CN104856995A - Application of lotus plumule active alkaloid in preparation of prostate drugs - Google Patents
Application of lotus plumule active alkaloid in preparation of prostate drugs Download PDFInfo
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- CN104856995A CN104856995A CN201510201825.4A CN201510201825A CN104856995A CN 104856995 A CN104856995 A CN 104856995A CN 201510201825 A CN201510201825 A CN 201510201825A CN 104856995 A CN104856995 A CN 104856995A
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- prostate
- medicine
- isoliensinine
- neferine
- liensinine
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Abstract
The invention discloses application of lotus plumule active alkaloid in preparation of prostate drugs, and the prostate tissue relaxation functions of three active alkaloids (liensinine, isoliensinine and neferine) which are extracted from lotus plumule are found. By use of in-vitro prostate tension tension force tracing technology, in vitro rabbit prostate relaxation function and in vitro rabbit prostate shrinkage antagonistic action caused by noradrenaline (NE) and phenylephrine (PE) of the three active alkaloids are investigated, research results show that the liensinine, isoliensinine and neferine can effectively relax in vitro prostate and play antagonism action against in vitro rabbit prostate shrinkage caused by noradrenaline (NE) and phenylephrine (PE), and the three active alkaloids are potential benign prostatic hyperplasia treatment drugs.
Description
Technical field
The invention belongs to compound pharmacological action field, relate to the pharmacological action of Plumula Nelumbinis active alkaloid, be specifically related to Plumula Nelumbinis active alkaloid and preparing the application in medicine for prostate disease.
Background technology
Benign prostatic hyperplasia (benign prostatic hyperplasia, BPH) prostatic hyperplasia is called for short, it is a kind of common male urinary system disease, its feature is the hypertrophy of prostate gland, smooth muscle and cellular tissue parenchyma, commonly encountered diseases and the frequently-occurring disease of middle-aging male, along with the increase of the aged, its sickness rate is in the trend risen year by year, and therefore the treatment of BPH more and more receives the concern of people.The main purpose of Drug therapy is specific lax prostate smooth musculature cells and the prostate volume reducing hypertrophy.α is rich in prostata tissue
1-AR, and with α
1A-AR is main, so α
1A-AR blocker is widely used in treating BPH.So exploitation has α
1Anew drug or the lead compound of the treatment BPH of-AR high selectivity have great importance.
Summary of the invention
The object of the present invention is to provide Plumula Nelumbinis active alkaloid preparing the application in medicine for prostate disease, find that Plumula Nelumbinis active alkaloid can be used in preparing medicine for prostate disease.
For achieving the above object, the technical solution used in the present invention is:
Plumula Nelumbinis active alkaloid is preparing the application in medicine for prostate disease.
Described Plumula Nelumbinis active alkaloid is liensinine, isoliensinine or (-)-Neferine.
Described medicine for prostate disease is the medicine being used for the treatment of benign prostatic hyperplasia.
Described medicine for prostate disease is the medicine with the effect of diastole prostate.
Described medicine for prostate disease is shrink the medicine with antagonism for the prostate caused by norepinephrine and phenylephrine.
Described medicine for prostate disease is for acting on α
1Athe medicine of-AR.
Relative to prior art, beneficial effect of the present invention is:
The invention discloses Plumula Nelumbinis active alkaloid and preparing the application in medicine for prostate disease, find that Plumula Nelumbinis active alkaloid can be used in preparing medicine for prostate disease.
Further, in the present invention, said Plumula Nelumbinis active alkaloid refers to from extract liensinine, isoliensinine, the (-)-Neferine Plumula Nelumbinis, finds that these three kinds of Plumula Nelumbinis active alkaloids are to α
1A-AR has good affinity, and has the action characteristic of similar Tamsulosin.The present invention uses in vitro tissue level to test, with isolated rabbit prostate model, the prostatic effect of this three kinds of Plumula Nelumbinis active alkaloids diastole is verified, find that these three kinds of Plumula Nelumbinis active alkaloids can the effectively contraction of Resected prostate that caused by norepinephrine (NE) and phenylephrine (PE) of diastole Resected prostate and antagonism, wherein acting on size is: (-)-Neferine > liensinine > isoliensinine.Illustrate these three kinds of Plumula Nelumbinis active alkaloids be can be used in preparing there is the effect of diastole prostate medicine, for the prostate that caused by norepinephrine and phenylephrine shrink there is antagonism medicine, act on α
1Athe medicine of-AR and be used for the treatment of the medicine of benign prostatic hyperplasia.
Accompanying drawing explanation
Fig. 1 is liensinine, (-)-Neferine and the isoliensinine diastole amount effect curve figure on isolated rabbit prostate, and wherein A is the diastole amount effect curve of liensinine, and B is the diastole amount effect curve of (-)-Neferine, and C is the diastole amount effect curve of isoliensinine.
Fig. 2 is the amount effect curve figure of liensinine to the antagonism that the isolated rabbit prostate that NE causes shrinks, and wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist liensinine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 3 is the amount effect curve figure of (-)-Neferine to the antagonism that the isolated rabbit prostate that NE causes shrinks, wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist (-)-Neferine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 4 is the amount effect curve figure of isoliensinine to the antagonism that the isolated rabbit prostate that NE causes shrinks, and wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isoliensinine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 5 is the amount effect curve figure of liensinine to the antagonism that the isolated rabbit prostate that PE causes shrinks, and wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist liensinine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 6 is the amount effect curve figure of (-)-Neferine to the antagonism that the isolated rabbit prostate that PE causes shrinks, wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist (-)-Neferine exists, and B is Ariens noncompetitive antagonism figure.
Fig. 7 is the amount effect curve figure of isoliensinine to the antagonism that the isolated rabbit prostate that PE causes shrinks, and wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isoliensinine exists, and B is Ariens noncompetitive antagonism figure.
Detailed description of the invention
Below in conjunction with accompanying drawing, the present invention is described in further details.
Liensinine, isoliensinine and (-)-Neferine are the active alkaloids extracted from Plumula Nelumbinis.Applicant utilizes α
1A-AR high expressing cell membrane chromatography (CMC) model, Late Cambrian this three kinds of Plumula Nelumbinis active alkaloids and α
1A-AR has good affinity, and has the action characteristic of similar Tamsulosin.Therefore, according to itself and α
1Athe affinity interaction of-AR, applicant uses that tissue water is plain to be tested, adopt Resected prostate tension force to trace technology, investigated their diastole effect and the antagonism to the isolated rabbit prostate contraction that NE and PE causes with isolated rabbit prostate model, and calculated its pEC
50value (medium effective concentration), E
maxand pD
2'.Result of study proves that liensinine, isoliensinine and (-)-Neferine can the effectively contractions of Resected prostate that caused by NE and PE of diastole Resected prostate and antagonism, illustrates that these three kinds of Plumula Nelumbinis active alkaloids are potential medicines preparing benign prostatic hyperplasia.
Below concrete experimentation is described.
1. experiment material
Instrument: DMT tension measuring system (Danish Myograph Technology AIS Inc.610M).
Animal: male and healthy new zealand white rabbit (body weight 2.5-3.5kg, Xi'an Jiaotong University Medical College's Experimental Animal Center)
Main agents: Kerb ' s buffer solution Krebs liquid (composition (g/L): 6.954NaCl, 0.343KCl, 1.260NaHCO
3, 0.187NaH
2pO
42H
2o, 0.166CaCl
2, 0.244MgCl
26H
2o, 1.090 glucose, PH=7.2 ~ 7.4), dimethyl sulfoxide (DMSO, Jinhuada Chemical Agent Co., Ltd., Guangzhou City), noradrenaline bitartrate (Norepinephrine Bitartrate Monohydrate, NE, Dalian Mei Lun Bioisystech Co., Ltd); Phenylephrine hydrochloride ((R)-(-)-Phenylephrine hydrochloride, PE, Shanghai Aladdin Reagent Company); Tamsulosin hydrochloride (HPLC purity >98%, Wuhan Chi Fei Chemical Co., Ltd.); Silodosin (HPLC purity >98%, Wuhan Chi Fei Chemical Co., Ltd.).
2. experimental technique
(1) diastole effect experiment
Get male and healthy new zealand white rabbit, after chloral hydrate anesthesia, hypogastric region otch, carefully cut page about prostate along urethra, put into the surface plate of Kerb ' the s buffer solution filling pre-cooling, remove blood stains, the fat that careful rejecting is unnecessary and connective tissue, prostata tissue is trimmed to the flesh bar of about 1cm × 2mm × 2mm, is connected with DMT antiotasis measuring system with fine rule, connect the change of computer record prostate tension force.Add containing 95%O in DMT bath
2, 5%CO
2kerb ' s buffer solution, and maintain the temperature at 37 DEG C.After zeroing no longer includes larger change to prostate tension force, give musculus prostaticus bar 4mN pretension, in 20min, regulate pretension to stable.After stable, allow musculus prostaticus bar at 37 DEG C, 95%O
2, 5%CO
260 ~ 90min (whole experimental session changes a Kerb ' s liquid every 20min) is balanced in saturated Kerb ' s liquid.
In order to detect musculus prostaticus bar in the reactivity of in vitro to medicine, before the formal experiment of beginning, with the K of 60mmol/L
+-Kerb ' s liquid preshrinking, after its contraction reaches stabilised platform, rinses 3 times with Kerb ' s liquid, returns to after baseline values until tension force, then use the K of 60mmol/L
+-Kerb ' s liquid preshrinking, repeats said process once.If flesh bar energy stabilized contraction and twice shrink platform unanimously, prove that its function is normal, can test, abnormal flesh bar is given it up.Formal experiment is started after musculus prostaticus bar tension stability balance 20min.
After ready to balance terminates, Kerb ' s buffer in bath is settled to 10mL, after baseline stability, NE injection 30uM is added respectively successively in bath, after stable contractile response to be obtained, in bath, add the Concentraton gradient solution of Tamsulosin, silodosin, liensinine perchlorate, (-)-Neferine and isoliensinine more respectively successively, each concentration adds 10uL, makes the drug level in bath be followed successively by 1 × 10
-9, 3 × 10
-9, 1 × 10
-8, 3 × 10
-8, 1 × 10
-7, 3 × 10
-7, 1 × 10
-6, 3 × 10
-6, 1 × 10
-5, 3 × 10
-5, 1 × 10
-4mol/L, the tension variation of computer record musculus prostaticus bar.Matched group adds the DMSO of respective concentration gradient.With prostatic diastolic rate (%) to drug level logarithm (logC) mapping, obtain the diastole effect curve of various medicine, and calculate pEC
50and E
max.
(2) to the antagonism experiment of shrinking
Preparation method and the reactive detection of musculus prostaticus bar are the same.After ready to balance terminates, use 60mmol/LK
+-Kerb ' s buffer preshrinking, after baseline stability, rinses 3 ~ 4 times with Kerb ' s buffer solution, after tension force returns to baseline values, adopts in cumulative concentrations image of Buddha bath and adds NE or PE solution (1 × 10
-8~ 1 × 10
-4mol/L), the concentration-shrinkage curve of two kinds of agonist is obtained.After obtaining maximum collapse effect, rinse 3 ~ 4 times with Kerb ' s buffer solution, after tension force restores balance, medicine to be measured is added bath and hatches 30min, solvent control group does not add drug incubation, and then NE or PE solution is added in bath, obtain second time concentration-shrinkage curve, obtain the antagonism curve chart that three kinds of Plumula Nelumbinis active alkaloids shrink the Resected prostate that NE or PE causes.With prostatic shrinkage factor (%), the log concentration (logC) of NE or PE is mapped, obtain the antagonistic effect curve of various medicine, and calculate pD
2' value.
3. experimental result
Data mean ± standard error (mean ± SEM) represents, graph making application Graphpad Prism5.0 software.
(1) pEC of liensinine, (-)-Neferine and isoliensinine
50and E
max(%) as shown in table 1, diastole effect curve as shown in Figure 1.
Table 15 kinds of medicines are to the pEC of Resected prostate diastole
50value and E
max(%) value (n=6)
Fig. 1 be three kinds of Plumula Nelumbinis active alkaloids with Tamsulosin and silodosin comparing (n=6) rabbit Resected prostate diastole effect curve, wherein A is liensinine and the comparing of Tamsulosin and silodosin, B is (-)-Neferine and the comparing of Tamsulosin and silodosin, and C is isoliensinine and the comparing of Tamsulosin and silodosin.
(2) liensinine, (-)-Neferine and isoliensinine are to the antagonism of the Resected prostate contraction caused by NE as in Figure 2-4.
Fig. 2 is the non-competitive antagonism that liensinine shrinks the Resected prostate that NE causes.
Wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist liensinine exists; B is Ariens noncompetitive antagonism figure, pA
2'=5.35.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 3 is the non-competitive antagonism that (-)-Neferine shrinks the Resected prostate that NE causes.
Wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist (-)-Neferine exists; B is Ariens noncompetitive antagonism figure, pA
2'=7.63.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 4 is the non-competitive antagonism that isoliensinine shrinks the Resected prostate that NE causes.
Wherein A is that NE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isoliensinine exists; B is Ariens noncompetitive antagonism figure, pA
2'=4.38.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
(3) liensinine, (-)-Neferine and isoliensinine are to the antagonism of the Resected prostate contraction caused by PE as illustrated in figs. 5-7.
Fig. 5 is the non-competitive antagonism that liensinine shrinks the Resected prostate that PE causes.
Wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist liensinine exists; B is Ariens noncompetitive antagonism figure, pA
2'=6.46.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 6 is the non-competitive antagonism that (-)-Neferine shrinks the Resected prostate that PE causes.
Wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist (-)-Neferine exists; B is Ariens noncompetitive antagonism figure, pA
2'=7.06.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
Fig. 7 is the non-competitive antagonism that isoliensinine shrinks the Resected prostate that PE causes.
Wherein A is that PE shrinks the prostatic amount-effect curve of isolated rabbit under noncompetitive antaganist isoliensinine exists; B is Ariens noncompetitive antagonism figure, pA
2'=5.88.(vs matched group, * P<0.05, * * P<0.01, * * * P<0.001, n=6)
4. conclusion
Can be found out by above-mentioned experiment and result, liensinine, (-)-Neferine and isoliensinine can effective diastole isolated rabbit prostate, its pEC
50be respectively 5.98,5.71,5.83, the pEC between three kinds of Plumula Nelumbinis active alkaloids
50no significant difference.Three kinds of Plumula Nelumbinis active alkaloids also have good antagonism to the Resected prostate contraction of being induced by NE or PE, and type of action is non-competitive antagonism, its irreversible and receptors bind is described, its action intensity is (-)-Neferine > liensinine > isoliensinine.
Can draw from above experiment, present invention finds the new pharmacological action of liensinine, (-)-Neferine and isoliensinine, namely they have the effect of good diastole Resected prostate, have opened up a new application, and the exploitation of BPH being treated to new drug is significant.
Claims (6)
1. Plumula Nelumbinis active alkaloid is preparing the application in medicine for prostate disease.
2. apply as claimed in claim 1, it is characterized in that: described Plumula Nelumbinis active alkaloid is liensinine, isoliensinine or (-)-Neferine.
3. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is the medicine being used for the treatment of benign prostatic hyperplasia.
4. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is the medicine with the effect of diastole prostate.
5. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is shrink the medicine with antagonism for the prostate caused by norepinephrine and phenylephrine.
6. apply as claimed in claim 1 or 2, it is characterized in that: described medicine for prostate disease is for acting on α
1Athe medicine of-AR.
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|---|---|---|---|
| CN201510201825.4A CN104856995A (en) | 2015-04-24 | 2015-04-24 | Application of lotus plumule active alkaloid in preparation of prostate drugs |
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|---|---|---|---|
| CN201510201825.4A CN104856995A (en) | 2015-04-24 | 2015-04-24 | Application of lotus plumule active alkaloid in preparation of prostate drugs |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111465403A (en) * | 2017-12-06 | 2020-07-28 | 赫利世弥斯株式会社 | Herbal composition for preventing or treating prostatic hypertrophy |
| CN114042068A (en) * | 2021-12-03 | 2022-02-15 | 宜春学院 | Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof |
| CN115645406A (en) * | 2022-11-16 | 2023-01-31 | 陕西省中医医院 | Application of liensinine in preparation of medicine for treating chronic prostatitis/chronic pelvic pain syndrome |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101862374A (en) * | 2010-06-12 | 2010-10-20 | 李宏 | Lotus plumule and new application of extractive thereof |
-
2015
- 2015-04-24 CN CN201510201825.4A patent/CN104856995A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101862374A (en) * | 2010-06-12 | 2010-10-20 | 李宏 | Lotus plumule and new application of extractive thereof |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111465403A (en) * | 2017-12-06 | 2020-07-28 | 赫利世弥斯株式会社 | Herbal composition for preventing or treating prostatic hypertrophy |
| CN114042068A (en) * | 2021-12-03 | 2022-02-15 | 宜春学院 | Medicine prepared from neferine, capsaicin and 6-gingerol for inhibiting benign prostatic hyperplasia and application thereof |
| CN115645406A (en) * | 2022-11-16 | 2023-01-31 | 陕西省中医医院 | Application of liensinine in preparation of medicine for treating chronic prostatitis/chronic pelvic pain syndrome |
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| PB01 | Publication | ||
| EXSB | Decision made by sipo to initiate substantive examination | ||
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Application publication date: 20150826 |