Coriaria sinica lactone compound, preparation method thereof and application of coriaria sinica lactone compound in anti-inflammatory activity

Abstract

The invention belongs to the technical field of biological medicine, and particularly relates to coriaria sinica lactone compounds, a preparation method thereof and application of the coriaria sinica lactone compounds in anti-inflammatory activity. The coriaria sinica lactone compound can significantly inhibit a TLR4 / NF-kappa B signal channel to inhibit downstream inflammatory protein nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and further inhibit inflammatory BV2 cells from generating nitric oxide, the inhibition rate can reach 65.5%, and it is indicated that the coriaria sinica lactone compound has an application prospect in treatment of neuroinflammatory diseases.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of biological medicine, and particularly relates to a Coriaria sinica inner lipid compound, a preparation method thereof and application thereof in anti-inflammatory activity. BACKGROUND

[0002] Neuroinflammation as a defense mechanism of the central nervous system in response to infection and injury, its abnormal activation has become the core pathological driving factor of Alzheimer's disease (AD), Parkinson's disease (PD) and other neurodegenerative diseases. In the context of the global aging population, PD as the second largest neurodegenerative disease after AD, the existing treatment methods are still limited to symptom relief, lacking fundamental intervention measures for disease progression, and the clinical needs are urgent. Existing studies have shown that chronic neuroinflammatory response can accelerate neuronal damage through a cascade amplification effect, and cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) as key regulatory molecules of the inflammatory pathway, their abnormal activation has been confirmed to be closely related to disease progression.

[0003] COX-2 is involved in the synthesis of prostaglandin E2 to participate in the deposition of beta amyloid protein (Aβ) and the formation of neurofibrillary tangles (NFTs), its high expression area in the brain of AD patients is highly consistent with the pathological damage area, and it can directly activate the pro-apoptotic signaling pathway; iNOS is rapidly induced in the neuroinflammatory microenvironment, and generates excessive nitric oxide (NO) to trigger oxidative stress and mitochondrial dysfunction. Both of them not only have synergistic effect, but also can activate glial cells to form an inflammatory positive feedback loop, continuously amplifying nerve damage. However, current anti-neuroinflammatory drug research and development focuses on single target intervention, and traditional COX-2 or iNOS inhibitors are difficult to meet the clinical needs due to the lack of target specificity, long-term drug safety problems and efficacy bottlenecks.

[0004] Based on the complex pathological network of neurodegenerative diseases, multi-target collaborative intervention strategy has gradually become a research consensus. Experiments have proved that simultaneous inhibition of COX-2 / iNOS pathway can improve the neuroprotective effect through multiple mechanisms such as reducing the release of inflammatory factors, blocking the excessive activation of glial cells, and showing better therapeutic potential than single-target drugs in PD animal models. However, the existing technology still faces the challenges of target selection specificity and long-term drug safety, and the development of new compounds with high selectivity, multi-pathway synergistic inhibition ability and good biological safety has become the key to breaking through the current treatment dilemma. SUMMARY

[0005] The application separates a Coriaria sinica resinoid compound from Coriaria sinica picked from a Qinling mountain area, the Coriaria sinica resinoid compound can inhibit TLR4 / NF-κB signal path to inhibit inflammatory proteins iNOS and COX-2, combine and occupy the active site of iNOS to inhibit the production of NO, and exhibits significant anti-neuroinflammatory activity.

[0006] In order to achieve the above-mentioned purpose, the application can adopt the following technical scheme:

[0007] The application provides a Coriaria sinica resinoid compound in one aspect, and a structural formula of the Coriaria sinica resinoid compound is as follows:

[0008]

[0009] The application provides a preparation method of the Coriaria sinica resinoid compound in another aspect, and the preparation method comprises the following steps:

[0010] (1) the ethanol extract is suspended in water, and then petroleum ether, ethyl acetate and n-butanol are sequentially used for extraction to obtain an extraction liquid;

[0011] (2) the extraction liquid is separated by silica gel column chromatography to obtain F4;

[0012] (3) F4 is separated by a reversed-phase C18 column to obtain F4-1, F4-2, F4-3, F4-4 and F4-5;

[0013] (4) F4-2 is purified by Sephadex LH-20 gel column chromatography and silica gel column chromatography to obtain purified F4-2;

[0014] (5) the purified F4-2 is separated by semi-preparative high performance liquid chromatography to obtain the Coriaria sinica resinoid compound;

[0015] In step (2), the silica gel column chromatography eluent is a chloroform-methanol mixed solvent, and the volume ratio of chloroform to methanol is 10:1;

[0016] In step (3), the gradient eluent of the reversed-phase C18 column separation is a 10% to 100% methanol aqueous solution in mass fraction;

[0017] In step (4), the silica gel column chromatography eluent is a petroleum ether-ethyl acetate mixed solvent, and the volume ratio of petroleum ether to ethyl acetate is 8:2;

[0018] In step (5), the eluent of the semi-preparative high performance liquid chromatography is a 38% methanol aqueous solution in mass fraction.

[0019] The application provides an anti-inflammatory active composition comprising the Coriaria sinica resinoid compound.

[0020] In another aspect of the present application, an anti-inflammatory active drug is provided, which comprises the above-mentioned coriariagenin compound or the above-mentioned anti-inflammatory active composition.

[0021] Preferably, the anti-inflammatory active drug is in the form of an injection, a tablet, a capsule, a granule or a patch.

[0022] In another aspect of the present application, the above-mentioned coriariagenin compound or the above-mentioned anti-inflammatory active composition is used for preparing an anti-neuroinflammatory drug.

[0023] Preferably, in the above-mentioned use, the neuroinflammation is Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease or Parkinson's disease.

[0024] Preferably, in the above-mentioned use, the use comprises: the use of the coriariagenin compound or the anti-inflammatory active composition in inhibiting the activity of nitric oxide synthase iNOS and / or cyclooxygenase COX-2.

[0025] Preferably, in the above-mentioned use, the use comprises: the use of the coriariagenin compound or the anti-inflammatory active composition in inhibiting the expression of downstream inflammatory proteins by inhibiting the TLR4 / NF-κB signaling pathway.

[0026] In another aspect of the present application, the above-mentioned coriariagenin compound or the above-mentioned anti-inflammatory active composition is used for inhibiting the production of nitric oxide by BV2 microglial cells in vitro.

[0027] Preferably, in the above-mentioned use, the use comprises: the use of the coriariagenin compound or the anti-inflammatory active composition in inhibiting the activity of nitric oxide synthase iNOS and / or cyclooxygenase COX-2.

[0028] Preferably, in the above-mentioned use, the use comprises: the use of the coriariagenin compound or the anti-inflammatory active composition in inhibiting the expression of downstream inflammatory proteins by inhibiting the TLR4 / NF-κB signaling pathway.

[0029] The beneficial effects of the present application include: the coriariagenin compound provided by the present application can significantly inhibit the TLR4 / NF-κB signaling pathway to inhibit downstream inflammatory proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and further inhibit the production of nitric oxide by BV2 cells, and the inhibition rate can reach 65.5%, indicating that the coriariagenin compound has application prospects for treating neuroinflammatory diseases. BRIEF DESCRIPTION OF DRAWINGS

[0030] Figure 1 is the carbon-hydrogen correlation, long-range carbon-hydrogen correlation and spatial correlation spectrum of the compound 1 of the present application;

[0031] Figure 2 is the hydrogen spectrum of the compound 1 of the present application;

[0032] Figure 3 This is the carbon spectrum of compound 1 of the present invention;

[0033] Figure 4 This is a hydrocarbon correlation diagram of compound 1 of the present invention;

[0034] Figure 5 This is a hydrocarbon long-range correlation diagram of compound 1 of the present invention;

[0035] Figure 6 The infrared spectrum of compound 1 of the present invention is shown below.

[0036] Figure 7 This is a high-resolution ESI-MS image of compound 1 of the present invention;

[0037] Figure 8 The effect of compound 1 of the present invention on LPS-induced NO production from BV-2;

[0038] Figure 9 The effect of compound 1 of the present invention on the level of enzyme marker proteins in LPS-stimulated BV-2 cells. Detailed Implementation

[0039] The embodiments described are provided to better illustrate the present invention, but are not intended to limit the scope of the invention to the embodiments described. Therefore, non-essential improvements and adjustments made to the embodiments by those skilled in the art based on the above description are still within the scope of protection of the present invention.

[0040] The terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit this disclosure. Singular expressions include plural expressions unless they have a distinct meaning in the context. As used herein, it should be understood that terms such as “comprising,” “having,” “including,” are intended to indicate the presence of features, numbers, operations, components, parts, elements, materials, or combinations thereof. The terminology of the invention is disclosed in the specification and is not intended to exclude the possibility that one or more other features, numbers, operations, components, parts, elements, materials, or combinations thereof may be present or added. As used herein, “ / ” may be interpreted as “and” or “or,” depending on the context.

[0041] In a first aspect, embodiments of the present invention provide a masalacinoid compound, the structural formula of which is:

[0042]

[0043] It should be noted that the *Corydalis oryzae* lipid compounds in this invention were isolated from *Corydalis oryzae* in the Qinling Mountains. These *Corydalis oryzae* lipid compounds can significantly inhibit the TLR4 / NF-κB signaling pathway to suppress downstream inflammatory proteins nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), thereby inhibiting nitric oxide production in inflamed BV2 cells, with an inhibition rate reaching 65.5%. This indicates that these *Corydalis oryzae* lipid compounds have potential applications in treating neuroinflammatory diseases.

[0044] Secondly, embodiments of the present invention provide a method for preparing the above-mentioned arbutin compounds, the method comprising:

[0045] (1) The ethanol extract was suspended in water and then extracted with petroleum ether, ethyl acetate and n-butanol in sequence to obtain the extract;

[0046] (2) The extract was separated by silica gel column chromatography to obtain F4;

[0047] (3) F4 was separated by a reverse-phase C18 column to obtain F4-1, F4-2, F4-3, F4-4 and F4-5;

[0048] (4) F4-2 was purified by Sephadex LH-20 gel column and silica gel column chromatography to obtain purified F4-2;

[0049] (5) F4-2 was purified and separated into masalacinoids by semi-preparative high performance liquid chromatography;

[0050] In step (2), the silica gel column chromatography eluent is a chloroform-methanol mixed solvent with a volume ratio of chloroform to methanol of 10:1.

[0051] In step (3), the gradient eluent for separation by the reverse-phase C18 column is a methanol aqueous solution with a mass fraction of 10% to 100%.

[0052] In step (4), the eluent for silica gel column chromatography is a mixture of petroleum ether and ethyl acetate, with a volume ratio of 8:2.

[0053] In step (5), the eluent for the semi-preparative high performance liquid chromatography is an aqueous solution containing 38% methanol by mass.

[0054] It should be noted that the aralia lactones in this invention are isolated from aralia as described above. Furthermore, it should be understood that the aralia lactones in this invention can also be synthesized using other existing organic synthesis methods.

[0055] Thirdly, embodiments of the present invention provide an anti-inflammatory composition comprising the above-mentioned arbutin compounds of the present invention.

[0056] It should be noted that the masalacin compounds in this invention can be combined with other anti-inflammatory active ingredients to form an anti-inflammatory active composition to enhance anti-inflammatory activity. Other anti-inflammatory active ingredients are known in the art.

[0057] Fourthly, embodiments of the present invention provide an anti-inflammatory active drug comprising the above-mentioned arbutin compounds or the above-mentioned anti-inflammatory active compositions.

[0058] It should be noted that the arbutin compounds or anti-inflammatory compositions in this invention can be prepared with excipients into anti-inflammatory drugs of different dosage forms. Dosage forms can be injections, tablets, capsules, granules, or patches. Furthermore, the preparation methods for different dosage forms are well known in the art.

[0059] Fifthly, embodiments of the present invention provide the use of the above-mentioned arbutin compounds or the above-mentioned anti-inflammatory active compositions in the preparation of anti-neuroinflammatory drugs.

[0060] It should be noted that this invention achieves multi-target synergistic anti-inflammatory effects by inhibiting the excessive nitric oxide production mediated by iNOS and its neurotoxic effects, while simultaneously blocking the prostaglandin inflammatory cascade reaction catalyzed by COX-2.

[0061] In some specific examples, the neuroinflammation described above is Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, or Parkinson's disease.

[0062] It should be noted that the neuroinflammation in this invention is known in the art, such as Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, or Parkinson's disease.

[0063] In some specific examples, the above applications include the use of masalacinoids or anti-inflammatory compositions in inhibiting the activity of nitric oxide synthase (iNOS) and / or cyclooxygenase (COX-2).

[0064] It should be noted that the masalacinoids in this invention can simultaneously inhibit the activities of nitric oxide synthase (iNOS) and cyclooxygenase (COX-2).

[0065] In some specific examples, the applications mentioned above include: the use of masalacinoids or anti-inflammatory compositions to inhibit downstream inflammatory proteins by suppressing the TLR4 / NF-κB signaling pathway.

[0066] Sixthly, embodiments of the present invention provide the application of the above-mentioned arbutin compounds or the above-mentioned anti-inflammatory active compositions in in vitro inhibition of nitric oxide production by inflammatory BV2 microglia.

[0067] It should be noted that nitric oxide is an important inflammatory mediator. Excessive production of nitric oxide is common in neurons and glial cells of the brain in patients with neurodegenerative diseases, suggesting that nitric oxide is involved in such neuroinflammatory processes.

[0068] In some specific examples, the above applications include the use of masalacinoids or anti-inflammatory compositions in inhibiting the activity of nitric oxide synthase (iNOS) and / or cyclooxygenase (COX-2).

[0069] In some specific examples, the applications mentioned above include: the use of masalacinoids or anti-inflammatory compositions to inhibit downstream inflammatory proteins by suppressing the TLR4 / NF-κB signaling pathway.

[0070] It is important to note that NF-κB is a well-characterized transcription factor considered a key factor in microglia-mediated neuroinflammation. Under normal conditions, NF-κB, as a p50 / p65 / IκB trimer, is bound to the repressor protein IκB and restricted in the cytoplasm. Once activated by various stimuli such as LPS, IκB is phosphorylated, ubiquitinated, and subsequently degraded by the IκB kinase IKK. Consequently, the nuclear localization signal (NLS) on NF-κB is exposed, leading to a nuclear translocation of the molecule. In the nucleus, NF-κB initiates the transcription of genes associated with inflammatory factors. Detecting the nuclear translocation of the NF-κB subunit p65 serves as an indicator of NF-κB activation.

[0071] To better understand the present invention, specific examples are provided below to further illustrate the content of the present invention, but the content of the present invention is not limited to the examples below.

[0072] The instruments used in the following examples are: Rudolph Autopol III polarimeter; LC-20AT high-performance liquid chromatograph; Thermo Evolution-300 ultraviolet spectrometer; Bruker TENSOR 27 infrared spectrometer (potassium bromide pellet method); Bruker Avance III 500 nuclear magnetic resonance spectrometer (TMS internal standard); Thermo Fisher LTQFleet low-resolution mass spectrometer; Agilent 6520 Accurate-Mass Q-TOF LC / MS high-resolution mass spectrometer; RE-2000A rotary evaporator; DLSB-10 / 20 cryogenic coolant circulation pump (Zhengzhou Changcheng Science & Industry Trade Co., Ltd.); SHB-III circulating water multi-purpose vacuum pump (Zhengzhou Changcheng Science & Industry Trade Co., Ltd.); SW-OJ-2F clean bench (Suzhou Antai Air Technology Co., Ltd., Suzhou Jingji Group); and MLS-3780 vertical steam sterilizer. The silica gel for column chromatography (100-200 mesh, 200-300 mesh, and 300-400 mesh) and the silica gel for thin-layer chromatography (Silica Gel H) were both produced by Qingdao Marine Chemical Plant; the liquid chromatography columns were Hypersil BDS 5μm C18 (250×4.6 and 250×10; Thermo); the hydroxypropyl dextran gel Sephadex LH-20 and RP-C18 reversed silica gel were both produced by Merk.

[0073] Preparation Examples

[0074] (1) 50 kg of *Cephalotaxus fortunei* plants were extracted with 95% ethanol (100 L × 4 times), and the extract was obtained by vacuum distillation.

[0075] (2) The obtained extract (9.8 kg) was suspended in water and then extracted with petroleum ether, ethyl acetate and n-butanol in sequence to obtain crude extract;

[0076] (3) The crude extract (450g) was separated by silica gel column chromatography and eluted with a chloroform-methanol gradient (100:1 200mL, 50:1 200mL, 25:1 200mL, 10:1 100mL, 5:1 100mL, and finally 100mL of methanol) to obtain 6 fractions: F1, F2, F3, F4, F5 and F6.

[0077] (4) Component F4 was separated into 5 components by reverse-phase C18 column (YMC packing, 50μm particle size, methanol-water, 10%~100%), namely: F4-1, F4-2, F4-3, F4-4 and F4-5;

[0078] (5) Fraction F4-2 was purified by Sephadex LH-20 gel column (methanol) and silica gel column chromatography (petroleum ether-ethyl acetate 8:2) to obtain purified F4-2;

[0079] (6) The purified F4-2 was separated into compound 1 (retention time 10 min, 110.0 mg) by semi-preparative high performance liquid chromatography (YMC-Pack ODS-A, 38% methanol-water, flow rate 2 mL / min).

[0080] Characterization test

[0081] The physicochemical properties of compound 1 are as follows: The molecular formula of compound 1 is C1 16 H 24 O8, a white powder; HR-ESI-MS (positive) m / z: 345.1545 [M+H] + .;

[0082] In addition, the proton and carbon spectral data of compound 1 are shown in Table 1 below;

[0083] Table 1. Proton NMR (500 MHz) and Carbon NMR (125 MHz) data

[0084]

[0085] In addition, the C-H correlation, long-range C-H correlation, and spatial correlation spectra of compound 1 are as follows: Figure 1 As shown.

[0086] In addition, the proton spectrum, carbon spectrum, hydrocarbon correlation diagram, and hydrocarbon long-range correlation diagram of compound 1 are as follows: Figure 2 , Figure 3 , Figure 4 and Figure 5 As shown.

[0087] Furthermore, the infrared spectrum and high-resolution ESI-MS image of compound 1 are shown below. Figure 6 and Figure 7 As shown.

[0088] Related tests

[0089] (I) NO (nitric oxide, lactate dehydrogenase) inhibitory activity

[0090] (1) BV-2 cells (2×10⁻⁶) 5BV-2 cells were seeded in 96-well plates at 37°C for 24 hours. Then, the cells were divided into a blank control group, an LPS treatment group, and a compound treatment group. The LPS treatment group was supplemented with 1 μg / mL LPS (lipopolysaccharide), the compound treatment group was supplemented with 1 μg / mL LPS and 50 μM compound 1, and the blank control group was supplemented with the same volume of DMSO (dimethyl sulfoxide). After each group was treated with the corresponding substance, they were incubated at 37°C for 24 hours.

[0091] (2) After incubation, the supernatant of BV-2 cells was used to test the nitrite concentration using a kit (Beyotime). Specifically, 50 μL of the BV-2 cell supernatant was reacted with Griess reagents (50 μL Griess reagent I and 50 μL Griess reagent II). The absorbance (A) was measured at 540 nm using a Bio-Tek microplate reader. Using sodium nitrite as a standard, the nitrite concentration was calculated using a nitrite standard curve to analyze NO production. NO inhibition rate % = (A...) / (N...) LPS处理 Group A compound treatment group) / (A LPS Treatment group - Blank control group) × 100.

[0092] The results are as follows Figure 8 As shown in the figure (the horizontal axis from left to right represents the blank control, LPS treatment group, and LPS + compound treatment group (i.e., compound treatment group)), the results showed that after LPS stimulation of BV-2 cells for 24 hours, NO production increased significantly by about 2 times, while compound 1 had a strong inhibitory effect on NO production, with an inhibition rate of 65.5%.

[0093] (II) Western Blot Analysis of Anti-inflammatory Proteins

[0094] (1) The BV-2 cell supernatant after treatment (I) was subjected to the above method to extract cell proteins according to the method described in the literature [Cheng Y, Yang C, Zhao J, TseHF, Rong J. Proteomic identification of calcium-binding chaperone calreticulinas a potential mediator for the neuroprotective and neuritogenic activities of fruit-derived glycoside amygdalin. J Nutr Biochem. 2015, 26(2):146-154.];

[0095] (2) Protein expression was analyzed using Western blotting, including: taking protein samples, adding sample buffer, boiling and denaturing, electrophoresis with 10% SDS-PAGE, and transferring to a nitrocellulose membrane; blocking the membrane overnight in TBST solution containing 5% BSA at 4°C, then incubating it for 4 hours at 4°C in a primary antibody solution containing iNOS, COX-2 and GAPDH (Cell Signaling Technology, Boston, MA, USA), rinsing three times with TBST, and then incubating it for 3 hours at 4°C in a secondary antibody solution containing horseradish peroxidase. After washing the membrane, it was tested according to the instructions of the GE Healthcare ECL kit.

[0096] Test results are as follows Figure 9 As shown, LPS significantly enhanced the expression of iNOS and COX-2, while compound 1 had a more significant inhibitory effect on the expression of iNOS and COX-2, with inhibition rates of 38.9% and 39.6%, respectively.

[0097] (III) The compound blocks the LPS-induced nuclear subunit p65 of NF-κB in BV-2 cells.

[0098] (1) The supernatant of BV-2 cells treated in (I) above was separated and the nuclear and cytoplasmic fractions were extracted using a nuclear and cytoplasmic protein extraction kit (according to the instructions). Then, the nuclear translocation of NF-κBp65 was analyzed by Western blotting (according to the analysis method in (II) above). The primary antibodies were: anti-NF-κBp65 (1:1000), anti-Lamin B1 (1:1000), and anti-GAPDH (1:1000).

[0099] Test results as follows Figure 9 As shown in the figure (the horizontal axis from left to right represents the blank control, LPS treatment group, and LPS + compound treatment group (i.e., compound treatment group)), the results showed that LPS-induced stimulation significantly increased the protein expression of dephosphorylated NF-κBp65 in the nucleus, while compound 1 significantly inhibited the expression of LPS-stimulated phosphorylated NF-κBp65 protein, with an inhibition rate of 66.6%.

[0100] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and not to limit it. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, and all such modifications or substitutions should be covered within the scope of the claims of the present invention.

Claims

1. Masalacinoids, with the following structural formula:

2. The method for preparing the masalacinoid compound according to claim 1, characterized in that, Preparation methods include: (1) The ethanol extract was suspended in water and then extracted with petroleum ether, ethyl acetate and n-butanol in sequence to obtain the extract; (2) The extract was separated by silica gel column chromatography to obtain F4; (3) F4 was separated by a reverse-phase C18 column to obtain F4-1, F4-2, F4-3, F4-4 and F4-5; (4) F4-2 was purified by Sephadex LH-20 gel column and silica gel column chromatography to obtain purified F4-2; (5) F4-2 was purified and separated into masalacinoids by semi-preparative high performance liquid chromatography; In step (2), the silica gel column chromatography eluent is a chloroform-methanol mixed solvent with a volume ratio of chloroform to methanol of 10:

1. In step (3), the gradient eluent for separation by the reverse-phase C18 column is a methanol aqueous solution with a mass fraction of 10% to 100%. In step (4), the eluent for silica gel column chromatography is a mixture of petroleum ether and ethyl acetate, with a volume ratio of 8:

2. In step (5), the eluent for the semi-preparative high performance liquid chromatography is an aqueous solution containing 38% methanol by mass.

3. An anti-inflammatory composition, characterized in that, Includes the masalacinoids as described in claim 1.

4. An anti-inflammatory drug, characterized in that, It includes the masalacinoid compound of claim 1 or the anti-inflammatory active composition of claim 3.

5. The anti-inflammatory active drug according to claim 5, characterized in that, Anti-inflammatory drugs are available in the form of injections, tablets, capsules, granules, or patches.

6. The use of the arbutin compound of claim 1 or the anti-inflammatory composition of claim 3 in the preparation of an anti-neuroinflammatory drug.

7. The application according to claim 6, characterized in that, Neuroinflammatory diseases include Alzheimer's disease, amyotrophic lateral sclerosis, Huntington's disease, or Parkinson's disease.

8. The use of the masalacinoid compound of claim 1 or the anti-inflammatory composition of claim 3 in in vitro inhibition of nitric oxide production by inflammatory BV2 microglia.

9. The application according to any one of claims 6 to 8, characterized in that, Applications include: The use of masalacinoids or anti-inflammatory compositions in inhibiting the activity of nitric oxide synthase (iNOS) and / or cyclooxygenase (COX-2).

10. The application according to any one of claims 6 to 8, characterized in that, Applications include: Application of masalacinoids or anti-inflammatory compositions in inhibiting downstream inflammatory proteins by suppressing the TLR4 / NF-κB signaling pathway.

Images