of synergistic effect on reducing TG content is also shown to a certain extent.
TABLE 3 CDI value scoring Table for different biochemical indicators for each protocol
10. Influence of compound on acute alcohol liver and alcohol metabolism gene expression quantity of juvenile zebra fish
The expression levels of two genes, cyp2y3 and cyp3a65, related to alcohol metabolism in each group of zebra fish were evaluated. CYP2y3 and CYP3a65 are members of the cytochrome P450 (CYP) family, and are mainly present in the liver of zebra fish, playing a vital role in alcohol metabolism. Blocking the expression of CYP homologous genes can reduce damage caused by alcohol metabolism and oxidative stress. Fig. 10 shows that the compound intervention significantly (p < 0.05) down-regulates the expression level of both, and speculates that the compound may have a preventive effect on acute alcoholic liver injury by promoting alcohol metabolism, reducing ROS content induced by CYP, and reducing the degree of oxidative damage to the liver.
11. Influence of compound on expression level of acute alcoholic liver lipid metabolism genes of juvenile zebra fish
In order to further evaluate whether the compound has the capacity of regulating lipid metabolism, improving lipid homeostasis, resisting liver steatosis caused by alcohol and the like, the application selects several key genes related to lipid metabolism, including fatty acid synthesis genes (acc 1 and fasn) and cholesterol synthesis genes (hmgcra and hmgcrb) for detection. The results of RT-qPCR (fig. 11) show that compared with the control group, the alcohol treatment resulted in significantly up-regulating the mRNA expression level of the young zebra fish (p < 0.05), while the complex intervention significantly (p < 0.05) down-regulated the expression of the fatty acid synthesis related genes (acc 1 and fasn), but did not significantly affect the cholesterol synthesis related genes (hmgcra and hmgcrb), indicating that the complex may regulate lipid metabolism by regulating the fatty acid synthesis pathway.
12. Influence of compound on acute alcohol liver oxidation injury gene expression level of juvenile zebra fish
In each pathological type of alcoholic liver injury, endoplasmic reticulum stress and DNA damage caused by oxidative damage play a key role. The present application compares the mRNA expression levels of gene atf6 and chop and gadd45 a associated with endoplasmic reticulum stress and DNA damage (fig. 12), confirming that the complex can significantly reduce the chop mRNA level (B, p <0.05 in fig. 12) raised by the influence of alcohol induction, but the influence on gadd45 a expression level is not significant (p > 0.05), showing only a trend of reduction. Compared with the model group, the expression quantity of the atf6 after the compound is interfered is not obvious. It is therefore speculated that the complex may alleviate alcohol-induced apoptosis of hepatocytes by inhibiting DNA damage pathways to achieve liver protection.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107811296A (en) * | 2017-11-03 | 2018-03-20 | 安徽生物肽产业研究院有限公司 | A kind of health-oriented products with effects of relieving alcoholism and protecting liver |
| CN112353792A (en) * | 2020-10-29 | 2021-02-12 | 南通大学 | Application of eupatilin in preparing medicament for preventing or treating alcoholic liver disease |
| US20210169961A1 (en) * | 2018-08-03 | 2021-06-10 | Shuguang Hospital Affiliated To Shanghai University Of Traditional Chinese Medicine | Hepatoprotective traditional chinese medicine composition, extract thereof, and pharmaceutical use thereof |
| CN118236421A (en) * | 2022-12-22 | 2024-06-25 | 浙江维康药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicines for treating or preventing alcoholic fatty liver |
-
2025
- 2025-01-13 CN CN202510046119.0A patent/CN119454895A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107811296A (en) * | 2017-11-03 | 2018-03-20 | 安徽生物肽产业研究院有限公司 | A kind of health-oriented products with effects of relieving alcoholism and protecting liver |
| US20210169961A1 (en) * | 2018-08-03 | 2021-06-10 | Shuguang Hospital Affiliated To Shanghai University Of Traditional Chinese Medicine | Hepatoprotective traditional chinese medicine composition, extract thereof, and pharmaceutical use thereof |
| CN112353792A (en) * | 2020-10-29 | 2021-02-12 | 南通大学 | Application of eupatilin in preparing medicament for preventing or treating alcoholic liver disease |
| CN118236421A (en) * | 2022-12-22 | 2024-06-25 | 浙江维康药业股份有限公司 | Application of traditional Chinese medicine composition in preparation of medicines for treating or preventing alcoholic fatty liver |
Non-Patent Citations (3)
| Title |
|---|
| NAN LI ET AL.: ""Targetable Brg1-CXCL14 axis contributes to alcoholic liver injury by driving neutrophil trafficking"", 《EMBO MOLECULAR MEDICINE》, vol. 15, 1 February 2023 (2023-02-01), pages 1 - 18 * |
| 于兰兰等: ""小麦低聚肽对急性酒精中毒小鼠 抗氧化功能的影响"", 《食品科学》, vol. 41, no. 7, 31 December 2020 (2020-12-31), pages 159 - 163 * |
| 梁婕等: ""葛根提取物对小鼠酒精性肝损伤的辅助保护效果"", 《江苏预防医学》, vol. 31, no. 3, 31 May 2020 (2020-05-31), pages 280 - 282 * |
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