CN117159533A - Application of sesquiterpenoids in preparation of medicines for inhibiting activation of inflammatory bodies and/or blocking cell apoptosis - Google Patents

Abstract

The invention relates to the technical field of biological medicines, and discloses application of a sesquiterpene compound in preparation of a medicine for inhibiting activation of inflammatory corpuscles and/or blocking cell apoptosis. The structural formula of the sesquiterpenoids is shown as a formula (1), and the molecular weight of the sesquiterpenoids is as follows: 286.322; the molecular formula: c (C) ₁₇ H ₁₈ O ₄ . The embodiment of the invention shows that CJB can inhibit cell apoptosis at the concentration of 2.5-10 mu M, improve the cell survival rate, reduce LDH release, reduce the mature release of pro-inflammatory factors IL-1 beta and IL-18 in concentration dependence, reduce the expression of Caspase-1 and GSDMD-NT proteins in the cell apoptosis process, and inhibit the activation of inflammatory corpuscle NLRP3, thus indicating that the CKB has the effects of inhibiting the activation of inflammatory corpuscles and inhibiting cell apoptosis through the classical pathway of apoptosis.

Description

Application of sesquiterpenoids in preparation of medicines for inhibiting activation of inflammatory bodies and/or blocking cell apoptosis

Technical Field

The invention relates to the technical field of biological medicines, in particular to application of a sesquiterpene compound in preparation of a medicine for inhibiting activation of inflammatory corpuscles and/or blocking cell apoptosis.

Background

Apoptosis, also known as inflammatory necrosis, is another programmed death that is different from apoptosis. It is usually characterized by cell expansion, protrusion, cell membrane formation, and cell death, and the process of cell death, which is accompanied by the release of a large amount of inflammatory factors, and thus, the tissue undergoes a strong inflammatory reaction. The mechanism of scorch is mainly that under the induction of inflammatory corpuscles, the family of inflammatory caspases (caspases) activates the Gasderm protein family, which is activated and cleaved to form an N-terminal domain with perforating activity, and is transferred to the cell membrane to perforate the cell membrane, so that the cell membrane is perforated to crack and die, and at the same time, the activated Caspase-1 cleaves pro-inflammatory factors IL-1 beta and IL-18 precursors, releasing active IL-1 beta and IL-18.

Cell apoptosis is a protective response of the body to infectious diseases, plays an important role in preventing infection and recognizing endogenous dangerous signals, and is widely involved in the development of tumors, infectious diseases, metabolic diseases, nervous system related diseases, cardiovascular diseases and other diseases. Cell apoptosis is widely involved in the regulation of inflammatory diseases, and blocking apoptosis to inhibit the conduction of inflammatory corpuscle signals is now becoming a new method for treating inflammation, and is probably a new pharmacological target of inflammatory diseases.

Chlojaponilactone B (CJB) is a linderane sesquiterpene compound separated from the ethnic medicine of herba Lespedezae Cuneatae (academic name: chloranthus japonicus Sieb.) and has good anti-inflammatory and antioxidant activities. Zhao et al found that CJB concentration-dependent inhibition of LPS-induced release of mouse RAW264.7 macrophage NO and inflammatory factors TNF-alpha, IL-6, iNOS by inhibiting activation of NF- κB signaling pathway, and inhibition of phorbol ester-induced ear swelling in mice, had good anti-inflammatory activity (Zhao J, guo Y Q, yang D P, et al, chloroponinactanone B from Chloranthus japonicus: suppression of inflammatory responses via inhibition of the NF-kappa B signaling pathway. J Nat Prod,2016,79 (9): 2257-2263.); ye et al studied the effects of CJB on LPS-induced mouse RAW264.7 macrophages by transcriptome sequencing, found that it exerts anti-inflammatory, antioxidant effects by inhibiting the TLR4/NF- κB signaling pathway, mimicking the binding of TLR4 to CJB by molecular docking techniques, presumably as a TLR4 receptor inhibitor (Ye S, zheng Q, zhou Y, et al, chlorponian B attenuates Lipopolysaccharide-induced inflammatory responses by suppressing TLR4-mediated ROS generation and NF-kappa B signaling pathway. Molecules,2019,24 (20)).

The inventions disclosed in the prior art that can be applied to inhibit activation of inflammatory bodies or block apoptosis of cells include:

[1] use of a flavone derivative for inhibiting activation of inflammatory bodies and/or blocking apoptosis of cells (CN 116019806A)

[2] She, zhong Lingfeng, dai Shanshan, fan Xiaoxi, lin Mote, citizen, use of the small molecule compound AQ-390 for the preparation of a medicament against apoptosis and inhibitors (CN 114469940B)

[3] Weng Changjiang, zheng Jun use and method of protease S273R to inhibit apoptosis of cells (CN 112704731 a)

[4] Xu Lin, wu Haoliang, cui Shengyu, tao Bo, han Danxiang use of fucoxanthin in the manufacture of a medicament for the treatment of diseases associated with NLRP3 induced hepatocyte coke death (CN 116159048A)

[5] Application of piperine in preparing medicines for resisting apoptosis and multiple organ injury (CN 106038563A) of Europe and Yangdong cloud, he Xianhui, liang Yidan, xu Lihui, li Chenan, wei Gongxia and Pan Hao

However, the CJB has no effect of inhibiting activation of inflammatory corpuscles and inhibiting apoptosis of cell coke found in the prior research results.

Disclosure of Invention

The invention provides an application of sesquiterpenoids (CJB) in preparing medicines for inhibiting activation of inflammatory bodies and/or blocking cell apoptosis, wherein the structural formula of the sesquiterpenoids (CJB) is shown as follows:

molecular weight: 286.322; the molecular formula: c (C) ₁₇ H ₁₈ O ₄ 。

Preferably, the blocking of cell apoptosis means inhibiting activated expression of inflammatory small NLRP3 and reducing expression of GSDMD-NT protein and Caspase-1.

Preferably, the concentration of sesquiterpene compounds in the medicament is 2.5-10. Mu.M.

In the medicine, when the concentration of the sesquiterpene compound is 2.5-10 mu M, 1) the cell survival rate in a scorching model can be obviously improved, the PI dyeing rate is obviously reduced, the LDH release amount is reduced, and the compound has better effect of inhibiting the occurrence of cell scorching; 2) Can obviously reduce the maturation and secretion of pro-inflammatory factors IL-1 beta and IL-18 in the cell apoptosis process; 3) Can inhibit the activation expression of inflammatory small NLRP3, reduce the expression of GSDMD-NT and the expression of Caspase-1, and inhibit the activation of classical focal death pathway to inhibit cell focal death. Therefore, the sesquiterpene compound can be used for preparing medicines for inhibiting inflammation bodies (such as inflammation bodies NLRP 3) and/or blocking cell apoptosis.

Preferably, the sesquiterpenoids are used for preparing a medicament for inhibiting the activation of NLRP3 inflammatory bodies.

More preferably, the NLRP3 inflammatory small-scale associated disease is gout, arthritis, alcoholic liver injury, non-alcoholic liver injury, atherosclerosis, type II diabetes, sepsis, multiple sclerosis, systemic lupus erythematosus, alzheimer's disease, parkinson's disease, acne, psoriasis, dandruff, tinea versicolor, seborrheic dermatitis, uv-induced skin injury, uv-induced skin tanning, uv-induced skin aging, or myocarditis.

Preferably, the sesquiterpenoids are used for preparing medicines for preventing, treating or improving diseases related to cell apoptosis.

More preferably, the disease associated with apoptosis is a tumor, a viral infection, a bacterial infection, an infectious disease, diabetes, a cardiovascular disease, a neurological disease, epilepsy, alzheimer's disease, parkinson's disease, a dermatological disease or an autoimmune disease.

Preferably, the medicament is a tablet, a capsule, a granule, a powder, an oral liquid, a granule, a pill, an injection, a powder injection, an aerosol, a film, a liniment or a lotion.

Compared with the prior art, the invention has the following advantages:

the invention discloses an application of sesquiterpenoids CJB in preparing medicines for inhibiting activation of inflammatory corpuscles and inhibiting apoptosis of cell coke, wherein CJB can inhibit apoptosis of cell coke, improve cell survival rate, reduce LDH release, reduce mature release of pro-inflammatory factors IL-1 beta and IL-18 in concentration dependence, reduce expression of Caspase-1 and GSDMD-NT proteins in the apoptosis process, and inhibit activation of inflammatory corpuscles NLRP3, which indicates that CJB has the effects of inhibiting activation of inflammatory corpuscles and inhibiting apoptosis of cell coke through the classical pathway of apoptosis.

Drawings

FIG. 1 is a graph showing the effect of cck8 experiments on the survival rate of apoptosis by CJB.

FIG. 2 shows the results of an experiment for observing the integrity of cell membranes by Hoechst/PI staining.

FIG. 3 is a bar graph of Lactate Dehydrogenase (LDH) release.

FIG. 4 shows the results of ELISA assay for IL-1. Beta. Release.

FIG. 5 shows the results of ELISA assay for IL-18 release.

FIG. 6 shows protein expression of NLRP3, GSDMD-NT and Caspase-1 detected by Western Blot.

Detailed Description

The present invention will be described in further detail with reference to examples and drawings, but embodiments of the present invention are not limited thereto. The raw materials related to the invention can be directly purchased from the market. For process parameters not specifically noted, reference may be made to conventional techniques.

Experimental materials:

THP-1 monocytes: purchased from Shanghai Biochemical and cell Biochemical institute of China academy of sciences

Lipopolysaccharide (LPS): purchased from Sigma-Aldrich Co., USA

Adenosine Triphosphate (ATP): purchased from Sigma-Aldrich Co., USA

Phorbol ester (PMA): purchased from Sigma-Aldrich Co., USA

CJB preparation method reference: zhao J J, guo Y Q, yang D P, et al, chloroaninolactone B from Chloranthus japonicus: suppression of inflammatory responses via inhibition of the NF-kappa B signaling path.J Nat Prod,2016,79 (9): 2257-2263.

Example 1: CCK8 cell viability assay

(1) Experimental method

Cells were packed at a density of 1X 10 ⁴ Culture in 96-well plates, 100. Mu.L/well medium, phorbol ester (tetradecanoyl phorbol acetate, phorbol myristate acetate, PMA) (100 nM) were added and cultured for 24h to induce differentiation of THP-1 monocytes into macrophages. The experiments set a blank control group (without cells, containing 1640 medium), a negative control group (cells were not dosed), a model group and a dosing group, wherein after the model group was stimulated with LPS (100 ng/mL) for 5h, ATP (5 mM) induced THP-1 macrophage coke-death model, and the dosing group was subjected to CJB (2.5, 5, 10 μM) synchronous treatment. After the cells were treated, 10. Mu.Lcck 8 solution was added to each well to avoid air bubbles during the operation, and the plates were placed in an incubator for incubation for 4 hours and then removed, and absorbance at 450nm was measured with a microplate reader. And (3) activity calculation: cell viability (%) = [ a (drug addition) -a (blank)]A (control) -A (blank)]×100％。

(2) Experimental results

As shown in FIG. 1, after LPS/ATP stimulation, cell viability was significantly reduced, and THP-1 macrophage coke death model was successfully induced, and CJB administration group could increase cell survival rate in a concentration-dependent manner, indicating that CJB could inhibit LPS/ATP induced THP-1 macrophage coke death.

Example 2: CJB reduces PI staining proportion, and experiment for inhibiting cell apoptosis effect

(1) Experimental method

THP-1 monocytes were pooled at 1.5X10 ⁶ Density of wells/plate in 6-well plate, and culture with PMA (100 nM) for 24h induced differentiation of THP-1 monocytes into macrophages. Discarding the old culture medium, pretreating with LPS (100 ng/mL) for 5 hours, and stimulating ATP (5 mM) for 1 hour to induce THP-1 macrophage pyrosis; CJB-administered group was given LPS/ATP and C was administered simultaneouslyJB (2.5. Mu.M, 5. Mu.M, 10. Mu.M) was treated. After cell treatment, the cells were removed and placed on ice, the old medium was discarded, washed 2 times with pre-chilled PBS, 0.8-1mL of cell staining buffer was added, 5. Mu.L of Hoechst staining solution was added, 5. Mu.L of PI staining solution was added, and the mixture was gently shaken and mixed, and incubated in ice bath or at 4℃for 30 minutes. After staining, the cells were washed once with PBS and placed under a fluorescence microscope to observe red and blue fluorescence.

(2) Experimental results

Propidium Iodide (PI) cannot penetrate the cell membrane, and for normal cells with intact cell membranes, staining is not possible, whereas for necrotic cells, PI can enter the cell to cause it to stain and fluoresce red due to loss of the integrity of the cell membrane. The experimental results are shown in fig. 2, in the scorched cells induced by LPS/ATP, the red fluorescence is obviously stronger, which indicates that the cell membrane is broken and the cells are cracked and dead, while the red fluorescence intensity of the CJB administration treatment group is obviously weaker, which indicates that the CJB has an inhibiting effect on the scorched cells, and the CJB administration can improve the survival rate of the cells and maintain the integrity of the cell membrane.

Example 3: lactate Dehydrogenase (LDH) release assay

(1) Experimental method

Cells were packed at a density of 1X 10 ⁴ Cells were seeded in 96-well plates and cultured with PMA (100 nM) for 24h to induce differentiation of THP-1 monocytes into macrophages. Cells were washed once with PBS prior to treatment. Fresh serum-free RPMI-1640 medium was changed and the culture wells were set to the following groups: background blank control wells, sample maximum enzyme activity control wells, LPS/ATP stimulated model wells, and CJB dosed wells, wherein the model wells induced THP-1 macrophage pyrosis model by ATP (5 mM) after 5h stimulation with LPS (100 ng/mL), CJB dosed wells were given CJB (2.5, 5, 10. Mu.M) synchronized and 200. Mu.L/well of medium was added. Before cell detection, 1h, 20 mu L of LDH release reagent is added into a 'sample maximum enzyme activity control hole', and the mixture is uniformly mixed and placed into an incubator for continuous culture. After a predetermined detection time point, the cell culture plate was removed, and centrifuged at 400g for 5min. The supernatant of each well was taken at 120. Mu.L, respectively, for sample measurement. Preparing an LDH detection working solution before measurement: a volume of 60. Mu.L per well was used, per 20. Mu.L of lactic acid solution, 20. Mu.L of INT solution (1X),the enzyme solution is prepared by 20 mu L, is prepared at present, and is used and stored in a dark place. During detection, 60 mu L of LDH detection working solution is respectively added into the supernatant of each hole, the mixture is uniformly mixed, incubated at room temperature for 30min in a dark place, and absorbance at 490nm is measured by using an enzyme-labeled instrument. LDH release in the sample to be tested = (absorbance of sample well-absorbance of background blank control well)/(absorbance of maximum enzyme activity of cell-absorbance of sample control well) ×100%.

(2) Experimental results

LDH is an enzyme stably existing in cells, and when cell membranes are damaged, LDH is released into the culture solution, and the released amount of LDH in the cell culture solution is measured to reflect the integrity of the cell membranes. Cell scorch can lead to pore formation of cell membranes, release of LDH in cytoplasm into cell supernatant, and quantitative analysis of cell viability by experimental determination of LDH activity from cell culture fluid. The results are shown in FIG. 3, the THP-1 macrophage has significantly increased LDH release after LPS/ATP stimulation, which indicates that the integrity of cell membrane is destroyed and the cell coke death model is successfully induced, and CJB administration group can inhibit cell coke death, thereby reducing LDH release.

Example 4: ELISA method for detecting inflammatory factor IL-1 beta and IL-18 release experiment

(1) Experimental method

(1) Cell treatment

THP-1 monocytes were pooled at 1.5X10 ⁶ Density of wells/plate in 6-well plate, and culture with PMA (100 nM) for 24h induced differentiation of THP-1 monocytes into macrophages. Discarding the old culture medium, pretreating with LPS (100 ng/mL) for 5 hours, and stimulating ATP (5 mM) for 1 hour to induce THP-1 macrophage pyrosis; CJB-administered groups were treated with LPS/ATP and CJB (2.5. Mu.M, 5. Mu.M, 10. Mu.M) at the same time.

(2) Working solution preparation and standard curve preparation

See in particularmouse TNF-αELISA kit、/>mouse IL-6ELISAkit instructions.

(3) Sample measurement

Diluting the cell supernatant according to a certain proportion, adding the diluted cell supernatant into a reaction hole, setting a blank control hole, attaching a sealing plate film to the blank control hole at 100 mu L/hole, and incubating the blank control hole in a constant box at 37 ℃ for 90min; removing samples in the reaction holes, adding 350 mu L of washing liquid into each hole, washing the plate for 5 times, each time for 30s, adding biotin antibody working solution after removing the washing liquid, 100 mu L/hole, and incubating for 60min at 37 ℃; washing the plate for 5 times, adding enzyme conjugate working solution after throwing the washing solution, and incubating for 30min at 37 ℃ in a dark place with 100 mu L/hole; washing the plate for 5 times, adding 100 mu L of chromogenic substrate (TMB) into each hole after the washing liquid is thrown out, and incubating for 15min at 37 ℃ in a dark place; 100. Mu.L of reaction termination solution was added to each well, and the blue color turned yellow immediately. Immediately after mixing, the OD value was measured with an enzyme-labeled instrument at a wavelength of 450 nm. And (3) taking the concentration of the standard substance as an abscissa and the OD value as an ordinate, and adopting a quadratic polynomial equation to fit to obtain a standard curve. According to the drawn standard curve, the expression conditions of inflammatory factors IL-1 beta and IL-18 in each group of samples are calculated.

(2) Experimental results

When the cells are in pyrosis, caspase-1 activates GSDMD to form active fragment GSDMD-N, and the active fragment GSDMD-N is transferred to cell membrane for perforation, and simultaneously, pro-inflammatory factors IL-1 beta and IL-18 are cut, so that the pro-inflammatory factors IL-1 beta and IL-18 are ripened and released outside the cells, and the release amount of IL-1 beta and IL-18 in the supernatant of cell culture fluid is detected by ELISA method, thus the inhibition effect of CJB on macrophage pyrosis can be observed. The results are shown in FIGS. 4 and 5, in which the release of IL-1β and IL-18 from THP-1 macrophages is significantly increased after LPS/ATP stimulation, whereas CJB administration reduces its production and release in a concentration-dependent manner.

Example 5: western Blot detection of Coke death related protein expression experiments

(1) Experimental method

(1) Cell treatment

THP-1 monocytes were pooled at 1.5X10 ⁶ Density of wells/plate in 6-well plate, and culture with PMA (100 nM) for 24h induced differentiation of THP-1 monocytes into macrophages. Discarding the old culture medium, pretreating with LPS (100 ng/mL) for 5 hours, and stimulating ATP (5 mM) for 1 hour to induce THP-1 macrophage pyrosis; CJB-administered groups were treated with LPS/ATP and CJB (2.5. Mu.M, 5. Mu.M, 10. Mu.M) at the same time. After the treatment, the cells are taken out and placed on ice, the culture medium is discarded,washing twice with precooled PBS, adding 100 μl of RIPA lysate containing protease inhibitor PMSF into each well, performing lysis on ice for 10min, scraping off cells with a cell scraper, collecting in a 1.5mL centrifuge tube, performing lysis on ice for 30min, and extracting total cell proteins. After the cells were sufficiently lysed, they were centrifuged at 12000rpm for 10min in a centrifuge at 4 ℃. The precipitate was discarded and the protein supernatant was collected. The BCA method is adopted to measure the protein concentration of the sample, and specific operation is shown in the specification of a BCA protein concentration measuring kit (P0010) in Biyundian days. The histones were uniformly loaded at 40 μg and a loading volume of 20 μl, and the tube samples were diluted to the same concentration, 2 μg/μl, with PBS. According to the volume of the prepared sample, 5 XSDS-PAGE loading buffer is added, the mixture is placed in a low-speed centrifuge for centrifugation for 1min after uniform mixing, and the protein is denatured after heating in a metal bath at 95 ℃ for 10min. Standing at room temperature, and storing in a refrigerator at-80deg.C.

(2) Western blot experiment

And (3) glue preparation: 8% or 10% of the separation gel and 5% of the concentrated gel were prepared according to the specification of the Biyundian SDS-PAGE gel rapid preparation kit (P0012 AC).

Electrophoresis: placing the fixed gel glass plate into an electrophoresis tank, adding electrophoresis buffer solution, then extracting a comb, slowly adding 20 mu L of protein sample into each hole, and respectively adding 5 mu L of protein pre-dyeing Marker into the outermost holes on two sides. And (3) covering an electrophoresis tank corresponding to the anode and the cathode, switching on a power supply, carrying out 70V electrophoresis for about 30min, regulating the voltage to 120V after observing that the sample enters the separation gel from the concentrated gel, and stopping electrophoresis after the bromophenol blue bubbles reach the gel bottom after electrophoresis for about 1 h.

Transferring: the gel was removed and the concentrated gel was partially discarded. And cutting the PVDF film into the size of 8.7cm multiplied by 5.5cm, soaking the cut PVDF film in methanol for 3min for activation, and then placing the PVDF film in a film transferring liquid for balancing. Spreading a sieve plate, placing a black electrode on the lowest layer, sequentially placing a sponge cushion and filter paper, lightly placing gel, spreading a PVDF film on the gel to remove bubbles, sequentially placing the filter paper and the sponge cushion, covering a white electrode, clamping, and fixing with the sieve plate. The operation process is carried out in the film transfer liquid, and no bubble generation between each layer is ensured. Placing the sieve trays into an electrophoresis tank, adding film transfer liquid, placing into an ice box, adjusting constant current to 220mA, and transferring films for 100min in an ice bath.

Closing: after the transfer, the PVDF membrane is soaked in 5% sealing liquid and is placed in a horizontal shaking table for 2h at room temperature. After the end of the blocking, TBST was added to wash the membrane 3 times for 5min each.

Incubation resistance: the antibodies were mixed in proportion 1 with the Biyundian Western primary antibody dilutions: diluted 1000, PVDF membrane containing the band of interest was placed in the corresponding primary antibody and incubated overnight at 4 ℃. Recovering primary antibody, taking out membrane, adding TBST, and rapidly washing membrane with shaking table for 3 times each for 10min.

Secondary antibody incubation: diluting the secondary antibody by using a Biyundian Western secondary antibody diluent according to the proportion of 1:5000, putting the membrane into the secondary antibody until the membrane is completely immersed, and placing the membrane into a shaking table for incubation for 1.5h at a low speed and room temperature. Recovering secondary antibody, adding TBST, and rapidly washing the membrane in a shaking table for 10min each time.

Developing: the developing luminous solution A and the developing luminous solution B are uniformly mixed in equal volumes (prepared in situ). The developing instrument is started up and precooled to-20 ℃. PVDF film is placed in the center of the luminous plate, mix (A+B) liquid is evenly dripped on the surface of the film, and the dark box door is closed. And adjusting the focal length, the exposure background and the exposure time, and obtaining a white light image and a developing image after the exposure is completed and the clear image is displayed. The WB bands were quantitatively analyzed using Image J software.

(2) Experimental results

Western blot analysis CJB focused on the classical pathway-related proteins: as shown in FIG. 6, the results of the effect of Caspase-1, NLRP3 and active GSDMD-N expression are shown that in the LPS/ATP induced model group, the expression level of Caspase-1, NLRP3 and GSDMD-N is increased, and compared with the model group, the expression level of the above protein CJB administration group is reduced, and the CJB inhibits the activation of THP-1 macrophage NLRP3 inflammatory body, which indicates that CJB can inhibit the pyrodeath by affecting the classical pyrodeath pathway of THP-1 macrophages.

The above examples are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above examples, and any other changes, modifications, substitutions, combinations, and simplifications that do not depart from the spirit and principle of the present invention should be made in the equivalent manner, and the embodiments are included in the protection scope of the present invention.

Claims (8)

1. The application of a sesquiterpenoid in preparing a medicament for inhibiting activation of inflammatory corpuscles and/or blocking cell apoptosis is provided, wherein the sesquiterpenoid has a structural formula shown as follows:

molecular weight: 286.322; the molecular formula: c (C) ₁₇ H ₁₈ O ₄ 。

2. The use according to claim 1, wherein the concentration of sesquiterpene compounds in the medicament is 2.5-10 μm.

3. The use according to claim 1, wherein said blocking of cell apoptosis is inhibition of activated expression of inflammatory small NLRP3, reduction of expression of GSDMD-NT protein and Caspase-1.

4. The use according to claim 1, characterized in that the sesquiterpenoids are used for the preparation of a medicament for inhibiting the activation of NLRP3 inflammatory bodies.

5. The use according to claim 4, wherein the NLRP3 inflammatory small-scale related disease is gout, arthritis, alcoholic liver injury, non-alcoholic liver injury, atherosclerosis, type II diabetes, sepsis, multiple sclerosis, systemic lupus erythematosus, alzheimer's disease, parkinson's disease, acne, psoriasis, dandruff, tinea versicolor, seborrheic dermatitis, uv-induced skin injury, uv-induced skin tanning, uv-induced skin aging, or myocarditis.

6. The use according to claim 1, wherein the sesquiterpenoid is used for the preparation of a medicament for the prevention, treatment or amelioration of a disease associated with apoptosis.

7. The use according to claim 6, wherein the disease associated with apoptosis is a tumor, a viral infection, a bacterial infection, an infectious disease, diabetes, a cardiovascular disease, a neurological disease, epilepsy, alzheimer's disease, parkinson's disease, a dermatological disease or an autoimmune disease.

8. The use according to any one of claims 1 to 7, wherein the medicament is in the form of a tablet, capsule, granule, powder, oral liquid, granule, pill, injection, powder for injection, aerosol, film, liniment or lotion.