A traditional Chinese medicine composition for clearing away heat and relieving summer heat, and its preparation method and application

Abstract

The present invention belongs to the technical field of Chinese medicine compositions, and relates to a Chinese medicine composition for clearing away heat and relieving summer heat, and a preparation method and application thereof. The present invention discloses a Chinese medicine composition for clearing away heat and relieving summer heat, and the Chinese medicine composition for clearing away heat and relieving summer heat is prepared from the following components, by weight: 5-30 parts of American ginseng, 90-120 parts of wax gourd peel, 5-30 parts of Adenophora, 5-30 parts of Asparagus cochinchinensis, 5-30 parts of Lycium bark, 5-30 parts of Scrophularia, 5-30 parts of Anemarrhena, 3-9 parts of Coptis chinensis, 2-8 parts of Phellodendron chinense, 5-15 parts of Phragmites australis, 5-25 parts of lotus leaves, 6-13 parts of Schisandra chinensis, 6-13 parts of Poria cocos, 5-15 parts of Orientalis, 1-15 parts of Licorice root, and 20-50 parts of Coix seeds. The present invention also provides a method for preparing a Chinese medicine composition for clearing away heat and relieving summer heat, comprising: first preparing the weighed components of the Chinese medicine into raw material particles with a particle size of 74 to 106 μm, then grinding them into particles with a particle size of 10 to 50 μm, and soaking them in hot water. The Chinese medicine composition for clearing away heat and relieving summer heat obtained by network pharmacology analysis of the present invention is used to prepare a drug for preventing / treating heat stroke, and effectively preventing / treating heat stroke.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese medicine compositions, and relates to a Chinese medicine composition for clearing away heat and relieving summer heat, and a preparation method and application thereof. Background Art

[0002] Heat stroke is a life-threatening disease, defined as a rapid increase in core body temperature above 40°C, accompanied by central nervous system abnormalities such as delirium, convulsions, or coma. Heat stroke is divided into two forms: classic heat stroke (CHS) and exertional heat stroke (EHS). CHS mainly occurs in young or elderly people, while EHS is more common in athletes and military personnel who engage in strenuous outdoor sports. With the ravages of global heat waves and the increased risk of EHS, EHS has become a hot topic of concern and a serious social problem. Unfortunately, the clinical treatments for EHS, including cooling, intravenous hydration, and hemodialysis filtration, are not satisfactory. In addition, there are few measures to help prevent EHS. Exertional heat stroke can cause kidney damage, and its pathogenesis may be closely related to renal tubular damage caused by electrolyte disorders and oxidative stress damage, toxic effects of high temperature, coagulation disorders, rhabdomyolysis syndrome, endotoxemia, and systemic inflammatory response syndrome. Acute stress reduces renal blood flow and causes ischemia, thereby inducing acute kidney injury. Potential pathogenesis includes nephron segmental damage, including ischemia itself and survival or death mechanisms caused by oxidative stress. At this time, it becomes extremely important to seek safer and more effective drugs to treat exertional heat stroke. Summary of the invention

[0003] The purpose of the present invention is to address the above-mentioned problems existing in the prior art and to propose a Chinese medicine composition for clearing away heat and relieving summer heat, which can enable the human body to absorb the effective ingredients of the Chinese medicine composition through the gastrointestinal tract, thereby achieving the purpose of clearing away heat and relieving summer heat and improving the kidney function of patients with exertional heat stroke.

[0004] The purpose of the present invention can be achieved by the following technical solutions:

[0005] A Chinese medicine composition for clearing away heat and relieving summer heat, the Chinese medicine composition for clearing away heat and relieving summer heat is made of the following components, calculated by weight:

[0006] 5-30 parts of American ginseng, 90-120 parts of wax gourd peel, 5-30 parts of Adenophora, 5-30 parts of Asparagus, 5-30 parts of Lycium bark, 5-30 parts of Scrophularia, 5-30 parts of Anemarrhena, 3-9 parts of Coptis chinensis, 2-8 parts of Phellodendron, 5-15 parts of Phragmites australis, 5-25 parts of lotus leaf, 6-13 parts of Schisandra chinensis, 6-13 parts of Poria, 5-15 parts of Alisma orientalis, 1-15 parts of Licorice, and 20-50 parts of Coix seeds.

[0007] In this prescription, American ginseng and wax gourd peel are the main drugs; American ginseng nourishes yin and replenishes qi, clears heat and produces body fluid, while wax gourd peel clears summer heat and removes dampness. Adenophora, Asparagus cochinchinensis, Scrophularia ningpoensis, and Rehmannia root bark are all assistant drugs; Adenophora ningpoensis clears the lungs, clears heat, cools blood, and produces body fluid, Asparagus cochinchinensis clears the heart and benefits the stomach, Scrophularia ningpoensis nourishes the liver and kidneys, and Rehmannia root bark penetrates the heat and removes it from the surface, helping American ginseng to clear heat, nourish yin, and produce body fluid. Anemarrhena asphodeloides, Coptis chinensis, and Phellodendron chinense clear heat and detoxify, Anemarrhena asphodeloides clears the heat in the upper jiao, Coptis chinensis clears the heat in the middle jiao, and Phellodendron chinense clears the heat in the lower jiao, and also prevents Adenophora ningpoensis, Asparagus cochinchinensis, and Scrophularia ningpoensis from being too nourishing and greasy; Lotus leaf and Schisandra chinensis clear summer heat and replenish qi; Phragmites australis, Poria cocos, and Alisma orientalis help wax gourd peel clear the three jiaos and lead the internal heat of summer heat and dampness to be discharged through urine, and are all adjuvant drugs. Coix seed and licorice are all guiding drugs, benefiting the stomach and harmonizing the middle jiao.

[0008] Preferably, the total amount of American ginseng and wax gourd peel added to the heat-clearing and summer-heat-relieving traditional Chinese medicine composition accounts for 42-49%.

[0009] Preferably, the total amount of Adenophora Root, Asparagus Cochinchinensis, Scrophularia ningpoensis and Cortex Lycii added accounts for 18-25%.

[0010] Preferably, the Chinese medicine composition for clearing away heat and relieving summer heat is made of the following components, calculated by weight:

[0011] 15 parts of American ginseng, 100 parts of wax gourd peels, 15 parts of Adenophora scutellariae, 15 parts of Asparagus cochinchinensis, 15 parts of Lycium bark, 15 parts of Scrophularia ningpoensis, 15 parts of Anemarrhena asphodeloides, 5 parts of Coptis chinensis, 5 parts of Phellodendron chinense, 10 parts of Phragmites australis, 10 parts of Lotus leaves, 10 parts of Schisandra chinensis, 10 parts of Poria cocos, 10 parts of Alismatis orientalis, 5 parts of Licorice root, and 30 parts of Coix seeds.

[0012] Preferably, the dosage form of the Chinese medicine composition includes one or more of decoction, pills, granules, capsules, and tablets.

[0013] The present invention also provides a method for preparing a Chinese medicine composition for clearing away heat and relieving summer heat, the preparation method comprising: first preparing the weighed components of the Chinese medicine into raw material particles with a particle size of 74 to 106 μm, then grinding them into particles with a particle size of 10 to 50 μm, and soaking them in hot water.

[0014] Compared with conventional Chinese medicine compositions that need to be decocted before being taken, the Chinese medicine composition of the present invention can be crushed and soaked in hot water, which is more convenient to carry and take.

[0015] Preferably, the temperature of the hot water is 80-90° C.; and the Chinese medicine composition is immersed in the hot water for 20-30 minutes.

[0016] Preferably, the mass volume ratio of the traditional Chinese medicine composition to hot water is (240-290) g:300 ml.

[0017] The present invention also provides the use of a traditional Chinese medicine composition for clearing away heat and relieving summer heat in the preparation of a medicine for preventing / treating heat stroke.

[0018] The combination of the drugs of the present invention can clear away heat, invigorate qi and cool blood, nourish yin, harmonize the stomach and produce body fluid, and can effectively reduce organ damage caused by high temperature in people suffering from exertional heat stroke. The whole formula can be used together to clear away heat and relieve summer heat, and can be used to effectively prevent / treat heat stroke.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] 1. The Chinese medicine composition for clearing away heat and relieving summer heat obtained by network pharmacology analysis of the present invention takes American ginseng and wax gourd peel as monarch drugs. American ginseng nourishes yin and replenishes qi, clears heat and produces body fluid, and wax gourd peel clears away summer heat and removes dampness; Adenophora, Asparagus cochinchinensis, Scrophularia ningpoensis, and Rehmannia root bark are all ministerial drugs. Adenophora clears the lungs, clears heat, cools blood and produces body fluid, Asparagus cochinchinensis clears the heart and benefits the stomach, Scrophularia ningpoensis nourishes the liver and kidneys, and Rehmannia root bark penetrates the surface and helps American ginseng to clear heat, nourish yin and produce body fluid; Anemarrhena asphodeloides, Coptis chinensis, and Phellodendron chinense clear heat and detoxify. Anemarrhena asphodeloides clears the heat in the upper burner, Coptis chinensis clears the heat in the middle burner, and Phellodendron chinense clears the heat in the lower burner, and prevents Adenophora asparagus, Asparagus cochinchinensis, and Scrophularia ningpoensis from being too nourishing and greasy; Lotus leaf and Schisandra chinensis clear away summer heat and replenish qi; Phragmites australis, Poria cocos, and Alisma orientalis help wax gourd peel to clear the three burners and lead the internal heat of summer heat and dampness out of the urine, and are all adjuvant drugs; Coix seed and Licorice are all guiding drugs, which benefit the stomach and harmonize the middle burner.

[0021] 2. The raw materials of the heat-clearing and summer-heat-relieving Chinese medicinal composition of the present invention are conventional commercial products, which are easily available; and the dosage can be increased or decreased according to the patient's symptoms.

[0022] 3. The raw materials of the Chinese medicine composition for clearing away heat and relieving summer heat of the present invention are low in price. Each dose contains 265 g of raw materials of the Chinese medicine composition, which is converted to about RMB 15 per dose. It can be taken 3 times a day, which is equivalent to about RMB 5 per time; it can be widely used by ordinary people.

[0023] 4. The present invention utilizes hot water to soak the Chinese medicine composition, which can release the medicinal effects of the raw materials; the method of use is comfortable and non-invasive, and has extremely rare adverse reactions, so patients have high compliance and are willing to cooperate with the treatment.

[0024] 5. The Chinese herbal composition for clearing away heat and relieving summer heat of the present invention can be used to prepare drugs for preventing / treating heat stroke. Currently, there is no effective drug for preventing / treating heat stroke. The Chinese herbal composition of the present invention can effectively prevent / alleviate the disease. The Chinese herbal composition for clearing away heat and relieving summer heat can effectively supplement the shortage of the market for drugs for preventing / treating heat stroke. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 The data diagram of rat kidney tissue after 24 hours for the blank group and the control group of the present invention, the low-dose group of Example 1 and the high-dose group of Example 1 using the decoction of the Chinese medicine composition for clearing away heat and relieving summer heat.

[0026] Figure 2These are histopathological images of the blank group (a), control group (b), low-dose group (c) of Example 1, and high-dose group (d) of Example 1 of the present invention.

[0027] Figure 3 The protein expression (upper) and quantitative (lower) graphs of cleaved caspase 3, total caspase 3, Bax, and Bcl-2 in rat kidney tissue of the blank group and control group of the present invention, the low-dose group of Example 1, and the high-dose group of Example 1 using the Chinese medicine composition decoction for clearing away heat and relieving summer heat.

[0028] Figure 4 The blank group and control group of the present invention, the low-dose group of Example 1 and the high-dose group of Example 1 using the decoction of the Chinese herbal composition for clearing away heat and relieving summer heat are shown in the graph (above) and the quantitative graph (below) of the protein expression results of HSP90, Akt, p-Akt and Bcl-xL.

[0029] Figure 5 The EHS target Venn diagram (a) and the cross-target Venn diagram (b) of the present invention.

[0030] Figure 6 The interactive PPT network (a) and PPI network (b-d) constructed by the String database of the present invention.

[0031] Figure 7 The diagrams show the results of GO (a) and KEGG (b) gene enrichment analysis of the present invention. DETAILED DESCRIPTION

[0032] The following are specific embodiments of the present invention, which further describe the technical solutions of the present invention, but the present invention is not limited to these embodiments.

[0033] The present invention has no special limitation on the source of raw materials, and conventional commercially available products known to those skilled in the art can be used; the dosage of raw materials is increased or decreased according to the symptoms of the patient; if the patient has constipation, 5g of rhubarb and 10g of sodium salide can be added; if the patient has hematuria, blood cooling and hemostatic products can be added, such as 5g of pyrrosia and 5g of cirsium japonicum.

[0034] Rats were purchased from SLAC Laboratory Animal Technology (Shanghai, China).

[0035] Example 1

[0036] Weigh the raw materials according to the following proportions: 15 parts of American ginseng, 100 parts of wax gourd peel, 15 parts of Adenophora scutellariae, 15 parts of Asparagus cochinchinensis, 15 parts of Lycium bark, 15 parts of Scrophularia ningpoensis, 15 parts of Anemarrhena asphodeloides, 5 parts of Coptis chinensis, 5 parts of Phellodendron chinense, 10 parts of Phragmites australis, 10 parts of lotus leaves, 10 parts of Schisandra chinensis, 10 parts of Poria cocos, 10 parts of Alisma orientalis, 5 parts of Licorice root, and 30 parts of Coix seeds.

[0037] Each raw material was ground into raw material particles with a particle size of 80 μm using a common grinder, and the raw material particles were ground into a Chinese medicine composition powder with a particle size of 20 μm using an ultrafine grinder; 250 g of the Chinese medicine composition powder was soaked in 90° C. water (300 ml) for 30 min to prepare a decoction.

[0038] Example 2

[0039] Compared with Example 1, the difference is that the raw materials are weighed according to the following proportions: 20 parts of American ginseng, 95 parts of wax gourd peel, 17 parts of Adenophora radix, 13 parts of Asparagus cochinchinensis, 16 parts of Lycium bark, 14 parts of Scrophularia ningpoensis, 15 parts of Anemarrhena asphodeloides, 5 parts of Coptis chinensis, 5 parts of Phellodendron chinense, 10 parts of Phragmites australis, 10 parts of lotus leaves, 10 parts of Schisandra chinensis, 10 parts of Poria cocos, 10 parts of Alisma orientalis, 5 parts of Licorice root, and 30 parts of Coix seeds.

[0040] Example 3

[0041] Compared with Example 1, the difference is that the weighed Chinese medicine composition is decocted, 4 times the weight of water of the Chinese medicine composition is added, decocted and concentrated to 1 times the weight of water, and filtered to obtain the decocted decoction.

[0042] Comparative Example 1

[0043] Compared with Example 1, the difference is that the raw materials are weighed according to the following proportions: 30 parts of American ginseng, 20 parts of Adenophora Root, 20 parts of Asparagus Cochinchinensis, 20 parts of Lycium bark, 20 parts of Scrophularia ningpoensis, 20 parts of Anemarrhena Rhizome, 10 parts of Coptis chinensis, 10 parts of Phellodendron Amurense, 20 parts of Phragmites australis, 20 parts of lotus leaves, 20 parts of Schisandra chinensis, 20 parts of Poria cocos, 15 parts of Alisma orientalis, 10 parts of Licorice, and 30 parts of Coix seeds.

[0044] Comparative Example 2

[0045] Compared with Example 1, the difference is that the raw materials are weighed according to the following proportions: 15 parts of American ginseng, 100 parts of wax gourd peel, 15 parts of Adenophora radix, 15 parts of Asparagus cochinchinensis, 15 parts of Lycium bark, 15 parts of Scrophularia ningpoensis, 15 parts of Phragmites australis, 15 parts of lotus leaves, 15 parts of Schisandra chinensis, 15 parts of Poria cocos, 15 parts of Alisma orientalis, 5 parts of Licorice root, and 30 parts of Coix seeds.

[0046] Comparative Example 3

[0047] Compared with Example 1, the difference is that the raw materials are weighed according to the following proportions: 30 parts of American ginseng, 100 parts of wax gourd peel, 20 parts of Anemarrhena asphodeloides, 10 parts of Coptis chinensis, 10 parts of Phellodendron chinense, 15 parts of Phragmites australis, 15 parts of lotus leaves, 15 parts of Schisandra chinensis, 15 parts of Poria cocos, 15 parts of Alisma orientalis, 10 parts of Licorice root, and 30 parts of Coix seeds.

[0048] (I) Animal experiments

[0049] 1. Selection and pretreatment of experimental animals

[0050] 1. Grouping:

[0051] 270 SPF male SD rats, weighing 180-220 g, were selected and randomly divided into 9 groups using the EXCEL table, including 30 control groups, 30 blank groups, 30 experimental groups (large-dose group in Example 1), 30 experimental groups (small-dose group in Example 1), 30 experimental groups (large-dose group in Example 2), 30 experimental groups (large-dose group in Example 3), 30 experimental groups (large-dose group in Comparative Example 1), 30 experimental groups (large-dose group in Comparative Example 2), and 30 experimental groups (large-dose group in Comparative Example 3).

[0052] 2. Feeding, medication and adaptive training:

[0053] The rats were placed in a simulated climate animal cabin with cages, with an ambient temperature of 27°C and a humidity of 55%±5%. The rats were given concentrated Chinese medicine orally at 6:00, 12:00, and 18:00 every day for 2 weeks. The rats in the high-dose group (dosage of 4 mL / 100 g) and the low-dose group (dosage of 2 mL / 100 g) were given concentrated Chinese medicine orally. The control group and the blank group were given the same amount of drinking water. The rats were free to eat and drink water during the rest of the period.

[0054] The rats were placed on a treadmill placed in a simulated climate animal cabin, and the running speed was set to 15 m / min, the slope was 0, the running time was 10 min, once a day, for 2 consecutive weeks; the experiment began the day after the 2-week training.

[0055] 2. Conduct of Animal Experiments

[0056] 1. Experimental preparation and parameter setting

[0057] A treadmill (Zhongshi Technology, Beijing, China) was set up to make a forced running system. The rats were trained to be familiar with the treadmill one week in advance, with the aim of allowing the rats to adapt to the system before the EHS was established. The runway was previously designed with electrodes at the end. The electrical stimulation was set to 1 mAh, and the rats were forced to run in a standard environment.

[0058] Before the experiment, the temperature of the climate chamber was preheated to 30°C. After 30 minutes, the parameters in the climate chamber were set to the experimental parameters: temperature (40.5±0.5)°C, relative humidity (65±5)%. The experiment began after the parameters stabilized.

[0059] 2. The experimental methods of each experimental group are as follows:

[0060] 1) Control group: Rats were placed on the experimental animal treadmill for load exercise, and the rat tail artery non-invasive blood pressure monitor and life detection system were used to closely monitor the body temperature and blood pressure of the rats. When the mean arterial pressure of the rats dropped by 25 mmHg and the anal temperature reached 42.5°C, the model of the control group was determined to be successfully established and the load exercise was terminated;

[0061] 2) High-dose group: Rats were placed on an experimental animal treadmill for load exercise, and the rat tail artery non-invasive blood pressure monitor and life detection system were used to closely monitor the blood pressure and body temperature of the rats. When the mean arterial pressure of the rats dropped by 25 mmHg and the anal temperature reached 42.5°C, the model of the control group was determined to be successfully established and the load exercise was terminated;

[0062] 3) Low-dose group: Rats were placed on an experimental animal treadmill for load exercise, and the rat tail artery non-invasive blood pressure monitor and life detection system were used to closely monitor the blood pressure and body temperature of the rats. When the mean arterial pressure of the rats dropped by 25 mmHg and the anal temperature reached 42.5°C, the experimental model standard was met and the load exercise was terminated;

[0063] 4) Blank group: The rats were placed naturally without additional exercise load training, and their body temperature and blood pressure were closely monitored. When the mean arterial pressure of the rats dropped by 25 mmHg and the anal temperature reached 42.5°C, the model was successfully established.

[0064] III. Collection and testing of animal experimental results

[0065] The time for the nine groups of rats to complete the modeling was recorded, and the rats were moved to a normal temperature laboratory. The corresponding clinical manifestations of the experimental animals were recorded at 0h, 0.5h, 1h, 2h, 6h, and 24h after the successful modeling. Five rats were selected from each group in each time period, and the values ​​were averaged.

[0066] After weighing, the rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (0.3 ml / 100 mg) (after weighing, the rats were intraperitoneally injected with 10% chloral hydrate 0.3 ml / 100 g (the abdomen of the rats was wiped and disinfected with alcohol cotton balls, the needle was inserted into the subcutaneous tissue of the left or right abdomen, and the needle was pushed forward along the subcutaneous tissue for about 0.5 cm, and then the needle was inserted into the abdominal cavity at a 45° angle to the skin. There was a sense of empty space, and after no intestinal fluid or urine was withdrawn, the drug was slowly pushed). The rats were fixed on the operating table in a supine position, the skin was shaved, and routinely disinfected with iodine tincture. The skin of the abdominal area was cut along the midline of the abdomen, the skin and subcutaneous tissue were bluntly peeled off on both sides, the abdominal cavity was exposed, and blood was collected through the abdominal aorta.

[0067] The kidneys were separated and removed, cut into small pieces and divided equally. One part was fixed in 4% paraformaldehyde for 24 hours, and pathological histological examination was performed by hematoxylin-eosin (HE) staining; the other part of the tissue was fixed with liquid nitrogen for 30 minutes and then stored in a -80°C low-temperature refrigerator until the determination of relevant test indicators; the kidney tissue was quickly placed in ice for precooling.

[0068] 1) Use biochemical detector to detect MBP, CK-MB, BUN, and SCr levels;

[0069] 2) Prepare pathological sections and observe the pathological changes of rat kidney tissue;

[0070] 3) Detection of renal cell function under electron microscope;

[0071] 4) kidney tissue homogenate was obtained and the protein expression of cleaved caspase 3, total caspase 3, Bax, and Bcl-2 in rat kidney tissue was analyzed by Western blotting;

[0072] 5) The protein expressions of HSP90, Akt, p-Akt, and Bcl-xL were determined using ELISA kits (Elabscience Biotechnology Inc., Texas, USA).

[0073] IV. Results

[0074] Table 1. Test results of rat kidney tissue after 24 hours

[0075]

[0076] (Data of the low-dose group in Example 1 and the high-dose group in Example 1 compared with the blank group p<0.01; data of the low-dose group in Example 1 and the high-dose group in Example 1 compared with the control group p<0.01)

[0077] According to the above table and Figure 1 It can be seen that compared with the blank group, the MBP (M±SD) of the control group mice decreased, and the levels of CK-MB, BUN, and SCr increased. After taking the decoction of the Chinese medicine composition of the present invention, there was a certain improvement. Compared with the control group, the drug-administered group can effectively reduce the level of change of biochemical parameters to a certain extent; the large-dose group of Example 1 compared with the small-dose group of Example 1 shows that a sufficient amount of Chinese medicine composition decoction can further slow down the change of biochemical parameters. The data of Examples 2 and 3 are similar to those in Example 1, indicating that adjusting the formula within a certain range and using the means of decoction can achieve better results; and the effects of Examples 1 to 3 are better than the values ​​of Comparative Examples 1 to 3 (the difference before and after use is statistically significant), confirming that the Chinese medicine composition of the present invention has a significant effect on clearing away heat and relieving summer heat. It is worth noting that the Chinese medicine composition in Example 1 has the best therapeutic effect, which produces unexpected technical effects.

[0078] The histopathological images of the blank group, the control group, and the low-dose group and the high-dose group of the Chinese medicine composition of Example 1 are shown in Figure 2 It can be seen that the rats in the control group had severe tubular damage accompanied by glomerular damage, and in the high-dose group of Example 1, tubular atrophy and granular degeneration showed partial recovery.

[0079] Protein expression (upper) and quantification (lower) of cleaved caspase 3, total caspase 3, Bax, and Bcl-2 in rat kidney tissue Figure 3 As shown, β-actin was used as a loading control (n=3), according to Figure 3 It can be seen that the levels of cleaved caspase 3 and Bax in the control group rats were significantly increased, while the expression of Bcl-2 in the blank group was reduced. In addition, significant inhibitory effects were observed in the low-dose group of Example 1 and the high-dose group of Example 1, and the trend was dose-dependent.

[0080] (p<0.01 between the data of the low-dose group of Example 1 and the high-dose group of Example 1 and the blank group; p<0.05 between the low-dose group of Example 1 and the control group, p<0.01 between the high-dose group of Example 1 and the control group)

[0081] The protein expression results (upper) and quantification (lower) of HSP90, Akt, p-Akt, and Bcl-xL are shown in Figure 4 And Table 2, according to Figure 4 It can be seen that the expression of HSP90 was significantly enhanced after administration; the phosphorylation level of Akt increased in the control group, the low-dose group of Example 1, and the high-dose group of Example 1; in the control group, the protein expression of Bcl-xL was significantly reduced, and the Bcl-xL signal was activated in the low-dose group of Example 1 and the high-dose group of Example 1.

[0082] Table 2. Quantitative expression of HSP90, Akt, p-Akt, and Bcl-xL proteins

[0083]

[0084] (p<0.01 between the data of the low-dose group of Example 1 and the high-dose group of Example 1 and the blank group; p<0.05 between the low-dose group of Example 1 and the control group, p<0.01 between the high-dose group of Example 1 and the control group)

[0085] The animal experiments of the present invention show that the Chinese medicinal composition preparation for clearing away heat and relieving summer heat can regulate the expression of HSP90 and the Akt / Bcl-xL pathway to improve the symptoms induced by EHS, thereby alleviating kidney damage and renal cell apoptosis.

[0086] 5. Network pharmacology analysis of traditional Chinese medicine combination preparations for clearing away heat and relieving summer heat

[0087] 1. Drug ingredient screening

[0088] Through the traditional Chinese medicine database and analysis platform TCMSP, the active compounds in the present invention were screened with oral bioavailability (OB) ≥ 30% and drug-like index (DL) ≥ 0.18 as the standards, including 11 American ginseng, 4 wax gourd peel, 82 Adenophora, 9 Asparagus, 13 Lycium bark, 9 Scrophularia, 15 Anemarrhena, 14 Coptis, 37 Phellodendron, 1 Phragmites australis, 15 Lotus leaf, 8 Schisandra, 15 Poria, 10 Alisma, 92 Licorice, and 9 Coix seeds.

[0089] 2. Screening of drug ingredient targets

[0090] The predicted targets were obtained using the TCMSP database and other databases. After merging and removing duplicates, there were 148 targets in total. Then, Ensembl, GeneCards, OMIM, PharmGkb, TTD and other databases were used to search for "heat stroke" and "heat shock" to screen disease-related targets. After removing duplicates, 4734 related targets were obtained ( Figure 5 a). Data was sorted using R, and the targets of effective ingredients of traditional Chinese medicine were integrated with the targets of heat stroke-related diseases in the database to obtain their intersection information, and a VENN diagram was constructed ( Figure 5 b), of which there are 113 targets in total.

[0091] 3. Construction of protein interaction network

[0092] The common information of traditional Chinese medicine and disease-related targets was entered into the String database to obtain protein-protein interaction (PPI) information and retain the full interaction map ( Figure 6 a). The interaction information data was entered into Cytoscape for data visualization conversion. The core targets of protein interaction network were screened through Cytoscape. The additional function of Cytoscape, CytoNCA, was used to calculate the four parameters DC / BC / CC / EC, which are the core parameters for evaluating the importance of network nodes in network pharmacology research. The larger the value, the closer the node is to the center of the network. The R language was used for data analysis, and finally 8 core genes with the highest degree values ​​were screened out ( Figure 6 b~6d), including STAT3, Akt1, RXRA, CTNNB1, MAPK1, RELA, MAPK3, and JUN.

[0093] 4.GO and KEGG gene enrichment analysis

[0094] The symbol ID conversion and target gene enrichment analysis were completed using R language. The analysis included two aspects: biological process and signal pathway. GO gene enrichment analysis and pathway analysis obtained 2240 GO entries (P<0.05). Figure 7The main biological processes include: response to exogenous stimuli, response to nutrient levels, response to alcohol, response to lipopolysaccharide, etc. KEGG enrichment analysis ( Figure 7 ), and 174 KEGG entries (P<0.05) were obtained, among which the signaling pathways with strong correlation included: Lipid and atherosclerosis, Chemical carcinogenesis-receptor activation, AGE-RAGE signaling pathway indiabetic complications, etc.

[0095] 5. Conclusion

[0096] Network pharmacology conducts relevant database matching analysis between drug core components and disease-related genes, and then integrates the intersection information of the screened traditional Chinese medicines and disease-related targets, constructs a protein interaction network (PPI) from the String database, screens out the target information with high correlation in the PPI, performs gene enrichment analysis in the KEGG database and marks the relevant signaling pathways; because it is multi-pathway and multi-target, the pathways downstream of HSP90 expression and AKT / Bcl-xL are selected.

[0097] The present invention uses network pharmacology to conduct the above analysis on the Chinese medicine composition preparation for clearing heat and relieving summer heat and heat stroke through the joint action of multiple drug components, multiple action targets, multiple biological processes, and multiple pathways, thereby concluding that the Chinese medicine composition preparation for clearing heat and relieving summer heat regulates HSP90 expression and Akt / Bcl-xL pathway. It can be inferred that the present invention can improve the disease development of heat stroke by resisting stress, improving metabolism, regulating inflammatory signal mechanisms, etc., and alleviate EHS symptoms and renal cell apoptosis in rats, thereby reducing kidney damage. The clinical application of Chinese medicine composition preparations for clearing heat and relieving summer heat has certain significance for drugs used to prevent / treat EHS.

[0098] The animal experiment results of the traditional Chinese medicine composition for clearing away heat and relieving summer heat of the present invention are consistent with the results of network pharmacology analysis, which verifies the effectiveness of the traditional Chinese medicine composition for clearing away heat and relieving summer heat.

[0099] (II) Clinical trials

[0100] Experimental personnel were selected, and their exposure to the outdoors for more than 8 hours during the day, with an average daytime temperature of 30-35°C.

[0101] A total of 12 people of the same type of work working in the same working environment were divided into 3 groups. The first group took the Chinese medicine composition preparation for clearing away heat and relieving summer heat in Example 1 of the present invention, the second group took Wang's Qingshu Yiqi Decoction; the third group took Chenpi Wumei Decoction; the three groups took the same dosage and time of taking the preparation.

[0102] The results showed that the first group had the least number of people with heat stroke / EHS symptoms and were basically asymptomatic; that is, the heat-clearing and heat-relieving Chinese medicinal composition preparation of the present invention had the best preventive effect.

[0103] Non-experimental personnel working in the same working environment who experience severe heatstroke symptoms such as nausea, vomiting, dizziness, and headache can also quickly relieve the symptoms after taking the Chinese medicine composition preparation for clearing away heat and relieving summer heat in Example 1 of the present invention.

[0104] In summary, the Chinese medicine composition and preparation of the present invention can alleviate the symptoms of heatstroke including CHS and EHS, and have the effects of clearing away heat and relieving summer heat; and can be used to prepare drugs for preventing / treating heat stroke. The Chinese medicine composition of the present invention can effectively prevent / alleviate the disease. The Chinese medicine composition for clearing away heat and relieving summer heat of the present invention can effectively supplement the deficiency of the market for drugs for preventing / treating heat stroke.

[0105] The specific embodiments described herein are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.

Claims

1. A Chinese medicine composition for clearing away heat and relieving summer heat, characterized in that: The raw materials of the traditional Chinese medicine composition are, by weight, 5-30 parts of American ginseng, 90-120 parts of wax gourd peel, 5-30 parts of Adenophora radix, 5-30 parts of Asparagus cochinchinensis, 5-30 parts of Lycium bark, 5-30 parts of Scrophularia ningpoensis, 5-30 parts of Anemarrhena asphodeloides, 3-9 parts of Coptis chinensis, 2-8 parts of Phellodendron chinense, 5-15 parts of Phragmites australis, 5-25 parts of lotus leaf, 6-13 parts of Schisandra chinensis, 6-13 parts of Poria cocos, 5-15 parts of Alisma orientalis, 1-15 parts of Licorice root, and 20-50 parts of Coix seeds.

2. The Chinese medicine composition for clearing away heat and relieving summer heat according to claim 1, characterized in that: The total amount of American ginseng and wax gourd peel added to the heat-clearing and summer-heat-relieving traditional Chinese medicine composition accounts for 42-49%.

3. The Chinese medicine composition for clearing away heat and relieving summer heat according to claim 1, characterized in that: The total added amount of Adenophora Root, Asparagus Cochinchinensis, Scrophularia Root and Cortex Lycii accounts for 18-25%.

4. The Chinese medicinal composition for clearing away heat and relieving summer heat according to claim 1, characterized in that: The Chinese medicine composition for clearing away heat and relieving summer heat is prepared from the following components, calculated by weight: 15 parts of American ginseng, 100 parts of wax gourd peels, 15 parts of Adenophora scutellariae, 15 parts of Asparagus cochinchinensis, 15 parts of Lycium bark, 15 parts of Scrophularia ningpoensis, 15 parts of Anemarrhena asphodeloides, 5 parts of Coptis chinensis, 5 parts of Phellodendron chinense, 10 parts of Phragmites australis, 10 parts of Lotus leaves, 10 parts of Schisandra chinensis, 10 parts of Poria cocos, 10 parts of Alismatis orientalis, 5 parts of Licorice root, and 30 parts of Coix seeds.

5. The Chinese medicinal composition for clearing away heat and relieving summer heat according to claim 1, characterized in that: The dosage form of the Chinese medicine composition is one or more of decoction, pills, granules, capsules, and tablets.

6. A method for preparing the heat-clearing and summer-heat-relieving Chinese medicinal composition as claimed in claim 1, characterized in that: The preparation method comprises: firstly preparing the weighed components of the traditional Chinese medicine into raw material particles with a particle size of 74-106 μm, then grinding them into particles with a particle size of 10-50 μm, and soaking them in hot water.

7. The preparation method according to claim 6, characterized in that: The temperature of the hot water is 80-90° C.; the Chinese medicine composition is immersed in the hot water for 20-30 minutes.

8. The preparation method according to claim 6, characterized in that: The mass volume ratio of the traditional Chinese medicine composition to hot water is (240-290) g:300 ml.

9. Use of the heat-clearing and summer-heat-relieving traditional Chinese medicine composition according to claim 1 in the preparation of a drug for preventing heat stroke.

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