Application of a processed product of Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of lipid-lowering and hyperlipidemia prevention and treatment products.

Abstract

This invention belongs to the field of traditional Chinese medicine technology. More specifically, it relates to the application of a processed product of Citrus reticulata peel or Citrus reticulata peel embryo (with bitterness removed) in the preparation of products for lowering lipids and preventing and treating hyperlipidemia. Compared with the original product, the processed product of Citrus reticulata peel or Citrus reticulata peel embryo provided by this invention significantly reduces bitterness while significantly enhancing its effects in lowering cholesterol and triglycerides and regulating blood lipids. This processed product helps maintain normal levels of serum cholesterol, triglycerides, and low-density lipoprotein, and can significantly improve liver damage caused by hyperlipidemia, thus having important application value in lowering lipids and protecting the liver.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology. More specifically, it relates to the application of processed Citrus reticulata peel or Citrus reticulata peel embryonic tissue in the preparation of lipid-lowering and hyperlipidemia prevention and treatment products. Background Technology

[0002] Huazhou tangerine peel (Exocarpium Citri Grandis) is a plant belonging to the Rutaceae family, specifically the Huazhou pomelo. Citrus grandis 'Tomentosa' or pomelo Citrus grandis The immature or nearly mature dried outer peel of (L.) Osbeck; Huazhou pomelo (Citrus reticulata var. huazhouensis) is a plant of the Rutaceae family, listed in the Guangdong Provincial Standard for Medicinal Materials. Citrus grandis The dried young fruit of 'Tomentosa'. Both *Citrus reticulata* peel and *Citrus reticulata* embryo are used in traditional Chinese medicine as *Citrus reticulata* peel, possessing the functions of regulating qi, relieving chest congestion, drying dampness, and resolving phlegm. It is used for cough with excessive phlegm, food stagnation, alcohol poisoning, nausea, and abdominal distension. Currently, research on the application of *Citrus reticulata* peel focuses primarily on expectorant and antitussive effects. With the advancement of modern pharmacological research, the flavonoids (such as naringin) abundant in *Citrus reticulata* peel are considered to have potential metabolic regulatory effects, exerting lipid-lowering and blood sugar-lowering effects. However, whether *Citrus reticulata* peel has a definitive lipid-lowering effect remains controversial in the academic community, with unclear conclusions and limited practical application effects. Therefore, exploring and developing application technologies for regulating metabolism using *Citrus reticulata* peel is of great significance.

[0003] Li Jinkun et al. (2024) developed a water extraction process for Citrus reticulata peel, and the test results showed that the obtained water extract had a significant lipid-lowering effect. The main components of the Citrus reticulata peel water extract are flavonoids, especially naringin. Studies have shown that naringin can inhibit lipid accumulation and triglyceride content in 3T3-L1 adipocytes, and the lipid-lowering effect of naringin treatment is better than that of naringin. However, naringin is also the main bitter component of Citrus reticulata peel, resulting in a heavy bitter taste in the water extract, which to some extent limits its application. Furthermore, as a deep-processed product, the water extract does not possess the unique advantages of Citrus reticulata peel / Citrus reticulata peel embryo as a traditional Chinese medicine product.

[0004] Processing is a distinctive feature of traditional Chinese medicine and a primary method for enhancing efficacy and improving taste. Currently, processing techniques for Huajuhong (Citrus reticulata peel) mainly include stir-frying, salt processing, honey processing, soil processing, ginger processing, and alum processing. Naringin is one of the main active ingredients in Huajuhong and Huajuhong embryo, and it is also the main component causing bitterness. Therefore, the challenge in processing Huajuhong or Huajuhong embryo lies in achieving the removal of bitterness without diminishing efficacy, or even enhancing it. The inventors' patent CN118634273B provides a processing method for Huajuhong / Huajuhong embryo, which significantly reduces the dissolution of the main bitter substance, naringin, after processing, and significantly improves its antitussive, expectorant, and lung-protective effects. However, due to the significant reduction in naringin content after processing, it is unknown whether this processed product has any effect on lowering blood lipids. Summary of the Invention

[0005] This invention aims to explore and expand the applications of Citrus reticulata peel and its processed products, especially in lipid-lowering. Our research unexpectedly revealed that the prepared Citrus reticulata peel and its processed products have a very positive effect on lipid-lowering; animal model experiments showed that the prepared Citrus reticulata peel and its processed products can regulate metabolism, lower lipids, promote weight loss, and protect the liver, demonstrating significant application value and promising prospects.

[0006] The purpose of this invention is to provide an application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of drugs with effects such as lowering blood lipids, lowering cholesterol, and protecting the liver. Compared with the original product, the processed product has significantly improved the effects of lowering cholesterol, lowering triglycerides, and lowering blood lipids, while also significantly improving the bitterness of the original Citrus reticulata peel.

[0007] The above-mentioned objective of this invention is achieved through the following technical solution: The Huazhou tangerine peel described in this invention is a plant of the Rutaceae family, specifically the Huazhou pomelo. Citrus grandis 'Tomentosa' or pomelo Citrus grandis The immature or nearly mature dried outer peel of (L.) Osbeck, without any other treatment; the Huazhou pomelo peel described in this invention is a Rutaceae plant. Citrus grandis The dried young fruit of 'Tomentosa', without any other treatment.

[0008] The inventors' team previously provided a method for processing Huajuhong (Citrus reticulata peel) / Huajuhong embryo in patent CN118634273B, and conducted a systematic component analysis on the processed Huajuhong embryo and the original product. The results showed that the original Huajuhong is rich in active ingredients such as naringin, vitexin, and arbutin, with naringin accounting for approximately 45% of the total active ingredients. After processing using the described bitter-removing and efficacy-enhancing method, the content of various substances in the processed product changed significantly. Specifically, the contents of naringin, vitexin, and arbutin decreased by approximately 43%, 32%, and 5%, respectively, compared to the original product. However, efficacy experiments of this invention found that although the naringin content was significantly reduced, the Huajuhong processed using this method showed significantly better bioactivity in lowering cholesterol, triglycerides, and blood lipids than the original product before processing. That is, the bitter-removing and efficacy-enhancing processing method described in this invention can improve the efficacy of Huajuhong while simultaneously reducing its bitterness.

[0009] Therefore, this invention claims protection for the following applications: This invention provides the application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of lipid-lowering products. The preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel raw material, mix it with sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak it at 50-90℃ for 6-72 h, and then dry it to obtain the processed product; wherein, the weight-volume ratio of the raw material and the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1g:(2-6)mL.

[0010] Preferably, in the above-mentioned method for preparing Citrus reticulata or Citrus reticulata var. reticulata products, the drying method is as follows: after soaking, the liquid is left, and the raw material is dried once until the moisture content is below 20%; then it is mixed with the liquid and dried a second time until the moisture content is below 5%.

[0011] Specifically, the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10% specifically refers to adding 0.5-10g of sodium bicarbonate or sodium carbonate to 100 mL of water.

[0012] Preferably, in the above-mentioned method for preparing Citrus reticulata or Citrus reticulata var. reticulata products, the mass-volume concentration of sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 0.5-5%.

[0013] Preferably, in the above-mentioned method for preparing Citrus reticulata or Citrus reticulata extract, the soaking time is 12-48 hours.

[0014] More preferably, in the above-mentioned method for preparing Citrus reticulata or Citrus reticulata extract, the soaking time is 24 hours.

[0015] Preferably, the raw material and sodium bicarbonate aqueous solution or sodium carbonate aqueous solution are mixed at a mass-volume ratio of 1g:(2-5)mL.

[0016] More preferably, the raw materials and the aqueous solution of sodium bicarbonate or the aqueous solution of sodium carbonate are mixed at a mass-to-volume ratio of 1 g: 5 mL.

[0017] Preferably, the temperature of the infiltration is 65 °C.

[0018] Preferably, the drying is carried out at 100-140 °C.

[0019] As an optional preferred scheme, the raw materials of Citrus reticulata Blanco cv. Tomentosa or its fetus can be sliced or cut into strips. Slicing or cutting the raw materials of Citrus reticulata Blanco cv. Tomentosa or its fetus before infiltration is beneficial to increase the contact area between the raw materials and the liquid, enabling the raw materials of Citrus reticulata Blanco cv. Tomentosa or its fetus to be better infiltrated.

[0020] The present invention provides the application of the above-mentioned processed products of Citrus reticulata Blanco cv. Tomentosa or its fetus in the preparation of products for preventing and treating hyperlipidemia or alleviating the symptoms caused by hyperlipidemia.

[0021] The present invention induced a hypercholesterolemia mouse model with a high-fat emulsion, measured the contents of related indexes in the serum, liver, and feces of mice in each group, liver pathological sections, oil red O staining, etc., and comparatively evaluated the cholesterol-lowering effects of the processed products of Citrus reticulata Blanco cv. Tomentosa fetus and the original product of Citrus reticulata Blanco cv. Tomentosa fetus (unprocessed). The experimental results prove that compared with the original product of Citrus reticulata Blanco cv. Tomentosa fetus (unprocessed), the processed product prepared by the processing method of the present invention can enhance the cholesterol-lowering effect of Citrus reticulata Blanco cv. Tomentosa fetus.

[0022] In addition, the present invention induced hypertriglyceridemia mice with Poloxamer 407 (P407), and further studied and verified the lipid-lowering effects of the processed products of Citrus reticulata Blanco cv. Tomentosa fetus and the original product of Citrus reticulata Blanco cv. Tomentosa fetus (unprocessed). The experimental results found that compared with the original product of Citrus reticulata Blanco cv. Tomentosa fetus, the processed product prepared by the processing method of the present invention can enhance the triglyceride-lowering effect of Citrus reticulata Blanco cv. Tomentosa.

[0023] Therefore, the present invention provides the application of the above-mentioned processed products of Citrus reticulata Blanco cv. Tomentosa or its fetus in the preparation of products for reducing cholesterol and / or triglyceride.

[0024] The present invention provides the application of the above-mentioned processed products of Citrus reticulata Blanco cv. Tomentosa or its fetus in the preparation of products for reducing low-density lipoprotein cholesterol and / or increasing high-density lipoprotein cholesterol.

[0025] The present invention provides the application of the above-mentioned processed products of Citrus reticulata Blanco cv. Tomentosa or its fetus in the preparation of products for protecting the liver, improving liver lesions or alleviating liver damage caused by hyperlipidemia.

[0026] The present invention provides the application of the above-mentioned processed products of Citrus reticulata Blanco cv. Tomentosa or its fetus in the preparation of products for improving liver lipid accumulation or preventing and treating fatty liver.

[0027] This invention provides the application of the above-mentioned Citrus reticulata peel or Citrus reticulata peel extract in the preparation of products that help maintain blood lipids.

[0028] Specifically, the phrase "helps maintain blood lipids" refers to helping maintain healthy levels of cholesterol or triglycerides.

[0029] This invention provides the application of the above-mentioned Citrus reticulata peel or Citrus reticulata peel extract in the preparation of products that help control body fat.

[0030] This invention provides the application of the above-mentioned Citrus reticulata extract or Citrus reticulata extract carcass in the preparation of weight-reducing products.

[0031] The present invention has the following beneficial effects: The inventors' team previously provided a method for processing Citrus reticulata peel / Citrus reticulata peel embryo in patent CN118634273B, and conducted a systematic component analysis on the processed Citrus reticulata peel embryo and the original product. The analysis results showed that the original Citrus reticulata peel is rich in active ingredients such as naringin, vitexin, and arbutin, with naringin accounting for approximately 45% of the total active ingredients. After processing, the naringin content in the processed product decreased by approximately 43% compared to the original product. However, this invention found that although the naringin content was significantly reduced after processing using the method described in this invention, the pharmacological activity of the processed product in lowering lipids and cholesterol was significantly enhanced. Compared with the unprocessed original product, the processed product showed better effects in lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), while significantly increasing high-density lipoprotein cholesterol (HDL-C) levels, effectively improving dyslipidemia.

[0032] Furthermore, the processed product of this invention not only has a direct lipid-lowering effect, but also significantly improves liver damage caused by hyperlipidemia. Experiments have shown that the processed product of this invention can reduce the liver index in hyperlipidemic model mice, alleviate hepatocyte edema and fat vacuolar degeneration, and reduce lipid accumulation in the liver. In addition, this processed product can also lower serum bile acid levels by promoting bile acid excretion, thereby exerting lipid-lowering and liver-protecting effects through multiple pathways. Attached Figure Description

[0033] Figure 1 The images show the original CG extract of Citrus reticulata and the processed PCG extract of Citrus reticulata (the left image shows the original extract of Citrus reticulata, and the right image shows the processed PCG extract of Citrus reticulata).

[0034] Figure 2The results show the effects of PCG on body weight and liver index in P407-induced hypertriglyceridemia mice.

[0035] Figure 3 The results show the effect of PCG on lipid accumulation in the liver of mice with P407-induced hypertriglyceridemia (Figure A shows the appearance of the liver of mice in each group in the P407-induced hypertriglyceridemia model; Figure B shows the HE and Oil Red O staining of the liver of mice in each group in the P407-induced hypertriglyceridemia model, 200X).

[0036] Figure 4 The results show the effects of PCG on blood lipid levels in mice with P407-induced hypertriglyceridemia (Figure A shows the changes in serum triglyceride levels in each group of mice in the P407-induced hypertriglyceridemia model; Figure B shows the changes in serum cholesterol levels in each group of mice in the P407-induced hypertriglyceridemia model; Figure C shows the changes in low-density lipoprotein cholesterol levels in each group of mice in the P407-induced hypertriglyceridemia model; Figure D shows the changes in high-density lipoprotein cholesterol levels in each group of mice in the P407-induced hypertriglyceridemia model; Figure E shows the changes in liver cholesterol levels in each group of mice in the P407-induced hypertriglyceridemia model; Figure F shows the changes in fecal cholesterol levels in each group of mice in the P407-induced hypertriglyceridemia model).

[0037] Figure 5 The results show the effects of PCG on serum lipid levels in mice with high-fat emulsion-induced hypercholesterolemia (Figure A shows the changes in serum cholesterol levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure B shows the changes in serum triglyceride levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure C shows the changes in serum low-density lipoprotein cholesterol levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure D shows the changes in serum high-density lipoprotein cholesterol levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure E shows the changes in serum alanine aminotransferase levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure F shows the changes in serum aspartate aminotransferase levels in each group of mice in the high-fat emulsion-induced hypercholesterolemia model).

[0038] Figure 6 The results show the effect of PCG on lipid accumulation in the liver of mice with hypercholesterolemia induced by high-fat emulsion (Figure A shows the appearance of the liver of mice in each group in the hypercholesterolemia model induced by high-fat emulsion; Figure B shows the HE and Oil Red O staining of the liver of mice in the hypercholesterolemia model induced by high-fat emulsion, 200X; Figure C shows the changes in cholesterol content in the liver of mice in each group in the hypercholesterolemia model induced by high-fat emulsion; Figure D shows the changes in triglyceride content in the liver of mice in each group in the hypercholesterolemia model induced by high-fat emulsion).

[0039] Figure 7 The results show the effect of PCG on cholesterol excretion in mice with high-fat emulsion-induced hypercholesterolemia.

[0040] Figure 8 The results show the effect of PCG on bile acid levels in mice with high-fat emulsion-induced hypercholesterolemia (Figure A shows the changes in serum bile acid content in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure B shows the changes in liver bile acid content in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure C shows the changes in gallbladder bile acid content in each group of mice in the high-fat emulsion-induced hypercholesterolemia model; Figure D shows the changes in fecal bile acid content in each group of mice in the high-fat emulsion-induced hypercholesterolemia model).

[0041] Note: # P< 0.05 and ## P< The difference of 0.01 compared to group N was statistically significant. * P< 0.05 and ** P< 0.01 indicates a significant difference compared to group P407 or M; & P< 0.05 and && P< 0.01 indicates a significant difference compared to the 1.0 g / kg-CG group. Detailed Implementation

[0042] The present invention will be further described below with reference to the accompanying drawings and specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in this technical field.

[0043] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0044] The preparation method of processed products of Citrus reticulata and Citrus reticulata var. reticulata is the same as the inventor's prior application (CN118634273B).

[0045] In the following examples, the high-fat emulsion was prepared as follows: 1g of propylthiouracil (brand: Yuanye, catalog number: Y35355-5g) was finely ground in a mortar and set aside. 30g of lard (brand: Yuanye, catalog number: S26610-1kg) was melted in a 60℃ water bath. 10g of cholesterol (brand: Yuanye, catalog number: S11040-500g) was added and stirred thoroughly to dissolve. Then, 1g of propylthiouracil was added and stirred. Next, 15mL each of Tween-80 (brand: Aladdin, catalog number: T104865-500ml) and propylene glycol (brand: Aladdin, catalog number: P108208-500ml) were added and ground until well mixed. Then, 20mL of a 10% sodium deoxycholate aqueous solution (brand: Maclean, catalog number: 774011-100g) was slowly added and ground to emulsify. Distilled water was then added to a final volume of 100mL. Store in a sealed container and refrigerate. Before use, melt in a 37°C water bath.

[0046] Example 1: Effects of the "Qu Ku" processed product of Huajuhongtai on P407-induced hypertriglyceridemia in mice.

[0047] I. Experimental Methods Seventy male C57BL / 6J mice, aged 6-8 weeks and weighing 18-22 g, were selected. The environment was maintained at a temperature of 18-22℃ and humidity of 40%-60%, with 12 hours of light per day. The animals were provided with normal feed and free access to drinking water daily. After one week of acclimatization, the mice were randomly divided into 7 groups of 10 mice each. (1) Normal group (N): During the experiment from day 1 to day 7, mice were injected intraperitoneally with physiological saline (0.1 ml / 10 g) and orally with physiological saline (0.1 ml / 10 g) according to their body weight.

[0048] (2) Model group (P407): From day 1 to day 7 of the experiment, mice were injected intraperitoneally with P407 (0.4 g / kg) and gavaged with physiological saline (0.1 ml / 10 g).

[0049] (3) Atorvastatin group (AVT, 0.01 g / kg): During the experiment from day 1 to day 7, mice were injected intraperitoneally with P407 (0.4 g / kg) and administered atorvastatin solution (0.01 g / kg) by gavage.

[0050] (4) Low-dose group of Huajuhong fetal product (CG-L, 0.5 g / kg): During the experiment from day 1 to day 7, mice were injected intraperitoneally with P407 (0.4 g / kg) and gavaged with Huajuhong fetal product 0.5 g / kg.

[0051] (5) High dose group of Huajuhong fetal product (CG-H, 1.0 g / kg): During the experiment from day 1 to day 7, mice were injected intraperitoneally with P407 (0.4 g / kg) and gavaged with Huajuhong fetal product 1.0 g / kg.

[0052] (6) Low-dose group of processed tangerine peel "Qu Ku" product (PCG-L, 0.5 g / kg): During the experiment from day 1 to day 7, mice were injected intraperitoneally with P407 (0.4 g / kg) according to their body weight and gavaged with processed tangerine peel "Qu Ku" product at a dose of 0.5 g / kg.

[0053] (7) High-dose group of processed tangerine peel "Qu Ku" product (PCG-H, 1.0 g / kg): During the experiment from day 1 to day 7, mice were injected intraperitoneally with P407 (0.4 g / kg) according to their body weight and gavaged with processed tangerine peel "Qu Ku" product at a dose of 1.0 g / kg.

[0054] The preparation method of the "bitterness-removing" processed product of Huajuhongtai is the same as that in Example 3 of CN118634273B.

[0055] From day 1 to day 7 of the experiment, except for the control group which received intraperitoneal injection of saline, all other groups of mice received intraperitoneal injection of P407 (0.4 g / kg) to establish a hypertriglyceridemia model. Simultaneously, each group received the same medication via gavage daily for 7 days, with mouse weight monitored and recorded daily. On the last day of the experiment, after a 12-hour fast with free access to water, fresh feces were collected from each group of mice. Mice were then anesthetized with sodium pentobarbital, blood samples were collected, and the mice were euthanized, with tissue samples collected.

[0056] Observation indicators: (I) Changes in mouse body weight and organ indices; (II) Pathological examination: hematoxylin-eosin staining (HE) and Oil Red O staining of the liver; (III) Serum, liver and fecal fat and cholesterol related indicators: triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).

[0057] II. Experimental Results 1. Effects on mouse body weight and organ indices: The results showed that the model group mice were lethargic, had dull and scraggly fur, and reduced food intake and defecation. After intervention with AVT, CG, and PCG, the mice's mental state improved significantly, and their defecation increased.

[0058] like Figure 2As shown, experimental data indicate that after modeling with P407 (brand: Yuanye, product number: V34652-50g), the weight of mice showed an increasing trend, and liver indices were significantly elevated. P< 0.01). Compared with the P407 group, treatment with 1 g / kg PCG significantly reduced body weight and liver index ( ). P< 0.05). The results showed that the "bitterness-removing" processed product of Citrus reticulata peel could effectively reduce the body weight and liver index of mice with hypertriglyceridemia.

[0059] 2. Effects on liver damage in hypertriglyceridemia mice: like Figure 3 As shown, the livers of normal mice were reddish-brown and glossy, with a smooth surface and clear edges. In contrast, the livers of P407-induced hypertriglyceridemia mice were enlarged, yellowish-white, greasy, and had rounded edges. Compared to the P407 group, atorvastatin treatment improved liver color and size, but some color lesions and uneven size remained. Low- and high-dose CG and PCG treatments improved liver color and size compared to the model group, restoring a uniform reddish-brown color. HE staining showed hepatocyte edema, ballooning degeneration with fat vacuoles, and disordered arrangement in the P407 group; Oil Red O staining revealed a large accumulation of lipid droplets. AVT, CG, and PCG treatments improved lesions and lipid accumulation, and the results showed that the processed tangerine peel "bitterness-removing" product was more effective than the original tangerine peel peel in improving liver lipid accumulation.

[0060] 3. Effects on blood lipid levels in mice: like Figure 4 As shown, compared with the normal group, the serum TG, TC, serum LDL-C and liver TC levels of P407 mice were significantly increased ( P< 0.05), while serum HDL-C levels were significantly reduced ( P< The result was 0.05, indicating that the hypertriglyceridemia model was successfully established. Compared with the P407 group mice, the serum TG, TC, and liver TC levels in the AVT group, high-dose CG group, and high-dose PCG group mice were significantly reduced ( P< 0.05), and the fecal TC level showed an increasing trend. Notably, the AVT group and the high-dose PCG group were able to restore HDL-C levels in mouse serum and downregulate LDL-C levels ( P< 0.05). In summary, the experimental results show that the processed product of Huajuhongtai (a type of tangerine peel) exhibits a more significant lipid-lowering effect.

[0061] Example 2: Effects of processed Citrus reticulata peel extract on mice with high-fat emulsion-induced hypercholesterolemia.

[0062] I. Experimental Methods Seventy male KM mice aged 6-8 weeks, weighing 18-22 g, were selected. The environment was maintained at a temperature of 18-22℃ and humidity of 40%-60%, with 12 hours of light per day. The animals were provided with normal feed and free access to drinking water daily. After 3 days of acclimatization, they were randomly divided into 7 groups of 10 mice each. Normal group (N): From day 1 to day 9 of the experiment, mice were given physiological saline (0.2 ml / 10 g) or physiological saline (0.1 ml / 10 g) by gavage according to their body weight.

[0063] Model group (M): From day 1 to day 9 of the experiment, mice were administered high-fat emulsion (0.2 ml / 10 g) or physiological saline (0.1 ml / 10 g) by gavage according to their body weight.

[0064] Atorvastatin group (AVT, 10 mg / kg): From day 1 to day 9 of the experiment, mice were administered a high-fat emulsion (0.2 ml / 10 g) or an atorvastatin solution (0.01 g / kg) by gavage according to their body weight.

[0065] Low-dose group of Citrus reticulata extract (CG-L, 0.5 g / kg): During the experiment from day 1 to day 9, mice were administered a high-fat emulsion (0.2 ml / 10 g) and Citrus reticulata extract 0.5 g / kg by gavage according to their body weight.

[0066] High-dose group of Citrus reticulata extract (CG-H, 1.0 g / kg): During the experiment from day 1 to day 9, mice were administered a high-fat emulsion (0.2 ml / 10 g) and Citrus reticulata extract (1.0 g / kg) by gavage according to their body weight.

[0067] Low-dose group of processed tangerine peel (PCG-L, 0.5 g / kg): During the experiment from day 1 to day 9, mice were administered a high-fat emulsion (0.2 ml / 10 g) by gavage according to their body weight, and 0.5 g / kg of processed tangerine peel "bitterness-removing" product by gavage.

[0068] High-dose group of processed tangerine peel (PCG-H, 1.0 g / kg). From day 1 to day 9 of the experiment, mice were administered a high-fat emulsion (0.2 ml / 10 g) and a 1.0 g / kg "bitterness-removing" processed tangerine peel by gavage according to their body weight.

[0069] The preparation method of the "bitterness-removing" processed product of Huajuhongtai is the same as that in Example 3 of CN118634273B.

[0070] In the morning, except for the normal group which was given distilled water by gavage, all other drug groups were given a high-fat emulsion (0.2 mL / 10 g) by gavage to establish the model, and the model was established continuously for 9 days. In the afternoon, except for the normal group and the model group which were given physiological saline (0.1 ml / 10 g) by gavage, all other groups were given the corresponding equal volume of drug by gavage.

[0071] Daily weight changes were recorded during the experiment. On the last day of the experiment, after fasting for 12 hours but not water, fresh feces were collected from each group of mice. Mice were then anesthetized with sodium pentobarbital, blood samples were collected, and the mice were euthanized and tissue samples were collected.

[0072] Observation indicators: (I) Lipid-related indicators in serum, liver, bile and feces: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total bile acids (TBA), alanine aminotransferase (ALT), and aspartate aminotransferase (AST); (II) Pathological examination: liver hematoxylin-eosin staining (HE) and oil red O staining.

[0073] II. Experimental Results 1. Effects on lipid disorders and liver function in hypercholesterolemia mice: like Figure 5 As shown, after 9 days of continuous oral administration of high-fat emulsion, compared with group N, the high-fat emulsion-induced hypercholesterolemia model group mice showed disordered blood lipid levels, specifically elevated serum TC and LDL-C, and decreased HDL-C, while serum TG levels showed no significant change, similar to the characteristics of clinical simple hypercholesterolemia. Compared with group M, the AVT, CG, and PCG administration groups significantly reduced serum TG, TC, and LDL-C levels ( P< 0.05), administration of 1 g / kg PCG significantly increased HDL-C levels ( P< 0.05). Serum ALT and AST are important indicators for assessing liver function. Compared with group N mice, group M mice showed significantly higher serum ALT and AST levels. Figure 5 (Figures E and F). Administration of AVT, CG, and PCG significantly reduced serum ALT and AST levels in hypercholesterolemic mice. These results indicate that CG and PCG can improve lipid disorders and restore liver function in hypercholesterolemic mice, and the processed product of Huajuhongtai "Quku" showed a more significant lipid-lowering effect.

[0074] 2. Effects on liver damage in hypercholesterolemic mice: like Figure 6 As shown, HE staining revealed hepatocyte edema, ballooning degeneration, and fat vacuoles with disordered arrangement in the model group mice; Oil Red O staining showed a large accumulation of lipid droplets. Treatment with AVT, CG, and PCG improved the lesions and lipid accumulation. The levels of TC and TG in the liver of the model group mice were significantly increased ( P<0.01), AVT and CG, and PCG high-dose groups can significantly reduce their levels ( P <0.05 or P <0.01), confirming that CG and PCG can improve lipid accumulation in the liver of mice with hypercholesterolemia, and that the processed product of Huajuhongtai "Quku" showed a stronger effect in regulating lipid accumulation in the liver.

[0075] 3. Effects on cholesterol excretion in mice: like Figure 7 As shown, the results indicated that, compared with the normal group, the fecal cholesterol content of mice in the model group was increased; compared with the model group, administration of AVT, CG, and PCG significantly reduced the fecal cholesterol content of mice. P< 0.05).

[0076] 4. Effects on bile acid levels in mice: like Figure 8 As shown, compared with group N mice, the serum and liver levels of total bile acids (TBA) in group M mice were increased ( P <0.01), and no significant changes were observed in TBA levels in the gallbladder and feces. Compared with group M, the levels of TBA in the serum of mice were significantly reduced after intervention with CG and PCG; at the same time, the levels of TBA in the liver of mice in the high-dose PCG group were reduced ( P <0.01, the TBA level in the feces of mice in the high-dose CG and PCG groups was significantly increased ( P <0.05, and the TBA level in the gallbladder of PCG group mice was also significantly increased ( P <0.01). The results showed that both CG and PCG could exert lipid-lowering effects by promoting bile acid excretion and reducing serum bile acid levels. Notably, processed tangerine peel (PCG) could also significantly promote the excretion of bile acids into the gallbladder. P <0.05).

[0077] The results above indicate that processed tangerine peel (PCG) has significant effects in lowering cholesterol, triglycerides, and blood lipids, and its effects are superior to those of unprocessed tangerine peel (CG).

[0078] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of lipid-lowering products, wherein the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: Citrus reticulata peel or Citrus reticulata peel embryo raw material is taken and mixed with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soaked at 50-90℃ for 6-72 h, and then dried to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

2. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of products for preventing or treating hyperlipidemia or alleviating symptoms caused by hyperlipidemia; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel embryo raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

3. The application of processed Citrus reticulata peel or Citrus reticulata peel extract in the preparation of products that lower cholesterol and / or triglycerides; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel extract is as follows: take Citrus reticulata peel or Citrus reticulata peel extract raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

4. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of products that lower low-density lipoprotein cholesterol and / or raise high-density lipoprotein cholesterol; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel embryo raw material, mix it with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak it at 50-90℃ for 6-72 h, and then dry it to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

5. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of products that protect the liver, improve liver lesions, or alleviate liver damage caused by hyperlipidemia; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel embryo raw material, mix it with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak it at 50-90℃ for 6-72 h, and then dry it to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

6. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of products that improve liver lipid accumulation or prevent fatty liver; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel embryo raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

7. The application of processed Citrus reticulata peel or Citrus reticulata peel embryo in the preparation of products that help maintain blood lipids; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel embryo is as follows: take Citrus reticulata peel or Citrus reticulata peel embryo raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

8. The application according to claim 7, characterized in that, The statement that it helps maintain blood lipids means that it helps maintain healthy levels of cholesterol or triglycerides.

9. The application of processed Citrus reticulata peel or Citrus reticulata peel extract in the preparation of products that help control body fat; the preparation method of the processed Citrus reticulata peel or Citrus reticulata peel extract is as follows: take Citrus reticulata peel or Citrus reticulata peel extract raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the processed product; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

10. Application of Citrus reticulata peel or Citrus reticulata peel extract in the preparation of weight-reducing products; the preparation method of Citrus reticulata peel or Citrus reticulata peel extract is as follows: take Citrus reticulata peel or Citrus reticulata peel raw material, mix with a sodium bicarbonate aqueous solution or sodium carbonate aqueous solution with a mass-volume concentration of 0.5-10%, soak at 50-90℃ for 6-72 h, and then dry to obtain the extract; wherein, The weight-to-volume ratio of the raw material to the sodium bicarbonate aqueous solution or sodium carbonate aqueous solution is 1 g: (2~6) mL.

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