Traditional chinese medicine composition for lipid reduction, preparation method therefor, and use thereof

Abstract

Provided are a traditional Chinese medicine composition for lipid reduction, a preparation method therefor, and use thereof. The traditional Chinese medicine composition comprises a lipid-reducing core component and auxiliary components. The lipid-reducing core component is composed of Mallotus oblongifolius and Dalbergiae Odoriferae Lignum, and the auxiliary components comprise Crataegi fructus and Salviae miltiorrhizae. The traditional Chinese medicine composition can ameliorate the hyperlipidemia condition and reduce the body weight of model animals, and can also reduce the expression of various inflammatory factors.

Description

A traditional Chinese medicine composition for lowering lipids, its preparation method and application

[0001] Priority application

[0002] This application claims priority to Chinese invention patent application No. [2024119186453] filed on December 24, 2024, entitled “A Traditional Chinese Medicine Composition for Lowering Lipids, Preparation Method and Application”, and Chinese invention patent application No. [2025100880461] filed on January 20, 2025, entitled “A Traditional Chinese Medicine Composition for Lowering Lipids, Preparation Method and Application”, both of which are incorporated herein by reference in their entirety. Technical Field

[0003] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for lowering lipids, its preparation method, and its application. Background Technology

[0004] Hyperlipidemia has become a common clinical disease and one of the "three major killers" threatening human health. It is closely related to the occurrence of various cardiovascular diseases. Therefore, researching effective lipid-lowering regimens is of great significance for the prevention and treatment of cardiovascular diseases. Statistics show that the market size of lipid-lowering drugs in my country has continued to grow, increasing from 27.44 billion yuan in 2017 to 40.23 billion yuan in 2021. In 2022, the market size of lipid-lowering drugs in my country was approximately 47 billion yuan, with a compound annual growth rate of 10.0%. Statins dominate the sales share of lipid-lowering drugs in public hospitals. Other traditional Chinese medicine lipid-lowering drugs, such as Xuezhikang and Probucol, also have a place in the market.

[0005] While chemical drugs offer significant clinical efficacy, they suffer from drawbacks such as limited target specificity and a tendency to cause adverse reactions (e.g., blood sugar disorders, rhabdomyolysis, abnormal liver function). Compared to chemical drugs, traditional Chinese medicine (TCM) offers advantages in lipid-lowering treatment, including high safety, multiple pathways, and low cost. Furthermore, TCM not only lowers blood lipids but also possesses multiple functions such as anti-oxidation, blood sugar reduction, and immune enhancement, achieving both symptomatic and root-cause treatment. Therefore, TCM lipid-lowering drugs can provide patients with a safer and more effective treatment option. However, TCM faces challenges such as unclear treatment mechanisms and limited efficacy; therefore, improving the efficacy and safety of TCM treatments is crucial for the development of novel TCM therapies.

[0006] Patent CN110742990A, entitled "A Traditional Chinese Medicine Composition, Preparation, and Application for Treating Non-Alcoholic Simple Fatty Liver Disease," discloses an active composition comprising 24-36 parts of partridge tea, 8-12 parts of Alisma plantago-aquatica, 8-12 parts of turmeric, 8-12 parts of Astragalus membranaceus, 8-12 parts of hawthorn, 8-12 parts of lotus leaf, 8-12 parts of Salvia miltiorrhiza, and 2-4 parts of Panax notoginseng powder. This active composition possesses the effects of resolving dampness and promoting bile secretion, eliminating greasiness, and lowering blood lipids. Experimental verification has shown its efficacy in treating non-alcoholic simple fatty liver disease, eliminating multiple abnormal liver function indicators in patients with this condition. However, this active composition contains multiple heat-clearing and purgative ingredients (such as Alisma plantago-aquatica and lotus leaf), but these ingredients can be quite irritating to the gastrointestinal tract. Furthermore, Panax notoginseng powder is not suitable for all populations.

[0007] In conclusion, it is necessary to propose new methods and strategies to improve existing technologies. Summary of the Invention

[0008] The purpose of this invention is to provide a traditional Chinese medicine composition for lowering lipids, its preparation method, and its application, thereby partially solving or alleviating the above-mentioned deficiencies in the prior art. The specific technical solution adopted by this invention is as follows.

[0009] This invention provides a traditional Chinese medicine composition for lowering lipids, comprising a lipid-lowering core component and auxiliary components. The lipid-lowering core component consists of partridge tea and sandalwood. The auxiliary components include hawthorn and salvia miltiorrhiza. The weight ratio of partridge tea to sandalwood in the lipid-lowering core component is 6-10:1. The weight ratio of hawthorn to salvia miltiorrhiza in the auxiliary components is 1:5-1. The total weight of the lipid-lowering core component is less than the total weight of the auxiliary components.

[0010] Furthermore, the weight ratio of partridge tea and sandalwood in the lipid-lowering core ingredients includes 6:1, 7:1, 8:1, 9:1 or 10:1.

[0011] Furthermore, the weight ratio of hawthorn and salvia miltiorrhiza in the auxiliary ingredients includes 1:1, 2:1, 3:1, 4:1 or 5:1.

[0012] In some preferred embodiments, the weight ratio of hawthorn and salvia miltiorrhiza in the auxiliary ingredients is 1:1.

[0013] Furthermore, the weight ratio of the lipid-lowering core component to the auxiliary component is 13:40 to 35:40.

[0014] In some preferred embodiments, the ratio of hawthorn, salvia miltiorrhiza, partridge tea, and sandalwood is 4:4:6:1.

[0015] Furthermore, the traditional Chinese medicine composition specifically includes the following materials in parts by weight: 10-40 parts of partridge tea, 3-10 parts of sandalwood, 20-40 parts of hawthorn, and 20-40 parts of salvia miltiorrhiza.

[0016] Furthermore, the traditional Chinese medicine composition specifically includes the following materials in parts by weight: 10-30 parts of partridge tea, 3-7 parts of sandalwood, 20-30 parts of hawthorn, and 20-30 parts of salvia miltiorrhiza.

[0017] In some preferred embodiments, the traditional Chinese medicine composition for lowering lipids includes 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and 5 parts sandalwood.

[0018] In some other preferred embodiments, the traditional Chinese medicine composition includes: 10-30g of partridge tea, 3-7g of sandalwood, 20-30g of hawthorn, and 20-30g of salvia miltiorrhiza.

[0019] More preferably, the traditional Chinese medicine composition includes: 10g of partridge tea, 3g of sandalwood, 20g of hawthorn, and 20g of salvia miltiorrhiza.

[0020] Furthermore, the fragrance includes agarwood and agarwood oil prepared from the agarwood in the specified weight proportions (for example, agarwood in the weight of 5 parts or agarwood oil extracted from 5 parts of agarwood can be used).

[0021] Furthermore, the fragrant medicinal material includes fragrant powder and / or fragrant sheets.

[0022] Furthermore, the traditional Chinese medicine composition is obtained by water extraction or alcohol extraction.

[0023] Another aspect of the present invention may provide a preparation method.

[0024] The preparation method of the above-mentioned traditional Chinese medicine composition includes the following steps:

[0025] S01: The first material consists of the following ingredients by weight: 10-40 parts of partridge tea, 20-40 parts of hawthorn and 20-40 parts of salvia miltiorrhiza; and 3-10 parts by weight of sandalwood as the second material.

[0026] S02: Add 10-20 times the volume of purified water by weight of the first material to the first material, soak it thoroughly, and then decoct and extract at 90-100℃ for 60-100 minutes. Filter to obtain the first extract. Add 5-10 times the volume of purified water by weight of the first material again, and continue to decoct and extract at 90-100℃ for 60-100 minutes. Then add the second material, decoct for 10-30 minutes, and filter to obtain the second extract. Combine the two extracts, concentrate, and dry to obtain a dry paste.

[0027] In some preferred embodiments, the decocting temperature is 95-100°C; the decocting time after adding the second material is 10-20 minutes.

[0028] Furthermore, the preparation method may also include the following steps:

[0029] S02: After mixing the first and second materials evenly, add 6-10 times the volume of high-concentration ethanol by weight of the materials, sonicate to ensure thorough mixing and soaking, then reflux extract at 60-75℃ for 60-100 min, and filter to obtain the first extract; add 6-10 times the volume of high-concentration ethanol again, reflux extract at 60-75℃ for 60-100 min, and filter to obtain the second extract; combine the two extracts, concentrate, and dry to obtain a dry paste.

[0030] In some preferred embodiments, the ultrasonic treatment time is 30-60 min; the reflux extraction temperature is 65-75°C; the ethanol used is high-concentration ethanol, such as 75% ethanol; and the volume of the first addition of high-concentration ethanol is 8-10 times the weight of the material.

[0031] A traditional Chinese medicine preparation comprising any one of the traditional Chinese medicine compositions described above.

[0032] Furthermore, the traditional Chinese medicine composition may also include other pharmaceutically acceptable excipients and / or adjuvants.

[0033] The term "pharmaceutically acceptable" as used in this invention refers to compounds, raw materials, compositions, and / or dosage forms that, within the limits of reasonable medical judgment, are suitable for contact with patient tissues without excessive toxicity, irritation, allergic reactions, other complications, or with a reasonable benefit / risk ratio. "Pharmaceutically acceptable excipients and / or adjuvants" refers to pharmaceutically acceptable carriers, diluents, or excipients added at appropriate steps in the drug preparation process.

[0034] Furthermore, the dosage forms of the traditional Chinese medicine preparations include granules, powders, tablets, capsules, and / or pills.

[0035] For example, for oral administration in tablet form, active traditional Chinese medicine compositions can be mixed with pharmaceutically acceptable oral non-toxic inert carriers (such as glycerol, mannitol, sorbitol, etc.), and can also be mixed with lubricants (such as talc, colloidal silica, magnesium stearate, etc.), preservatives, dispersants or disintegrants to prepare a predetermined dosage form.

[0036] In the lipid-lowering traditional Chinese medicine composition provided by this invention, partridge tea has the effects of lowering lipids and aiding digestion; Dalbergia odorifera is warm in nature, fragrant and pungent, warming and promoting circulation, and has the effects of activating blood circulation, removing blood stasis, stopping bleeding and relieving pain; these, combined with partridge tea, constitute the core lipid-lowering component of this invention. In addition, hawthorn and salvia miltiorrhiza are also added. Hawthorn is sour and sweet in taste, neutral in nature, and enters the Spleen and Liver meridians of Foot Taiyin and Foot Jueyin, eliminating accumulations and stagnation, promoting blood circulation and removing blood stasis. It can eliminate and dissolve all stagnant food, blood stasis, and qi stagnation. Salvia miltiorrhiza is bitter and slightly cold in taste, and enters the Blood meridian of Hand Shaoyin and Foot Jueyin, acting as an assistant herb. The *Compendium of Materia Medica* states that it can grind hardened masses, break up stagnant blood, generate new blood, dredge blood vessels, and is a good product for promoting blood circulation.

[0037] In another aspect, the present invention can also provide the application of the above-mentioned traditional Chinese medicine composition.

[0038] The above-mentioned traditional Chinese medicine composition is used in the preparation of lipid-lowering drugs.

[0039] The above-mentioned traditional Chinese medicine composition is used in the preparation of drugs for weight loss.

[0040] Beneficial technical effects:

[0041] (1) This invention provides a novel lipid-lowering traditional Chinese medicine composition. This composition has a simplified structure containing only four components, yet it demonstrates significant lipid-lowering effects in both cell experiments and animal studies. Verification shows that the lipid-lowering traditional Chinese medicine composition provided by this invention can significantly improve various lipid indicators in hyperlipidemic animal models, reduce the body weight of these models, and decrease the expression of the inflammatory factor TNF-α in hyperlipidemic animal models. Furthermore, its efficacy is superior to that of the chemical drug rosuvastatin. These results demonstrate that the lipid-lowering traditional Chinese medicine composition provided by this invention has excellent lipid-lowering effects (including reducing blood lipids and body weight). In addition, due to the simplified composition, the overall safety of the drug is high, and standardized quality control monitoring is easier to achieve in industrial production.

[0042] (2) Specifically, the lipid-lowering traditional Chinese medicine composition provided by this invention uses partridge tea and sandalwood as the core lipid-lowering components, combined with hawthorn and salvia miltiorrhiza. Through rigorous exploration of the material ratio, this invention has obtained a final compound that can simultaneously achieve good efficacy and high safety.

[0043] (3) This invention establishes a lipid accumulation model using HepG2 cells to screen the optimal ratio and extraction method of lipid-lowering compositions. The optimally matched lipid-lowering traditional Chinese medicine composition can reduce lipid accumulation in HepG2 cells and decrease intracellular triglyceride (TG) content.

[0044] (4) This invention established an acute hyperlipidemia animal model by intraperitoneal injection of 75% egg yolk milk into mice. The levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in mouse serum were measured. The high-dose group of the lipid-lowering traditional Chinese medicine composition showed significantly reduced levels of TC, TG, and LDL-C in mouse serum, and significantly increased HDL-C levels. In reducing TC and TG, the lipid-lowering traditional Chinese medicine composition group was superior to the rosuvastatin group (positive control group). The experimental results indicate that the lipid-lowering traditional Chinese medicine composition of this invention can significantly reduce the levels of TC, TG, and LDL-C in the serum of hyperlipidemic mice, and increase HDL-C levels, demonstrating good in vivo lipid-lowering activity.

[0045] (5) This invention establishes a high-fat diet-induced hyperlipidemia rat model to investigate the effect of a lipid-lowering traditional Chinese medicine composition on the body weight of hyperlipidemic rats. The lipid-lowering traditional Chinese medicine composition of this invention can significantly reduce the levels of TC, TG, and LDL-C in the serum of hyperlipidemic rats, and increase the level of HDL-C, demonstrating good in vivo lipid-lowering activity. Furthermore, the weight gain rate of rats given the lipid-lowering traditional Chinese medicine composition decreased, and the effect was better than that of the positive control group, further proving that the lipid-lowering traditional Chinese medicine composition of this invention has a body weight-reducing effect.

[0046] (6) Finally, this invention also discovered that this novel lipid-lowering traditional Chinese medicine composition, at high doses (MLG), can regulate lipid metabolism, improve insulin resistance, and inhibit inflammatory responses through the synergistic effects of multiple components and multiple targets, providing a natural and safe alternative for the prevention and treatment of hyperlipidemia. Its low toxicity and suitability for long-term use can reduce adverse reactions such as liver damage caused by Western medicine treatment and lower medical costs. A lipid accumulation model was established using HepG2 cells, and the in vitro efficacy under different ratios, extraction methods, and feeding methods was compared. Simultaneously, it was compared with partridge tea extract, ultimately determining the optimal compound as hawthorn: danshen: partridge tea: jiangxiang (4:4:6:1). Based on the in vitro efficacy, acute and chronic hyperlipidemia animal models were established, further confirming that the synergistic lipid-lowering effect of MLG was significant and superior to that of a single compound. MLG significantly reduced TG, TC, and LDL-C, and to some extent increased HDL-C. MLG can effectively alleviate the sudden increase in blood lipids caused by acute hyperlipidemia, accelerate the recovery of blood indicators, and stabilize them. In addition, MLD can improve weight gain and liver and spleen weight gain caused by a high-fat diet. Lipid metabolism and inflammatory response interact to cause hyperlipidemia. After MLGH treatment, the plasma TNF-α level in rats was significantly reduced in a dose-dependent manner. MLGM also had a significant effect on reducing IL-6 and CXCL1 in the body. Attached Figure Description

[0047] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the 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. The elements or parts in the drawings are not necessarily drawn to scale. Obviously, the drawings described below are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without any creative effort.

[0048] Figure 1 shows the weight gain rate of a chronic hyperlipidemia model rat in one embodiment of the present invention;

[0049] Figure 2 shows the liver condition of a rat model of chronic hyperlipidemia in one embodiment of the present invention;

[0050] Figure 3 shows the measurement of inflammatory factor content in the serum of a chronic hyperlipidemic model rat in one embodiment of the present invention;

[0051] Figure 4 shows an in vitro experiment of the preferred lipid-lowering compound and lipid-lowering granules in one embodiment of the present invention (A is the effect of different groups of compound on lipid accumulation in HepG2 cells; B is the toxicity experiment of HepG2 oleic acid model; C is the CCK-8 toxicity test of MLG group; D is the triglyceride determination of each group and the triglyceride reduction rate; E is Oil Red O lipid staining).

[0052] Figure 5 shows a comparison of the differences in metabolite expression abundance in samples from different experimental groups in one embodiment of the present invention (the vertical axis represents the mass spectrometry intensity value);

[0053] Figure 6 shows the changes in weight gain and organ weight gain in hyperlipidemic rats in different experimental groups in one embodiment of the present invention (A: Changes in weight gain in hyperlipidemic rats: Hyperlipidemia model established from week 0-4, drug administration started in week 5. Growth rate of rat weight GRa after modeling, growth rate of rat weight GRb after drug administration; B: Liver weight gain; C: Spleen weight gain);

[0054] Figure 7 shows the detection of rat blood indexes and the comparison of inflammatory factors in brown rats in each experimental group in one embodiment of the present invention.

[0055] Figure 8 shows a clustering diagram of six levels in one embodiment of the present invention. Detailed Implementation

[0056] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0057] In this document, "and / or" includes any and all combinations of one or more of the listed related items.

[0058] In this article, "multiple" means two or more, that is, it includes two, three, four, five, etc.

[0059] As used in this specification, the term "about" typically means + / -5% of the value, more typically + / -4%, more typically + / -3%, more typically + / -2%, even more typically + / -1%, and even more typically + / -0.5%.

[0060] In this specification, certain embodiments may be disclosed in a range-bound format. It should be understood that this "range-bound" description is merely for convenience and brevity and should not be construed as a rigid limitation on the disclosed range. Therefore, the description of a range should be considered as having specifically disclosed all possible subranges and the individual numerical values ​​within those ranges. For example, a description of the range 1-6 should be considered as having specifically disclosed subranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6, etc., and the individual numbers within those ranges, such as 1, 2, 3, 4, 5, and 6. This rule applies regardless of the breadth of the range.

[0061] Example 1

[0062] This embodiment provides an example of a traditional Chinese medicine composition for lowering lipids, comprising the following raw materials in parts by weight: 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and 5 parts sandalwood powder; wherein, partridge tea and sandalwood powder constitute the core lipid-lowering components; hawthorn and salvia miltiorrhiza serve as auxiliary components. The preparation method includes pretreatment, extraction, and post-treatment, as detailed below.

[0063] A. Pre-treatment: The raw materials hawthorn, salvia miltiorrhiza and partridge tea in the formula are crushed and passed through a 40-60 mesh sieve to obtain material a for later use. The raw material sandalwood in the formula is crushed and passed through a 40-60 mesh sieve to obtain material b for later use.

[0064] B. Extraction: Add 10 times the weight of purified water to material a, soak for 30 minutes, then decoct at 95-100℃ for 60 minutes. Filter to obtain the first extract. Add 8 times the weight of purified water again, and continue decoction at 95-100℃ for 80 minutes. Then add material b, decoct for 10 minutes, and filter to obtain the second extract. Combine the two extracts, concentrate, and dry to obtain a dry paste.

[0065] C. Post-processing: The dry paste is pulverized into a fine powder, and an appropriate amount of excipients are added and mixed evenly to obtain a traditional Chinese medicine preparation that helps lower blood lipids.

[0066] The lipid-lowering traditional Chinese medicine composition (hereinafter referred to as composition 1) provided in this embodiment was used to detect the effect of composition 1 on Oil Red O staining of HepG2 cells and to determine the intracellular TG content. The degree of damage to HepG2 cells by composition 1 was detected by MTT assay, and the in vitro lipid-lowering activity of composition 1 was evaluated.

[0067] The results showed that, compared with the control group, the model group (without any drug treatment) exhibited a large number of red lipid droplets, and the TG content in the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in the experimental group were significantly reduced (P<0.001), showing a good dose-dependent effect. Furthermore, the higher the concentration of composition 1, the fewer the number of red lipid droplets. These results indicate that composition 1 prepared in this embodiment can effectively reduce the TG content in oleic acid-induced HepG2 cells and reduce lipid accumulation in HepG2 cells, demonstrating good in vitro lipid-lowering activity.

[0068] Table 1. CCK8 toxicity test of the lipid-lowering composition in Example 1

[0069] Table 2. Efficacy of the lipid-lowering composition in Example 1 of cell experiments.

[0070] Further validation was achieved by establishing animal models of hyperlipidemia, including an acute hyperlipidemia model in mice and a chronic hyperlipidemia model in rats.

[0071] Mouse model of acute hyperlipidemia:

[0072] An acute hyperlipidemia animal model was established by intraperitoneal injection of 75% egg yolk milk in mice. The lipid-lowering composition of Example 1 was further verified by detecting total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in the serum of the mouse model.

[0073] Experimental methods:

[0074] Take several fresh eggs, make a small opening at the bottom to remove the egg white, and gently place the yolks in an empty beaker. Insert a syringe into the yolk membrane to draw up the yolk liquid and transfer it to a 100mL volumetric flask. Measure 75mL of the yolk liquid and dilute it to 100mL with physiological saline. Stir the egg yolk emulsion solution with a magnetic stirrer for 10 minutes to ensure it is homogeneous and to minimize errors. Prepare the solution on demand.

[0075] Accurately weigh 5.00 g of CMC-Na and place it in a beaker. Add 800 mL of purified water and stir well. Transfer the mixture to a 1000 mL volumetric flask and add purified water to the mark. Prepare a 0.5% CMC-Na solution.

[0076] Accurately weigh 6.5 mg of rosuvastatin (1.30 mg / kg) and place it in a 100 mL volumetric flask. Suspend and dilute to 100 mL with 0.5% CMC-Na solution. Prepare a drug solution sample with a concentration of 0.065 mg / mL.

[0077] Accurately weigh 1.23g of the compound (2.47g / kg) into separate 10mL volumetric flasks, suspend in 0.5% CMC-Na solution, and dilute to 10mL. Prepare a compound drug solution sample with a concentration of 123mg / mL.

[0078] Mice were randomly divided into 6 groups of 6 mice each: a blank control group, a 75% egg yolk milk high-fat model group, a combination 1 treatment group (low dose 1.24 g / kg, medium dose 2.47 g / kg, high dose 4.94 g / kg), and rosuvastatin as a positive control group. Administered via gavage, the blank control group and the 75% egg yolk milk high-fat model group received 0.2 mL / 10 g of 0.5% CMC-Na daily, while the other drug groups received 0.2 mL / 10 g of the corresponding drug daily via gavage. Administration continued for 5 days. Two hours after the last administration, each group received an intraperitoneal injection of 0.5 mL / mouse of 75% egg yolk milk saline solution to induce experimental hyperlipidemia. After 8 hours of fasting, administration was performed 12 hours later, and blood was collected 1 hour later. Serum was separated by centrifugation using the enucleation method to determine the levels of TC, TG, LDL-C, and HDL-C. Experiments have shown that the high-dose group of composition 1 has a significant effect in reducing TC, TG, and LDL-C.

[0079] Table 3. Evaluation of the efficacy of the lipid-lowering composition in Example 1 based on mouse experiments.

[0080] Note: Compared with the blank group a p<0.05, b p<0.01; compared with the model group c p<0.05, d p<0.01.

[0081] Compared with the control group, the serum levels of TC, TG, and LDL-C in the model group mice were significantly increased, while the HDL-C level was significantly decreased. Compared with the model group, the serum levels of TC, TG, and LDL-C in the positive control group mice were significantly decreased, while the HDL-C level was significantly increased. In the high-dose group of composition 1 mice, the serum levels of TC, TG, and LDL-C were significantly decreased, while the HDL-C level was significantly increased.

[0082] The above results indicate that the experimental group was superior to the positive control group in reducing TC and TG. Specifically, composition 1 can significantly reduce the levels of TC, TG, and LDL-C in the serum of hyperlipidemic mice, and increase the level of HDL-C, demonstrating good lipid-lowering activity in vivo.

[0083] Rat model of chronic hyperlipidemia:

[0084] A high-fat diet-induced hyperlipidemia model was established in rats. The total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) in rat serum were measured. The composition 1 provided by this invention has an improving effect on blood lipid indicators in rats in the high-fat diet group.

[0085] Table 4. Evaluation of the efficacy of the lipid-lowering composition in Example 1 based on rat experiments.

[0086] Note: The high / medium / low doses of Composition 1 in Table 4 are 3.9 g / kg, 1.95 g / kg and 0.975 g / kg, respectively.

[0087] Compared with the control group, the serum levels of TC, TG, and LDL-C in the model group rats were significantly increased, while the HDL-C level was significantly decreased. Compared with the model group, the serum levels of TC, TG, and LDL-C in the positive control group mice were significantly decreased, while the HDL-C level was significantly increased. The high-dose group of Composition 1 mice showed significantly decreased serum levels of TC, TG, and LDL-C, and significantly increased HDL-C levels. Furthermore, Composition 1 was superior to the positive control group in reducing TC, TG, and LDL-C. Specifically, Composition 1 can significantly reduce the serum levels of TC, TG, and LDL-C in hyperlipidemic rats and increase HDL-C levels, demonstrating good in vivo lipid-lowering activity.

[0088] Furthermore, 60 qualified SPF-grade SD rats were randomly divided into six groups according to their weight: a high-dose group, a medium-dose group, a low-dose group, a positive control group (administered rosuvastatin), a model group, and a normal control group (n=10 per group). The model group and the normal control group were given the same volume of solvent (0.5% carboxymethyl cellulose solution). The hyperlipidemia model animals were fed a high-fat diet, while the normal control group animals were fed a reproductive diet, both for 4 weeks before administration. During the administration period, the normal control group animals were fed a reproductive diet, while the other groups were fed a high-fat diet. The rats were weighed before the experiment, after modeling, and after administration. The results are shown in Figure 1, where the administration group represents the high dose of Composition 1 at 3.9 g / kg. Figure 1 shows that under continuous high-fat feeding conditions, the weight gain rate of the rats in the administration group decreased, and the effect was better than that of the positive control group, proving that the traditional Chinese medicine composition used for lipid reduction in Example 1 also has a weight-reducing effect.

[0089] Furthermore, the day after the last administration, the patient was anesthetized with chloral hydrate, blood was drawn from the abdominal aorta, body weight was measured, and liver tissue was taken (see Figure 2).

[0090] As shown in Figure 2, the color and appearance of the livers of rats in the high (MLGmH), medium (MLGmM), and low (MLGmL) dose groups of Composition 1, as well as the model control group, were significantly different from those in the normal control group. The model group had fatty liver induced by hyperlipidemia; the cross-section of a normal liver was uniform in color and had no obvious fat particles. However, obvious yellow fat particles could be seen on the cross-section of the fatty liver.

[0091] Therefore, Composition 1 improves the pathological changes in liver tissue of hyperlipidemic rats; it can effectively reduce hepatocyte vacuolation, reduce fat accumulation in the liver, and effectively restore the normal morphology of liver cells.

[0092] The levels of the inflammatory factor TNF-α in rat serum were further measured, and the results are shown in Figure 3. The results showed that compared with the control group, the level of TNF-α in the serum of the model group rats was significantly increased. After administration, the levels of TNF-α inflammatory factor in the positive control group and the medium and high dose groups of Composition 1 were significantly reduced, and the efficacy of Composition 1 was significantly better than that of the positive control group, with the high dose group of Composition 1 showing the best effect.

[0093] Example 2

[0094] This embodiment provides another example of a traditional Chinese medicine composition for lowering lipids, comprising the following raw materials in parts by weight: 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and dalbergia odorifera oil (volatile oil extracted from 5 parts of dalbergia odorifera); wherein, partridge tea and dalbergia odorifera oil constitute the core lipid-lowering components; hawthorn and salvia miltiorrhiza serve as auxiliary components. The preparation method includes pretreatment, extraction, and post-treatment, as detailed below.

[0095] A. Pre-treatment: The raw materials hawthorn, salvia miltiorrhiza, and partridge tea in the formula are crushed and passed through a 40-60 mesh sieve to obtain material a for later use. The aromatic oil in the formula is used as material b for later use.

[0096] B. Extraction: Add 10 times the weight of purified water to material a, soak for 30 minutes, then decoct at 95-100℃ for 60 minutes, and filter to obtain the first extract; add 8 times the weight of purified water again, and continue to decoct at 95-100℃ for 80 minutes, then add material b, decoct for 10 minutes, and filter to obtain the second extract. Combine the two extracts, concentrate, and dry to obtain a dry extract.

[0097] C. Post-processing: The dry paste is pulverized into a fine powder, and an appropriate amount of excipients is added and mixed evenly to obtain a traditional Chinese medicine composition that helps lower blood lipids.

[0098] This embodiment provides a traditional Chinese medicine composition for lowering lipids (hereinafter referred to as composition 2). Cell experiments were conducted to detect the effect of composition 2 on Oil Red O staining of HepG2 cells and to determine the intracellular TG content. The degree of damage to HepG2 cells by composition 2 was detected by MTT assay, and the in vitro lipid-lowering activity of composition 2 was evaluated.

[0099] Compared with the control group, the model group showed a large number of red lipid droplets, and the TG content in the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in composition 2 were significantly reduced (P<0.001), showing a good dose-dependent effect. The higher the concentration of composition 2, the fewer the number of red lipid droplets. These results indicate that composition 2 can reduce the TG content in oleic acid-induced HepG2 cells and reduce lipid accumulation in HepG2 cells, demonstrating good in vitro lipid-lowering activity.

[0100] Table 5. CCK8 toxicity test of the lipid-lowering composition in Example 2.

[0101] Table 6. Efficacy of the lipid-lowering composition in Example 2

[0102] Using the same measurement method as in Example 1, composition 2 was further confirmed to have a significant lipid-lowering effect in animal experiments.

[0103] Experimental methods:

[0104] Take several fresh eggs, make a small opening at the bottom to remove the egg white, and gently place the yolk in an empty beaker. Insert a syringe into the yolk membrane to draw up the yolk liquid and place it in a 100mL volumetric flask. Measure 75mL of the yolk liquid and dilute it with physiological saline to 100mL. Stir the yolk emulsion solution with a magnetic stirrer for 10 minutes to make the yolk emulsion solution uniform and reduce errors. Prepare it on the spot when using.

[0105] Accurately weigh 5.00 g of CMC-Na and place it in a beaker. Add 800 mL of purified water and stir well. Transfer the mixture to a 1000 mL volumetric flask and add purified water to the mark. Prepare a 0.5% CMC-Na solution.

[0106] Accurately weigh 6.5 mg of rosuvastatin (1.30 mg / kg) and place it in a 100 mL volumetric flask. Suspend the flask with 0.5% CMC-Na solution and dilute to 100 mL to prepare a drug solution sample with a concentration of 0.065 mg / mL.

[0107] Accurately weigh 1.17g of the compound (2.34g / kg) into separate 10mL volumetric flasks, suspend in 0.5% CMC-Na solution, and dilute to 10mL. Prepare a 117mg / mL compound drug solution sample.

[0108] Mice were randomly divided into 6 groups of 6 mice each: a blank control group, a 75% egg yolk milk high-fat model group, and drug treatment groups (low dose 1.17 g / kg, medium dose 2.34 g / kg, and high dose 4.68 g / kg). Rosuvastatin served as a positive control group. Administered via gavage, the blank control group and the 75% egg yolk milk high-fat model group received 0.2 mL / 10 g of 0.5% CMC-Na daily, while the other drug groups received 0.2 mL / 10 g of the corresponding drug daily via gavage. After 5 consecutive days of administration, 2 hours after the last administration, each group received an intraperitoneal injection of 0.5 mL of 75% egg yolk milk saline solution to induce experimental hyperlipidemia. After 8 hours of fasting, the mice were administered the drug via gavage 12 hours later, and blood was collected 1 hour later. Serum was separated by centrifugation using the enucleation method to determine the levels of TC, TG, LDL-C, and HDL-C.

[0109] Table 7. Evaluation of the efficacy of the lipid-lowering composition in Example 2 based on animal experiments.

[0110] Note: Compared with the blank group a p<0.05, b p<0.01; compared with the model group c p<0.05, d p<0.01.

[0111] Example 3

[0112] This embodiment provides another example of a traditional Chinese medicine composition for lowering lipids, comprising the following parts by weight of medicinal herbs: 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and 5 parts sandalwood. Partridge tea and sandalwood constitute the core lipid-lowering components; hawthorn and salvia miltiorrhiza serve as auxiliary components. The preparation method includes pretreatment, extraction, and post-treatment.

[0113] Mix all materials thoroughly, add 8 times the weight of the materials by volume of 75% ethanol, sonicate for 30 min, reflux extract at 65-75℃ for 60 min, filter to obtain the first filtrate, add 6 times the weight of the materials by volume of 75% ethanol again, reflux extract at 65-75℃ for 60 min, filter to obtain the second filtrate. Combine the two extracts, concentrate, and dry to obtain the dry extract.

[0114] This embodiment provides a traditional Chinese medicine composition for lipid-lowering (hereinafter referred to as Composition 3). Cellular experiments were conducted to detect the effect of Composition 3 on Oil Red O staining of HepG2 cells and to measure intracellular TG content. The degree of damage to HepG2 cells by Composition 3 was detected using an MTT assay to evaluate the in vitro lipid-lowering activity of Composition 3. Compared with the control group, the model group showed a large number of red lipid droplets, and the TG content in the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in Composition 3 were significantly reduced (P<0.001), exhibiting a good dose-dependent effect; the higher the concentration of Composition 3, the fewer the number of red lipid droplets. These results indicate that Composition 3 can reduce the TG content in oleic acid-induced HepG2 cells and reduce lipid accumulation in HepG2 cells, demonstrating good in vitro lipid-lowering activity.

[0115] Table 8. CCK8 toxicity test of the lipid-lowering composition in Example 3

[0116] Table 9. Efficacy of the lipid-lowering composition in Example 3 of cell experiments.

[0117] Example 4

[0118] This embodiment provides another example of a traditional Chinese medicine composition for lowering lipids, comprising the following raw materials in parts by weight: 20 parts hawthorn, 20 parts salvia miltiorrhiza, 30 parts partridge tea, and dalbergia odorifera oil (volatile oil extracted from 5 parts of dalbergia odorifera). The preparation method includes pretreatment, extraction, and post-treatment.

[0119] Mix all materials thoroughly, add 8 times the weight of the materials by volume of 75% ethanol, sonicate for 30 min, reflux extract at 65-75℃ for 60 min, filter to obtain the first filtrate, add 6 times the weight of the materials by volume of 75% ethanol again, reflux extract at 65-75℃ for 60 min, filter to obtain the second filtrate; combine the two extracts, concentrate, and dry to obtain the dry extract.

[0120] This embodiment provides a traditional Chinese medicine composition for lipid-lowering (hereinafter referred to as Composition 4). Cellular experiments were conducted to detect the effect of Composition 4 on Oil Red O staining of HepG2 cells and to measure intracellular TG content. The degree of damage to HepG2 cells by Composition 4 was detected using an MTT assay to evaluate the in vitro lipid-lowering activity of Composition 4. Compared with the control group, the model group showed a large number of red lipid droplets, and the TG content in the model group was significantly increased (P<0.001). Compared with the model group, the number and size of red lipid droplets in Composition 4 were significantly reduced (P<0.001), exhibiting a good dose-dependent effect; the higher the concentration of Composition 4, the fewer the number of red lipid droplets. These results indicate that Composition 4 can reduce the TG content in oleic acid-induced HepG2 cells and reduce lipid accumulation in HepG2 cells, demonstrating good in vitro lipid-lowering activity.

[0121] Table 10. Toxicity test of the lipid-lowering composition CCK8 in Example 4

[0122] Table 11. Efficacy of the lipid-lowering composition in Example 4 of cell experiments.

[0123] Example 5

[0124] This embodiment further provides the component screening and verification of the above-mentioned traditional Chinese medicine composition for lowering lipids.

[0125] Preferred, this embodiment provides a composition without sandalwood as a comparison.

[0126] Comparative composition 1: 30 parts partridge tea, 10 parts alisma, 10 parts turmeric, 10 parts astragalus, 10 parts hawthorn, 10 parts lotus leaf, 10 parts salvia miltiorrhiza, and 3 parts notoginseng powder.

[0127] Table 12 Comparison of cell viability in CCK-8 toxicity tests

[0128] Note: Generally, a cell viability rate of less than 50% indicates high toxicity. Therefore, a drug concentration with a cell viability rate greater than 70% is typically selected as the effective drug concentration.

[0129] Table 13. Pharmacodynamic testing based on triglyceride reduction rate.

[0130] Note: A higher triglyceride reduction rate (TG) indicates better drug efficacy.

[0131] The above experimental results show that, at the same drug dosage, the lipid-lowering composition shown in Composition 1 has a more significant triglyceride-lowering efficiency than the control composition; in addition, at the same drug dosage, the lipid-lowering composition shown in Composition 1 has a higher cell survival rate than the control composition, proving that Composition 1 has less toxicity and is safer to use.

[0132] In addition, this embodiment also provides verification of the effects of other composition ratios.

[0133] Table 14 Comparison of cell viability in CCK-8 toxicity tests

[0134] Table 15. Pharmacological efficacy testing based on triglyceride reduction rate.

[0135] The above experimental results show that when the total amount of the lipid-lowering core component is greater than the total amount of the auxiliary components (comparison composition 3), the composition has the lowest toxicity but the weakest efficacy. When the total amount of the auxiliary components is increased and the total amount of the lipid-lowering core component is further reduced (comparison composition 4), the toxicity of the composition is enhanced. However, the highest dose of 1200 μg / mL can still make the cell survival rate higher than 50%. Therefore, the weight ratio of the lipid-lowering core component to the auxiliary components in the composition should not be less than 13:40.

[0136] Furthermore, the efficacy of composition 1 and comparative composition 2 was verified in a mouse model of acute hyperlipidemia. The establishment of the mouse model of acute hyperlipidemia was the same as in Example 1.

[0137] An acute hyperlipidemia animal model was established by intraperitoneal injection of 75% egg yolk milk into mice. The total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) levels in mouse serum were measured. The composition 1 provided by this invention improved the lipid indicators in the hyperlipidemia group mice, reducing the levels of TC, TG, and LDL-C in the mouse serum while increasing the HDL-C level. The efficacy was significantly enhanced after the addition of sandalwood.

[0138] Table 16 Comparison of Blood Lipid Detection in Mice

[0139] Note: The high / medium / low doses of Composition 1 are 4.94 g / kg, 2.47 g / kg, and 1.24 g / kg, respectively. The dose of Comparative Composition 2 is 4.94 g / kg.

[0140] Example 6

[0141] Partridge tea, sandalwood, hawthorn and salvia miltiorrhiza were weighed and prepared into a traditional Chinese medicine preparation according to the method of Example 1 or Example 3, and then the following experiments were conducted to verify the results.

[0142] 1. A lipid-lowering traditional Chinese medicine composition significantly reduces intracellular lipid accumulation in HepG2 cells.

[0143] Oleic acid and palmitic acid were dissolved in 0.1 mmol / L NaOH solution and heated in a 70°C water bath for 20 min. The solution was then diluted with 10% BSA solution to obtain a 10 mmol / L free fatty acid (FFA) working solution. Blank, model, and drug-treated groups were set up. Hep-G2 cells were seeded in 12-well plates at a cell density of 1 × 10⁻⁶ cells / well. 5 Inoculation was performed at a concentration of 1 / mL. After inoculation, the cells were cultured for 24 h. The model group was treated with 1 mmol / L FFA for 24 h, while the drug-treated groups were treated with compound extracts of different ratios and cultured for 24 h. The compound extracts of different ratios are shown in Table 17.

[0144] Table 17 List of compound prescriptions with different combinations

[0145] 100 mg of Oil Red O dye was accurately weighed and added to 20 mL of isopropanol. The solution was wrapped in aluminum foil and placed in a 70°C water bath to dissolve, yielding a 0.5% Oil Red solution. 12 mL of the 0.5% Oil Red solution was added to 8 mL of pure water, mixed thoroughly, and filtered to prepare the Oil Red O working solution. The 12-well plates were removed from the incubator, the culture medium was aspirated, and the plates were washed three times with PBS. The plates were then fixed in 4% paraformaldehyde for 20 min. After aspirating the fixative, the plates were washed three times with pure water. Oil Red O working solution was then added, the plates were wrapped in aluminum foil, and incubated in a 37°C oven for 30 min. The working solution was then aspirated, and the plates were rinsed with 60% isopropanol solution for 30 s, followed by three washes with pure water. The cell morphology and lipid droplet distribution of each group were observed under a microscope.

[0146] Cells were seeded in 6-well plates. After drug administration, the culture medium was aspirated, and the cells were washed twice with PBS. 100 μL of cell lysis buffer was added to each well, and the cells were incubated on ice for 30 min to lyse. The intracellular TG content was measured using a TG kit.

[0147] Oil Red O staining was used to detect the effects of different compound formulations on lipid accumulation in HepG2 cells. The effects of different compound formulations on lipid surface area and lipid clearance rate in HepG2 cells were calculated and analyzed; the results are shown in Figure 4.

[0148] Experimental Results: First, the differences in lipid accumulation in HepG2 cells under different compound formulations were compared (Figure 4A). Comparing the intracellular TG content of HepG2 cells under different compound formulations, group 2 showed a significantly significant effect in reducing TG (P<0.0001). Compared with the model group, the number and size of red lipid droplets in each compound group were reduced. Among all groups, group 2 was more effective than the others in reducing lipid accumulation in HepG2 cells. Therefore, it was concluded that the optimal ratio of hawthorn: danshen: partridge tea: jiangxiang (Dalbergia odorifera) to herbal medicine composition (4:4:6:1) resulted in the best lipid-lowering effect. Therefore, this optimal ratio was subsequently used to prepare the lipid-lowering compound formulation (MLG). Figure 4B shows the effect of different molar amounts of oleic acid on cell viability; it can be seen that the higher the oleic acid concentration, the lower the cell viability. The degree of cell damage caused by MLG was then detected by the MTT assay. Drug concentrations of 50 μg / mL-400 μg / mL did not cause damage to HepG2 cells, and the cell viability was greater than 70%. Cell viability was greater than 55% at drug concentrations ranging from 600 μg / mL to 1200 μg / mL. The final drug concentration was determined to be 400 μg / mL (Figure 4C). The in vitro lipid-lowering activity of MLG was evaluated (Figure 4D), with MLGH at 400 μg / mL, MLGM at 200 μg / mL, and MLGL at 100 μg / mL. Compared to the control group, the number of red lipid droplets and TG content in HepG2 cells induced by free fatty acids (FFA) were significantly increased; however, after MLG intervention, the number and volume of intracellular lipid droplets decreased in a dose-dependent manner (Figure 4E), and TG content was also significantly reduced. These results indicate that MLG can effectively inhibit FFA-induced lipid accumulation in HepG2 cells, reduce TG content in cells, and exhibit clear in vitro lipid-lowering activity.

[0149] 2. A lipid-lowering traditional Chinese medicine composition regulates lipid metabolism and alleviates acute hyperlipidemia caused by 75% of egg yolk milk.

[0150] In a study on the treatment of acute hyperlipidemia in experimental mice, several fresh eggs were taken, and 75 mL of egg yolk liquid was diluted with physiological saline to 100 mL. The egg yolk emulsion was stirred with a magnetic stirrer for 10 min to ensure uniformity and reduce error, thus preparing a 75% egg yolk emulsion solution. 5.00 g of CMC-Na was accurately weighed and placed in a beaker, 800 mL of purified water was added, and the mixture was stirred until homogeneous. The solution was then transferred to a 1000 mL volumetric flask and purified water was added to the mark. A 0.5% CMC-Na solution was prepared. 1.23 g of the screened lipid-lowering composition (Group 2) (2.47 g / kg) was accurately weighed and placed in a 10 mL volumetric flask, suspended in 0.5% CMC-Na solution, and diluted to 10 mL. A 123 mg / mL compound drug solution sample was prepared. 6.5 mg of rosuvastatin (1.30 mg / kg) was accurately weighed and placed in a 100 mL volumetric flask, suspended in 0.5% CMC-Na solution, and diluted to 100 mL. Prepare a positive drug solution sample with a concentration of 0.065 mg / mL.

[0151] SPF-grade KM mice that passed quarantine were randomly divided into 6 groups of 6 mice each: a blank control group, a 75% egg yolk milk high-fat model group, a partridge lipid-lowering compound treatment group (low dose 1.24 g / kg, medium dose 2.47 g / kg, high dose 4.94 g / kg), and a rosuvastatin positive control group. Administered medication by gavage, the blank control group and the 75% egg yolk milk high-fat model group received 0.2 mL / 10 g of 0.5% CMC-Na daily, while the other drug groups received 0.2 mL / 10 g of the corresponding drug daily by gavage. After 5 consecutive days of administration, 2 hours after the last administration, each group received an intraperitoneal injection of 0.5 mL / mouse of 75% egg yolk milk saline solution to induce experimental hyperlipidemia. After 8 hours of fasting, the mice were administered medication by gavage after 12 hours, and blood and liver tissue were collected 1 hour later.

[0152] An acute hyperlipidemia animal model was established by intraperitoneal injection of 75% egg yolk milk into mice. Control, Model, High-dose MLG (MLGH), Medium-dose MLG (MLGM), Low-dose MLG (MLGL), and a positive control group (rosuvastatin) were established. Serum TC, TG, LDL-C, and HDL-C levels in mice were measured. MLGH significantly reduced plasma TC, TG, and LDL-C levels in mice, while significantly increasing HDL-C levels. MLGH was superior to the positive control group in reducing TC and TG, demonstrating good in vivo lipid-lowering activity. MLG significantly improved rapidly elevated lipid-related indicators, and high doses of MLG showed a significant lipid-lowering effect. Detailed results are shown in Table 18.

[0153] Blood from experimental animals was collected and placed in centrifuge tubes, then allowed to stand at room temperature for 1 hour to allow for coagulation and stratification. The supernatant was then centrifuged at 3000 rpm for 5 minutes, and the supernatant was collected and centrifuged at 12000 rpm and 4℃ for 10 minutes. The supernatant was then aliquoted and frozen.

[0154] The system was based on ultra-high performance liquid chromatography-tandem Fourier transform mass spectrometry (UHPLC-Q Exactive HF-X) by Thermo Fisher Scientific. An Accucore C30 column (100 mm × 2.1 mm id, 2.6 μm; Thermo) was used. Mobile phase A was 50% acetonitrile aqueous solution (containing 0.1% formic acid and 10 mmol / L ammonium acetate), and mobile phase B was acetonitrile / isopropanol / water (10 / 88 / 2) (containing 0.02% formic acid and 2 mmol / L ammonium acetate). The injection volume was 3 μL, and the column temperature was 40 °C.

[0155] Metabolic pathway annotation of differentially metabolites was performed using the KEGG database to identify the pathways involved by these metabolites. Pathway enrichment analysis was conducted using the Python package scipy.stats, and Fisher's exact test was used to identify the biological pathways most relevant to the experimental treatment.

[0156] By analyzing serum samples isolated from Control, Model, and MLGH mice, the differences in lipid metabolism induced by MLG were determined. PCA revealed different clusters of serum metabolites in each experimental group. Both Model and MLG interventions induced significant metabolic changes. Significant differences existed in the overall state between Control and Model, indicating that a high-fat diet altered the overall lipid metabolism state in mouse blood. Since MLG intervention altered the metabolic changes associated with hyperlipidemia, significant differences also existed in metabolites between Model and MLG. The metabolic characteristics of MLG were closer to those of Control, suggesting its potential to reverse metabolic disorders. 222 differentially regulated metabolites were detected between Control and Model, including 139 upregulated metabolites and 83 downregulated metabolites. 217 differentially regulated metabolites were detected between MLG and Control, including 73 upregulated metabolites and 144 downregulated metabolites. 208 differentially regulated metabolites were detected between MLG and Model, including 46 upregulated metabolites and 162 downregulated metabolites, demonstrating a significant downregulation of metabolism after MLG intervention (Figure 5). Cluster analysis was performed on lipid differences in mice from different groups. The top 30 differentially expressed metabolites with VIP>1 and Student's t-test p<0.05 were selected. The results showed that TG, DG, PC, CL, LPE, and PE were all significantly downregulated after MLG intervention. Among them, the downregulation of ceramide (Cer(d18:1 / 16:0), Cer(d18:1 / 22:0)), polyunsaturated fatty acid glycerides (DG(18:2 / 20:4)) and glycerophospholipid (PC(20:5 / 20:4)) may be related to increased lipid peroxidation and impaired cell membrane stability. Changes in LPC(24:0), LPC(22:0), and TG(18:0 / 18:0 / 18:1) indicated abnormal lipolysis and lipid storage imbalance. MLG intervention significantly restored the aforementioned lipid expression; Cer(d18:1 / 25:0), which was upregulated in Model, returned to baseline levels after administration. Simultaneously, molecules such as hexose ceramide (Hex1Cer(t18:0 / 23:1) and Cer(d18:1 / 23:1) were significantly upregulated in MLG, potentially serving as core biomarkers for MLG intervention. Sphingolipids, as structural components of cell membranes and precursors of signaling molecules, are closely associated with metabolic abnormalities in inflammation, insulin resistance, and neurodegenerative diseases. MLG may regulate lipid homeostasis by inhibiting key enzymes in sphingolipid metabolism. Significantly enriched metabolic pathways involving lipid metabolism, inflammation regulation, and energy balance were screened using a test (P<0.05). Core regulatory pathways included the sphingolipid signaling pathway, lipid digestion and absorption, cholesterol metabolism, glycerophospholipid metabolism, insulin resistance pathway, and the AGE-RAGE signaling pathway in diabetic complications.

[0157] Table 18 summarizes the results of four lipid assays in 18 groups of mice (n=6)

[0158] Note: Compared to the blank group, a p<0.05, b p<0.01; compared to the model group, c p<0.05, d p<0.01.

[0159] 3. MLG reduces weight gain and hyperlipidemia caused by HFD.

[0160] In a study on the treatment of chronic hyperlipidemia in rats, 48 ​​qualified SPF-grade SD rats were randomly divided into six groups (n=8 per group): a high-dose group (3.9 g / kg), a medium-dose group (1.95 g / kg), a low-dose group (0.975 g / kg), a positive control group (rosuvastatin 2 mg / kg), a model group, and a normal control group. The model and normal control groups received the same volume of 0.5% CMC-Na solution. Except for the normal control group, which was fed a breeding diet, all other groups were fed a high-fat diet for 4 weeks before starting the drug treatment for 14 days. During the drug treatment period, the normal control group was fed a breeding diet, while the other groups were fed a high-fat diet. Weight changes in the mice were recorded weekly, and feces were collected from each group in sterile cryovials and frozen for intestinal flora analysis. The day after the last drug administration, blood was collected from the abdominal aorta under anesthesia, and liver and spleen tissues were harvested.

[0161] Throughout the experiment, rats in all groups had free access to food and water. During the modeling period, compared with the control group, the model rats showed a significant increase in body weight and obvious obesity. As shown in Figure 6A, the difference in body weight between the control and model groups was significant with increasing modeling time (P < 0.01). During the drug administration period, the body weight of the control rats remained stable, while the body weight of the model rats continued to increase. The positive control group significantly slowed the rate of body weight gain in mice (P < 0.01), while MLGH significantly slowed the rate of body weight gain (P < 0.001). Other drug administration groups had an effect on body weight but no biological significance. The decrease in the rate of body weight gain in rats given MLG, and the effect was better than that in the positive control group, demonstrates that MLG has a downregulating effect on body weight gain induced by a high-fat diet.

[0162] As shown in Figures 6B-6C, due to the high-fat diet, the liver and spleen weights of the Model rats were significantly increased compared to the Control group, with highly significant differences in liver and spleen indices. Compared to the Model group, the liver indices of rats in all treatment groups were lower than those in the model group. The positive control group, MLGH, and MLGM significantly inhibited the increase in liver indices, while MLGH significantly inhibited the increase in spleen indices. These results indicate that MLGH can significantly reduce liver and spleen weight gain, demonstrating a significant effect.

[0163] Furthermore, compared to the control group, the serum levels of TC, TG, and LDL-C in the model were significantly increased. Treatment with different doses of MLG significantly reduced these levels, with MLGH showing better efficacy than positive control drugs. MLGH also increased HDL-C (Table 19), demonstrating good in vivo lipid-lowering activity. This confirms the significant lipid-lowering effect of MLG.

[0164] Table 19 Summary of Rat Blood Index Detection

[0165] Note: Compared with the blank group, a p<0.05, b p<0.01; compared with the model group, c p<0.05, d p<0.01.

[0166] Furthermore, lipid metabolism disorders can lead to inflammatory responses, which in turn can further exacerbate these disorders. The interaction between lipid metabolism and inflammation can cause hyperlipidemia (Figure 7). TNF-α, CXCL1, IL-6, and IL-1β are pro-inflammatory factors, and their levels in plasma can preliminarily reflect changes in inflammation. IL-6 accelerates lipolysis, increasing the delivery of free fatty acids to the liver, converting them into triglycerides that accumulate in liver tissue. TNF-α inhibits the transcription and expression of CYP7A1, leading to cholesterol accumulation in the liver and weakening insulin signaling, reducing signal transduction efficiency and inducing insulin resistance. The presence of abundant functional CXCL1 blocks LPA receptors, leading to hyperlipidemia-induced atherosclerosis. Compared to the control group, the model group showed significantly higher levels of TNF-α, CXCL1, IL-1β, and IL-6 in plasma, indicating that hyperlipidemia leads to inflammatory responses. Compared to the model group, the positive group showed significantly lower levels of TNF-α and CXCL1. Treatment with MLGH, MLGM, and MLGL significantly reduced the levels of TNF-α, IL-6, IL-1β, and CXCL1 in rat plasma in a dose-dependent manner, and the effect was superior to that of the positive control drug. This indicates that MLG can effectively reduce the inflammatory response caused by hyperlipidemia.

[0167] 4. Elucidating the regulatory network of MLG in treating chronic hyperlipidemia based on the gut-liver axis.

[0168] By analyzing the metagenomic sequences of microbial samples isolated from the feces of Model, MLG, and Control rats, the impact of MLG on the overall structure of the gut microbiota was determined. Based on genus- and species-level (Figure 8) gut microbiota clustering analysis data, the differences in gut microbiota structure and their biological significance among the groups can be systematically elucidated. Significant dysbiosis was observed in the Model group. Compared to the Control group, the abundance of beneficial bacteria with anti-inflammatory effects and short-chain fatty acid (SCFA) production functions, such as *Bacteroides* species *B. thetaiotaomicron* and *B. vulgatus*, and the mucus-protecting bacterium *Akkermansia muciniphila*, was significantly reduced. Simultaneously, the abundance of potentially pathogenic *Desulfovibrio* species was significantly increased. The reduction in Bacteroides led to a decrease in SCFA production, weakening its energy supply and anti-inflammatory effects on intestinal epithelial cells. Meanwhile, the proliferation of Desulfovibrio, through its unique sulfate-reduction metabolic pathway, produced cytotoxic metabolites such as hydrogen sulfide, further exacerbating intestinal oxidative stress and barrier function damage. After drug intervention, different dose groups exhibited a clear gradient effect, with MLGH showing the best gut microbiota regulation effect. It not only significantly restored the abundance of Bacteroides and Akkermansia muciniphila but also effectively inhibited the growth of Desulfovibrio, while promoting the proliferation of SCFA-producing bacteria such as Lactobacillus and Roseburia. This comprehensive gut microbiota reconstruction effect may stem from the anti-inflammatory active ingredients in high-dose drugs, which, by providing selective nutrient substrates and regulating the intestinal microenvironment, create more favorable colonization conditions for beneficial bacteria. While MLGM and MLGL also showed some regulatory trends and partially improved gut microbiota structure, such as increasing Prevotella, their regulatory effects on strictly anaerobic opportunistic pathogens like Clostridioides were limited. This may be related to insufficient drug concentrations, which limited their effective duration and range of action in the gut. Although Positive showed a promoting effect on Lactobacillus and Bifidobacterium, its restorative effect on specific anti-inflammatory bacteria such as Parabacteroides distasonis was not as good as MLGH, and its inhibitory effect on Desulfovibrio was weak. MLG may have achieved a more comprehensive gut microbiota regulation effect than traditional positive drugs by regulating bile acid metabolism and other multiple pathways, with the effect decreasing with decreasing dosage.MLGH closely resembles the healthy gut microbiota state of the control group, and can most effectively rebuild gut microbiota homeostasis, promote the proliferation of SCFA-producing bacteria to enhance intestinal barrier function, inhibit the overgrowth of pathogens to reduce inflammatory stimulation, maintain microbial diversity and functional balance, and more effectively alleviate intestinal inflammation and metabolic disorders through anti-inflammatory and nutrient competition mechanisms.

[0169] The embodiments of the present invention have been described above with reference to the accompanying drawings. However, the present invention is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of the present invention without departing from the spirit and scope of the claims. All of these forms are within the protection scope of the present invention.

Claims

1. A traditional Chinese medicine composition for lowering lipids, characterized in that, It includes a lipid-lowering core component and auxiliary components. The lipid-lowering core component consists of partridge tea and sandalwood. The auxiliary components include hawthorn and salvia miltiorrhiza. The weight ratio of partridge tea to sandalwood in the lipid-lowering core component is 6-10:

1. The weight ratio of hawthorn to salvia miltiorrhiza in the auxiliary components is 1:5-1. The total weight of the lipid-lowering core component is less than the total weight of the auxiliary components.

2. The traditional Chinese medicine composition as described in claim 1, characterized in that, The weight ratio of the lipid-lowering core component to the auxiliary component is 13:40 to 35:

40.

3. The traditional Chinese medicine composition according to claim 1, characterized in that, The ratio of hawthorn, salvia miltiorrhiza, partridge tea, and sandalwood is 4:4:6:

1.

4. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition comprises the following materials in parts by weight: 10-40 parts of partridge tea, 3-10 parts of sandalwood, 20-40 parts of hawthorn, and 20-40 parts of salvia miltiorrhiza.

5. The traditional Chinese medicine composition as described in claim 3, characterized in that, The traditional Chinese medicine composition comprises the following materials in parts by weight: 10-30 parts of partridge tea, 3-7 parts of sandalwood, 20-30 parts of hawthorn, and 20-30 parts of salvia miltiorrhiza.

6. The traditional Chinese medicine composition as described in claim 4 or 5, characterized in that, The fragrance includes the medicinal material of Dalbergia odorifera and the fragrance oil prepared by extracting from the medicinal material of Dalbergia odorifera in the specified weight proportions.

7. The traditional Chinese medicine composition according to claim 1, characterized in that, The traditional Chinese medicine composition is obtained by water extraction or alcohol extraction.

8. A method for preparing the traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, Includes the following steps: S01: The first material consists of the following ingredients by weight: 10-40 parts of partridge tea, 20-40 parts of hawthorn and 20-40 parts of salvia miltiorrhiza; and 3-10 parts by weight of sandalwood as the second material. S02: Add 10-20 times the volume of purified water by weight of the first material to the first material, soak it thoroughly, and then decoct and extract at 90-100℃ for 60-100 minutes. Filter to obtain the first extract. Add 5-10 times the volume of purified water by weight of the first material again, and continue to decoct and extract at 90-100℃ for 60-100 minutes. Then add the second material, decoct for 10-30 minutes, and filter to obtain the second extract. Combine the two extracts, concentrate, and dry to obtain a dry paste.

9. The preparation method according to claim 8, characterized in that, The preparation method may also include the following steps: S02: After mixing the first and second materials evenly, add 6-10 times the volume of high-concentration ethanol by weight of the materials, sonicate to ensure thorough mixing and soaking, then reflux extract at 60-75℃ for 60-100 min, and filter to obtain the first extract; add 6-10 times the volume of high-concentration ethanol again, reflux extract at 60-75℃ for 60-100 min, and filter to obtain the second extract; combine the two extracts, concentrate, and dry to obtain a dry paste.

10. A traditional Chinese medicine preparation, characterized in that, Includes the traditional Chinese medicine composition according to any one of claims 1-5.

11. The traditional Chinese medicine preparation as described in claim 10, characterized in that, It also includes other pharmaceutically acceptable excipients and / or auxiliaries.

12. The traditional Chinese medicine preparation as described in claim 10, characterized in that, The dosage forms of the traditional Chinese medicine preparations include granules, powders, tablets, capsules and / or pills.

13. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a lipid-lowering drug.

14. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a weight-loss drug.

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