CN107982269A - Application of the crocetin in the medicine or health products for preparing prevention Stein-Leventhal syndrome - Google Patents

Application of the crocetin in the medicine or health products for preparing prevention Stein-Leventhal syndrome Download PDF

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Publication number
CN107982269A
CN107982269A CN201711146515.2A CN201711146515A CN107982269A CN 107982269 A CN107982269 A CN 107982269A CN 201711146515 A CN201711146515 A CN 201711146515A CN 107982269 A CN107982269 A CN 107982269A
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crocetin
stein
leventhal syndrome
mouse
follicle
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CN107982269B (en
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盛亮
金晶
胡巧云
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Nanjing University
Nanjing Medical University
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Nanjing Medical 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
    • A61K31/557Eicosanoids, e.g. leukotrienes or prostaglandins

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
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  • Pharmacology & Pharmacy (AREA)
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  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
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Abstract

The invention discloses application of the crocetin in the medicine or health products for preparing prevention Stein-Leventhal syndrome.The present invention, using the Stein-Leventhal syndrome mouse model of foetal period protona induction, furthers investigate its therapeutic effect on the basis of the existing effect of crocetin.The result shows that crocetin can significantly improve the oestrous cycle rhythm disorder of Model of Polycystic Ovarian Syndrome mouse, reduce ovary weight and locking ovary quantity, increase corpus luteum, big antral follicle count and preovulatory follicle quantity, estradiol, lutropin, follicle-stimulating hormone, progesterone, the testosterone levels of Model of Polycystic Ovarian Syndrome mouse are significantly improved, there is good treatment Stein-Leventhal syndrome.And in experimentation, do not occur obvious adverse reaction, it is safe.

Description

Crocetin is in the medicine or health products for preparing prevention Stein-Leventhal syndrome Using
Technical field
The present invention relates to a kind of new application of traditional Chinese medicine monomer crocetin treatment Stein-Leventhal syndrome, belong to medical science Field.
Background technology
Stein-Leventhal syndrome is common Procreation model, have impact on the Female in child bearing period of 4-8%.It main It is characterized in:It is dilute to send a manuscript to the compositor ovum or No-clay weak interbed, excessive androgen clinical manifestation (crinosity, acne etc.) and/or hyperandrogenism, ovary More capsule samples change.Adolescent-anovulation bleeding or oligomenorrhea, breeding time ovulation failure are the major reasons of infertility, at a specified future date Diabetes, nonalcoholic fatty liver, hyperlipidemia, hypertension, gestational diabetes, the hypertension of pregnancy and endometrium can also be increased The risk of cancer.It is phenotype more than one, refractory disease more, with double risks recent and at a specified future date.
At present mainly with hormone control drug therapy Stein-Leventhal syndrome.Diane 35 is suitable for having excessive androgen clinic table Existing or hyperandrogenism patient, is the current drop most common medicine of androgen.And adjusting the menstrual cycle can also take the cycle Property progestational hormone is withdrawn and other Short-term effective oral contraceptives.It is non-in recent years to swash due to the taboos disease of hormone therapy and side effect Extract for treating also enters research sight.For example the vitamin D level of clinically patients with polycystic ovary syndrome is usually relatively low, supplement Vitamin D is considered as a kind of method for improving Stein-Leventhal syndrome.
The traditional Chinese medical science thinks that Stein-Leventhal syndrome belongs to models such as " infertile " " hypomenorrhia " " delayed menstrual cycle " " amenorrhoea ” " Disorder lumps in the abdomen " Enclose.This disease is mainly using zang-fu disharmony as this, and phlegm is turbid, hemostasis is mark.Morbidity is how closely related with kidney,liver,spleen, but with kidney deficiency, spleen Based on void, the pathological product such as phlegm wet, hemostasis acts on body in addition, causes "-uterus is appointed in kidney-day decyl- punching " reproduction s function disorderly Disorderly cause a disease.The disease side of Chinese traditional treatment at present card unification plus-minus.
Safflower is a kind of flowering perennial of Iridaceae crocus, and a kind of common spices.There is calmness, dispel Phlegm, spasmolysis, the treatment for stomach trouble, menstruation regulating, measles, fever, jaundice, hepatosplenomegaly etc..Crocetin is safflower One of main component, can also extract from cape jasmine.It has been reported that, crocetin can be used to treat breast cancer, lung cancer, pancreas at present The tumours such as cancer, can also treat Alzheimer disease, treatment insulin resistance and angiocardiopathy.But there has been no crocetin at present Treat the relevant report of Stein-Leventhal syndrome purposes.
The content of the invention
Goal of the invention:The present invention is screened on the basis of crocetin exercise use by many experiments, and it is new to develop it Clinical application, there is provided new application of the crocetin in Stein-Leventhal syndrome is prevented.
Technical solution:The present invention provides crocetin in the medicine or health products for preparing prevention Stein-Leventhal syndrome Using.The structural formula of crocetin is:
Molecular formula is C20H24O4
The present invention applies protona to pregnant mouse, and elicitor is for female mice Stein-Leventhal syndrome.Treat that filial generation is ripe and is formed After Stein-Leventhal syndrome, treated with crocetin.Observation locking ovary, corpus luteum, antral follicle count and ripe sinus shape are dyed with H&E Ovarian follicle quantity, additional ovary weight, oestrous cycle, and estradiol, lutropin, follicle-stimulating hormone, progesterone and testosterone Level, as Stein-Leventhal syndrome evaluation index.
Test result indicates that crocetin can significantly improve the oestrous cycle rhythm and pace of moving things of Model of Polycystic Ovarian Syndrome mouse Disorder, reduces ovary weight and locking ovary quantity, increase corpus luteum, antral follicle count and ripe antral follicle count quantity, significantly improve Estradiol, lutropin, follicle-stimulating hormone, progesterone and the testosterone levels of Model of Polycystic Ovarian Syndrome mouse, show Well the effect of prevention Stein-Leventhal syndrome.
Brief description of the drawings
Fig. 1 is mouse weight and the block diagram of ovary weight change after protona modeling and crocetin treatment.
Fig. 2 is the curve map that crocetin influences Stein-Leventhal syndrome Mouse Oestrous Cycle.
Fig. 3 is the block diagram that crocetin influences Stein-Leventhal syndrome Mouse Oestrous Cycle.
Fig. 4 is crocetin to Stein-Leventhal syndrome mouse atretic follicle, corpus luteum, great Dou Like ovarian follicles and preovulatory follicle The block diagram that quantity influences.
After Fig. 5 is protona modeling and crocetin treatment, lutropin, rush Folliculogenesis in mice serum Element, estradiol, the block diagram of testosterone and progesterone level.
Embodiment
According to following embodiments, the present invention may be better understood.It is however, as it will be easily appreciated by one skilled in the art that real Apply example described specific material proportion, process conditions and its result and be merely to illustrate the present invention, without that will not should limit The present invention described in detail in claims processed.
The mouse Stein-Leventhal syndrome therapeutic effect research that 1 crocetin of embodiment induces protona.
1. experiment material
1.1 experimental drug things and reagent
Crocetin is purchased from Shanxi Sen Fu natural products Co., Ltd.
1.2 experimental animals and raising
Adult male and female mouse (C57Bl/6J × A/J) F1 (B6A) is used for this research, by this offer of Cavan, quality certification number: 201602427.All mouse are all raised in SPF grades of animal houses, and light and shade replaces when 12- is small, 22-24 DEG C, humidity 55%-65%. Free water is ingested.
2. method
The Stein-Leventhal syndrome mouse model modeling method of 2.1 protonas induction
Male and female mouse mates, and during pregnant 16-18 days, protona (250 μ g), control group mice are subcutaneously injected daily Injection solvent.
The Stein-Leventhal syndrome mouse therapeutic effect of 2.2 crocetin protonas induction.
Filial generation female mice grows into 8 weeks, treatment group:With 50mg/kg/d dosage gavage crocetins, successive administration 5 weeks.In dynamic Feelings early period or anoestrum put to death mouse.Model group and control group give physiological saline.
2.3 mouse POCS indexs
[1] mouse ovarian and weight:Measurement weight, wins ovary after execution, weighs before mouse is put to death.
[2] Mouse Oestrous Cycle measures:After female mice sexal maturity, hyperplasia occurs for reproductive organs, the periodicity degenerated becomes Turn to the oestrous cycle (4~5d).It is generally divided into the fourth phase:Preoestrus (0.5~1.5d), estrus (1~3d), metaoestrus (1 ~3d) and anoestrum (2~4d).Mouse vagina cast-off cells feature within the different oestrous cycles is different, passes through vagina Cell smear is observed, and judges the oestrous cycle residing for mouse:
Preoestrus is entirely to have core epithelial cell, occasionally there is seedless superficial cell
Estrus is entirely seedless superficial cell, and have has core epithelial cell on a small quantity
There is leucocyte in metaoestrus, superficial cell is reduced, and three kinds of cells have
The a large amount of leucocytes of anoestrum, have core epithelial cell, mucous membrane on a small quantity
[3] mouse ovarian structure is investigated:Side ovary soaks fixed 24h, paraffin embedding, H&E dyes through formalin solution Color, then carries out pathologic structure analysis.
[4] serum hormone detects:Estradiol, lutropin, rush in serum reagent box detection preoestrus mice serum Folliculogenesis element, progesterone, testosterone levels.
2.4 statistical analysis
Data useRepresent, tested using one-way analysis of variance (ANOVA), p<0.05 has system for difference Meter learns meaning.
3. experimental result
3.1 crocetins reduce the weightening of Stein-Leventhal syndrome mouse ovarian.
By Fig. 1, test result indicates that, control group, model group and administration group mouse weight do not have a significant difference, but mould Type group ovary weight dramatically increases (* p<0.05), and the results show crocetin can substantially reverse the abnormal weightening (#p of ovary< 0.05)。
3.2 crocetins improve Stein-Leventhal syndrome Mouse Oestrous Cycle.
By Fig. 2 and Fig. 3's test result indicates that, model group Mouse Oestrous Cycle is overall significantly to be extended, after showing as emotionally Phase, growth (the * p of anoestrum<0.05).After crocetin is treated, metaoestrus, anoestrum and total oestrous cycle All significantly shorten (#p<0.05).
3.3 crocetins improve the pathologic structure of Stein-Leventhal syndrome mouse ovarian
By Fig. 4's, test result indicates that, the modeling of protona causes dramatically increasing for mouse atretic follicle quantity, and subtracts Few corpus luteum, great Dou ovarian follicles and preovulatory follicle quantity (* p<0.05).After crocetin is treated, atretic follicle quantity is notable Decline, corpus luteum, great Dou ovarian follicles and preovulatory follicle quantity are significantly gone up (#p<0.05).
3.4 crocetins improve Stein-Leventhal syndrome mouse hormonal readiness
By Fig. 5's, test result indicates that, lutropin and testosterone significantly raise in model group mice serum, estradiol, Follicle-stimulating hormone, progesterone are remarkably decreased (* p<0.05).The treatment of crocetin then reverses lutropin and testosterone levels Abnormal rise, and lift relatively low estradiol, follicle-stimulating hormone and progesterone level (#p<0.05).
The pregnant mouse that the present invention is pregnant 16-18 days using protona processing, causes Female offspring Stein-Leventhal syndrome.Mould Type mouse ovarian increases weight, and the oestrous cycle is disorderly, and lutropin and testosterone rise, estradiol, follicle-stimulating hormone, progesterone are notable Decline;Atretic follicle quantity dramatically increases, and corpus luteum, big antral follicle count and preovulatory follicle quantity are reduced.The model can be fine The classical symptom of simulation Stein-Leventhal syndrome, has good reappearance, validity and ease for use.Above pharmacodynamics test Increase weight extremely the results show that crocetin significantly reduces ovary, improve the disorder of oestrous cycle and hormone serum level, finally subtract Few atretic follicle quantity, up-regulation corpus luteum, great Dou ovarian follicles and preovulatory follicle quantity, show treatment polycystic ovary synthesis well The effect of sign.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art For member, various improvements and modifications may be made without departing from the principle of the present invention, these improvements and modifications also should It is considered as protection scope of the present invention.

Claims (2)

1. application of the crocetin in the medicine or health products for preparing prevention Stein-Leventhal syndrome.
2. crocetin according to claim 1 answering in the medicine or health products for preparing prevention Stein-Leventhal syndrome With, it is characterised in that by crocetin and pharmaceutically or food acceptable carrier prepares piece agent, granule, pill, capsule Agent, dripping pill, oral liquid or injection.
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN113304157A (en) * 2021-06-15 2021-08-27 黑龙江中医药大学 Active composition for treating polycystic ovarian syndrome (PCOS)
WO2022232482A1 (en) * 2021-04-30 2022-11-03 Majeed, Muhammed Compositions for management of polycystic ovary syndrome

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
HAFSA MAJID, ET AL.: "Homeostatic Model Assessment for Insulin Resistance (HOMA-IR): A Better Marker for Evaluating Insulin Resistance Than Fasting Insulin in Women with Polycystic Ovarian Syndrome", 《JOURNAL OF THE COLLEGE OF PHYSICIANS AND SURGEONS PAKISTAN》 *
QU J, WANG Y, WU X, ET AL.: "Insulin resistance directly contributes to androgenic potential within ovarian theca cells", 《FERTILITY AND STERILITY》 *
XI L ET AL.: "Crocetin Prevents Dexamethasone-Induced Insulin Resistance in Rats", 《PLANTA MED》 *
刘东博等: "西红花酸主要药理作用及其机制研究进展", 《中草药》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022232482A1 (en) * 2021-04-30 2022-11-03 Majeed, Muhammed Compositions for management of polycystic ovary syndrome
CN113304157A (en) * 2021-06-15 2021-08-27 黑龙江中医药大学 Active composition for treating polycystic ovarian syndrome (PCOS)

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