Application of rhizoma polygonati and pharmaceutical composition thereof in preparation of medicine for preventing and treating kidney and liver injury

Abstract

The invention discloses application of rhizoma polygonati and a pharmaceutical composition thereof in preparation of a medicine for preventing and treating kidney and liver injury. Polygonatum sibiricum plays an anti-inflammatory role by inhibiting an NF-kappa B signal channel, in addition, the anti-oxidation defense capability can be enhanced by activating an Nrf2 / ARE channel, and the acute alcoholic liver injury is remarkably improved through anti-inflammatory and anti-oxidation dual mechanisms. The invention further provides application of the rhizoma polygonati composition to preparation of a medicine for preventing and treating kidney and liver injury, compared with a single rhizoma polygonati medication group, the rhizoma polygonati and hormone combined medication can effectively reduce the content of MDA, TNF-alpha and IL-1beta in liver tissue after drinking a large amount, and improve the content of SOD and IL-10. The compound composition provided by the invention shows a remarkable synergistic effect in prevention and treatment of kidney injury and / or liver injury, can reduce the dosage of a single drug and reduce the risk of side effects, and has a relatively high pharmaceutical application value in preparation of drugs for treating acute alcoholic liver and kidney injury.

Description

Technical Field

[0001] The present invention belongs to the technical fields of pharmacology and medicinal chemistry, and particularly relates to the application of polygonatum sibiricum and its pharmaceutical composition in the preparation of drugs for preventing and treating kidney and liver injuries. Background Art

[0002] Excessive alcohol consumption not only causes abnormal liver function, but also causes serious damage to the kidneys, cardiovascular system and nervous system. Among them, the liver and kidneys are the organs most easily affected by ethanol and its metabolites (such as acetaldehyde). Alcoholic liver injury is a type of liver injury induced by long-term excessive alcohol consumption. According to different pathological characteristics, it can progress from alcoholic liver injury to alcoholic fatty liver, alcoholic hepatitis, alcoholic liver fibrosis, alcoholic cirrhosis and even liver cancer, etc. Among them, acute alcoholic kidney injury specifically refers to the acute deterioration of renal function caused by a large amount of alcohol consumption in a short period of time. In terms of the kidneys, acute alcohol intake also causes abnormal renal function, manifested as elevated levels of serum creatinine (Scr) and blood urea nitrogen (BUN). After a large amount of ethanol is ingested into the body, it promotes the large production of reactive oxygen species such as superoxide anion and hydrogen peroxide, and causes a decrease in antioxidant components such as glutathione (GSH) and superoxide dismutase (SOD) in the body, thereby triggering oxidative stress. This process causes toxic effects such as peroxidation of macromolecular substances in liver and kidney cells, resulting in elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum urea nitrogen (BUN), and serum creatinine (Scr) in the serum, and a series of excessive inflammatory reactions in liver and kidney cells and leading to cell necrosis. At present, there is no clinically effective drug for the treatment of acute alcoholic liver and kidney injuries, and there is an urgent need to develop safe and effective preventive and treatment drugs. Summary of the Invention

[0003] In order to overcome the problems existing in the above-mentioned prior art, one of the purposes of the present invention is to provide the application of polygonatum sibiricum or its extract. Another purpose of the present invention is to provide the application of a pharmaceutical composition.

[0004] Polygonatum sibiricum is a plant of the genus Polygonatum in the family Liliaceae, and it is the dried rhizome of Polygonatum kingianum Coll. et Hemsl., Polygonatum sibiricum Red. and Polygonatum cyrtonema Hua, plants of the genus Polygonatum in the family Liliaceae. Polygonatum sibiricum contains various nutrients, such as vitamins, amino acids, minerals, starch, and dietary fiber, etc. It is rich in a large number of active ingredients such as polysaccharides, polyphenols, saponins, flavonoids, alkaloids, and lectins, and has functions such as anti-fatigue, anti-inflammatory, antioxidant, hypoglycemic, immune-enhancing, and anti-cancer effects. However, at present, the research on the prevention and treatment mechanisms of Polygonatum sibiricum on acute alcohol-induced liver and kidney injuries is still insufficient, especially the specific molecular mechanisms of antioxidant and anti-inflammatory effects and the combination of drugs need to be further explored. The present invention applies Polygonatum sibiricum to the drugs for preventing and treating alcoholic liver and kidney injuries, and through experiments, it is found that Polygonatum sibiricum has a good effect on preventing and treating alcoholic liver and kidney injuries, providing a theoretical basis for the development of new treatment strategies based on Polygonatum sibiricum and expanding the new applications of Polygonatum sibiricum.

[0005] In order to achieve the above object, the technical solution adopted by the present invention is:

[0006] The first aspect of the present invention provides the application of Polygonatum sibiricum in the preparation of drugs for preventing and treating kidney injury and / or liver injury.

[0007] Preferably, the application of Polygonatum sibiricum or its extract in the preparation of drugs for preventing and treating kidney injury and / or liver injury, wherein the traditional Chinese medicine extract is a product formed by taking traditional Chinese medicine as raw materials and applying modern physical and chemical extraction, separation, and purification technologies to obtain one or more target components therein according to the needs of the final product's use. It can be either a single compound (a single active ingredient with a clear structure, such as polysaccharides or flavonoids of Polygonatum sibiricum) or a mixture containing multiple components (such as water extract or alcohol extract).

[0008] More preferably, the Polygonatum sibiricum extract includes at least one of polysaccharides, flavonoids, anthraquinone compounds, and steroidal saponins of Polygonatum sibiricum.

[0009] Preferably, the kidney injury includes alcoholic kidney injury, chemical kidney injury, and immune kidney injury; the liver injury includes alcoholic liver injury, chemical liver injury, and immune liver injury.

[0010] Preferably, the alcoholic kidney injury includes acute alcoholic kidney injury; the alcoholic liver injury includes acute alcoholic liver injury.

[0011] The second aspect of the present invention provides the application of a drug composition in the preparation of drugs for preventing and treating alcoholic liver injury and / or alcoholic kidney injury, wherein the drug composition includes Polygonatum sibiricum and hormones.

[0012] Preferably, the hormones include at least one of peptide hormones, amino acid hormones, amine hormones, and steroid hormones.

[0013] More preferably, the amine hormone includes at least one of serotonin and melatonin.

[0014] More preferably, the steroid hormone includes at least one of glucocorticoid and mineralocorticoid.

[0015] Further preferably, the glucocorticoid includes at least one of dexamethasone, betamethasone, triamcinolone acetonide, fluticasone, budesonide, clobetasol propionate, and hydrocortisone butyrate.

[0016] Preferably, the mass ratio of the polygonatum sibiricum to the hormone is 10:(0.1 - 3).

[0017] More preferably, when the hormone is melatonin, the mass ratio of the polygonatum sibiricum to the hormone is 10:(0.5 - 2).

[0018] More preferably, when the hormone is dexamethasone, the mass ratio of the polygonatum sibiricum to the hormone is 10:(1 - 2.5).

[0019] Preferably, the polygonatum sibiricum is used as the active ingredient.

[0020] More preferably, the polygonatum sibiricum is used as the sole active ingredient.

[0021] Preferably, the drug further includes a pharmaceutically acceptable excipient.

[0022] More preferably, the excipient includes at least one of a desiccant, a stabilizer, an antioxidant, a disintegrant, a lubricant, a colorant, and a dispersant.

[0023] Substances that can be used as pharmaceutically acceptable excipients include, but are not limited to, ion exchangers; aluminum; aluminum stearate; lecithin; serum proteins such as human serum albumin; buffering substances such as phosphates; glycine; sorbic acid; potassium sorbate; partial glyceride mixtures of saturated vegetable fatty acids; water; salts or electrolytes such as protamine sulfate, disodium hydrogen phosphate, potassium hydrogen phosphate, sodium chloride, zinc salts; colloidal silicon; magnesium trisilicate; polyvinylpyrrolidone; polyacrylates; waxes; polyethylene-polypropylene-block polymers; lanolin; sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose and cellulose acetate; gum powder; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; diol compounds such as propylene glycol and polyethylene glycol; esters such as ethyl oleate and ethyl laurate; agar; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic salts; Ringer's solution; ethanol; phosphate buffer solution; and other non-toxic and suitable lubricants such as sodium lauryl sulfate and magnesium stearate; coloring agents; release agents; preservatives and antioxidants.

[0024] Preferably, the drug includes an oral preparation or an injection preparation.

[0025] More preferably, the dosage forms of the oral preparation include granules, tablets, powders, capsules, oral solutions, oral suspensions, dry suspensions, oral emulsions, mucilages, oral liquids, emulsions, colloidal solutions, mixtures, tinctures, drops, suspension drops, syrups, sustained-release tablets, sustained-release coated tablets, controlled-release tablets, sustained-release capsules, controlled-release capsules.

[0026] More preferably, the dosage forms of the injection preparation include injections, injection solutions, injection solutions for use, intravenous drip injection solutions, injection suspensions, sterile powders for injection, intravenous injection needles, injection emulsions, emulsion injections, powder injections, injection needles, sterile powder injections, freeze-dried powder injections, concentrated solutions for injection.

[0027] The beneficial effects of the present invention are:

[0028] 1. The present invention proposes the application of polygonatum sibiricum in the preparation of drugs for preventing and treating kidney injury and / or liver injury. Polygonatum sibiricum can significantly improve acute alcoholic liver injury through dual mechanisms of anti-inflammation and antioxidant. Among them, polygonatum sibiricum can regulate the decrease of TNF-α and IL-1β levels and the increase of IL-10 level in liver tissue, and can play an anti-inflammatory role by inhibiting the NF-κB signaling pathway, reducing the liver inflammatory response caused by alcohol. In addition, polygonatum sibiricum can regulate the significant increase of glutathione peroxidase (GSH-Px) and superoxide dismutase (T-SOD) levels and the significant decrease of lipid peroxide (MDA) level in liver tissue, and can also enhance the antioxidant defense ability by activating the Nrf2 / ARE pathway, producing an antioxidant effect on the liver tissue with acute alcohol injury. Therefore, developing polygonatum sibiricum into a drug for preventing and treating kidney injury and / or liver injury, and further as a drug for acute alcoholic kidney and liver injury, has great application potential.

[0029] 2. The present invention also proposes the application of a composition containing polygonatum sibiricum in the preparation of drugs for preventing and treating kidney injury and / or liver injury. Among them, the TNF-α inhibitory effect of the combined use of polygonatum sibiricum and hormones (further glucocorticoids or amine hormones) is significantly better than that of the single polygonatum sibiricum group, and can effectively reduce the contents of MDA, TNF-α, and IL-1β in liver tissue after a large amount of alcohol consumption, and increase the contents of T-SOD and IL-10. The compound composition provided by the present invention shows a significant synergistic effect in preventing and treating kidney injury and / or liver injury, can reduce the dosage of a single drug, and reduce the risk of side effects, and has high pharmaceutical application value in the preparation of drugs for treating acute alcoholic liver injury and kidney injury. Brief Description of the Drawings

[0030] Figure 1 It is the experimental process of endotoxemia modeling and drug administration in mice;

[0031] Figure 2 It is the effect of polygonatum sibiricum at different concentrations on the body weight of mice;

[0032] Figure 3 It is the liver index of mice in different groups;

[0033] Figure 4 It is the kidney index of mice in different groups;

[0034] Figure 5 It is the content of ALT in mice in each group after modeling on the 7th day;

[0035] Figure 6 It is the content of AST in mice in each group after modeling on the 7th day;

[0036] Figure 7 It is the content of ALT in mice in each group after modeling on the 8th day;

[0037] Figure 8 It is the content of AST in mice in each group after modeling on the 8th day;

[0038] Figure 9 The content of UREA in mice of each group after modeling on the 7th day;

[0039] Figure 10 The content of UREA in mice of each group after modeling on the 8th day;

[0040] Figure 11 The content of CREA in mice of each group after modeling on the 7th day;

[0041] Figure 12 The content of CREA in mice of each group after modeling on the 8th day;

[0042] Figure 13 The content of TNF-α in the liver tissue of mice of each group after modeling on the 7th day;

[0043] Figure 14 The content of IL-1β in the liver tissue of mice of each group after modeling on the 7th day;

[0044] Figure 15 The content of IL-10 in the liver tissue of mice of each group after modeling on the 7th day;

[0045] Figure 16 The content of TNF-α in the liver tissue of mice of each group after modeling on the 8th day;

[0046] Figure 17 The content of IL-1β in the liver tissue of mice of each group after modeling on the 8th day;

[0047] Figure 18 The content of IL-10 in the liver tissue of mice of each group after modeling on the 8th day;

[0048] Figure 19 The content of GSH-PX in the liver tissue of mice of each group after modeling on the 7th day;

[0049] Figure 20 The content of MDA in the liver tissue of mice of each group after modeling on the 7th day;

[0050] Figure 21 The content of T-SOD in the liver tissue of mice of each group after modeling on the 7th day;

[0051] Figure 22 The content of GSH-PX in the liver tissue of mice of each group after modeling on the 8th day;

[0052] Figure 23 The content of MDA in the liver tissue of mice of each group after modeling on the 8th day;

[0053] Figure 24 The content of T-SOD in the liver tissue of mice of each group after modeling on the 8th day;

[0054] Note: *, P < 0.05 compared with the control group; #, P < 0.05 compared with the model group; △, P < 0.05 compared with the low-dose polygonatum group; □, P < 0.05 compared with the medium-dose polygonatum preventive group; ●, P < 0.05 compared with the medium-dose polygonatum treatment and preventive group. Detailed implementation manners

[0055] The content of the present invention will be further described in detail below through specific embodiments. The raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and separated by simple synthesis unless otherwise specified; the processes used, unless otherwise specified, are conventional processes in the art.

[0056] Example 1

[0057] 1. Experimental supplies and preparations before the experiment

[0058] (1) Experimental animals: A total of 48 SPF-grade male KM mice, 5 - 6 weeks old, weighing 25 - 30 g, were purchased from Zhuhai Bestong Biotechnology Co., Ltd. [License number: SYXK (Guangdong) 2023 - 0183]. They were caged separately for five days before the experiment, and were allowed free movement and diet during this period.

[0059] (2) The experimental reagents and kits are shown in Table 1:

[0060] Table 1 Reagents required for the experiment, batch numbers, and manufacturers

[0061]

[0062] (3) Preparation of experimental reagents:

[0063] Polygonatum mother liquor: Weigh 140 mg of polygonatum and dissolve it in 7 mL of hot purified water to prepare a mother liquor with a concentration of 20 mg / mL.

[0064] High-dose polygonatum solution: Take 0.7 mL of the polygonatum mother liquor and add 6.3 mL of hot purified water to prepare a solution with a concentration of 2 mg / mL.

[0065] Medium-dose polygonatum solution: Take 4.5 mL of the high-dose polygonatum solution and add 4.5 mL of hot purified water to prepare a solution with a concentration of 1 mg / mL.

[0066] Low-dose polygonatum solution: Take 1.5 mL of the medium-dose polygonatum solution and add 1.5 mL of hot purified water to prepare a solution with a concentration of 0.5 mg / mL.

[0067] Dexamethasone solution: Take 1 mL of 5 mg / 5 mL dexamethasone injection and add 5 mL of 0.9% normal saline to prepare a solution with a concentration of 0.167 mg / mL.

[0068] Melatonin solution: Weigh 100 mg of melatonin powder and dissolve it in 0.5 mL of 95% ethanol, then add 19.5 mL of 0.9% sodium chloride solution to prepare a solution with a concentration of 5 mg / mL. Then take 1 mL of this solution and dilute it 50 times with 0.9% sodium chloride to prepare a solution with a concentration of 0.1 mg / mL.

[0069] (4) Number 48 female Kunming (KM) mice one by one, and use a random mouse to divide the animals into 8 groups, with 6 mice in each group. The specific grouping of experimental animals and the dosage of drug administration are shown in Table 2:

[0070] Table 2 Grouping of experimental animals and drug administration methods

[0071]

[0072] For the above groups of polygonatum sibiricum, they were respectively administered by gavage at the corresponding doses, dexamethasone by tail vein injection, and melatonin by intraperitoneal injection. According to the prepared concentration, the volume of each drug administration was 0.1 mL·10 g -1 , and 0.5 mL of 0.9% sodium chloride solution was intraperitoneally injected for all. Administer the drugs continuously for 8 days, once a day. On the 8th day, the medium-dose prevention group was intraperitoneally injected with 0.9% sodium chloride solution, and the remaining groups were still administered according to the original method.

[0073] (5) The method for establishing acute alcohol-induced liver and kidney injury is as follows:

[0074] 2 - 3 hours after drug administration on the 6th day, except for the control group, the remaining mice were gavaged with white liquor at a dose of 13 mL / kg, once every two days, with a 12-hour interval between the two gavages.

[0075] (6) The process of experimental animal modeling and drug administration is as Figure 1 shown, and the specific steps are as follows:

[0076] After 3 days of adaptive cultivation of all Kunming (KM) mice, they were randomly divided into 8 groups. On the 1st and 6th days during the drug administration period, the body weight of each mouse was measured once before drug administration. The dosage of each mouse was 0.1 mL / 10 g. The control group of mice was continuously injected with normal saline for 8 days, once a day, and no modeling treatment was carried out during this period; the remaining groups other than the control group were continuously administered prophylactically for 6 days, once a day, and modeling was carried out 2 hours after drug administration on the 6th day. On the 7th day, continue the modeling and drug administration. 12 hours after the end of modeling, 3 mice in each group of all groups were sacrificed for liver tissue sampling and preservation. On the 8th day, the body weight was measured once before drug administration. The normal group, the model group, and the medium-dose prevention group were intraperitoneally injected with 0.5 mL of normal saline, and the remaining groups were treated with therapeutic drug administration according to the above drug administration method. 12 hours after the end of treatment, the remaining 3 mice in each group were sacrificed, and the liver tissue was also sampled and preserved.

[0077] 2. Index test methods

[0078] (1) Serum liver and kidney biochemical detection

[0079] On the 7th and 8th days of the experiment, blood was collected before killing, and after 0.5 h of stratification, the cells were rotated at 3500 r / min. -1 Centrifuge for 10 minutes, use a pipette to absorb the separated serum and transfer it to a new centrifuge tube. If the serum contains trace blood cells, place the serum sample at 3500r / min again. -1 The samples were centrifuged for 5 min to separate the remaining red blood cells. The aliquoted serum was stored in a -80°C refrigerator. The liver biochemical indicators alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and the kidney biochemical indicators creatinine (CREA) and urea (UREA) activity were detected using an automatic biochemical analyzer.

[0080] (2) Detection of inflammatory factors and oxidative stress indicators in liver tissue (ELISA test)

[0081] After removing the eyeballs and collecting blood, the mice were killed by cervical dislocation, and the mice were immediately dissected. The mouse liver tissue was placed in a 1.5mL EP tube and immediately placed in a -80℃ refrigerator for freezing. A certain amount of liver tissue was cut, PBS, pH7.4 was added, and it was fully homogenized with a homogenizer, centrifuged at 2000r·min-1 for 20min, and the supernatant was taken on ice for testing. Samples were added according to the steps in the instructions of the corresponding kit, and the contents of oxidative stress indicators GSH-PX, T-SOD and MDA in the liver tissue of each group of mice were determined; the contents of inflammatory factors IL-1β, IL-10 and TNF-α were also detected.

[0082] (3) Statistical methods

[0083] The statistical results of the experimental data were presented as "mean ± standard deviation (x ± s). SPSS26.0 software was used to compare the data among the groups through one-way analysis of variance. In the variance homogeneity test, if P>0.05, it indicated that the variance was homogeneous. The LSD method was used for post hoc multiple comparisons, otherwise the Tamhane method was used. When performing multiple comparisons, if P<0.05, it means that the data difference is statistically significant. At the same time, GraphPad Prism10.0 was used to draw the graphs and intuitively express the data.

[0084] 3. Experimental results

[0085] (1) Changes in body weight of mice before and after modeling

[0086] The weight changes of mice before and after modeling Figure 2 The specific data are shown in Table 3.

[0087] On the morning of the first day of the experiment, the mice were weighed as the initial body weight of the experiment. On the morning before drug administration on the sixth day of the experiment, they were weighed as the final body weight of the experiment. The results are shown in Table 3. The results show that there was no significant difference in the body weight of the mice in the experimental groups of Polygonatum sibiricum at different doses compared with the control group (P>0.05), indicating to a certain extent that intragastric administration of low, medium, and high doses of Polygonatum sibiricum had no significant effect on the growth of mice.

[0088] Table 3 Effects of Polygonatum sibiricum on the body weight of mice

[0089] Group Initial weight (g) Final weight (g) Control group 30.07±1.20 37.09±2.01 Polygonatum sibiricum low-dose prevention and treatment group 31.32±1.05 37.93±1.34 Polygonatum sibiricum medium-dose prevention and treatment group 30.82±1.15 36.00±2.82 Polygonatum sibiricum high-dose prevention and treatment group 29.30±1.77 35.92±3.90

[0090] (2) Liver index of mice

[0091] Determination of liver index: After collecting blood by enucleating the eyeballs, the mice were sacrificed by cervical dislocation, dissected to take the liver, rinsed with pre-cooled physiological saline and blotted dry with filter paper, and then weighed. The liver index of each group was calculated according to the following formula (1):

[0092]

[0093] L = liver index, %; m = liver mass, g; m0 = mouse mass, g;

[0094] Table 4 Liver indices of each experimental group

[0095] Group Liver index Control group 4.59±0.38 Model group 5.58±0.35* Polygonatum sibiricum low-dose prevention and treatment group <![CDATA[4.72±0.70 # > Polygonatum sibiricum medium-dose prevention group <![CDATA[3.96±0.64 # > Polygonatum sibiricum medium-dose prevention and treatment group <![CDATA[4.54±0.66 # > Polygonatum sibiricum high-dose prevention and treatment group <![CDATA[4.58±0.51 # > Polygonatum sibiricum medium-dose + melatonin prevention and treatment group <![CDATA[4.54±0.77 # > Polygonatum sibiricum medium-dose + dexamethasone prevention and treatment group <![CDATA[4.69±0.32 # >

[0096] Note: *, P<0.05 compared with the control group; #, P<0.05 compared with the model group.

[0097] The results are shown in Table 4 and Figure 3 as follows. After the experiment, compared with the control group, the liver index level of the model group was significantly increased (P<0.05); compared with the model group, the liver indices of the low, medium, and high dose groups of Polygonatum sibiricum, the medium dose group of Polygonatum sibiricum + melatonin, and the dexamethasone group all showed a downward trend, and the differences were all significant (P<0.05).

[0098] (3) Kidney index of mice

[0099] The calculation method of the kidney index is the same as that of the liver index. The kidney indices of each group were calculated according to the following formula (2):

[0100]

[0101] L’ = kidney index, %; W = liver mass, g; W0 = mouse mass, g;

[0102] Table 5 Kidney indices of each experimental group

[0103] Group Kidney index Control group 1.44±0.07 Model group 1.46±0.06 Polygonatum sibiricum low-dose prevention and treatment group 1.50±0.14 Polygonatum sibiricum medium-dose prevention group 1.33±0.10 Polygonatum sibiricum medium-dose prevention and treatment group 1.33±0.16 Polygonatum sibiricum high-dose prevention and treatment group 1.38±0.10 Polygonatum sibiricum medium-dose + melatonin prevention and treatment group 1.37±0.15 Polygonatum sibiricum medium-dose + dexamethasone prevention and treatment group 1.37±0.12

[0104] The results are shown in Table 5 and Figure 4 as follows. After the experiment, compared with the control group, the kidney index of the model group increased slightly, but the difference was not significant (P>0.05); compared with the model group, the levels of the low-dose group were higher but the difference was not significant (P>0.05), and the levels of the high-dose and medium-dose groups all decreased, but the differences were not significant (P>0.05).

[0105] (4) Changes in liver biochemical indexes of mice

[0106] The data of the contents of ALT and AST in serum after modeling on the 7th day are as Figure 5 - Figure 6 shown in and Table 6. Compared with the control group, the contents of ALT and AST in the model group both increased, and the difference was significant (P<0.05). Compared with the model group, the contents of AST in the low-, medium-, and high-dose polygonatum groups all decreased, and the differences were significant (P<0.05); the content of ALT in the low-dose polygonatum preventive treatment group also decreased, but the difference was not significant (P>0.05); the content of ALT in the medium-dose polygonatum preventive treatment group decreased, and the difference was significant (P<0.05); the content of ALT in the high-dose polygonatum preventive treatment group decreased, and the difference was significant (P<0.05).

[0107] The contents of ALT and AST in serum after treatment on the 8th day are as Figure 7 - Figure 8 shown in and Table 7. Compared with the control group, the contents of ALT and AST in the model group both increased, and the difference was significant (P<0.05); compared with the model group, the contents of ALT and AST in the low-dose polygonatum preventive treatment group increased, and the difference in the content of AST was significant (P<0.05) while the difference in the content of ALT was not significant (P>0.05); the contents of ALT and AST in the medium-dose polygonatum preventive treatment group both decreased, but the difference was not significant (P>0.05); the content of ALT in the high-dose polygonatum preventive treatment group decreased, and the difference was significant (P<0.05); while the content of AST increased, but the difference in content was not significant (P>0.05).

[0108] Table 6 Contents of ALT and AST in serum of each group after modeling on the 7th day

[0109] Group ALT (U / L) AST (U / L) Control group 40.97±1.05 90.93±19.97 Model group 115.33±4.04* 361.20±60.62* Polygonatum sibiricum low-dose prevention and treatment group 99.90±7.05 <![CDATA[211.63±44.88 # > Polygonatum sibiricum medium-dose prevention and treatment group <![CDATA[72.10±20.33 # > <![CDATA[209.23±42.40 # <!-- 8 -->]]> Polygonatum sibiricum high-dose prevention and treatment group <![CDATA[52.83±11.30 # > <![CDATA[224.02±15.38 # >

[0110] Table 7 Contents of ALT and AST in serum of each group after treatment on the 8th day

[0111] Group ALT (U / L) AST (U / L) Control group 36.37±3.36 144.87±16.16 Model group 58.30±3.03* 183.50±12.26* Polygonatum sibiricum low-dose prevention and treatment group 65.77±20.16 215.67±18.85# Polygonatum sibiricum medium-dose prevention and treatment group 56.52±10.44 181.46±22.23 Polygonatum sibiricum high-dose prevention and treatment group 28.05±5.65# 191.5±3.90

[0112] Note: *, P<0.05 compared with the control group; #, P<0.05 compared with the model group.

[0113] (5) Changes in kidney biochemical indexes of mice

[0114] The data of the contents of UREA and CREA in serum after modeling on the 7th and 8th days are as Figure 9 - Figure 12 shown in Table 8 - Table 9. According to the data presented in the following table and figure, it can be seen that after modeling on the 7th day, compared with the control group, the levels of UREA and CREA - S in the model group both increased, but the differences were not significant (P > 0.05); compared with the model group, the levels of UREA and CREA - S in the low - and medium - dose prevention and treatment groups decreased, the level of CREA - S in the high - dose prevention and treatment group decreased, while the level of UREA increased, but the differences were not significant (P > 0.05). After treatment on the 8th day, compared with the control group, the levels of UREA and CREA - S in the model group both increased, but the differences were not significant (P > 0.05); compared with the model group, the levels of CREA - S in the low -, medium - and high - dose prevention and treatment groups all increased, but the differences were not significant (P > 0.05); while the levels of UREA in the medium - and high - dose prevention and treatment groups both decreased, and the differences were not significant (P > 0.05); the level of UREA in the low - dose prevention and treatment group increased, but the difference was not significant.

[0115] Table 8 Contents of UREA and CREA in serum of each group after modeling on the 7th day

[0116]

[0117]

[0118] Table 9 Contents of UREA and CREA in serum of each group after treatment on the 8th day

[0119] Group UREA (mmol / L) CREA (μmol / L) Control group 8.11±1.16 23.29±8.12 Model group 10.64±1.7 31.87±4.3 Polygonatum sibiricum low-dose prevention and treatment group 11.56±1.98 37.63±4.93 Polygonatum sibiricum medium-dose prevention and treatment group 9.28±2.44 32.9±0.41 Polygonatum sibiricum high-dose prevention and treatment group 9.18±0.98 34.87±2.15

[0120] (6) Anti - inflammatory effect of Polygonatum sibiricum

[0121] (6.1) Results of the contents of TNF - α, IL - 1β, and IL - 10 in liver tissue after modeling on the 7th day are shown in Table 10 and Figure 13 - Figure 15 , and the specific analysis is as follows:

[0122] Compared with the control group, both TNF - α and IL - 1β in the model group increased, and the differences were both significant (P < 0.05); while the content of IL - 10 decreased, and the difference was significant (P < 0.05).

[0123] Compared with the model group, the levels of IL-1β in the low, medium, and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all decreased. Among them, the differences in the IL-1β levels in the medium- and high-dose polygonatum sibiricum preventive and treatment groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were significant (P < 0.05). The levels of TNF-α in the medium-dose polygonatum sibiricum preventive group, the medium- and high-dose polygonatum sibiricum preventive and treatment groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all decreased. Among them, the differences in the TNF-α levels in the medium-dose polygonatum sibiricum preventive group, the high-dose polygonatum sibiricum preventive and treatment group, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were significant (P < 0.05). The TNF-α level in the low-dose polygonatum sibiricum preventive and treatment group increased slightly, but the difference was not significant (P > 0.05). The levels of IL-10 in the medium- and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all increased. Among them, the differences in the IL-10 levels in the medium-dose polygonatum sibiricum preventive group, the medium-dose polygonatum sibiricum + dexamethasone group, and the high-dose polygonatum sibiricum preventive and treatment group were significant (P < 0.05). The IL-10 level in the low-dose polygonatum sibiricum preventive and treatment group increased slightly, but the difference was not significant (P > 0.05).

[0124] Compared with the low-dose polygonatum sibiricum preventive and treatment group, the levels of IL-1β in the medium- and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all decreased. Among them, the difference in the IL-1β level in the high-dose polygonatum sibiricum preventive and treatment group was significant (P < 0.05). The levels of TNF-α in the medium- and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all decreased. Among them, the differences in the TNF-α levels in the medium-dose polygonatum sibiricum preventive group, the medium-dose polygonatum sibiricum + melatonin group, and the high-dose polygonatum sibiricum preventive and treatment group were significant (P < 0.05). The levels of IL-10 in the medium- and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all increased. Among them, the differences in the IL-10 levels in the medium-dose polygonatum sibiricum preventive group, the medium-dose polygonatum sibiricum + melatonin group, and the high-dose polygonatum sibiricum preventive and treatment group were significant (P < 0.05).

[0125] Compared with the medium-dose polygonatum sibiricum preventive group, the levels of TNF-α in the medium- and high-dose polygonatum sibiricum preventive and treatment groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all increased. Among them, the difference in the TNF-α level in the medium- and high-dose polygonatum sibiricum preventive and treatment group was significant (P < 0.05). The levels of IL-1β in the medium-dose polygonatum sibiricum preventive and treatment group and the medium-dose polygonatum sibiricum + melatonin group increased, but the differences were not significant (P > 0.05). The IL-1β level in the high-dose polygonatum sibiricum preventive and treatment group decreased, but the difference was not significant (P > 0.05). The levels of IL-10 in the medium- and high-dose polygonatum sibiricum preventive and treatment groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group were all decreased. Among them, the differences in the IL-10 levels in the medium-dose polygonatum sibiricum preventive and treatment group and the medium-dose polygonatum sibiricum + melatonin group were significant (P < 0.05).

[0126] Compared with the medium-dose preventive and treatment group of Polygonatum sibiricum, the TNF-α and IL-1β in the high-dose preventive and treatment group, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups decreased. Among them, the content of IL-1β in the high-dose preventive and treatment group was significantly different (P<0.05); the IL-10 in the high-dose preventive and treatment group, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups increased; among them, the content of IL-10 in the high-dose preventive and treatment group and the medium-dose Polygonatum sibiricum + dexamethasone group was significantly different (P<0.05).

[0127] (6.2) The results of the contents of TNF-α, IL-1β, and IL-10 in the liver tissue after modeling on the 8th day are shown in Table 11 and Figure 16 - Figure 18 , and the specific analysis is as follows:

[0128] Compared with the control group, the TNF-α and IL-1β in the model group increased, and the differences were both significant (P<0.05); while the content of IL-10 decreased, and the difference was significant (P<0.05).

[0129] Compared with the model group, the IL-1β in the low-, medium-, and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups decreased; among them, the content of IL-1β in the medium-dose preventive, medium-dose preventive and treatment, medium-dose + dexamethasone group, and high-dose preventive and treatment group of Polygonatum sibiricum was significantly different (P<0.05); the TNF-α in the low-, medium-, and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups decreased; among them, the content of TNF-α in the medium-dose preventive group and the high-dose preventive and treatment group of Polygonatum sibiricum was significantly different (P<0.05); the IL-10 in the low-, medium-, and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups increased; among them, the content of IL-10 in the medium-dose preventive group, the medium-dose + melatonin, dexamethasone group, and high-dose preventive and treatment group of Polygonatum sibiricum was significantly different (P<0.05).

[0130] Compared with the low-dose preventive and treatment group, the IL-1β in the medium- and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups decreased; among them, the content of IL-1β in the medium-dose preventive group of Polygonatum sibiricum was significantly different (P<0.05); the TNF-α in the medium- and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups decreased; among them, the content of TNF-α in the medium-dose preventive group and the high-dose treatment preventive group of Polygonatum sibiricum was significantly different (P<0.05); the IL-10 in the medium- and high-dose groups of Polygonatum sibiricum, the medium-dose Polygonatum sibiricum + melatonin, and dexamethasone groups increased; among them, the content of IL-10 in the medium-dose preventive group and the medium-dose Polygonatum sibiricum + melatonin group was significantly different (P<0.05).

[0131] Compared with the medium-dose prevention group, the IL-1β levels in the high- and medium-dose preventive treatment groups of polygonatum sibiricum, the polygonatum sibiricum medium-dose + melatonin, and dexamethasone groups all increased, and the differences were all significant (P < 0.05); the TNF-α levels in the high- and medium-dose preventive treatment groups of polygonatum sibiricum, the polygonatum sibiricum medium-dose + melatonin, and dexamethasone groups all increased, and the differences were not significant (P > 0.05); the IL-10 levels in the high- and medium-dose preventive treatment groups of polygonatum sibiricum, the polygonatum sibiricum medium-dose + melatonin, and dexamethasone groups all decreased, and the difference in the IL-10 content in the polygonatum sibiricum medium-dose preventive treatment group was significant (P < 0.05).

[0132] Compared with the medium-dose preventive treatment group, the IL-1β levels in the high-dose preventive treatment group of polygonatum sibiricum and the polygonatum sibiricum medium-dose + melatonin group both increased, while the IL-1β level in the polygonatum sibiricum medium-dose + dexamethasone group decreased, but the differences in their contents were not significant (P > 0.05); the TNF-α levels in the high-dose preventive treatment group of polygonatum sibiricum, the polygonatum sibiricum medium-dose + melatonin, and dexamethasone groups all decreased, but the differences were not significant (P > 0.05); the IL-10 levels in the high-dose preventive treatment group of polygonatum sibiricum, the polygonatum sibiricum medium-dose + melatonin, and dexamethasone groups all increased, and the difference in the IL-10 content in the polygonatum sibiricum medium-dose + dexamethasone group was significant (P < 0.05).

[0133] Table 10 Levels of inflammatory factors in liver tissue after modeling on the 7th day

[0134] Group TNF-α (pg / ml) IL-1β (pg / ml) IL-10 (pg / ml) Control group 228.73±47.78 48.88±10.82 45.33±0.27 Model group 450.61±63.96* 93.51±14.57* 20.51±6.37* Polygonatum sibiricum low-dose prevention and treatment group 450.84±42.73 78.23±6.16 20.05±7.07 Polygonatum sibiricum medium-dose prevention group <![CDATA[214.98±18.26 #△ > <![CDATA[63.24±3.28 # > <![CDATA[39.94±4.19 #△ > Polygonatum sibiricum medium-dose prevention and treatment group <![CDATA[368±52.83 □ > <![CDATA[72.79±6.13 # > <![CDATA[25.93±3.59 □ > Polygonatum sibiricum medium-dose + melatonin group <![CDATA[297.43±24.39 #△ > <![CDATA[70.46±10.68 # > <![CDATA[27.61±1.73 △□ > Polygonatum sibiricum medium-dose + dexamethasone group <![CDATA[294.37±47.87 #△ > <![CDATA[64.06±5.06 # > <![CDATA[34.91±3.54 #●△ > Polygonatum sibiricum high-dose prevention and treatment group <![CDATA[327.37±90.95 #△□ > <![CDATA[52.26±15.43 #●△ > <![CDATA[34.58±1.44 #●△ >

[0135] Table 11 Levels of inflammatory factors in liver tissue after treatment on the 8th day

[0136]

[0137]

[0138] Note: *, P < 0.05 compared with the control group; #, P < 0.05 compared with the model group; △, P < 0.05 compared with the low-dose polygonatum sibiricum group; □, P < 0.05 compared with the polygonatum sibiricum medium-dose prevention group; ●, P < 0.05 compared with the polygonatum sibiricum medium-dose treatment and prevention group.

[0139] (7) Antioxidant effect of polygonatum sibiricum

[0140] (7.1) Results of the contents of GSH-Px, MDA, and T-SOD in liver tissue after modeling on the 7th day are shown in Table 12 and Figure 19 - Figure 21 , and the specific analysis is as follows:

[0141] Compared with the control group, the GSH-Px and T-SOD in the model group decreased, and the differences in the contents were both significant (P < 0.05); the MDA content increased, and the difference was significant (P < 0.05).

[0142] Compared with the model group, the GSH-Px and T-SOD in the low, medium, and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group increased, and the content differences were all significant (P < 0.05); the MDA in the low, medium, and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group decreased, and except for the medium-dose polygonatum sibiricum preventive treatment group, the content differences in other groups were significant (P < 0.05).

[0143] Compared with the low-dose group, the GSH-Px in other groups increased except for the medium-dose polygonatum sibiricum preventive group, but the content differences were not significant (P > 0.05); the T-SOD in the medium-dose polygonatum sibiricum preventive group and the medium-dose polygonatum sibiricum + dexamethasone group increased, among which, the content difference in the medium-dose polygonatum sibiricum + dexamethasone group was significant (P < 0.05); the T-SOD in the medium- and high-dose polygonatum sibiricum preventive treatment groups and the medium-dose polygonatum sibiricum + melatonin group decreased, among which the content difference in the medium-dose polygonatum sibiricum preventive treatment group was significant (P < 0.05); the MDA in the medium- and high-dose polygonatum sibiricum groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group decreased, among which, the content difference in the medium-dose polygonatum sibiricum preventive group was significant (P < 0.05).

[0144] Compared with the medium-dose preventive group, the GSH-Px in other groups increased except for the high-dose polygonatum sibiricum preventive treatment group, but the content differences were not significant (P > 0.05); the T-SOD in the medium-dose polygonatum sibiricum + dexamethasone group increased, and the content difference was significant (P < 0.05); the T-SOD in the medium- and high-dose polygonatum sibiricum preventive treatment groups and the medium-dose polygonatum sibiricum + melatonin group decreased; among which, the content difference in the medium-dose polygonatum sibiricum preventive treatment group was significant (P < 0.05); the MDA in the medium- and high-dose polygonatum sibiricum preventive treatment groups, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group increased, but the differences were not significant (P > 0.05).

[0145] Compared with the medium-dose preventive treatment group, the GSH-Px in the high-dose polygonatum sibiricum preventive treatment group, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group increased, but the differences were not significant (P > 0.05); the T-SOD in the high-dose polygonatum sibiricum preventive treatment group, the medium-dose polygonatum sibiricum + melatonin group, and the dexamethasone group increased, and the content differences were all significant (P < 0.05); the MDA in the medium-dose polygonatum sibiricum + melatonin group and the dexamethasone group increased, but the content difference was not significant (P > 0.05); the MDA in the high-dose polygonatum sibiricum preventive treatment group decreased, but the content difference was not significant (P > 0.05).

[0146] (7.2) The results of the contents of GSH-Px, MDA, and T-SOD in the liver tissue after modeling on the 8th day are shown in Table 13 and Figure 22 - Figure 24 , and the specific analysis is as follows:

[0147] Compared with the control group, the levels of GSH-Px and T-SOD in the model group decreased, and the differences were significant (P<0.05); the level of MDA increased, and the difference was significant (P<0.05).

[0148] Compared with the model group, the levels of GSH-Px in the low-, medium-, and high-dose polygonatum groups and the medium-dose polygonatum + dexamethasone group all increased; among them, the differences in the levels in the medium-dose prevention group, medium-dose prevention and treatment group, and medium-dose + dexamethasone group were significant; the level of GSH-Px in the medium-dose polygonatum + melatonin group decreased, but the difference was not significant (P>0.05); the levels of T-SOD in the low-, medium-, and high-dose polygonatum groups, the medium-dose polygonatum + melatonin, and dexamethasone group all increased, and the differences were all significant (P<0.05); the levels of MDA in the low- and high-dose polygonatum groups, the medium-dose polygonatum prevention group, the medium-dose polygonatum + melatonin, and dexamethasone group all decreased; among them, the difference in the level in the medium-dose polygonatum prevention group was significant (P<0.05); the level of MDA in the medium-dose polygonatum prevention and treatment group increased, but the difference was not significant (P>0.05).

[0149] Compared with the low-dose group, the levels of GSH-Px in all groups except the medium-dose polygonatum + melatonin group increased; among them, the difference in the level in the medium-dose polygonatum prevention and treatment group was significant (P<0.05); the levels of T-SOD in the medium-dose polygonatum prevention group and the medium-dose + dexamethasone group both increased, but the differences were not significant (P>0.05); the levels of T-SOD in the medium- and high-dose polygonatum prevention and treatment groups and the medium-dose + melatonin group all decreased, but the differences were not significant (P>0.05); except that the level of MDA in the medium-dose polygonatum prevention and treatment group increased, the levels in other groups all decreased, but the differences were not significant (P>0.05).

[0150] Compared with the medium-dose prevention group, the levels of GSH-Px in the medium-dose polygonatum prevention and treatment group and the medium-dose polygonatum + dexamethasone group both increased; but the differences were not significant (P>0.05); the levels of GSH-Px in the medium-dose polygonatum + melatonin group and the high-dose prevention and treatment group both decreased; among them, the difference in the level in the medium-dose polygonatum + melatonin group was significant (P<0.05); except that the level of T-SOD in the medium-dose polygonatum + dexamethasone group increased, the levels of T-SOD in other groups all decreased, but the differences were not significant (P>0.05); the levels of MDA in the medium- and high-dose polygonatum prevention and treatment groups, the medium-dose polygonatum + melatonin, and dexamethasone group all increased; among them, the difference in the level in the medium-dose polygonatum prevention and treatment group was significant (P<0.05).

[0151] Compared with the medium-dose preventive treatment group, the contents of GSH-Px and MDA in the groups of medium-dose polygonatum sibiricum + melatonin, dexamethasone, and high-dose polygonatum sibiricum preventive treatment group decreased, but the differences in their contents were not significant (P>0.05); the T-SOD in the groups of medium-dose polygonatum sibiricum + melatonin, dexamethasone, and high-dose polygonatum sibiricum preventive treatment group increased; among them, the content difference in the group of medium-dose polygonatum sibiricum + dexamethasone was significant (P<0.05).

[0152] Table 12 Oxidative stress level in liver tissue after modeling on the 7th day

[0153]

[0154]

[0155] Table 13 Oxidative stress level in liver tissue after treatment on the 8th day

[0156] Group GSH-Px (ng / ml) MDA (nmol / ml) T-SOD (ng / ml) Control group 18.61±0.88 4.51±0.79 78.43±3.04 Model group 12.89±0.39* 7.1±0.77* 39.94±3.6* Polygonatum sibiricum low-dose prevention and treatment group 13.85±0.58 6.22±0.73 <![CDATA[58.73±9.39 # <!-- 13 -->]]> Polygonatum sibiricum medium-dose prevention group <![CDATA[15.53±1.05 # > <![CDATA[5.28±0.33 # > <![CDATA[62.17±14.39 # > Polygonatum sibiricum medium-dose prevention and treatment group <![CDATA[15.95±1.63 #△ > <![CDATA[7.14±1.09 □ > <![CDATA[52.04±8.37 # > Polygonatum sibiricum medium-dose + melatonin group <![CDATA[12.27±0.43 □ > 6.17±1.18 <![CDATA[55.32±11.31 # > Polygonatum sibiricum medium-dose + dexamethasone group <![CDATA[15.71±2.24 # > 6.04±0.77 <![CDATA[70.01±4.26 #● > Polygonatum sibiricum high-dose prevention and treatment group 14.37±1.04 5.77±0.74 <![CDATA[57.98±9.27 # >

[0157] Note: *, compared with the control group, P<0.05; #, compared with the model group, P<0.05; △, compared with the low-dose polygonatum sibiricum group, P<0.05; □, compared with the medium-dose polygonatum sibiricum preventive group, P<0.05; ●, compared with the medium-dose polygonatum sibiricum treatment and prevention group, P<0.05.

[0158] 4. Summary of experimental results

[0159] This invention explored the anti-inflammatory and antioxidant mechanisms of polygonatum sibiricum on acute alcoholic liver and kidney injury. The research results not only verified the therapeutic potential of polygonatum sibiricum, but also revealed its dose-dependent efficacy and synergistic effect with melatonin or dexamethasone.

[0160] The decrease in the levels of serum ALT and AST in the polygonatum sibiricum intervention group was consistent with previous studies, that is, polysaccharide of polygonatum sibiricum reduced alcohol-induced liver cell membrane permeability damage by inhibiting oxidative stress. It is worth noting that the medium-dose polygonatum sibiricum group (10mg / kg) had the most significant effect, suggesting the existence of a dose-dependent therapeutic window. The decrease in the levels of TNF-α and IL-1β and the increase in IL-10 indicate that polygonatum sibiricum may play a role by inhibiting the NF-κB signaling pathway - this pathway can be activated by acetaldehyde, a metabolite of ethanol. This hypothesis is further supported by oxidative stress markers: MDA (a lipid peroxidation marker) decreased significantly, while the activities of T-SOD and GSH-Px increased, suggesting that polygonatum sibiricum enhanced antioxidant defense ability by activating the Nrf2 / ARE pathway.

[0161] The results of the present invention are consistent with the previous evidence of the antioxidant properties of Polygonatum sibiricum. This study further reveals the synergistic effect of Polygonatum sibiricum and dexamethasone: the inhibitory effect of TNF-α in the combined medication group (Polygonatum sibiricum + dexamethasone) is significantly better than that in the single drug group (P < 0.05), which may be related to the inhibitory mechanism of pro-inflammatory cytokines mediated by glucocorticoid receptors - this mechanism has not been explored in the combined therapy of Polygonatum sibiricum before.

[0162] The present invention clarifies that the medium dose of Polygonatum sibiricum (10 mg / kg) significantly improves acute alcoholic liver injury by dual regulation of inflammation (inhibiting TNF-α / IL-1β) and oxidative stress (reducing MDA and enhancing T-SOD / GSH-Px). Its synergistic effect with dexamethasone provides a new combined treatment strategy for severe cases.

[0163] Further analysis of the above experimental results (1): In this study, before drug administration on the first day of the experiment and after drug administration on the sixth day of the experiment, the weight gain of the Polygonatum sibiricum control group was (7.01 ± 0.87) g, the weight gain of the low-dose preventive administration group of Polygonatum sibiricum was (6.62 ± 1.17) g, the weight gain of the medium-dose preventive administration group of Polygonatum sibiricum was (6.62 ± 2.35) g, and the weight gain of the high-dose preventive administration group of Polygonatum sibiricum was (5.32 ± 2.18) g. Compared with the control group, there was no significant difference in the weight gain of mice in the low-, medium-, and high-dose preventive administration groups of Polygonatum sibiricum (P > 0.05). According to the above experimental results, it can be concluded that the preventive administration of Polygonatum sibiricum has no significant effect on the weight of mice in the short term.

[0164] Further analysis of the above experimental results (2) and (4): In this study, compared with the control group, the liver index of the model group was significantly increased, and the difference was significant (P < 0.05); compared with the model group, the liver indexes of the low-, medium-, and high-dose groups of Polygonatum sibiricum, the medium-dose group of Polygonatum sibiricum + melatonin, and the dexamethasone group all showed a downward trend, and the differences were all significant (P < 0.05); it shows that high-dose ethanol gavage will cause significant liver damage to mice, resulting in liver swelling and lipid accumulation, initially indicating that the liver modeling of this experiment is successful. Each group of Polygonatum sibiricum significantly decreased the liver index. Among them, the liver index of the preventive group of Polygonatum sibiricum decreased by (1.65 ± 0.29)% compared with the model group, which was the group with the largest decrease in the liver index among the groups of Polygonatum sibiricum, indicating that to a certain extent, the preventive group of Polygonatum sibiricum has a better effect on reducing the liver index than other groups of Polygonatum sibiricum.

[0165] When the body is in a normal state, the contents of two important transaminases, aspartate aminotransferase (ALT) and aspartate aminotransferase (AST), in the hepatocyte cytoplasm and mitochondria are both maintained at relatively low levels. When hepatocytes are damaged, the cell membrane permeability increases, and a large amount of ALT and AST are released into the blood, and their contents in the serum increase. They are sensitive indicators reflecting hepatocyte damage, and the level of their increase represents the degree of hepatocyte damage and necrosis. In this study, compared with the control group, the levels of ALT and AST in the serum of the model group mice on the 7th and 8th days were significantly increased (P<0.05); to a certain extent, it indicated that the alcohol-induced model took effect on the liver. Considering the ALT and AST levels on the 7th and 8th days comprehensively, compared with the model group, the treatment effect of the low-dose polygonatum preventive treatment group was not good, and the treatment effects of the medium- and high-dose polygonatum preventive treatment groups were better. Thus, to a certain extent, it indicated the repair and improvement effects of polygonatum at different doses on the liver. The decrease in the serum ALT and AST levels in the polygonatum intervention group was consistent with previous studies. It is worth noting that the medium-dose polygonatum group (10mg / kg) had the most significant effect, suggesting the existence of a dose-dependent treatment window.

[0166] Further analysis of the above experimental results (3) and (5): In this study, compared with the control group, the kidney index, UREA, and CREA of the model group increased slightly, and the difference was not significant (P>0.05); compared with the model group, the kidney index, UREA, and CREA of the medium-dose treatment group of polygonatum decreased slightly, indicating that polygonatum also had a certain treatment effect, but the difference was not significant (P>0.05); thus, it can be seen that the alcohol-induced model in this experiment had a low possibility of affecting kidney injury, polygonatum itself had a low possibility of causing damage to the renal function of mice, and polygonatum had a low possibility of reversing the potential risk of kidney injury caused by alcohol.

[0167] Further analysis of the above experimental result (6): IL-1β exacerbates the inflammatory response by inducing neutrophil chemotactic factors. IL-10 is an anti-inflammatory and immunosuppressive cytokine, and TNF-α is a pro-inflammatory cytokine mainly produced by macrophages and monocytes and participates in the processes of inflammation and immune response. Therefore, by measuring the levels of the above contents, the degree of liver damage caused by the inflammatory response can also be comprehensively analyzed.

[0168] On the 7th and 8th days, compared with the control group, the levels of TNF-α and IL-1β in the model group were significantly increased, while the level of IL-10 was significantly decreased (P<0.05), indicating that inflammation occurred in the liver tissues of mice with acute alcohol injury and the modeling was effective. On the seventh day, compared with the model group, the levels of TNF-α and IL-1β in other groups decreased, while the level of IL-10 increased, except for the low-dose preventive treatment group of Polygonatum sibiricum. Among them, the contents of TNF-α and IL-1β in the medium-dose Polygonatum sibiricum + melatonin, dexamethasone group, and high-dose preventive treatment group of Polygonatum sibiricum were significantly different (P<0.05); the contents of IL-10 in the medium-dose preventive group of Polygonatum sibiricum, medium-dose Polygonatum sibiricum + dexamethasone group, and high-dose preventive treatment group of Polygonatum sibiricum were significantly different (P<0.05). Based on the above results, it can be concluded that the high-dose Polygonatum sibiricum and the medium-dose Polygonatum sibiricum + dexamethasone group have a certain preventive effect on liver tissue inflammation in mice with acute alcohol injury. The preventive treatment effects of low- and medium-dose Polygonatum sibiricum alone were not obvious; on the eighth day, compared with the control group, the levels of TNF-α and IL-1β in the model group were significantly increased, while the level of IL-10 was significantly decreased (P<0.05). Among them, compared with other treatment groups, the levels of TNF-α and IL-1β in the medium-dose preventive group decreased, while the level of IL-10 increased, and the changes of the three were the most prominent. Therefore, it is shown that preventive administration of medium-dose Polygonatum sibiricum has a good effect on anti-inflammation in the liver of mice, and its clinical application can be considered. The above results further illustrate that Polygonatum sibiricum may play a role by inhibiting the NF-κB signaling pathway, which can be activated by acetaldehyde, a metabolite of ethanol.

[0169] Further analysis of the above experimental results (7): The levels of MDA, T-SOD, and GSH-PX can better reflect the degree of liver oxidation. Compared with the control group on the 7th and 8th days, the levels of GSH-Px and T-SOD in the model group were significantly decreased, and the level of MDA was significantly increased (P<0.05), which preliminarily indicated that oxidative stress occurred in the liver tissue of mice with acute alcohol injury and the modeling was effective. On the seventh day, compared with the model group, the levels of GSH-Px and T-SOD in the low-dose and high-dose preventive treatment groups of Polygonatum sibiricum, the medium-dose preventive group of Polygonatum sibiricum, the medium-dose of Polygonatum sibiricum + melatonin, and dexamethasone group were significantly increased, and the level of MDA was significantly decreased (P<0.05). The above data indicated that Polygonatum sibiricum had an inhibitory effect on oxidative stress; on the eighth day, compared with the model group, the levels of GSH-Px and T-SOD in the low-dose and high-dose preventive treatment groups of Polygonatum sibiricum, the medium-dose of Polygonatum sibiricum + dexamethasone group, and the medium-dose preventive group of Polygonatum sibiricum were significantly increased, and the level of MDA was significantly decreased (P<0.05). Among them, compared with the medium-dose preventive group, the levels of GSH-Px and T-SOD in the medium-dose of Polygonatum sibiricum + dexamethasone group were significantly increased, but the content difference was not significant (P>0.05); and the MDA levels of other drug-administered groups were not lower than that of the medium-dose preventive group. It can be seen from this that based on the preventive administration in the first 6 days of this experiment, the therapeutic administration of the Polygonatum sibiricum + dexamethasone group had a certain antioxidant effect on the liver tissue of mice with acute alcohol injury. MDA (lipid peroxidation marker) was significantly decreased, while the activities of T-SOD and GSH-Px were enhanced, suggesting that Polygonatum sibiricum enhanced the antioxidant defense ability by activating the Nrf2 / ARE pathway.

[0170] The above embodiments are the preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principle of the present invention shall be equivalent replacement methods and are all included in the protection scope of the present invention.

Claims

1. Use of Polygonatum sibiricum in preparing medicines for preventing and treating kidney damage and / or liver damage.

2. The use according to claim 1, characterized in that: The kidney damage includes alcoholic kidney damage, chemical kidney damage, and immune kidney damage; the liver damage includes alcoholic liver damage, chemical liver damage, and immune liver damage.

3. The use according to claim 2, characterized in that: The alcoholic kidney injury includes acute alcoholic kidney injury; the alcoholic liver injury includes acute alcoholic liver injury.

4. Use of a pharmaceutical composition in the preparation of a drug for preventing and treating alcoholic liver injury and / or alcoholic kidney injury, characterized in that: The pharmaceutical composition comprises polygonatum and hormone.

5. The use according to claim 4, characterized in that: The hormone includes at least one of peptide hormones, amino acid hormones, amine hormones, and steroid hormones.

6. The use according to claim 5, characterized in that: The amine hormones include at least one of 5-hydroxytryptamine and melatonin; And / or, the steroid hormone includes at least one of dexamethasone, betamethasone, triamcinolone acetonide, fluticasone, budesonide, clobetasol propionate, and hydrocortisone butyrate.

7. The use according to claim 4, characterized in that: The mass ratio of polygonatum to hormone is 10:(0.1-3).

8. The use according to claim 4, characterized in that: The drug also includes pharmaceutically acceptable excipients.

9. The use according to claim 4, characterized in that: The medicine includes oral preparations or injection preparations.

10. The use according to claim 4, characterized in that: The medicine is a medicine for reducing the damage of TNF-α to the liver.

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