CN115819378A - Coffee diterpenoid compounds and application thereof in preparation of medicines with effects of improving skin cell activity and inhibiting skin cell inflammatory injury - Google Patents
Coffee diterpenoid compounds and application thereof in preparation of medicines with effects of improving skin cell activity and inhibiting skin cell inflammatory injury Download PDFInfo
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Abstract
The invention discloses a coffee diterpenoid compound and application thereof in preparation of a medicine for improving skin cell activity and inhibiting skin cell inflammatory injury. The coffee diterpenoid compound is characterized by having a structure shown in a formula I or a formula II. The composition and the extract comprise coffee diterpenoid compounds with structures shown in formula I and formula II. The coffee diterpenoid compound or the composition thereof with the structure shown in the formula I or the formula II has the effects of improving the vitality of skin cells and inhibiting inflammatory injury of the skin cells; therefore, the coffee diterpenoid compound with the structure shown in the formula I or the formula II or the composition thereof or the extract containing the coffee diterpenoid compound with the structure shown in the formula I and/or the formula II is used as an active ingredient for preparing cosmetics, skin care products or medicines which have the functions of improving the vitality of skin cells or inhibiting the inflammatory injury of the skin cells or having the anti-inflammatory function, and have important application value.
Description
Technical Field
The invention relates to the technical field of biomedicine, in particular to a coffee diterpenoid compound and application thereof in preparation of a medicine for improving skin cell activity and inhibiting skin cell inflammatory injury.
Background
As the first defense barrier of the human body, the utility model has the protection function of preventing the invasion of foreign matters, bacterial infection and the like. With aging, the metabolism of oxidative free radicals in skin cells is slowed, and the increase of oxidative free radicals in cells is closely related to the exposure of environmental pollutants and ultraviolet irradiation. Research reports that UVB exposure induces unsaturated fatty acid oxidation in skin cells to form lipid free radicals, further damages cells, destroys cell membranes, induces protein and enzyme denaturation and inactivation, and finally causes skin aging.
Natural active small molecules are well known for their excellent ability to scavenge free radicals and have been widely used in the fields of food, pharmaceutical products, cosmetics, and the like. The anti-inflammatory, antioxidant and anti-aging functions of natural active small molecules are also paid attention by people, and the natural active small molecules not only can promote metabolism and enhance immunity, but also play an important role in the processes of cell signal transduction, cell fate regulation and the like.
Coffee is a popular dietary supplement, and coffee beans have a wide range of biological activities and are rich in chemical components such as alkaloids, sugars, organic acids, esters, sterols, and diterpenes. Meanwhile, coffee has high medicinal value, such as anticancer, anti-inflammatory, antioxidant, liver protection and the like. The coffee extract is proved to have the effects of resisting oxidation, regulating immunity, reducing blood fat and the like, and the coffee extract is also widely applied to cosmetics to play the effects of resisting oxidation and inflammation. However, it is very clear that active small molecules in coffee can relieve oxidative damage and inflammatory damage of skin cells, and research and report on whether the active small molecules in coffee can relieve the oxidative damage and the inflammatory damage of the skin cells.
Disclosure of Invention
In order to overcome at least one of the technical problems of the prior art, the invention firstly provides a coffee diterpenoid. Researches show that the coffee diterpenoid compound not only can improve the activity of skin cells, but also can inhibit inflammatory injury of the skin cells.
The technical scheme of the invention is as follows:
a coffee diterpenoid compound has a structure shown in formula I or formula II;
the inventor surprisingly finds that the coffee diterpenoid compounds with the structures shown in the formulas I and II can not only improve the activity of skin cells, but also inhibit inflammatory injury of the skin cells.
The invention also provides a composition which comprises the coffee diterpenoid compounds with the structures shown in the formulas I and II.
The inventor further surprisingly discovers in the research that the composition formed by combining the coffee diterpenoid compounds with the structures shown in the formulas I and II has further improved skin cell activity improving effect and skin cell inflammatory injury inhibiting effect, and the skin cell activity improving effect and the skin cell inflammatory injury inhibiting effect are obviously higher than those of the natural active small molecular compound with the structure shown in the formula I or II.
Preferably, the weight ratio of the coffee diterpenoid compounds with the structures shown in the formula I and the formula II is 1-100.
More preferably, the weight ratio of the coffee diterpenoid compounds with the structures shown in the formula I and the formula II is 1-10.
Most preferably, the weight ratio of the coffee diterpenoids with the structures shown in the formulas I and II is 1:1.
The invention also provides an extract which contains the coffee diterpenoid compounds with the structures shown in the formula I and/or the formula II.
Preferably, the content of the coffee diterpenoid compounds with the structures shown in the formula I and/or the formula II in the extract is 1-99% by weight.
More preferably, the content of the coffee diterpenoid compounds with the structures shown in the formula I and/or the formula II in the extract is 30-95% by weight.
More preferably, the content of the coffee diterpenoid compounds with the structures shown in the formula I and/or the formula II in the extract is 50-90% by weight.
Preferably, the extract is a coffee extract.
The invention also provides application of the coffee diterpenoid compound, the composition or the extract in preparation of a product with the effect of improving skin cell vitality.
The invention also provides application of the coffee diterpenoid compound, the composition or the extract in preparing a product with the effect of inhibiting skin cell inflammatory injury.
The invention also provides application of the coffee diterpenoid compound, the composition or the extract in preparation of products with anti-inflammatory effects.
Preferably, the product is a cosmetic, skin care or pharmaceutical product.
Has the beneficial effects that: the invention provides a coffee diterpenoid compound with a brand-new structure; researches show that the coffee diterpenoid compound has the effects of improving the activity of skin cells and inhibiting inflammatory injury of the skin cells; particularly, the composition formed by combining the coffee diterpenoid compounds with the structures shown in the formulas I and II has the functions of improving the vitality of skin cells and inhibiting the inflammatory injury of the skin cells, is further improved, and has more excellent functions of improving the vitality of the skin cells and inhibiting the inflammatory injury of the skin cells; the effects of improving the skin cell vitality and inhibiting the skin cell inflammatory injury are obviously higher than those of the coffee diterpenoid compound with the structure shown in the formula I or the formula II. The coffee diterpenoid compound or the composition thereof with the structure shown in the formula I or the formula II has the effects of improving the vitality of skin cells and inhibiting inflammatory injury of the skin cells; therefore, the coffee diterpenoid compound with the structure shown in the formula I or the formula II or the composition thereof or the extract containing the coffee diterpenoid compound with the structure shown in the formula I and/or the formula II is used as an active ingredient for preparing cosmetics, skin care products or medicines which have the functions of improving the vitality of skin cells or inhibiting the inflammatory injury of the skin cells or having the anti-inflammatory function, and have important application value.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the embodiments or the prior art descriptions will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1 shows coffee diterpene compounds with structure shown in formula I 1 H NMR、 13 C NMR and DEPT135 spectra.
FIG. 2 shows the diterpenoid compounds of coffee represented by formula I 1 H- 1 H COSY, HMBC, and NOESY spectra.
FIG. 3 is a NOESY correlation diagram and calculated and experimental ECD spectra of key atoms of coffee diterpenoids with structures shown in formula I.
FIG. 4 shows the structure of coffee diterpene compound represented by formula II 1 H NMR spectrum, 13 C NMR and DEPT135 spectra.
FIG. 5 shows the diterpenoid compounds of coffee represented by formula II 1 H- 1 H COSY, HMBC, and NOESY spectra.
FIG. 6 is a NOESY correlation diagram of key atoms of coffee diterpenoids with the structures shown in formula II.
Figure 7 is a graph of the effect of the composition on human skin fibroblast viability and the effect of a coffee diterpene composition on UVB-exposed human skin fibroblast viability.
FIG. 8 is a graph of the effect of the compositions on the secretion of fibroblast inflammatory factors from UVB exposed human skin.
FIG. 9 is a graph showing the effect of the composition on the expression of NF-. Kappa.B and NLRP3 signaling pathway-related proteins in UVB-exposed human skin fibroblasts.
FIG. 10 is a graph of the effect of the composition on the secretion of inflammatory factors by UVB-exposed mouse skin cells.
FIG. 11 is a graph showing the effect of the composition on the expression of NF-. Kappa.B and NLRP3 signaling pathway-related proteins in UVB-exposed mouse skin cells.
Detailed Description
The technical solution of the present invention will be clearly and completely described with reference to the following examples. It is to be understood that the described embodiments are merely exemplary of the invention, and not restrictive of the full scope of the invention. All other embodiments, which can be obtained by a person skilled in the art without inventive step based on the embodiments of the present invention, are within the scope of protection of the present invention.
EXAMPLE 1 preparation of coffee diterpenes of the formulae I and II
(1) 1kg of coffee beans (raw) are crushed, extracted by 15 times of ethanol with the volume fraction of 50% in a leakage way, and the extracting solution is merged and concentrated under reduced pressure to obtain the extract.
(2) Suspending the extract with water to obtain suspension, and extracting with ethyl acetate and chloroform respectively. Freeze-drying the extract to respectively obtain ethyl acetate, chloroform and water layer extract.
(3) The ethyl acetate extract was chromatographed on a silica gel column using 5 gradients of chloroform-methanol (100: 10, 100: 30, 100: 50, 100: 90) to obtain 5 fractions (Fr.1-5, respectively.
(4) Gradient elution is carried out on Fr.3 (30 g) with 5 gradients of chloroform-methanol (100: 20, 100: 60, 100: 80; separating and purifying Fr.3-4 with preparative HPLC to obtain coffee diterpenoid compounds (2.21 g) with structure shown in formula I and coffee diterpenoid compounds (2.14 g) with structure shown in formula II;
the specific conditions for preparative HPLC were:
RP-HPLC (Agilent 1200 HPLC) was separated on a Zorbax, SB C-18 column (9.4X 250mm,5 μm). The elution solvent system consisted of water-trifluoroacetic acid (solvent A;100, 0.1,v/v) and acetonitrile-trifluoroacetic acid (solvent B; 100. Eluting with a gradient of 30% to 60% solvent B at a flow rate of 5.0mL/min for 25min, with the detection wavelength set at 300nm; collecting eluate corresponding to chromatographic peak at 11.87min, concentrating, and drying to obtain coffee diterpene compound with structure shown in formula I; collecting eluate corresponding to chromatographic peak at 10.15min, concentrating, and drying to obtain coffee diterpene compound with structure shown in formula II.
The structural analysis of the coffee diterpenoid compound with the structure shown in the formula I is as follows: white powder, HR-ESI-MS m/z 439.2481[ 2 ], [ M ] +Na] + (calcd for C 25 H 36 NaO 5 439.2455 Indicating that the compound has the formula C 25 H 36 O 5 And the molecular weight is 416.
1 H NMR(300MHz,CDCl 3 ) Spectrum (FIG. 1A), the compound has 4 methyl proton signals [ delta ] H 1.48(3H,s),1.33(3H,d,J＝5.4Hz),1.24(3H,s),1.01(3H,s)]2 olefin proton signals [ delta ] H 4.77(1H,s),4.72(1H,s)]And hydrogen proton signal [ delta ] of 2 vicinal oxygen carbons H 4.46(1H,dd,J＝12.0,4.5Hz),3.34(1H,dd,J＝10.8,5.4Hz)]。
13 C NMR(75MHz,CDCl 3 ) Spectra (fig. 1B) and DEPT spectra (fig. 1C) analyzed, and the compound had 4 methyl groups, 9 methylene groups, 5 methine groups, and 25 carbon signals total. Including 3 vicinal oxygen carbon signals (δ C80.5,58.2,57.8), 2 carbonyl carbon signals (δ C179.9,171.5) and 2 double bond carbon signals (δ C155.5,103.7).
From 1 H- 1 H-3 (. Delta.) can be seen in the H COSY spectrum (FIG. 2A) H 4.47 With H2-2 (. Delta.) H 2.33,1.75) are of interest.
In the HMBC spectra (FIG. 2B), H-3 and C-19 (. Delta.) can be observed C 179.9)、C-1'(δ C 171.5)、C-4(δ C 48.0)、C-18(δ C 24.0 ) are correlated. This proves that the (2 'R,3' S) -or (2 'S,3' R) -2',3' -epoxy-2-methylbutyl group-substituted group in the structure of the compound is bonded to the C-3 position.
In the NOESY spectrum (FIG. 2C), H-3 (. Delta.) was observed H 4.47 Respectively with H-5 (. Delta.) H 1.09)、H-18(δ H 1.24 Are related, H-3 is therefore on the same side as H-5, H-18. At the same time, H-4' (delta) H 1.33 Delta) with H-5' (delta) H 1.48 Related, so that H-4 'and H-5' are on the same side (FIG. 3A).
The ECD map of this compound was similar to the map of ECD calculated values of the 3R,4S,5S,8S,9R,10S,13R,2'R,3' configuration (FIG. 3B), and a positive Cotton effect was exhibited at 226nm, so that it was determined that the absolute configuration of the compound was 3R,4S,5S,8S,9R,10S,13R,2'R,3' S. By combining the analysis and map information, the coffee diterpenoid compound with the structure shown in the formula I is identified and named as coffee diterpene-1.
The structural analysis of the coffee diterpenoid compound with the structure shown in the formula II is as follows: white powder, HR-ESI-MS m/z 469.2360[ m ] +Na] + (calcd for C 29 H 34 NaO 4 469.2349 And simultaneously combining the NMR spectrum of the compound to indicate that the compound has the molecular formula C 29 H 34 O 4 And the molecular weight is 446.
1 H NMR(300MHz,CDCl 3 ) In the spectrum (FIG. 4A), the compound has a benzene ring structure sheetSection [ delta ] H 7.46-7.44(2H,overlapped),7.23-7.16(3H,overlapped)]5 olefin proton signals [ delta ] H 7.64(1H,d,J＝15.9Hz),6.38(1H,d,J＝15.9Hz),5.24(1H,s),4.91(1H,br s),4.80(1H,br s)]2 methyl unimodal proton signal [ delta ] H 1.32(3H,s),1.16(3H,s)]And hydrogen proton signal [ delta ] of 1 vicinal oxygen carbon H 4.73(1H,dd,J＝11.7,4.2Hz)]。
13 C NMR(75MHz,CDCl 3 ) Spectra (fig. 4B) and DEPT spectra (fig. 4C), compounds with 2 methyl groups, 8 methylene groups, 11 methine groups, 8 quaternary carbons, for a total of 29 carbon signals.
1 H- 1 H COSY spectrum (FIG. 5A), H-11 (. Delta.) H 5.24 With H2-12 (. Delta.) H 2.59,2.40).
HMBC spectra (FIG. 5B), H-11 and C-13 (. Delta.) (FIG. 5B) C 41.3),H2-7(δ H 2.00,1.51)，H2-15(δ H 2.60,2.19)/H-20(δ H 1.16 Is with C-9 (. Delta.) C 158.2 C-9 and C-11, thereby demonstrating the manner of attachment between C-9 and C-11. NOESY spectrum (FIG. 5C), H-3 (. Delta.) H 4.73 Respectively with H-5 (. Delta.) H 1.82)、H-18(δ H 1.32 Are related, so that H-3 is located on the same side as H-5, H-18 (FIG. 6).
In summary, the absolute configuration of the compound is 3R,4S,5S,8S,10S,13R. And (3) integrating the spectrogram information and analyzing, and identifying the coffee diterpenoid compound with the structure shown in the formula II, namely the coffee diterpenoid-2.
Example 2 coffee extract
(1) 1kg of coffee beans (raw), crushing, carrying out leakage extraction by using 15 times of ethanol with the volume fraction of 50%, and combining the decompression and concentration extracting solutions to obtain an extract;
(2) Suspending the extract with water to obtain suspension, and extracting with ethyl acetate and chloroform respectively. Freeze-drying the extract to respectively obtain ethyl acetate, chloroform and water layer extract; and taking the ethyl acetate layer extract to obtain the coffee extract.
Example 3 composition
The coffee diterpene-1 and the coffee diterpene-2 are uniformly mixed according to the mass ratio of 1:1 to obtain the composition.
Experimental example 1 experiment for improving skin cell viability
Human skin fibroblasts in MEM medium (containing 5% fetal calf serum), 5% CO 2 Humidity 95%, and culturing at 37 deg.C. Seeding cells in 96-well plates (1X 10) 3 Perwell), after cell attachment, 10. Mu.L of each of 200. Mu.g/mL coffee diterpene-1 (FT-1), coffee diterpene-2 (FT-2) and composition (composition consisting of coffee diterpene-1 and coffee diterpene-2 at a mass ratio of 1:1) solutions was added to the cells, and the same volume of PBS buffer was added as a blank control. Cells were cultured after adding coffee diterpene-1, coffee diterpene-2 and composition solution 24h, and cell activity was measured by CCK 8.
The experimental results show (fig. 7A) that the cell viability of the human skin fibroblasts is greatly improved after the coffee diterpene-1, the coffee diterpene-2 and the composition are co-cultured with the human skin fibroblasts, which indicates that the coffee diterpene-1, the coffee diterpene-2 and the composition have a great improvement effect on the viability of the human skin fibroblasts cultured in vitro.
Compared with a blank control group, the cell viability of the coffee diterpene-1, the coffee diterpene-2 and the composition group is respectively improved by 11.3% (p < 0.05), 9.27% (p < 0.05) and 20.5% (p < 0.01). Meanwhile, the composition has better activity than coffee diterpene-1 and coffee diterpene-2 under the same concentration in the aspect of improving the activity of human skin fibroblasts.
Experimental example 2 inhibition of inflammatory injury of skin cells caused by Ultraviolet (UVB) irradiation
Human skin fibroblasts in MEM medium (5% fetal bovine serum) in 5% CO 2 Humidity 95%, and incubation overnight in 37 ℃ incubator. Seeding cells in 96-well plates (1X 10) 3 /well), irradiation of UVB after cell attachment. UVB radiation intensity of 5.0 x 10 -5 J/cm 2 The irradiation light source is 14cm away from the human skin fibroblasts. During irradiation, the cell culture fluid was aspirated, washed 2 times with PBS, and a small amount of water was added to cover the bottom surface to avoid drying. Irradiating the culture plate in room temperature water bath to avoid overheating after irradiation, discarding PBS after irradiation, adding DMEM culture medium or coffee diterpene-1 (FT-1), coffee diterpene-2 (FT-2) and composition (composition comprising coffee diterpene-1 and coffee diterpene-2 at a mass ratio of 1:1)The solution (400. Mu.g/mL) was cultured for another 24h. Then, collecting cells and culture solution, detecting the cell activity by a CCK 8 kit, and detecting the content of related inflammatory cytokines by an ELISA kit; western blotting was used to detect changes in the associated proteins.
The results of the experiment (fig. 7B) show a significant decrease in human skin fibroblast viability following UVB exposure, indicating that UVB exposure damages human skin fibroblasts. Compared with the UVB exposure group, the human skin fibroblast viability is respectively improved by 8.93% (p < 0.05), 9.44% (p < 0.05) and 15.6% (p < 0.01) after the coffee diterpene-1, the coffee diterpene-2 or the composition thereof is treated, and the coffee diterpene-1, the coffee diterpene-2 or the composition thereof has certain inhibitory activity on the human skin fibroblast damage and the cell viability reduction caused by the UVB exposure. Further analysis shows that the coffee diterpene-1 and coffee diterpene-2 composition has better activity than coffee diterpene-1 or coffee diterpene-2 with the same concentration in the aspects of inhibiting the injury caused by human skin fibroblasts caused by UVB exposure and improving cell viability. We speculate that the coffee diterpene-1 and the coffee diterpene-2 can exert a synergistic effect by the combination, so that the damage of human skin fibroblasts caused by UVB exposure is better inhibited, and the cell viability is improved.
Further, we examined the effect of coffee diterpene-1, coffee diterpene-2 and compositions thereof on increased secretion of human dermal fibroblast inflammatory factors resulting from UVB exposure.
The results are shown in FIG. 8, where the skin fibroblast inflammatory factor secretion is increased after UVB irradiation compared to the blank control (blank, IL-4, IL-6, IL-13, TNF-alpha, IFN-gamma and PGE2 content set as 100%). Indicating that UVB irradiation damages cells and induces a cellular inflammatory response, which in turn increases inflammatory cytokine secretion. After UVB exposure, IL-4, IL-6, IL-13, TNF- α, IFN- γ and, PGE2 levels increased 151% (p < 0.01), 125% (p < 0.01), 232% (p < 0.01), 101% (p < 0.01), 112% (p < 0.01), 88.4% (p < 0.01), respectively, compared to the blank. And increased secretion of human dermal fibroblast inflammatory factors induced by UVB radiation is inhibited following treatment with cafe diterpene-1, cafe diterpene-2 and combinations thereof; the coffee diterpene-1, the coffee diterpene-2 and the composition can inhibit excessive secretion of human skin fibroblast inflammatory factors induced by UVB irradiation, further relieve inflammatory reaction induced by UVB irradiation and reduce inflammatory injury. Further analysis results show that under the same concentration condition, the composition of the coffee diterpene-1 and the coffee diterpene-2 can inhibit the activity of excessive secretion of human skin fibroblast inflammatory factors induced by UVB irradiation, and has better effect than the single use of the coffee diterpene-1 or the coffee diterpene-2. Meanwhile, the composition of coffee diterpene-1 and coffee diterpene-2 also shows similar effect in inhibiting the secretion of histamine of human skin fibroblasts induced by UVB irradiation, and the activity of inhibiting the secretion of histamine of human skin fibroblasts induced by UVB irradiation by the composition of coffee diterpene-1 and coffee diterpene-2 is stronger than that of coffee diterpene-1 or coffee diterpene-2 under the same concentration condition.
The experimental results are shown in fig. 9, compared with the blank control group, after UVB exposure, NF- κ B and NLRP3 signal pathways of human skin fibroblasts are activated, protein phosphorylation of IKK α, IKK β, ikb α and p65 is increased, and expression of Caspase-1, ASC and NLRP3 proteins related to NLRP3 inflammasome is significantly increased. We speculate that UVB exposure damages human skin fibroblasts and induces an inflammatory response, probably by activating NF-kb and NLRP3 signaling pathways to induce inflammatory cytokine overexpression. After the coffee diterpene-1, the coffee diterpene-2 and the composition thereof are used for treating, the NF-kB and NLRP3 signal channel activation of the human skin fibroblasts caused by UVB exposure is inhibited, and the coffee diterpene-1, the coffee diterpene-2 and the composition thereof are supposed to be capable of inhibiting the NF-kB and NLRP3 signal channel activation of the human skin fibroblasts caused by UVB exposure, so that the inflammatory injury of the human skin fibroblasts caused by UVB exposure is inhibited. Compared with coffee diterpene-1, coffee diterpene-2 and coffee extract groups, the composition has better inhibitory activity on the activation of NF-kB and NLRP3 signal pathways of human skin fibroblasts caused by UVB exposure under the same concentration condition.
Experimental example 3 inhibition of inflammatory injury in mouse skin caused by UVB exposure
Mice (nude mice) were randomly divided into 6 groups of 8 mice each: blank control group: no treatment was given; UVB control group: is not coated withThe UVB irradiation method is the same as that of each drug group; UVB irradiation +100mg/mL coffee diterpene-1 (FT-1) solution group; UVB irradiation +100mg/mL coffee diterpene-2 (FT-2) solution group; a UVB irradiation +100mg/mL composition (composition consisting of coffee diterpene-1 and coffee diterpene-2 in a mass ratio of 1:1) solution group; UVB irradiation +100mg/mL coffee bean extract solution group (FTT). The mice in each group were applied with the corresponding drug to the skin of the area 2cm x 2cm on the back 1 day before the start of the experiment, and then administered with 500mJ/cm after 20min 2 UVB irradiation, 1 time 1 day for 4 consecutive weeks, cervical dislocation, and mice were sacrificed. And (3) taking skin tissues of the irradiated parts of the mice, shearing the skin tissues, and detecting the content changes of related inflammatory factors (IL-4, TNF-alpha, IL-6, IFN-gamma, PGE2 and IL-13) and histamine in the skin of the mice according to the use instruction of an ELISA detection kit, and detecting the expression changes of NF-kappa B and NLRP3 signal channel related proteins in skin cells of the mice.
And (4) analyzing results:
the results are shown in FIG. 10, where the secretion of inflammatory factors in mouse skin cells after UVB exposure is significantly increased compared to the blank control group (IL-4, IL-6, IL-13, TNF-alpha, IFN-gamma and PGE2 content set as 100%). There was a 201% (p < 0.01), 152% (p < 0.01), 252% (p < 0.01), 125% (p < 0.01), 158% (p < 0.01), 104% (p < 0.01) increase in mouse skin inflammatory factor secretion following UVB exposure compared to the blank control group. We speculate that UVB exposure damages skin cells and induces an inflammatory response. While the increased secretion of inflammatory factors in mouse skin cells caused by UVB exposure was inhibited after treatment with coffee diterpene-1, coffee diterpene-2 and the compositions of the invention, we speculate that coffee diterpene-1, coffee diterpene-2 and the compositions thereof can inhibit the inflammatory response and induced inflammatory injury in mouse skin cells caused by UVB exposure. The inhibitory effect of the composition on the excessive secretion of inflammatory factors of skin cells of mice caused by UVB exposure was most significant compared to the group of cafe diterpene-1, cafe diterpene-2 and cafe extract. Compared with UVB exposure group, after coffee diterpene-1 and coffee diterpene-2 composition treatment, the content of IL-4, IL-6, IL-13, TNF-alpha, IFN-gamma and PGE2 is respectively reduced by 47.1% (p < 0.01), 46.8% (p < 0.01), 42.8% (p < 0.01), 44.4% (p < 0.01), 59.1% (p < 0.01) and 9.71%. Meanwhile, as a result of an analysis experiment, it was found that the coffee extract, although being capable of inhibiting the secretion of inflammatory factors caused by UVB exposure, did not exhibit a significant inhibitory effect. Meanwhile, the composition of coffee diterpene-1 and coffee diterpene-2 also shows similar effects on inhibiting the secretion of histamine of mouse skin cells induced by UVB irradiation, and the composition of coffee diterpene-1 and coffee diterpene-2 has stronger inhibitory activity on the secretion of histamine of mouse skin cells induced by UVB irradiation than coffee diterpene-1 or coffee diterpene-2 under the same concentration condition and stronger inhibitory activity than coffee bean extract under the same concentration condition.
The experimental results are shown in fig. 11, compared to the blank control group, after UVB exposure, NF- κ B and NLRP3 signal pathways of mouse skin cells are activated, wherein IKK α, IKK β, ikb α and p65 protein phosphorylation is increased, and further, caspase-1, ASC and NLRP3 protein expression in mouse skin cells is also significantly increased after UVB exposure. We speculate that UVB exposure damages mouse skin cells and induces inflammatory responses and excessive secretion of inflammatory factors probably by activating NF- κ B and NLRP3 signaling pathways in mouse skin cells. In this experiment, after the treatment of coffee diterpene-1, coffee diterpene-2, coffee extract and composition, the activation of NF- κ B and NLRP3 signaling pathways in mouse skin cells induced by UVB exposure was inhibited, and we speculate that coffee diterpene-1, coffee diterpene-2, coffee extract and composition could inhibit the activation of NF- κ B and NLRP3 signaling pathways in mouse skin cells induced by UVB exposure, thereby inhibiting inflammatory damage in mouse skin cells induced by UVB exposure. Compared with coffee extracts, the coffee diterpene-1, the coffee diterpene-2 and the composition have more obvious effects of inhibiting the NF-kB and NLRP3 signal pathway activation of mouse skin cells caused by UVB exposure. Furthermore, under the same concentration condition, the NF-kB and NLRP3 signal pathway activation inhibition activity of the coffee diterpene-1 and coffee diterpene-2 composition on mouse skin cells caused by UVB exposure is stronger than that of the coffee diterpene-1 and coffee diterpene-2 which are used alone, and the coffee diterpene-1 and coffee diterpene-2 are supposed to play a synergistic role to further inhibit the NF-kB and NLRP3 signal pathway activation of the mouse skin cells.
Finally, it is noted that the above-mentioned preferred embodiments illustrate rather than limit the invention, and that, although the invention has been described in detail with reference to the above-mentioned preferred embodiments, it will be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the scope of the invention as defined by the appended claims.
Claims (10)
1. A coffee diterpenoid compound is characterized by having a structure shown in a formula I or a formula II;
2. a composition comprising coffee diterpenes having the structures shown in formula I and formula II.
3. The composition according to claim 2, wherein the weight ratio of the coffee diterpenoid compounds having the structures represented by formula i and formula ii is 1-100.
4. The composition according to claim 2, wherein the weight ratio of the coffee diterpenoid compounds having the structures represented by formula i and formula ii is 1-10;
most preferably, the weight ratio of the coffee diterpenoids of the structures shown in formula I and formula II is 1:1.
5. An extract, characterized by comprising coffee diterpenoids represented by the structures of formula I and/or formula II.
6. The extract according to claim 5, wherein the content of the coffee diterpenoid compounds of the structures represented by the formulae I and/or II in the extract is 1 to 99% by weight.
7. The extract of claim 5, wherein the extract is a coffee extract.
8. Use of a coffee diterpene, composition or extract according to any one of claims 1 to 7 for the preparation of a product with skin cell viability enhancing effect.
9. Use of the coffee diterpenoid, composition or extract according to any one of claims 1 to 7 for the preparation of a product having an effect of inhibiting inflammatory damage of skin cells.
10. Use according to claim 9, wherein the product is a cosmetic, skin care or pharmaceutical product.
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| CN114907199A (en) * | 2022-06-17 | 2022-08-16 | 诺斯贝尔化妆品股份有限公司 | Anti-inflammatory and antipruritic dandelion diterpenoid compound and preparation method and application thereof |
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| CN114907199A (en) * | 2022-06-17 | 2022-08-16 | 诺斯贝尔化妆品股份有限公司 | Anti-inflammatory and antipruritic dandelion diterpenoid compound and preparation method and application thereof |
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