CN112891350B - Application of trigonelline in preparing medicine for preventing or treating prostatic hyperplasia - Google Patents
Application of trigonelline in preparing medicine for preventing or treating prostatic hyperplasia Download PDFInfo
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- A61K36/18—Magnoliophyta (angiosperms)
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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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Abstract
The invention discloses an application of trigonelline in preparing a medicament for preventing or treating prostatic hyperplasia. The invention establishes a benign prostatic hyperplasia model of a rat by a testosterone propionate induction method, and verifies that trigonelline can obviously reduce the wet weight of the prostate and reduce the prostate index by adopting methods of histology and molecular biology; a clear reduction in prostate hyperplasia was morphologically observed; a significant reduction in PSA levels in serum; the improvement effect of the trigonelline on rat BPH is proved, and the trigonelline can be used for preparing the medicine for preventing or treating prostatic hyperplasia.
Description
Technical Field
The invention relates to the technical field of medicine application, in particular to application of trigonelline in preparation of a medicine for preventing or treating prostatic hyperplasia.
Background
Prostate hyperplasia generally refers to benign prostate hyperplasia. Benign Prostatic Hyperplasia (BPH) is a common progressive disease in middle-aged and elderly men. The incidence of BPH has increased dramatically due to the growing prominence of the aging problem of the population. It has been found that BPH incidence is about 50% in men over 50 years old, the incidence rate is up to 90% in men over 80 years old, bladder outlet obstruction is further caused by excessive enlargement of prostate tissue, and patients over 50% 60 years old show different degrees of clinical symptoms, such as urinary frequency, urinary urgency, urinary anergy, urinary retention or occasional urge incontinence due to bladder detrusor hypersensitivity, which seriously affects the quality of life of the patients. Currently, drug therapy is still the first line treatment for BPH and is the first line treatment for patients with mild or moderate BPH.
The fenugreek is dry mature seeds of Trigonella Foenum-graecum L (TF) which is a leguminous plant, has bitter taste, warm nature and no toxicity, belongs to one of the common traditional Chinese medicinal materials, is recorded as a medicine for nourishing and strengthening essence in the pharmacology of national medicine, has the functions of warming kidney and tonifying yang, dispelling cold and relieving pain and assisting bladder gasification, and is clinically compatible for treating prostatic hyperplasia. Trigonelline (Trigonelline) is one of the main effective components of semen Trigonellae, and has effects of lowering blood sugar, reducing cholesterol, resisting cancer, resisting oxidation, tranquilizing, etc. as found in modern pharmacological research. Whether the trigonelline has an improvement effect on the BPH is not reported. Therefore, the research on the effect of trigonelline on BPH has practical significance for solving the problem of prostatic hyperplasia of the middle-aged and the elderly.
Disclosure of Invention
The invention aims to provide application of trigonelline in preparation of a medicament for preventing or treating prostatic hyperplasia, so as to solve the problems in the prior art, a rat benign prostatic hyperplasia model is established by a testosterone propionate induction method, and histology and molecular biology methods are adopted to verify that the trigonelline has an obvious improvement effect on rat BPH, and can be used for preparing the medicament for preventing or treating prostatic hyperplasia.
In order to achieve the purpose, the invention provides the following scheme:
the invention provides an application of trigonelline in preparing a medicament for preventing or treating prostatic hyperplasia.
Preferably, the main active ingredient of the medicament is trigonelline or a pharmaceutically acceptable salt thereof.
Preferably, the prostate hyperplasia is benign prostate hyperplasia.
The invention discloses the following technical effects:
according to the invention, a benign prostatic hyperplasia model of a rat is established by a testosterone propionate induction method, and a histology and molecular biology method is adopted, so that the trigonelline can obviously reduce the wet weight of the prostate and reduce the prostate index; a clear reduction in prostatic hyperplasia was morphologically observed; PSA levels in serum were significantly reduced. Fully verifies that the trigonelline has obvious improvement effect on rat BPH, and can be used for preparing the medicine for preventing or treating prostatic hyperplasia.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings without creative efforts.
FIG. 1 is a graph of the effect of trigonelline on prostate wet weight, prostate index in BPH rats; a: effect on prostate wet weight in BPH rats, B: effect on prostate index in BPH rats; comparison with sham group: ## P<0.01; comparison with BPH group: p<0.05，**P<0.01；
FIG. 2 is the effect of trigonelline on the morphology of prostate tissue in BPH rats (. times.100); a: a sham operation group; b: a model group; c: finasteride group; d: 25 mg/kg -1 Trigonelline group; e: 50 mg/kg -1 Trigonelline group; f: 100 mg/kg -1 Trigonelline group;
FIG. 3 is a graph showing the effect of trigonelline on PSA in the serum of BPH rats.
Detailed Description
Reference will now be made in detail to various exemplary embodiments of the invention, the detailed description should not be construed as limiting the invention but rather as a more detailed description of certain aspects, features and embodiments of the invention.
It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Further, for numerical ranges in this disclosure, it is understood that each intervening value, between the upper and lower limit of that range, is also specifically disclosed. Every smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in a stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included or excluded in the range.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although only preferred methods and materials are described herein, any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention. All documents mentioned in this specification are incorporated by reference herein for the purpose of disclosing and describing the methods and/or materials associated with the documents. In case of conflict with any incorporated document, the present specification will control.
It will be apparent to those skilled in the art that various modifications and variations can be made in the specific embodiments of the present disclosure without departing from the scope or spirit of the disclosure. Other embodiments will be apparent to those skilled in the art from consideration of the specification. The specification and examples are exemplary only.
As used herein, the terms "comprising," "including," "having," "containing," and the like are open-ended terms that mean including but not limited to.
Reagents or materials used in the following examples are commercially available, unless otherwise specified.
Example 1 model construction and pathological examination of benign prostatic hyperplasia in rat
1. Materials and methods
1.1 animal selection
Clean, healthy, male SD rats 60, body weights (250 ± 20) g (ningxia university of medicine experimental animals center, certification No. SYXK (ning) 2009-0001). The animals were kept in the barrier animal facility SYXK 2016001 and were given humane care according to the 3R principle used by the animals.
1.2 drugs and reagents
Trigonelline hydrochloride (Beijing Solebao science and technology Co., Ltd., purity: 98%, batch No. 20201025); testosterone propionate injection (Tianjin Jinyao pharmaceutical Co., Ltd., batch No. 1706061); finasteride tablets (Hangzhou Moshadong pharmaceutical Co., Ltd., batch No. R008311), Prostate Specific Antigen (PSA) (Shanghai Jianglai Biotech Co., Ltd., batch No. JL10345)
1.3 instruments
-20 ℃ low temperature refrigerator (Synfei Shida refrigerator Co., Ltd.); low temperature high speed centrifuge (hemmer, germany); automatic microplate readers (Shanghai Thermo Labsystems Co.); OLYMPUS CHC-212 model optical microscope (Olympus, Japan).
1.4 Experimental methods
1.4.1 grouping
60 male cleaning grade SD rats, randomly divided into 6 groups: sham operation group, model group, and positive drug group (finasteride 10mg kg) -1 ) Low content of trigonelline (25 mg/kg) -1 ) Middle (50mg kg) -1 ) High (100mg kg) -1 ) Dose groups of 10 individuals each. In the feeding process, the room temperature is controlled to be 20-26 ℃, the humidity is controlled to be 40-70%, the illumination is 12h/d, food and water are freely taken and drunk, and the experiment is started after the environment is adapted for one week.
1.4.2 Molding and administration methods
The 2% sodium pentobarbital (40mg kg) is injected into abdominal cavity of model-making rat -1 ) Performing general anesthesia, cutting skin and fascia layer by layer under aseptic condition, opening abdominal cavity to expose testis at both sides, ligating vas deferens, removing testis at both sides, and suturing layer by layer. Sham operated groups opened the abdominal cavity only and did not remove the testes. On day 8, the rats were injected with testosterone propionate 5 mg/kg subcutaneously -1 A rat prostatic hyperplasia model was established, and the sham-operated group was given a subcutaneous injection of olive oil of the same volume for 28 days. Simultaneously administering the positive drug group and the low, medium and high dose groups of trigonelline according to finasteride 10mg kg -1 Trigonelline 25 mg/kg -1 、50mg·kg -1 、100mg·kg -1 The dose is intragastrically administered, and the sham operation group and the model group are administered with equal volume of physiological saline for intragastrically administering for 1 time/d and continuously administering for 28 d.
1.4.3 specimen Collection and processing
After 24h of last administration, the weight of each group of rats is weighed and recorded, and 6 mL/kg of 20% urethane is used -1 Abdominal injection of anesthetized rats and abdominal dissectionCollecting blood via abdominal aorta, standing at room temperature for 1 hr, centrifuging at low temperature (4 deg.C, 3500 r.min) -1 And 10min) separating the serum and storing at-20 ℃. Bilateral prostate tissues were enucleated, surrounding fascia and adipose tissues were carefully removed, rinsed in pre-cooled physiological saline, and the prostate weight was weighed on an electronic balance after drying with filter paper, and the Prostate Index (PI) (wet mass (g)/bulk mass (g) × 100) was calculated. Fixing the dorsolateral prostate leaves in 4% paraformaldehyde solution, and performing histomorphology detection.
1.4.4 pathological assays
Fixing rat prostate dorsal lateral lobe in 4% formaldehyde solution for 48h, washing with flowing water for 3h, gradient dehydrating with ethanol, clearing xylene, embedding with conventional paraffin, cooling at room temperature overnight, trimming, slicing to obtain 4 μm pathological section, staining with hematoxylin-eosin staining method, sealing with neutral resin, and observing morphological change of prostate tissue under optical microscope.
1.4.5PSA assay
Rat serum frozen at-20 ℃ in a refrigerator is taken and strictly determined according to the operation instructions of the PSA ELISA detection kit.
1.5 statistical methods
The experimental results are expressed as mean. + -. standard deviation
And (4) showing. Statistical analysis was performed using the SPSS Statistics 20 software. The average numbers among the groups are compared by adopting One-way ANOVA (One-way ANOVA), and the difference is that P is less than or equal to 0.05, so that the difference has statistical significance.
2. Results
2.1 Effect of Trigonelline on prostate Wet weight, prostate index in BPH rats
As shown in FIG. 1A, B, the prostate wet weight and prostate index of the model group rats were significantly increased (P < 0.01) compared to the sham-operated group; compared with the model group, the low, medium and high dosage groups of trigonelline and finasteride can obviously reduce the wet weight of prostate and reduce the prostate index (P is less than 0.05 and P is less than 0.01); the differences are statistically significant.
2.2 Effect of Trigonelline on prostate tissue morphology in BPH rats
In the sham operation group (fig. 2A), the prostate gland bodies are arranged tightly under the mirror, the glandular epithelium and the interstitial fibrous tissue are not proliferated, and the gland cavities are not expanded; compared with the sham operation group, the model group (figure 2B) has disordered glandular arrangement, irregular glandular cavity, glandular cavity expansion, plica formation of mucosa epithelium, protrusion to the lumen, interstitial neutrophilic infiltration, and hyperplasia of blood vessels and interstitial fiber connective tissue; compared with the model group, the finasteride group (figure 2C) and the low, medium and high dose groups of trigonelline (figures 2D-F) have the advantages of reduced number of glands, regular shape, single-layer arrangement of glandular epithelial cells, less outburst into the lumen, reduced plica, reduced proliferation of interstitial fiber tissue and no obvious inflammatory cell infiltration.
2.3 Effect of Trigonelline on PSA in serum of BPH rats
As shown in FIG. 3, the PSA level in the serum of the rats in the model group was significantly increased (P < 0.01) compared to the sham-operated group; compared with the model group, the PSA level in the serum of rats in the finasteride group and the trigonelline low, medium and high dose groups is obviously reduced (P is less than 0.01).
The above-described embodiments are merely illustrative of the preferred embodiments of the present invention, and do not limit the scope of the present invention, and various modifications and improvements of the technical solutions of the present invention can be made by those skilled in the art without departing from the spirit of the present invention, and the technical solutions of the present invention are within the scope of the present invention defined by the claims.
Claims (1)
1. The application of the trigonelline as the only active component in the preparation of the medicine for preventing or treating the prostatic hyperplasia is characterized in that the main active component of the medicine is the trigonelline or the medically acceptable salt thereof;
the prostate hyperplasia is benign prostate hyperplasia.
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| CN1843399A (en) * | 2006-02-14 | 2006-10-11 | 郭凯 | Medicine for treating benign prostate hyperplasia and its preparation process |
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| CN102697781A (en) * | 2011-06-21 | 2012-10-03 | 中国人民解放军第三军医大学第二附属医院 | Application of trigonelline in preparation of medicament for preventing and treating diabetes and complication thereof |
| CN102824341A (en) * | 2011-06-16 | 2012-12-19 | 苏州凯祥生物科技有限公司 | Application of gallocatechin in preparation of drugs for resisting benign prostatic hyperplasia |
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| CN101496828B (en) * | 2009-02-27 | 2011-07-27 | 湖南今汉生物医药技术有限公司 | Use of total saponin extract of fenugreek |
| CN104257734A (en) * | 2014-09-22 | 2015-01-07 | 殷永洲 | Prescription for treating prostatic hyperplasia |
| KR101552813B1 (en) * | 2015-05-18 | 2015-09-11 | 충남대학교산학협력단 | Compositions for preventing or treating benign prostatic hyperplasia comprising extracts of Quisqualis indica |
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Patent Citations (4)
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|---|---|---|---|---|
| CN1843399A (en) * | 2006-02-14 | 2006-10-11 | 郭凯 | Medicine for treating benign prostate hyperplasia and its preparation process |
| CN101385662A (en) * | 2008-10-15 | 2009-03-18 | 南开大学 | Method for establishing rat laboratory animal model with prostate interstitial proliferation |
| CN102824341A (en) * | 2011-06-16 | 2012-12-19 | 苏州凯祥生物科技有限公司 | Application of gallocatechin in preparation of drugs for resisting benign prostatic hyperplasia |
| CN102697781A (en) * | 2011-06-21 | 2012-10-03 | 中国人民解放军第三军医大学第二附属医院 | Application of trigonelline in preparation of medicament for preventing and treating diabetes and complication thereof |
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