CN105997974A - Application of rosmarinic acid to preparing medicines for treating asthma - Google Patents

Application of rosmarinic acid to preparing medicines for treating asthma Download PDF

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Publication number
CN105997974A
CN105997974A CN201610570798.2A CN201610570798A CN105997974A CN 105997974 A CN105997974 A CN 105997974A CN 201610570798 A CN201610570798 A CN 201610570798A CN 105997974 A CN105997974 A CN 105997974A
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China
Prior art keywords
rosmarinic acid
group
treating asthma
asthma
application
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CN201610570798.2A
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Chinese (zh)
Inventor
何家康
梁正敏
严寒
陈文�
徐杨峰
文雪梅
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Guangxi University
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Guangxi University
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/21Esters, e.g. nitroglycerine, selenocyanates
    • A61K31/215Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
    • A61K31/216Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acids having aromatic rings, e.g. benactizyne, clofibrate

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  • Health & Medical Sciences (AREA)
  • Emergency Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention discloses application of rosmarinic acid to preparing medicines for treating asthma. The application has the advantages that mouse asthma models are built under the induction effects of ovalbumin, and accordingly effects of the rosmarinic acid for treating asthma can be proved; the rosmarinic acid is low in toxicity and few in toxic effects when used for treating asthma, excellent cure effects can be realized when the rosmarinic acid is used for treating asthma, and the like.

Description

Rosmarinic acid application in preparation treatment asthmatic medicament
Technical field
The present invention relates to pharmaceutical technology field, the application in preparation treatment asthmatic medicament of a kind of rosmarinic acid.
Background technology
Rosmarinic acid, English name: rosmarinci acid, is in labiate Herba Rosmarini Officinalis the one of isolated Plant water miscible natural phenolic acid compounds.Chemical name is R (t) 2-[[3-(3,4. dihydroxy phenyl)-1-oxo-2-propylene Base] epoxide]-3,4-dihydroxy benzenes propanoic acid, by a part caffeic acid and a part 3,4. DLA condensation forms.Fan The most fragrant acid is widely distributed in plant, is distributed mainly on many plantations such as Labiatae, Boraginaceae, Umbelliferae, Cucurbitaceae and Duan Shu section In thing, rosmarinic acid is dietotherapeutic herbaceous plant, is available for viewing and admiring and extracting fragrance, is alternatively arranged as food seasoning.Numerous studies Show that rosmarinic acid has many-sided pharmacological action such as antioxidation, antibacterial, antiviral, antidepressant.At present, rosmarinic acid is in system The fields such as medicine, food, cosmetics have embodied its important using value.But there are no rosmarinic acid for treating asthma Relevant report.
Asthma is a serious health problems all existed all over the world, badly influences daily life, has Time even fatal harm.Allergic asthma is the conducting airways obstacle of a kind of heterogeneity, including chronic airway inflammation, air flue Function reduction and air flue tissue remodeling.Its major pathologic features is that mucus hypersecretion, airway obstruction, airway inflammation and air flue are high anti- Ying Xing etc..Asthma is considered as to be caused by the interaction of inherited genetic factors and environmental effect, the infective dose of such as anaphylactogen With infection time and contact infection etc..At present, inhaled plays a major role in preventing and treating asthma.Although sucking Glucocorticoid is typically effective, but their high dose or long-time use can cause serious side effect, such as growth Impaired development, adrenal gland's suppression, fracture, hepatic injury, cancer and apoplexy equivalent risk so that it is on Clinical practice, face one for a long time Predicament.Therefore, find new, safety, effective medicine to prevent or treat asthma to have become urgent needs.
Summary of the invention
It is an object of the invention to provide the new application of a kind of rosmarinic acid, specifically rosmarinic acid in preparation treatment asthma Application in medicine.Rosmarinic acid has the advantages such as low toxicity, side effect is little, curative effect is more preferable.
In order to realize object above, the technical solution used in the present invention is as follows:
The present invention provides rosmarinic acid application in preparation treatment asthmatic medicament.
The present invention sets up mouse asthmatic model by ovalbumin (OVA) induction, re-uses dexamethasone and rosmarinic acid Treatment asthma, confirms the effect of rosmarinic acid treatment asthma by contrast.
The above dexamethasone is the synthetic chemicals effectively treating asthma, is often used as asthma Chinese medicine The control drug of screening study, but this medicine is asthma chemical drugs, and toxic and side effects is relatively big, and long-term a large amount of uses easily cause exempts from Epidemic disease suppresses, and causes the side effect such as Abwehrkraft des Koepers decline, growth retardation.
Present invention also offers the pharmaceutically acceptable dosage form of rosmarinic acid, including tablet, powder, granule, injection, Aerosol and capsule.
Compared with prior art, beneficial effects of the present invention:
The present invention, by substantial amounts of comparative study and pharmacological evaluation, finds that rosmarinic acid has had in preparation treatment asthmatic medicament new Application, rosmarinic acid is the Chinese medicine monomer extracted from Chinese herbal medicine, has that low toxicity, side effect is little, curative effect is good Advantage, provides more efficiently medicine for asthmatic patient.
Accompanying drawing explanation
Fig. 1 is the pathological change figure after mouse lung tissue carries out HE dyeing;
Fig. 2 is the pathological change figure after mouse lung tissue carries out AB-PAS dyeing.
In figure: A is normal group, B is model group, and C is rosmarinic acid group, and D is Dexamethasone group.
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is further described, but is not limited to protection scope of the present invention.
Embodiment 1
1, mouse asthmatic model is set up
Randomly select the female BABL/c mice 48 that body weight is 18-20g, be divided into blank group, model group, rosmarinic acid group And Dexamethasone group, often group 12;At the 0th day, the 7th day, the 14th day, model group, rosmarinic acid group, Dexamethasone group little Mus is respectively at lumbar injection OVA(ovalbumin) sensitization liquid, the concentration of OVA is 100 μ g/mL, every injection mice 0.2mL, empty The PBS of the injected in mice equivalent of white matched group.At the 22-27 days, model group, rosmarinic acid group, Dexamethasone group mice every It collunarium concentration after etherization is the OVA of 2mg/mL, every mice 50 μ L, Normal group mice collunarium equivalent PBS. At the 25th, 26,27 days, rosmarinic acid and dexamethasone medicine group every day at mouse peritoneal drug administration by injection, wherein rosmarinic acid: 20mg/kg, dexamethasone: 2mg/kg, excites administration in latter 1 hour.Model group and Normal group inject equivalent at mouse peritoneal Normal saline, collunarium operation terminated after 24 hours the last time, and sampling carries out follow-up experiment.
, rosmarinic acid is on the impact of classified counting of leucocyte in bronchoalveolar lavage fluid (BALF)
After the operation of above-mentioned mice collunarium the last time terminates 24 hours, ether excessively anaesthetizes execution mice, fixing mice, cuts Open mice skin of neck, separation and fully expose trachea, above trachea, doing " one " shape otch, inserting self-control and intubate, with injection Device injects the pre-cooling PBS of 0.5mL, sucking-off after flushing, in triplicate, gathers bronchoalveolar lavage fluid after BALF with 4 DEG C, The rotating speed of 3000r/min is centrifuged 10 minutes, and supernatant is placed in 80 DEG C of Refrigerator stores for measuring cytokine content in BALF. Bottom cell precipitation is resuspended in PBS, and cell smear dyes with Switzerland Ji nurse Sa dye liquor, for classified counting of leucocyte.Cell Differential counting result is as shown in table 1.
Differential blood count (10 in table 1:BALF6Individual/mL)
Group Total cellular score Neutrophilic granulocyte Eosinophil
Blank group 1.29±0.39 0.38±0.12 0.016±0.0021
Model group 5.60±1.10# 1.67±0.37# 1.62±0.42#
Rosmarinic acid group 2.87±1.00* 0.86±0.33** 0.54±0.18**
Dexamethasone group 2.37±0.85** 0.71±0.27** 0.38±0.12**
Note: # P < 0.01vs. model group, * P < 0.05, * * P < 0.01vs. medicine group.
The above results shows, OVA stimulation causes total cellular score in BALF, neutrophilic granulocyte number and eosinophilic granulocyte's number pole Significantly increase (p < 0.01).But, rosmarinic acid significantly decreases total cellular score in BALF (p < 0.05), neutrophilic granulocyte number (p < 0.01) and eosinophilic granulocyte's number (p < 0.01).
, rosmarinic acid is on the impact of IL-4, IL-5 and IL-13 in BALF
After collecting bronchoalveolar lavage fluid, survey according to mice IL-4, IL-5 and IL-13 ELISA detection kit description Determine the secretion level of IL-4, IL-5 and IL-13 in the mouse allelgic asthma air flue BALF of OVA induction.
Table 2: IL-4, IL-5 and IL-13 concentration (pg/mL) in bronchoalveolar lavage fluid
Group IL-4 IL-5 IL-13
Blank group 43.19±7.66 11.78±1.02 19.73±2.31
Model group 104.75±4.97# 33.09±4.83# 57.50±0.69#
Rosmarinic acid group 63.39±7.42** 22.21±3.02* 37.28±4.23**
Dexamethasone group 50.70±6.61** 15.20±1.42** 29.56±5.96**
Note: # P < 0.01vs. model group, * P < 0.05, * * P < 0.01vs. medicine group.
Result shows, compared with normal blank matched group, stimulates through ovalbumin and causes IL-4, IL-5 in model group BALF Significantly raising (p < 0.01) with IL-13 content, compared with model group, rosmarinic acid and dexamethasone significantly reduce in BALF Th2 cytokine IL-4(p < 0.01), IL-5(p < 0.05) and IL-13(p < 0.01) concentration.
, rosmarinic acid on asthmatic mouse pathological change affect
The operation of mice collunarium the last time terminates 24 hours, and ether excessively anaesthetizes execution, takes mouse lung tissue respectively, with 4% Paraformaldehyde solution is fixed, and the dehydration through routine is transparent, waxdip embeds and section exhibition sheet processes, and finally enters lung tissue section Row HE and AB-PAS dyes, and observes the pathological change of hyper responsiveness of allergic asthmatic mice pulmonary.Result is as depicted in figs. 1 and 2.
As it is shown in figure 1, HE coloration result display blank group alveolar wall structural integrity, alveolar septum thicken without edema and Inflammatory cell infiltration, OVA induction model group, rosmarinic acid group and Dexamethasone group, mice alveolar septal thickening, bronchus and Having substantial amounts of inflammatory cell infiltration, and air flue luminal stenosis around blood vessel, generate with rheuminess thing, tracheal smooth muscle is obvious Thicken, but after rosmarinic acid is treated, around bronchus and blood vessel, lung tissue inflammatory cell number substantially reduces, and tracheal wall is not Water breakthrough swells, and smooth muscle is also without substantially thickening.
As in figure 2 it is shown, AB-PAS coloration result shows, compared with blank group, the model group of OVA induction, Herba Rosmarini Officinalis Acid group and Dexamethasone group, epithelial cell number showed increased positive in PAS above mice tracheal wall and with goblet cell The phenomenon of hypertrophy, mucous secretion significantly increases, and compared with model group, rosmarinic acid group can substantially reduce goblet cell and mucus Secretion, further relates to rosmarinic acid and has significant therapeutic effect to asthma.

Claims (1)

1. rosmarinic acid application in preparation treatment asthmatic medicament.
CN201610570798.2A 2016-07-19 2016-07-19 Application of rosmarinic acid to preparing medicines for treating asthma Pending CN105997974A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1315863A (en) * 1998-05-16 2001-10-03 财团法人牧岩生命工学研究所 Use of rosmarinic acid and derivatives thereof as immunosuppressant or inhibitor of SHz-mediated process
CN1767844A (en) * 2003-04-08 2006-05-03 草本制药科学有限责任公司 Rosmarinic acid composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1315863A (en) * 1998-05-16 2001-10-03 财团法人牧岩生命工学研究所 Use of rosmarinic acid and derivatives thereof as immunosuppressant or inhibitor of SHz-mediated process
CN1767844A (en) * 2003-04-08 2006-05-03 草本制药科学有限责任公司 Rosmarinic acid composition

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
C.SANBONGI等: "Rosmarinic acid in perilla extract inhibits allergic inflammation induced by mite allergen, in a mouse model", 《CLIN EXP ALLERGY 》 *

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