Camellia nitidissima terpenoid, extraction method thereof and application of camellia nitidissima terpenoid in preparation of ACL inhibitor

Abstract

The invention discloses a camellia chrysantha terpenoid, an extraction method thereof and application of the camellia chrysantha terpenoid in preparation of an ACL inhibitor, and belongs to the field of biological medicine, and the terpenoid (the structure is shown in the following formula 1 and formula 2) is separated from branches and leaves of camellia camellia plant camellia chrysantha of the theaceae family, the compound 1 is guaiane type sesquiterpene lactone, and the compound 2 is guaiane type sesquiterpene lactone. And the compound 2 is an ursane type triterpenoid compound. Multiple in-vitro activity tests show that the two terpenoids have significant ATP-citrate lyase inhibitory activity, and can be applied to preparation of drugs for preventing, delaying or treating ACL-mediated glucose and lipid metabolism disorders and other related diseases. The compound provided by the invention can also provide a lead compound for research and development of novel drugs for diseases related to glucose and lipid metabolism disorders.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to two terpenoid compounds isolated from Camellia petelotii (Merr.) Sealy, a plant of the genus Camellia in the family Theaceae, their preparation methods, and their use in the preparation of ACL inhibitors. Background Technology

[0002] ATP-citrate lyase (ACL) is a key enzyme in carbohydrate metabolism and the biosynthesis of fatty acids and cholesterol. The human ACL protein is a homotetramer composed of four identical 120 kDa subunits (Singh et al., J. Biol. Chem. 1976, 251:5254-5250). The main function of ACL is to hydrolyze citrate produced and transported from mitochondria into acetyl-CoA and oxaloacetate (Beigneux et al., J. Biol. Chem. 2004, 279:9557-9564). Acetyl-CoA can then serve as a substrate for de novo cholesterol synthesis. This demonstrates that ACL is closely related to the synthesis of fatty acids and cholesterol, and its expression level is closely associated with hyperlipidemia and the cardiovascular diseases (CVDs) it causes (Granchi, Expert Opin. Ther. Pat. 2022, 32:731-742; Verbark et al, Trends Mol. Med. 2021, 27:1095-1105; Burke et al., Curr. Opin. Lipidol. 2017, 28:193-200). Simultaneously, abnormal triglyceride metabolism also increases the risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD) and type II diabetes mellitus (T2DM) (Eslam et al., Hepatol. Int. 2025, 19:261-30). Therefore, ACL can also serve as a potential therapeutic target for MAFLD and T2DM (Morrow et al, CellMetab. 2022, 7, 34: 919-936; Armstrong et al., Hepatology 2014, 59: 1174-1197; Cohenet et al, Science 2011, 332: 1519-1523.).

[0003] As a novel drug target for disorders of glucose and lipid metabolism, ACL has become a hot topic in innovative drug research in recent years. With the widespread use of high-throughput screening technologies, many types of small-molecule ACL inhibitors have been discovered. However, currently only bempedoic acid, an ACL small-molecule inhibitor developed by Esperion Therapeutics (ESPR) in the United States, has been approved by the FDA for the treatment of hypercholesterolemia and atherosclerotic cardiovascular disease. Apart from bempedoic acid, the development of other ACL inhibitors is limited due to their low cell penetration, low affinity for ACL, and lack of specificity. Therefore, finding highly efficient, selective, and pharmacokineticly favorable small-molecule ACL inhibitors is of great significance and has broad application prospects for the treatment of disorders of glucose and lipid metabolism and cardiovascular diseases.

[0004] Natural products, characterized by structural complexity and diversity, are a crucial source for new drug discovery. The unique chemical structures of natural products and their derivatives offer advantages such as low toxicity, high efficacy, high selectivity for specific targets, and potentially unique mechanisms of action (Atanasov et al., Nat. Rev. Drug Discov. 2021, 20:200-216; Newman et al., J. Nat. Prod. 2020, 83:770-803; Tiago et al., Nat. Chem. 2016, 8:531-541). Meanwhile, single-target drugs often have poor efficacy, while traditional Chinese medicine / herbal medicines and their components possess novel structures (chemical components), multiple targets, and multiple pathways of action, offering unique advantages in treating complex diseases. Therefore, identifying and developing novel, highly effective, and low-toxicity ACL inhibitors from natural sources (especially plant-based chemical components) is of significant research value. Natural products with unique sources and structural characteristics are expected to gain an advantage in the current fierce competition for new drugs in the field of glucose and lipid metabolism disorders. Statistical analysis of the natural sources of drug molecules revealed that drug molecules derived from terrestrial plants are concentrated in specific families (active natural products originate from 792 out of 6763 families in nature, accounting for only 11.7%), and marketed drugs and clinical-stage candidate drugs are concentrated in 144 of these families. The vast majority of rare and endangered plants are clearly found within these drug-producing plant families and genera (Zhu et al., Proc. Natl. Acad. Sci. USA 2011, 108: 12943-12948; Mohamed et al., Proc. Natl. Acad. Sci. 2013, 110: 16832-16837.). This demonstrates that the novelty and drug potential of natural products from rare and endangered plants are far higher than the average level of those from general plants.

[0005] Golden camellia (scientific name: *Camellia petelotii*) is an evergreen shrub belonging to the genus *Camellia* in the family Theaceae. It is a rare and endangered ornamental plant, currently a Class I protected plant in China. The tree grows to 2–5 meters tall, with sparse branches, pale grayish-yellow bark, and dark green, narrowly oblong leaves. The flowers are golden yellow. Golden camellia is a common traditional medicine and is also considered a novel food. This plant, used for both medicinal and edible purposes, exhibits various pharmacological effects, including antioxidant, anticancer, antibacterial, hypoglycemic, hypolipidemic, immunomodulatory, anti-allergic, anti-anxiety, and antidepressant effects (Wu et al., Foods 2023, 12:3010). Currently, only a few triterpenoid saponins with α-glucosidase inhibitory activity have been reported from C. petelotii (Cuc et al., Chem. Biodivers. 2023, 20:e202300093; CN 115403648 B, 20221129), and their chemical composition still needs further research. Summary of the Invention

[0006] This application involves the protective harvesting of Camellia chrysantha branches and leaves, and the isolation of terpenoid compounds (structures shown in Formulas 1 and 2) from the ethyl acetate fraction of the methanol extract of Camellia chrysantha branches and leaves. Compound 1 is a guaiacolane-type sesquiterpene lactone, a novel compound, while compound 2 is a ursane-type triterpenoid compound, previously isolated from Camellia ptilosperma (Ma et al., Molecules 2023, 28:7058). Pharmacological studies have revealed for the first time that both compounds exhibit significant ACL inhibitory activity. This suggests potential therapeutic effects on hyperlipidemia, atherosclerosis, fatty liver, type II diabetes, and other ACL-mediated diseases, thus possessing significant potential applications in the pharmaceutical field.

[0007] Based on the isolated compounds and the medicinal value of the compounds discovered through research, this application first provides a terpenoid compound, namely a guaiacolane-type sesquiterpene lactone and a triterpenoid compound (ursane-type triterpenoid). The structure of the guaiacolane-type sesquiterpene lactone is shown in Formula 1 (hereinafter also referred to as Compound 1), and the structural formula of the triterpenoid compound is shown in Formula 2 (hereinafter also referred to as Compound 2):

[0008]

[0009] This application also provides the use of the aforementioned terpene compound in the preparation of ATP-citrate lyase inhibitors. Either compound shown in Formula 1 or Formula 2 can be used in the preparation of ATP-citrate lyase inhibitors, or two compounds can be used in combination.

[0010] This application also provides the use of the aforementioned terpenoid compounds in the preparation of drugs for the prevention, delay, or treatment of diseases mediated by ATP-citrate lyase. Either compound shown in Formula 1 or Formula 2 may be used, or two compounds may be used in combination.

[0011] Optionally, the disease is a disorder of glucose and lipid metabolism and its complications; further, the disease is hyperlipidemia, atherosclerosis, fatty liver, or type II diabetes.

[0012] Based on the advantages of novel chemical structure and biological activity, this type of compound has great development prospects and is expected to be developed into novel therapeutic drugs or lead compounds for ACL-mediated diseases.

[0013] This application also provides a pharmaceutical composition in which the active ingredient is a compound of Formula 1 or a combination of compounds of Formula 1 and Formula 2. The composition comprises a pharmaceutically effective amount of compound 1 or a combination of compound 1 and compound 2.

[0014] Optionally, pharmaceutically acceptable excipients may also be included, such as carriers, excipients, adjuvants, or diluents. This drug combination may be used to develop drugs for the prevention, delay, or treatment of ACL-mediated glucose and lipid disorders (particularly hyperlipidemia and its associated cardiovascular diseases) or as a lead compound for such drugs.

[0015] This application also provides a method for extracting the terpenoid compounds, wherein dried Camellia chrysantha branches and leaves are air-dried and pulverized at room temperature, and extracted once or multiple times at room temperature with a methanol-water solution of 70% or higher concentration. The extract is concentrated, suspended in water, and extracted sequentially with petroleum ether and ethyl acetate to obtain a petroleum ether extract and an ethyl acetate extract. The ethyl acetate extract is concentrated under reduced pressure and then subjected to silica gel column chromatography and MCI column chromatography, followed by separation by Sephadex LH-20 gel electrophoresis and reversed-phase semi-preparative high-performance liquid chromatography to obtain the terpenoid compounds shown in Formula 1 and Formula 2.

[0016] Specifically:

[0017] S1: Dry the dried Camellia chrysantha branches and leaves at room temperature, pulverize them, and extract them once or multiple times at room temperature with a methanol-water solution of 70% or higher concentration. Concentrate the extract, suspend it in water, and extract it three times each with equal volumes of petroleum ether, ethyl acetate, and n-butanol to obtain four components: petroleum ether, ethyl acetate, n-butanol, and water.

[0018] S2: The ethyl acetate component was eluted by silica gel column chromatography with a petroleum ether-ethyl acetate gradient to obtain 6 components Fr.1-~Fr.6.

[0019] Optionally, the methanol-water solution used for methanol extraction is a 90% methanol-water solution, i.e., a methanol-water solution with a volume ratio of 90:10.

[0020] Optionally, the methanol-water solution in S1 can be extracted at room temperature 3 times or more, up to 5 times. There is no special limit to the extraction time at room temperature, which can be 12 hours or more per extraction.

[0021] Optionally, when the ethyl acetate component in S2 is eluted by silica gel column chromatography gradient, the elution gradient is set as follows: petroleum ether-ethyl acetate volume ratio 15:1 → 10:1 → 5:1 → 3:1 → 1:1 → 0:1, to obtain 6 components (Fr.1-~Fr.6) before entering the MCI column chromatography stage.

[0022] Preferably, the eluent Fr.3 with a petroleum ether-ethyl acetate volume ratio of 5:1 was separated by MCI column chromatography and eluted with a methanol-water gradient to obtain four subfractions Fr.3A to Fr.3D; the eluent Fr.3D with a methanol-water volume ratio of 100:0 was eluted with Sephadex LH-20 with methanol as the mobile phase, and four subfractions Fr.3D1 to Fr.3D4 were obtained by combining the colorimetric results of thin-layer chromatography and Rf values. Subfraction Fr.3D1 with a thin-layer chromatography (CH2Cl2:CH3OH, 15:1 v / v) and an Rf value of 0.3 to 0.4 was further separated by semi-preparative high-performance liquid chromatography (mobile phase: MeOH-H2O, 88:12, volume ratio; flow rate: 3 mL / min), and the t was collected. R The components at 11.7 min yielded a compound with the structural formula shown in formula (2);

[0023] Preferably, the eluent Fr.4 with a petroleum ether-ethyl acetate volume ratio of 3:1 is separated by MCI column chromatography and eluted with a methanol-water gradient to obtain four subfractions Fr.4A to Fr.4D; the eluent Fr.4B with a methanol-water volume ratio of 80:20 is eluted with Sephadex LH-20 with methanol as the mobile phase, and four subfractions Fr.4B1 to Fr.4B4 are obtained by combining the colorimetric results of thin-layer chromatography and Rf values; Fr.4B1 with a thin-layer chromatography (CH2Cl2:CH3OH, 15:1 v / v) and an Rf value of 0.2 to 0.3 is further separated by semi-preparative high-performance liquid chromatography (mobile phase: MeOH-H2O, 65:35, volume ratio; flow rate: 3 mL / min), and the t is collected. R =14.6 min of the component, and the compound with the structural formula shown in formula (1) was obtained;

[0024] The compounds described in this invention can be obtained by isolation and purification from plants; they can also be synthesized by chemical methods well known to those skilled in the art.

[0025] Compared with the prior art, this application has the following beneficial effects:

[0026] (1) This application is the first to isolate two compounds from Camellia chrysantha. Compound 1 is a guaiacolane-type sesquiterpene lactone and compound 2 is a ursane-type triterpene. Compound 1 is a new compound that was isolated for the first time in this application.

[0027] (2) This application is the first to discover that these two terpenoid compounds have significant ACL inhibitory activity, and the activity is comparable to that of the positive control BMS303141. They will have important application prospects for diseases related to glucose and lipid metabolism disorders that are prevalent in modern populations, such as hyperlipidemia, metabolic-related fatty liver disease, and type II diabetes. Attached Figure Description

[0028] Figure 1 This is the 1H NMR spectrum of compound 1 (in CD3OD, 400M).

[0029] Figure 2 This is the 13C NMR spectrum of compound 1 (in CD3OD, 100M).

[0030] Figure 3 This is the 1H NMR spectrum of compound 2 (in CD3OD, 400M).

[0031] Figure 4 This is the 13C NMR spectrum of compound 2 (in CD3OD, 100M). Detailed Implementation

[0032] The technical solution of this application will be clearly and completely described below with reference to specific embodiments. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. Based on the embodiments in this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0034] Golden flower tea leaves were harvested from Pingbian County, Yunnan Province, and dried in the shade before being pulverized into powder. Specific rotation was measured using an SGW-1 polarimeter at 25℃. Ultraviolet (UV) spectral data were obtained using a Shimadzu PharmaSpec-1800 UV spectrometer. High-resolution mass spectrometry (HR-ESI-MS) was performed using a Thermo Fisher Q-Exactive mass spectrometer, employing an ESI ion source to simultaneously obtain both positive and negative ion modes. NMR was obtained using a Bruker Avance II 400 nuclear magnetic resonance spectrometer, with chemical shifts referenced to the undeuterated residual solvent peaks, expressed as δ (ppm). Thin-layer chromatography (TLC) plates were purchased from Qingdao Ocean Chemical Co., Ltd., and UV (λ: 254nm, 365nm) and sulfuric acid-vanillin solution were used for color development. Column chromatography primarily used MCI microporous resin CHP 20P (Mitsubishi Chemical Industries, 75-150μm) and Sephadex LH-20 gel (GE Healthcare BioSciences). AB); The Shimadzu CBMA-20A analytical and semi-preparative liquid chromatography system is equipped with an SPD-20A photodiode array detector (PDA) and a Cosmosil Packed Column (10×250mm, 5μm, 5C18-MS-II or πNAP).

[0035] Example 1: Preparation of the compound

[0036] 8.6 kg of dried Camellia chrysantha branches and leaves were thoroughly pulverized and extracted four times with 10 L of 90% methanol at room temperature for 24 hours each time. The extracts were combined and concentrated under reduced pressure to obtain 700 g of total extract. The extract was dispersed in 2 L of water and extracted three times each with equal volumes of petroleum ether, ethyl acetate, and n-butanol to obtain four fractions: petroleum ether, ethyl acetate, n-butanol, and water. The ethyl acetate fraction, totaling 50.1 g, was eluted by silica gel column chromatography with a petroleum ether-ethyl acetate gradient (15:1→10:1→5:1→3:1→1:1→0:1, v / v) to obtain six fractions (Fr.1-~Fr.6).

[0037] Fraction Fr.3 (5:1 elution fraction, 12.6 g) was first crudely separated by MCI column chromatography, followed by gradient elution with methanol-water (MeOH / H2O, 70:30→80:20→90:10→100:0, v / v) to obtain four subfractions (Fr.3A~Fr.3D). Fr.3D (100:0 elution fraction) was purified by Sephadex LH-20 (methanol as mobile phase), and the four subfractions Fr.3D1~Fr.3D4 were obtained by combining the colorimetric results and Rf values ​​of thin-layer chromatography. Fr.3D1 (thin-layer chromatography CH2Cl2:CH3OH, 15:1, v / v, Rf value 0.3~0.4) was further separated by semi-preparative high-performance liquid chromatography (methanol-water, 88:12, v / v) to finally obtain compound 2 (5.5 mg, t). R =11.7min).

[0038] Fraction Fr.4 (15.5 g of 3:1 eluent) was separated by MCI column chromatography using a methanol-water gradient elution (70:30→80:20→90:10→100:0, v / v), yielding four subfractions (Fr.4A~Fr.4D). Fr.4B (80:20 eluent) was purified using Sephadex LH-20 (methanol as mobile phase), and then combined with TLC colorimetry and Rf values ​​to obtain four subfractions Fr.4B1~Fr.4B4. Fr.4B1 (TLC CH2Cl2:CH3OH, 15:1, v / v, Rf value 0.2~0.3) was further separated by semi-preparative high-performance liquid chromatography (methanol-water, 65:35, v / v) to finally obtain compound 1 (3.7 mg, t). R =14.6min).

[0039] Compound 1, its NMR and physicochemical data are as follows:

[0040] White, amorphous powder; [α] 25 D -23.4(c 0.10,MeOH); UV(MeOH)λ max (logε):207(3.76),256(3.51)nm; ECD(MeOH)λ max (Δε)217(-25.1)nm; 1 H NMR (in CD3OD, 400MHz): δ H2.49(1H,m,H-2α),3.05(1H,m,H-2β),4.10(1H,m,H-3),2.93(1H,m,H-5),4.42(1H,t,J=10.6Hz,H-6),3.25( 1H,m,H-7),5.73(1H,m,H-8),2.46(1H,dd,J=15.6,7.5Hz,H-9α),2.97(1H,dd,J=15.6,5.9Hz,H-9β),5.58(1 H,d,J=3.3Hz,H-13a),6.17(1H,d,J=3.3Hz,H-13b),3.79(1H,d,J=12.3Hz,H-14a),4.00(1H,d,J=12.3Hz,H- 14b),1.38(3H,s,H-15),6.09(1H,m,H-3′),1.86(3H,dd,J=7.2,1.5Hz,H3-4′),1.77(3H,t,J=1.5Hz,H3-5′); 13 CNMR (in CD3OD, 100MHz): δ C 132.8(C-1),39.3(C-2),66.5(C-3),81.6(C-4),57.7(C-5),78.5(C-6),54.3(C-7),66.5(C-8),35.4(C-9),133.2(C-10),137.2(C-11 ),170.7(C-12),120.6(C-13),65.4(C-14),17.3(C-15),168.3(C-1′),128.9(C-2′),139.3(C-3′),16.2(C-4′),20.8(C-5′); HRESIMS m / z 419.1239[M+CH3CN] + ,(calcd for C 22 H 29 NO3, 419.1240).

[0041] Compound 2, its NMR and physicochemical data are as follows:

[0042] White, amorphous powder; [α] 25 D +17.8(c 0.10,MeOH); UV(MeOH)λ max (logε):195(2.42)nm; ECD(MeOH)λ max (Δε)195(+8.0),241(-1.4)nm; 1 H NMR (in CD3OD, 400MHz): δH 1.21(1H,m,H-1α),2.19(1H,dt,J=14.0,3.2Hz,H-1β),1.53(1H,m,H-2),3.04(1H,m,H-3),0.95(1H,m,H-5),1.42(1H,m,H-6α),1.74(1H,m,H-6β),1.27(1H,m,H-7α),1.41(1H,m,H-7β),1.62(1H,d,J=9.2Hz,H-9),3.87(1H,t,J=8.2Hz,H-11),0.98(1H,m,H-15α),1.59(1H,m,H-15β),1.05(1H,m,H-16α),2.10(1H,m,H-16β),2.54(1H,d,J=11.2Hz,H-18),1.92(1H,m,H-19),1.08(1H,m,H-20),4.06(1H,m,H-21),1.29(3H,s,H3-23),0.86(3H,s,H3-25),0.94(3H,s,H3-26),1.23(3H,s,H3-27),0.91(3H,s,H3-28),0.93(3H,d,J=6.6Hz,H3-29),1.07(3H,d,J=6.6Hz,H3-30),3.57(3H,s,H3-1′); 13 C NMR(in CD3OD,100MHz):δ C 40.7(C-1),27.9(C-2),76.5(C-3),49.1(C-4),55.7(C-5),19.7(C-6),33.1(C-7),41.7(C-8),52.6(C-9),37.8(C-10),68.1(C-11),148.0(C-12),109.3(C-13),40.0(C-14),25.3(C-15),27.5(C-16),47.5(C-17),46.7(C-18),38.4(C-19),46.9(C-20),75.6(C-21),215.0(C-22),23.9(C-23),176.0(C-24),14.2(C-25),17.5(C-26),23.1(C-27),20.5(C-28),16.1(C-29),16.6(C-30),51.0(C-1′);HRESIMS m / z 555.3297[M+Na] + ,(calcd for C 31 H 48 O7Na,555.3298)。

[0043] The 1H NMR spectrum of compound 1 (in CD3OD, 400M) is as follows: Figure 1 As shown, the 13C NMR spectrum (in CD3OD, 100M) of compound 1 is as follows. Figure 2 As shown; the 1H NMR spectrum of compound 2 (in CD3OD, 400M) is as follows. Figure 3 As shown, the 13C NMR spectrum of compound 2 (in CD3OD, 100M) is as follows. Figure 4 As shown.

[0044] Example 2: ACL inhibitory activity test of the compounds in this invention

[0045] Experimental Methods: In this experiment, ACL catalyzes the conversion of citrate to acetyl-CoA, which in turn produces the precursor molecule of fatty acid synthesis—malonyl-CoA. This reaction is accompanied by ATP consumption; therefore, ADP-Glo ​​and a kinase assay kit were used to detect changes in ATP to indirectly reflect the inhibitory effect of the compounds on ACL enzyme activity. Specifically, the percentage inhibition rate of the compounds at a concentration of 20 μg / ml was initially investigated. The results showed that all the aforementioned compounds had inhibitory effects on enzyme activity. Further determination of IC50 was performed. 50 Values: Before use, the sample was dissolved in DMSO to prepare an appropriate concentration, diluted 3-fold, 7 times, and in triplicate. 2 μL of the sample solution was added to a standard activity assay system (40 mM Tris, pH 8.0, 10 mM MgCl2, 5 mM DTT, ATP, CoA, sodium citrate, and ACL), and incubated at 37°C for 30 min. Then, 25 μL of ADP-Glo ​​reagent was added, and the system was incubated at room temperature for 30 min to terminate the reaction and consume any remaining ATP. After adding the kinase detection reagent and incubating for another 30 min, the fluorescence signal was read by EnVision, and the slope of the first-order reaction of the kinetic curve was used as the enzyme activity indicator.

[0046] Plotting relative activity against compound concentration, the formula v / v0 = 100 / (1 + b*[I] / IC) is used. 50 IC was obtained by fitting. 50 Values, where v is the enzyme reaction rate at inhibitor concentration [I], v0 is the reaction rate without inhibitor, and b is the slope factor or correction parameter. The experiment was repeated three times, and the result was the average of the three times. The IC50 of the positive control BMS303141 was... 50 The value was 0.36±0.04μM, and the results are shown in Table 1.

[0047] Table 1. ACL inhibitory activity data of terpenoid compounds in Camellia chrysantha.

[0048]

[0049] The above test results show that the terpenoid compounds described in this patent exhibit significant inhibitory activity against ACL, indicating that the compounds described in this invention can be used to prepare drugs for treating diseases related to glucose and lipid metabolism disorders or as lead compounds for such drugs.

[0050] The embodiments described above are merely illustrative of several implementation methods of this application, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the invention patent. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of this application, and these all fall within the protection scope of this application. Therefore, the protection scope of this patent application should be determined by the appended claims.

Claims

1. Use of a terpenoid compound for the preparation of an ATP-citrate lyase inhibitor, characterized in that, The terpenoid compound is a compound shown in formula 1 or / and formula 2: 。 2. The use of terpenoids for the preparation of a medicament for the prevention, delay or treatment of a disease mediated by ATP-citrate lyase, characterized in that, The terpenoid compound is a compound shown in formula 1 or / and formula 2: 。 3. Use according to claim 2, characterized in that, The disease is hyperlipidemia, atherosclerosis, fatty liver or type II diabetes.

4. Terpenoid compounds characterized in that, The structural formula is shown in formula 1: 。 5. A pharmaceutical composition, characterized by, The compound shown in formula 1 or the combination of the compound shown in formula 1 and the compound shown in formula 2 is used as an active ingredient: 。 6. A method for extracting terpenoids, characterized by, The method comprises the following steps: Dry the branches and leaves of Camellia pitardii var. pubipetala at room temperature, crush them, and extract them with a methanol-water solution with a concentration of more than 70% at room temperature for one or more times; concentrate the extract, suspend it in water, and sequentially extract it with petroleum ether, ethyl acetate and n-butanol each for three times to obtain four components of petroleum ether, ethyl acetate, n-butanol and water; and the ethyl acetate component is subjected to silica gel column chromatography with petroleum ether-ethyl acetate gradient elution to obtain six components Fr.1-Fr.

6. The elution fraction Fr.3 of petroleum ether-ethyl acetate volume ratio 5:1 was separated by MCI column chromatography and eluted with methanol-water gradient to obtain four sub-fractions Fr.3A~Fr.3D; the elution fraction Fr.3D of methanol-water volume ratio 100:0 was purified by Sephadex LH-20 and methanol as mobile phase, and four sub-fractions Fr.3D1~Fr.3D4 were obtained according to the color development and Rf value of thin layer chromatography; the sub-fraction Fr.3D1 of thin layer chromatography CH2Cl2:CH3OH, 15:1 v / v, Rf value 0.3~0.4 was further separated by semi-preparative high performance liquid chromatography, and the collected fractions of = 11.7 min were combined to obtain a compound with structural formula as shown in formula (2). t R = 11.7 min, to obtain a compound with structural formula as shown in formula (2). The elution fraction Fr.4 of petroleum ether-ethyl acetate (3:1, v / v) was separated by MCI column chromatography and eluted with methanol-water gradient to give four sub-fractions Fr.4A~Fr.4D; the elution fraction Fr.4B of methanol-water (80:20, v / v) was purified by Sephadex LH-20 and methanol as mobile phase, and four sub-fractions Fr.4B1~Fr.4B4 were obtained by combining according to the color development and Rf value of thin layer chromatography; Fr.4B1 with Rf value of 0.2~0.3 in thin layer chromatography CH2Cl2:CH3OH, 15:1 v / v was further separated by semi-preparative high performance liquid chromatography, and the collected fractions with retention time of 14.6 min gave a compound with structural formula as shown in formula (1). t R = 14.6 min, a compound with structural formula as shown in formula (1); 。 7. The extraction method according to claim 6, characterized in that, The methanol-water solution used for extraction has a volume ratio of 90:10; and when the ethyl acetate component is subjected to silica gel column chromatography gradient elution, the elution gradient is set as follows: the volume ratio of petroleum ether-ethyl acetate is 15:1→10:1→5:1→3:1→1:1→0:

1.

8. The extraction method of claim 6, wherein, When the compound shown in formula (2) is separated, the elution gradient of MCI column chromatography is set as follows: the volume ratio of methanol-water is 70:30→80:20→90:10→100:0; and the eluent of semi-preparative high performance liquid chromatography is methanol-water with a volume ratio of 88:

12.

9. The extraction method of claim 6, wherein, When the compound shown in formula (1) is separated, the elution gradient of MCI column chromatography is set as follows: the volume ratio of methanol-water is 70:30→80:20→90:10→100:0; and the eluent of semi-preparative high performance liquid chromatography is methanol-water with a volume ratio of 65:35.

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