CN115737641B - Application of pure green penicillium alcohol in preparing medicine for treating inflammatory bowel disease - Google Patents
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Abstract
The invention relates to application of pure green penicillium alcohol in preparing a medicament for treating inflammatory bowel disease, belongs to the technical field of new medical application, and particularly relates to application of pure green penicillium alcohol in preparing a medicament for treating inflammatory bowel disease.
Description
Technical Field
The invention belongs to the technical field of new medical application, and in particular relates to application of pure penicillium viridian in preparation of medicines for treating inflammatory bowel diseases.
Background
Inflammatory bowel disease (inflammatory bowel diseases, IBD) is a collective term for gastrointestinal diseases that exhibit chronic or recurrent immune responses and inflammatory symptoms. With the increasing changes in people's lifestyle and the increasing pressure of life, the global incidence of IBD is on a year-by-year trend, with our country suffering from disease in asia. Clinical manifestations of IBD patients mainly include: intestinal manifestations such as abdominal pain, diarrhea, mucous bloody stool, fistula formation, intestinal manifestations such as perianal abscess, bloody stool, abdominal cramps, fever, fatigue, severe cramps in the pelvic region, muscle cramps, loss of appetite, weight loss, and the like. At present, the IBD treatment medicine is lack of variety, no effective treatment means exists, the conventional treatment can improve symptoms, but the recurrence rate is high, the curative effect on severe patients is poor, and the overall clinical remission rate is not more than 50%. Innovative drug development for the treatment of IBD has become a clinical urgent need.
Copper sulfate (CuSO) 4 ) Is widely used for establishing the acute neurogenic inflammation model of the zebra fish. Copper sulfate damages peripheral organ nerve hills of the body surface side line of the zebra fish, so that inflammatory cells of the zebra fish migrate to the periphery (side line part) of the nerve hills; a model of systemic infectious inflammation caused by Lipopolysaccharide (LPS); the two above-mentioned inflammatory models are different from those of inflammatory bowel disease caused by 2,4,6-trinitrobenzenesulfonic acid (TNBS).
2,4,6-trinitrobenzenesulfonic acid (2, 4,6-trinitrobenzenesulfonic acid, TNBS), dextran sodium sulfate (dextran sodium sulfate, DSS), oxazolone, and the like are all mutagens of the commonly used zebra fish IBD disease model. The TNBS induction has the advantages of short molding time, high repeatability, easy induction and the like, and is a classical IBD chemical mutagen. TNBS can cause the disappearance of intestinal peristalsis, the expansion of intestinal tracts and the formation of intestinal obstruction of zebra fish, and can also cause the shortening of intestinal villus length and the increase of goblet cell quantity, which are very similar to pathological manifestations of IBD patients.
Fleming et al used TNBS in experimental mouse models to induce intestinal inflammation in zebra fish, and soaked zebra fish in TNBS, the zebra fish showed enlarged intestinal lumen, lost intestinal folds, increased goblet cell numbers, and positive tumor necrosis factor-alpha (TNF-alpha) staining in the epithelial cells. Oscar et al used zebra fish as a model for studying intestinal inflammation, exposed zebra fish larvae from 72hpf to 120hpf to TNBS, and observed that TNBS resulted in neutrophil recruitment to the intestinal tract, demonstrating that TNBS can induce zebra fish intestinal inflammation. He and the like induced and collected zebra fish larvae of the zebra fish juvenile fish IBD-like enterocolitis by TNBS, and researches show that the expression of toll-like receptor 3 (TLR 3) and TLRs signaling pathway molecules MyD88 and TRIF, the activation of NF- κB and the production of inflammatory cytokine tumor necrosis factor-alpha in the zebra fish treated by TNBS are stimulated.
Pure green penicillium alcohol is a quinolinone alkaloid separated from secondary metabolite of marine fungus Aspergillus australis (Aspergillus austroafricanus) Y32-2, and has molecular formula of C 15 H 11 NO 3 。
Pure penicillium has been reported to have strong antibacterial activity against staphylococcus aureus, but no effect on inflammatory bowel disease has been reported for pure penicillium.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides the application of pure green penicillium alcohol in preparing the medicines for treating inflammatory bowel diseases.
The technical scheme of the invention is as follows:
use of pure penicillium alcohol in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein the pure penicillium alcohol has the structural formula:
according to a preferred aspect of the invention, in said use, said medicament acts to treat inflammatory bowel disease by activating ppar gamma expression, modulating MAPK and NF- κB signaling pathways.
A medicament for treating inflammatory bowel disease, which comprises pure green penicillium alcohol.
According to the invention, the medicament preferably contains a pharmaceutically acceptable carrier and/or auxiliary materials.
Preferably, the medicament is in the form of tablets, capsules, granules, pellets, dripping pills, oral liquid, water injection, powder injection, infusion solution, ointment, gel or microemulsion.
Advantageous effects
The invention discovers that the pure green penicillium can treat inflammatory bowel disease for the first time, increases the new application of the pure green penicillium, provides a new treatment means for treating inflammatory bowel disease, and also provides reference for the application and development of the pure green penicillium.
Drawings
FIG. 1 is a schematic representation of the effect of pure green penicillium on TNBS-induced migration of inflammatory cells in the intestinal tract of zebra fish;
in the figure: TNBS represents 2,4,6-trinitrobenzenesulfonic acid; the red frame is provided with a part for counting the number of intestinal inflammatory cells of the zebra fish, and the right side is provided with an enlarged picture of an intestinal statistical region.
FIG. 2 is a statistical bar graph of the effect of pure green penicillium on TNBS-induced migration of inflammatory cells in the zebra fish intestinal tract;
in the figure: in contrast to the blank group, ## P<0.01; in contrast to the TNBS building module, * P<0.05， ** P<0.01。
FIG. 3 is a schematic representation of the effect of pure green penicillium on intestinal tissue structure of inflammatory bowel disease zebra fish;
in the figure: the black solid arrow indicates necrotic dissolution of mucosal epithelium, the black dashed arrow indicates disappearance of intestinal folds, and the scale of the intestinal taken picture is 50 μm.
FIG. 4 is a schematic representation of the effect of pure green penicillium on the intestinal ultrastructure of inflammatory bowel disease zebra fish;
in the figure: black arrows indicate intestinal micro-villus status; mv represents microvilli, ec represents epithelial cells; the scale of the intestinal tract photographed picture is 20 μm.
FIG. 5 is a schematic representation of the effect of pure green penicillium on the expression level of inflammatory bowel disease zebra fish genes;
in the figure: ppar gamma represents peroxisome proliferator-activated receptor gamma, zak represents a protein kinase; hsp70.1 denotes a heat shock protein, ap-1 denotes activin-1, map3k8 denotes a serine/threonine kinase, ikb αa denotes a nuclear transcription factor inhibitor gene, nf- κb denotes a nuclear transcription factor, il8a denotes an inflammatory factor; in contrast to the blank group, # P<0.05， ## P<0.01; in contrast to the TNBS building module, * P<0.05， ** P<0.01。
FIG. 6 is a schematic representation of the effect of pure penicillium viridogon systemic infectious inflammation caused by LPS;
in the figure: LPS represents lipopolysaccharide; the picture is the overall inflammatory cell distribution of zebra fish.
FIG. 7 is a graph of epimedin B versus CuSO 4 Schematic of the effect of inducing acute neurogenic inflammation in zebra fish;
in the figure: cuSO 4 Represents copper sulfate; the picture is an enlarged picture of the migration of inflammatory cells of zebra fish to the periphery of the nerve hill (side line part) and the area thereof.
FIG. 8 is a graph of epimedin B versus CuSO 4 Histogram of anti-inflammatory effects inducing acute neuroinflammation in zebra fish;
in the figure: cuSO 4 Represents copper sulfate; in contrast to the blank control, ### P<0.001; with CuSO 4 Model group comparison P<0.001。
FIG. 9 is a schematic representation of the effect of epimedin B on tail break induced local inflammation in zebra fish;
in the figure: the picture shows the magnified picture of the migration of inflammatory cells of zebra fish to the tail-breaking part and the region thereof.
FIG. 10 is a histogram of anti-inflammatory effects of epimedin B on tail-break induced local inflammation in zebra fish;
in the figure: in contrast to the blank control, ### P<0.001; p compared to the tail-biting model group<0.001。
FIG. 11 is a graph showing the effect of epimedin B on the aggregation and migration of inflammatory cells in the zebra fish intestinal tract;
in the figure: TNBS represents 2,4,6-trinitrobenzenesulfonic acid; the red frame is provided with a part for counting the number of inflammatory cells in the intestinal tract of the zebra fish, and the right side is provided with an enlarged picture of an intestinal tract counting area.
FIG. 12 is a histogram of epimedin B versus TNBS-induced aggregation migration of inflammatory cells in the intestinal tract of zebra fish; in the figure: in contrast to the blank control, ### P<0.001; p compared to the TNBS model group<0.001。
Detailed Description
The invention is further described below with reference to the drawings and specific examples, but the embodiments of the invention are not limited thereto.
The drugs and reagents used in the examples are common products on the market unless otherwise specified, and the details not specifically described in the examples are all in accordance with the prior art.
Source of main materials
2,4,6-trinitrobenzenesulfonic acid (TNBS) was purchased from Sigma company, the electron microscope fixing solution was purchased from Wohange biotechnology Co., ltd, the 812 embedding medium was purchased from SPI company, and the culture water of young fish of zebra fish was 0.4mM CaCl 2 ，5mM NaCl，0.17mM KCl，0.16mM MgSO 4 。
Pure penicillium chlorohydrin: pure penicillium was purchased from TargetMol company (production lot number: 155521; purity 98%).
Epimedin B: purchased from Shanghai leaf Source Biotechnology Co., ltd (production lot number: J12HB184812; purity. Gtoreq.98%).
Lipopolysaccharide LPS: purchased from Sigma, USA (manufacturing lot number: 0000155411).
Example 1
Effect of pure green penicillium on aggregation degree of intestinal inflammatory cells
Transgenic zebra fish with 3dpf healthy inflammatory cells marked with green fluorescence is taken as a test animal, and randomly divided into a blank control group (fish culture water), a model group (TNBS) and a sample group with different concentrations (TNBS+30 mug/mL of pure green penicillium, TNBS+60 mug/mL of pure green penicillium, TNBS+90 mug/mL of pure green penicillium). Each group of 10 fries was provided with 2 duplicate wells. The model group and the sample group with different concentrations (without adding pure green penicillium) were added with 2,4,6-trinitrobenzene sulfonic acid (TNBS) with a final concentration of 50 mug/mL. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and incubated continuously for 2 days in the dark. And after the completion, cleaning each group of fish fries, respectively placing the blank control group and the model group of zebra fish in fresh culture water, and placing the sample groups of zebra fish with different concentrations in culture water containing samples to be tested with different concentrations. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and continuously acted for 1 day. After the treatment was completed, the zebra fish was anesthetized with 0.2% ethyl metaaminobenzoate mesylate and photographed under a fluorescent microscope. The number of inflammatory cells showing green fluorescence in the intestinal tract of zebra fish was counted.
Hematoxylin-eosin (H & E) staining of zebra fish intestinal sections: the compound-treated zebra fish were collected and fixed with 4% paraformaldehyde. And (3) trimming, dehydrating, embedding, slicing, dyeing and sealing the zebra fish sample strictly according to a pathological experiment detection program. The intestinal tissue section was observed under a microscope and a typical lesion was imaged.
Zebra fish intestinal tract transmission electron microscope detection: the zebra fish after compound treatment is collected and fixed for 2-4 hours at 4 ℃ by adopting an electron microscope fixing solution, and then rinsed for 3 times by using 0.1M phosphate buffer solution PB (PH 7.4) for 15min each time. Fixing, dehydrating, penetrating, embedding, slicing and dyeing to obtain the target slice. Intestinal tissues were observed under a transmission electron microscope and image analysis was performed.
PCR detects key gene expression associated with inflammatory bowel disease: zebra fish tissues (blank, TNBS, TNBS+90. Mu.g/mL pure green penicillium) after pure green penicillium treatment were collected, and RNA was extracted with FastPure Cell/Tissue Total RNA Isolation Kit V2. cDNA was obtained by reverse transcription of each sample RNA, and the expression level of the gene related to inflammation was measured by using the BIO-RAD CFX96 real-time system, and the measurement was repeated 3 times. The QRT-PCR amplification reaction conditions were 95℃for 30s 1 cycle followed by 10s denaturation at 95℃and 10s annealing at 60℃for 40 cycles, and finally 95℃for 15s 60s and 95℃for 15s 1 cycle. And in the result analysis, beta-actin is taken as an internal reference, and the result is subjected to relative quantitative analysis. The PCR primers of the target gene and the reference gene are synthesized and purified by Shanghai JieRui bioengineering Co., ltd, and subjected to quality detection. The relevant primer gene sequences are shown in Table 1.
TABLE 1 Gene amplification primer sequences for real-time fluorescent quantitative PCR
Experimental results:
(1) Effect of pure green penicillium on aggregation and migration of inflammatory cells in intestinal tract of zebra fish
And (3) utilizing TNBS to induce the inflammatory cells in the zebra fish to gather to the intestinal tract, and establishing a TNBS-induced inflammatory bowel disease model of the zebra fish. The anti-inflammatory activity of the compound against intestinal inflammation of zebra fish is evaluated by counting the number of inflammatory cells at the intestinal site of zebra fish. As shown in fig. 1 and 2, compared with the blank group, the number of inflammatory cells migrating to the intestinal tract by the TNBS group zebra fish was significantly increased. At 60, 90 mug/mL of pure green penicillium alcohol concentration, the intestinal inflammatory cell number of zebra fish is significantly reduced compared with the model group.
(2) Effect of pure green penicillium on intestinal tissue of inflammatory bowel disease zebra fish
The intestinal section hematoxylin-eosin (H & E) staining was performed on zebra fish from the blank, TNBS, and pure green penicillium alcohol (90 μg/mL) groups. Experimental results show that the structures of the intestinal tissue mucous membrane layer, the muscular layer and the serosa layer of the zebra fish in the blank group are clear, the single-layer columnar epithelium lining is attached to the surface of the mucous membrane, the intestinal tissue is highly columnar and orderly arranged, and no obvious pathological change is seen; the TNBS group zebra fish intestinal tissue cells are sparsely arranged, so that necrosis and dissolution of mucous membrane epithelium (black solid arrow) can be seen, and intestinal folds disappear (black arrow). Compared with TNBS group, zebra fish intestinal tissue fold recovery after pure green penicillium administration, cell arrangement is more compact, see figure 3.
(3) Effect of pure green penicillium on intestinal ultrastructure of inflammatory bowel disease zebra fish
And (5) observing and analyzing intestinal ultrastructures of the zebra fish in each group by using a transmission electron microscope technology. The intestinal cell membrane of the blank group is complete, the organelle is rich, the microvilli (Mv) are orderly arranged, and the thickness is uniform (shown by an arrow). The TNBS group intestinal microvilli are unevenly distributed, and are slightly sparse and disordered locally (shown by arrows). The intestinal microvilli shown in the pure green penicillium group tablet recovered to a rich state (indicated by the arrow) as shown in fig. 4.
(4) Effect of pure green penicillium on key genes of inflammatory bowel disease
The PCR results showed a significant decrease in mRNA expression of ppaγ, zak in TNBS group zebra fish (P < 0.01) and an increase in mRNA expression of hsp70.1, ap-1, map3k8, il8a, ibbαa, nf- κb, as compared to the blank control group. Compared to TNBS group, mRNA expression of ppaγ, zak was significantly increased in zebra fish in the pure green penicillium treatment group, and mRNA expression of hsp70.1, ap-1, map3k8, il8a, ibbαa, nf- κb was significantly decreased (P < 0.01), see FIG. 5.
The result shows that compared with a blank group, the TNBS group zebra fish has the advantages that the TNBS is used for causing the intestinal inflammation of the zebra fish, the number of the intestinal inflammatory cells of the TNBS group zebra fish is obviously increased, the intestinal tissue cells are arranged sparsely, the intestinal folds disappear, the intestinal microvilli are unevenly distributed, and the local part is slightly sparse and disordered. The compound pure green penicillium can obviously reduce the aggregation of inflammatory cells in the intestinal tract of the zebra fish caused by TNBS, restore the folds and microvilli in the intestinal tract, up-regulate the expression of ppar gamma and regulate the signal paths of MAPK and NF- κB, thereby effectively relieving the inflammatory diseases in the intestinal tract of the zebra fish.
Experimental example 1
Pure penicillium has no anti-inflammatory effect on systemic infectious inflammation caused by endotoxicity (LPS)
Transgenic zebra fish with 3dpf healthy inflammatory cells marked with green fluorescence are taken as test animals, and randomly divided into a blank control group (fish culture water), an LPS inflammatory model group (LPS, 25 ug/mL), and pure green penicillium treatment groups with different concentrations (LPS+30 mug/mL pure green penicillium, LPS+60 mug/mL pure green penicillium, LPS+90 mug/mL pure green penicillium). The model group and the pure green penicillium treatment group (without pure green penicillium) with different concentrations are respectively added with endotoxity (LPS) with the final concentration of 25 mug/mL simultaneously, and each group of 10 fries is provided with 2 repeated holes simultaneously. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and incubated continuously for 2 days in the dark. And after the completion, cleaning the fries of each group, respectively placing the blank control group and the model fries in fresh culture water, and placing the fries of the sample groups with different concentrations in culture water containing samples to be tested with different concentrations. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and continuously acted for 1 day. After the treatment, zebra fish were anesthetized with 0.2% ethyl metaaminobenzoate mesylate, and the inflammatory cell aggregation change of each group of zebra fish was observed under a fluorescence microscope. And (5) counting and analyzing the number of inflammatory cells of the zebra fish body.
As shown in fig. 6, the number of inflammatory cells of zebra fish body in the LPS model group was significantly increased compared to the control group. Compared with the model group, the number of inflammatory cells of the zebra fish organism in each concentration group of the pure green penicillium has no obvious change. Shows that the pure green penicillium alcohol has no anti-inflammatory effect on systemic infectious inflammation caused by LPS.
From the above experimental results, it can be seen that there is a model of systemic infectious inflammation caused by endotoxicity (LPS); unlike the inflammatory bowel disease model caused by 2,4,6-trinitrobenzenesulfonic acid (TNBS), the anti-inflammatory effects of both pure penicillins are not relevant.
Experimental example 2
Epimedin B vs CuSO 4 The resulting acute neurogenic inflammation model and tail-breaking induced local inflammation of zebra fish have anti-inflammatory effect, but have no effect on inflammatory bowel diseases caused by TNBS
(1) Epimedin B vs CuSO 4 Anti-inflammatory effect inducing acute inflammation of zebra fish
The transgenic zebra fish with 72hpf healthy inflammatory cells marked with green fluorescence is selected as an experimental animal. Setting blank control group (fish culture water) and inflammation model group (CuSO) 4 ) Positive control group (CuSO) 4 +ibuprofen 10. Mu.M) and epimedin group B (CuSO 4 +epimedin B80, 160, 320 μm). Each group of 10 zebra fish is provided with 2 compound holes at the same time. The zebra fish is exposed in the epimedin B liquid medicine for 24 hours, and CuSO is added into other groups except the blank control group 4 (40. Mu.M) was exposed to light for 1h. And observing the condition of inflammatory cells migrating to the side line under a Zeiss fluorescence microscope, photographing, and counting the number of inflammatory cells migrating to the side line.
(2) Anti-inflammatory effect of epimedin B on tail breakage induction of local inflammation of zebra fish
The transgenic zebra fish with 72hpf healthy inflammatory cells marked with green fluorescence is selected as an experimental animal. A blank group (unbroken tail zebra fish + fish-raising water), a tail-breaking model group (tail zebra fish + fish-raising water) and a epimedin B group (tail zebra fish + epimedin B80, 160, 320. Mu.M) were set. The blank is a normal developing zebra fish, and the other groups are cut off the tail of the same length at a fixed position under a microscope with a surgical knife. The zebra fish are moved into 24-hole plates, 10 zebra fish are arranged in each hole, and two compound holes are arranged. After the zebra fish after tail breaking is exposed in epimedin B liquid medicine for 6 hours, the aggregation condition of inflammatory cells at the tail breaking position is observed under a zeiss fluorescence microscope.
(3) Influence of epimedin B on TNBS-induced aggregation level of inflammatory cells in intestinal tract of zebra fish
Transgenic zebra fish with 3dpf healthy inflammatory cells marked with green fluorescence is taken as a test animal, and randomly divided into a blank control group (fish culture water), a model group (TNBS) and a sample group with different concentrations (TNBS+80 mu M epimedin B, TNBS +160 mu M epimedin B, TNBS +320 mu M epimedin B). 2,4,6-trinitrobenzene sulfonic acid (TNBS) with a final concentration of 50 mug/mL was added simultaneously to the model group and the sample group (without epimedin B), 10 fish larvae per group were each provided with 2 duplicate wells. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and incubated continuously for 2 days in the dark. And after the completion, cleaning the fries of each group, respectively placing the blank control group and the model fries in fresh culture water, and placing the fries of the sample groups with different concentrations in culture water containing samples to be tested with different concentrations. The zebra fish of each group are placed in a constant temperature incubator at 28.5 ℃ and continuously acted for 1 day. After the treatment was completed, the zebra fish was anesthetized with 0.2% ethyl metaaminobenzoate mesylate and photographed under a fluorescent microscope. The number of inflammatory cells showing green fluorescence in the intestinal tract of zebra fish was counted.
Experimental results:
1.1 epimedin B vs CuSO 4 Anti-inflammatory effect inducing acute neurogenic inflammation in zebra fish
As shown in fig. 7 and 8, compared with the blank group, cuSO 4 The number of inflammatory cells migrating to the lateral line of the zebra fish in the model group is obviously increased, and the copper sulfate causes inflammatory reaction in the zebra fish body. The number of inflammatory cells migrating to the lateral line site in the zebra fish organism in the positive drug (ibuprofen) group and the epimedin B administration group is remarkably reduced compared with that in the copper sulfate model group. As the concentration of epimedin B administration increases, the number of inflammatory cells migrating to the side line decreases, and when the concentration of epimedin B administration is 320 μm, the number of inflammatory cells migrating to the side line decreases to 73.5% of the inflammatory model group. Description of epimedin B vs CuSO 4 The induced acute neurogenic inflammation of the zebra fish is obviousAnti-inflammatory effect.
1.2 anti-inflammatory action of epimedin B on the induction of local inflammation in zebra fish by tail breakage
As shown in fig. 9 and 10, the number of inflammatory cells at the tail-biting portion of the zebra fish was increased in the tail-biting model group compared to the blank group. As the dose of epimedin B increases, the number of inflammatory cells at the tail-biting site of zebra fish decreases compared to the tail-biting model group. It is illustrated that epimedin B has anti-inflammatory effect on the induction of local inflammation in zebra fish by tail breakage.
1.3 epimedin B has no anti-inflammatory effect on inflammatory bowel disease caused by TNBS
As shown in fig. 11 and 12, the number of zebra fish intestinal inflammatory cells in the TNBS model group was significantly increased compared to the control group. Compared with the model group, the number of the zebra fish intestinal inflammatory cells in each concentration group of epimedin B is not changed significantly. It was shown that epimedin B had no anti-inflammatory effect on inflammatory bowel disease caused by TNBS.
As can be seen from the above experimental results, the pair CuSO of HodingB 4 The resulting inflammatory model has anti-inflammatory effect on partial inflammation of zebra fish induced by tail break, but has no effect on inflammatory bowel disease caused by TNBS. It can be demonstrated that the anti-inflammatory effect of the same drug on different inflammatory models is not relevant; further prove CuSO 4 The resulting neurogenic inflammation model and the inflammatory bowel disease caused by TNBS are different in mechanism and inflammatory effect, and are not related.
The invention discovers that the pure green penicillium can treat inflammatory bowel disease for the first time, increases the new application of the pure green penicillium, provides a new treatment means for treating inflammatory bowel disease, and also provides reference for the application and development of the pure green penicillium.
Claims (2)
1. Use of pure penicillium alcohol in the preparation of a medicament for the treatment of inflammatory bowel disease, wherein the pure penicillium alcohol has the structural formula:
。
2. the use according to claim 1, wherein the medicament is prepared by activatingpparγExpression, modulation of MAPK and NF- κB signaling pathways, and effects in the treatment of inflammatory bowel disease.
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| CN110368389A (en) * | 2019-08-06 | 2019-10-25 | 自然资源部第三海洋研究所 | The preparation method and applications and Claritin of phenolic compound |
| BR102020017899A2 (en) * | 2020-09-01 | 2022-03-15 | Universidade De São Paulo - Usp | Use of viridicatin and viridicatol in the preparation of cosmetic formulations with photoprotective and antioxidant activity and of pharmaceutical formulations for the prevention and/or treatment of inflammatory and parasitic diseases |
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| CN110368389A (en) * | 2019-08-06 | 2019-10-25 | 自然资源部第三海洋研究所 | The preparation method and applications and Claritin of phenolic compound |
| BR102020017899A2 (en) * | 2020-09-01 | 2022-03-15 | Universidade De São Paulo - Usp | Use of viridicatin and viridicatol in the preparation of cosmetic formulations with photoprotective and antioxidant activity and of pharmaceutical formulations for the prevention and/or treatment of inflammatory and parasitic diseases |
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| Viridicatol from Marine-derived Fungal Strain Penicillium sp SF-5295 Exerts Anti-inflammatory Effects through Inhibiting NF-kappa B Signaling Pathway on Lipopolysaccharide-induced RAW264.7 and BV2 Cells;Ko, Wonmin等;Natural Product Sciences;第21卷(第4期);240-247 * |
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