Application of heart washing decoction in preparation of medicine for reducing soluble epoxide hydrolase in liver

Abstract

The invention discloses application of heart washing soup in preparation of a medicine for reducing soluble epoxide hydrolase in liver. The heart washing decoction disclosed by the invention can regulate and control soluble epoxide hydrolase and 14, 15-epoxy eicosatrienoic acid, and can improve central neuron insulin resistance, so that diabetes mellitus can be treated, and symptoms of Alzheimer disease can be improved.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to the application of a heart-cleansing decoction in the preparation of drugs that reduce soluble epoxide hydrolase in the liver. Background Technology

[0002] Alzheimer's disease (AD) is a degenerative disease of the central nervous system that primarily occurs in old age or pre-old age. The main characteristics of the disease include progressive cognitive impairment and behavioral disturbances. Alzheimer's disease is the most common form of dementia, accounting for approximately 60-70% of cases. The risk of developing Alzheimer's disease increases with age.

[0003] Symptoms of Alzheimer's disease include memory impairment, aphasia, apraxia, agnosia, and visuospatial impairment. In addition, patients also experience impairment in abstract thinking and calculation abilities, often accompanied by personality and behavioral changes. This disease is not contagious but is the result of a combination of genetic, lifestyle, and environmental factors.

[0004] This disease typically requires long-term treatment. Currently, the medical community mainly uses medication and psychotherapy to control disease progression and slow symptom deterioration. Although there is currently no cure for Alzheimer's disease, good lifestyle habits, including regular physical exercise, a healthy diet, and appropriate social activities, can help prevent the onset and progression of the disease.

[0005] Diabetes mellitus is a chronic disease characterized by hyperglycemia, caused by an absolute or relative deficiency of insulin secretion and impaired utilization. It is mainly classified into three types: type 1, type 2, and gestational diabetes. The etiology is primarily attributed to the combined effects of genetic and environmental factors, including decreased insulin secretion due to pancreatic islet cell dysfunction, or insensitivity to insulin, or both, resulting in the ineffective utilization and storage of glucose in the blood. Some diabetic patients and their families exhibit disease clustering. Furthermore, the incidence and prevalence of diabetes are on the rise globally.

[0006] The main treatment for diabetes is to maintain blood sugar levels within the normal range through scientific and reasonable treatment methods, prevent the occurrence of acute metabolic disorders, prevent or delay the onset and development of complications, and improve quality of life. Prognosis depends on disease control and the presence or absence of complications. Prevention of diabetes mainly relies on a healthy lifestyle, including a balanced diet, appropriate exercise, maintaining a normal weight, and regular checkups. Summary of the Invention

[0007] The purpose of this invention is to provide an application of Xixin Decoction in the preparation of drugs that reduce soluble epoxide hydrolase in the liver. Xixin Decoction of this invention can regulate soluble epoxide hydrolase and 14,15-epoxyeicosatetrienoic acid, and can improve insulin resistance in central neurons, thereby achieving the treatment of diabetes and improving the symptoms of Alzheimer's disease.

[0008] In order to achieve the above-mentioned objectives of the present invention, the following technical solution is adopted:

[0009] The first aspect of this invention provides the application of Xixin Decoction in the preparation of drugs that reduce soluble epoxide hydrolase in the liver.

[0010] Preferably, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0011] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0012] A second aspect of the present invention provides the use of Xixin Decoction in the preparation of drugs that enhance plasma and / or brain 14,15-epoxyeicosatetrienoic acid.

[0013] Preferably, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0014] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0015] The third aspect of this invention provides the application of Xixin Decoction in the preparation of drugs to improve insulin resistance in central neurons.

[0016] Preferably, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0017] Ginseng 12-18 parts, Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, Citrus reticulata peel 7-11 parts, Massa fermentata 7-11 parts, Acorus tatarinowii 7-11 parts, Glycyrrhiza uralensis 4-8 parts, and processed Aconitum carmichaelii 2-4 parts.

[0018] The fourth aspect of this invention provides the application of Xixin Decoction in the preparation of drugs for treating diabetes.

[0019] Preferably, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0020] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0021] The fifth aspect of this invention provides the application of Xixin Decoction in the preparation of a drug to improve the symptoms of Alzheimer's disease.

[0022] Preferably, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0023] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0024] Compared with the prior art, the beneficial effects of the present invention include at least the following:

[0025] The present invention, Xixin Decoction, can regulate soluble epoxide hydrolase and 14,15-epoxyeicosatotrienoic acid, and can improve central neuronal insulin resistance, thereby achieving the treatment of diabetes and improving the symptoms of Alzheimer's disease. Attached Figure Description

[0026] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the accompanying drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. In all the drawings, similar elements or parts are generally identified by similar reference numerals. In the drawings, the elements or parts are not necessarily drawn to scale.

[0027] Figure 1 These are the results of water maze experiments and immunohistochemical analysis in different groups in the embodiments of the present invention;

[0028] Figure 2 These are the WB and ELIS detection results for different groups in the embodiments of the present invention;

[0029] Figure 3 The results of insulin resistance index, brain tissue ROS, MDA, and WB detection in different groups of rats in this embodiment of the invention are shown. Detailed Implementation

[0030] The embodiments of the technical solution of the present invention will be described in detail below with reference to the examples. The following embodiments are only used to illustrate the technical solution of the present invention more clearly, and are therefore only examples, and should not be used to limit the scope of protection of the present invention.

[0031] It should be noted that, unless otherwise stated, the technical or scientific terms used in this application should have the ordinary meaning as understood by one of ordinary skill in the art to which this invention pertains.

[0032] This invention provides an application of Xixin Decoction in the preparation of drugs that reduce soluble epoxide hydrolase in the liver.

[0033] In one embodiment, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0034] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0035] Another embodiment of the present invention provides the application of Xixin Decoction in the preparation of drugs that enhance plasma and / or brain 14,15-epoxyeicosatetrienoic acid.

[0036] In one embodiment, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0037] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0038] Another embodiment of the present invention provides the application of Xixin Decoction in the preparation of drugs to improve central neuronal insulin resistance.

[0039] In one embodiment, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0040] Ginseng 12-18 parts, Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, Citrus reticulata peel 7-11 parts, Massa fermentata 7-11 parts, Acorus tatarinowii 7-11 parts, Glycyrrhiza uralensis 4-8 parts, and processed Aconitum carmichaelii 2-4 parts.

[0041] Another embodiment of the present invention provides the application of Xixin Decoction in the preparation of drugs for treating diabetes.

[0042] In one embodiment, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0043] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0044] Another embodiment of the present invention provides the application of Xixin Decoction in the preparation of a drug to improve the symptoms of Alzheimer's disease.

[0045] In one embodiment, the heart-cleansing decoction is prepared from the following ingredients in parts by weight:

[0046] Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

[0047] The technical solution of the present invention will be further described in detail below through specific embodiments.

[0048] Example

[0049] This example verifies the efficacy of the Heart-Cleansing Decoction:

[0050] 1. Materials and Methods

[0051] Methods for establishing the AD rat STZ induction model: SPF-grade male SD rats, weighing (160±10) g, were purchased from Beijing Vital River Co., Ltd. After routine anesthesia, the rats' head hair was removed, and they were fixed on a rat stereotaxic apparatus. After disinfection of the scalp, a sagittal incision was made in the midline of the skull. The periosteum was then bluntly dissected, and a hole was drilled in the skull using a craniotomy instrument. After these procedures, 10 µL of 10% streptozotocin (STZ) (purchased from Sigma-Aldrich, USA) was injected into each lateral ventricle. The injection coordinates were based on the "Stereotactic Atlas of the Rat Brain": 1.5 mm anterior to the anterior fontanelle, 1.5 mm laterally to each side of the sagittal suture, and 3.5 mm below the brain surface. Control rats received the same volume of physiological saline. The animal housing environment was controlled as follows: temperature maintained at 22-25℃, relative humidity maintained at 50-60%, light cycle with 12-hour light-dark alternation, and rats allowed free access to food and water. All procedures in this experiment complied with the relevant requirements of the "Regulations on the Management of Laboratory Animals" and strictly followed the ethical guidelines formulated by the institution's Laboratory Animal Ethics Committee, and were approved by the institution's Animal Ethics Committee.

[0052] 2. Formula for Xixin Decoction: Based on the original formula of Xixin Decoction, the ingredients are: ginseng 15 g, ginger-processed pinellia 15 g, poria cocos 30 g, jujube seed 30 g, tangerine peel 9 g, medicated leaven 9 g, acorus tatarinowii 9 g, licorice root 6 g, and processed aconite root 3 g. All medicinal materials were purchased from Beijing Tongrentang Pharmaceutical Company (Beijing, China). The preparation process of dissolving the medicinal materials is as follows: each medicinal material was added to water and boiled to extract the extract. The extract was then filtered, concentrated, and dried to obtain the extract. The extract was then dissolved in double-distilled water to prepare three concentrations of traditional Chinese medicine solution (the drug concentrations of the low, medium, and high dose groups of Xixin Decoction were 0.125, 0.25, and 0.5 g / mL, respectively), and stored at 4℃ for later use. Based on the dose equivalence conversion method between individual animals and between animals and humans in pharmacological experiments, the final low, medium, and high dose groups of Xixin Decoction were determined to be 0.703, 1.406, and 2.813 g / (kg·d), respectively.

[0053] 3. Grouping and Dosing

[0054] 3.1 Experimental rats were randomly divided into 5 groups, with 8 animals in each group: control group, AD group, AD + low-dose Xixintang group, AD + medium-dose Xixintang group, and AD + high-dose Xixintang group. The low-, medium-, and high-dose groups were administered Xixintang at doses of 0.703, 1.406, and 2.813 g / (kg·d) daily, respectively. Forty-eight hours after surgery, the rats were administered Xixintang via gavage once daily for 28 days. The control group and AD model group received the same volume of double-distilled water. Behavioral assessments were performed at the end of the treatment period. The Morris water maze test was used to assess the rats' learning and memory functions. Orientation training was conducted for 4 consecutive days, 4 times daily, with escape latency recorded simultaneously. On day 5, a spatial exploration test was performed, recording the time spent in the target quadrant and the number of times the rats traversed platforms. The training phase lasted for 3 days, with 3 training sessions per day, and the escape latency of the rats was recorded. Twenty-four hours after the end of training, an exploration test was conducted, recording the time spent in the target quadrant. The entire behavioral testing process was recorded using a video tracking system, and data analysis was performed blinded. After the behavioral experiment, the rats were perfused with phosphate-buffered saline (PBS) and fixed with 4% paraformaldehyde. Brain tissue was harvested, embedded in paraffin, and 4-5 µm thick sections were prepared for immunohistochemical analysis, targeting neurofibrillary tangles in the hippocampal region (NFTs). The immunohistochemical procedure was as follows: Sections were dewaxed and subjected to antigen retrieval. Endogenous peroxidase was first blocked with 3% hydrogen peroxide (H2O2), followed by blocking non-specific binding sites with 5% bovine serum albumin (BSA). The sections were then incubated overnight at 4°C with anti-phosphorylated Tau protein primary antibody. The next day, horseradish peroxidase (HRP)-labeled secondary antibody was added, followed by 3,3'-diaminobenzidine (DAB) staining and counterstaining with hematoxylin. Images were taken randomly in the CA1, CA3, and dentate gyrus regions of the hippocampus using an optical microscope. The area or integrated optical density (IOD) of positive regions was quantitatively analyzed using ImageJ software.

[0055] 3.2 SPF-grade male SD rats were randomly divided into a control group, an AD group, an AD + high-dose Xixintang group (2.813 g / kg·d), an AD + high-dose Xixintang + AAV8-NC group, and an AD + high-dose Xixintang + AAV8-EPHX2 group. The Xixintang group received daily gavage once a day for 28 days, starting 48 h post-surgery; the control and AD groups received an equal volume of distilled water. AAV8-NC or AAV8-EPHX2 (Hanheng Biotechnology, titer approximately 1×10^12 vg / mL) was injected into both hippocampi (AP-3.6 mm, ML±2.0 mm, DV-2.8 mm) on day 3 of modeling, at a rate of 2 µL per side, 0.2 µL / min, with the needles retained for 5 min.

[0056] At the end of the experiment, brain, liver, and plasma were collected. Western blot was used to detect hippocampal EPHX2 protein (EPHX2 antibody, 10833-1-AP, Proteintech Group, Inc., USA; internal control β-actin antibody, #4970, Cell Signaling Technology, USA), using a biuretine acid (BCA) quantitative protein kit (P0012, Beyotime, China). ELISA was used to detect liver sEH activity (No. 10011671, Cayman, USA) and 14,15-EET levels in plasma and brain tissue (DM-D9702, Duma Biotechnology, China), all performed according to the manufacturer's instructions; results were normalized by protein content or tissue weight.

[0057] 3.3 SPF-grade male SD rats (weighing 160±10 g) were randomly divided into 5 groups: control group, AD group, AD + high-dose Xixintang group (2.813 g / kg·d), AD + high-dose Xixintang + AAV8-NC group, and AD + high-dose Xixintang + AAV8-EPHX2 group. The high-dose Xixintang intervention group received gavage treatment starting 48 h post-surgery for 28 days. Adeno-associated virus (AAV) was injected into the bilateral hippocampus (AP-3.6 mm, ML±2.0 mm, DV-2.8 mm) using stereotactic technique on the 3rd day after modeling, at a dose of 2 µL per side, at a rate of 0.2 µL / min, with the needle remaining in place for 5 min. After behavioral or predetermined endpoints, rats were sacrificed for sampling: After a 12-hour fast, blood samples were collected from rats to measure fasting glucose (FG) and fasting insulin (FI). The insulin resistance index (HOMA-IR) was then calculated using the standard formula: HOMA-IR = FG (mmol / L) × FI (μU / mL) / 22.5. Hippocampal and cortical tissues were isolated from the brain. A portion of the tissue was sectioned for dihydroethidium (DHE) staining to detect reactive oxygen species (ROS) (DHE probe, Invitrogen; section thickness 10-20 µm, 10 µM DHE, incubation at 37°C in the dark for 30 min, photographed under a fluorescence microscope and semi-quantitatively analyzed using ImageJ). A portion of the homogenate was used for the thiobarbituric acid (TBA) method to determine malondialdehyde (MDA), and the results were standardized according to tissue wet weight or protein content.

[0058] Protein detection experimental procedure: Hippocampal tissue samples were taken and lysed with RIPA lysis buffer to obtain protein extracts. Protein concentration was determined using the BCA protein quantification method. Based on the quantification results, an equal amount of protein was loaded onto an SDS-PAGE gel for electrophoretic separation. The separated proteins were then transferred to a PVDF membrane. After blocking non-specific binding on the PVDF membrane, a specific antibody was added for incubation. Subsequent development was performed using ECL chemiluminescence immunoassay for Western blot detection. This study covered the following indicators: phosphorylation sites of insulin receptor substrate 1 (IRS-1) pS307, pS612, and pS636 (ELK8434, ELK Biotechnology, China); glucose transporter type 4 (GLUT4) (ELK5796, ELK Biotechnology, China); Aβ42 (ELK4897, ELK Biotechnology, China); phosphorylated Tau protein (ELK9247, ELK Biotechnology, China); and total Tau (ELK10040, ELK Biotechnology, China). β-actin was used as an internal control, and ImageJ was used for semi-quantitative normalization, expressed as mean ± SD.

[0059] 4. Statistical Analysis:

[0060] Statistical analysis was performed using GraphPad Prism 10. One-way ANOVA (Tukey post-hoc test) was used for comparisons between groups, and non-normal data were analyzed using corresponding non-parametric tests. P < 0.05 was considered significant.

[0061] 5. Experimental Results

[0062] 5.1 Results of the water maze test and immunohistochemical analysis are as follows: Figure 1 As shown, Figure 1 In the image, A: The Morris water maze test is used to assess rats' learning and memory abilities regarding spatial location and orientation; B: Water maze trajectory diagram; C: Immunohistochemical analysis of the expression level and phosphorylation of total Tau protein in the hippocampus.

[0063] Depend on Figure 1It was found that high-dose Xixin Decoction significantly alleviated Alzheimer's disease. The AD model rats induced by STZ exhibited significant cognitive impairment. Compared with the control group, the model group showed a significantly prolonged escape latency, a significantly reduced number of platform crossings, and a significantly shorter dwell time in the target quadrant during the Morris water maze test. These behavioral differences suggest that the AD rat model constructed in this experiment was successful. Further research revealed that Xixin Decoction intervention improved the cognitive function of AD model rats. The medium-dose Xixin Decoction group significantly shortened the escape latency, demonstrating an improvement effect on cognitive impairment. The high-dose group not only had a significantly shorter escape latency than the AD group, but also significantly more platform crossings and longer dwell time in the target quadrant, showing a more significant improvement in learning and memory function. Molecular-level experiments showed that the expression level of phosphorylated Tau protein in the hippocampus was significantly increased in the AD group, while the high-dose Xixin Decoction group significantly reduced Tau phosphorylation levels, showing a statistically significant difference compared to the AD group. This suggests that Xixin Decoction has an ameliorative effect on abnormal Tau phosphorylation and neuropathological changes. Overall results indicate that Xixin Decoction, especially at high doses, has a significant protective effect on learning and memory function and Tau abnormalities in AD model rats.

[0064] 5.2 WB test results and ELIS test results are as follows Figure 2 As shown, Figure 2 In the above, A: Western blot was used to detect EPHX2 expression in the liver of rats in each group; B: ELISA was used to detect sEH activity in the liver of rats in each group; C: ELISA was used to detect 14,15-EET levels in plasma and brain of rats in each group.

[0065] Depend on Figure 2 It is known that Xixin Decoction inhibits the increase in plasma and brain 14,15-EET levels by suppressing hepatic sEH. Figure 2The experimental results showed that the expression level of EPHX2 in the liver and the activity of sEH in the AD group were significantly higher than those in the control group and the AD + high-dose Xixintang group. Simultaneously, the levels of 14,15-EET in plasma and brain tissue were significantly reduced, suggesting that the AD model induced the upregulation of hepatic sEH and the decrease of 14,15-EET. High-dose Xixintang intervention effectively reduced hepatic EPHX2 expression and sEH activity, and significantly increased plasma and brain 14,15-EET levels, indicating its regulatory role in the sEH / 14,15-EET pathway. Further verification through AAV8-EPHX2 intervention showed that the expression level of hepatic EPHX2 and the activity of sEH in the AD + high-dose Xixintang + AAV8-EPHX2 group were significantly higher than those in the AD + high-dose Xixintang + AAV8-NC group, while the levels of 14,15-EET in plasma and brain were significantly reduced, suggesting that overexpression of EPHX2 can reverse the regulatory effect of Xixintang on the sEH / 14,15-EET pathway. Overall results indicate that Xixin Decoction exerts a potential neuroprotective effect by inhibiting hepatic sEH expression and activity and increasing plasma and brain 14,15-EET levels.

[0066] 5.3 Results of insulin resistance index, brain tissue ROS, MDA, and WB in different groups of rats are as follows: Figure 3 As shown, Figure 3 In the table, A: Insulin resistance index of rats in each group was detected; B: ROS content in brain tissue of rats in each group was detected by DHE probe; C: MDA level in brain tissue of rats in each group was detected by TBA method; D: IRS1 S307, IRS1 pS612, IRS1 pS636, GLUT4, Aβ42 and p-Tau / Tau levels in brain tissue of rats in each group were detected by WB.

[0067] Depend on Figure 3It is known that Xixin Decoction can improve neuronal insulin resistance by inhibiting hepatic sEH. Experimental results showed that the insulin resistance index of AD rats was significantly increased, and the contents of ROS and MDA in brain tissue were significantly increased. The phosphorylation levels of IRS1 Ser307, Ser612, and Ser636, as well as Aβ42 and Tau phosphorylation levels, were significantly higher than those in the control group, while GLUT4 level was significantly decreased, suggesting that the AD model can induce significant neuronal oxidative stress and insulin resistance. High-dose intervention with Xixin Decoction can significantly reduce the insulin resistance index, decrease the contents of ROS and MDA in brain tissue, inhibit abnormal phosphorylation of IRS1, Aβ42 aggregation, and abnormal phosphorylation of Tau, and restore GLUT4 level, indicating that it can improve neuronal insulin sensitivity and oxidative stress state. Further validation through AAV8-EPHX2 intervention showed that the AD + high-dose Xixintang + AAV8-EPHX2 group had significantly higher insulin resistance index, brain ROS, MDA content, and IRS1 phosphorylation, Aβ42 and Tau phosphorylation levels than the AD + high-dose Xixintang + AAV8-NC group, while GLUT4 levels were significantly decreased, suggesting that EPHX2 overexpression can reverse the effect of Xixintang in improving neuronal insulin resistance. Overall, the results indicate that Xixintang improves neuronal insulin resistance and oxidative stress by inhibiting hepatic sEH expression and activity.

[0068] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features therein. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention, and they should all be covered within the scope of the claims and specification of the present invention.

Claims

1. Application of Xixin Decoction in the preparation of drugs that reduce soluble epoxide hydrolase in the liver.

2. The application according to claim 1, characterized in that, The heart-cleansing decoction is prepared from the following ingredients in parts by weight: Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

3. Application of Xixin Decoction in the preparation of drugs that enhance plasma and / or brain 14,15-epoxyeicosatotrienoic acid.

4. The application according to claim 3, characterized in that, The heart-cleansing decoction is prepared from the following ingredients in parts by weight: Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

5. Application of Xixin Decoction in the preparation of drugs to improve central neuronal insulin resistance.

6. The application according to claim 5, characterized in that, The heart-cleansing decoction is prepared from the following ingredients in parts by weight: Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

7. Application of Xixin Decoction in the preparation of drugs for treating diabetes.

8. The application according to claim 7, characterized in that, The heart-cleansing decoction is prepared from the following ingredients in parts by weight: Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

9. Application of Xixin Decoction in the preparation of drugs to improve the symptoms of Alzheimer's disease.

10. The application according to claim 9, characterized in that, The heart-cleansing decoction is prepared from the following ingredients in parts by weight: Ginseng 12-18 parts, ginger-processed Pinellia ternata 12-18 parts, Poria cocos 25-35 parts, Ziziphus jujuba var. spinosa 25-35 parts, tangerine peel 7-11 parts, medicated leaven 7-11 parts, Acorus tatarinowii 7-11 parts, licorice root 4-8 parts, and processed aconite root 2-4 parts.

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