CN114533752A - Application of naringin in preparing medicament for treating chronic obstructive pulmonary disease - Google Patents
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- CN114533752A CN114533752A CN202210331739.5A CN202210331739A CN114533752A CN 114533752 A CN114533752 A CN 114533752A CN 202210331739 A CN202210331739 A CN 202210331739A CN 114533752 A CN114533752 A CN 114533752A
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- 239000001606 7-[(2S,3R,4S,5S,6R)-4,5-dihydroxy-6-(hydroxymethyl)-3-[(2S,3R,4R,5R,6S)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxyoxan-2-yl]oxy-5-hydroxy-2-(4-hydroxyphenyl)chroman-4-one Substances 0.000 title claims abstract description 40
- DFPMSGMNTNDNHN-ZPHOTFPESA-N naringin Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](OC=2C=C3O[C@@H](CC(=O)C3=C(O)C=2)C=2C=CC(O)=CC=2)O[C@H](CO)[C@@H](O)[C@@H]1O DFPMSGMNTNDNHN-ZPHOTFPESA-N 0.000 title claims abstract description 40
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Classifications
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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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/75—Rutaceae (Rue family)
- A61K36/752—Citrus, e.g. lime, orange or lemon
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- Natural Medicines & Medicinal Plants (AREA)
- Veterinary Medicine (AREA)
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- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
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- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Biotechnology (AREA)
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- General Chemical & Material Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract
The invention discloses a new application of naringin in preparing a medicine for treating chronic obstructive pulmonary disease. In particular to application of naringin in preparing medicaments for treating chronic obstructive pulmonary diseases induced by diesel PM2.5 particles, which comprises preparing medicaments for treating reduction of lung tissue elastic resistance, increase of lung tissue airway resistance or lung airway wall or alveolar cavity thickening induced by diesel PM2.5 particles. Tests prove that the naringin can be used as a pharmaceutical active ingredient and matched with a pharmaceutically acceptable carrier, provides basis for preventing and treating chronic obstructive pulmonary disease and improves the life quality of patients.
Description
Technical Field
The invention relates to the application of naringin in preparing medicine, in particular to the application of naringin in preparing medicine for treating chronic obstructive pulmonary disease.
Background
Naringin is an effective monomer extracted from exocarpium Citri Grandis (Lingnan) of Lingnan, is widely present in Citrus plants of Rutaceae, and has significant effects in relieving cough, eliminating phlegm, relieving inflammation, and resisting oxidation. Naringin has the following structure:
chronic Obstructive Pulmonary Disease (COPD) is a pulmonary disease characterized by airflow limitation which is not completely reversible and progresses in a progressive manner, the occurrence of which is associated with an abnormal inflammatory response of the lungs to harmful gases or harmful particles. With repeated attack and acute exacerbation, the lung function gradually declines, and shortness of breath is felt even during daily activities and even rest. COPD is of high prevalence, more common in the elderly, mainly caused by smoking, and is also associated with environmental pollutant concentrations. Approximately 300 million people die worldwide each year from COPD. With the increasing population of cigarette smokers in developing countries and the aging population in high income countries, the prevalence of COPD will continue to increase, estimated at 2030 that 450 million people will die from COPD-related diseases. While there are a number of pharmacological and non-pharmacological interventions currently available to prevent the onset of acute exacerbations of COPD, these approaches still have limited reduction in the frequency of episodes of acute exacerbations in patients. Therefore, it is important to develop a novel drug capable of effectively treating COPD.
Disclosure of Invention
The invention aims to disclose a new application of naringin in preparing a medicament for treating chronic obstructive pulmonary disease.
In particular to application of naringin in preparing medicaments for treating chronic obstructive pulmonary diseases induced by diesel PM2.5 particles, which comprises preparing medicaments for treating reduction of lung tissue elastic resistance, increase of lung tissue airway resistance or lung airway wall or alveolar cavity thickening induced by diesel PM2.5 particles.
The naringin can be matched with a pharmaceutically acceptable carrier and prepared into various common preparations according to a conventional production method. It is safe for oral administration and non-oral administration, and can be made into any conventional forms, such as granule, tablet, capsule, pill, oral liquid, spray or aerosol, suppository, injection, ointment, inhalant, etc.
The medicine for treating chronic obstructive pulmonary disease can be prepared into different formulations by a conventional method by selecting conventional auxiliary materials suitable for corresponding formulations or adding no auxiliary materials. The adjuvant can be solid, semisolid or liquid, and can be used as vehicle, excipient or medium of naringin.
According to the invention, Diesel Particulate Matters (DPM) serving as PM2.5 simulative agents are instilled to induce mice to generate COPD, and the treatment effect of naringin on COPD is researched on the basis. The experimental results show that: 1. the naringin of 30, 60 and 120mg/kg administered by intragastric administration has protective effect on lung function of COPD mice induced by DPM; 2. naringin has certain relieving effect on the pathological change of lung tissues of COPD mice; 3. naringin has inhibitory effect on DPM-induced inflammatory cell infiltration and inflammatory factor expression in COPD mice. The naringin can be used as a medicine active component and matched with a pharmaceutically acceptable carrier to prepare a medicine for treating chronic obstructive pulmonary disease, provides basis for preventing and treating COPD and improves the life quality of patients.
Detailed Description
The invention is further illustrated by the following examples. The examples of the present invention are intended to illustrate the present invention, not to limit the present invention. Simple modifications of the invention in accordance with its spirit fall within the scope of the claimed invention.
Example 1 Effect of Naringin on Lung function in mice model for COPD
Male ICR mice (SPF grade) weighing around 20g of 48 mice were randomly divided into six groups of 8 mice each. Normal control group, model group, naringin low and medium dosage group (30, 60, 120mg/kg) and positive control group. After the mice were adapted to be raised for 1 week, the mice were molded, injected with 10% chloral hydrate intraperitoneally, anesthetized, and placed on an inclined stand so as to be supine at an angle of 45 °. The mouth of the mouse was opened using a spatula, the glottis was found, the trachea was inserted through the glottis to the lungs using a special microinjection syringe, and DPM (0.5 mg/mouse, 50 μ L/mouse) was instilled. Keeping for 1-2min to uniformly diffuse DPM. The administration is performed by intragastric administration 1h before each instillation (the intragastric administration volume is 0.2mL), the administration doses of naringin are respectively 30, 60 and 120mg/kg (calculated by the prepared dry powder), the dose of the roflumilast in a positive control group is 5mg/kg, and the intragastric administration of the normal control group and a molding group is performed by using physiological saline with the same volume. After instillation and molding, the injection is continuously administered by gavage for 40 days in groups, once a day, and the mice are treated for test after administration for 1 hour on the 40 th day of the test.
And (3) lung function measurement: the mouse static compliance (Cchord), dynamic lung compliance (Cdyn), airway Resistance (RI), peak expiratory flow rate (PEF) were determined using a Buxco small animal lung function analysis system.
The experimental results are as follows: compared with a normal control group, the model group mice Ccpord and RI are increased, and Cdyn and PEF are reduced (p is less than 0.05 or p is less than 0.01). Naringin can reduce Cward and RI in a dose-dependent manner with significant differences (p < 0.05 or p < 0.01) compared with the model group. The naringin of 120mg/kg can increase mouse Cdyn and PEF, and has obvious difference compared with a model group (p is less than 0.05). The naringin is prompted to relieve the reduction of the elastic resistance of the lung tissue of the mouse caused by DPM, inhibit the collapse of the elastic fiber, reduce the airway resistance and improve the function of the small airway. The positive control drug roflumilast can also reduce Ccpord and RI, has a significant difference (p is less than 0.05) compared with a model group, and has no significant regulation and control on Cdyn and PEF. The results are shown in Table 1.
Note: compared with the normal group, # p < 0.05 or # p < 0.01; p < 0.05 or p < 0.01 compared to model groups.
Example 2 Effect of Naringin on pathological changes in the Lung of mice model COPD
The experimental groups, the molding method and the administration method were the same as in example 1.
Pathological observation of lung tissues of mice: and (4) preparing a section, staining by hematoxylin-eosin, and observing pathological changes of lung tissues of the mouse.
The experimental results are as follows: the normal group of mice has regular lung tissue structure, uniform alveoli distribution, complete alveolar wall without obvious collapse, complete tracheal wall without thickening and no obvious inflammatory cell aggregation and bleeding sites in tissues. Compared with the normal group of mice, the lung structure of the model group of mice is obviously changed, and the lung structure of the model group of mice comprises: the change of the tissue structure reduces the contact area of the lung gas exchange and increases the difficulty of the gas exchange, thereby reducing the lung function and influencing the normal respiratory physiological process. Naringin can attenuate DPM-induced lung tissue structural abnormalities to some extent, including: the regulation and control effects of recovering tracheal wall and alveolar cavity structures and inhibiting inflammatory cell aggregation and tissue bleeding have obvious dose-effect relationship, and the high dose has more obvious recovery effect. The positive control drug roflumilast can also inhibit lung tissue damage induced by DPM to a certain extent.
Example 3 Effect of Naringin on the number of blood leukocytes in mice model for COPD
The experimental groups, the molding method and the administration method were the same as in example 1.
Mouse orbital bleeds and leukocyte division counts: cutting two-side beard of each group of mice, using an elbow forceps to pull out one side of eyeball, collecting the flowing blood in a blood collection tube containing heparin sodium, using a full-automatic blood cell analyzer to perform blood leukocyte classification and counting, and respectively detecting the total number of leukocytes and the number of lymphocytes.
The experimental results are as follows: the total number of leukocytes and the number of lymphocytes were increased in the model group mice as compared with the normal group (p < 0.05). Compared with the model group, the total leukocyte and lymphocyte of the naringin administration group are obviously reduced (p is less than 0.05 or p is less than 0.01). Naringin mainly controls lymphocyte to increase DPM induced leukocyte. The roflumilast has obvious effect on inflammatory cells in blood of COPD mice, and the total number of leucocytes and the number of lymphocytes are obviously reduced (p is less than 0.05) compared with a model group. The results are shown in Table 2.
Note that # p is less than 0.05 compared with the normal group; p < 0.05 or p < 0.01 compared to model groups.
Example 4 Effect of Naringin on Lung tissue inflammation in COPD model mice
The experimental groups, the molding method and the administration method were the same as in example 1.
Mouse lung tissue immunohistochemistry: after cervical dislocation, the chest was opened to isolate lung tissue, which was fixed in 4% paraformaldehyde solution. After the tissues are embedded in paraffin and sliced, the tissues are baked for 2 hours at 60 ℃. The tissue slices are washed by water after dewaxing treatment, antigen retrieval is carried out, and then sealing treatment is carried out. Primary antibodies (IL-8, TNF-. alpha.and NF-. kappa.B) were incubated separately at 4 ℃ overnight. After washing with PBS, a secondary poly-HRP-labeled anti-mouse IgG antibody was added and incubated at room temperature for 1 h. And after being washed by PBS, the color is developed, the running water is turned to blue, and the water is dehydrated. The sections were finally mounted and observed under a microscope.
The experimental results are as follows: the lung tissues of normal mice have no obvious IL-8, TNF-alpha and NF-kappa B expression, and the lung tissues have regular structure, uniform alveolar distribution, complete alveolar walls without obvious collapse, complete tracheal walls without thickening and no obvious inflammatory cell aggregation. Compared with the normal group of mice, the lung IL-8, TNF-alpha and NF-kappa B expressions of the model group of mice are all obviously increased and are obviously expressed near the deposition of trachea ring DPM. Naringin can significantly reduce the expression of IL-8, TNF-alpha and NF-kappa B in tissues, and has anti-inflammatory effect. The effect of high-dose naringin on inhibiting the increase of the expression of the inflammatory factors induced by the DPM is more obvious. In addition, naringin can restore tissue structure, and inhibit thickening of trachea wall and alveolar cavity caused by DPM. The positive control drug roflumilast can also obviously inhibit the DPM-induced increase of IL-8, TNF-alpha and NF-kappa B expression and tissue structure lesion, and has anti-inflammatory effect.
Claims (5)
1. Application of naringin in preparing medicine for treating chronic obstructive pulmonary disease is provided.
2. Application of naringin in preparing medicine for treating chronic obstructive pulmonary disease induced by diesel PM2.5 particulate matter is provided.
3. Application of naringin in preparing medicine for treating lung tissue elastic resistance reduction induced by diesel PM2.5 particulate matter is provided.
4. Application of naringin in preparing medicine for treating lung tissue airway resistance increase induced by diesel PM2.5 particulate matter is provided.
5. Application of naringin in preparing medicine for treating lung trachea wall or alveolar cavity thickening induced by diesel PM2.5 particulate matter is provided.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN115463142A (en) * | 2022-10-14 | 2022-12-13 | 广东省科学院动物研究所 | Application of naringin dihydrochalcone in preparation of medicine for treating pulmonary fibrosis |
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
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CN115463142A (en) * | 2022-10-14 | 2022-12-13 | 广东省科学院动物研究所 | Application of naringin dihydrochalcone in preparation of medicine for treating pulmonary fibrosis |
CN115463142B (en) * | 2022-10-14 | 2023-06-30 | 广东省科学院动物研究所 | Application of naringin dihydrochalcone in preparation of medicines for treating pulmonary fibrosis |
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