Process for the preparation of compound ss-23 and use thereof for the preparation of a medicament for the prevention and / or treatment of atherosclerosis

Abstract

The application provides a preparation method of a compound SS-23 and an application of the compound SS-23 in preparing medicines for preventing and / or treating atherosclerosis, and belongs to the technical field of chemical medicines. The compound SS-23 is a compound shown in formula I or a pharmaceutically acceptable salt thereof. The phenolic acid glyceride compound SS-23 is obtained by separation and purification from Sparganium stoloniferum Buch. The compound can play a role in preventing and / or treating atherosclerosis by regulating blood lipid levels, reducing plaque area and improving blood vessel function. The compound SS-23 has significant potential in preventing and / or treating atherosclerosis, provides a new treatment strategy for clinic, and has a good application prospect. Formula I.

Description

Technical Field

[0001] This invention belongs to the field of chemical pharmaceutical technology, specifically relating to the preparation method of compound SS-23 and its use in the preparation of drugs for the prevention and / or treatment of atherosclerosis. Background Technology

[0002] Cardiovascular disease (CVD) is the leading cause of death worldwide, seriously endangering public health. Atherosclerosis (AS) is the common pathological basis of most cardiovascular diseases. Its main characteristics are lipid deposition under the arterial intima, accompanied by chronic inflammatory response, smooth muscle cell proliferation and migration, and fibrous cap formation, ultimately forming atherosclerotic plaques, leading to narrowing and hardening of the vascular lumen, and causing serious events such as myocardial infarction and stroke.

[0003] In the clinical treatment of atherosclerosis, statins and antiplatelet drugs (such as aspirin) are currently the main first-line treatment options. Statins effectively reduce plasma cholesterol levels and stabilize plaques by inhibiting cholesterol synthesis in hepatocytes and upregulating low-density lipoprotein (LDL) receptors, and have been proven to significantly reduce the incidence of cardiovascular events. However, this type of drug treatment also has significant limitations: first, some patients experience side effects such as elevated liver enzymes, muscle pain, and even rhabdomyolysis, leading to discontinuation of the drug; second, there is a phenomenon of "statin resistance"; more importantly, even with intensive statin therapy, many patients still have significant residual cardiovascular risk, which is closely related to other pathological mechanisms such as persistent inflammatory responses.

[0004] In Traditional Chinese Medicine (TCM) theory, atherosclerosis is often categorized under "blood stasis," "phlegm turbidity," and "pulse obstruction," with its pathogenesis considered to hinge on impaired blood and qi circulation and blood stasis obstructing the meridians. Therefore, TCM herbs that promote blood circulation and remove blood stasis are frequently used in clinical practice for prevention and treatment, demonstrating unique advantages. Sparganium rhizome ( Sparganium stoloniferum As a common blood-activating and stasis-removing medicine, it has shown great potential in the treatment of atherosclerosis. If an active ingredient with the potential to treat atherosclerosis could be isolated from *Sparganium stoloniferum*, it would be of great value for clinical treatment of atherosclerosis. Summary of the Invention

[0005] The purpose of this invention is to provide a method for preparing compound SS-23 and its use in the preparation of medicaments for the prevention and / or treatment of atherosclerosis.

[0006] This invention provides the use of compounds of Formula I or pharmaceutically acceptable salts thereof in the preparation of medicaments for the prevention and / or treatment of atherosclerosis:

[0007]

[0008] Formula I.

[0009] Furthermore, the drug is a drug that improves blood lipid levels, promotes the regression of atherosclerotic plaques, and / or improves vascular function.

[0010] Furthermore, the improvement of blood lipid levels refers to reducing the levels of total cholesterol, triglycerides, and / or low-density lipoprotein cholesterol in the serum, and / or increasing the levels of high-density lipoprotein cholesterol in the serum.

[0011] Furthermore, the promotion of atherosclerotic plaque regression includes reducing the area of ​​aortic atherosclerotic plaques, reducing the area of ​​the necrotic core within atherosclerotic plaques, and / or inhibiting collagen fiber deposition within atherosclerotic plaques.

[0012] Furthermore, the improvement in vascular function refers to reducing arterial stiffness and / or inhibiting the formation of arterial plaques.

[0013] Preferably, the reduction of arterial stiffness refers to reducing the pulse wave conduction velocity level at the aortic root.

[0014] Furthermore, the drug is a formulation prepared by using a compound of Formula I or a pharmaceutically acceptable salt thereof as the active ingredient, plus pharmaceutically acceptable excipients or auxiliary ingredients.

[0015] Furthermore, the formulation is a liquid formulation, a solid formulation, a semi-solid formulation, or a gaseous formulation.

[0016] The present invention also provides a method for preparing the compound shown in Formula I, comprising the following steps:

[0017] (1) Weigh the three-edged medicinal material, crush it, add ethanol, heat and reflux to extract it, and then remove the solvent from the extract under reduced pressure to obtain ethanol extract.

[0018] (2) Add ultrapure water to the ethanol extract and disperse it evenly. Then extract with ethyl acetate. The solvent of the ethyl acetate extract is recovered under reduced pressure to obtain ethyl acetate extract.

[0019] (3) The ethyl acetate extract was separated by silica gel column chromatography. The petroleum ether-ethyl acetate mixed solvent was used for gradient elution. The volume ratio of petroleum ether to ethyl acetate in the elution system was 50:1, 40:1, 30:1, 20:1, 10:1, 1:1 and 0:1, respectively. The elution volume of each gradient was 10 times the column volume. During the elution process, every 500 mL of eluent was collected as one fraction. The eluents containing similar components were combined to obtain 17 elution fractions. The 8th elution fraction was concentrated under reduced pressure. After the solvent was recovered, the target component SR8 was obtained.

[0020] (4) Take component SR8 and use a reversed-phase C18 column to perform gradient elution with methanol-water mixed solvent as the mobile phase. The volume ratio of methanol to water is 10:90, 30:70, 50:50, 60:40, 80:20, and 100:0. Collect the eluted portion corresponding to the volume ratio of methanol to water of 30:70 in the mobile phase and record it as SR8-2.

[0021] (5) After solvent recovery of SR8-2, it was separated and purified by reversed-phase preparative liquid chromatography. The mobile phase was 60% methanol aqueous solution, the flow rate was set to 2.5 mL / min, the detection wavelength was 254 nm, and the chromatographic peak fraction with a retention time of 17.7 min was collected to obtain the compound shown in Formula I.

[0022] The compound of formula I is shown below:

[0023]

[0024] Formula I.

[0025] Furthermore,

[0026] In step (1), the amount of ethanol used is 6 to 8 times that of the Sparganium rhizome.

[0027] And / or, in step (1), the heating reflux extraction time is 3~5h;

[0028] And / or, in step (2), the mass ratio of the ethanol extract to ultrapure water is 1:(1~5).

[0029] And / or, in step (2), during the extraction, the mass ratio of ethanol extract to ethyl acetate is 1:(1~5).

[0030] And / or, in step (2), the extraction is performed 3 to 10 times.

[0031] Furthermore,

[0032] In step (1), the ethanol is anhydrous ethanol;

[0033] And / or, in step (1), the amount of ethanol used is 6 times that of the Sparganium rhizome;

[0034] And / or, in step (1), the heating reflux extraction time is 3 hours;

[0035] And / or, in step (2), the mass ratio of the ethanol extract to ultrapure water is 1:1;

[0036] And / or, in step (2), during the extraction, the mass ratio of ethanol extract to ethyl acetate is 1:1;

[0037] And / or, in step (2), the extraction is performed 6 times.

[0038] Compared with the prior art, the present invention has achieved the following beneficial effects:

[0039] This invention discloses a phenolic glyceride compound (SS-23) isolated and purified from *Pteris vittata*. This compound can prevent and / or treat atherosclerosis by regulating blood lipid levels, reducing plaque area, and improving vascular function. Specifically, it reduces serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels while increasing high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, Doppler ultrasound examination revealed that SS-23 significantly improves vascular function, reduces arterial stiffness, and inhibits plaque formation. Pathological analysis further indicates that SS-23 significantly reduces plaque area in the aorta (grossly) and its root, and reduces collagen deposition in the aortic root, thereby effectively delaying the progression of atherosclerosis. The compound SS-23 of this invention has significant potential in the prevention and / or treatment of atherosclerosis, providing a new treatment strategy for clinical application and showing promising prospects.

[0040] Obviously, based on the above description of the present invention, and according to common technical knowledge and conventional methods in the field, various other modifications, substitutions or alterations can be made without departing from the basic technical concept of the present invention.

[0041] The following detailed embodiments further illustrate the above-described content of the present invention. However, this should not be construed as limiting the scope of the present invention to the following embodiments. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Attached Figure Description

[0042] Figure 1 The image shows the HR-ESI-MS spectrum of compound SS-23.

[0043] Figure 2 For compound SS-23 1 H-NMR spectrum.

[0044] Figure 3 For compound SS-23 13 C-NMR spectrum.

[0045] Figure 4 The results of Oil Red O staining of the aorta in mice treated with compound SS-23 and the statistical diagram of plaque area are shown.

[0046] Figure 5The image shows the HE, Masson's red, and Sirius red staining results of the aortic root in mice treated with compound SS-23 for atherosclerosis.

[0047] Figure 6 A statistical graph showing the HE, Masson's red, and Sirius red staining results of the aortic root in mice treated with compound SS-23 for atherosclerosis.

[0048] Figure 7 The figure shows the serum total cholesterol (TC), serum triglycerides (TG), serum low-density lipoprotein cholesterol (LDL-C), and serum high-density lipoprotein cholesterol (HDL-C) levels in mice treated with compound SS-23 for atherosclerosis.

[0049] Figure 8 Echocardiogram and aortic pulse wave velocity (PWV) results of mice treated with compound SS-23 for atherosclerosis. Detailed Implementation

[0050] The raw materials and equipment used in the specific embodiments of the present invention are all known products, obtained by purchasing commercially available products.

[0051] Example 1, 1-O-feruloyl-3-O- p Extraction, separation, purification and structural identification of coumaroyl glycerol (compound SS-23)

[0052] 1. Experimental materials

[0053] (1) Medicinal materials

[0054] The Sparganium rhizome was purchased from Sichuan Provincial Traditional Chinese Medicine Pieces Co., Ltd., and is classified as Sparganium rhizome (family Sparganaceae). Sparganium stoloniferum The dried tubers of Buch.-Ham. meet the pharmacopoeia standards for medicinal materials.

[0055] (2) Reagents and fillers

[0056] Column chromatography silica gel, 200-300 mesh (reagent grade), purchased from Qingdao Marine Silica Gel Desiccant Factory;

[0057] GF Chromatography Silica Plate 254 Purchased from Anhui Liangchen Silicon Source Materials Co., Ltd.

[0058] Octadecylsilane-bonded silica filler, 50 μm, purchased from Shanghai Jinpan Biotechnology Co., Ltd.

[0059] Chromatographic methanol, 4L / bottle, purchased from Sigma-Aldrich, USA;

[0060] Analytical grade reagents such as petroleum ether, ethyl acetate, methanol, and dichloromethane were purchased from Chengdu Kelong Chemical Co., Ltd.

[0061] The deuterated reagent was purchased from CIL Corporation, USA.

[0062] (3) Experimental instruments

[0063] Bruker high-resolution mass spectrometer (Bruker GmbH, Germany).

[0064] Bruker Avance NEO 600 nuclear magnetic resonance spectrometer (Bruker, Switzerland).

[0065] Agilent 1220 semi-preparative high performance liquid chromatograph (Agilent Technologies, USA);

[0066] Rudolph Autopol I automatic polarimeter (Rudolph Corporation, USA).

[0067] SQP-Sartorius analytical balance (Sartorius GmbH, Germany);

[0068] RE-52A rotary evaporator (Shanghai Yarong Biochemical Instrument Factory).

[0069] 2. Extraction of medicinal materials and separation and purification of components

[0070] (1) Weigh 50 kg of Sparganium rhizome, crush it, add 6 times the amount of anhydrous ethanol, heat and reflux for 3 h, and then remove the solvent from the extract under reduced pressure to obtain ethanol extract.

[0071] (2) Weigh an appropriate amount of ethanol extract, add ultrapure water of the same mass as the extract, and vortex thoroughly to disperse it evenly to prepare a stable suspension system; then use ethyl acetate of the same mass as the extract as the extraction solvent to perform liquid-liquid extraction on the suspension system, repeat the extraction operation 6 times, and combine all ethyl acetate extract phases; transfer the combined extract to a rotary evaporator, and distill and concentrate it under reduced pressure to recover the solvent, and finally obtain ethyl acetate extract.

[0072] (3) The ethyl acetate extract was separated by silica gel column chromatography using a gradient elution with a petroleum ether-ethyl acetate mixed solvent. The volume ratios of petroleum ether to ethyl acetate in the elution system were 50:1, 40:1, 30:1, 20:1, 10:1, 1:1, and 0:1, with each gradient elution volume being 10 column volumes (CV). During elution, 500 mL of eluent was collected as one fraction. Subsequently, thin-layer chromatography (TLC) was used to trace the components of each fraction. The TLC conditions were: silica gel GF... 254The plate was developed using a dichloromethane-methanol system as the developing solvent, with color development achieved by spraying a 10% sulfuric acid-ethanol solution. Eluents containing similar components (with similar Rf values) were combined, resulting in 17 eluent fractions. The 8th eluent fraction was concentrated under reduced pressure, and after solvent recovery, the target component SR8 was obtained.

[0073] (4) Take component SR8 and elute it using a reversed-phase C18 column. Use methanol-water as the mobile phase and perform gradient elution at the following ratios (v / v): 10:90, 30:70, 50:50, 60:40, 80:20, 100:0. Collect the eluent corresponding to 30% methanol (i.e., methanol-water = 30:70) in the mobile phase, and denote it as SR8-2. After solvent recovery of SR8-2, further separate and purify the target sample using reversed-phase preparative liquid chromatography. Use 60% methanol-water as the mobile phase, set the flow rate to 2.5 mL / min, the detection wavelength to 254 nm, and collect the chromatographic peak fraction with a retention time of 17.7 min to obtain the target product (compound SS-23).

[0074] 3. Structural identification of components

[0075] The target product was a pale yellow oil; it turned yellow when sprayed with a 10% sulfuric acid ethanol solution at 105°C; according to HRESIMS m / z 437.1209 [M + Na] + The molecular formula can be determined to be C. 22 H 22 O8.

[0076] 4. Proton nuclear magnetic resonance spectrum (NMR) 1 H-NMR and carbon spectroscopy (H-NMR) 13 C-NMR data:

[0077] Spectral data were measured using a Bruker-AVIIIHD 600 spectrometer. Specific spectral data are shown below: 1 H NMR (CD3OD, 600 MHz): δ H 7.66 (2H, d, J = 16.0, H-7′, H-7″), 7.44 (2H, d, J = 8.0, H-2″and H-6″), 7.18 (1H, br s, H-2′), 7.07 (1H, d, J = 8.4, H-5′), 6.80 (1H, br d, J = 8.4, H-6′), 6.79 (2H, d, J= 8.0, H-3″ and H-5″), 6.40 (1H, d, J = 16.0, H-8′), 6.36 (1H, d, J = 16.0, H-8″), 4.29 (4H, overlap, H2-1, H2-3), 4.17 (1H, m, H-2)and 3.87 (3H, s, OMe); 13 C NMR (CD3OD, 150 MHz): δ C 66.4 (C-1), 68.6 (C-2), 66.4(C-3), 127.1 (C-1′), 111.7 (C-2′), 150.7 (C-3′), 161.3 (C-4′), 124.5(C-5′),116.5 (C-6′), 147.2 (C-7′), 115.1 (C-8′), 169.0 (C-9′), 127.7 (C-1″), 116.8(C-2″), 131.2 (C-3″), 149.4 (C-4″), 131.2 (C-5″), 116.8 (C-6″), 147.0 (C-7″),114.8 (C-8″), 169.0 (C-9″) and 56.4 (OMe).

[0078] The HR-ESI-MS spectrum of the target product (compound SS-23) is shown below. Figure 1 As shown, 1 H-NMR spectrum as shown Figure 2 As shown, 13 C-NMR spectrum as shown in Figure Figure 3 As shown.

[0079] The structure of the target product (compound SS-23) is shown below:

[0080] .

[0081] Example 2, APOE - / - Mouse atherosclerosis experiment

[0082] 1. Experimental materials

[0083] (1) Reference standard

[0084] Atorvastatin was purchased from Chengdu Pusi Biotechnology Co., Ltd.

[0085] (2) Drugs

[0086] Accurately weigh the 1-O-feruloyl-3-O- prepared in Example 1 p - Coumaroyl glycerol (compound SS-23) and the positive control drug atorvastatin were placed in 10 mL EP tubes, dissolved in a mixed solvent (composed of 2% DMSO, 40% PEG300 and 58% physiological saline), vortexed, and sonicated for 10 min to ensure thorough vortexing, thus preparing SS-23 solutions with concentrations of 1 mg / mL and 2 mg / mL, and an atorvastatin solution with a concentration of 1 mg / mL. The gavage administration volume was 0.1 mL / 10 g (i.e., the dosage of SS-23 was 10 mg / kg and 20 mg / kg, and the dosage of atorvastatin was 10 mg / kg).

[0087] (3) Animals

[0088] C57BL / 6J mice and ApoE - / - Male mice, 20 g ± 2 g, were purchased from Vital Rivers (Sichuan) Laboratory Animal Technology Co., Ltd., approval number: SCXK(Sichuan)2023-0040. This experiment was approved by the Animal Experiment Ethics Committee of Chengdu University of Traditional Chinese Medicine, experimental animal license number: SYXK(Sichuan)2025-0294. ApoE - / - The mouse is a mouse model in which the apolipoprotein E (APOE) gene is knocked out through genetic engineering. It is one of the most commonly used animal models for studying atherosclerosis.

[0089] (4) Reagents

[0090] PEG300 (Selleck, batch number: S670425);

[0091] DMSO (Boster Biological Engineering Co., Ltd., Batch No.: 20B17B40);

[0092] Physiological saline (Sichuan Kelun Pharmaceutical Co., Ltd., batch number: N24120317);

[0093] Serum biochemistry kits (TC, TG, LDL-C, HDL-C, AST, ALT, purchased from Shenzhen Mindray Bio-Medical Electronics Co., Ltd., batch numbers: ZD04ZTDP5357);

[0094] 4% Paraformaldehyde (Beijing Lanjieke Technology Co., Ltd., batch number: 23237838);

[0095] Saturated Oil Red O staining solution (Wuhan Sewell Biotechnology Co., Ltd., batch number: 2503E043);

[0096] 1% Sodium Pentobarbital (Sigma-Aldrich, Inc., USA, Batch No.: 230203);

[0097] D12108C high-fat diet (Research Diets, batch number: 25031304A2-CD).

[0098] (5) Experimental instruments

[0099] Animal blood biochemistry analyzer (Shenzhen Mindray Bio-Medical Electronics Co., Ltd.);

[0100] Allegra X-12R centrifuge (Beckman Coulter, Inc., USA);

[0101] Upright optical microscope (Nikon Corporation, Japan);

[0102] Imaging system (Nikon Corporation, Japan);

[0103] High-resolution small animal ultrasound imaging system (Fujifilm Visualsonics, Canada).

[0104] 2. Experimental Methods

[0105] C57BL / 6J wild-type mice and males in the C57BL / 6J background were compared. ApoE − / − After acclimatizing to a standard diet for one week, the 8-week-old mice were divided into 5 groups. Wild-type C57BL / 6J mice were in the normal group and fed a standard diet for 14 weeks. ApoE − / − Mice were randomly divided into four groups: a model group (HFD), a low-dose SS-23 group (10 mg / kg / d), a high-dose SS-23 group (20 mg / kg / d), and a positive control group (atorvastatin, 10 mg / kg / d). All mice were fed a high-fat diet (HFD) for 14 weeks while simultaneously receiving the drug. Mice in the low-dose, high-dose, and positive control groups were administered the drug via gavage once daily for 14 weeks, while mice in the normal and HFD groups received an equal volume of the drug. Body weight was recorded twice weekly. Echocardiographic analysis was performed before the end of the experiment. After the experiment, all mice were fasted for 12 hours and then anesthetized with sodium pentobarbital. Relevant tissues were collected and stored at -80°C for further analysis.

[0106] (1) Echocardiography

[0107] Ultrasound imaging was used to assess aortic function in mice. Mice were anesthetized with isoflurane and fixed in a supine position on a temperature-controlled imaging table. B-mode, M-mode, and Doppler blood flow spectra of the aortic arch were then acquired using a Vevo 2100 high-resolution small animal ultrasound imaging system (equipped with a Vevo MS550D probe). All image data were processed using Vevo Vasc professional analysis software to calculate the aortic arch pulse wave velocity (PWV).

[0108] (2) Gross Oil Red O staining of the aorta

[0109] After dissection and dissection, aortic samples were fixed with 4% paraformaldehyde. Following fixation, the samples were rinsed with PBS or 60% isopropanol, then immersed in freshly prepared Oil Red O working solution for staining in the dark for 10-15 minutes. Subsequently, differentiation was performed using 60% isopropanol until the background was clean and the lipid plaques were clearly visible. Finally, the samples were rinsed with distilled water, revealing that the atherosclerotic plaques on the arterial intima were stained bright red, and photographs were taken for recording.

[0110] (3) Preparation and observation of aortic tissue pathology

[0111] Aortic root tissue was taken from five mice in each group, fixed with 4% paraformaldehyde, embedded in paraffin, sectioned, and dried.

[0112] Hematoxylin-eosin (HE) staining: Dewax with xylene (I, II), then rinse and rehydrate sequentially with 95% ethanol (I, II), 80% ethanol, 70% ethanol, and distilled water. Next, immerse the sections in Harris hematoxylin staining solution for 3-8 minutes, then rinse with running water and differentiate with 1% hydrochloric acid alcohol for a few seconds. Finally, return to blue with 0.6% ammonia. Stain with eosin for 1-3 minutes and rinse with distilled water to complete cytoplasmic staining. After staining, mount the slides.

[0113] Masson staining: Dewax using xylene I for 20 minutes x 3 times, followed by rehydration with 100%, 95%, 80%, 70% and distilled water respectively. Stain with Weigert's iron hematoxylin solution or Regaud's hematoxylin solution for 5-10 minutes; then treat with 1% hydrochloric acid alcohol or acidic ethanol (0.2% glacial acetic acid + weak acid) for a few seconds until light brown, to distinguish muscle fibers from collagen fibers; blue again with 1% concentrated ammonia water or a weak acid solution (such as 0.1-0.3% acetic acid) for 3-5 minutes to enhance the blue color of collagen fibers; stain with Masson's Ponceau S acid fuchsin solution for 5-10 minutes, then wash with weak acid for 1 minute; treat with 1% phosphomolybdic acid aqueous solution for 3-5 minutes, then wash with weak acid for 1-2 minutes; counterstain directly with aniline blue or light green solution for 1-2 minutes, without washing. Mount the slide after staining.

[0114] Sirius red staining: Dewaxing and washing are performed sequentially using xylene (I→II), anhydrous ethanol (I→II), 95%-70% alcohol, and distilled water until a clear state is achieved. The dewaxed sections are then immersed in a saturated picric acid-Sirius red staining solution, typically for 1 hour. After staining, differentiation and dehydration are performed directly with ethanol, specifically: 75%-95% ethanol for 1 minute each → anhydrous ethanol for 1 minute → xylene (I→II) for 1-2 minutes each. The sections are then mounted after staining.

[0115] Observe pathological tissue sections under a microscope.

[0116] (4) Detection of biochemical indicators in mouse serum using a blood biochemistry analyzer

[0117] After the animal experiments were completed, mice were anesthetized with sodium pentobarbital, and whole blood samples were collected via the orbital venous plexus. The samples were left at room temperature for 2 hours, and then centrifuged at 3000 rpm for 15 minutes at 4°C to separate the serum. Finally, the concentrations of AST, ALT, TC, TG, HDL-C, and LDL-C in the serum were determined using a fully automated biochemical analyzer and matching reagent kits manufactured by Shenzhen Mindray Bio-Medical Electronics Co., Ltd. All procedures were strictly performed according to the kit instructions.

[0118] 3. Experimental Results and Evaluation

[0119] Figure 4 The results of Oil Red O staining of the aorta in mice treated with compound SS-23 and the statistical diagram of plaque area are shown. Figure 4 The normal group had a high-fat diet, SS-23, and atorvastatin all being "-", the model group had a high-fat diet, SS-23, and atorvastatin all being "-", the positive drug group had a high-fat diet, SS-23 was "10", and atorvastatin was "-", the low-dose SS-23 group had a high-fat diet, SS-23 was "20", and atorvastatin was "-", the high-dose SS-23 group. Figure 4 The symbol #### indicates that compared with the normal group, P < 0.0001; This indicates that, compared to the model group, P < 0.0001. Figure 4 The results showed that a large amount of lipid deposition was visible in the aortic wall of the model group, and both atorvastatin and compound SS-23 could effectively reduce lipid deposition. The effects of compound SS-23 and atorvastatin were comparable.

[0120] Figure 5 and Figure 6 HE, Masson's red, and Sirius red staining results of the aortic root of mice treated with compound SS-23, along with statistical results. Figure 5The blank control group corresponds to the normal group, the high-fat diet group corresponds to the model group, the atorvastatin group corresponds to the positive drug group, SS-23 (10mg / kg) corresponds to the low-dose SS-23 group, and SS-23 (20mg / kg) corresponds to the high-dose SS-23 group. Figure 6 The representation methods of each group in the middle and Figure 4 same. Figure 6 In the figure, #### indicates that compared with the normal group, P < 0.0001; This indicates that compared to the model group, P < 0.05; This indicates that compared to the model group, P < 0.01; This indicates that compared to the model group, P < 0.001; The results showed that, compared with the model group, P < 0.0001. HE staining revealed abundant cholesterol crystal deposition, foam cell aggregation, and a significant necrotic core area in the aortic root of the model group; while the atorvastatin and SS-23 treatment groups showed significantly reduced pathological changes and a marked reduction in necrotic area. Masson and Sirius red staining further indicated a significant increase in collagen fiber content within the plaques of the model group, suggesting increased plaque vulnerability; after SS-23 intervention, collagen fiber deposition decreased. These results demonstrate that compound SS-23 can effectively reduce collagen fiber deposition and plaque area in atherosclerosis, thus improving atherosclerosis.

[0121] Figure 7 The graph shows the results of TC, TG, LDL-C and HDL-C levels in mice treated with compound SS-23 for atherosclerosis. Figure 7 The representation methods of each group in the middle and Figure 4 same. Figure 7 In the table, # indicates that compared with the normal group, P < 0.05; ## indicates that compared with the normal group, P < 0.01; #### indicates that compared with the normal group, P < 0.0001. This indicates that compared to the model group, P < 0.05; This indicates that compared to the model group, P < 0.001; This indicates that, compared to the model group, P < 0.0001. Figure 7 The results showed that, compared with the model group, all dose groups of SS-23 significantly improved blood lipid levels, with a significant decrease in TC, TG and LDL-C, and an increase in HDL-C, indicating that SS-23 has good lipid-lowering activity.

[0122] Figure 8 Echocardiogram and aortic pulse wave velocity (PWV) results of mice treated with compound SS-23 for atherosclerosis. Figure 8 The representation methods of each group in the middle and Figure 4 same. Figure 8In the figure, #### indicates that compared with the normal group, P < 0.0001; The result indicates that, compared with the model group, P < 0.0001. The occurrence and development of atherosclerosis are closely related to vascular structure and function. Doppler ultrasound examination revealed that the aortic arch pulse wave velocity (PWV) was increased in the model control group, indicating increased aortic stiffness and decreased elasticity. SS-23 administration significantly improved vascular function, reduced arterial stiffness, and delayed plaque formation.

[0123] The above experimental results show that the compound SS-23 of this invention exhibits clear pharmacological activity in the treatment of atherosclerosis, has good development potential, and provides a new candidate compound for clinical screening and preparation of anti-atherosclerotic drugs.

[0124] In summary, the phenolic acid glyceride compound (SS-23) isolated and purified from *Sparganium stoloniferum* in this invention can prevent and / or treat atherosclerosis by regulating blood lipid levels, reducing plaque area, and improving vascular function. Compound SS-23 of this invention has significant potential in the prevention and / or treatment of atherosclerosis, providing a new treatment strategy for clinical application and showing promising prospects.

Claims

1. Use of the compound of Formula I or a pharmaceutically acceptable salt thereof in the preparation of medicaments for the prevention and / or treatment of atherosclerosis: Formula I.

2. The use according to claim 1, characterized in that: The drug is a formulation prepared by using a compound of Formula I or a pharmaceutically acceptable salt thereof as the active ingredient, plus pharmaceutically acceptable excipients or auxiliary ingredients.

3. The use according to claim 2, characterized in that: The formulation may be a liquid formulation, a solid formulation, a semi-solid formulation, or a gaseous formulation.

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