CN104188994A - Application of swertiamarin serving as drug for treating cholestasis - Google Patents
Application of swertiamarin serving as drug for treating cholestasis Download PDFInfo
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- CN104188994A CN104188994A CN201410417573.4A CN201410417573A CN104188994A CN 104188994 A CN104188994 A CN 104188994A CN 201410417573 A CN201410417573 A CN 201410417573A CN 104188994 A CN104188994 A CN 104188994A
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Abstract
The invention discloses an application of swertiamarin serving as a drug for treating cholestasis. According to the application of the swertiamarin serving as the drug for treating the cholestasis, disclosed by the invention, by means of the swertiamarin, bile acid components of serum can be remarkably reduced, so that the liver injury and the liver necrosis caused by the cholestasis are remarkably reduced, the serum inflammation caused by the cholestasis is remarkably inhibited and a remarkable curative effect is provided to the cholestasis.
Description
Technical field
The invention belongs to cholestasis medicine technical field, specifically, relate to a kind of application as the medicine for the treatment of cholestasis with swertiamarin.
Background technology
Cholestasis occurs, the underlying cause of development is the toxicity bile acid of hepatocyte inner accumulated.Cholestasis can cause liver failure, hepatic fibrosis, liver cirrhosis even dead.Because the toxicity bile acid of excess accumulation surpasses after hepatocellular compensatory capacity, damage hepatocyte, and bring out inflammation, inflammation is further damaged again hepatocyte then, thereby enters vicious cycle.Treat at present the active drug ursodesoxycholic acid (UDCA) of the unique generally acknowledged and extensive use of cholestasis, there is bile acid excretion and the slightly effect of inflammation-inhibiting in enhance hepatocyte, its molecular mechanism is mainly to increase the expression such as liver detoxification enzyme CYP3A, UGT2B and cholic acid transport protein MRP2, BSEP, thereby strengthen the water solublity of free bile acid and from the speed of liver excretion, but approximately there is more than 1/3 cholestasis patient to UDCA insensitive or even worsen the treatment that therefore a lot of people can not improve.Therefore the medicine of, actively researching and developing for cholestasis has very important clinical meaning.
In prior art, swertiamarin has pharmacological action:
(1) spasmolysis: the bitter glycosides of jade tablet tooth dish is to the sphincteral independent rhythm sexual activity of experimental animal Ileum From A White, uterus, smooth muscle of bile vesica and bile duct, all there is inhibitory action, and can resist second phthalein choline, histamine, norepinephrine, barium chloride, the excitation of pituitrin to above-mentioned histoorgan.Test also shows that the bitter glycosides of jade tablet tooth dish system directly acts on intestinal smooth muscle, presents spasmolysis.The bitter glycosides intravenous injection of jade tablet tooth dish can suppress the independent rhythm sexual activity in rabbit original position small intestinal and uterus, and antagonism second phthalein choline or the excitation of pituitrin to above-mentioned histoorgan.
(2) analgesic effect: there are some researches show that swertiamarin can obviously suppress central nervous system, has significant analgesia and sedation.And analgesia and spasmolysis are the pharmacological basis of swertiamarin treatment gastrointestinal tract pain.
(3) other effect: swertiamarin has antiinflammatory, antivirus action; Swertiamarin is easy to absorb through skin surface in addition, after absorption, decompose and produce red arrow car rhzomorph (erythrocentaurin), expansible blood capillary, and the enzyme system of activation or promotion Skin Cell, the biochemical function that improves Skin Cell, is widely used in preparation hair stimulator in Japan.
Summary of the invention
The technical problem solving: in order to overcome the defect of existing treatment cholestasis medicine, simultaneously, for traditional Gentianaceae (Gentianaceae) Swertia (Swertia L.) Herba Swertiae yunnanensis extract swertiamarin is expanded new application, the present invention is applied to swertiamarin the treatment of cholestasis, has positive effect.
The object of the present invention is achieved like this: a kind of application as the medicine for the treatment of cholestasis with swertiamarin.Described swertiamarin is extracted from Gentianaceae (Gentianaceae) Swertia (Swertia L.) Swertia mussotii Franch., and manufacturer is that upper sea base is exempted from Industrial Co., Ltd., and described swertiamarin is iridoid, and molecular formula is: C
16h
22o
10, structural formula is:
The mechanism of action of its treatment cholestasis is: by synthesizing of induction liver bile acid biosynthesis enzyme CYP8B1, make bile acid biosynthesis synthetic to the less CA of toxicity from the large bile acid CDCA of toxicity; Raise liver detoxification enzyme CYP3A, UGT2B, SULT2A1, strengthen the water solublity of bile acid, reduce its toxicity; Increase the expression of liver protein called membrane transporters MDR1, MRP3, MRP4, reduce toxicity bile acid gathering in hepatocyte, thus the symptoms such as the hepar damnification that treatment is caused by cholestasis, hepatic necrosis, serum inflammation, jaundice.Therefore, swertiamarin has fundamentally been treated cholestasis.
Instructions for use: administering mode is oral, the body weight of corresponding respective patient, its consumption is 100mg/kg/d;
Use object: cholestasis patient.
Beneficial effect:
A kind of application as treatment cholestasis medicine with swertiamarin of the present invention, swertiamarin can significantly reduce serum and respectively organize Bile acid, thereby significantly reduce hepatic injury, the hepatic necrosis being caused by cholestasis, significantly suppress the serum inflammation being caused by cholestasis, cholestasis is had to significant curative effect.
Accompanying drawing explanation:
Fig. 1 is experimental group liver H.E coloration result figure in embodiment 1;
Fig. 2 is matched group liver H.E coloration result figure in embodiment 1.
The specific embodiment
Below in conjunction with embodiment, the invention will be further described:
Embodiment 1:
One, serum ELISA detects:
1, detect serum bile acid component target: CDCA (chenodeoxycholic acid), TCDCA (taurochenodeoxycholic acid), CA (cholic acid), TCA (taurocholic acid), DCA (deoxycholic acid), TDCA (taurodeoxycholic acid), TUDCA (tauroursodeoxycholic acid), T α/β MCA (tauro-alpha/beta-muricholic acid), α MCA (alpha-muricholic acid), β MCA (beta-muricholic acid).
2, detect hepar damnification index ALT, AST, ALP.
3, liver H.E staining examine hepatic necrosis situation.
4, detect serum levels of inflammatory cytokines TNF α, IL-1 β, IL-6.
Two, experimental result:
1, serum bile acid component target result:
(a) obviously reduce serum bile acid CDCA: the BDL group (2.2 ± 1.2) that false ligation group (22.4 ± 15.8), BDL group (14.0 ± 14.1), swertiamarin are processed, p<0.01;
(b) obviously reduce serum bile acid CA: the BDL group (1.4 ± 0.3) that false ligation group (2.2 ± 0.2), BDL group (2.1 ± 0.3), swertiamarin are processed, p<0.01;
(c) obviously reduce serum conjugated bile acids salt TCA: the BDL group (0.3 ± 0.1) that false ligation group (0.8 ± 0.2), BDL group (1.0 ± 0.2), swertiamarin are processed, p<0.01;
(d) obviously reduce serum bile acid DCA: the BDL group (0.1 ± 0.2) that false ligation group (2.0 ± 0.4), BDL group (1.7 ± 0.6), swertiamarin are processed, p<0.01;
(e) obviously reduce serum conjugated bile acids salt TDCA: the BDL group (1.1 ± 1.7) that false ligation group (0.1 ± 0.1), BDL group (3.0 ± 2.0), swertiamarin are processed, p<0.01;
(f) obviously reduce serum conjugated bile acids salt TUDCA: the BDL group (0.01 ± 0.03) that false ligation group (0.29 ± 0.18), BDL group (0.4 ± 0.09), swertiamarin are processed, p<0.05;
(g) obviously reduce serum bile acid β MCA: the BDL group (0.7 ± 0.5) that false ligation group (4.7 ± 2.7), BDL group (2.1 ± 0.5), swertiamarin are processed, p<0.05;
(h) serum TC DCA, T α/β MCA and α MCA are had no significant effect, but this result does not affect the effect of cholestasis treatment, because these three kinds of bile acids content in serum is lower, and toxicity is less than CDCA and CA.
In sum: swertiamarin 100mg/kg/d can significantly reduce the various Bile acids of serum (unit: ng/ml), can effectively treat cholestasis.
2, the testing result of hepar damnification index ALT, AST, ALP:
(a) ALT (glutamate pyruvate transaminase) experimental group significantly lowers with respect to matched group: blank group (30.4 ± 4.7), matched group (105.6 ± 46.6), experimental group (57.4 ± 16.4), p<0.05;
(b) AST (glutamic oxaloacetic transaminase, GOT) experimental group significantly lowers with respect to matched group: blank group (89.0 ± 15.1), matched group (388.8 ± 87.5), experimental group (177.8 ± 96.9), p<0.05;
(c) ALP (alkali phosphatase) is without significant change: blank group (198.6 ± 16.3), matched group (489.2 ± 186.4), experimental group (521.6 ± 243.3).
In sum: swertiamarin 100mg/kgd processes can significantly alleviate the hepar damnification being caused by cholestasis in 14 days.
3, liver H.E staining examine hepatic necrosis situation: the results are shown in Figure 1 (matched group liver H.E coloration result figure) and Fig. 2 (experimental group liver H.E coloration result figure); By Fig. 1 and Fig. 2, contrast discovery, hepatic necrosis area experimental group is obviously little than matched group, illustrates that swertiamarin is used for the treatment of the hepatic necrosis being caused by cholestasis and has remarkable result.
4, detect serum levels of inflammatory cytokines TNF α, IL-1 β, IL-6.
(a) obviously reduce serum levels of inflammatory cytokines IL1 β: the BDL group (71.8 ± 37.6) that false ligation group (101.6 ± 24.2), BDL group (171.0 ± 5.4), swertiamarin are processed, p<0.05;
(b) significantly suppress serum levels of inflammatory cytokines IL6: the BDL group (82.0 ± 14.6) that false ligation group (92.4 ± 20.5), BDL group (133.7 ± 41.4), swertiamarin are processed, p<0.05;
(c) within 14 days, do not observe the impact of swertiamarin on TNF α, but the experimental result of BDL 3 days and 7 days show, swertiamarin was BDL 3 days and within 7 days, can significantly reduce the level of serum TNF α.
In the time of 3 days, significantly reduce serum levels of inflammatory cytokines TNF α: the BDL group (4.9 ± 4.6) that false ligation group (8.0 ± 7.9), BDL group (18.4 ± 5.3), swertiamarin are processed, p<0.05;
In the time of 7 days, significantly reduce serum levels of inflammatory cytokines TNF α: the BDL group (13.0 ± 9.9) that false ligation group (2.3 ± 2.1), BDL group (48.2 ± 19.7), swertiamarin are processed, p<0.05.
Three, in sum: when swertiamarin is applied to treat cholestasis, can directly reduce the content of Bile acid, thereby effectively solve the problems such as the hepar damnification that caused by cholestasis, hepatic necrosis, serum inflammation.
Embodiment 2:
One, quantitative fluorescent PCR and protein immunoblot detect: 1, bile acid biosynthesis enzyme: CYP7A1, CYP7B1, CYP8B1, CYP27A1; 2, liver detoxification enzyme: CYP3A, UGT2B, SULT2A1, GSTA1-A4, GSTM1-M4; 3, liver protein called membrane transporters: tubule facial film transport protein MRP2, BSEP, MDR1, MDR2; Base side protein called membrane transporters: MRP3, MRP4, OST α, OST β, the expression of NTCP.
Two, immunofluorescence technique detects: liver protein called membrane transporters: tubule facial film transport protein MRP2, BSEP, MDR1, MDR2; Base side protein called membrane transporters: MRP3, MRP4, OST α, OST β, the expression of NTCP.
Three, experimental result:
1, bile acid biosynthesis enzyme detects: the expression of cholic acid synzyme CYP8B1,1.7 times of 1.8 times of mRNA levels and protein levels, p<0.05;
Swertiamarin 100mg/kgd processes the expression that normal rat can significantly increase cholic acid synzyme CYP8B1 for 7 days, and to CYP7A1, CYP7B1 and CYP27A1 express and have no significant effect.
2, the detection of liver detoxification enzyme:
(a) increase the expression of liver CYP3A: 2.3 times of mRNA levels, 3.8 times of protein levels, p<0.05;
(b) increase the expression of liver UGT2B: 2.4 times of mRNA levels, 3.8 times of protein levels, p<0.05;
(c) increase the expression of liver CYP3A: 2.3 times of mRNA levels, 2.1 times of protein levels, p<0.05.
Swertiamarin 100mg/kgd processes normal rat can significantly increase the expression of liver detoxification enzyme CYP3A, UGT2B, SULT2A1, GSTA1 in 7 days, and GSTA2-A4 and GSTM1-M4 are had no significant effect.
3, the detection of hepatic transporters:
(a) increase the expression of liver MDR1: mRNA level is unchanged, 3.4 times of protein levels, p<0.05;
(b) increase the expression of liver MRP3: 1.8 times of mRNA levels, 1.9 times of protein levels, p<0.05;
(c) increase the expression of liver MRP4: 1.5 times of mRNA levels, 2.2 times of protein levels, p<0.05.
Swertiamarin 100mg/kgd processes normal rat can significantly increase the expression of liver tubule facial film transport protein MDR1, substrate side transport protein MRP3, MRP4 for 7 days, and other transport proteins are had no significant effect.
Four, the molecular mechanism that draws in sum swertiamarin treatment cholestasis is: swertiamarin is synthetic by induction liver bile acid biosynthesis enzyme CYP8B1, makes bile acid biosynthesis synthetic to the less CA of toxicity from the large bile acid CDCA of toxicity; The water solublity that raises liver detoxification enzyme CYP3A, UGT2B, SULT2A1 enhancing bile acid, reduces its toxicity; Increase the expression of liver protein called membrane transporters MDR1, MRP3, MRP4, reduce toxicity bile acid gathering in hepatocyte, thereby alleviate hepar damnification.
Claims (1)
1. the application as the medicine for the treatment of cholestasis with swertiamarin.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116098932A (en) * | 2022-12-26 | 2023-05-12 | 重庆三峡医药高等专科学校 | Swertia pseudochinensis extract for improving cholestatic liver injury and application thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634099A (en) * | 2003-12-31 | 2005-07-06 | 昆明同持医药研究有限公司 | Swerianmarin injectio, its preparation process and application |
| CN1704086A (en) * | 2004-06-03 | 2005-12-07 | 昆明聚智达医药技术有限公司 | Method for preparing drug material of swertiamarin |
| CN1966511A (en) * | 2005-11-16 | 2007-05-23 | 上海诺德生物实业有限公司 | Swertiamarin monomer separation and purification method |
| CN102138966A (en) * | 2010-01-29 | 2011-08-03 | 天津药物研究院 | Tibetan capillaris extract and preparation method, pharmaceutical composition and use thereof |
| CN103040854A (en) * | 2013-01-17 | 2013-04-17 | 上海中医药大学附属曙光医院 | Swertiamarin and medical application of swertiamarin |
-
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- 2014-08-22 CN CN201410417573.4A patent/CN104188994A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1634099A (en) * | 2003-12-31 | 2005-07-06 | 昆明同持医药研究有限公司 | Swerianmarin injectio, its preparation process and application |
| CN1704086A (en) * | 2004-06-03 | 2005-12-07 | 昆明聚智达医药技术有限公司 | Method for preparing drug material of swertiamarin |
| CN1966511A (en) * | 2005-11-16 | 2007-05-23 | 上海诺德生物实业有限公司 | Swertiamarin monomer separation and purification method |
| CN102138966A (en) * | 2010-01-29 | 2011-08-03 | 天津药物研究院 | Tibetan capillaris extract and preparation method, pharmaceutical composition and use thereof |
| CN103040854A (en) * | 2013-01-17 | 2013-04-17 | 上海中医药大学附属曙光医院 | Swertiamarin and medical application of swertiamarin |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116098932A (en) * | 2022-12-26 | 2023-05-12 | 重庆三峡医药高等专科学校 | Swertia pseudochinensis extract for improving cholestatic liver injury and application thereof |
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