- Hypericum perforatum

29/01/2019

St. John's wort


: Hypericaceae ( - Clusiaceae)

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-24 , . ( ) .

. (hyper eikon = / ) (- , ). 

(Hyperion) (Helios; , ) .

(perforatum / ) , .

-. , .

.

, ,   "" (Remotiv).

 

.

 

: .

: .

: , .

 

( 0.05%-0.6%, " -0.2% . hypericin -pseudohypericin " ", (biapigenin, quercetrin, rutin), ( phloroglucinol hyperforin*, adhyperforin), (sitosterol), (lutein), (pectin), , .

 

* (hyperforin): ( ), , (1-4).

 

, , (), , , (OCD), , (PMS), .

, , , , , .

 

1:3, 45% – 4-10 " .

0.3% hypericin – 300-900 " .

– 3-12 .

– 20%-30%.

 

(1) UV.

47 ( , -, , , , ), (5).

 

( 0%-5.9%), (6,7).

( -0.0003%)(8).

, (), , , , , , , (9-15).

(16).

2000-2013 -SSRI’s 5 (447 84 ). . , Fluoxetine . , . , . SSRI’s , (403).

( , , ) :

  • (14 , / )(17-23)

  • (5 (24-28); , 3 (25); (26)

  • (5 )(5,29)

  • ( )(30-32)

  • -TSH ( 37 )(33,34)

  • (35)

  • (2 , )(36,37)

  • (, , , , ; 8 ) (38)

  • (39) 26 HIV ( (40,41))

  • ( , )(42)

  • 67(43)

  • (2 ; 3.6 Sertraline (44), , -(45))

  • ( C, 51 )(46)

() ( )(47). .

, (48-54).

 

- (UV), , , 24 (1).

5-10 "(11), HIV ( C) 0.05-0.5 " " (40,41,55,56).

, UV, 2.7-5.4 " ( 7-15 )(57-59), .

( Hypericism), - 10-40 " ( 30-50 )(60-63). 1 " (62).

(27) (7,57).

(1,24-26,47).

16 4.5 ( ), 15 . , (64).

 

(65), , (1,66-68). , , ( )(1).

4-6 , (1).

MAO , (1) ( , ) L-dopa.

(phototoxicity) , UVA / ( ).

-2.7 " UVA (26).

– 10-14 , (67-75).

( Metformin).

10 , . 240-294 , 900 , . 21 6 , -40% . , (399)

 

, (1,10,17-23,68,76).

 

2 " (77,78).

, (genotoxicity) (43,79).

LD50: ; 780 " -4.3 " (80).

 

/ /

 

(81-83) P450 ( CYP 3A4) P-gp.

(96,105,176,192,411) , ( 300-500 " ) CYP3A4 (96,105,176,192) Midazolam. , (105,412).

( ) .

(84-87) hyperforin.

(413) 31 ( ) ( 10 " ) CYP3A ( -4 " ) .

pregnane steroid X ( : SXR PXR). , , (88-90) ( CYP3A4) P-gp.

. (82,83) CYP 3A4, (91). , (92) CYP 3A4 , Voriconazole ( -22%).

, (93,94,402) CYP 2C19 -2E1.

CYP2C19 (414)
(415) 12 , CYP2C19 , ( 0.3% 4% ) 900 " -151.5% (p=0.0156) . CYP1A2 .

(95,96) Ibuprofen -Tolbutamide, CYP2C9, .

(152) 12 , ( 0.825 "/ ) (Warfarin) S-warfarin -R-warfarin (-29% -23% ) CYP2C9 .
(165) 21 , 900 " ( ) 15 ( ) Gliclazide -35% -22% CYP2C9.
(93,96-99) , CYP 1A2, (100), 8 ( ), (68).

CYP 2D6: (93), (101,102).

(416), 1800 " 16 P-gp 4.2 (p<0.05) . 

, P-gp (103) Vincristine, Vinblastine, , (Epipodophyllotoxins, Etoposide) (Docetaxel, Paclitaxel), .

(417) CYP3A4 -CYP2C9 P-gp .

, (1) ( ),  .

, .

 

(Cyclosporin, Tacrolimus)

.

(40-47%), (418) (5,104-121,419-420), (P-gp, CYP 3A4).

, (-0.1%) Cyclosporin (106,108,119).

, (68,122,123) Rapamycin, .

(421), (115) Tacrolimus, (mycophenolate mofetil) 600 " 14 .
:

 

: (Digoxin)

.

(18-27%)(87,99,124-126), (87,127), (P-gp).

 

(Fentanyl, Propofol, Sevoflurane, NO)

.

(70,74).

(67-69), (Meperidine) (72,73,128) ( pseudoephedrine).

 

(, SSRI's, SNRI’s, NSRI’s, MAO )

.

() .

Amitriptyline . 900 " , (129), (CYP 3A4, P-gp).

, (68) Imipramine -Amoxapine, SSRI’s Citalopram, Fluvoxamine, Naratriptan, Rizatriptan, Sumatriptan -Zolmitriptan MAO, (128,130-133).

, , (134-140,403).

(141-148)  Paroxetine, Sertraline, Venlafaxine, Trazodone -Nefazodone.

(washout) 2-3 (149).

(422), (423) 52 , , Venlafaxone (Hypericum perforatum). , CYP2D6 .

, .

Buproption – .

(421) (424) () 975 " bupropion ( CYP2B6) . 

58 300 , (dystonia, - ) , 4 . (150).

 

(Clozapine)

(CYP2D6, CYP2C9, CYP2C19, CYP3A4, CYP1A2, P-gp).
(421) (425) 41 - Clozapine . . .
(421) Olanzapine, Quetiapine, Risperidone, Ziprasidone .
 

Warfarin . (39%)(151-152,426-427) ( CYP2C9, CYP1A2 -CYP3A4).

12 INR (153-155).

Phenprocoumon . (153,156).

Cidogrel  .

, .

, 900 - 10%-20% (157-159).

  davigatran, rivaroxaban, apixaban -edoxaban.  (rivaroxaban, apixaban -edoxaban)  CYP3A4 P-gp (427-431).

 


.
CYP3A4 - CYP2C9 P-gp , . 
Imatinib -Irinotecan, -40% (160-162,432).
, (421) (433) , 900 " Docetaxel ( CYP3A4 -CYP2C8) (p=0.045) (p=0.045), .
(68,122,123)   Cyclophosphamide, Tamoxifen, Taxol, Etoposide, Dactinomycinn, Amsacrine.
(405)
Abiraterone, Afatinib, Axitinib, Crizotinib, Cyclophosphamide, Dabrafenib, Dasatinib, Docetaxel, Enzalutamide, Erlotinib, Etoposide, Everolimus, Exemestane, Gefitinib, Idelalisib, Imatinib,Irinotecan, Lapatinib, Nilotinib, Paclitaxel, Pazopanib, Pomalidomide, Procarbazine, Regorafenib, Ruxolitinib, Sorafenib, Sunitinib, Tamoxifen, Vandetanib, Vemurafenib 
, (164), Temozolomide.


(Metformin, Gliclazide, Tolbutamide, Rosiglitazone)

Metformin –  .  , , ( ) (400).

Gliclazide – . , (165).

Tolbutamide – . (92) (CYP 2C9), ()(96,99).

Rosiglitazone – . (166).

Repaglinide – . (434) (435) 975 " 14 repaglinide . , .

 

(Nifedipine, Verapamil, Amlodipine)

.

(51-63%)(167-169), (CYP3A4).

, (68) Dilitiazem, .

 

: (Talinolol)

.

(170), (P-gp).

 

(Carbamazepine, Mephenytoin, Phenobarbitone, Phenytoin)

.

, , (164,171,172);

(173) Carbamazepine, (174) mephenytoin.

(175) CYP450.

, (68) Phenobarbital, (122,123) CYP 3A4.

 

(Ethinylestradiol, Desogestrel, Dienogesterol, Norethindrone, Levonorgestrel)

, .
(CYP 3A4), , , , (436) (110,116,123,153,176-182). (421) (184) 15 (loestrin 1/20) , - .

 

(Cortisol)

.

, (91,185,186).

Prednisolone (187).

 

(Etoricoxib/Arcoxia, Ibuprofen, Indometacin, Aspirin)
, Etoricoxib. , .

(437) (438) 900 " Ibuprofen ( CYP2C9) .

, (439) (440) 25 "/" Etoricoxib (p<0.05) CYP3A4 P-gp.

(437) (306,441), 100-200 "/" Indometacin -Aspirin . , 2 "/" (441) Indometacin.

 

: (Alprazolam, Midazolam, Quazepam), (Zolpidem)

Alprazolam – . (188), (CYP 3A4).

( ) (99,189,190).

Midazolam – .

(93,98) (CYP 3A4), (11%-79%)(96,105,176,191-193).

, (105,190,193).

Quazepam – ( CYP3A4 -CYP2C9). , (194).
lorazepam -Oxazepam - . (421) lorazepam -oxazepam , .

Zolpidem - . .
, CYP3A4.
(195) 14 () 900 " Zolpidem (p=0.00) (p=0.04).

Eszopiclone -Zaleplon - . (421), CYP3A4 -CYP2E1 .

 

()

.

Atorvastatin, Rosuvastatin, Simvastatin – .

(-30%), (196-199), (CYP 3A4 -P-gp).

Pravastatin – (196).

 

(Methylphenidate)

.

(200).

 

: (Ivabradine)

.

, (201).

 

(Theophylline)

.

( ) .

(202) ( ), (203), 15 .

 

(Fexofenadine)

.

(105,192,204), (P-gp).

 

: NNRTI – (Nevirapine)

.

(205), ( -35%), (CYP 3A4, P-gp).

, (68) Delavirdine -Efavirenz, CYP 3A4.

 

(Indinavir)
:

Atazanavir (Reyataz), Darunavir (Prezista), Fosamprenavir (Lexiva), Indinavir (Crixivan), Lopinavir/Ritonavir (Kaletra), Nevirapine, Nelfinavir (Viracept),Ritonavir (Norvir), Saquinavir (Invirase), Tipranavir (Aptivus), Atazanavir/Cobicistat (Evotaz), Darunavir/Cobicistat (Prezcobix)

.
16 , (%57)(206), (CYP3A4, P-gp).
, (68) Amprenavir, Nelfinavir, Ritonavir -Saquinavir CYP 3A4.
, (421) (442) 11 600 " 14 Boceprevir C CYP3A4 - CYP3A5.
(443) (444) HIV Nevirapine ( CYP3A4 -P-gp) -35% -176 . 
 

 

(Ketoconazole, Itraconzaole, Voriconazole)

.

(-43%), (CYP3A4, 2C19, 2C9). (421) (207), 16 Voriconazole . 22% , 59% .

 

Erythromycin

.

(208) (CYP3A4).

 

: (Finasteride)

. (209). (421) (209) 12 (), Finasteride 600 " , (Carboxy-finasteride) CYP3A4 . 

 

Chlorzoxazone ( )

.

, (CYP2E1) -28%(93,98).

 

(Methadone)

.

, (-47%) (210).

 

(Oxycodone)

. .
(421) (211), 900 " 15 -50% ( AUC, p<0.001) CYP3A .

 

(Ketamine)
. .
(421) (445), 900 " 14 ( 58% AUC 66% Cmax, p<0.001) CYP3A .
 

( Piroxicam, Tetracycline)

.

, (1,27,68,128).

δ-ALA) delta-Aminolevulinic acid) – , ( ), 19 - δ-ALA , (212).

 

(Omeprazole)

.

(-38%)(213), (CYP 3A4, 2C19).

 

(Rhodiola rosea)

     .

-, 250-500 ( 125 ) .

salidroside ( 312 ) - (125 ) (397). (20 3% rosavin -3.12% salidroside, 624 salidroside ) (398).

, .

 

(Remotiv)

( Ze 117  0.2% ),  (<1%).

, ,   . 

,   , ,   Tolbutamide ( ), .

 

(1) , (68,79,214) , (215,216).
(217) 54 ( 615 " ), 56 -56 . . (20.3% 12.5% -8.9%) (5% 4% -0%) . , ; , 3%-5% .
(404) 38 90,128 . , , , . (8.1% 3.3%), (p=0.13) .
, (218-220).
, , (100 "/ ") (221).

 

 

, , (1,79).

, (222).

( -2.5 " )(222,223).

(16% 3% ). (224).

33 705 " , -4.2 , (225).

 

 

 | 

 

( ) , , (6,10,14,15,226-261, 406).

, -SSRI’s.

, , , .

, .

:

  • (410) - (2017) (Hypericum perforatum) . 27 , 3,808 . - 300-1,800 " 12 - (SSRIs). . . , , .
  • 2008, ,   , .   . 29 5489 , 18 , -17 . . -9 , 1.28, -9 1.87.  . , -SSRI,  1.02 -1.00 .  .    : 1. , 2. , 3. (229).
  • (406) 2016, 64 ( 18-70) ( 22-25 HAM-D), (251) 2005. , ( 3-7:1, 3-6% 0.1-0.3%, 6% , 1.5% ) 900 " 6 (paroxetine  20 ")(p<0.001). ( 50% ) (87.1% -60.6% , p=0.017). (71% 42.4%, p=0.001).
  • 2000 (Ze 117) Flouxetine ( -SSRI’s)  -. , 16-24 . 240 (114 )  (126 ). 6 , -11.54 12.2 -SSRI.  CGI . ,  23% ( , , , , , ),  8% . , (239).

900 , 0.3% .

(3-5%), . , , 900-1800 .

, (262-264).

(Seasonal affective disorder), ()(265-267).

 

, (268-270) , , -GABA;

, - (Blood-Brain Barrier) , (1,271).

- ( 0.9 ) 35 . -GABA, (272).

, , (273-275) (Growth Hormone) (273,275,276), . ACTH ( ) (277); (275,276) - (5HT2).

, (273,277) ( (274,275))  (dihydroxyphenylacetic acid), () , dihydroxyphenylglycol. dopamine beta-hydroxylase, (278).

 

, (279-282).

(283-288) (289,290) (quercetin, amentoflavone, biapigenin) .

, (291).

: ()(292), ()(284). (0.5%) 42 , (5%) (900 ), (286). (1.5-3%) Fluoxetine ( -SSRI’s) (293).

1998, , (1,294).

, , (275).

 

, (294).

 

 |  (OCD) | 

 

, , ( ), (, State-Trait Anxiety Inventory, )(241,258,295-299).

100-1800 .

, (Piper methysticum).

:

2004 (LI 160) . 151 600 " 6 . -15.39 -6.64 , -15.55 -11.07 . , , , CGI, SCL-90 . .

(295).

2004 173 , 6 . ( , , SCL90R, CGI ) ( 45.4% , 20.9% ). (296).

2009 (MDD) 28 . (1.8 990 " , 9 " -15 " , 3 ) (2.66 50 " -, 3 ) , 4 ( cross-over). Beck Depression Inventory , , , . , (300).

1995 100-120 " , 97 . , . , – 38-39% State-Trait Anxiety Inventory ( : STAI), 19-20% . (241).

2001 ( 0.3% ) (GAD), (Piper methysticum) - ( 280-900 ) (297)

1800 , , , , . 12 .

1800 ; , .

50% 900 , -1500 " ( , -30 -10 )(297).

2003 (GAD), 12 , 450-1800 (298);

( -21 -6 ), Citalopram .

( -14 -1 ).

( )(298).

. 2005 . 40 ( 600-1800 " ) , 12 (301).

 

(OCD) –

2000 (LI 160) . 12 900 , 12 . Yale-Brown Obsessive Compulsive Scale ( : Y-BOCCS), Clinical Global Impression (: CGI). , . , 7.4 Y-BOCS. , 43% (5 ) CGI, -50% , (8%) (302).

, 2005 , . 60 600-1800 " , 12 . Y-BOCS (3.43) (3.60), . , (303).

 

, (304-309), (304), (309).

, , GABAɑ, GABAb (407), GABA (310), 5-HT2 (409,407,311,312), - -(407).

 

, ( ) ( )(313,314).

:

2010 , . 100 ( 50.4) , 8 . ( ) 3 , 0.2 " ". -54% 32% . -51% 23% , -60% 26% (315).

2009, . 47 40-65 ( 3 ) 2700 , 12 . , , 3 . . ( 2.3 , 1.0 ), ( 3.8 1.8 ). 3 , , (316).

- 2007 77 , . 12 264 ", -1 " , -84 " 0.25 " . KI 4 -12 , (317).

2007 . 6141 -1287 , 6 12 . . , . (318).

1986 12 (60 ) -40 Diazepam ( ), 20 . 72% ( 37% ), 46%

( 31% )(319)

- 2006 (Cimicifuga racemosa) 301 . 16 . -8 2 , -8 , . 245-350 " 0.25 " , - 22.5-41.25 " ( 1 " ). -50% , 19.6% . -41.8% ( 18.9 -11) 12.7% ( 18.9 -16.5) .

(320).

2000, 6 , ( ) 179 , ( , , , ), . KI, -31.4 -18.7 (40% ) 30.3 22.3 (23% ) (321).

1999 (LI 160) . 12 , 2700 , 111 43-65 . (, , , ) ( , , ). (-79%). (322).

- 2009, (Vitex angus castus) . 93 , ( ), . – 300 " ( -1800 " , 990 " , 9 " -18 " ). 3 , 2 , -500 " . 16 .  ( 4, 8 -12) . , (323).

 

(PMS)

( ) .

( ).

2011 -PMS . 170 -PMS , (2 680 " ) (2 ), 8 . ( , , ), ( , ), (, , ) ( , ) -1 ( ) 6 (). -PMS , . (71%) (52%)(324).

2010 -PMS. 36 18-45 (25-35 ) PMS. , (900 " , 0.18% , 3.38% ) .  washout , . PMS . PMS, , , (325).

2005 70 -PMS. (60 , ; ) . : 46.45% , -18.1% (326)

2004, -PMS. 125 -PMS ; 600 " ( 1800 " ) ( ). , . , (327).

-2003 PMS 14 (328). (5400 " , 2.97 " , 27 " -54 " ; -1000 " ) . (16 ), PMS. , AMSQ, PMS-D, PMS-C. 

2003 - (Premenstrual dysphoric disorder), -900 " ; 5 (329). -SSRI’s.

2000 (LI160) . 19 18-50 , -PMS. ( 300 " , 900 " ). . 51%, 50% . : , , , , , , , , , , , , , , , (craving) . (330).

 

( )

, :

2009 160 " 50 18-50. 4 ,  (IELT- intravaginal ejaculatory latency time). (331).

2007 16 35, . 20 " 15-30 , 4 . (IELT), -246 -331 ; 14 16 (87.5%) – – -IELT. ( -4.9 -5.2). (332).

( 2008) 10 , 8 . 4 5 -90 , -58 -131 . 3 , 266 , 391 . 7 10   . 5 (333).

 

 |   | 

 

0.3% , . 90 , 900 " , -1800 . . , . (334,335).

 

. 149 18-55 HSV-1 HSV-2. : ( -) 5%, Dynamiclear – . 2, 3, 8 -14. . 1.9 , , 1.8, 2.4 -4.4 (336).

 

-pseudohypericin (337,338); (339-342), ( )(337,340). (339,341,343,344), (1,40).

 

 | 

 

, :

2010 ; 144 ( 23.5), -3 : , (20% , 80% ' ) 3 16 – -24 . -10 -40, . . -10 -40 . . , (345).

2001 (Calendula officinalis), 24 . - , 320:1000 ( ). 70% -30% . 16 , -37.6% , 15.83% (346).

2014 (ONE)  ( ). 15 76.87 , 10.9 ", 4.8 " . 8.1 . , 4 -11 15 (73%). ONE , . -56.7 , , (347).

(Holoil®)     (Azadirachta indica), . 28 ( , ) . , . (401)

2013 , . 9 1-11 . 50.76 " . . 10-22 . . 6 5 , 7-8 10, -0 10 . . (348).

II 2003 . 1.5% ( ). 18 ( SCORAD 44.5) , ( ) . 4 . ,   ( 7, 14 -28). Staphylococcus aureus , . (336).

 

, (350-352)  COX -LOX, ROS (353) (354) NO.

(355), , (356).

, -amentoflavone (357), Indomethacin ( -NSAIDs).

-, (carrageenan; )(352,357), NO -COX.

(358) , amentoflavone, -pseudohypericin.

(359).

 

 | 

 

II 2010  (Cutaneous T-Cell lymphoma) . , 6 , 24 . ( 0.05-0.1%)   , .

(360).

2008 . 34 , 21 (Basal cell carcinoma – BCC), (Actinic keratosis – AK) -5 (Squamous cell carcinoma – SCC). (0.07% ) 10 " 1 ", , , 6 . -50% -AK, -28% -BCC -40% . BCC . 11% BCC , -80% . (361).

 

(350), ( - - )(1).

, ROS , - / (362,363).

/ (362).

- (339,362-373)  (Mesothelioma) (374).

, -: , (375). ( 40-200 , ) , 3-5 , 2-6 .

 

()

 | 

 

(Ze 117) -, 43% . , 240 500 " Fluoxetine ( -SSRI’s) 6 ; , (299).

- 900 (LI 160) 4 , EEG. , , , (376).

 

cross-over - (377) 4 -12 , ( 2.7 ) ( EEG ), REM, MAO.  ( , , , ), .

13 , , 3 ( -0.5 )(378).

, 20 (LI 160) (600 1800 ) 7 , (276).

(polysomnogram) cross-over - 0.9 1.8 . , REM ( 15-40 ). (379).

 

   

- , (900 , 8 ) (5% 0.5%) (288)  .

, - (1,380); , (381-384) ( STAT-1alpha COX -LOX -iNOS(350,351), IL-6(408,409),  ROS (353)), - (385,386), (387), NMDA ( )(388), amyloid-beta (380,381,389).

(390,391), - () (392-394).

100 200 , (395,396), (nootropic, ), Piracetam ( GABA), .

 

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