انخظبئض ان ؼًبدة نهخأكسذ ن ًشخمبث انُبخخ ٍ ٍ انطبٍخ ٍ ٍ انجضائشٌخ ٍ ٍ Salvia officinalis و Phlomis samia وحأثٍشهب ػهى َشبؽ انغذة انذسلٍت و األؼػبء راث انؼاللت
انس ُت انجبيؼ ٍت 2008-2009 و
ان ًحخىٌبث
VI IX... X .. 1
3 I 1ان ـذة انذسقٛت 3
3 1 1
3 2 1
3 2
4 1 2
4
4 .
5 .
6 . 2 2
7 . 3 2
8 .. 4 2
9 .. 5 2
9 . .. 6 2
9 .
10
I 10 10
11 Propylthioracyl (PTU)
11 iodides
11 11
12 12
12 ………………………………………. 13 II
13 1-II 13 1 13 2
14 3 15 2-II 15 1
15 1 1
16
16 2 1
16 3 1
16 1.3 1
17 2.3 1
18 3 3 1
19 4 3 1
II 20 5 3 1
20 ...... NAD(P)H oxydase 6 . 3 -1
20 Xanthine oxidase 7. 3 -1
21 4 1
21 1 4 1
22 2 4 1
23 ADN 3 4 1
24 4 4 1
24 2
25 1 2
25 superoxide dimutase (SOD)
26 catalase enzyme (CAT)
26 Glutathione peroxidase
28 2 2
28 1 2 2
29 2 2 2
29 E 3 2 2
29 C 4 2 2
30 5 2 2
30 6 2 2
33 Glutathione(GSH)
34
34 ...Thioredoxine
34 III 35
37 III
37 1
37 2
37 3
40 4
41 5
41 6
41 7
42 8
42 9 44 Phlomis samia IV
44 1
46 2
46 3
48 4
50
50
55
60
انذساست .اال دظبئٛت ...... 79 85 152
185 IV 187
209
207
I
I
V (1.1-diphenyl 2-picril-hydrazyl) 2 1 1 DPPH
catalase CAT
Deciliter dl
Degre celcus C°
Deoxyribonucleic acid DNA
Glutathione peroxidase GSH-Px
Gram g
Heamoglobin Hb
High density lipoprotein cholesterol HDL
Cholesterol Cholesterol
Intraperitonial i-p
Kilogram Kg
liter L
Lower density lipoprotein LDL
Cholesterol Cholesterol
Microgram µg
Micromol µmol
Milligram mg
VI Milliter ml
Millimolar mM Millimol mmol
Molar M
Myeloperoxidase MPO
Non-protein sulfhydryl NPSH Sulfahydryl
Opticaldensity of standard ODstand
Optical density of test ODtest
Percent %
Per.Os p-o
Reactive Nitrogen species RNS
Reactive Oxygen species ROS
Reduced glutathione GSH
Sulfhydryl SH
Superoxide dismutase SOD
Tetraiodthyronine(thyroxine) T4
Triiodothyronine T3
Thyroid peroxidase TPO
Thyroid stimulating autoantibodies TSHBs
Thyroid stimulating recepters TSHr
VII Thyroid stimulating hormone (thyrotrophine) TSH
Total thiobarbituric acid TBARs
Type 1 iodothyronine deiodenase D1
Unit U
Volum V
Weight W
Liver weight Lgh
Haert weight Hgh
Kideny weight Kgh
VIII
...... 7 1
2 اال َ ٕاع االكغ ٛج ُٛ ٛت انُشـت 15......
16...... SOD 3
25...... Natural antioxidants 4
26...... )SOD( 5
...... 40 6
7
SOME ٔان ًغخخهض انًبئ ٗ SOI 41......
47...... P. bovei 8
85...... 9
10
...... 91 P. bovei .S.officinalis
IX
)1(يظٓش ٔيكب ٌ ح ػٕغ ان ـذة انذسقٛت...... 3 )2( يشا د م انخخه ٛق ان ذ ٛ ٕ ٘ نه ٓشي َٕبث انذسقٛت...... 6 )3( يٛخبب ٕنٛضو T4 ٔ َ ٕاحج ّ االعخقالبٛت ……….……...…..…………...…...... 8 )4( اإلجٓبد انخبكغذ ٖ...... 14 )5( ي ٕاقغ حشك م انجزٔس انذشة ػبش يؼقذاث انغهغهت انخُفغٛت...... 17 21...... …...... ……………….……...... …… 6 ؿ 7بؼٛت انخ ـٛشاث انخ ٙ انخ ٙ ح ظ ٛب األ دًب ع االو َٛ٘ت نهغالع م انجبَبٛت نهبشٔح ٛ ٍ بؼذ ْج ٕو انجزٔس انذشة...... 22 )8( ح ٓهكت جضٚئت انـ ADN...... 23 9 بؼ غ انٛبث انخأثٛش نه ُظبو ان ؼًبد نهخأكغذ...... 27
29...... α-tocophérol 10
30...... C 11
)12( انب ُٛت األعبعٛت نهفالف ٕ َ ٕ ٚذاث...... 31 )13( ب ُٛت انـ Quercetin...... 31 )14( أقغبو انفالف ٕ َ ٕ ٚذاث...... 33 )15( ط ٕس ف ٕح ؿٕشافٛت نُببث Salvia officinalis...... 39 )16( ط ٕس ف ٕح ؿٕشافٛت نُببث Phlomis samia ...... 45 )17( بؼ غ ان ًك َٕبث انك ًٛبئٛت نُببث Phlomis samia ...... 46 18 ان ظ ؾٛ انك ًٛبئٛت نبؼ غ ان ًك َٕبث...... 47 19 يشا د م ػ ًهٛت االعخخالص...... 61 20 ان ً ُ ذ ُ ٗ انقٛبع ٙ نهـ rutineٔ quercetine ...... 63 ػٕ ٚ 21خ ان ً ُ ذ ُ ٗ انقٛبع ٙ ن ذ ً غ انـبن ٛك ...... 64 22 ان ً ُ ذ ُ ٗ انقٛبع ٙ نهـ BHT ...... 66 23 حك ٕ ٌ انجغ ٕس ي ٍ َ ٕع MDA-TBA...... 77 24 ان ً ُ ذ ُ ٗ انقٛبع ٙ نهـ MDA...... 79 25 ان ً ُ ذ ُ ٗ انقٛبع ٙ نهجهخبث glutathione ٌ ٕ ٛ ان ًخخضل (GSH)...... 82
X )A )26 ك ًٛت ػذ ٚذاث انف ٛ ُ ٕل انكهٛت ف ٙ ان ًغخخه ظ ٛ ٍ انُببح ٛ ٛ ٍ يهؾ يكبفئ ن ذ ً غ انـبن ٛك /ؽ ي ٍ انٕص ٌ انجبف...... 86 B ك ًٛت انفالف ٕ َ ٕ ٚذاث يهؾ يكبفئ ن ذ ً غ انكشعخ ٛ ٍ ٔ انشٚخ ٛ ٍ يٍ/ؽ انٕص ٌ...... 86 )27( َغبت حثب ؾٛ جزس انـ DPPH حبؼب نخشكٛض ك م ي ٍ انـ BHT فالف َٕ ٕٚذ قٛبع ٙ ٔ يغخخهض Salvia Phlomis samiaٔ officinalis ...... 88 B الحشكٛض انًثبؾ نـ 50% ي ٍ جزس DPPH ...... 88 )28 ا(نُشبؽ انًثبؾ ألكغذة د ً غ linoléique بذالنت انضي ٍ ...... 90 )B ٔ A )29 قٛى انُشبٛؿت ان ؼًبدة نألكغذة نه ًغخخهظبث انُببحٛت ػ ُذ 24 عبػت ...... 92 Salvia officinalis Phlomis samia 30 بـ 200
101...... Phlomis samia Salvia officinalis )31( 200
104......
Phlomis samia Salvia officinalis 32 200
107......
Phlomis samia Salvia officinalis )33( 200
110......
Phlomis samia Salvia officinalis )34( 200
113......
114...... )35(
117...... )36(
XI S.officinallis 37
118...... 200
P.samia 38
120...... 200
L-thyroxine 39
121...... 0.3
L-thyroxine 40
123...... S.officinallis 200
L-thyroxine 41
124...... P.samia 200
Phlomis samia Salvia officinalis 42
126......
Phlomis samia Salvia officinalis 43
انغكش ...... 128 Phlomis samia Salvia officinalis )44( 129...... creatinine
Phlomis samia Salvia officinalis )45(
131......
Phlomis samia Salvia officinalis )46(
133......
Phlomis samia Salvia officinalis )47(
135...... LDL
Phlomis samia Salvia officinalis )48(
137...... HDL
Phlomis samia Salvia officinalis )49(
139......
XII )50(
Phlomis samia Salvia officinalis
141...... )51(
145......
Salvia officinalis )52(
148...... Phlomis samia
149...... sulfahydryl (NPSH) )53( . )sulfahydryl (NPSH) )54 ف ٙ انكهٛت..150
)sulfahydryl (NPSH) )55 ف ٙ انقهب..151
166...... )56(
XIII
104 T4 .)105(
107 106 68 108 126
Flavanol Flavonols (Flavon-3-ols) Flavones anthocyanidin
)70( Flavanol
)69(
109 . (111) )110(
134
propil galate (PG) butylated hydroxy toluene (BHT) butylated hydroxyanisol
1 resmary and sage tocopherol 69
Lamiaceae بشك م ٔاعغ ف ٙ انجضائش ي ٍ ب ٛ ُٓب انُبخخ ٛ ٍ
Salvia officinalis ٔ Phlomis bovei , syn. Phlomis samia 139
102 103
. Phlomis samia ٔببنخبن ٙ فبالقخشاح انز ٘ ػٔغ ن ٓز ِ األؿشٔ دت ٚك ًٍ ف ٙ حقذٚش يذ ٖ انخأثٛشاث انب ٛ ٕن ٕجٛت نُبخخ ٛ ٍ انـبٛخ ٛ ٍ انجضائشٚخ ػ Salvia officinalis ٔ Phlomis samia ٍ ٛه ٗ ان ـذة انذسقٛت ٔ األؼػبء راث انؼالقت ٔ دبنت انجٓبص انذفبٙ ػ ان ؼًبد نهخأكغذ نهجشرا ٌ ان ًظببت بذبنت فشؽ انذسقٛت انخجشٚب ٙ.
2
اسخؼشا ع انًشاجغ
I - انغذة انذسلٍت و اػطشاببحهب : Thyroid gland and her disorder Thyroid gland 1 Morphology 1 1
THYREOS )1( )2( )14( شكم 1 10 15
)3( 1 1 6 4 )4(
شكم 1: يظهش ويكب ٌ حىػغ انغذة انذسلٍت Histology 2 1
)4( µm 500 50 (37)
colloïd
3 40 20 (3) thyroglobulin
c calcitonin )1(
colloïd
)3(
Thyroid hormones : -2 Hormones biosynthesis 1-2
T4 %8 (38) calcitonine triiodothyronine T3 thyroxine T4
T3 T3
)6( T4 The iodide traping
أول مزحهت في عمهيت تخهيق انهزمىواث انذرقيت هي قبط انيىديذاث iodide م ه قب م
انخاليا انحىيصهيت ،حيث يؤخذ iodide م ه انغذاء و يىق م ان ً انخاليا انحىيصهيت بىاسطت
ميكاويزو مضخت وشطت تشبت مضخت انصىديىو Na+/K+ATPASE . و هذي االخيزة تحم م iodide عكس تذرج انتزكيز االنكتزوكميائ ً )5( تتزاو ذ كميت iodide داخ م انغذة 20 )3()41( 100
(157) )8( 40 iodide
Tyroglobulin synthesis
thyroglobulin Tg
120 (34) 600
4 iodine )7( follicular lumen
MIT
)14( Diiodotyronine )DIT( monoiodotyronire
)10 ( T4 T3 (colloidal lumen) Oxidation ,Iodination and coupling
(thyroid Acinar cells) iodide
(12) )14( )9( iodine peroxidase
- peroxidase(TPO) I I2 tyrosine iodine
peroxidase(Tpo) iodine
thyroglobulin H2O2
)13( )11( Tg
microrvelli
diiodothyronine monoiodothyronine (MIT)
DIT T4 DIT )7( (DIT)
)4( T3 MIT Storage and release hormones
T4 T3 )7(
iodothyronine )42( )3(
TSH
phagolysosomes proteases )4( )11( شكم 2
5 T3 iodide MIT DIT tyrosine
)5( T4
شكم 2 : يشاحم انخخه ٍك انحٍىي نههشيىَبث انذسلٍت. Thyriod hormones in circulation 2 2
.(40))5(
T3 %0.03 T4
)11( %0.3 %99.7
(35) tyroscine binding globulin (TBG) T4 T3
tyroxine binding )TBPA( T4
T4 T3 Albumin (40) prealbumin
T3 %0.3 %0.03 T4 . )12( )7(
6 Metabolisme of thyroid hormones 3 2
T3 T4
T3 T4 T3 T4
5 deiodininases T3 T4 )4(
5 deiodinase type I
5'- deiodinasc type II )10()11()1(
deiodinase enzyme ي ٍ ب ٛ ٍ ْز ِ اال َ ٕاع deiodinase 5 r T3 T4 inner ring position 5 شكم 3
- T2 T3 5
T3 T4 )11( 3,3'
decarboscylation deamination
oxidative deamination
triiodothyroacetic triac tetraiodothyroacetic acide tetrac T3 T4
O2 triac tetrac )7( 3,5,3 acid )4(
-جذول 1- ي ًٍضاث اال َض ًٌبث انُبصػت نهٍىد نهجشر .
-جذول 1- ي ًٍضاث اال َض ًٌبث انُبصػت نهٍىد نهجشر .
7
شكم سلى- 3- ٌىػح يٍخببىنٍضو T4و َىاحجه االسخمالبٍت .
Action of the thyroid hormones 4-2
9 basal métabolic rate)BMR(
)16( S CNS
genomic and non genomic action
++caٔ انخ ـٛشاث ف ٗ اَش ـت انبشٔح ٛ ٍ ك ُٛبص kinase
T3 RNA
)15( T3
8 B3 B1 α B3،B2 B1 α
B2
T3 ADN
thyroid
TRE responceElements
)16( )3( )11( RNAm
Regulation of thyroid secretion 5-2
.(36) thyroid stimulating hormone TSH
T3 T4 TSH
(39) )9( Tg (pinocytotic) Tg
Adenyl cyclase TSH
)17( AMPc
thyrotrophin releasing factor TRF T4 T3
llong feed back contro
)7( )9( loop 6-2 Anapropreate secretion of thyroid hormones Hyperthyroidism and it treatment
)3( (2)
9 thyrotoxicosis toxic goitre grave disease
15 5 (17) Gaves disease
%1 %99
%0.2 %2
TSH
(5)
Immunoglobulin Thyroid Stimulating Antibody (TSAB)
(Adenoma) (TSI) .(17) Antithyroid drugs
thiocyanate propul thioracil
carbimazole (17)
Thiocyanate
nitrate Perchlorate Thiocyanate
Tg Thiocyanat Goiter
10 TSH T4 T3 Tg (19) ،(17) )4(
Propylthioracyl (PTU)
Tg Tg methimazol (MMI) PTU
(7) (8) T3 T4 MMI PTU
Iodides
100 Tg (18)
2
3 (17)
Removal of part or all the thyroid
(8) (2)
Hypothyroidism and its treatment
(primary hypothyroidism)
tertiary (secondary hypothyroidism) (3)
4000 1 (critinism) (5)
11 Hachimoto disease
cell mediated immune respense TSH %80
. (2) (5) %1
Endemic colloid goiter Goiter TSH Tg (17) 20 10
Idiopathic non toxic colloid goiter :
(17)
Treatment of hypothyroidism )7(
(5)
T4 levothyroxine
. (7) T3 liothyronine
12 Stress oxidative and Thyroid gland II 1- II Introduction 1
O2
ATP
%5 2
ROS ROS(reactive oxygene spaces)
Definition of stress oxidative -2
)107()106()44( )52( 4
δ )43(
ADN
)54( apoptos )256( )43(
13
. 4 -3
)54( )54(
)72(
stress oxidative
ischémies /reperfusions
)43(
14 2 -II 1
1 1
)72()52(
. . OH (hydroxyl radical) O2 (superoxide anion radical) (radical oxygéne species) ROS
RNS(radical nitrogene species) )75(
2
1 ONOOH )72( H2O2 o2
(nitroperoxide) )80()61()43(
- 2- اال َىاع االكس ٍج ٍ ٍُت انُشطت
15 DAN )44(.
3 تفاعالت الجذر الحز Free radical reaction تجزيد الهدروجين A . + RH AH + R . Hydrogen abstraction نقل االل كتزونX -. + Y X + Y-. Electron transfer
X االضافة Addition R R . X . + RCH=CHR
. . النهاية)التعديل( A + A A 2 Termination . CH3CH2 .+CH 3 CH2 CH3 CH3 +CH2 = CH2 Disproportionation
2 1
)260( )65(
3 1
)57(
ROS
. )77( NADPH oxidase O2 .)76( P450 aldhyd oxydase xanthine oxidase
Mitochondrial electron transport 1.3.1
%2 )55( ) 5 ( submitochondrial particals
16 )44( ROS
4
I succinate NADH و II
II (NADH dehydrogenase I (coenzyme q or uq) ubiquinone
ubiquinol ubisemiquinone )succinate dehydrogenase(
IV reductase III
. . O2 dismutation O2 O2
)48( )46( H2O2
O2 انحشىة
5
Peroxisome 2.3.1
monoamidoxidase B )47( ،
)ٚ ) 173ُخج ػ ُٓب H2O2
.)76( )48( H2O2
17 Phagocytes 3.3.1
NADPH
. O2 oxidase
myeloperoxidase hypohalous H2O2 )44(
NO.
NO. macrophage
- .- ONOO peroxynitrite O2 )43(
oesinophil monocytes neutrophils
phagosome
.- )55(O2 O2 NADP+ DADPH+H
+ + .- NADPH + 2O2 DADP +H +2O2 . .- O2 O2 2+ H2O2 Fe }Fe–S{ . Fenton reaction OH
2+ - . Fe +H2O2 Fe(III)+OH + OH
superoxide dismutation H2O2
: dismutase (SOD) .- + 2O2 +2 H H2O2 + O2 . nitric oxide synthase )NOS( )NO(
ONOO- .- . - O2 +NO ONOO - ONOO
. . (184) OH NO2 ONOOH
. . ONOOH OH +NO2
18 ONOO- - - ONOO +CO2 ONOOCO2 - . .- ONOOCO2 NO2 + CO3
)44( )50(
myeloperoxidase (MPO) % 5 2
- hypochlorus (HOCl) Cl H2O2
- - Cl +H2O2 OCl +H2O OCl - +H + HOCl
Cl2 HOCl
ADN NH2 HOCl )50(
+ - HOCl + H +Cl H2O +Cl2 )50(
- - 1 OCl + H2O2 Cl +H2O + O2
Microsomal eletron transport system 4.3.1
)173( O2 e - P450
.- O2 )48( كًب
NADPH oxidase
ROS )44( ROS )173(
19 Transition metals 5.3.1
cupper iron Fe+2
ADN ،
)44(،
chelating proteins
ferritin metallothioneins
iron (Fe+2)
)49( )44(
6.3.1 ـNAD(P)H oxydase : NAD(P)H oxydase
NADH NADPH
)174(
)173( 258
.- O2 NAD(P)H oxydase .)174(
: Xanthine oxidase 7.3.1 KD 300
Xanthine
Xanthine Xanthine Hypoxanthine ROS oxidase
.(174) Acide urique
20 Targets of ROS 4.1
ADN
Lipide peroxidation 1.4.1
. . . . CCl 3 O 2 O 2 OH NO2
. (peroxyl radical) ROO )257( )78( )47( 6 C.
)43( )78()47()259(
isoprostanes ، Alcan malondialdehyde )47()260(
-شكم سلى 6- حىػ ٍح نًشاحم فىق االكسذة انهٍب ٍذٌت)43(.
21 Proteins oxidation 2.4.1
)7 ( SH
réticulation SH
tyrosine ONOO- )43()48(
glutamine nitrotyrosine
)47( SOD
. O 2 C
. . 2 RO RO 2 O 2 Fe )56( NO
شكم 7 : طبؼٍت انخغٍشاث انخ ً انخ ً ح ظ ٍب األحًب ع االي ٍُت نهسالسم انجبَبٍت نهبشوح ٍ ٍ بؼذ هجىو انجزوس انحشة )43( .
22 ADN oxidation :ADN 3.4.1
OH ADN
H2O2
.OH Zn+ Fe2+
neclease enzyme
2+ Ca dependonuclease Ca2+
.OH )53 ( )51( ADN
8-hydroxyguanine 8-hydroxyguanine guanine )52(
ADN
ADNguanine ADN
lysinoguanine )174( 8
شكم 8 : حههكت جضٌئت انـ ADN)43(
23 Carbohydrate damage 3.4.1
C-H
C. (OH)RR
HOBr HOCL )49( ،
OH. H2O2 cétoaldhydes
)43(
System antioxidant 2
)61( )256(
)43( )256(
24
جذول 4 : ان ُظبو ان ؼًبد نهخبن طد اال َض ٌ ًى و انال اَض ٌ ًى )61(. Antioxydant system 1-2
catalase (SOD) superoxide dismutase
peroxidase 1.1.2انـ (Superoxide dimutase (SOD : . )62( H2O2 O2
SOD )75()43(
cupper –zink SOD SOD1
SOD-Mn SOD2
SOD جذٔل 5 )45( )63(
. )58( O2 SOD
SOD-Mn
(c SOD Cu-Zn) SOD
)57( (pSOD Cu-Zn ) (ec SOD Cu-Zn )
25 انجذول سلى- 5- ححج ا َىاع اَضٌى انـسىبش اوكس ٍذ دٌس ًخبص )SOD( )63(.
SOD )60(
2+ . - + SOD-Cu +O2 SOD-Cu +O2 + .- + 2+ SOD-Cu + O2 +2H SOD -Cu + H2O2
. - . - + Bilan: O2 + O2 +2H O2 + H2O
Catalase enzyme (CAT) 2.1.2
H2O2 Catalase
.)57( )60( H2O2
3+ Catalase- Fe + H2O2 compowned I + H2O 3+ Compowned I + H2O2 Catalase- Fe + H2O + O2
Billon : 2 H2O2 2 H2O + O2 )60( )53( Catalase
Catalase Fe+2
)57( NAD(P)H
Glutathione peroxidase (GSH-PX ) 3 1.2
GSH-PX
hydroperoxides H2O2
26 NADH la glutathione )63(
cytocrome C cytocrome C peroxidase peroxidase
)GPx ٔ )64
(cGPx) GPx (pGPx)
GPx (PH GPx) GPx
.)65( )57( (GI GPx)
GIGPx > PHGPx > pGPx = cGPx ROOH +GPx-Se-+ H+ ROH + GPx-SeOH
GPx-SeOH + GSH GPx-Se-SG + H2O GPx-Se-SG + GSH GPx-Se- + GSSG + H+
Billan : ROOH +2GSH GSSG + ROH + H2O
)57( glutathion (GSH)
)43( )64( GPx
)57( NADPH+H GPx
hème oxidase thiorédoxine peroxidase thiorédoxine reductase glutathion transférase .)57(
شكم 9 : بؼ غ انٍبث انخأثٍش نه ُظبو ان ؼًبد نهخأكسذ )57(.
27 2.2
)66(
انجذول سلى - 6- يؼبداث انخبكسذ انطبؼٍٍت Natural antioxidants
Zink : 1.2.2
9
200 )66(
.OH SOD ADN
antagoniste )67(
28 Selinium 2.2.2
.)66(GPx selenoproteins
Hg )64( déiodinase
As Cd Pb
)67( 40 20
Vitamine E E 3.2.2
VitE
α ∆ ، δ ، β ، α %90 )66( E )67(
α-tocophérol LDL
E C
)60( )66( 10 9
شكم سلى - 10- ٌىػح انب ٍُت انفشاغٍت نـ α-tocophérol )66(.
vitamine C C 4.2.2 C C )66(
29 )68( tocopherole )67(
-شكم سلى 11- ٌىػح انٍت الخُبص انفٍخبي ٍ ٍ C النكخشو ٌ انجزس انحش)68( .
Carotinoids 5.2.2
β α 600
VitE B-caroteine . A )68( O2 )74(
)67(
Flavonoides 6.2.2
)180( )69(
)175( P 1950 )12( 4000
flavanones flavone calcones
)71( flavonols flavanols
30 . )70(
شكم سلى 12 : انب ٍُت االسبسٍت نهفالفى َىو ٌذاث )176( شكم سلى 13 : ب ٍُت انـ Quercetin)176(
flavonols Quercetin )177(
7 5 OH
)178( )176( B 4' 3' A
. . O2 OH
PH )179(
.)179( )178( )LOO.( lipid peroxyl
lipid ( LO0. ، ) ( Xo. ، ) ( LH chain-interrupting antioxidant ( InH ، ) lipid hydroperoxides( LOOH ، ) peroxyl radicals( .)176(
31 3’,4’dihydroxy structure (catechol structure) -1
B
.C 3 2 -2
4-oxo function 4 C=O -3
OH -4 3 5ٔ )181()71(
32 انشكم سلى 14 : السبو انفالفى َى ٌذاث )175(.
7.2.2 انـ GlutathionGSH
Y-GLU-CYS-GLY
glutamic y-peptide GSH disulfide
glycine y-glutamyle-cycteine synthase
)72( )63( GSH synthase
33 peroxide radical GSH
H2O2 ، GSSG,GSH disulfide glutathione peroxidase
GSSG reductase GSSG GSH )183(
)65( )63( NADPH+H
L-glutamate + L-cysteine + ATP L- y-glutamyl-L-cysteine + ADP + Pi )1( L- y-glutamyl-L-cysteine + glycine + ATP GSH + ADP + Pi )2( .(182)
Phenolic acids 8.2.2
ferulic acid )70(
9.2.2 انـ )Thioredoxine)TRX
SH (dithiol) TRX : cys-gly-pro-cys
thioredoxine NADPH+H GSH
)65( disulfides TRX
Thioredoxine
TRX2 TRX1 TRX )185( )63()65(
synthetic antioxidants 10.2.2
( propil galate butylated hydroxy toluene) PG (butylated hydroxyanisol) BHT
sage resmary tocopherol .)70(
34 Thyroid hormone & stress oxidative 3 -II
.(20) experimental hyperthyroidism TBARs T3 (26) (25) HPS (28) (32) 4 T3 (30) TBARs
( 26) DNA oxidative damage (27) (24)
3 T3 prooxidant-antioxidant
(31) NOS
(23) GSH-Px
H2O2 TPO
(19) H2O2
(21) O2
BMR
(ROS)
ADN ROS
(33) (20)
T2 T3
oxidase C
35 mitochondrial thyroid receptor (mTR) nuclear thyroid receptor (nTR)
(nTRs) nuclear thyroid respance element
mitochondrial thyroid respance element (mTRs)
ATP . (22) (21)
T3 oppenheimer 1985
T3 %8
20 metogen activated protien kinase (MAP)
MAP kinase
T3
.) 15 ( MAP kinase
36 Salvia officinalis - III 1
Salvia officinalis
)103( )101( 2
Salvia officinalis 30-20
)155( 4 2
13
.)100()99(
)99( taxonomie 3 3000 200
)81( 900 Salvia Phylogénic Classification Order : lamiales Familly : lamiaceae
37 )155(Classic classification :
مملكة Kingdom : plantae تحت مملكة Subkingdom : Tracheobionta
فرع Embrenchement : spermatophytes تحت فرع Subembrenchement : Angiospermes قسم Division : Magnoliopsides صنف Class : Magnoliopidae تحت صنف Subclass : Asteridae رتبة Order : Lamiliales عائلة (Familly : Lamiliacea (Labiées جنس Genre : Salvia نوع Espece : Officinalis
Nom binomial : Salvia officinalis
38
Salvia officinalis 15
39 4
cineol ، salviol )84( Salvia officinalis ،
thuyone ، borneol )101( )85( )88( )83( (6)
6
5-o-caffeoylquinic acid ، 3-ocaffeoylquinic ، gallic acid ،
.)92( )88( )95( rosmarinic acid caffeic acid
cirsimaritin ، genkwanin, hispidulin ، apigenin ، hesperetin )11( galangin chricin ،chrysin ، kaempferol )90( luteolin ، quercetin
.)82( )86( honey 100 g ùg 589.8 109.4
methylcarnosate )85( )86( )186( rosmadial ، carnosic acid
، epirosmanol carnosol ، epirosmanol methyl ether ، epirosmanol ethylether )95( . )102(
œstrogène asparagine saponine résine tanins
)95( sels vitamines
40 -انجذول سلى 7 - ان ًكىَبث انف ٍ ُىنٍت )ان ًسخخهض يهغ (كهغ/ نه ًسخخهض ان ًٍثب َىنى SOME وان ًسخخهض انًبئى SOI. )81(
Salvia officinalis 5 Salvia officinalis
(100)
6
Salvia officinalis .(101) 7
)88( salvare Salvia
ٲ
)102(
41 )؟ 137( . 8
Salvia officinalis 700 .)99( 9
Salvia officinalis
) 155( كًب )88(
thujone )95( rosmarinic
Estrogen
)102( كًب حذخ ٕ ٖ انًش ًٛ ٚت ػه ٗ د ً غ rosmarinic
)155( )103( )100()103( )91( )97( )102( )155(
)155(
42 )83(
Azathioprine (AZP) ,
{ 6-(1-methyl-4-nito-5-imidazolyl) thiopurine }
)94 ( )93(
)87( GST GSH
acetyl choline esterase )96 ( )98 ( )95( )84( .)155(
43 Phlomis bovie De Noé sub sp(bovie) syn Phlomis samia desfantaines -IV 1
100 Phlomis samia desfantaines
250 )149(
4 45 54 URSS 60
Phlomis bovei Phlomis herba-venti ،
Phlomis samia desfantaines )140( P. crinita Phlomis caballeroi )155( 80 50
141
Phlomis bovie De Noé )155( 8/1
Phlomis samia desfantaines
Phlomis samia 139 maroccana Maire P. bovei .)155(
sticky jerusalem sage jerusalem sage 139
Phlomis sp
20 –
.)139( )142(
44 4
انشكم 16 : طىس فىحىغشاف ٍت نُببث Phlomis samia .
45 2 الح ظ ُ ٍف )155( : مملكة Kingdom : plantae تحت مملكة Subkingdom : Tracheobionta فرع Embrenchement : spermatophytes تحت فرع Subembrenchement : Angiospermes قسم Division : Magnoliopsides صنف Class : Magnoliopidae تحت صنف Subclass : Asteridae رتبة Order : Lamiliales عائلة (Familly : Lamiliacea (Labiées جنس Genre : Phlomis نوع Espece : samia تحت نوع Sub sp : desfantaines
3
)144 ( )134 ( )149( iridoid glucoside
)140( phenylethanoid glycosides )138( verbenalin aucubin loganin
4oacetylmartynoside 1 17 martynosid )151 ( )149(
)143( 3 17 samioside )2 17
46 شكم 17 : بؼ غ ان ًكىَبث انك ًٍبئٍت نُببث Phlomis samia . monomeric phenylpropanoidٔ lignane 1 )18(
2 glucoside, 2,6-dimethoxy-4-hydroxyphenol-1-O-D-glucopyranoside
phlomuroside (=3hydroxy-5,6-epoxyionol-9O-Dglucopyranoside) megastigmaneglucoside
.)144( uridine 3
شكم 18 : ان ظ ٍغ انكًبئٍت نبؼ غ ان ًكىَبث . naringenin ،iriodictyol )140( )152( luteolin apiginine chrysoeriol،
)148( )148( )152( flavanones
P. bovei 8
%8.43 β-caryophyllene 146 139 21.45 D germacrene
)139( %5.84 hexahydrofarnesyl acetone )154( )139( %7.05 thymol
47 )151( )139( )154( )139( 4
Staphylococcus pyogenes Escherichia coli Enterotoxins
Clostridium Yersinia Salmonella
)149( phlomis
phlomis
phenylthanoid phenylpropanoid flavonoid iridoid
)147( phlomis )156( )150( )158( )149( )138 ( )163( (158)(160)
phenylpropanoides )138(
)141 ( )158(
iridoid )164( )149( )165( )164()162(
sedative
(138) purgative
)153(
48 )145(
CAT ،SOD،
)145( GPx )162()138(
49
ان ًىاد وطشق انؼ ًم :
Phlomis samia Salvia officinalis
I
II
Salvia officinalis Phlomis samia III
DPPH Salvia officinalis Phlomis samia V β-carotene /linoleic acid IV
Phlomis samia Salvia officinalis
I Phlomis samia Salvia officinalis II
Phlomis samia Salvia officinalis
1 Body weight, thyroid and relative thyroid weight.
50 2 Body weight ,liver weight and relative liver weight .
3 Body weight ,kidney weight and kidney relative weight .
4 Body weight ,heart weight and relative heart weight . III thyroid morphology and histopathology stady IV free triiodothyronine(T3) 1 free thyroxine(T4). 2 V
Glucose 1 2 Triglycerides 3 Cholesterole 4 Creatinine 5 HDL 6 LDL 7
Phlomis samia Salvia officinalis VI
1 VI TBARS 1
51 TBARS 1 1 Determination of hepatic total thiobarbituric reactive substances (TBARS) TBARS 2 1 Determination of heart total thiobarbituric reactive substances (TBARS) TBARS 3 1 Determination of kidney total thiobarbituric reactive substances (TBARS)
sulfahydryl 2
sulfahydryl 1 2 Hepatic nom protein sulfahydryl (NPSH) reactivity. sulfahydryl 2 2 heart nom protein sulfahydryl (NPSH) reactivity. sulfahydryl 3 2 kidney nom protein sulfahydryl (NPSH) reactivity. Enzymatic antioxydant 2 VI Determination of hepatic catalase 1 (CAT) Determination of kedny catalase activety 2 Determination of heart catalase activity 3
43 wistar albino rats 7 6 200 140
20 200
52 10
Phlomis samia Salvia officinalis
NaCL 0.9 200
83 10 % 0.3
L-thyroxine (114) ip
Gastric tupe
3 4 8
10 7 0.9%
L-thyroxine 0.3mg /kg 7
Experimental
hyperthyroidism
L- thyroxine 0.3mg /kg 7 Phlomis samia 200
Phlomis samia 200mg/kg 7
53 7 Salvia officinalis 200
200 7 Salvia officinalis
54
19 Phlomis samia 3 2008
2008 2 Salvia officinalis
retary evaporator 20 37
Phlomis samia Salvia officinalis
55 wistar albinos 15
gestante 28 21 21
200 140 7 6 10 200
chemicals
(1)KCL : 100 1.15
(2) GN()
(3) ellma’s reagent (5,5’dithio-bis-(2-nitrobenzoic acid) DTNB ; 3-carboxy - 5- nitrophyl disulfide) phosphate buffer PH 5 20
sulfahydryl(NPSH)
(4)glutathione (GSH) :N-(N-L-Y+glutamyl-L-cysteinyl)glycine (sigma)
56 40 20
1 1 saline
sulfahydryl
(NPSH
(5) hydrogene peroxide (sigma)
19
(6) malondialdehyde(MDA) (1,11,3,3-tetramethoxy propane ) (sigma)
TBARs
(7) n-butanol (poreac) TBARs (8) thiobarbituric acid (TBA) (sigma)
100 thiobarbituric acid 600
TBBARs 10
(9) trichloro acetic acid (TCA) (poreac) :
10 %100 TCA 1
SH)
(10) TSH reagent kit :
(11) T3 reagent kit ; T3
57 (12) T4 reagent kit : T4
(13) protein totaux reagent :
(14) cholesterol reagent kit : (15) glycaemia reagent kit: (16) cholesterol HDL : (17) triglycerides : (18) creatinine: (19) quercetin: 50 125
(20) methanol:
(21) ALCL3: 150 3
(22) B-caroteine : 1 0.5 B-caroteine (23) chlorophorme : B-carotene (24) BHT 1 2
58 (25) linolieque acid : 25
(26) tween :
(27) DPPH : 10 40
(28) K3Fe(CN) 6 : 100 25 (30) gumme arabique 1% : 100 gumme arabique 1
(31) acid phosphorique 84% :
bufer and solution
13.6 phosphate buffer solution (ph 7.4 PH8) 0.1M
1 1000 (potassium dihydrogen-phosphate
1000 K2HPO4 14.98 PH
PH 7.4 PH
8 PH
. sulfahydryl (NPSH)
59 انطشق: ان ط ش ق Phlomis samia Salvia officinalis
83 I Phlomis samia Salvia officinalis
macération 1
rotary
evaporator
20
60 ج ًغ انُببث ح ُمٍخه غسهه و حجفٍفه ثى طح ُه
Macération غًش انبىدسة انُببحٍت فى ان ًحهىل كحىنى (methanol 90%) ن ًذة 7 اٌبو
انخشش ٍح ببنمط ٍ ثى وسق واثًب ٌ سلى 1و َح ظم ػهى ػ ًهٍت اػبدة غًش ثب ٍَت وثبنثت
انبذسة انُببحٍت انببلٍت فى انم ًغ ؼٌبد حشش ٍحهب يشة ثب ٍَت و ثبنثت انشاشح 1 و2 و3
حجف ٍف بجهبص rotary evaporator حفظ ان ًبدة انُبحجت ػهى دسجت حشاسة -20 °و 37 حخى ان ؼًبيهت
. 19
61 II
1 .
trichlorure
. d’aluminium)172(
. 1- quercetine 50ùg /1 ml 2 - rutine 2- rutine
3- AlCl3 (2 %, dans le méthanol). 4- methanol .
rutine quercetine
μg/ml 40 0
AlCl3 (2 %, dans le méthanol). 1 rutine quercetine 10 3 430
AlCl3 1 1 10 430
.
rutine quercetine
1 rutine quercetine
.(mg ER / g E). (mg EQ / g E)
62 1,8 y = 0,0393x + 0,0223 1,6 quercetine R2 = 0,9985 1,4 rutine شدة ا 1,2 ال 1 0,8 0,6 الضوئى متصبص الضوئى 0,4 y = 0,0179x + 0,0319 0,2 R2 = 0,994 0 0 10 20 30 40 50 التركيز ug/ml
. rutine quercetine 20
2 .
bleu de Prusse 1977
. )171(Graham 1992 )170(
ferricyanide de potassium (K3Fe[CN]6)
2+ chlorure de fer (FeCl3) ions ferreux (Fe )
. nm 700
.
1- K3Fe(CN)6 (0.016 M)0.5%
2- FeCl3 (0.02 M, dans le HCl 0.1N) 3- solution stabilisante : 3-1 gamme arabique 1% 3-2 acide phosphorique 85%
63 3-3 eaux distillées 180 ml
. 3 (extract) 0.1
0.02 ( (, K3Fe(CN)6 (0.016 M) 1
5 15 HCl 0.1N FeCl3)M
30 ml Gomme Arabic 1% 90 ml 30 ml phosphoric acid 85 %, 700
gallic acid
acide gallique (500ùg /ml )
700
1,2
1
0,8
0,6 y = 0,0046x + 0,0331 0,4 R2 = 0,9979
0,2
0 0 50 100 150 200 250 تركيز حمض الغبليك )مكروغرام/مل(
: 21
.
gallic acid
(mg EAG / g E).
64
Salvia officinalis Phlomis samia III
: DPPH . انًبذأ : انًبذأ
Salvia officinalis Phlomis samia
DPPH DPPH in vitro
2,2'-diphenyl-1- (2,2'-diphenyl-1-picrylhydrazyl)
picrylhydrazine (Cuendet et al., 1997; Burits and Bucar, 2000)
)168( nm517
)169(
1- methanol .
2-DPPH (2,2'-diphenyl-1-picrylhydrazyl) 0.004 %.. 3-different [] of Phlomis samia extract.
4- different [] of Salvia officinalis extract
50 μl
% 0.004 DPPH 5
nm 517 30
BHT
.
: DPPH (I %)
I % = [(AC – AE) / AC] × 100
65 . ) ( :AC
AE
(IC50) DPPH %50
µg / ml
. BHT
90 y = 479,78x + 34,709 80 R2 = 0,9354 70 60 50 40
30 التثبيظ )%( نسبت التثبيظ )%( 20 10 0 0 0,02 0,04 0,06 0,08 0,1 0,12 تركيز الـ µg/ml) BHT (
. BHT 22
66 Salvia officinalis Phlomis samia IV β-carotene / linoleic acid .
Salvia officinalis Phlomis samia
β-carotene / acid linoleic
. )167(linoleic diene hydroperoxydes .
1 B-caroteine 0.5
tween linoleic acid 25
100 retary evaporation 200
(100 ml / min / 30 min) .
2.5 (extract) 350 μl 490 6 3 48 24
BHT 1
3 μl350 2
2
24 6 5 4 3 2 1 490 nm 3
. 48
.
(AA %)
AA % = (AE / AC) × 100
67
. : AE
BHT AC
(AA %) 24
68 V 1 GN 25 9 2
3
discs 5 1
4 48 24 37
inhibition zones
Aspergillus sp
Pseudomonas sp gram (-)
Staphylococcus sp gram (+)
Klebsiella sp gram (-)
Esherichia coli gram (-)
Condida
69 Phlomis samia Salvia officinalis
I
200 140
NaCL 0.9%
0.3
L- thyroxine
0.3 L- thyroxine 10 200 Salvia officinalis Phlomis samia 200 20 Salvia officinalis Phlomis samia
: % 50 Preliminary LD 50 test 8
0.9% Nacl 5000 4000 2000 1000 500 400 200 S officinalis
5000 4000 2000 1000 500 300 150 P samia
70 72
Phlomis samia Salvia officinalis II
Effect of salvia officinalis and phlomis samia and hyperthyroidism state on thyroid gland :
1 Body weight , thyroid and relative thyroid weights:
28
2- Liver and relative liver weight .
3- Kidney and relative kidney weight .
4- Heart and relative heart weight
71 III Thyroid morphological and histological study
10% Neutral buffred formalin
%10
24
l’éclaircissement
le xylène
Embadded in paraffin)
5 microtome
37
72 Hematoxylin l’éosine-ématoxilne
l’éosine
Thyroid hormones assay IV
6000
15
20-
TSH T4 T3
commercially available kit
V
(Technicon RA et Opera systems № de ref. T01-2801-56) auto analyseur
1
glucose يغ إَضٚى glucose-oxydase . .
ٚ glucose-oxydaseؤكغذ glucose إن ٗ hydrogène (H2O2) ٔ gluconique l’acide
peroxyde انُبحج ٚغخقبم ي ٍ قب م phénol-aminophenazone ف ٗ ٔج ٕد اَضٚى (peroxydase (POD دغب انخفبػ م االح ٗ :
73
GOD β-Glucose + O2 + H2O Acide Gluconique + H2O2
POD H2O2 + Phénol + Aminophenazone Quinone + H2O
شذة انكثبفت انؼٕئٛت ن ًج ً ػٕت انك ٛ ُ ٛ ٍ انُبحجت حقب ط ػه ٗ ؿ ٕل ي ٕجت 505 َب َ ٕيخش ٔحذل ْز ِ انكثبفت ػه ٗ حشكٛض انغكش ف ٗ ان ً ظ م)91( )92(
2 حمذٌش حشكٍض انكهسخشول انكهى :
93
Boehring Mannhein Trinder .
Cholestérol estérase Cholestérol estérifié + H2o Cholestérol + acide gras.
Cholestérol oxydase Cholestérol + O 2 ∆- 4Cholesténone + H2O2.
H2O2 + phénol + chromogène (amino 4 phénazone) Peroxydase Quinone imine
nm500
3 - حمذٌش ك ً ٍت انغهٍسش ٌذاث انثالث ٍت ف ً ان ً ظم : حى حقذٚش ان ـه ٛغش ٚذاث انثالثٛت حبؼب نـشٚقت إَض ًٛ ٚت ن ٕ َٛت . . :انًبذأ
ؼٚخ ًذ يبذأ انخفبػم ػه ٗ حقذٚش ان ـه ٛغشٔل ان ًخذشس َخ ٛجت فؼ م إَضٚى ْذو انهٛب ٛذاث lipase enzym . Lipase Triglycérides Glycérol + acides gras Glycerol Kinase Glycerol + ATP Glycerol 3 phosphate + ADP
74 Glycerol 3 phosphate Oxydase Glycerol 3 phosphate Dihydroxyacétone phosphate + H2O2
Peroxydase 2H2O2 +Phénol +amino-4-phénézone Quinone imine + 4 H2O
nm 500
4 - حمذٌش كهسخشول انـ HDL : حقذٚش كهغخشٔل VLDL. ٔ LDL HDL ح ذج حبثٛش يفؼ م انـ phosphotungstique انًشحبؾ بـ ref.T01-2801-56, 6×5ml) ، chlorure de magnésium) ارا ٚخى
حقذٚش انـ HDL ف ٗ انقـفت انـبفٛت انُبحجت ػ ٍ ػ ًهٛت انـشد انًشكض ٖ نه ًشكببث ان ًخشعبت بُف ظ انـشٚقت ان ًخبؼت ف ٗ حقذٚش انكهغخشٔل انكه ٗ )93( .
5 - حمذٌش كهسخشول انـ LDL : LDL Friedewald (1972)
(4 mmol/l) 3,5 g/l TG
LDL-C = CT - [ HDL-C + (TG/5) ]
6 - حمذٌش ك ً ٍت انبشوح ٍُبث انكه ٍت :
. :ان ًبذأ
540
75 7 - حمذٌش ك ً ٍت انـ créatinine فى انؼ ٍ ُت : créatinine
l’acide picrique créatinine
créatinine
preparation of liver cytosolic fraction
(NACL 0.9%)
1
(1.15%) KCL 9
ultra turex
4 10 4000
20 )122(
( TABPS ) (CAT)
sulfahydryl (NPSH)
spectrophotometre
76 1 VI TBARS 1
MDA-TBA 23
Principle .
thiobarbituric MDA
3 2 PH
(pigment pink ) 15 95
535 n-butanol
nm reagent and solvents
1-thiobarbituric acid . 2-TCA 20% 3-n-butanol . 4- malondialdehyde standart : (1.1.3.3-tetramethoxy propane) MDA
MDA MDA
77 TBARS
0.5 10 1
thiobarbituric acid 1 TCA(20%) 0.5
15 100 2
4
n -butanol 3
15 3000
530 spectrophotometre
MDA
TBARS
calculation .
MDA TBARS
78 1 0.9 y = 0.0184x 0.8 R 2 = 1 0.7 0.6 0.5 0.4
Absorbance 0.3 0.2 0.1 0 0 10 20 30 40 50 60 Concentration de l'MDA (nmol/ml)
MDA 24
79 sulfahydryl (NPSH) 2 Determination of hepatic nom protein sulfhydryl contents (234) (ellman 1959)
( ellman reagent ) ellman sulfahydryl
sulfahydryl (NPSH)
2 1 spectrophotommetre
nitro-5 mercaptobezoic acid
1 ellman’s (5’,5’-dithio-bis(2nitro bezoic acid ))
sulfhydryl
1-10% TCA-6mn NA2EDTA . 2-potassium phosphat buffer PH8 0.1M . 3-ellman’s reagent (5’,5’-dithio-bis(2nitro bezoic acid ) 0.396g/100ml .phosphat buffer 4-sample . 5- reduced glutathione (GSH) standard .
1 1 2 1
glutathion (9-1cycteine s-glycine)
glutathione
0.5 (TCA10%)1 0.5
(homogenat) 5 2000 15 10 0.2
ellman’s reagent 100 phosphat buffer PH8 1.7
412 dupliquat
80 5 spectrophotometre
(reagent blank) calculation
×F × × n × ×
n 2 0.2 F
Glutathione content ùmol /g tissue or haemoglobin =
ODtest× total volume ×F ×con of stand (ùmol ) ODstand ×volume used of sample ×n
N= estimated g haemoglobinper volume used . 2= total volum . 0.2= volum used . F= dilution factor .
81 0,7 y = 0,0617x + 0,0197 2 0,6 R = 0,9973 0,5 0,4 0,3 0,2 0,1 0 0 2 4 6 8 10 12 تركيز الـ GSH مقدرة بـ Ug/ml
(GSH) glutathione 25
: (235) (CAT) 2 VI principle .
H2O2 (CAT)
240
(CAT) .
1- potassium phosphate buffer PH 7.4( 0.1M ). 2- hydrogen peroxide (H2O2) 19 mmol
:
3 1
H2O2 2.95 50
19 mmol /l
82 240 2
3
calculation
(CAT)
K= 2.303/T * log A1/A2
K T A1
A2
K/n
n
One unit of CAT activity was calculated by using =
K= 2.303/T * log A1/A2
K= first order reaction rate constant. T= time interval in min. A1= absorbance in time 0. A2= absorbance in 1 min .
83
Specific activity was calculated as K/n =U/mg protein or haemoglobin
Were n= mg protein or haemoglobin in the used volume of sample used
Statistical analysis
( means ± SD) ±
Tukey-kramer(test)
ns 0.05 < P * 0.05 > P ** 0.01 > P *** 0.001 > P
*
84
Phlomis samia Salvia officinalis
I
9
كتهت انمادة انىباتيت ان دافت انىبتت كتهت انمستخهص انمزدود انميثاوىن ً انىاتح
100 غ Salvia officinalis 15غ 15 %
200 غ Phlomis samia 30 غ 15 %
II
± 73,14
0,017 ±116,76 0,016
A 26 Salvia officinalis Phlomis samia انشك م )B 26(
46,37 Phlomis samia
21,61
30,327 Salvia officinalis
14,301
85
CE mgEAG/g E
140
120
100
80 CE mgEAG/g E 60
40
20
0 Phlomis samia extract 0,5mg/ml Salvia officinalis extract 0,5mg/ml
A 26
50 45 40 35 30 Phlomis samia 0,5 mg/ml 25 Salvia officinalis 0,5mg/ml 20 15 10 5 0 CE mgEQ/g CE mgER/g
B 26
86
Salvia officinalis Phlomis samia III
DPPH
DPPH A 27
Phlomis samia Salvia officinalis BHT
BHT DPPH
%100 Salvia officinalis
Phlomis samia BHT
0.069 %2.73 ± 93.85 DPPH
0.0384 % 0.52 ± 94.53 DPPH
0.0038 % 0.51±18.33 DPPH
0.011 %1.10 ±17.56 Salvia officinalis
50.93 DPPH BHT Phlomis samia
0.0219 %2.23±
DPPH %50
Phlomis samia IC50 B 27
IC50 BHT IC50 0.0009 ± 0.0324
Salvia officinalis 0.017 ± 0.0006 /يهؾيم IC50
DPPH
50% ي ٍ جزس P DPPH < 0.001
BHT
87
100 90 80 70 60 BHT 50 P, samia 40
S, officinalis التثبيظ % نسبت التثبيظ % 30 20 10 0 0 0,05 0,1 0,15 0,2 التركيز )mg/ml(
BHT DPPH A 27
Phlomis samia Salvia officinalis
0,04
0,035
0,03
0,025
0,02 *** 0,015 IC 50 IC (mg/ml)50 0,01
0,005
0 BHT(control) salvia officinalis phlomis samia
DPPH %50 B 27
88 Salvia officinalis Phlomis samia V β-carotene / acide linoleic
linoleic 28
28
β-carotene Phlomis samia Salvia officinalis
0.001 > P
BHT
29 24 BHT
% 2.832±97.05 Phlomis samia B A
% 0.749±95.58 Salvia officinalis
24 %0.92±99.97 BHT
89 120
100 BHT 80 phlomis samia 60 Salvia officinalis
MeOH 40 التثبيظ% نسبت التثبيظ % H2O 20
0 0 10 20 30 40 50 60 الزمن )سبعت(
linoleic 28
120 *** *** *** 100
80
60
40
20 للتبكسد% المضبد للنشبط المئويت النسبت المئويت للنشبط المضبد للتبكسد% 0 BHT p, samia s, officinalis MeOH H2O العينبث
(A ) (A)
H2O
MeOH
s, officinalis ***
p, samia ***
BHT ***
0 20 40 60 80 100 120 النسبت المئويت للنشبط المضبد لالكسدة % عند 24 سبعت
(B ) (B) 24 B A : 29
90
IV
S.officinalis 10
7 Staphylococcus sp gram (+)
P.samia Esherichia coli gram (-)
يغبدت انخثب ؾٛ نـ يغبدت انخثب ؾٛ نـ سقى ان ظ ٕسة العى انؼه ً ٗ انخ ٕع Me Me P.samia انخ ٛ ػٕ ذٛت S.officinalis فـش Aspergillus sp 1
2 Pseudomonas sp gram (-)
Staphylococcus sp gram 7 يه ًخش 3 (+)
بكخٛشٚب (-) Klebsiella sp gram 4
5 Esherichia coli gram (-)
6 Condida
S.officinalis 10 . P.samia
Me (+) (-)
Staphylococcus sp S.officinalis
P.samia
91
S.officinalis :S P.samia PH M P.samia : PPH Puits P S.officinalis : PS
92
S
PS PPH P
1 P.samia
93
PH PS S
PPH
Pseudomonas sp gram (-) 2
94 PS PPHPH
M
PH S
PPH PS
S
M
PH S
10 Staphylococcus sp gram (+) 3 PPH P.samia 11 S.officinalis 7
95
PS
M PPH
S
P
Klebsiella sp gram (-) 4
P.samia S.officinalis 5
96 PPH PS
M
S
PH
S.officinalis 5
Esherichia coli gram (-) P.samia
P.samia S.officinalis
97
P PS
S PPH
6 Condida
98 Phlomis samia Salvia officinalis
: -I
Preliminary LD 50 test
5
Salvia officinalis Phlomis samia - II
Effect of both Salvia officinalis & Phlomis samia extract on thyroid gland
- 1
Body weight ; thyroid and relative thyroid weights
Salvia officinalis
ٔانخٛبؿت Phlomis samia 200
. )30(
31
200
17.45 17.08
200
36.71 54.57
24
200 Phlomis samia
99 Salvia officinalis Phlomis samia 30 200
Effect of both Salvia officinalis & Phlomis samia extract (200/mg/kg/day p.o for 3 weeks) and experimental hyperthyroidism on rat body weights.
L-thyroxine 0.3 ANOVA
SD ± ( n ):10=n SD
100 200 180 160 control 140 phlomis samia 120 salvia officinalis 100 hyperthyropidism 80 hyper+phlomis 60 hyper+salvia 40
Body weight (g) in weight (g) Body week first 20 0 301
250 ***
200 control * phlomis samia 150 *** salvia officinalis hyperthyropidism 100 hyper+phlomis hyper+salvia 50
body weight (g) body weight (g) in third the week 0 301
80 ** 60 ** 40 control phlomis samia 20 salvia officinalis
0 hyperthyropidism hyper+phlomis
differences (g) (g) differences 1 -20 hyper+salvia
-40
** -60 30
101 Salvia officinalis
200 Phlomis samia
)31(
P 0.001
% 211.22
% 117.10 108.09
( P 0.001 )
absolute
Phlomis samia Salvia officinalis
% 18.41 200 200 . % 21.27
(relative) %200.3
%47 Phlomis samia %94.38 200 %54.70 Salvia officinalis
102 Phlomis Salvia officinalis 31
200 samia . Effect of both Salvia officinalis & Phlomis samia extract (200/mg/kg/day p.o for 3 weeks) on rat body and thyroid weights.
L-thyroxine 0.3 ANOVA
SD ±
( n ):10=n SD
103 160
140
120 phlomis samia 100 salvia officinalis 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
body body weight (% of control) 20
0 311 1
250
*** 200 phlomis samia 150 salvia officinalis ### ### hyperthyropidism 100 hyper+phlomis hyper+salvia 50
0 absolute thyroid absolute weight (%of control) 31 1
250 ***
200 phlomis samia 150 salvia officinalis ## ### hyperthyropidism 100 hyper+phlomis hyper+salvia 50
relative thyroid relative weight (% of control) 0 131
104 -2
Body weight,liver weight and relative liver weight
3 200) Phlomis samia officinalis Salvia ( 32
%20 %79.94 Phlomis samia
%138 %125
Salvia officinalis
%87.48 Phlomis samia
Salvia officinalis %99.07
105 Phlomis Salvia officinalis 32
200 samia . Effect of both Salvia officinalis & Phlomis samia extract (200/mg/kg/day p.o for 3 weeks) on rats Body weight ,liver weight and relative liver weight.
L-thyroxine 0.3 ANOVA
SD ±
( n ):10=n SD
106 160
140
120 phlomis samia 100 salvia officinalis 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
body body weight (% of control) 20
0 321
120
115
110 phlomis samia salvia officinalis 105 hyperthyropidism hyper+phlomis 100 hyper+salvia
95
absolute liverabsolute weight (% of control) 90 321
160
140 *** 120 ## phlomis samia 100 salvia officinalis *** 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
20
relative liver relative wieght (%of control) 0 321
107 -3 Body weight, kidney weight and relative kidney weight:
Salvia officinalis
200 Phlomis samia
)10(
%144.4
% 165
%139.5 %162
108 Phlomis samia Salvia officinalis 33 200 .
Effect of both Salvia officinalis & Phlomis samia extract (200/mg/kg/day p.o for 3 weeks) on rats Body weight ,kidney weight and relative kidney weight.
L-thyroxine 0.3 ANOVA
SD ±
( n ):10=n . SD
109 160
140
120 phlomis samia 100 salvia officinalis 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
body body weight (% of control) 20
0 331
160 *** 140
120 phlomis samia 100 salvia officinalis 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
20
0 absolute kidney absolute weight (%of control ) 331
180 *** 160 140 120 phlomis samia salvia officinalis 100 hyperthyropidism 80 hyper+phlomis 60 hyper+salvia 40 20
relative kidney relative weight (% of cntrol ) 0 1 33
110 -4 Body weight, heart weight and relative heart weight : Salvia officinalis
200 Phlomis samia
)34(
%127
Phlomis samia %157 %138
Salvia officinalis
%123.61 Salvia officinalis
Salvia
%108.28 officinalis
%87.11 Phlomis samia
111 Phlomis samia Salvia officinalis 34 200 . Effect of both Salvia officinalis & Phlomis samia extract (200/mg/kg/day p.o for 3 weeks) on rats Body weight ,heart weight and relative heart weight.
L-thyroxine 0.3 ANOVA
SD ±
( n ):10=n . SD
112 160
140
120 phlomis samia 100 salvia officinalis 80 hyperthyropidism
60 hyper+phlomis hyper+salvia 40
body body weight (% of control) 20
0 341
140
120
100 phlomis samia
80 salvia officinalis hyperthyroidism 60 hyper+phlomis 40 hyper+salvia
20
absolute heart weight (% heart absolute of control ) 0 341
180 ## 160
140 ** 120 phlomis samia salvia officinalis 100 hyperthyroidism 80 * hyper+phlomis 60 hyper+salvia 40 20
relative heart weight ( %heart relative of control ) 0 341
113
-III Thyroid morphological and histological study
A35
B 35
114 Thyroid histological study
stroma 36
Endocrine cells Parenchyma
Trabeculae Capsule
Thyroid follicles
l’éosine-ématoxilne Stored colloïd
Interfollicular cell
200 S.officinallis
)37(
200 P.samia
)38(
0.3 L-thyroxine
)39(
115 L-thyroxine
S.officinallis 200
)40(
P.samia
)41(
116 )36(
●
Δ
● Δ
حكبٛش 100
◄ حكبٛش 400
● Δ
*
117 )انشكم 37 ( ي ٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌانؼًبيهت ب ًسخخهض S.officinallis بجشػت 200 يهغكهغ/
Δ ●
▲ ▲ *
▲ ●
حكبٛش 100
* ◄ ● ◄ Δ
حكبٛش 400
118
)انشكم 37 ( ي ٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌانؼًبيهت ب ًسخخهض S.officinallis بجشػت 200 يهغكهغ/
*
Δ
●
◄ ◄
حكبٛش 400 ◄ .جش ٚب ؿΔشٔا َ ٗ ، ● ان ُغ ٛج ػٔبء دي ٕ ٘ شؼش ٘ . *
119 )انشكم 38 ( ي ٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌانؼًبيهت ب ًسخخهض P.samia بجشػت 200 يهغ/كهغ ن ًذة ثال د اسبب ٍغ
Δ ◄ * Δ
Δ
حكبٛش 100
◄
* Δ
حكبٛش 400
◄
Δ *
120 )انشكم 39 ( يٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌ انؼًبيهت بًبدة L-thyroxine بجشػت 0.3 يهغ/كهغ ن ًذة ثالثت اسبب ٍغ
Δ Δ * ◄
Δ ●
●
حكبٛش 100
Δ ●
*
Δ
حكبٛش 400
121 )انشكم 39 ( يٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌ انؼًبيهت بًبدة L-thyroxine بجشػت 0.3 يهغ/كهغ ن ًذة ثالثت اسبب ٍغ
● * ◄ ◄
* Δ Δ
حكبٛش 400 ● ◄
Δ*
122 )انشكم 40 ( ي ٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌ انؼًبيهت بـ L-thyroxine و انخ ً حأخز جشػت 200 يهغ/كهغ ي ٍ يسخخهض S.officinallis
◄ Δ *
◄
حكبٛش 100
Δ ◄
*
◄ Δ حكبٛش 400
*
123 )انشكم 41 ( ي ٍكشوغشاف يمطغ نُس ٍج انغذة انذسلٍت ن ًج ًىػت انجشرا ٌ انؼًبيهت بـ L-thyroxine و انخ ً حأخز جشػت 200 يهغ/كهغ ي ٍ يسخخهض P.samia .
◄ ◄
Δ
حكبٛش 100
Δ
◄
*
حكبٛش 400 Δ ◄
*
124 : (T4,T3) - IV Serum thyroïd hormones T3,T4
Salvia officinalis
200 Phlomis samia T3 42 T4 T3
%84.37 Phlomis samia T3
%75 Phlomis samia
T3
%136.06 Salvia officinalis
%119.45 T4
Phlomis %98.30
Salvia officinalis samia T4 %918.99
% 97.35 Phlomis samia T4
% 126.10 Salvia officinalis
125 Phlomis Salvia officinalis 42
samia Effect of both Salvia officinalis & Phlomis samia extract on rat serum thyroid hormones
40 # # 35
30 *** control 25 phlomis samia 20 # salvia officinalis hyperthyroid 15 hyper+phlomis serum T3serum (pmol/l) 10 hyper+salvia 5 ***
0 1
70 *** 60
50 control *** phlomis samia *** 40 salvia officinalis
30 hyperthyroid hyper+phlomis
serum serum T4(pmol/l) 20 hyper+salvia
10
0 1
SD SD ± # P≤0.01 0.01 ANOVA
126 V- حمذٌش حأثٍش كهى ان ًسخخه ظ ٍ ٍ وحبنت فشؽ انذسلٍت انخجشٌب ً ػهى ان ًؤششاث انب ٍىك ًٍبئٍت انخبنٍت: blood glucose : 1
Salvia officinalis
Phlomis samia 43 %72.30 p=0.01
p=0.001 Phlomis samia
Salvia officinalis %65.21
% 72.41
%58.20 Phlomis samia
: creatinine 2 Serum creatinine, in differant groups of rats Salvia officinalis
creatinine Phlomis samia 44 0.05 ≤ p(
Phlomis samia %121.76
% 73.82 ) p 0.01(
creatinine
creatinine Salvia officinalis
Salvia officinalis % 86.14 Phlomis samia
80.36 %
127 )الشكل رقم Phlomis Salvia officinalis : )43 samia انسكش . انس كش Effect of both Salvia officinalis & Phlomis samia extract on rat serum glucose .
90 80
70 ** control phlomis samia 60 ** *** *** salvia officinalis 50 *** hyperthyroid 40 hyper+phlomis 30 hyper+salvia
serum serum glycemie(mg/l) 20 10 0 1
SD SD ±
#
ANOVA )P ≤ 0.01(0.01
128 )الشكل رقم Phlomis Salvia officinalis : )44 . creatinine samia Effect of both Salvia officinalis & Phlomis samia extract on rat serum ceatinine .
10 9
8 7 cotrol phlomis samia 6 *** salvia officinalis 5 hyperthyroid 4 hyper+phlomis 3 hyper+salvia
serom creatinine (mg/l) creatinine serom 2 1 0 1
SD SD ±
#
ANOVA P ≤ 0.01 0.01
129 serum cholesterol 3
Salvia officinalis
Phlomis samia 45
% 67.96 Phlomis samia
% 73.62 Salvia officinalis
% 63.36 ) p 0.001 (
Salvia Phlomis samia
) p 0.001( % 153.53 )p 0.01( % 145.49 officinalis
130 )الشكل رقم Phlomis Salvia officinalis : )45 . samia Effect of both Salvia officinalis & Phlomis samia extract on rat serum cholesterol.
120 ## # 100
*** control 80 *** *** phlomis samia salvia officinalis 60 hyperthyroid
40 hyper+phlomis hyper+salvia
serum cholesterol serum (mg/dl)cholesterol 20
0 1
SD SD ±
#
ANOVA P ≤ 0.01(0.01
131 Serum protides totaux 4
Salvia officinalis
Phlomis samia 46
) p 0.01(
Phlomis samia % 110.69 % 155.88
Salvia officinalis
% 114.30 ) p 0.05 (
% 102.51 Salvia officinalis Phlomis samia
. % 103.77
132 Phlomis samia Salvia officinalis 46 .
Figure (46)Effect of both Salvia officinalis & Phlomis samia extract on rat serum protides totaux
9 8 * ** 7 control 6 phlomis samia salvia officinalis 5 hyperthyroid 4 hyper+phlomis 3 hyper+salvia 2
serum protides Totaux (mg/dl)serum Totaux protides 1 0 1
SD SD ±
#
ANOVA P ≤ 0.01 0.01
133 LDL 5 Serum LDL Salvia officinalis
LDL Phlomis samia
47
p 0.01
% 73.16 Phlomis samia
Salvia % 61.11 p 0.001
officinalis
% 68.77 )p 0.001(
) p 0.05(
% 130.81 Phlomis samia
LDL
Salvia officinalis
134 Phlomis samia Salvia officinalis 47 .LDL
Figure (46)Effect of both Salvia officinalis & Phlomis samia extract on rat serum LDL
60
50 #
control 40 ** *** phlomis samia *** 30 salvia officinalis hyperthyroid 20 hyper+phlomis hyper+salvia 10 serum serum LDLcalcule (mg/dl)
0 1
SD SD ±
#
ANOVA P ≤ 0.01 0.01
6 135 HDL serum )HDL( Salvia officinalis
HDL Phlomis samia 48
HDL ) p 0.01(
% 77.61 Salvia officinalis % 79.89
) p 0.001(
135.45 Salvia officinalis % % 89.66 HDL
% 93.15 Phlomis samia
Phlomis samia
Phlomis samia Salvia officinalis 48 136 . HDL Figure (47)Effect of both Salvia officinalis & Phlomis samia extract on rat serum HDL
45 ### 40
35 ** ** control 30 phlomis samia 25 salvia officinalis 20 hyperthyroid 15 hyper+phlomis hyper+salvia 10
serum cholesterol HDL(mg/l) cholesterol serum 5 0 1
SD SD ±
#
ANOVA P ≤ 0.01 0.01
: 7 137 Serum tri glycerides Salvia officinalis
Phlomis samia 48
p 0.01
Phlomis % 135.41
p 0.001 samia
% 142.12
% 83.89
Salvia officinalis
%123.37 % 115.67 Salvia officinalis Phlomis samia
Phlomis samia % 86.8 % 81.38
Salvia officinalis
)شكل رقم Phlomis Salvia officinalis : )49 138 . samia
Effect of both Salvia officinalis & Phlomis samia extract on rat serum Tri Glycerides
90 *** 80 ** 70 control 60 phlomis samia 50 salvia officinalis 40 hyperthyroid 30 hyper+phlomis 20 hyper+salvia
serum serum Trigcerides (mg/dl) 10 0 1
SD SD ±
#
ANOVA P ≤ 0.01 0.01
salvia oifficinalis VI phlonis samia
139 Effect of salvia officinalis and phlonis samia on liver .kedny and heart, antioxydant status . Hepatic antioxidant status 1
p 0.05 50
Phlomis CAT
samia
. p 0.001
p 0.001 CAT
Phlomis samia .
p 0.05
Salvia
p 0.001 officinalis
Phlomis samia
50
Phlomis samia Salvia officinalis
Effect of salvia officinalis and phlonis samia on liver antioxydant status . 140
SD SD ±
#
ANOVA P ≤ 0.01 0.01
141
180 *** 160
140 control 120 ### phlomis samia 100 ### salvia officinalis 80 hyperthyropidism 60 hyper+phlomis 40 hyper+salvia
liver lipid (µmol/g)peroxides 20 0 1
70 ### 60 control 50 # * phlomis samia * 40 salvia officinalis
30 hyperthyropidism hyper+phlomis liver CAT (K/g) liver (K/g) CAT 20 hyper+salvia 10
0 1
kidney antioxidants status 2
142 : )51(
p 0.001
p 0.05
Salvia officinalis
p 0.01
p 0.05
Salvia
officinalis
Phlomis
samia
143
Salvia 51
Phlomis samia officinalis
Effect of salvia officinalis and phlonis samia on kedny antioxydant status .
SD SD ±
#
ANOVA P ≤ 0.01 0.01
144 140
120 * # control 100 phlomis samia 80 salvia officinalis * 60 hyperthyropidism hyper+phlomis 40 hyper+salvia 20 kidney kidney lipid (µmol/g)peroxides 0 51 1
80 *** 70 ** * 60 ### control 50 phlomis samia salvia officinalis 40 hyperthyropidism 30 hyper+phlomis
kidney CAT (k/g) (k/g) kidney CAT 20 hyper+salvia
10
0 511
heart antioxidants status 3 52 145 p 0.01
Phlomis samia
Salvia officinalis
p 0.001
Salvia officinalis Phlomis samia
p 0.001
Salvia
p 0.05 officinalis
Phlomis samia
146 52
Phlomis samia Salvia officinalis
Effect of salvia officinalis and phlonis samia on heart antioxydant status .
SD SD ±
#
ANOVA P ≤ 0.01 0.01
147
200 180 *** 160 ### ### control 140 phlomis samia 120 salvia officinalis 100 *** hyperthyropidism 80 *** hyper+phlomis 60 hyper+salvia 40
Heart lipidHeart (µmol/g)peroxides 20 0 521
35 # 30 control 25 phlomis samia 20 salvia officinalis ** 15 hyperthyropidism hyper+phlomis Heart CAT (k/g) (k/g) CAT Heart 10 hyper+salvia 5
0 521
148 sulfahydryl (NPSH) 2
sulfahydryl (NPSH) 1 2 انكبذ ٌت 53
Salvia officinalis GSH
P ≤ 0.001 200
GSH
GSH
Salvia officinalis
Phlomis samia GSH
sulfahydryl 53 (NPSH) انكبذٌت
6 ***
5 control 4 phlomis samia # salvia officinalis 3 hyperthyropidism ** 2 hyper+phlomis hyper+salvia 1 Liver Liver GSH (umol/g tissue)
0 153
SD SD ±
#
ANOVA P ≤ 0.01(0.01
149 sulfahydryl (NPSH) 2 2 ف ً انكهٍت
54 GSH
GSH
L-thyroxine
GSH Salvia officinalis
sulfahydryl 54 (NPSH) ف ً انكهٍت
4,5 ## 4 3,5 control 3 phlomis samia 2,5 ** salvia officinalis 2 hyperthyropidism 1,5 hyper+phlomis 1 hyper+salvia
Kidney GSH Kidney (umol/g tissue) 0,5 0 541
SD SD ±
#
ANOVA P ≤ 0.01 0.01
150 sulfahydryl (NPSH) 3 2 ف ً انمهب GSH GSH GSH
Phlomis samia ،
Salvia officinalis 55 sulfahydryl 55 (NPSH) ف ً انمهب
4,5 4 3,5 ## control 3 phlomis samia 2,5 salvia officinalis 2 *** hyperthyropidism 1,5 hyper+phlomis 1 hyper+salvia
Heart GSH (umol/g Heart tissue) 0,5 0 551
SD SD ±
#
ANOVA P ≤ 0.01 0.01
151
O2
4 O2
Hydrogene Anion superoxide radical (O2.) (ROS)
. Hydroxyl radical ( OH) peroxide (H2O2)
ROS 20
Superoxide dismutase (SOD)
15 Vit E Ascorbate
20
20
134 21
T3 T4 )250( 11 129
122 123
152 20 23
125
Endemic colloid goiter 113 230
Isoflavones 229
Soybean 128
2
Flavones Flavans Aurones Chalcones
133
)126( )13( Thyroid peroxidase (TPO)
P-coumaric 231 126 232 233
Salvia Phlomis samia 124 125 … officinalis
153 S. officinalis P. samia
3 200
225
188
3000 200
8000 192 177 P. samia lamiaceae
S. officinalis
P. samia S. officinalis
. gallic acid
Alcl3
Rutine quercitin
quercitin Rutine .
DPPH 212 202 203 201
DPPH 204 203 205
154 DPPH
(2.2’diphenylpicrylhydrazyl)
DPPH 217 214 diphenylpicrylhydrazine 214
DPPH
. BHT Phlomis samia Salvia officinalis
0.001± 0.017 IC50 Salvia officinalis
IC50( Phlomis samia =0.033± 0.009 يهؾ (يم/ BHT
0.032 ±0.066 مهػ (مم/ . (مم/ مهػ S. officinalis
1990 و )S. officinalis )188
(EC50 S. sclarea ug/ml 41
(EC50 =80 ug /ml) S. lavandulifolia (EC50 =50 ug /ml) S. triloba، =45 ug /ml). rosemary abietane
)rosmarinic acid( caffeic acid )189()carnosol ٔ carnosic acid ( )190(
)191(
Salvia sclareol ferruginol camphor cryptotanshinone )222،223(
ortho- Rosmarinic acid
position
antitumor HIV-1
lipoxygenases
cyclooxygenases
155 Xanhine )224،210( α tocopherol trolox
Oxidase
-1 1/2 561mg kg LD 50 )t =9min(
98
Samioside 2001
DPPH Phlomis samia
Phlomis 7 . 200
chrysoeriol rutin 5 DPPH caucasica acteoside naringenin chrysoeriol 7-O-glucoside ، kaempferol 3-O-glucoside 7-O-rutinoside
4.97 IC50 forsythoside B
199 4.27 ug /ml
DPPH 206،207،201
DPPH
BHT butylated hydroxyamidol
TBHQ BHT TBHQ tert-butylhydroquinone
liver damage
)208،209()211 ،210 (
.)201(
1 . . O 2 OH O 2 )195( )197،95(
BHT
B-carotene/linoliec acid
B-carotene
linoleic linoliec B-carrtene
156 diallylic methylene
B-carotene
(chromophor)
linoliec )218 ،214(
Lamiaceae )214(
salvianolic carnosic acid rosmarinic acid sage
methyl carnosate rosmadial epirosmanol rosmanol carnosol acid )224،
rosmanol )226 )228( )227(
. ROS ArO aroxyl radicals
ascorbate
.)178( Glutathione ascorbate αtocopherol
4000
microphlora Aglycone )176( )221(
low lipoprotein LDL )181(
220
157 LDL
176 atheroxlerose
B انت ً تعذل خذر peroxyl و peroxynitrite
B catechol
3’,4’ catechol 3 OH peroxynitrite
O-methylation 10 4 3 2
. )187()221( carnosol S. officinalis
rosmadial genkwanin caffeic acid carnosol carnosic acid rosmarinic acid
)196( rosmanol
carnosol carnosic )194،193،95(
P.samia
)99.97 %(BHT 97.05 % linoleic
S.officinalis )85.69 %(S.officinalis
% 56-53
. % 56-48
Phlomis Phlomis megalantha Diels
umbrosa Turcz
linoleic
158 protocatechic rosmarinic acid )198(
S.officinalis P.samia Rutine quercitin
97
P.samia S.officinalis
Pseudomonas P.samia S.officinalis
Aspergillus sp Condida Klebsiella sp (-) sp gram (-)
S.officinalis
Staphylococcus sp gram 7
Esherichia coli (-) )-(
mucopolysaccharides )+(
147 mucopolysaccharides peptidoglycanes
159 Staphylococcus sp
salvia
pseudomonas sp clavibacter sp hydrangea
salmonella klebsiella staphylococcus sp
salvia 79 1,8 cineole camphor
P.samia
200 Salvia officinalis Phlomis samia
3
3 L-thyroxine (0.3 mg/kg body weight)
T3 T4 thyroglobuline L thyroxine 119 250
Phlomis L–thyroxine
Salvia officinalis samia
body weight T3 14
gaine 2 3 52،119،120،127،248 .
160 Adipocyte direved (Adiponectine)
glyconeogenesis
T4 134
Browne adipocyte culture 134 20
120 17 33
diodirat
1916
L-thyroxine desoxycorticosterone
%50 30%
L-thyroxine
3 40 30
244 hypertrophy parenchyma
L-thyroxine
mitosis hypertrophy
Lumina
hyperplasia hypertrophy
244 thyroxine androsterone estradiol
161 L-thyroxine
E sinozoid spaces 242 %10 5
stereospecific transport
Albumin prealbumin thyroxine binding globuline % 90
118
rT3 T3
sick euthyroid syndrom
rT3 D3 rT3 T3 T3 T4 D1
rT3: T3 T3
rT3 : T3 rT3 T3
T3
intrinsic
cirhotic thyroid disease
T4
free T4
T4 : T3 T4
162 T3 T4 D1
thyrotoxicosis
cholestatic
ALT( alanine aminotransferase) AST( Aspartat amino transferase) 37 27
(kupffer cell hyperplasia) kupffer
isocitrate perivenular centrizonal necrosis
dehydrogenase
thyrotoxicosis
17 glutamyl trans- peptidase % 64 Alkaline phosphate
cholestatic %5 bulirubine %
LDL
(TH ،LDL (low density lipoprotein
HDL Apoprotein A1
Atheroscelerosis
Arrhythmias
163 Thyronine (3’,5 diodo-3aryl substituted)
TR1
dimethyl-isopropyl-benzylphenoxy acetic acid TH (GC1)
TRB
TRα
238
increase heart rate cardiac out put
decrease peripheral resistance 115 15
cardiac hypertrophy 15
164 ß
cathecholamine
ROS 136 122 %10 5%
Euthyroid
ß blockade
T3
α1 T3 α2 56 α natriuritic peptid ß و 23
T3
12 T4 . T3 236
165
236 56
NR: triiodothyronine nuclear receptor; TRE: thyroid hormone responsive element.
licopus SP
L-thyroxine 5
130 etenolol
T3 T4 % 519 % 918 52 115 135
166 200 P.samia S.officinallis
)150( )158( 149 )138( 163(
)233(
oxygene consuption
248
4 100 T4
TSH
262
167 TSH
9 5 24 12 T4
TGB T4
TGB
Prealbumin
TGB
TGB T3 Prealbumin
T3
10 T4
14 TSH
S.officinallis
TSH
L-thyroxine T4 T3
30 2 sulfonamide
168 263
TSH
TSH
P.samia
T3 200
TSH T3
263
T3 T4
D1 TPO
T3 T4
S. P. samia
T4 T3 officinalis
3 200 P. samia
L–thyroxine T3 3 0.3
T4
15 15 propulthioracil 0.025 253 113،120
169 254 28 I 5 deiodinase 255 8
Phlomis samia
P. samia L–thyroxine
L–thyroxine
T4
T3
TRH TSH
Hypothalamus
T3 T4 P. samia
Aegle
B. monmmieri Aloe vera Bocopa monmmieri marmilor
T4
246 PTU %62 T3 Aegle marmilor
P. samia
170 5’-deiodinase annona squamosa
quercetin
decrease thyroid hormone
131 dependant function
African millet
peroxidase 245
50% D1
catechine 13 micro M quercitin 11 micro M baicalain 70 micro M fistin 68 micro M rutin 55 micro M morin 17 micro M
77 micro M kaempherol )240(
Soy
Genistin Soy )241( peroxidase
TPO minocycline .)252(
phloritin luteoline quercitin
(5’D1)5’- iodothyronine deiodinase
(T3) 3,3’,5’ triiodothyronine prohormone thyroxine(T4) deiodinase 25
EMD (21388)
5’D1 EMD (21388)
T4
T4 TTR (thyroid binding prealbumine)
171 EMD TBG T4
T4 T4 TTR (21388)
T4
T4 TSH
TSH EMD (21388) TSH
EMD (21388) T4 T4
T3 5’D1 TSH .)242(
EMD (21388)
.)251( T4 T3
iodide
T3 T4 organification
iodine deficiency
EMD (21388) 100
20 umol/ kg body weight )251( 25ugKI/day
EMD 21388
5’-D1 T4
EMD 21388 T4 T3
T3
T4
bromid EMD 21388 EMD49209
172 T4 I131 EMD49209 I 125 I EMD49209 14 EMD49209
T4
T4 TTR EMD49209
glucoronic acid
)245( T4
T3 T4 EMD (21388)
T4 rT3 T3
)251( PTU methimazole
. Phlomis samia
T3 Salvia officinalis
l –thyroxine
Salvia officinalis 200
L–thyroxine
Salvia officinalis Phlomis samia
173 S. officinalis P. samia
L–thyroxine
Salvia officinalis
Salvia officinalis
70 Streptozotocin 92
Phlomis samia
Salvia officinalis P.anisodonta
Phlomis
Stegmasterol 145
T3 T4 butea monosperma
Insuline glucose 6 phosphatase
)129(antiperoxidase
P. samia
)129( catalase
)112( )111( )116(
)4(. diabete mellitus
L–thyroxine
créatinine
Phlomis
174 créatinine
Creatinine
Creatinine phosphate Creatinuria phosphate
ATP ADP )4(
LDL (low densety lipoprotein HDL (hight densety lipoprotein cholesterol)
cholesterol)
hyperglycenemia
Diabete NO. 5’-deiodinase α amylase
mellitus
ß NO.
Diabette mellitus
TH )124( hypothyroidism
Adenyl cyclase AMP system
Glycocorticoids Glycagon Catecholamines
4
atherosclerosis LDL HDL 124
HDL LDL atherosclerosis
HDL
175 B NO. cholesterol
cholesterol
Phlomis samia
cholesterol LDL
HDL LDL
Methimazol 6 HDL LDL 112 124 127
118 L-thyroixine Hashimot’os thyroiditis
S.officinalis P.samia
lipo protein lipase
NADH2 FADH2
15 Citric acid Acetyl COA
4 Lipoprotein Lipase 112 118
176 Phlomis samia
thyroid dectomized
L-thyroxine Glycine (N13)
thyrotoxicosis 4
Phlomis
Salvia officinalis samia
GSH GPx SOD
24 100 0.4L-thyroxine
H2O2 SOD GPx .- GPx O2 GPx SOD
129 GPX SOD SOD
% 25 16 Basal metabolic rate BMR 21
3,3’,5 3.5diiodothyronine (3,5 T2)
(cytochrome C triiodothyronine (T3)
oxidase)
177 T3 21
Xanthine oxidase
21 (NOS)
.- O2
Follicular adenoma Follicular carcinomas Grav disease GPx XOR (xanthine oxidase)
Follicular
papillary carcinoma MDA adinoma
Grave desease papillary carcinoma H2O2 NADPH SOD
TPO iodothyronine
H2O2 SOD
TPO GPx
GPx H2O2
GPx
243 كما أن ت دارب أخزي أظهزث أن
. . OH H2O2 O2
serum aspartate 121 T3 120
serum alanineaminotransferase(AlaAT) aminotransferase (ASPAT)
178 121
B carotene 129 (ischemia/repezrfusion)
Retinine A
4 Ascorbic acid B12 Riboflavine Thiamine
GPX SOD CAT
125
H2O2 100
H2O2 100 H2O2 33
(catalase enzyme)
L-thyroxine L-thyroxine
118 Hachimot’os thyroiditie
T4 Hachimot’os thyroiditie
L-thyroxine %126.9
)112( 5 % 0.0012 . SOD H2O2 O2 H2O2
H2O2 )118(
179 12 L-thyroxine
)122( . O2 SOD )122(
)40( 15 10 5 L-thyroxine 0.3 10 100 10 )45( 12
GPx CAT )248(
Propilthioracyl
H2O2 28
30 Methimazole Ophtalmopathy 3 17 5
T3 H2O2
H2O2 H2O2
ß
GPX T3
121 down regulation of the catalase expretion
200 P. samia
quercetin S. officinalis
180 131
quercetin
TBARS
S. officinalis ; P. samia
TBARS 122 125 122
125
TBARS
52
MDA 2.53 5.84
247 MDA E
1. oxygene O
singulet
. H2O2 O2 superoxide anion 118
GPx
TBARS 248
181 125 Thiol
S. officinalis
P. samia
TBARS
TBARS
(Euthyroid)
E 125
121 TBARS
)122( GSH
glycine cysteine glutamat
GSSG GSH H2O2 GPx .)113(
NADPH GSH GR
)121( ROS GSH
GSH GST
GSH NADPH GSH
GST )121( H2O2
L-thyroxine )122( كما و
GR GST GPX
GSSG GSH
GSH )121( SH
peroxides
182 T4 )118( hydroperoxide
GSH T3
GSH 121 T3 T4
.)118( GPx
GSH
GSH
GSH )113(
GSH T3
)239(
GSH
)113( PTU
GSH %21 %46 GSH
myocardium %82 GSSG :GSH mg/l 12 )122( ٔ ْز ِ االخٛشة ي ٕافقت نًب
GSH
. L- GSH thyroxine GSH : GSSG GSSG ADN GSH PTU
)239( 15 % 0.04 methemazole
183 GSH S.officinalis
L-thyroxine
P.samia S.officinalis
.)239(
E
GPx GSH
1 E 500 mg/kg
GSH 24 21 18 14 11 7 4
GSH
GSH E
)121( GSH E
GSH
GSSG GSH GSH GSH
T4 GSH
T3
GSH
184
T4 T3
5% Goiter
P. samia S. officinalis
wistar albino
L-thyroxine 3 0.3 3 200
185 P. S. officinalis; samia
L-thyroxine
P. samia
S. officinalis
P. samia S. officinalis
Antigoitrogenes
. TBARs Salvia officinalis P. samia S. officinalis P.samia
186
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206
Iodine uptake 1
Hydroxylation 2
Iodide trapping 3
Iodothyronine deiodinase 4
Reactive oxygen species 5
Reactive nitrogen species 6
Tumors 7
Blood vessels 8
Autoimmune thyroid desorders 9
Isthumus 10
Thyroid hormones biosyntheses 11
Feed back 12
Radical scavenger 13
Peroxidative damage 14
Residues 15
Thyroglobulin (colloid) 16
207 Experimental hyperthyroidism 17
Parafollicular cells 18
Experimental studies 19
Goiter -20
Thyroid goiter 21
Endemic goiter 22
Blocage of iodine uptacke 23
Oxidative injury 24
Blood pressure 25
Antithyroid agents 26
Basement membrane 27
Hyperthyroidism 28
Hypertrophy 29
Lipoperoxidation 30
Hydrogen peroxide 31
Hypothyroidism 32
Primary hypothyroidism 33
Central hypothyroidism 34
Serum cholesterol 35
208 Hight density lipoprotein 36
Low density lipoprotein 37
Connective tissue 38
Growth 39
Thyroid hormon 40
Hypothalamus 41
209
English summary
Extracts antioxidant properties of some Algerian medicinal plant and their effect on the thyroid activity and the related organs.
The thyroid gland is one of the largest of endocrine tissues and the only one to function as an purely as an endocrine gland by producing thyroid hormones , thyroxine (T4) and triiodothyronine (T3) , with essential for normal growth and development of the central nerves systems (CNS) and metabolism, by increasing basal metabolic rate (BMR) , this involves an increase , en carbohydrate metabolism and increase in the synthesis. goiter is a diffuse or nodular enlargement of the gland usually resulting from ,benign process or a a process of unknown origin that attack no less than 5 % of word’s population , most of them located in developing countries , many of these are associated with other disorders and constitute a major public health problems .disorders affecting thyroid function resuit in rather hypothyroidism or hyperthyroidism , the effect could at any level of the pituitary thyroid axis. hyperthyroidism is the condition reflecting excess thyroid hormone section the most common situation of hyperthyroidism is grave’s disease , an autoimmune disorder in wich the body produces thyroid stimulating immunoglobulin (TSI) , TSI stimulates both growth and secretion of thyroid gland in manner similar to TSH , however, unlike TSH , TSI is not subject to negative feed back inhibition .A prominent feature of grav’s disease is exophthalmoses , or bulging eyes and a hypersecreting thyroid tumer and excess TRH secretion are less frequent causes of hyperthyroidism could result from (a) primary failure of the gland , or it could be secondary to (b) deficiencies in thyrotropin releasing hormone (TRH) , TSH , or both , altematively , it could arise from (c) a dietary iodine deficiency ,iodine deficiency and hashimot’os throiditis , an autoimmune disorder , are the most frequent causes of hypothyroidism . Ase thyroid hormones essential for normal growth and central nervous development , hypothyroidism at birth leads to creatinism , a condition characterized by dwarfism and mental retardation .
I Hypermetabolic state in hyperthyroidism is associated with tissues oxidative injury a available data indicate that hyperthyroid tissues exhibit an increased ROS and RNS
production , the increase mitochondrial ROS generation is a Sid effect of the enhanced level of electron carriers , by which hyperthyroid tissues increase their metabolic capacity . Phlomis bovei , syn. Phlomis samia and Salvia officinalis, both frome Lamiaceae family, are algerian endemic medicinal herbs traditionally employed to treat fever, Indigestion , diabetes, in -flammatory processes and hyperthyroidism. Hyperthyroidism is known to involve oxidative stress witch lead to several molecular damages. These damages may be managed by natural antioxidant products such as polyphénols and flavonoids. Flavonoids are widely distributed in plant-derived foods that have a variety of biological activities including antioxidant effects and antithyroid . It has previously been reported that the consumption of flavonoids and other xenobiotics by experimental animals reduced both thyroid iodide ion uptake and TPO activity, producing enlargement and histological changes in the thyroid gland However, there are only few studies about the pharmacological effects of this plant, and there seems to be no information about the possible antioxidative or antithyroid capacity of Phlomis samia and Salvia officinalis So the aim of this study was to determine activity antioxidant and antithyroid of both Phlomis samia and Salvia officinalis. In conclusion The present data clearly show that administration of P. samia crud extract has a antithyroid effect by decreasing T3 and T4 concentration with may be antigoitrogenic effect of both P. samia and S. officinalis by decreasing relative thyroids weight in rats suffering from experimental hyperthyroidism .and it’s hypoglycaemic effect managed a hyperglycemias caused by hyperthyroidism cases . In adition to this prosperity , data shown a strong antioxidant and scavenger activity by inhibition lipid peroxidation .
II
Résumé en langue française
Titre de la thèse : Les propriétés antioxydantes des extraits de quelques plantes médicinales Algérienne et leur effet sur l’activité de la glande thyroïde et les organes luis sont relier.
La glande thyroïdiennes c’est l’une parmi les tissus endocrinienne la plus large, elle est la seule qui à la fonction pure endocrinienne , sa fonction principale et de produire les hormones thyroidienes , thyroxine (T4) et triiodothyronine (T3) , ses sécrétions ne sont pas indispensables pour la vie bien qu’elles sont nécessaires pour le développement et la maturation et à la différenciation de nombreux tissus, en particulier du cerveau et du squelette. Les secrétions débutent pendant le 3em mois du développement de la vie fœtal Le synthèse des hormones thyroïdiennes dépend de façon critique d’un apport exogène d’iode très variable dans l’alimentation . Les hormones thyroïdiennes augmentent le niveau de métabolisme de base , contrôle les hormones de croissances et du développement . le manque de la synthèse , la sécrétion des hormones thyroïdiennes causent le retard de croissance ,l’obésité , la diminution de la fertilité et l’hyperplasie (goitre). le goitre touche plus de 5% de la population mondial , surtout dans les pays sous- développés , l’hypersécrétion des hormones thyroïdiennes favorise la surconsommation de l’oxygène au niveau des mitochondries tissus cibles et la surproduction des radicaux libres causant les dégâts de stress oxydatif et probablement responsable des perturbations immunitaires . les flavonoides et les les polyphenol ont un effets sur la glande thyroïde et la prévention du stress oxydative . les Extraits des plantes médicinales riches en flavonoid et polyphenol ont été utilisés en médicine traditionnelle pour le traitement des perturbation de la glande thyroïdienne et sa sécrétion sans base scientifique réelle.
I
le but de notre recherche et d’explore les effets des extraits pour traiter la glande thyroïdienne chez des rats soufrant d’une expérimentale hyperthyroïdisme .qu’ont à provoquée par une injection ip de 0.3 mg/kg L-thyroxine pendant 30 jours.à des rats normaux conclusion : -durant nos recherches l’analyse des resultas pratiques demontre que chaque extrait à une action antioxydant et un pouvoir de pieger les ROS avec efficacité Nous avons remarqué une régression apparante du poids des rats ciblés et des augmentations du poids de la glande thyroïdienne , du foie et des reins ceux qui confirment l’expérimentale hyperthyroïdisme . la régression des concentrations des hormones thyroidiennes dans le sérum , et la stabilité du poids des rats traités par l’extrait méthanolique Phlomis samia , prouve L’effet antithyroid l’extrait de Salvia officinalis à un pouvoir sur l’augmentation des concentration des hormones thyroïdiennes sans influence sur le poids de la glande thyroïdienne. les resultats demontrent que les extrait des deux plantes(Phlomis samia et Salvia officinalis) ont un pouvoir sur régression des poids de la glande thyroïde chez des rats soufrant d’un expérimental hyperthyroïdismes ce qui confirme une action antigoitrogene . en ce qui concerne le système de défense antioxydant , les résultats prouvent que les l’extraits des deux plants favorisent la diminution des marqueurs de la lipide peroxidation dans le foie, le cœur.et additionelement l’extrait Salvia officinalis à une influance sur la diminution du TBARS au nivaux des reins En conclusion les resultats positifs decouvert durant nos recherches nous encouragent à les diversifier et les meltiplier pour identifier les composants chimiques respansable de ces influence afin de modifier les traitements médicaux actuels par des traitement naturels .
II : : : :
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T4 T3
Goiter 5%
Salvia officinalis Phlomis samia wistar albino
Phlomis samia Salvia officinalis
Phlomis samia Antigoitrogene activity
: Phlomis samia Salvia officinalis
: