Novel compounds for promoting hair growth or inhibiting inflammatory disorders and their use

Abstract

This invention provides novel compounds for promoting hair growth or inhibiting inflammatory disorders, and their uses. [Solution] Compounds such as the following formula SSA are provided. JPEG2026076464000035.jpg5063

Description

[Technical Field]

[0001] The present invention relates to novel compounds for promoting hair growth or inhibiting inflammatory disorders and the use thereof; in particular, to novel compounds for promoting hair growth or inhibiting inflammatory disorders comprising formula (I), formula (II), or formula (III) and the use thereof. [Background technology]

[0002] Alopecia can be classified into various patterns, including diffuse alopecia, specific pattern alopecia, and localized alopecia. Furthermore, it can be classified into two types based on damage to hair follicle cells: scarring and non-scarring.

[0003] Scarring alopecia typically refers to pathological changes or necrosis of hair follicles in the scalp due to wounds or diseases, resulting in permanent scarring. Common causes include infections, trauma, or diseases. Non-scarring alopecia, on the other hand, refers to hair follicles that retain the ability to produce new hair without damage to their regeneration centers. Common types of non-scarring alopecia include male pattern baldness, alopecia areata, telogen effluvium, anagen effluvium, secondary syphilis, and trichotillomania.

[0004] The liver is one of the most important organs in the human body, but it can be damaged by drugs, alcohol, diet, and insufficient work and rest. Liver damage can lead to degeneration, necrosis, fibrous tissue hyperplasia, and other lesions of liver cells, resulting in a range of hepatic pathological changes and potentially leading to secondary diseases such as hepatitis, cirrhosis, and liver cancer.

[0005] Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) are primarily involved in the metabolism of amino acids and proteins in the human body. Because GOT and GPT are present in high concentrations in liver cells, they can enter the bloodstream if the liver is damaged. Consequently, they are used as biological markers to detect liver damage in blood tests.

[0006] Acute respiratory distress syndrome (ARDS) is a severe inflammatory lung condition that impairs the normal function of the alveoli and leads to insufficient blood oxygen levels. This can cause damage to other organs and can be fatal. Treatment for ARDS primarily involves supportive care, including the use of mechanical ventilation.

[0007] These diseases continue to affect many people, and research into alternative or more effective medications is ongoing.

[0008] Natural compounds are valuable due to their abundant supply and diverse structures, and they serve as a crucial foundation for drug development. Between 1981 and 2019, nearly half of the new drugs approved by the FDA were derived from natural products or their derivatives. Examples include vincristine, doxorubicin, and paclitaxel for cancer treatment, and penicillin derived from fungi used as an antibiotic. Current research is actively focused on identifying natural compounds with potential for development as novel drugs for promoting hair growth, protecting the liver, and preventing ARDS. [Overview of the project] [Problems that the invention aims to solve]

[0009] The present invention aims to promote hair growth or inhibit inflammatory disorders through the use of novel compounds and their applications. [Means for solving the problem]

[0010] The present invention relates to a compound having a skeleton comprising the following formula (I).

[0011] [ka]

[0012] In formula (I), R3 is hydrogen (H), and R1 and R2 together form a sesquiterpenoid; R2 is a C1-C6 alkyl group, and R1 and R3 together form a sesquiterpenoid.

[0013] Preferably, the compounds of the present invention having formula (I) include any of the following compounds SSA (Chemical Formula 2), compound SSB (Chemical Formula 3), compound SSC (Chemical Formula 4), compound SSE (Chemical Formula 5), and compound SSL (Chemical Formula 6).

[0014]

Chemical Formula

[0015]

Chemical Formula

[0016]

Chemical Formula

[0017]

Chemical Formula

[0018]

Chemical Formula

[0019] Furthermore, the present invention relates to compounds having a skeleton containing the following formula (II).

[0020]

Chemical Formula

[0021] In formula (II), R1 is a sesquiterpenoid.

[0022] Preferably, the compound of the present invention having formula (II) is the following compound SSLH-8 (Chemical Formula 8).

[0023] [ka]

[0024] Furthermore, the present invention relates to a compound having a skeleton comprising formula (III).

[0025] [ka]

[0026] In formula (III), R1 is a sesquiterpenoid, and R2 is hydrogen (H), an acetoxy group, an acetyl group, a hydroxyl group, a methyl group, a formyl group, a formic acid group, a methyl ester group, or a halogen.

[0027] Preferably, the compound of the present invention having formula (III) is compound SSF (Chemical Formula 10) or compound SSG (Chemical Formula 11).

[0028] [ka]

[0029] [ka] [Brief explanation of the drawing]

[0030] [Figure 1] The chemical structure of the novel compound of the present invention is shown. [Figure 2] The novel compounds of the present invention demonstrate inhibition of superoxide anion generation and elastase release at different concentrations. Compared to the untreated group, * indicates p<0.05, ** indicates p<0.01, and *** indicates p<0.001. [Figure 3]This shows the cell viability of human neutrophils treated with the novel compound of the present invention. [Figure 4] SSC and SSE have been shown to inhibit the production of reactive oxygen species (ROS) in neutrophils activated by formyl peptide receptor 1 (FPR1) agonists. [Figure 5] This study demonstrates that SSCs dose-dependently block the binding of FPR1 agonists (such as formil-NIe-Leu-Phe-NIe-Tyr-Lys (fNLFNYK)) to FPR1. [Figure 6] This study demonstrates that SSE dose-dependently blocks the binding of FPR1 agonists (such as fNLFNYK) to FPR1. [Figure 7] The growth rate of human dermal papilla cells (HHDPCs) cultured in a culture medium without fetal bovine serum (0% FBS) after treatment with the novel compound of the present invention is shown. Compared to the control group (DMSO), * indicates p<0.05. [Figure 8] The growth rate of human dermal papilla cells (HHDPCs) cultured in a culture medium containing 5% fetal bovine serum (FBS) after treatment with the novel compound of the present invention is shown. Compared to the control group (DMSO), * indicates p<0.05. [Figure 9] This document describes an experimental procedure for testing the effect of the novel compound of the present invention on improving acute respiratory distress syndrome (ARDS). Explanation of symbols: % indicates administration; * indicates induction of ARDS; ! indicates euthanasia. [Figure 10] The image shows hematoxylin and eosin (H&E) stained tissue sections of the lungs of experimental animals. [Figure 11A] The quantitative results of stained lung tissue sections from experimental animals are shown. This is an analysis of Ly6G+ protein, and * indicates p<0.05 compared to the untreated group. [Figure 11B] The quantitative results of stained lung tissue sections from experimental animals are shown. This is an analysis of elastase release (elastase+), and * indicates p<0.05 compared to the untreated group. [Figure 11C]The quantitative results of stained lung tissue sections from experimental animals are shown. This is an analysis of 4-hydroxy-2-nonenal (4-HNE+), and * indicates p<0.05 compared to the untreated group. [Figure 11D] The quantitative results of stained lung tissue sections from experimental animals are shown. This is an analysis of citrullinated histone H3 (CitH3+), and * indicates p<0.05 compared to the untreated group. [Figure 11E] The quantitative results of stained lung tissue sections from experimental animals are shown. This is an analysis of interleukin-1β (IL-1β), and * indicates p<0.05 compared to the untreated group. [Figure 12] The biochemical analysis results of the experimental animals' blood (glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine (CRE), blood urea nitrogen (BUN)) are shown. When compared to the untreated group, * indicates p<0.05. [Figure 13] This document describes an experimental procedure for testing the effect of the novel compound of the present invention on improving liver injury. Explanation of symbols: % indicates administration. * indicates induction of acute liver injury (ALI). ! indicates sacrificial. [Figure 14] This shows hematoxylin and eosin (H&E) stained tissue sections of the liver of experimental animals. [Figure 15] The biochemical analysis results of the experimental animals' blood (glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine (CRE), blood urea nitrogen (BUN)) are shown. When compared to the untreated group, * indicates p<0.05. [Modes for carrying out the invention]

[0031] The present invention relates to a pharmaceutical composition for promoting hair growth, the pharmaceutical composition comprising a compound having formula (I), formula (II), or formula (III), or a medically acceptable salt thereof, wherein if the compound has the structure of formula (I), R3 is hydrogen (H) and R1 and R2 together form a sesquiterpenoid; if R2 is a C1-C6 alkyl group and R1 and R3 together form a sesquiterpenoid; if the compound has the structure of formula (II), R1 is a sesquiterpenoid; and if the compound has the structure of formula (III), R1 is a sesquiterpenoid and R2 is hydrogen (H), an acetoxy group, an acetyl group, a hydroxyl group, a methyl group, a formyl group, a formic acid group, a methyl ester group, or a halogen.

[0032] The present invention relates to a pharmaceutical composition for inhibiting inflammatory disorders, wherein the pharmaceutical composition comprises a compound having formula (I), formula (II), or formula (III), or a pharmaceutically acceptable salt thereof, wherein if the compound has the structure of formula (I), R3 is hydrogen (H) and R1 and R2 together form a sesquiterpenoid; if R2 is a C1-C6 alkyl group and R1 and R3 together form a sesquiterpenoid; if the compound has the structure of formula (II), R1 is a sesquiterpenoid; and if the compound has the structure of formula (III), R1 is a sesquiterpenoid and R2 is hydrogen (H), an acetoxy group, an acetyl group, a hydroxyl group, a methyl group, a formyl group, a formic acid group, a methyl ester group, or a halogen.

[0033] Preferably, the compound of the present invention having formula (I) includes any of the following compounds: compound SSA (Chemical Formula 12), compound SSB (Chemical Formula 13), compound SSC (Chemical Formula 14), compound SSE (Chemical Formula 15), and compound SSL (Chemical Formula 16).

[0034] [ka]

[0035] [ka]

[0036] [ka]

[0037] [ka]

[0038] [ka]

[0039] The compound having formula (II) is compound SSLH-8 (Chemical Formula 17).

[0040] [ka]

[0041] Compounds having formula (III) are the following compounds SSF (Chemical Formula 18) or SSG (Chemical Formula 19).

[0042] [ka]

[0043] [ka]

[0044] The present invention also relates to the use of compounds having formula (I), formula (II), or formula (III), or pharmaceutically acceptable salts thereof, for the preparation of pharmaceutical compositions for promoting hair growth.

[0045] The present invention also relates to the use of compounds having formula (I), formula (II), or formula (III), or pharmaceutically acceptable salts thereof, for the preparation of pharmaceutical compositions for inhibiting inflammatory disorders.

[0046] In the present invention, inflammatory disorders include lung injury or liver injury.

[0047] In this invention, the subject of the invention is humans or mammals.

[0048] The pharmaceutical compositions of the present invention may contain pharmaceutically acceptable excipients, particularly a predetermined solvent or oil, and optionally a pH adjuster, and may also contain a dispersant. Examples of solvents used in the present invention include, but are not limited to, water, ethanol, isopropanol, 1,3-butanediol, propylene glycol, and glycerin. Examples of oils used in the present invention include, but are not limited to, corn oil, sesame oil, linseed oil, cottonseed oil, soybean oil, peanut oil, monoglycerides, diglycerides, triglycerides, mineral oil, squalene, jojoba oil, olive oil, evening primrose oil, borage oil, grapeseed oil, coconut oil, sunflower oil, shea butter, and any combination thereof.

[0049] In a preferred method, the solvent and the oil can be used individually or in any combination thereof.

[0050] Examples of useful dispersants beneficial to the present invention include, but are not limited to, lecithin, organic monoglycerides, sorbitan fatty acid esters, polyoxyethylene fatty acid esters, and sorbitan stearate. These raw materials can also be used individually or in any combination thereof.

[0051] In the present invention, the pharmaceutical composition is preferably administered orally or prepared as a topical preparation; examples of topical preparations include, but are not limited to, creams, ointments, gels, cleansing lotions, patches, or inhalants, aerosols, suppositories, etc.

[0052] When a drug is used as a topical preparation, it can be used as an aqueous solution, non-aqueous solvent, suspension, emulsion, lyophilized preparation, etc., based on a suitable topical skin preparation, and can be used and sterilized according to known methods. Compositions in the form of gels, creams, and ointments can be prepared according to the form of the composition by adding known emollients, emulsifiers, and thickeners or other materials known in the art using known methods. Gel-type compositions can be prepared, for example, by adding emollients such as trimethylolpropane, polyethylene glycol, and glycerol, solvents such as propylene glycol, ethanol, and isocetyl alcohol, and pure water.

[0053] In the present invention, liver injury includes, but is not limited to, liver injury (including, but not limited to, acute or chronic liver injury), liver disease, such as hepatitis (including, but not limited to, alcoholic hepatitis, drug-induced hepatitis, fatty liver disease, viral hepatitis, and chronic hepatitis), fatty liver, liver fibrosis, cirrhosis, liver cancer, and other liver diseases caused by liver injury.

[0054] In this invention, lung injury includes, but is not limited to, acute respiratory distress syndrome (ARDS).

[0055] This embodiment describes the best embodiment and does not limit the invention.

[0056] 1. Extraction of compounds In this invention, a sample of leaves from *Schizygium schmire* (10.8 kg) was collected and dried (5.5 kg). The dried leaf sample was immersed in methanol at room temperature for 3 days, and this was repeated a total of three times. The resulting extract was reduced and compressed to obtain a methanol extract (650 g). The methanol extract was split into n-hexane / water (1:1, v / v) to obtain an n-hexane layer (220 g) and an aqueous layer (22.5 L). 180 g of the n-hexane layer was collected and separated by gravity column chromatography. Using silica gel (SiliaFlash®) as the stationary phase, gradient extraction was performed with an n-hexane / acetone (98:2, v / v) solvent system, gradually increasing the proportion of acetone, and finally extracting the highly polar portion with methanol to obtain a total of 14 fractions. Next, using medium-pressure liquid chromatography (MPLC) and preparative thin-layer chromatography (preparative TLC), compounds simisyzygin A (SSA), simisyzygin B (SSB), simisyzygin E (SSE), and simicadinene A (SSLH-8) were obtained from fraction 10, simisyzygin C (SSC), simisyzygin E (SSE), and simisyzygin L (SSL) were obtained from fraction 7, and simisyzygin F (SSF) and simisyzygin G (SSG) were obtained from fraction 11. The structures of these compounds were further confirmed by mass spectrometry, ultraviolet spectrometry, infrared spectrometry, polarimeter, circular dichroism spectrophotometer, and X-ray diffractometer.

[0057] The structure of the above compound is shown in Figure 1.

[0058] 2. Superoxide anion and elastase release inhibition assay In this invention, the anti-inflammatory activity of the above compounds was evaluated by superoxide anion and elastase release inhibition assays.

[0059] First, prepare the neutrophils.

[0060] Blood (approximately 50 mL) was collected from healthy blood donors (age 20-35 years, with regular lifestyle habits, and no medication use for at least one week) who voluntarily supported or expressed interest in the project. Blood was collected from the elbow vein using a sterile vacuum tube and mixed with an equal volume of 3% dextran solution. The mixture was allowed to stand to allow the red blood cells to settle. The supernatant containing neutrophils was carefully placed on a centrifuge tube containing Ficolpack cell isolation solution. After centrifugation, various blood cells were separated by density gradient, with neutrophils and a small amount of red blood cells pelleting at the bottom. The remaining red blood cells were dissolved using different concentrations of sodium chloride (NaCl) solution, taking advantage of the difference in osmotic fragility, to retain the desired neutrophils. Unless otherwise specified, in anti-inflammatory experiments, neutrophils were suspended in Hanks equilibrium salt solution (HBSS) containing 1 mM calcium chloride (CaCl2) and 1 mM magnesium chloride (MgCl2).

[0061] The anti-inflammatory effects of the compounds of the present invention on neutrophils were evaluated using a respiratory burst assay and degranulation evaluation.

[0062] Respiratory bursts are mainly caused by superoxide anions. JPEG2026076464000021.jpg615 and reactive oxygen species (ROS) are produced, and superoxide anions are produced. Detection of JPEG2026076464000022.jpg615 was performed using a neutrophil suspension (6*10) containing 0.6 mg / mL of felicitochrome c. 5 The compound was added to cells ( / mL) at 37°C for 2 minutes, followed by treatment with 1 μg / mL of cytochalasin B (CB) for 3 minutes. Next, the cells were activated for 10 minutes using N-formyl-L-methionyl-L-leucinoyl-L-phenylalanine (fMLF) as a stimulant. Then, absorbance values ​​were measured at a wavelength of 550 nm using a UV spectrophotometer.

[0063] In the elastase release experiment, a neutrophil suspension (6*10) containing 100 μM methoxysuccinyl-ala-ala-proline-valine-p-nitroanilide (MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide) was used. 5 Cells (at / mL) were incubated with the compound at 37°C for 2 minutes. Next, cells were treated with 0.5 μg / mL cytochalasin B (CB) for 3 minutes, and neutrophils were activated by adding 0.1 μM fMLF for 10 minutes. Absorbance values ​​were measured at 405 nm using a UV spectrophotometer. Experimental results were expressed as inhibition rates.

[0064] The results shown in Table 1 suggest that all compounds significantly inhibited neutrophil inflammation, with compounds SSC and SSE exhibiting the most potent effects.

[0065] [Table 1]

[0066] Human neutrophils were treated with 0.1% dimethyl sulfoxide (DMSO, control group) or a compound (experimental group) for 5 minutes, followed by the addition of fMLF / CB for 10 minutes.

[0067] Inhibition rate at 3 μM (Inh%) The results are shown as mean ± SEM (n=6). ***P<0.005 compared to the control group. I C 50 This refers to the concentration required for 50% inhibition.

[0068] Figure 2 shows the results for different concentrations (0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM) of compounds that inhibit the release of superoxide anion and elastase. The results show that SSC and SSE at all concentrations inhibited the release of superoxide anion and elastase in a dose-dependent manner, and significant inhibition was observed for each compound from 0.1 μM upwards.

[0069] Lactate dehydrogenase (LDH) is normally present in the cytoplasm of cells. When cells die, LDH is released into the extracellular space. Measuring the extracellular LDH concentration can help determine whether a compound is cytotoxic.

[0070] Neutrophil suspension (6*10 5 Cells ( / mL) were incubated with the compound or TritonX-100 (as total LDH release) at 37°C for 15 minutes. The samples were centrifuged at 4°C and 200×g for 8 minutes, and the supernatant was collected and the LDH content was measured using an LDH ELISA kit.

[0071] Figure 3 shows the cell viability of neutrophils treated with various compounds of the present invention, demonstrating that none of the compounds exhibit cytotoxicity.

[0072] The effect of the compound on reactive oxygen species (ROS) was analyzed using chemiluminescence. A neutrophil suspension containing 37.5 μM luminol was placed in a 96-well white plate (7*10 5 Cells ( / mL) were preheated at 37°C for 5 minutes. The test compound was then added and incubated for 5 minutes. Neutrophils were stimulated to produce ROS by adding N-formylmethionine-leucylphenylalanine (fMLF; 0.1 μM) for 6 minutes. ROS production was measured using a luminescence plate reader.

[0073] Figure 4 shows the results of ROS inhibition by compounds at different concentrations (0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM). The results indicate that all concentrations of SSC and SSE have the ability to inhibit neutrophil-mediated ROS formation in a dose-dependent manner.

[0074] In the experiment, neutrophils (2*10 6Cells (per mL) were suspended in Hanks equilibrium salt solution (HBSS) without calcium chloride (CaCl2) and magnesium chloride (MgCl2). The test compound was added at 4°C for 10 minutes, followed by the addition of formyl-NIe-Leu-Phe-NIe-Tyr-Lys (fNLFNYK; 2nM) for 20 minutes. The fluorescence expression of fNLFNYK on the cells was measured using flow cytometry.

[0075] Based on the experimental results shown in Figures 5 and 6, SSC and SSE at various concentrations (0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM) exhibit a dose-dependent decrease in the binding of fNLFNYK (2 nM) to FPR1. This indicates that SSC and SSE have the ability to bind to FPR1 on neutrophils.

[0076] These experimental results indicate that SSCs and SSEs bind to FPR1 on neutrophils, thereby influencing the neutrophil's inflammatory response, including the release of superoxide anions, elastase, and ROS produced by neutrophils. Based on the above data, SSCs and SSEs have potential for development as therapeutic agents for immune-related inflammatory diseases.

[0077] 3. Evaluation of the effectiveness of hair growth promotion Human dermal papilla cells (HHDPCs) are placed in 24-well plates in a 2x10 grid. 3 Cells were seeded at a cell / well density and cultured in C-MSCM medium at 37°C. After 24 hours of incubation, the old C-MSCM medium was aspirated and removed.

[0078] Each well was supplemented with 400 μL of C-MSCM medium, either without fetal bovine serum (FBS) or containing 5% FBS, followed by the addition of a control solution or a test compound at different concentrations. The plates were then incubated at 37°C for 48 hours. After incubation, 20 μL of WST-1 was added to each well, and the plates were incubated further at 37°C for 2 hours. Absorbance was measured at 450 nm and 620 nm.

[0079] The results shown in Figure 7 indicate that under 0% FBS conditions, SSE at concentrations of 0.01–10 μM promotes HHDPC proliferation, with the best effect observed at 1 μM. In the case of SSC, the results indicate that concentrations of 0.01–1 μM effectively promote HHDPC proliferation.

[0080] Under 5% FBS conditions (Figure 8), no promotion of HHDPC proliferation by SSE was observed. However, the results for SSC indicate that a 10 μM concentration of SSC had a proliferative effect on HHDPC cells.

[0081] SSE and SSC can effectively promote the proliferation of HHDPC and can be developed as hair growth ingredients.

[0082] 4. Evaluation of the effect on improving acute respiratory distress syndrome (ARDS) All animal experiments were approved by the Animal Care Committee (IACUC) of Chang Gung University.

[0083] Eighteen male BALB / c mice, 7-10 weeks old and weighing 20-25 grams, were randomly divided into the following six groups: negative control group (untreated, no induction; n=3), lipopolysaccharide (LPS)-inducing control group (untreated, LPS-induced ARDS; n=3), low-dose SSC group (administered 5 mg / kg body weight of SSC, LPS-induced ARDS; n=3), high-dose SSC group (administered 15 mg / kg body weight of SSC, LPS-induced ARDS; n=3), low-dose SSE group (administered 5 mg / kg body weight of SSE, LPS-induced ARDS; n=3), and high-dose SSC group (administered 15 mg / kg body weight of SSE, LPS-induced ARDS; n=3).

[0084] As shown in Fig. 9, at the start of the experiment, except for the negative control group and the LPS control group, different compounds of the present invention were intravenously (IV) administered to experimental animals according to the group. One hour after the administration of different compounds, LPS at 5 mg / kg body weight was administered to all experimental animals except the negative control group using a pulmonary administration nebulizer (purchased from Shanghai Yuyan Instruments Co., Ltd.). All experimental animals were euthanized 24 hours after ARDS induction, blood was collected and centrifuged, the supernatant was collected, and then biochemical values were detected. The lungs were extracted under a 21 cmH2O column pressure, half of which was used for hematoxylin & eosin (H&E) staining, and the other half was frozen at -80°C.

[0085] The results of lung tissue staining shown in Fig. 10 indicate that the compounds of the present invention can effectively improve the onset of ARDS in a dose-dependent manner or reduce the severity of ARDS.

[0086] As shown in Figs. 11A - 11E, the quantitative results of lung tissue staining and blood biomarkers such as Ly6G+ protein, interleukin-1β (IL-1β), elastase release, 4-hydroxy-2-nonenal (4-HNE + ), and citrullinated histone H3 (CitH3 + ) indicate that the compounds can effectively improve the onset of ARDS in a dose-dependent manner or reduce the severity.

[0087] The blood analysis results shown in Fig. 12 indicate that in experimental animals treated with the compounds of the present invention, the levels of glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), creatinine (CRE), and blood urea nitrogen (BUN) did not increase abnormally. All levels were within the normal range, indicating no harm to the liver or kidneys.

[0088] 5. Evaluation of the effect on the improvement of acute liver injury (ALI) All animal experiments were approved by the Animal Care Committee (IACUC) of Chang Gung University.

[0089] As shown in Figure 13, 18 male BALB / c mice, 7-10 weeks old and weighing 20-25 grams, were randomly divided into the following six groups: Vehicle group (saline, no LPS + D-galactosamine (D-GalN) induction, no compound administration), LPS + D-GalN control (LPS, 40 μg / kg body weight; D-GalN, 500 mg / kg body weight, no compound administration), LPS + D-GalN + SSC low-dose group (LPS, 40 μg / kg body weight; D-GalN, 500 mg / kg body weight; SS The mice were divided into three groups: C (1 mg / kg-body weight), LPS+D-GalN+SSC high-dose group (LPS, 40 μg / kg-body weight; D-GalN, 500 mg / kg-body weight; SSC, 10 mg / kg-body weight), LPS+D-GalN+SSE low-dose group (LPS, 40 μg / kg-body weight; D-GalN, 500 mg / kg-body weight; SSE, 1 mg / kg-body weight), and LPS+D-GalN+SSE high-dose group (LPS, 40 μg / kg-body weight; D-GalN, 500 mg / kg-body weight; SSE, 10 mg / kg-body weight). Each mouse received an intravenous injection of the corresponding group's different concentration of SSC or SSE over 1 hour, followed by an intraperitoneal injection of physiological saline or LPS+D-GalN over 5 hours. Blood samples were collected and the levels of glutamate pyruvate transaminase (GPT), glutamate oxaloacetate transaminase (GOT), creatinine (CRE), and blood urea nitrogen (BUN) were analyzed. Liver samples were collected, the larger section on the right was used for H&E staining, and the remaining samples were frozen at -80°C.

[0090] The H&E staining results shown in Figure 14 indicate that SSC and SSE can improve the pathological condition of acute lung injury (ALI).

[0091] The results of the blood biochemical analysis shown in Figure 15 indicate that D-GalN / LPS induced significant acute liver tissue damage, as clearly demonstrated by the elevated serum levels of GOT and GPT. Treatment with SSC and SSE effectively reduced the elevated levels of GOT and GPT.

[0092] Although the present invention has been described and illustrated in sufficient detail for those skilled in the art to create and use it, various substitutions, modifications, and improvements are evident without departing from the spirit and scope of the invention.

[0093] Those skilled in the art will readily understand and implement the objectives of the present invention and achieve the aforementioned results and advantages. The sources of physiological signals, weights, or gene sets used in the present invention are provided for illustrative purposes only and are not intended to limit the scope or application of the invention. Modifications or alternative uses generated by those skilled in the art in carrying out or using this technology are included within the spirit of the invention and are defined by the claims.

Claims

1. Compounds containing formula (I): 【Chemistry 1】 (In formula (I), R ３ is hydrogen (H), and R １ and R ２ They combine to form sesquiterpenoids, R ２ is a C1-C6 alkyl group, and R １ and R ３ (These substances combine to form sesquiterpenoids.)

2. Compound SSA 【Chemistry 2】 Compound SSB 【Transformation 3】 Compound SSC 【Chemistry 4】 Compound SSE 【Transformation 5】 ,or Compound SSL 【Transformation 6】 The compound according to claim 1, comprising:

3. Compounds containing formula (II): 【Transformation 7】 Formula (II); (In the formula, R １ (These are sesquiterpenoids.)

4. Compound SSLH-8 【Transformation 8】 The compound according to claim 3, comprising:

5. Compounds containing formula (III): 【Chemistry 9】 Formula (III); In formula (III), R １ is a sesquiterpenoid, and R ２ is hydrogen (H), an acetoxy group, an acetyl group, a hydroxy group, a methyl group, a formyl group, a formic acid group, a methyl ester group, or a halogen.

6. Compound SSF 【Chemistry 10】 ,or Compound SSG 【Chemistry 11】 The compound according to claim 5, comprising:

7. A pharmaceutical composition comprising a compound according to any one of claims 1 to 6, or a medically acceptable salt thereof.

8. Use of a compound or a medically acceptable salt thereof according to any one of claims 1 to 6 for the manufacture of a pharmaceutical composition for promoting hair growth.

9. Use of a compound or a medically acceptable salt thereof according to any one of claims 1 to 6 for the production of a pharmaceutical composition for inhibiting inflammatory disorders.

10. The use according to claim 9, wherein the inflammatory disorder includes lung injury or liver injury.

11. The use according to claim 9, wherein the liver injury includes acute liver injury, chronic liver injury, alcoholic hepatitis, drug-induced hepatitis, fatty liver, viral hepatitis, chronic hepatitis, liver cancer, cirrhosis, liver fibrosis, fatty liver, or acute respiratory distress syndrome (ARDS).

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