CN106389396A - Use of xanthohumol in prevention and treatment of acute lung injury and acute respiratory distress syndrome - Google Patents
Use of xanthohumol in prevention and treatment of acute lung injury and acute respiratory distress syndrome Download PDFInfo
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- CN106389396A CN106389396A CN201611100897.0A CN201611100897A CN106389396A CN 106389396 A CN106389396 A CN 106389396A CN 201611100897 A CN201611100897 A CN 201611100897A CN 106389396 A CN106389396 A CN 106389396A
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- xanthohumol
- lung injury
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
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Abstract
The invention provides use of xanthohumol in the prevention and treatment of acute lung injury and acute respiratory distress syndrome. The xanthohumol can be used for preventing and treating the acute lung injury and the acute respiratory distress syndrome. By treating the acute lung injury or the acute respiratory distress syndrome by virtue of xanthohumol, the toxic and side effects are small, clinical symptoms are obvious, and the curing rate is high.
Description
Technical field
The invention discloses purposes in preventing and treating acute lung injury with adult respiratory distress syndrome for the xanthohumol, belong to doctor
Medicine field.
Background technology
Xanthohumol（Xanthohumol）Extract the Flos lupuli (Flos Humuli Lupuli) being a kind of one of important source material from industrial beer brewing
Natural iso-amylene flavone compound, have anticancer, antiviral, prevention and treatment diabetes, atherosclerotic work
With.But have not yet to see xanthohumol for treating the report of acute lung injury.
Acute lung injury（ALI）And its severe form adult respiratory distress syndrome（ARDS）Refer to by wound, blood transfusion and
The many factors such as infection are led to, and with the releases of inflammatory factor a large amount of in interstitial lung, the gathering of inflammatory cell and pulmonary edema are
The acute progressive respiratory insufficiency of pathophysiological features or respiratory failure symptom, are that the main vital in Intensive Care Therapy is former
Cause.The pathogenesis of acute lung injury are intricate, relate generally to inflammatory reaction, oxidative stress and inflammation corpusculum etc. multiple logical
Road, and between individual channel be connect each other, influencing each other forms complicated cellular network and signal path network.Exactly by
In the complexity of its pathogenesis, although multiple large-scale clinical trials have been used to detect multiple therapeutic strategies（Including using sugar
17-hydroxy-11-dehydrocorticosterone, Ketoconazole, suck NO or the potential of surfactant etc. supplementing, still neither one is feasible so far, have
The Therapeutic Method of effect reduces its mortality rate.Compared with modern medicine conventional therapy means, Chinese herbal treatment advantage is to pass through
Multipath, too many levels adjust the immunoreation of body, thus affecting disease each factor pathogenetic and general action mechanism.In order to
Seek more preferable Therapeutic Method, have the angle from the multiple target effect of Chinese medicine for a lot of scholars, Study of Traditional Chinese Medicine list
The protective effect of the acute lung injury that body induced by endotoxin causes and mechanism although making some progress, but still in starting
In the stage, there is huge development prospect.Present invention firstly discovers that xanthohumol passes through to activate the performance of AMPK/AKT/Nrf2 signal path
Antioxidation, antiinflammatory and the effect of anti-inflammatory corpusculum, can be used for treating acute lung injury.
Content of the invention
The invention discloses purposes in preventing and treating acute lung injury with adult respiratory distress syndrome for the xanthohumol.
The invention discloses purposes in preparation prevention and treatment acute lung injury medicine for the xanthohumol.
The invention discloses the purposes in xanthohumol preparation treatment adult respiratory distress syndrome medicine.
The invention discloses treatment acute lung injury or adult respiratory distress syndrome are prepared for active component with xanthohumol
Medicine can be any pharmaceutical preparation pharmaceutically.
The molecular formula of xanthohumol of the present invention is：C21H22O5；Molecular weight 354.4
Xanthohumol of the present invention can have preferable therapeutical effect by rats with lipopolysaccharide-induced acute lung injury mice；
Xanthohumol of the present invention can activate AMPK/AKT/Nrf2 signal path；
Xanthohumol of the present invention can strengthen the antioxidase of Nrf2 regulation and control and the expression of metabolic enzymes；
Xanthohumol of the present invention can inhibited oxidation stress, the expression of the associated protein such as inflammation and inflammation corpusculum；
Xanthohumol of the present invention is to rely on AMPK/AKT/Nrf2 signal shaft to the therapeutical effect of mice with acute lung injury
Activation；
Invention also provides application in preparation treatment acute lung injury medicine for the xanthohumol；
Application in preparation treatment acute lung injury medicine for the preferred xanthohumol of technical solution of the present invention；
The present invention prepares treatment acute lung injury with xanthohumol for active component or the medicine of adult respiratory distress syndrome is permissible
It is any pharmaceutical preparation pharmaceutically；Xanthohumol and pharmaceutically acceptable adjuvant can be prepared into various dosage forms.
Xanthohumol is preferably prepared into the dosage forms such as injection, capsule, tablet, injectable powder by the present invention.
The positive effect of the present invention is：Provide the new medical application of xanthohumol, can be used for prevent and treat acute lung injury with
Adult respiratory distress syndrome.Treat acute lung injury or adult respiratory distress syndrome using xanthohumol, there are toxic and side effects
Little, substantially, cure rate is high for clinical symptoms.
Brief description
The protective effect that Fig. 1 changes to mice with acute lung injury pathologic state colony for xanthohumol of the present invention；
Fig. 2 is xanthohumol of the present invention in mice with acute lung injury bronchoalveolar lavage fluid（A）Neutrophilic granulocyte and (B) inflammatory cell because
The inhibitory action of son；
Fig. 3 is the inhibitory action to ROS product in mice with acute lung injury bronchoalveolar lavage fluid for the xanthohumol of the present invention；
Fig. 4 is the inhibitory action in vitro to the inflammation related proteins expression of LPS induction for the xanthohumol of the present invention；
Fig. 5 is xanthohumol of the present invention (A-C) inflammatory factor in vitro to LPS induction and the inhibitory action of (D) ROS；
Fig. 6 is the xanthohumol of the present invention activation to anti-oxidation stress signal path and antioxidase in vitro；
In the mice with acute lung injury lung tissue that Fig. 7 induces to LPS for xanthohumol of the present invention, Txinp activation and Trx-1 consume,
The adjustment effect of the NF- κ B inflammatory signal path of NLRP3 inflammatory corpusculum sum；
Fig. 8 is the activation to the protein expression of Nrf2, AMPK and GSK3 β in mice with acute lung injury lung tissue for the xanthohumol of the present invention
Effect；
Fig. 9 is xanthohumol of the present invention to wild type and Nrf2-/-(A-C) inflammatory factor in mice with acute lung injury bronchoalveolar lavage fluid
(D) inhibitory action of ROS；
Figure 10 is xanthohumol of the present invention to wild type and Nrf2-/-Txinp, NLRP3 inflammatory in mice with acute lung injury lung tissue
Corpusculum and the inhibitory action of NF- κ B signal path；
Figure 11 is the xanthohumol of the present invention activation to AMPK, GSK3 β and Nrf2 signal path in vitro；
Figure 12 adds after AMPK and Nrf2 inhibitor for xanthohumol of the present invention, to Nrf2 activation.
Specific embodiment
By testing to the therapeutical effect of chmice acute injury of lung in xanthohumol body, extracorporeal anti-inflammatory, antioxidant activity and right
The test of signal path adjustment effect and inside and outside antiinflammatory and the test of antioxidative mechanism of action confirm that xanthohumol can be by swashing
AMPK/AKT/Nrf2 signal shaft alive, plays the effect for the treatment of acute lung injury.
Experimental example 1
Therapeutical effect to mice with acute lung injury in xanthohumol body
Chmice acute model of lung injury is set up：60 male C57/B mices（6～8 week old, 18-20g）, random point 6 groups, every group
10：Blank group, LPS（0.5 mg/kg）Group, xanthohumol administration group（50 mg/kg）, xanthohumol（10、50 mg/kg）+ LPS
Group, dexamethasone（5 mg/kg）+ LPS group is as positive controls.Operational approach：First, normal saline dilution xanthohumol and
Dexamethasone intraperitoneal injection of mice, blank group and the isopyknic normal saline of LPS group lumbar injection.After being administered 1 h, LPS nasal cavity
Instillation modeling, blank group and the xanthohumol administration group mice nasal cavity isopyknic normal saline of instillation.After LPS instils 12 h, place
Dead mice, and collect mouse bronchial bronchoalveolar lavage fluid（BALF）And lung tissue, carry out corresponding Indexs measure.
Experimental result：
To the protective effect of the mice with acute lung injury that LPS induces referring to Fig. 1-3, xanthohumol can significantly inhibit LPS to xanthohumol
The mice with acute lung injury pathologic state colony of induction changes；Suppress internal inflammatory cell to invade profit to increase with inflammatory cytokine；
The excessive ROS that suppression LPS induction produces, plays protective effect to chmice acute injury of lung.
Experimental example 2
Xanthohumol extracorporeal anti-inflammatory, antioxidant activity and to signal path adjustment effect test
Cell model is set up：RAW 264.7 cell of exponential phase is laid in 96 well culture plates, after cultivating 24 hours, plus
Enter variable concentrations xanthohumol act on 1 hour, after give LPS（1 μg/ml）Effect 24 hours, MTT detects cytotoxicity；Cell
Be laid in 24 well culture plates, processing method ibid,（a）Collect supernatant ELISA detection cytokine, collect cell Western
Bloting detects iNOS, COX-2 and HMGB1 expression；B () is by the DCFH-DA having prepared（Final concentration：10 μM）It is added to
In each hole, it is placed in 37 °C of incubators and detects ROS product after reacting 30 min.
Cell is laid in 6 well culture plates, after culture 24 h, adds variable concentrations xanthohumol to process 18 h or xanthohumol（5
μM）Process cell different time, collect cell detection GCLC, GCLM, the protein expression of HO-1, NQO1 and Trx-1.
Experimental result：
As Fig. 4-6, xanthohumol has significant antiinflammatory antioxidant activity in vitro：Xanthohumol can significantly inhibit LPS induction inflammation phase
Close protein expression；Significantly inhibit inflammatory mediator and ROS product；Notable activation antioxidation signal path and the table of multiple antioxidase
Reach.
Experimental example 3
Inside and outside antiinflammatory and the research of antioxidation mechanism
Internal chmice acute model of lung injury is set up：In order to probe into the acute lung injury protection that xanthohumol induces to LPS further
Mechanism of action, wild type（WT）Knock out with Nrf2（Nrf2-/-）Mice, builds LPS inducing mouse acute lung injury model（Modeling
Method is ibid）, take lung tissue and the bronchoalveolar lavage fluid of mice（BALF）, carry out following related experiment.
Experimental result：Xanthohumol significantly inhibits oxygen to mice with acute lung injury Protective effects such as Fig. 7-10, xanthohumol
Change the Txinp activation of stress-induced and Trx-1 consumes, the NF- κ B inflammatory signal path of suppression NLRP3 inflammatory corpusculum sum；Significantly
Activation Nrf2, AMPK and GSK3 β；Significantly inhibit TNF-α, the generation of IL-6, IL-1 β and ROS, but in Nrf2-/-Press down in mice
Declines processed；Nrf2-/-In mouse lung tissue, Txinp, NLRP3 inflammatory corpusculum and NF- κ B letter that xanthohumol activates to LPS
The inhibitory action of number path is hence it is evident that weaken.
In vitro cell model is set up：Associated protein detection method is ibid.Additionally, cell is laid in 96 well culture plates, culture
After 24 h, treat that cell density grows to 70% about, add xanthohumol（5 μM）Process cell（1st, 3 or 6 hours）Afterwards, using double glimmering
Light element enzyme reagent kit detection ARE activity.Cell is laid in 6 well culture plates, after culture 24 h, adds CC（3 μM, the suppression of AMPK
Agent）Process cell 18 hours or add BT（The inhibitor of 100 nM, Nrf2）Process cell after 1 hour, be subsequently adding xanthohumol
（5 μM）Process cell 3 hours, collect cell detection correlative protein expression situation.
Experimental result：
Xanthohumol Antioxidation in vitro mechanism such as Figure 11-12, xanthohumol antioxidation in vitro depends on AMPK/GSK3 β/Nrf2 letter
Number channel axis.Xanthohumol can significantly activate AMPK, GSK3 β and Nrf2 signal path in vitro；Add AMPK and Nrf2 suppression
After agent, xanthohumol disappears to Nrf2 activation.
Claims (4)
1. purposes in preventing and treating acute lung injury with adult respiratory distress syndrome for the xanthohumol.
2. purposes in preparation prevention and treatment acute lung injury medicine for the xanthohumol.
3. purposes in preparation treatment adult respiratory distress syndrome medicine for the xanthohumol.
4. preparing treatment acute lung injury or the medicine of adult respiratory distress syndrome with xanthohumol for active component can be medicine
Any pharmaceutical preparation in thing.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201611100897.0A CN106389396A (en) | 2016-12-05 | 2016-12-05 | Use of xanthohumol in prevention and treatment of acute lung injury and acute respiratory distress syndrome |
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| CN201611100897.0A CN106389396A (en) | 2016-12-05 | 2016-12-05 | Use of xanthohumol in prevention and treatment of acute lung injury and acute respiratory distress syndrome |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524476A (en) * | 2018-07-09 | 2018-09-14 | 南京农业大学 | Purposes of the xanthohumol in preparing porcine epidemic diarrhea resisting virus drugs |
| CN112402402A (en) * | 2020-11-20 | 2021-02-26 | 青岛海洋科学与技术国家实验室发展中心 | Application of xanthohumol in preparation of novel coronavirus inhibitor |
| CN114432290A (en) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | Application of methylflavonoid compound in preparation of medicine for preventing or treating acute lung injury and/or acute respiratory distress syndrome |
| CN114432291A (en) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | Application of isopentene flavonoid compound in preparation of medicine |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080051465A1 (en) * | 2001-06-20 | 2008-02-28 | Metaproteomics, Llc | Xanthohumol and tetrahydro-isoalpha acid based protein kinase modulation cancer treatment |
| CN103735537A (en) * | 2014-01-06 | 2014-04-23 | 中国海洋大学 | Application of xanthohumol in preparation of drug or health-care product for inhibiting alpha-glucosaccharase activity |
-
2016
- 2016-12-05 CN CN201611100897.0A patent/CN106389396A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080051465A1 (en) * | 2001-06-20 | 2008-02-28 | Metaproteomics, Llc | Xanthohumol and tetrahydro-isoalpha acid based protein kinase modulation cancer treatment |
| CN103735537A (en) * | 2014-01-06 | 2014-04-23 | 中国海洋大学 | Application of xanthohumol in preparation of drug or health-care product for inhibiting alpha-glucosaccharase activity |
Non-Patent Citations (3)
| Title |
|---|
| KRISTIN ZIMMERMANN等: "Activated AMPK boosts the Nrf2/HO-1 signaling axis—A role for the unfolded protein response", 《FREE RADICAL BIOLOGY AND MEDICINE》 * |
| YALI ZHANG等: "Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury", 《SCIENTIFIC REPORTS》 * |
| 廉玉兰等: "HO-1和Nrf2在氧化/抗氧化肺部疾病中的研究进展", 《中国实验诊断学》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108524476A (en) * | 2018-07-09 | 2018-09-14 | 南京农业大学 | Purposes of the xanthohumol in preparing porcine epidemic diarrhea resisting virus drugs |
| CN114432290A (en) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | Application of methylflavonoid compound in preparation of medicine for preventing or treating acute lung injury and/or acute respiratory distress syndrome |
| CN114432291A (en) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | Application of isopentene flavonoid compound in preparation of medicine |
| CN112402402A (en) * | 2020-11-20 | 2021-02-26 | 青岛海洋科学与技术国家实验室发展中心 | Application of xanthohumol in preparation of novel coronavirus inhibitor |
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