CN114191431A - Extraction method of alkaloid and application of alkaloid in preparation of anti-inflammation and anti-acne product - Google Patents
Extraction method of alkaloid and application of alkaloid in preparation of anti-inflammation and anti-acne product Download PDFInfo
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- CN114191431A CN114191431A CN202111650896.4A CN202111650896A CN114191431A CN 114191431 A CN114191431 A CN 114191431A CN 202111650896 A CN202111650896 A CN 202111650896A CN 114191431 A CN114191431 A CN 114191431A
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- alkaloid
- homocrepidine
- acne
- inflammatory
- inflammation
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P17/10—Anti-acne agents
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
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- C07D—HETEROCYCLIC COMPOUNDS
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Abstract
The invention provides an extraction method of alkaloid and application of the alkaloid in preparation of anti-inflammation and acne-removing products. The alkaloid is (+/-) -Homocrepidine A, a racemic mixture, and is separated and prepared from dendrobium officinale. The (+/-) -Homocrepidine A can remarkably inhibit the expression and secretion levels of inflammatory factors IL-1 beta and IL-8 in human acute monocyte THP-1 caused by propionibacterium acnes, thereby showing obvious anti-inflammatory and anti-acne activity, and being used for preparing cosmetics or external ointment with anti-inflammatory and anti-acne effects.
Description
Technical Field
The invention relates to the technical field of traditional Chinese medicine extracts, in particular to an extraction method of alkaloid and application of the alkaloid in preparation of anti-inflammation and anti-acne products.
Background
Acne is a chronic fatty skin inflammatory disease located on the face, chest and back. This skin disease affects approximately 85% of people, and is especially common in adolescents. This disease is characterized by the formation of non-inflammatory comedones, commonly known as blackheads or whiteheads; in more severe cases, inflammatory papules, pustules, nodules, and cysts may form. The lesions and scars formed by acne on visible areas of the skin not only affect the aesthetic appearance, but also the patient's confidence and esteem, creating a tremendous psychological problem. Acne is therefore becoming a popular research direction in the field of skin diseases. Currently, methods for treating acne include treatment of inflammation by chemical agents such as retinoids and benzoyl peroxide and use of antibiotics such as erythromycin, clindamycin and tetracycline to combat pathogenic bacteria. However, retinoids and the like cause skin allergy, erythema and desquamation, and the continuous use of antibiotics also causes the increase of bacterial resistance.
At present, the treatment of acne clinically is limited by drug resistance and drug side effect, so that the search for new drugs for treating acne is a problem which needs to be solved urgently at present. Active ingredients in natural plants are favored by more and more people due to the characteristics of small irritation, good permeability, high safety, remarkable curative effect and the like.
The Dendrobium roseum is a perennial epiphytic herb plant of the genus Dendrobium of the family Orchidaceae, and has high health care and medicinal values. The traditional Chinese medicine believes that the traditional Chinese medicine has the effects of nourishing yin, benefiting stomach, promoting the production of body fluid, relieving restlessness and the like. However, no research report on the aspects of diminishing inflammation and removing acnes is available.
Disclosure of Invention
The invention aims to provide an extraction method of alkaloid and application of the alkaloid in preparation of anti-inflammation and anti-acne products. The extracted alkaloid can inhibit expression and secretion of inflammatory factors IL-1 beta and IL-8 in human acute monocyte THP-1 caused by Propionibacterium acnes (P.acnes), and has good anti-inflammatory activity.
In order to achieve the purpose, the invention provides the following technical scheme:
provides an application of alkaloid in preparing anti-inflammatory and acne-removing products, wherein the alkaloid is (+/-) -Homocrepidine A, a racemic mixture, and the structural formula of the racemic mixture is shown as the formula (I):
further, the (+/-) -Homocrepidine A realizes inflammation diminishing and acne removing by inhibiting the expression and secretion of inflammatory factors caused by propionibacterium acnes.
Further, the inflammatory factors include IL-1. beta. and IL-8.
Further, the anti-inflammation acne product is an acne-removing cosmetic or an external acne-removing ointment.
The invention also provides an extraction method of the alkaloid, wherein the alkaloid is obtained by separating and extracting the dendrobium officinale.
Further, the extraction method comprises the following steps:
s1: extracting dried stems of dendrobium officinale with 80% ethanol with the volume 10 times that of the crude drug for 2-4 times, 2-3 hours each time, filtering, combining extracting solutions, and removing the solvent under reduced pressure to obtain a total extract;
s2: dissolving the total extract in water, filtering, extracting for 2-4 times by using ethyl acetate with the same volume, combining and concentrating the extract, and performing gradient elution by silica gel column chromatography to obtain 6 components A-F;
s3: performing gradient elution on the component F through silica gel column chromatography again to obtain 6 sub-components F1-F6;
s4: purifying the F2 on an RP-18 silica gel column to obtain the alkaloid (+/-) -Homocrepidine A.
Further, in the step S2, the eluent for gradient elution is petroleum ether and ethyl acetate, and gradient elution is performed according to the volume ratio of the petroleum ether to the ethyl acetate of (98: 2) to (1: 1).
Further, in step S3, the eluent of the gradient elution is CHCl3And MeOH, as CHCl3And MeOH in a volume ratio of (100:1) to (5: 1).
The invention has the following beneficial effects: the alkaloid (+/-) -Homocrepidine A extracted from the dendrobium officinale can obviously inhibit the expression and secretion levels of inflammatory factors IL-1 beta and IL-8 in human acute monocyte THP-1 caused by propionibacterium acnes, is in a dose-dependent relationship, can be used for preparing cosmetics or external ointments with the effects of diminishing inflammation and removing acnes, and provides a new additive for improving the skin state.
Drawings
FIG. 1 is a schematic representation of the compound Homocrepidine A1H NMR spectrum;
FIG. 2 is a schematic representation of the compound Homocrepidine A13C NMR spectrum;
FIG. 3 is a schematic representation of the compound Homocrepidine A1H-1H COSY spectrum;
FIG. 4 is an HSQC spectrum of compound Homocrepidine A;
FIG. 5 is an HMBC spectrum of the compound Homocrepidine A;
FIG. 6 is an HRESIMS spectrum of compound Homocrepidine A;
FIG. 7 is a UV spectrum of the compound Homocrepidine A;
FIG. 8 is an IR spectrum of the compound Homocrepidine A;
FIG. 9 is a graph showing the results of X-ray single crystal diffraction of the compound Homocrepidine A;
FIG. 10 is an HPLC chromatogram of compound (. + -.) -Homocrepidine A;
FIG. 11 is a photograph of the compound (+) -Homocrepidine A1H NMR spectrum;
FIG. 12 is a drawing of the compound (-) -Homocrepidine A1H NMR spectrum;
FIG. 13 is an ECD spectrum of compound (+) -Homocrepidine A;
FIG. 14 is an ECD spectrum of compound (-) -Homocrepidine A;
FIG. 15 is a graph of the effect of the compound Homocrepidine A on the expression levels of IL-1 β (A) and IL-8 (B);
FIG. 16 is a graph of the effect of the compound Homocrepidine A on the level of secretion of IL-1 β (A) and IL-8 (B).
Detailed Description
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Further, it should be understood that various changes or modifications of the present invention may be made by those skilled in the art after reading the teaching of the present invention, and such equivalents may fall within the scope of the present invention as defined in the appended claims.
The raw materials in the embodiment of the invention are as follows: fresh or dried stem of Dendrobium officinale Kimura et Migo of Dendrobium of Orchidaceae, collected from Menglan county, Yunnan province. Reagents such as ethanol, ethyl acetate, and dimethyl sulfoxide (DMSO) were all commercially available analytical reagents.
An apparatus or device: the ultraviolet spectrum is analyzed by Shimadzu UV1800 spectrophotometer, Jasco J-810 spectrophotometer, Shimadzu 8400s Plus infrared spectrometer, Agilent 6210LC/MSD TOF mass spectrometer and Bruker AV-300 spectrometer.
Example 1 extraction and structural identification of Homocrepidine A
1.1 extraction of the Compound Homocrepidine A
Extracting dry stem of herba Dendrobii with 10 times of 80% ethanol for 3 times (2.5 hr each time), filtering, mixing extractive solutions, and removing solvent under reduced pressure to obtain total extract;
dissolving the total extract in water, filtering, extracting with ethyl acetate of the same volume for 3 times, combining the extracts, concentrating, and performing gradient elution through silica gel column chromatography, wherein the eluent is petroleum ether and ethyl acetate, and the gradient elution is performed according to the gradient change that the volume ratio of the petroleum ether to the ethyl acetate is 98:2 → 1:1 within 1h to obtain six components A-F; by passing each of the components A-F through again separatelyGradient eluting with silica gel column chromatography, wherein the eluent is CHCl3And MeOH, as CHCl over 1h3And MeOH with a volume ratio of 100:1 → 5:1, wherein the F fraction elutes to give 6 subfractions F1-F6; subfraction F2 was purified on a column of RP-18 silica gel to give the racemic mixture.
The alkaloid compounds are dissolved in dimethyl sulfoxide (DMSO) to prepare liquid medicine for activity research.
1.2 structural identification of the Compound Homocrepidine A
And carrying out structural identification on the extracted compound Homocrepidine A. According to the characterization results in fig. 1 to fig. 14 and table 1, the structure of compound Homocrepidine a is identified as follows: the compound Homocrepidine A is a white crystal. According to HRESIMS M/z 517.3436[ M + H ]]+Determining the formula of the compound as C33H44N2O3Unsaturation degree is 13; IR spectra show the presence of hydroxyl groups (3421 cm)-1) Aromatic hydrogen (1639, 1447 and 759 cm)-1) And carbonyl (1720 cm)-1)；1The H-NMR spectrum and the HSQC spectrum show 10 aromatic proton signals [ delta ]H7.51(2H, brd,7.7Hz, H-12,12 '), 7.13(2H, brd,7.1Hz, H-13,13 '), 7.03(2H, m,7.5Hz, H-14,14 '), 7.21(2H, brd,7.1Hz, H-15,15 ') and 7.29(2H, brd,7.7Hz, H-16,16 ')]6 methylene signals [ delta ]H1.80-1.82(2H, overlap, H-7,7 '), 2.18-1.20(2H, overlap, H-9,9 ') and 3.03(2H, dd,2.9 and 6.2Hz, H-5,5 ')]And two methyl signals deltaH 0.49(6H,d,6.6,H3-10,10′)。
13The C-NMR spectrum showed 33 carbon signals including: 1 carbonyl signal, 2 quaternary carbon signals, 6 sp3The hybridized methine signal, 10 methylene signals, 2 methyl signals, 10 carbon signals on the phenyl ring and 2 tertiary carbon-to-oxygen signals. The substitution of phenyl and hydroxyl groups on C-6 (. delta.) can be determined from the correlation of H-12/H-16/6-OH with C-6, H-5 with C-6/C-7/C-11 and H-12/H-16 with C-14 in the HMBC spectrumC 76.6)；H3Correlation of-10 with C-6/C7/C-8 confirms that the methyl group is at C-7.
1H-1H COSY spectra show C-1/C-3 and C-7/C-9 spinsAnd (4) preparing the system. The structure of the a subunit was determined from the above data. Combining ESIMS data and unsaturation, by HMBC spectroscopy H-5 with C-11/C-17 and H2The correlation of-17 with C-5/C-6/C-18 defines the B subunit structure. The two A subunit moieties are linked by C-18 to form a dimer. Wherein, the A subunit and the B subunit have the structure shown in formula (II):
the NOESY correlation of H-5/H-7/H-9 indicates that they are on the same side of the structure; furthermore, H3-10/6-OH/H2-17 is also located on the same side of the structure. The structure and relative configuration of the Homocrepidine A are determined by X-ray single crystal diffraction results. The crystal structure of which shows a centrosymmetric space group P1—And [ alpha ] is]DThe value was (-2.8), indicating that Homocrepidine A is a racemic mixture.
On an Agilent 1100 liquid chromatograph, CHIRALPAK AD-H chromatographic column (10 x 250mm) is adopted, n-hexane/2-propanol (95:5) is used as eluent, the flow rate is 0.8mL/min, a VWD ultraviolet spectrophotometer (220nm) is used as detection wavelength, the compound is subjected to enantiomer separation, and enantiomers (+) -Homocrepidine A and (-) -Homocrepidine A are obtained, and the peak area ratio of the two is 1: 1. The retention time is (+) -Homocrepidine A at 5.96min, and the retention time is (-) -Homocrepidine A at 7.00 min. The mass spectrum and nuclear magnetic resonance spectrum of (+) -Homocrepidine A and (-) -Homocrepidine A are the same. The absolute configuration of (-) -Homocrepidine A is determined to be 5R, 6S, 7R, 9S, 5 'R, 6' S, 7 'R and 9' S by X-ray single crystal diffraction results. The absolute configuration of (+) -Homocrepidine A is 5S, 6R, 7S, 9R, 5 'S, 6' R, 7 'S, 9' R. The ECD spectrum also shows its enantiomeric relationship.
TABLE 1 NMR spectroscopic data (delta in ppm, J in Hz) for the compound Homocrepidine A
The structural formula of the separated target compound (+/-) -Homocrepidine A determined by the method is shown as the formula (I):
the following examples 2-5 are adopted to study the anti-inflammatory and anti-acne effects of the (+/-) -Homocrepidine A obtained by extraction.
The culture method of the human acute monocyte THP-1 used in examples 2-5 was as follows: is cultured in RPMI1640 containing 10% fetal calf serum at 37 deg.C under 5% CO2Subculturing in a constant temperature incubator. The propionibacterium acnes (p.acnes) culture mode used was: the cells were cultured anaerobically in a minced meat medium containing 1/3 volumes of bacon beef granules at 37 ℃ in a thermostated incubator.
Example 2 Effect of HomocrepidineA on THP-1 cell survival
2.1 Experimental methods
Taking THP-1 cells in logarithmic growth phase, adjusting cell density to 2 × 105one/mL, inoculated in a 96-well plate at 100. mu.L per well, 100. mu.L of Homocrepidine A diluted in serum-free medium at different concentrations were added to give final concentrations of 10. mu. mol/L, 20. mu. mol/L, 40. mu. mol/L and 80. mu. mol/L, respectively, 6 replicates of each concentration, at 37 ℃ and 5% CO2And (5) standing and culturing for 36h in a constant-temperature incubator. When the cell survival rate is measured, 20 mu L of MTT solution with the concentration of 5mg/mL is added into each hole, the mixture is cultured in an incubator for 4h, the supernatant is centrifuged and discarded, 150 mu L of dimethyl sulfoxide (DMSO) is added into each hole, the mixture is placed on a vibrator to be vibrated for 10min, after crystals are fully dissolved, the OD value is measured at 570nm, and the reference wavelength is 630 nm. The cell viability was calculated as the cell viability as OD value of experimental group/OD value of control group × 100%.
2.2 results of the experiment
TABLE 2 influence of Homocrepidine A on THP-1 cell survival
The experimental results are shown in Table 2, when the concentration of the Homocrepidine A is in the range of 0-40 mu mol/L, after the co-incubation is carried out for 36h, the survival rate of the THP-1 cells is over 80%, and the cell morphology is good and has no significant difference when observed under a microscope. Thus, the concentration range of the Homocrepidine A in the subsequent experiment is determined as follows: 0-40 mu mol/L.
Example 3 determination of minimal inhibitory concentration of p.acnes by HomocrepidineA
3.1 Experimental methods
Taking P.acnes in logarithmic growth phase, and adjusting the bacterial concentration to be 2 multiplied by 106CFU/mL, inoculating 100 μ L per well in 96-well plate, adding 100 μ L of Homocrepidine A diluted with ground meat culture medium, setting 3 parallel per concentration, adding anaerobic gas-producing bag in 37 deg.C incubator to provide anaerobic condition, and culturing for 24 hr. Whether the bacterial proliferation is completely inhibited or not is judged by measuring the OD value at 600nm with the reference wavelength of 630nm, and the minimum inhibitory concentration (MIC value) of Homocrepidine A is determined.
3.2 results of the experiment
The MIC value of the Homocrepidine A for P.acnes is measured, and is found to be far higher than 40 mu mol/L, so that the condition that the concentration range of the Homocrepidine A is kept between 0 and 40 mu mol/L in subsequent experiments can be proved, and the anti-inflammatory and anti-acne activity of the Homocrepidine A is related to the anti-inflammatory activity of the Homocrepidine A and is unrelated to the antibacterial activity of the Homocrepidine A.
Example 4 Effect of HomocrepidineA on the expression of the inflammatory factors IL-1 β, IL-8 in THP-1 cells
4.1 Experimental methods
Taking THP-1 cells in logarithmic growth phase, adjusting cell density to 2 × 106one/mL, seeded at 1mL per well in 6-well plates and added 1mL of Homocrepidine A at various concentrations diluted in serum-free medium at 37 deg.C, 5% CO2And (5) standing and culturing for 4 hours in a constant-temperature incubator. Collecting P.acnes thallus in logarithmic growth phase, washing with sterile PBS buffer solution, and resuspendingViable bacteria suspension according to bacteria: cell 100: adding the mixture into a 6-well plate according to the proportion of 1, taking the condition that bacteria are added in the mixture with the Homocrepidine A as an experimental group, taking the condition that the bacteria are added without the Homocrepidine A as a negative control group, and taking the condition that the bacteria are not added with the Homocrepidine A as a blank control group. Placing at 37 ℃ and 5% CO2And (5) standing and culturing for 18h in a constant-temperature incubator. Cells were collected by centrifugation and RNA was extracted from THP-1 cells using a total RNA extraction kit. The light absorption values were measured at 260nm and 280nm, and the concentration of mRNA was estimated.
Reverse transcription reaction systems were configured for each set of samples on ice: mu.g of mRNA was taken from each sample, DNase and buffer were added, and RNase Free dH was added2O the reaction system was brought to 10. mu.L, mixed and reacted at 42 ℃ for 2min to remove genomic DNA from mRNA. Adding reverse transcriptase and buffer solution into the reaction solution on ice respectively, mixing uniformly, reacting for 15min at 37 ℃ to make mRNA reverse transcribe into cDNA. The reaction was terminated by heating the above-mentioned sample at 85 ℃ for 5 seconds after completion of the reaction.
Primers needed in the experiment are shown in table 3, a qRT-PCR reaction system is configured on ice according to the qRT-PCR amplification system in table 4, and the amplification conditions of the experiment are as follows: the pre-denaturation condition is set at 95 ℃ for 30 s; the denaturation conditions were set at 95 ℃ for 5 s; the annealing condition is set to be 60 ℃ for 30 s; the extension conditions were set at 72 ℃ for 60 s; a total of 40 cycles of reaction were carried out. Analyzing the obtained experimental data, and concretely calculating the method as follows: delta Ct (experimental group) ═ Ct value of target gene in experimental group-Ct value of reference gene in experimental group; delta Ct (control group) is the Ct value of the target gene in the control group-the Ct value of the reference gene in the control group; Δ Δ Ct ═ Δ Ct (experimental group) - Δ Ct (control group); final calculation 2-ΔΔCtThus obtaining the expression condition of the target gene mRNA of the experimental group.
Table 3 primer List
TABLE 4 qRT-PCR amplification System
4.2 results of the experiment
As shown in FIG. 15, the transcription levels of the inflammatory factors IL-1 β and IL-8 in the experimental group and the negative control group were significantly higher than that in the blank control group, while the transcription levels of the inflammatory factors IL-1 β and IL-8 in the experimental group were significantly lower than that in the negative control group. According to the experimental result, the induction of P.acnes can obviously improve the transcription levels of inflammatory factors IL-1 beta and IL-8 in THP-1 cells (##P<0.01). After the pretreatment of the Homocrepidine A, the transcription levels of L-1 beta and IL-8 are obviously reduced in a dose-dependent manner, which indicates that the Homocrepidine A has good anti-inflammatory activity (the formula (I) (II))*P<0.05，**P<0.01)。
Example 5 Effect of Homocrepidine A on secretion of inflammatory factors IL-1 beta, IL-8 in cells
5.1 Experimental methods
Taking THP-1 cells in logarithmic growth phase, adjusting cell density to 1 × 106one/mL, seeded at 100. mu.L per well in 96-well plates, 100. mu.L of Homocrepidine A at different concentrations, diluted in serum-free medium, 3 replicates per concentration, at 37 ℃ with 5% CO2And (5) standing and culturing for 4 hours in a constant-temperature incubator. Collecting P.acnes thalli in logarithmic growth phase, washing with sterile PBS buffer solution, and then resuspending to prepare viable bacteria suspension according to the following bacteria: cell 100:1, adding the mixture into a 96-well plate, taking the condition that the bacteria are added with the Homocrepidine A as an experimental group, taking the condition that the bacteria are added without the Homocrepidine A as a negative control group, and taking the condition that the bacteria are not added with the Homocrepidine A as a blank control group. Placing at 37 ℃ and 5% CO2And (5) standing and culturing for 24 hours in a constant-temperature incubator. Centrifuging to collect supernatant, and detecting the content of IL-1 beta and IL-8 in the supernatant by an enzyme-linked immunosorbent kit. The inhibition rates of IL-1 β and IL-8 expression were calculated as inhibition rate (negative control group-experimental group)/negative control group × 100%.
5.2 results of the experiment
As shown in FIG. 16, the stimulation of P.acnes resulted in the generation of inflammatory reaction of THP-1 cells, which resulted in the secretion of extracellular inflammatory factors IL-1 β and IL-8, compared to the blank control groupThe amount is remarkably increased (##P is less than 0.01). Compared with a negative control group, the addition of different concentrations of Homocrepidine A can inhibit the expression quantity of IL-1 beta and IL-8 in cell supernatant and show dose dependence, and the inhibition rates of the Homocrepidine A concentration of 40 mu mol/L on IL-1 beta and IL-8 are 72.01% and 66.52%, (*P<0.05，**P<0.01)。
The experimental results show that the (+/-) -Homocrepidine A can remarkably inhibit the expression and secretion levels of inflammatory factors IL-1 beta and IL-8 in human acute monocyte THP-1 caused by propionibacterium acnes (P.acnes), and is in a dose-dependent relationship. The invention shows that the skin care product can be used for preparing cosmetics or external ointment with acne removing and inflammation diminishing effects, and provides a new additive for improving skin conditions.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and improvements can be made without departing from the principle of the present invention, and these modifications and improvements should also be considered as the protection scope of the present invention.
Sequence listing
<110> university of east China's college of science
<120> extraction method of alkaloid and application of alkaloid in preparation of anti-inflammation and acne-removing products
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Claims (8)
1. An application of alkaloid in preparation of anti-inflammation and acne-removing products is characterized in that the alkaloid is (+/-) -Homocrepidine A, a racemic mixture, and the structural formula of the racemic mixture is as shown in formula (I):
2. the application of alkaloid in preparation of anti-inflammation and acne-removing products according to claim 1, wherein (±) -Homocrepidine A realizes anti-inflammation and acne-removing by inhibiting the expression and secretion of inflammatory factors caused by propionibacterium acnes.
3. The use of an alkaloid in the preparation of an anti-inflammatory and anti-acne product according to claim 2, wherein the inflammatory factors comprise IL-1 β and IL-8.
4. The use of an alkaloid in the preparation of an anti-inflammatory and anti-acne product according to claim 1, wherein the anti-inflammatory and anti-acne product is an anti-acne cosmetic or an external anti-acne ointment.
5. The method for extracting alkaloid according to any one of claims 1 to 4, wherein the alkaloid is separated and extracted from Dendrobium officinale Kimura et Migo.
6. The extraction method according to claim 5, characterized by comprising the steps of:
s1: extracting dried stems of dendrobium officinale with 80% ethanol with the volume 10 times that of the crude drug for 2-4 times, 2-3 hours each time, filtering, combining extracting solutions, and removing the solvent under reduced pressure to obtain a total extract;
s2: dissolving the total extract in water, filtering, extracting for 2-4 times by using ethyl acetate with the same volume, combining and concentrating the extract, and performing gradient elution by silica gel column chromatography to obtain 6 components A-F;
s3: performing gradient elution on the component F through silica gel column chromatography again to obtain 6 sub-components F1-F6;
s4: purifying the F2 on an RP-18 silica gel column to obtain the alkaloid (+/-) -Homocrepidine A.
7. The extraction method according to claim 6, wherein in the step S2, the eluent for gradient elution is petroleum ether and ethyl acetate, and gradient elution is performed according to the volume ratio of the petroleum ether to the ethyl acetate of (98: 2) to (1: 1).
8. The extraction method according to claim 6, wherein the elution of the gradient elution in the step of S3The liquid is CHCl3And MeOH, as CHCl3And MeOH in a volume ratio of (100:1) to (5: 1).
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Non-Patent Citations (3)
| Title |
|---|
| YANG HU等: "(±)-Homocrepidine A, a Pair of Anti-inflammatory Enantiomeric Octahydroindolizine Alkaloid Dimers from Dendrobium crepidatum", 《JOURNAL OF NATURAL PRODUCTS》 * |
| 张汝峰: "《观手知健康》", 30 June 2018, 天津科学技术出版社 * |
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| CN114848639A (en) * | 2022-05-09 | 2022-08-05 | 中国药科大学 | Application of rhodizine A in preparation of medicines or health products for preventing cerebral ischemia |
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