CN115192644A - Application of eucommia ulmoides compound preparation in preparation of medicines for treating non-alcoholic fatty liver disease - Google Patents
Application of eucommia ulmoides compound preparation in preparation of medicines for treating non-alcoholic fatty liver disease Download PDFInfo
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- CN115192644A CN115192644A CN202210545995.4A CN202210545995A CN115192644A CN 115192644 A CN115192644 A CN 115192644A CN 202210545995 A CN202210545995 A CN 202210545995A CN 115192644 A CN115192644 A CN 115192644A
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Abstract
The invention discloses application of a eucommia ulmoides compound preparation in preparing a medicine for preventing and treating non-alcoholic fatty liver disease. According to the invention, through constructing a non-alcoholic fatty liver disease in-vivo and in-vitro model, the eucommia compound preparation is found through screening to act on a plurality of targets, so that the accumulation of lipid in liver cells is reduced, the content of inflammatory factors (IL-6 and TNF-alpha) and blood sugar in serum is reduced, the content of free fatty acid and low-density lipoprotein in serum is reduced, the disorder of lipid metabolism pathways is inhibited, the fatty degeneration of liver is improved, the glucose tolerance and the insulin sensitivity are increased, and the further occurrence and development of metabolic-related fatty liver disease are effectively inhibited; the compound can be applied to the prevention and treatment of metabolic-related fatty liver diseases in the future, provides a new drug selection for metabolic-related fatty liver patients, and has important effects and significance for the prevention and treatment of the current world number one liver disease-metabolic-related fatty liver disease.
Description
Technical Field
The invention belongs to the technical field of new application of traditional Chinese medicines, and particularly relates to application of a eucommia ulmoides compound preparation in treating non-alcoholic fatty liver disease.
Background
The eucommia bark compound preparation is a Guizhou folk medicine formula preparation and has the effects of tonifying the kidney, calming the liver and clearing heat. It is mainly used for hypertension due to kidney deficiency and liver hyperactivity. The main raw material components comprise eucommia bark, motherwort, common selfheal fruit-spike, baical skullcap root, common andrographis herb, hawthorn and uncaria.
Non-alcoholic Fatty Liver Disease (NAFLD) is an acquired metabolic Disease characterized by Liver fat deposition caused by metabolic stress, which is now the first major Liver Disease worldwide over viral hepatitis, in addition to alcohol and other well-defined Liver injury factors. If NAFLD is not controlled, the liver cancer can be further developed into nonalcoholic steatohepatitis, liver cirrhosis, hepatic fibrosis and liver cancer. Meanwhile, NAFLD has become one of the main causes of diseases related to cardiovascular and cerebrovascular diseases, diabetes, heart diseases, chronic kidney diseases, and the like worldwide. In recent years, the incidence of NAFLD diseases has been increasing year by year and becoming younger with the increase in the living standard and the change in lifestyle of people. According to statistics, the prevalence rate of the NAFLD in the world is about 25.24%, wherein the prevalence rate in China reaches 32.9%, and the treatment cost of the NAFLD and related diseases reaches billions of dollars every year. NAFLD has become a current global, rapidly growing economic burden due to high incidence and lack of therapeutic drugs, seriously interfering with people's healthy lives. Therefore, the development of the medicine for treating NAFLD has important social significance and medical research value.
At present, no specific medicine for treating NAFLD exists. Previous therapeutic measures for NAFLD are mainly classified into 4 categories: (1) exercise therapy, which has the disadvantages of being difficult to adhere to and not able to completely control the progression of the disease; (2) surgical treatment (bariatric surgery and liver transplantation) has the disadvantages of high cost and high recurrence rate; (3) diet therapy has the disadvantages that no exact NAFLD diet therapy scheme exists, and the treatment effect is not easily repeated in clinical practice; (4) drug therapy, lipid-lowering and inflammation-inhibiting drugs (such as metformin, statins, thiazolidinediones, ursodeoxycholic acid, vitamin E and the like) can only alleviate NAFLD symptoms to some extent, but the effectiveness and safety of the drugs are still lack of clinical examination. Therefore, it is urgent to find an effective and safe drug for treating non-alcoholic fatty liver disease. NAFLD is a genetic, environmental, metabolic, stress-related disease, the pathogenesis of which is complex and has not yet been fully elucidated. The pathogenesis factors influencing the NAFLD do not exist independently, but promote the generation and development of the NAFLD through mutual causal, mutual promotion and mutual cooperation relations. At present, the theory of "secondary hit" is commonly used to explain the pathogenesis of NAFLD: accumulation of liver fat, liver steatosis (hepatic steatosis), is the first hit, leading to a disturbance in liver lipid metabolism, which is more susceptible to further damage; the second hit is an inflammatory factor, a adipokine, an oxidative stress, a mitochondrial function damage, etc., causing liver damage, and gradually leading to steatohepatitis (NASH) and hepatic fibrosis. However, in recent years, research on the "liver-intestine axis" shows that insulin resistance, liver inflammation and lipid metabolism disorder caused by imbalance of intestinal flora induced by high fat diet are closely related to occurrence and development of NAFLD. Thus, disorders of intestinal flora and disorders of liver lipid metabolism are important factors in the formation of NAFLD. Because the incidence of NAFLD is caused by the simultaneous abnormality of multiple signal paths, the medicine targeting a single signal path is difficult to be cured radically and is easy to have drug resistance. Therefore, it is imperative to develop innovative drugs with high efficacy and low toxicity to regulate lipid metabolism disorder, eliminate inflammation and promote the liver to recover normal functions.
Non-alcoholic fatty liver disease is named by modern medicine aiming at the comprehensive definition of pathogenesis, disease location and pathological changes of the disease. There is no name in TCM, but it is well documented that the symptoms and etiology and pathogenesis are similar to those of nonalcoholic fatty liver disease. For example, in Su Wen Qi Bing Lun: "fat people are full of internal heat and sweet people are full of middle-jiao", which means that overeating fat, sweet and thick taste can damage spleen and stomach, damp-heat is generated internally, and liver meridian is stagnated, resulting in liver qi failing to disperse and disperse. The four eighteenth record of Taiping Shenghui Fang Ju records that "treating the fat gas under the left hypochondrium is like covering a cup. Sore throat and vomiting of water, sallow complexion and unfavorable chest diaphragm ", the manifestations of the disease are also described. The classic treatise on the classic on winged pain and hypochondriac pain of Jinyin is: the symptoms of liver depression and hypochondriac pain, sadness, anger and liver qi impairment caused by depression indicate that emotional disorder, long-term depression or anger, and qi stagnation affect the transportation and transformation of water, and dampness turns into phlegm after a long time, which results in liver depression and spleen deficiency, and finally forms the disease. The Jingyue quan Shu and phlegm-fluid retention: the kidney governs water and water retention is phlegm, while phlegm is not always in the kidney and the medical records and accumulations: the formation of accumulation of qi, deficiency of healthy qi and accumulation of pathogenic qi indicates that liver and kidney are homologous, kidney deficiency causes liver disharmony, and phlegm-dampness stagnation in liver causes the disease. In the book of ancient and modern medical science and hypochondriac pain: in this case, the blood is obstructed by phlegm-dampness, which eventually leads to obstruction of collaterals by blood stasis and accumulation of phlegm-dampness, resulting in this disease. Especially in the book golden doctor Biaojie Xindian: "food retention in Taiyin, du Fuqi, inhibits liver qi, so the disease is localized in the hypochondrium. The spleen and stomach can be directly injured by overeating the fat, sweet and thick taste, spleen qi deficiency can not transport and transform and spread food essence, and the spleen qi is transformed into phlegm, dampness, turbidity and fat to be accumulated in the body, so that the qi movement is blocked; meanwhile, spleen fails to transport and dampness is generated internally, the qi movement of the middle energizer is not smooth, the smoothing and flow of the liver is affected, and various pathological products are accumulated in the liver to form NAFLD. By combining the theory and the traditional Chinese medicine clinical practice, the disease is considered to be mainly formed by liver dysfunction and spleen dysfunction caused by improper diet, emotional disorder and the like, which lead to phlegm-dampness and blood stasis and mutual obstruction, blood stasis and collateral obstruction and phlegm-dampness accumulation. Therefore, soothing the liver, strengthening the spleen, relieving depression, clearing heat and eliminating dampness are the key points for treating the disease.
The pathogenesis of NAFLD involves multiple complex factors, and therefore western medicine with a single therapeutic target has difficulty in effectively treating the NAFLD. Under the guidance of holistic concept and dialectical treatment theory, the traditional Chinese medicine has the obvious advantages of obvious treatment effect on NAFLD, few adverse reactions, low price, difficult occurrence of drug resistance and the like clinically through the characteristics of multiple ways, multiple targets, holistic regulation and the like, becomes an important means for treating the NAFLD, and provides a new direction for researching and developing new drugs for preventing and treating the nonalcoholic fatty liver disease.
Disclosure of Invention
The invention aims to provide the application of a eucommia ulmoides compound preparation in preparing a medicament for preventing and treating non-alcoholic fatty liver disease; the eucommia ulmoides compound preparation can effectively inhibit the accumulation of lipid in liver cells, reduce the content of inflammatory factors and blood sugar in serum and the weight of a mouse, improve the intestinal flora disorder of the mouse and effectively inhibit the further occurrence and development of metabolic-related fatty liver diseases.
In order to achieve the purpose, the technical scheme of the invention is as follows:
an application of a eucommia ulmoides compound preparation in treating nonalcoholic fatty liver diseases is prepared from 200 parts by weight of eucommia ulmoides, 200 parts by weight of motherwort, 150 parts by weight of selfheal, 100 parts by weight of scutellaria baicalensis, 100 parts by weight of andrographis paniculata, 100 parts by weight of hawthorn and 50 parts by weight of uncaria rhynchophylla.
The application of the eucommia ulmoides compound preparation comprises the following steps: weighing eucommia ulmoides, motherwort, selfheal, scutellaria baicalensis, andrographis paniculata, hawthorn and uncaria, cutting into segments, uniformly mixing, adding water, decocting twice, wherein the water amount added for the first time is 3 times of the weight of the medicinal materials, decocting for 4 hours, the water amount added for the second time is 2 times of the weight of the medicinal materials, decocting for 2 hours, combining decoction liquids, filtering, concentrating the filtrate under reduced pressure until the relative density is 1.25 at 80 ℃, spray-drying to obtain dry powder extract, and then adding auxiliary materials or not to prepare various oral preparations.
The eucommia ulmoides compound preparation is a capsule preparation prepared by adding a proper amount of starch, dextrin, sucrose and ethylparaben serving as auxiliary materials into the extract, uniformly mixing, granulating, drying and subpackaging.
The main raw materials in the invention have the following functional activities:
eucommia bark (monarch drug): pungent taste and mild nature; enter the kidney meridian. Has effects of nourishing liver and kidney, strengthening tendons and bones, and can be used for treating soreness of waist and back, weakness of feet and knees, dribbling urination, and hypertension.
Motherwort (ministerial drug): bitter and pungent taste, slightly cold nature; it enters liver, pericardium and bladder meridians. Has effects of promoting blood circulation, regulating menstruation, inducing diuresis, relieving swelling, clearing away heat and toxic materials, and can be used for treating menoxenia, dysmenorrhea, amenorrhea, lochiorrhea, edema, oliguria, and pyocutaneous disease.
Selfheal (a guiding drug): pungent and bitter in flavor and cold in nature. Has effects of clearing liver-fire, improving eyesight, resolving hard mass and detumescence, and can be used for treating conjunctival congestion, swelling and pain, eyeball nyctalgia, headache, giddiness, scrofula, goiter, mammary abscess, nodules of breast, and breast pain.
Scutellaria (adjuvant): bitter taste and cold nature; it enters lung, gallbladder, spleen, large intestine and small intestine meridians. Has effects of clearing heat, eliminating dampness, clearing pathogenic fire, removing toxic substance, stopping bleeding, and preventing miscarriage, and can be used for treating damp warmth, summer dampness, chest distress, nausea, dysentery, jaundice, cough due to lung heat, hyperpyrexia, dipsosis, hematemesis, carbuncle, sore, and threatened abortion.
Hawthorn fruit (messenger drug): sour and sweet in flavor, slightly warm in nature, entering spleen, stomach and liver meridians. Has effects of resolving food stagnation, invigorating stomach, activating qi-flowing, removing blood stasis, eliminating turbid pathogen and reducing blood lipid, and can be used for treating diseases such as meat food stagnation, gastric cavity distention, dysentery abdominal pain, blood stasis amenorrhea, puerperal blood stasis, heart and abdomen stabbing pain, thoracic obstruction, cardialgia, hernia pain, hyperlipidemia, etc.
Ramulus Uncariae cum uncis (guiding drugs): sweet in flavor, cool in nature, entering liver and pericardium meridian. Has effects in calming endogenous wind, clearing away heat, and calming liver, and can be used for treating liver wind stirring, infantile convulsion, febrile convulsion, common cold with convulsion, infantile cry, preeclampsia, headache, and vertigo.
Compared with the prior art, the invention has the beneficial effects that:
the invention discloses an effect of an eucommia ulmoides compound preparation on effectively preventing and treating non-alcoholic fatty liver disease for the first time, which is derived from a Guizhou folk Chinese medicine proved prescription and consists of 6 medicines of eucommia ulmoides, motherwort, selfheal, scutellaria baicalensis, hawthorn and uncaria. The prescription has the effects of clearing away heat and toxic materials, eliminating dampness, promoting blood circulation, removing blood stasis and benefiting liver and kidney, wherein eucommia ulmoides is used as a monarch drug in the prescription to play the roles of protecting liver and tonifying kidney, motherwort is used as a ministerial drug to play the roles of clearing away heat and promoting blood circulation, scutellaria baicalensis is used as an adjuvant drug to play the roles of clearing away heat and drying dampness, soothing liver and relieving depression, hawthorn, uncaria and selfheal are used as conductant drugs to play the roles of relieving dyspepsia, clearing away turbid qi, removing toxicity, reducing fat, promoting qi circulation and removing blood stasis, all the drugs are used together to take effect synergistically, and multiple-path and multi-target regulation is performed on MAFLD key links. The occurrence and development of the disease course of the MAFLD can be effectively regulated and controlled by improving insulin resistance, adjusting lipid metabolism abnormality and reducing the content of inflammatory factors IL-6 and TNF-alpha; meanwhile, the defects of high cost and adverse drug reactions caused by western medicine combination treatment are overcome, the use is convenient, safe and effective, and a new choice is provided for clinical medication for treating the MAFLD disease.
The method builds an in-vivo and in-vitro model of the metabolic correlation fatty liver disease and utilizes the in-vivo and in-vitro screening model to perform activity screening on a plurality of Guizhou folk prescriptions. Experiments show that the eucommia ulmoides compound preparation can inhibit the accumulation of lipid in liver cells by acting on a plurality of targets, reduce the content of inflammatory factors (IL-6 and TNF-alpha) and blood sugar in serum, reduce the content of free fatty acid in serum, inhibit the disturbance of a lipid metabolism pathway, improve the fatty degeneration of liver, increase the glucose tolerance and the insulin sensitivity, inhibit the disturbance of intestinal flora, and effectively inhibit the further occurrence and development of the metabolism-related fatty liver disease. The eucommia ulmoides compound preparation can be expected to be applied to prevention and treatment of non-alcoholic fatty liver diseases in future, provides a new medicine selection for non-alcoholic fatty liver disease patients, and has important significance and medical value on prevention and treatment of non-alcoholic fatty liver diseases, which are the first liver diseases in the world at present.
Drawings
FIG. 1 shows the effect of eucommia ulmoides compound preparation on the body weight of NAFLD mice; CN is normal group; MET is metformin group, DZ is eucommia ulmoides compound preparation treatment group, and M is NAFLD model group;
FIG. 2 shows the effect of eucommia ulmoides compound preparation on regulating blood sugar content of NAFLD mice; FIG. 2-A shows the fasting blood glucose level (n.gtoreq.6) of mice measured by a glucometer after fasting for 12 hours without water supply; FIG. 2-B is the glycated hemoglobin content in the serum of a mouse, FIG. 2-C is the insulin resistance index of a mouse, FIG. 2-D is the insulin content in the serum of a mouse, FIG. 2-E is the glucose tolerance assay (n is more than or equal to 6) of a mouse measured by injecting glucose into the abdominal cavity after the mouse is fasted for 12 hours without water prohibition, and FIG. 2-F is the area under the OGTT curve of the mouse; CN is normal group; MET is metformin group, DZ is eucommia ulmoides compound preparation treatment group, and M is NAFLD model group;
FIG. 3 shows H & E (A) and oil red O (B) staining observation of the protective effect of eucommia ulmoides compound preparation (DZ) on NAFLD mouse liver; DZ is eucommia ulmoides compound preparation treatment group, MET is metformin group, and M is NAFLD model group;
FIG. 4 shows the effect of treatment with the eucommia ulmoides compound preparation on low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), and Total Cholesterol (TC) in the serum of mice; CN is normal group; MET is metformin group, DZ is eucommia ulmoides compound preparation treatment group, and M is NAFLD model group;
FIG. 5 shows the effect of the compound preparation of eucommia bark on the regulation of inflammatory factors (IL-6 and TNF-alpha) in mouse serum; CN is a normal group; MET is metformin group, DZ is eucommia ulmoides compound preparation treatment group, and M is NAFLD model group;
FIG. 6 shows the serum contents of alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione peroxidase (GPx) in mice; CN is a normal group; MET is metformin group, DZ is eucommia ulmoides compound preparation treatment group, and M is NAFLD model group;
FIG. 7 is a mouse serum metabolomics analysis; DZ is eucommia bark compound preparation processing group, M is NAFLD model group, CN is normal group.
Detailed Description
weighing 200 parts by weight of eucommia bark, 200 parts by weight of motherwort, 150 parts by weight of selfheal, 100 parts by weight of scutellaria baicalensis, 100 parts by weight of andrographis paniculata, 100 parts by weight of hawthorn and 50 parts by weight of uncaria, cutting into sections, uniformly mixing, adding water, decocting twice, wherein the water amount added for the first time is 3 times of the weight of the medicinal materials, decocting for 4 hours, the water amount added for the second time is 2 times of the weight of the medicinal materials, decocting for 2 hours, combining decoction liquids, filtering, concentrating filtrate under reduced pressure until the relative density is 1.25 at 80 ℃, drying by microwave to obtain clear dry paste, crushing to 100-mesh powder, then adding auxiliary materials of starch and dextrin, granulating, drying, and encapsulating to obtain the traditional Chinese medicine.
The obtained capsule can be directly used for preventing/treating metabolism-related fatty liver disease. The usage and dosage are as follows: it is administered orally 2-4 granules at a time, 3 times daily.
Example 2: the application of the eucommia ulmoides compound preparation comprises the following steps:
weighing 200g of eucommia bark, 200g of motherwort, 150g of selfheal, 100g of scutellaria baicalensis, 100g of common andrographis herb, 100 parts by weight of scutellaria baicalensis and 50g of uncaria, and preparing various oral preparations by adopting a conventional extraction process and a preparation forming process.
The obtained oral preparation can be directly used for preventing and treating non-alcoholic fatty liver disease. The usage and dosage are as follows: it is administered orally at a dose of 1-2g once and 3 times daily.
Example 3: the application of the eucommia ulmoides compound preparation comprises the following steps:
weighing 200g of eucommia bark, 200g of motherwort, 150g of selfheal, 100g of scutellaria baicalensis, 100g of andrographis paniculata, 100 parts by weight of scutellaria baicalensis and 50g of uncaria, cutting into sections, uniformly mixing, adding water, decocting twice, wherein the water amount added for the first time is 6 times of the weight of the medicinal materials, decocting for 4 hours, the water amount added for the second time is 4 times of the weight of the medicinal materials, decocting for 3 hours, combining the decoctions, standing for 24 hours, taking the supernatant, concentrating to 70% of the total amount, and adding auxiliary materials or not into the obtained liquid medicine to prepare various oral preparations.
The obtained oral preparation can be directly used for preventing and treating non-alcoholic fatty liver disease. The usage and dosage are as follows: it is administered orally at a dose of 1-2g, 3 times a day.
Example 4: the application of the eucommia ulmoides compound preparation comprises the following steps:
the eucommia ulmoides compound preparation sold in the market can be directly used for preventing and treating the non-alcoholic fatty liver disease. The usage and dosage are as follows: it is administered orally 3-5 granules at a time, 2-3 times daily.
Experimental example:
1. experimental Material
1.1 materials and methods
SPF grade C57/6J mice, male mice, 6 weeks old, weight 20 + -2g, total 50, purchased from Nanjing model animal institute. The mouse is fed with growth breeding feed and high-fat feed, the rat is fed with growth breeding feed, the feed is produced by Shanghai Huayasi Chuang biology company, drinking water is sterilized tap water, animals freely eat drinking water during the experiment, the temperature of the laboratory is 21 +/-2 ℃, the humidity is 40-70%, and the license number of the laboratory is as follows: SYXK (Qian) 2018-0001.
1.2 instruments
Bench centrifuge (Beckman), biosafety cabinet (Thermo Scientific), fluorescence inverted microscope (Olympus), constant temperature water bath (Grant), autoclave (Shenan), milli-Q water generator (BioGen), multifunctional microplate reader (Bio tek).
1.3 grouping and building NAFLD model
After the animals are purchased and adapted for one week, the animals enter the experimental state. 50 mice were randomly divided into 5 groups of 10 mice each, each group being: normal group, model group, metformin group and eucommia ulmoides compound preparation group. All the groups were given high fat diet, drinking 10% fructose water, and continuously fed for 12 weeks, except for the normal group given normal diet and sterilized tap water.
1.4 administration by groups
Gavage dosing was started on week 4 of the experimental modeling. 1.125g of crude drug/kg of eucommia ulmoides compound preparation is administrated by intragastric administration, and the dosage of metformin administration is 0.075g/kg. The normal group and the model group were subjected to intragastric administration of physiological saline of the same volume once a day for 8 weeks. During the administration period, the mice in each group were molded continuously except for the normal group. The mice were weighed once a week and the dosage was varied according to the body weight.
1.5 treatment of laboratory animals
At the end of week 12, animals were fasted for 12h without water deprivation and weighed. After the mice in each group were anesthetized with 10% chloral hydrate, the mice were sacrificed by dislocation, blood was taken from the orbit, and the mouse serum was collected. The mouse liver is frozen and stored in a refrigerator at the temperature of 80 ℃ below zero for subsequent transcriptome analysis and detection.
Serum metabolomics:
a. mouse serum acquisition: the eucommia ulmoides compound preparation is used for treating a NAFLD mouse for 12 weeks and then blood is obtained, the blood taking mode is eyeball blood taking, and after the NAFLD mouse is treated by the medicament for 12 weeks, the blood of the mouse is obtained through the eyeball blood taking mode. Standing whole blood on ice at 4 deg.C for 0.5-1h, after blood is completely coagulated, centrifuging at 3000rpm for 15min, collecting supernatant, and storing at-80 deg.C.
b. The sample extraction method comprises the following steps: slowly thawing a sample at 4 ℃, adding a proper amount of sample into a precooled methanol/acetonitrile/water solution (2: 1, v/v), carrying out vortex mixing, carrying out low-temperature ultrasonic treatment for 30min, standing at-20 ℃ for 10min, centrifuging at 12000rpm for 20min at 4 ℃, taking a supernatant, carrying out vacuum drying, adding 100 mu L of acetonitrile aqueous solution (acetonitrile: water = 1: 1, v/v) for redissolving during mass spectrometry, carrying out vortex, centrifuging at 12000rpm for 15min at 4 ℃, and taking a supernatant for sample injection analysis.
c. Serum sample analysis: the prepared mouse serum sample was sent to Suihai New Life Co., ltd and subjected to measurement and analysis.
1.6 detection index
1.6.1 mice fasting plasma glucose and glucose tolerance assay
After the administration of the drug is finished, after the mice are fasted for 12 hours without water inhibition, the tail venous blood of the mice is taken to detect the blood sugar content by a Roche glucometer. Glucose tolerance assay: after fasting blood glucose is measured, glucose (dosage is 1.5 g/kg) is injected into abdominal cavity, and the blood glucose content of the glucose injected into abdominal cavity in different time periods (0 min, 15min, 30min, 60min and 120 min) is respectively measured by a Roche glucometer from the tail vein blood of the mouse.
1.6.2 liver samples
After the administration is finished, taking a part of liver sample and a part of feces sample of the mouse, and sending the liver sample and the feces sample to a large gene for transcriptome sequencing analysis; after the administration, a liver sample and a colon sample of the mouse were collected and sent to Wuhanseville Biotech Co., ltd for liver histopathological analysis (H & E staining and oil red O staining).
1.6.3 the enzyme-linked immunosorbent assay detects the contents of glutamic-pyruvic transaminase (ALT), glutamic-oxalacetic transaminase (AST), triglyceride (TG), total Cholesterol (TC), glycosylated hemoglobin (HbAlc), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GPx), high-density lipoprotein (HDL-L) and low-density lipoprotein (LDL-L) in serum samples of each group of mice.
The biochemical index detection of the blood of the mouse uses a 1.5 prepared serum sample of the mouse to detect the content of indexes such as ALT, AST, TG, TC, hbAlc, SOD, MDA, GPx, HDL-L, LDL-L and the like by a kit produced by Nanjing Bioproducts Limited through an enzyme labeling instrument.
1.6.4 enzyme-linked immunosorbent assay (ELISA) for detecting the contents of IL-6, TNF-alpha and insulin in the serum of each group of mice
The biochemical indexes of the blood of the mouse are detected, and the indexes of IL-6, TNF-alpha, insulin and the like are detected by using a mouse serum sample prepared by 1.5 and adopting an ELISA kit through an enzyme-linked immunosorbent assay (ELISA) instrument.
1.7 statistical methods
The experimental result adopts SPSS 22.0 statistical software, all data are expressed by mean +/-standard deviation, and the difference of two-two comparison is statistically significant by adopting t test p less than 0.05.
2 results of the experiment
2.1 influence of eucommia ulmoides Compound preparation treatment group on mouse weight
As shown in fig. 1, it can be seen from the experimental results of the control groups that the weight of the NAFLD model group induced by high fat diet is significantly higher than that of the normal group (p < 0.001), and the weight of the mice treated by the eucommia ulmoides compound preparation is lower than that of the NAFLD model group.
2.2 fasting blood glucose and blood glucose tolerance assay for groups of mice
The experimental results are shown in fig. 2A and B, the fasting blood sugar (M) content of the model group mice is significantly higher than that of the normal group (CN) (p < 0.001), and the blood sugar and glycosylated hemoglobin content of the eucommia ulmoides compound preparation (DZ) group mice of the invention is significantly lower than that of the M group (p < 0.05). After the eucommia ulmoides compound preparation is treated, the content of insulin in the serum of a mouse is remarkably reduced (p is less than 0.05), and the effect is equivalent to that of a positive medicine group (figure 2D). From fig. 2E and F, it can be seen that after 1.5g/kg of glucose was intraperitoneally injected into mice for 15min, the blood glucose levels of mice in MET and DZ groups showed a trend of significantly decreasing with time, which indicates that the tolerance of the mice to glucose was significantly enhanced after the treatment of the metformin and eucommia ulmoides compound preparation. The results show that the metformin and the eucommia ulmoides compound preparation reduce the blood sugar content of mice after treatment, and simultaneously increase the glucose tolerance of the mice. In addition, it is worth noting that the result of comparing the fasting blood glucose content and the glucose tolerance of the mice shows that the result of the eucommia ulmoides compound preparation for improving the blood glucose content and the glucose tolerance of the mice is obviously improved compared with the model group after the eucommia ulmoides compound preparation is treated.
2.3 influence of eucommia ulmoides compound preparation treatment group on NAFLD mouse bullous fatty degeneration
H & E staining showed that high lipid-induced NAFLD model mice all had somewhat necrotic and inflammatory cell infiltrates and varying degrees of steatosis and vacuolization, while the liver of NAFLD model mice was significantly larger than that of the DZ formula group (fig. 3A) and its liver appeared to be milky white in color to varying degrees (fig. 3C). The results of oil red O staining showed a significant increase in fat content in the liver of high fat induced NAFLD model mice (figure 3B). After the eucommia ulmoides compound preparation (DZ) is treated, the mouse liver steatosis, vacuole-like change and lipid accumulation are obviously improved, and the mouse liver shape is consistent with that of a normal group (figure 3C).
2.4 influence of eucommia bark Compound preparation treatment group on low density lipoprotein content (LDL-C), high density lipoprotein content (HDL-C), triglyceride (TG) and Total Cholesterol (TC) in NAFLD mouse serum
Abnormal changes in low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), triglyceride (TG), and Total Cholesterol (TC) in mouse serum are one of the most sensitive indicators of lipid metabolism disorder. Experiments show that the eucommia ulmoides compound preparation has the regulation effect on abnormal mouse lipid metabolism by measuring the contents of LDL-C, HDL-C, TG and TC in mouse serum. As shown in FIG. 4, compared with the normal group, the eucommia ulmoides compound preparation reduces LDL-C, TG and TC contents in mouse serum, increases HDL-C content, promotes liver lipid output, inhibits lipid repeat synthesis, and reduces liver lipid accumulation.
2.5 influence of eucommia ulmoides compound preparation treatment group on the content of inflammatory factors IL-6 and TNF-alpha in serum of NAFLD mice
In order to further explore whether the eucommia ulmoides compound preparation can inhibit in-vivo inflammatory reaction of mice caused by lipid peroxidation, the content of inflammatory factors IL-6 and TNF-alpha in serum of the mice is respectively measured by an Elisa method. As shown in figure 5, the experimental results of each group of control show that the eucommia ulmoides compound preparation reduces the content of inflammatory factors IL-6 and TNF-alpha in mouse serum and inhibits the inflammatory reaction induced by lipid peroxidation in a NAFLD mouse.
2.6 influence of eucommia ulmoides compound preparation treatment group on contents of alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GPx) in blood serum of NAFLD mice
In order to further analyze the treatment effect of the eucommia ulmoides compound preparation on NAFLD mice, biochemical index contents such as ALT, AST, GPx, MDA, SOD and the like in serum of each group of mice are also determined in experiments. As shown in fig. 4, compared with the normal group, the eucommia ulmoides compound preparation reduces the contents of alanine Aminotransferase (ALT), aspartate Aminotransferase (AST), malondialdehyde (MDA) and glutathione peroxidase (GPx) in the serum of the mice, and increases the content of superoxide dismutase (SOD). The results show that the eucommia ulmoides compound preparation can reduce the excessive accumulation of lipid and the damage of lipid peroxidation to liver cells.
2.7 influence of eucommia ulmoides compound preparation treatment group on NAFLD mouse serum metabonomics
Alterations in metabolites in mouse serum are the most important indicators of lipid metabolism disorders. The experiment reveals the regulation effect of the eucommia ulmoides compound preparation on the mouse serum metabolite by measuring the content of the metabolite in the mouse serum. Through clustering analysis (as shown in fig. 7), compared with a model group, the eucommia ulmoides compound preparation obviously influences the serum metabolites of mice, and promotes the serum metabolites of high-fat diet mice to be normal.
2.8 intestinal flora analysis
In recent years, the research finds that intestinal microbial disorder is closely related to the occurrence and development of NAFLD. Lipopolysaccharide (LPS) which is a metabolite generated by the disturbance of the intestinal flora enters the liver through the absorption of intestinal epithelial cells and activates an NF-kB signal channel together with ROS generated by lipid peroxidation, so that the generation and the development of inflammatory reaction are induced. Compared with the model group, the eucommia ulmoides compound preparation treatment group provided by the invention has the advantages that the proportion of intestinal firmicutes of NAFLD mice is obviously reduced, the proportion of bacteroidetes is increased to promote intestinal microecological balance, and the beneficial regulation effect on intestinal flora is superior to that of a MET group (figure 8).
Claims (3)
1. The eucommia ulmoides compound preparation is prepared from 200 parts by weight of eucommia ulmoides, 200 parts by weight of motherwort, 150 parts by weight of selfheal, 100 parts by weight of scutellaria baicalensis, 100 parts by weight of andrographis paniculata, 100 parts by weight of hawthorn and 50 parts by weight of uncaria as raw material medicines.
2. The use of the eucommia ulmoides compound preparation according to claim 1, wherein: the preparation method of the eucommia ulmoides compound preparation comprises the following steps: weighing eucommia ulmoides, motherwort, selfheal, scutellaria baicalensis, andrographis paniculata, hawthorn and uncaria, cutting into segments, uniformly mixing, adding water, decocting twice, wherein the water amount added for the first time is 3 times of the weight of the medicinal materials, decocting for 4 hours, the water amount added for the second time is 2 times of the weight of the medicinal materials, decocting for 2 hours, combining decoction liquids, filtering, concentrating the filtrate under reduced pressure until the relative density is 1.25 at 80 ℃, spray-drying to obtain dry powder extract, and then adding auxiliary materials or not to prepare various oral preparations.
3. The use of the eucommia ulmoides compound preparation according to claim 2, wherein: the eucommia ulmoides compound preparation is a capsule preparation prepared by adding a proper amount of starch, dextrin, sucrose and ethylparaben serving as auxiliary materials into the extract, uniformly mixing, granulating, drying and subpackaging.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109692214A (en) * | 2017-10-23 | 2019-04-30 | 康普药业股份有限公司 | It is a kind of for treating the pharmaceutical composition of hypertension |
| CN113717295A (en) * | 2021-09-28 | 2021-11-30 | 遵义医科大学 | Eucommia acidic polysaccharide, extraction method and application of eucommia acidic polysaccharide in preparation of medicine for treating fatty liver |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN109692214A (en) * | 2017-10-23 | 2019-04-30 | 康普药业股份有限公司 | It is a kind of for treating the pharmaceutical composition of hypertension |
| CN113717295A (en) * | 2021-09-28 | 2021-11-30 | 遵义医科大学 | Eucommia acidic polysaccharide, extraction method and application of eucommia acidic polysaccharide in preparation of medicine for treating fatty liver |
Non-Patent Citations (2)
| Title |
|---|
| 张佳等: "基于数据挖掘的盛国光教授治疗非酒精性脂肪性肝病用药规律分析", 中西医结合肝病杂志, vol. 31, no. 2, pages 125 - 129 * |
| 陶峥辉: "长期大剂量饮用单味山楂对高脂肪饮食导致的非酒精性脂肪肝患者血脂的影响", 光明中医, vol. 36, no. 12, pages 1991 - 1993 * |
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