تٍؼيبجنا تُسنا
2008
-2009
و
ٍ ٍ خٌشئاضجنا ٍ ٍ خٍبطنا ٍ ٍ خخبُنا ثبمخشً ن ذسكأخهن ةدبؼً نا ضئبظ خنا
Salvia officinalis
و
Phlomis samia
ؽبشَ ىهػ بهشٍثأحو
تللاؼنا ثار ءبؼػلأا و تٍلسذنا ةذغنا
ثبٌىخحً نا
VI
IX...
..
X
1
I
3
1
تٛقسذنا ةذـ نا
3
1
1
3
1
2
3
2
3
2
1
4
4
.
4
.
5
2
2
.
6
2
3
.
7
2
4
..
8
2
5
..
9
2
6
..
.
9
.
9
10
10
10
(PTU) Propylthioracyl11
iodides11
11
11
12
12
……….
12
II
13
1-II
13
1
13
2
13
3
14
2-II
15
1
15
1
1
15
16
1
2
16
1
3
16
1
1.3
16
1
2.3
17
1
3
3
18
1
3
4
19
1
3
5
201
-3
.
NAD(P)H oxydase 6
...
20
1
-
3
.
7
Xanthine oxidase
20
1
4
21
1
4
1
21
1
4
2
22
1
4
3
ADN23
1
4
4
24
2
24
2
1
25
superoxide dimutase (SOD)
25
catalase enzyme (CAT)
26
Glutathione peroxidase26
2
2
28
2
2
1
28
2
2
2
29
2
2
3
E29
2
2
4
C29
2
2
5
30
2
2
6
30
Glutathione(GSH)
33
34
Thioredoxine
...
34
34
35
III
37
1
37
2
37
3
37
4
40
5
41
6
41
7
41
8
42
9
42
IV
Phlomis samia
44
1
44
2
46
3
46
4
48
50
50
55
60
تساسذنا
تٛئبظ د لاا
.
....
...
79
85
152
185
187
209
207
I
I
DPPH
1
1
2
(1.1-diphenyl 2-picril-hydrazyl)CAT
catalasedl
DeciliterC°
Degre celcusDNA
Deoxyribonucleic acidGSH-Px
Glutathione peroxidaseg
GramHb
HeamoglobinHDL
High density lipoprotein cholesterol
Cholesterol
Cholesteroli-p
IntraperitonialKg
KilogramL
literLDL
Lower density lipoprotein
Cholesterol
Cholesterolµg
Microgramµmol
Micromolmg
Milligramml
MillitermM
Millimolarmmol
MillimolM
MolarMPO
MyeloperoxidaseNPSH
Non-protein sulfhydryl SulfahydrylODstand
Opticaldensity of standardODtes
t
Optical density of test%
Percent
p-o
Per.Os
RNS
Reactive Nitrogen species
ROS
Reactive Oxygen species
GSH
Reduced glutathioneSH
SulfhydrylSOD
Superoxide dismutaseT4
Tetraiodthyronine(thyroxine)T3
TriiodothyronineTPO
Thyroid peroxidaseTSHBs
Thyroid stimulating autoantibodies
TSHr
TSH
Thyroid stimulating hormone (thyrotrophine)
TBARs
Total thiobarbituric acid
D1
Type 1 iodothyronine deiodenase
U
UnitV
VolumW
WeightLgh
Liver weightHgh
Haert weightKgh
Kideny weight1
...
7
2
تـ شُنا تُٛ ٛ جٛ غكلاا عإ َ لاا
...
15
3
SOD
...
16
4
Natural antioxidants
...
25
5
(
SOD
)
...
26
6
...
40
7
SOME
ٗ ئبًنا ضهخخغً نأ
SOI
...
41
8
P. bovei...
..
.
47
9
...
.
.
...
85
10
S.officinalis . P. bovei...
91(
1
)
تٛقسذنا ةذـ نا غػٕ ح ٌ بكئ شٓظي
...3
(
2
)
تٛقسذنا ثبَٕ يشٓهن ٘ ٕ ٛ ذ نا قٛ هخخنا م د اشي
...6
(
3
)
وضٛنٕببخٛي
T4
تٛبلاقخعلاا ّ جحإ َ ٔ
……… . …… ... … .. …...………… ...8
(
4
)
ٖ ذغكبخنا دبٓجلإا
...14
(
5
)
تٛغفُخنا تهغهغنا ثاذقؼي شبػ ةشذ نا سٔزجنا م كشح غقإ ي
...17
6
…… ... ……….…… ... … ...21
7
ولاا ع بًد لأا بٛ ظ ح ٙ خنا ٙ خنا ثاشٛـ خنا تؼٛبؿ
٘
ٍ ٛ حٔشبهن تٛبَبجنا م علاغهن تَٛ
سٔزجنا وٕ جْ ذؼب
ةشذ نا
...22
(
8
)
ـنا تئٚضج تكهٓ ح
ADN
...23
9
ذغكأخهن دبؼً نا وبظُ هن شٛثأخنا ثبٛنا غ ؼب
...27
10
tocophérol -α ...29
11
C
.
...30
(
12
)
تُٛ بنا
تٛعبعلأا
ثاذٚ ٕ َ ٕ فلافهن
... .. .31
(
13
)
ـنا تُٛ ب
Quercetin
...31
(
14
)
وبغقأ
اذٚ ٕ َ ٕ فلافنا
ث
...33
(
15
)
ثببُن تٛفاشؿٕ حٕف سٕط
Salvia officinalis
. ...39
(
16
)
ثببُن تٛفاشؿٕ حٕف سٕط
Phlomis samia
. ....
45
(
17
)
ثببُن تٛئبًٛكنا ثبَٕ كً نا غ ؼب
Phlomis samia
. ....
46
18
ثبَٕ كً نا غ ؼبن تٛئبًٛكنا ؾٛظ نا
.
...47
19
صلاخخعلاا تٛهً ػ م د اشي
...61
20
ٗ ُ ذ ُ ً نا
ٙ عبٛقنا
ـهن
quercetine
ٔ
rutine
. ...63
21
كٛ نبـنا غ ً ذ ن ٙ عبٛقنا ٗ ُ ذ ُ ً نا خػٕ ٚ
. ...64
22
ٗ ُ ذ ُ ً نا
ٙ عبٛقنا
ـهن
BHT
. ...66
23
عٕ َ ٍ ي سٕغجنا ٌ ٕ كح
MDA-TBA
. ...77
24
ٗ ُ ذ ُ ً نا
ٙ عبٛقنا
ـهن
MDA
. ...79
25
ٗ ُ ذ ُ ً نا
ٙ عبٛقنا
ٌ ٕ ٛ ثبخهجهن
glutathione
لضخخً نا
(GSH)
...82
(
26
)
A
تٛهكنا لٕ ُ ٛ فنا ثاذٚ ذػ تًٛ ك
ٙ ف
ؾهي ٍ ٛ ٛ حببُنا ٍ ٛ ظ هخخغً نا
ئفبكي
غ ً ذ ن
كٛ نبـنا
/
فبجنا ٌ صٕنا ٍ ي ؽ
.
...86
B
ؾهي ثاذٚ ٕ َ ٕ فلافنا تًٛ ك
غ ً ذ ن ئفبكي
ٍ ٛ خٚشنا ٔ ٍ ٛ خعشكنا
/
ٍ ي ؽ
ٌ صٕنا
... ..86
(
27
)
ـنا سزج ؾٛ بثح تبغَ
DPPH
ـنا ٍ ي م ك ضٛكشخن بؼبح
BHT
ضهخخغي ٔ ٙ عبٛق ذٚ ٕ َ ٕ فلاف
Salvia
officinalis
ٔ
Phlomis samia
...88
B
لا
ـن ؾبثًنا ضٛكشح
50
%
سزج ٍ ي
DPPH
...88
(
28
)ا
غ ً د ةذغكلأ ؾبثًنا ؽبشُن
linoléique
ٍ يضنا تنلاذب
. ...90
(
29
)
A
ٔ
B
ذُ ػ تٛحببُنا ثبظ هخخغً هن ةذغكلأن ةدبؼً نا تٛؿبشُنا ىٛق
24
تػبع
...92
30
Phlomis samia Salvia officinalisـب
200
...101
(
31
)
Salvia officinalis Phlomis samia200
...104
32
Salvia officinalis Phlomis samia200
...107
(
33
)
Salvia officinalis Phlomis samia200
. ...110
(
34
)
Salvia officinalis Phlomis samia200
. ...113
(
35
)
. ...114
(
36
)
...117
37
S.officinallis200
...118
38
P.samia200
...120
39
L-thyroxine
0.3
...121
40
L-thyroxine200
S.officinallis ...123
41
L-thyroxine200
P.samia ...124
42
Salvia officinalis Phlomis samia ...126
43
Salvia officinalis Phlomis samiaشكغنا
...128
(
44
)
Salvia officinalis Phlomis samia creatinine ...129
(
45
)
Salvia officinalis Phlomis samia ... ... ...131
(
46
)
Salvia officinalis Phlomis samia ...133
(
47
)
Salvia officinalis Phlomis samiaLDL
...135
(
48
)
Salvia officinalis Phlomis samiaHDL
...137
(
49
)
Salvia officinalis Phlomis samia ...139
(
50
)
Salvia officinalis Phlomis samia ... . ...141
(
51
)
...145
(
52
)
Salvia officinalis samia Phlomis ...148
(
53
)
sulfahydryl (NPSH) ...149
.
(
54
)
sulfahydryl (NPSH)تٛهكنا ٙ ف
.
.150
(
55
)
sulfahydryl (NPSH)بهقنا ٙ ف
.
.151
(
56
)
...166
04
1
T4
(
105
).
68
106
107
126
108
anthocyanidin Flavones Flavonols (Flavon-3-ols) Flavanol Flavanol(
70
)
(
69
)
109
(
110
)
.
(111)
134
butylated hydroxyanisol butylated hydroxy toluene (BHT)tocopherol resmary and sage
69
Lamiaceae
شئاضجنا ٙ ف غعأ م كشب
ٍ ٛ خخبُنا بُٓ ٛ ب ٍ ي
Phlomis bovei , syn. Phlomis samia
ٔ
Salvia officinalis139
103
102
Phlomis samia .تٛجٕ نٕٛ بنا ثاشٛثأخنا ٖ ذي شٚذقح ٙ ف ٍ ً كٚ تد ٔشؿلأا ِ زٓ ن غػٔ ٘ زنا حاشخقلابف ٙ نبخنببٔ
ٍ ٛ خٚشئاضجنا ٍ ٛ خٛبـنا ٍ ٛ خخبُن
Phlomis samiaٔ
Salvia officinalisءبؼػلأا ٔ تٛقسذنا ةذـ نا ٗ هػ
ٙ بٚشجخنا تٛقسذنا ؽشف تنبذب تببظ ً نا ٌ ارشجهن ذغكأخهن دبؼً نا ٙ ػبفذنا صبٓجنا تنبد ٔ تقلاؼنا ثار
.
غجاشًنا ع اشؼخسا
I
-
بهحبباشطػا و تٍلسذنا ةذغنا
:
Thyroid gland and her disorder
1
Thyroid gland
1
1
Morphology
THYREOS
(
1
)
(
2
)
(
14
)
مكش
1
10
15
(
3
)
4
6
1 1(
4
)
مكش
1
:
تٍلسذنا ةذغنا غػىح ٌ بكيو شهظي
1
2
Histology
50 500 µm(
4
)
(37)
colloïdthyroglobulin
(3)
20 40calcitonin
c(
1
)
colloïd(
3
)
-2
:
Thyroid hormones
2
-1
Hormones biosynthesis
T4 thyroxine T3 triiodothyronine calcitonine
(38)
8 % T4 T3 T3 T4(
6
)
The iodide traping
ثاذيدىينا طبق يه تيقرذنا ثاوىمزهنا قيهخت تيهمع يف تهحزم لوأ
iodideم بق ه م
ذخؤي ثيح، تيهصيىحنا ايلاخنا
iodideتطساىب تيهصيىحنا ايلاخنا ً نا م قىي و ءاذغنا ه م
وىيدىصنا تخضم تبشت تطشو تخضم وزيواكيم
Na+/K+ATPASE.
م محت ةزيخلاا يذه و
iodideً ئايمكوزتكنلاا زيكزتنا جرذت سكع
(
5
)
تيمك ذ وازتت
iodideةذغنا م خاد
20
100
(
41
()
3
)
iodide40
(
8
)
(157)
Tyroglobulin synthesis
Tg thyroglobulin 600(34)
120follicular lumen
(
7
)
iodine MIT monoiodotyronire ( DIT ) Diiodotyronine(
4
1
)
(colloidal lumen)
T3 T4(
10
)
Oxidation ,Iodination and
coupling
iodide
(thyroid Acinar cells)peroxidase iodine
(
9
( )
14
)
(12)
I
-peroxidase(TPO)
I
2iodine tyrosine iodine peroxidase(Tpo) H2O2 thyroglobulin Tg
(
11
( )
13
)
microrvelli monoiodothyronine (MIT) diiodothyronine (DIT)(
7
)
DIT T4 DIT MIT T3(
4
)
Storage and release hormones
T3 T4
(
7
)
iodothyronine(
3
( )
42
)
TSH phagolysosomes proteases(
4
( )
11
)
مكش
2
tyrosine DIT MIT iodide
T3
T4(
5
)
مكش
2
:
تٍلسذنا ثبَىيشههن يىٍحنا كٍ هخخنا محاشي
.
2
2
Thyriod hormones in circulation
(
5
)
(40
) . T4 0.03%
T3 99.7 % 0.3 %(
11
)
T3 T4(35)
tyroscine binding globulin (TBG)T4 ( TBPA ) tyroxine binding prealbumin
(40)
Albumin T3 T4 T4 0.03%
0.3%
T3(
7
( )
12
)
.
2
3
Metabolisme of thyroid hormones
T4 T3 T4 T3
T4
T3(
4
)
T4 T3 deiodininases 5 deiodinase type I 5 5'- deiodinasc type II(
1
()
11
()
10
)
deiodinase enzyme
عإ َ لاا ِ زْ ٍ ٛ ب ٍ ي
deiodinase 55
inner ring positionT4
r T3
مكش
3
5
T3 2 T - ' 3,3(
11
)
T4 T3 deamination decarboscylation oxidative deamination T4 T3 tetrac tetraiodothyroacetic acide triac triiodothyroacetic acid 3,5,3(
7
)
tetrac triacO
2(
4
)
لوذج
-1
رشجهن دىٍهن تػصبُنا ثبًٌ ضَلاا ثاضًٍي
.
لوذج
-1
رشجهن دىٍهن تػصبُنا ثبًٌ ضَلاا ثاضًٍي
.
ىلس مكش
-3
وضٍنىببخٍي حػىٌ
T4
تٍبلامخسلاا هجحاىَ و
.
2
-4
Action of the thyroid hormones
( BMR ) métabolic rate basal
9
CNS S(
16
)
genomic and non genomic action
ca++
صبُٛك ٍ ٛ حٔشبنا تـ شَا ٗ ف ثاشٛـ خنا ٔ
kinase T3RNA
T3(
15
)
α B1 B2 ، B3 α B1 B3 B2 ADN
T3
thyroid responceElements TRE RNAm(
11
( )
3
)
(
16
)
2
-5
Regulation of thyroid secretion
TSH thyroid stimulating hormone
(36)
.
TSH T4 T3 Tg (pinocytotic) Tg(
9
)
(39)
TSH Adenyl cyclase c AMP(
17
)
T3 T4 TRFthyrotrophin releasing factor feed back contro
llong loop
(
9
( )
7
)
2
-6
Anapropreate secretion of thyroid hormones
Hyperthyroidism and it treatment
(2)
(
3
)
toxic goitre
thyrotoxicosis
grave disease
5 15(17)
Gaves disease
99 % 1 % 2 % 0.2 % TSH(5)
Thyroid Stimulating Antibody (TSAB) Immunoglobulin (TSI)
(Adenoma)
(17)
.
Antithyroid drugs
propul thioracil thiocyanate carbimazole(17)
Thiocyanate
Thiocyanate Perchlorate nitrate Goiter ThiocyanatTg
TSH
Tg
T3
T4
(19)
،
(17)
(
4
)
(PTU)
Propylthioracyl
PTU (MMI) methimazol Tg TgPTU
MMI T4 T3(8)
(7)
Iodides
100Tg
(18)
2 3(17)
Removal of part or all the thyroid
(2)
(8)
Hypothyroidism and its treatment
(
primary hypothyroidism)
(secondary hypothyroidism)
tertiary
(3)
(critinism
)
1 4000(5)
Hachimoto disease
cell mediated immune respense
TSH
80
%
1 %(5)
.
(2)
Endemic colloid goiter
Goiter
Tg
TSH
10
20
(17)
:
Idiopathic non toxic colloid goiter
(17)
Treatment of hypothyroidism
(
7
)
(5)
levothyroxine T4 liothyronine T3.
(7)
II
Stress oxidative and Thyroid gland
-
II
1
1
Introduction
O2 ATP 2 5 %ROS(reactive oxygene spaces) ROS
2
-Definition of stress oxidative
4
(
52
)
(
44
)(
106
()
107
)
δ
(
43
)
ADN apoptos(
54
)
(
256
)
(
43
)
4
.
3
-(
54
)
(
54
)
(
72
)
stress oxidative ischémies /reperfusions(
43
)
-II
2
1
1
1(
52
()
72
)
(radical oxygéne species) ROS O2. (superoxide anion radical)
. OH (hydroxyl radical)
(
75
)
RNS(radical nitrogene species)
2 1
o
2 H2O2(
72
)
ONOOH (nitroperoxide)(
43
()
61
()
80
)
-2
تطشُنا تٍُ ٍ جٍ سكلاا عاىَلاا
DAN
(.
44
)
3
Free radical reaction زحلا رذجلا تلاعافت
A . + RH AH + R . Hydrogen abstraction نيجوردهلا ديزجت X -. + Y X + Y-. Electron transferنوزتك للاا لقن
.
X . + RCH=CHR Addition ةفاضلاا A . + A . A 2 Termination )ليدعتلا(ةياهنلا CH3CH2.+CH 3 CH2 . CH3 CH3 +CH2 = CH2 Disproportionation1
2(
65
)
(
260
)
1
3(
57
)
ROSO
2 . NADPH oxidase(
77
)
xanthine oxidase aldhyd oxydase P450(
76
.)
1.3.1
Mitochondrial electron transport
submitochondrial particals
(
5
)
(
55
)
2 % X R RROS
(
44
)
4 NADH succinate I و II ubiquinone (coenzyme q or uq) I (NADH dehydrogenase II ( succinate dehydrogenase ) ubisemiquinone ubiquinol III reductase IV O2O
2 . dismutationO
2 .H
2O
2(
46
( )
48
)
5
2.3.1
Peroxisome
B monoamidoxidase(
47
)
،
(
173
)
بُٓػ جخُٚ
H
2O
2H
2O
2(
48
( )
76
).
ةىشحنا O23
.3.1
Phagocytes
NADPH oxidaseO
2 .H
2O
2 hypohalousmyeloperoxidase
(
44
)
NO. macrophage NO.O
2 .-peroxynitriteONOO
-(
43
)
neutrophils monocytesoesinophil phagosome DADPH+H NADP+
O
2O
2 .-(
55
)
NADPH + 2O
2DADP
++H
++2O
2.-O
2.-O
2.{
Fe–S
}
Fe
2+H
2O
2 .OH
Fenton reactionFe
2++H
2O
2Fe(III)+OH
-+
.OH
H
2O
2 dismutation superoxide dismutase (SOD) :+2 H
+H
2O
2+ O
22O
2.-(
NO
.)
(
NOS
)
oxide synthase nitricONOO-O
2 .-+NO
.ONOO
ONOO
-ONOOH
NO
2.OH
.(184)
ONOOH OH
.+NO
.ONOO-ONOO
-+CO
2ONOOCO
2-ONOOCO
2 -NO
2 .+ CO
3.-(
50
( )
44
)
myeloperoxidase (MPO)2
5
%
H2O2Cl
-hypochlorus (HOCl
)Cl
-+H
2O
2OCl
-+H
2O
OCl
-+H
+HOCl
HOCl
Cl
2HOCl
NH2
ADN
(
50
)
HOCl + H
++Cl
-H
2O +Cl
2(
50
)
OCl
-+ H
2O
2Cl
-+H
2O +
1O
2 4.3.1
Microsomal eletron transport system
(
173
)
P450
e
-O2
O
2.-(
48
)
بًك
NADPH oxidase ROS(
44
)
ROS(
173
)
5
.3.1
Transition metals
iron Fe+2 cupper ADN،
(
44
)
، chelating proteins metallothioneins ferritin iron (Fe+2)(
44
( )
49
)
6.3.1
ـ
NAD(P)H oxydase
:
NAD(P)H oxydase NADPH NADH(
174
)
258
(
173
)
NAD(P)H oxydaseO
2.-(
174
.)
7.3.1
Xanthine oxidase
:
300
KD Xanthine oxidase ROS Hypoxanthine Xanthine Xanthine Acide urique.
(174)
4.1
Targets of ROS
ADN 1.4.1
Lipide peroxidation
NO2. .OHO
2 .CCl 3 O 2. 6
(
47
( )
78
)
(
257
)
(peroxyl radical) ROO.
C
.(
259
)
(
47
()
78
)
(
43
)
malondialdehyde Alcan ، isoprostanes(
47
)(
260
)
ىلس مكش
-6
-تٌذٍ بٍهنا ةذسكلاا قىف محاشًن حٍ ػىح
(
43
.)
2
.4.1
Proteins oxidation
SH
(
7
)
SH
réticulation(
48
()
43
)
ONOO -tyrosine nitrotyrosineglutamine
SOD(
47
)
CO
2 . 2Fe
O
2.RO
2 .RO
NO
(
56
)
مكش
7
:
وىجه ذؼب ٍ ٍ حوشبهن تٍبَبجنا مسلاسهن تٍُ يلاا ع بًحلأا بٍ ظ ح ً خنا ً خنا ثاشٍغخنا تؼٍبط
ةشحنا سوزجنا
(
43
. )
3
.4.1
ADN
:
ADN oxidation
ADN
OH
H2O2 Fe2+ Zn+ .OH neclease enzyme + 2 Ca dependonuclease + 2 Ca ADN(
51
( )
53
)
.OH guanine 8-hydroxyguanine 8-hydroxyguanine(
52
)
ADN ADN ADNguanine lysinoguanine8
(
174
)
مكش
8
:
ـنا تئٌضج تكههح
ADN
(
43
)
3
.4.1
Carbohydrate damage
C-H C. (OH)RR HOCL HOBr(
49
)
،
cétoaldhydes H2O2 . OH(
43
)
2
System antioxidant
(
61
)
(
256
)
(
43
)
(
256
)
لوذج
4
:
نبخهن دبؼً نا وبظُ نا
ط
ىً ٌ ضَا لانا و ىً ٌ ضَلاا د
(
61
)
.
2
-1
Antioxydant system
superoxide dismutase(SOD)
catalase peroxidase1.1.2
ـنا
Superoxide dimutase (SOD)
:
.O2
H2O2(
62
)
(
43
()
75
)
SOD SOD1 cupper –zink SODSOD2 Mn -SOD SOD
لٔذج
5
(
45
( )
63
)
SOD
.O2
(
58
)
Mn -SOD SOD (c SOD Cu-Zn)(ec SOD Cu-Zn ) (pSOD Cu-Zn )
(
57
)
ىلس لوذجنا
-5
صبخًسٌد ذٍ سكوا شبىسـنا ىٌضَا عاىَا جحح
(
SOD
( )
63
.)
SOD
(
60
)
SOD-Cu2+ +O 2. - SOD-Cu+ +O2 SOD-Cu+ + O 2.-+2H+ SOD -Cu2+ + H2O2 Bilan: O2. -+ O2. -+2H + O2 + H2O 2.1.2
Catalase enzyme (CAT)
Catalase
H
2O
2 H2O2(
60
( )
57
).
Catalase- Fe3+ + H 2O2 compowned I + H2O Compowned I + H2O2 Catalase- Fe3+ + H2O + O2 Billon : 2 H2O2 2 H2O + O2 Catalase(
53
( )
60
)
Fe+2 Catalase NAD(P)H(
57
)
31.2
Glutathione peroxidase (GSH-P
X)
GSH-PXH2O2 hydroperoxides
(
63
)
la glutathione NADH peroxidase cytocrome C peroxidase cytocrome C(
64
)
ٔ
GPx (pGPx) GPx (cGPx) GPx (PH GPx) GPx (GI GPx)(
57
( )
65
).
GIGPx > PHGPx > pGPx = cGPx ROOH +GPx-Se-+ H+ ROH + GPx-SeOHGPx-SeOH + GSH GPx-Se-SG + H2O
GPx-Se-SG + GSH GPx-Se- + GSSG + H+
Billan : ROOH +2GSH GSSG + ROH + H2O
glutathion (GSH)
(
57
)
GPx(
64
( )
43
)
GPx NADPH+H(
57
)
glutathion transférasethiorédoxine reductase
thiorédoxine peroxidase oxidase hème(
57
.)
مكش
9
:
ذسكأخهن دبؼً نا وبظُ هن شٍثأخنا ثبٍنا غ ؼب
(
57
)
.
2.
2
(
66
)
ىلس لوذجنا
-6
تٍؼٍبطنا ذسكبخنا ثادبؼي
Natural antioxidants
1.2.2
:
Zink
9(
66
)
200 ADN SOD OH . antagoniste(
67
)
2
.2.2
Selinium
selenoproteinsGPx
(
66
).
déiodinase(
64
)
Hg Pb Cd As 20 40(
67
)
3.2.2
E
Vitamine E
VitE α،
β،
δ،
∆ α 90 %(
66
)
(
67
)
E
LDL-tocophérol
α C E 9 10(
66
( )
60
)
ىلس مكش
-10
ـن تٍغاشفنا تٍُ بنا حػىٌ
tocophérol
-α
(
66
)
.
4.2.2
C
vitamine C
C
(
66
)
C
tocopherole
(
68
)
(
67
)
ىلس مكش
-11
ٍ ٍ يبخٍفنا صبُخلا تٍنا حػىٌ
C
شحنا سزجنا ٌ وشخكنلا
(
68
. )
5.2.2
Carotinoids
600 α β B-caroteine VitE .O
2(
68
)
A(
74
)
(
67
)
6.2.2
Flavonoides
(
69
( )
180
)
1950 P(
175
)
(
12
)
4000
calcones flavone flavanones flavanols flavonols(
71
)
(
70
)
.
ىلس مكش
12
:
ثاذٌ وىَىفلافهن تٍسبسلاا تٍُ بنا
(
176
)
ىلس مكش
13
:
ـنا تٍُ ب
Quercetin
(
176
)
Quercetin flavonols(
177
)
OH 5 7 A 3' 4' B(
176
( )
178
)
OH. O2.(
179
)
PH
lipid peroxyl ( . LOO )(
178
)
( 179 ).
LH ( ) ، Xo. ( ) ، LO0. ( lipid peroxyl radicals ) ، LOOH ( lipid hydroperoxides ) ، InH ( chain-interrupting antioxidant ) ( 176 .)1 -3’,4’dihydroxy structure (catechol structure)
B 2 -2 3 C . 3 -C=O 4 4-oxo function 4 -OH 3 ٔ 5
(
71
)(
181
)
ىلس مكشنا
14
:
ثاذٌ ىَىفلافنا وبسلا
(
175
.)
7.2.2
ـنا
GlutathionGSH
Y-GLU-CYS-GLY GSH disulfide y-peptide glutamic y-glutamyle-cycteine synthase glycine GSH synthase(
63
( )
72
)
GSH peroxide radical glutathione peroxidase GSSG,GSH disulfide ، H2O2
(
183
)
GSH GSSG GSSG reductase NADPH+H(
63
( )
65
)
( 1 ) L-glutamate + L-cysteine + ATP L- y-glutamyl-L-cysteine + ADP + Pi( 2 ) L- y-glutamyl-L-cysteine + glycine + ATP GSH + ADP + Pi
(182)
.
8.2.2
Phenolic acids
ferulic acid(
70
)
9.
2.2
ـنا
(
TRX
)
Thioredoxine
SH (dithiol)TRX : cys-gly-pro-cys
GSH NADPH+H thioredoxine TRX disulfides(
65
)
Thioredoxine(
185
)
TRX TRX1 TRX2(
65
()
63
)
10.2.2
synthetic antioxidants
(butylated hydroxyanisol) BHT ( propil galate butylated hydroxy toluene) PGtocopherol resmary sage
(
70
.)
-II
3
Thyroid hormone & stress oxidative experimental hyperthyroidism
(20)
.
T3
TBARs
(32)
(28)
HPS
(25)
(26)
T3
4
TBARs
(30)
(27)
DNA oxidative damage
)
26
(
(24)
prooxidant-antioxidant T3 3 NOS(31)
GSH-Px(23)
TPO H2O2 H2O2(19)
O2(21)
BMR (ROS) ROS ADN(20)
(33)
T3 T2 oxidase C
(nTR) nuclear thyroid receptor
(mTR)
mitochondrial thyroid receptornuclear thyroid respance element
(nTRs)mitochondrial thyroid respance element (mTRs) ATP
(21)
(22)
.
5 198 oppenheimer T38
%
T3metogen activated protien kinase (MAP) 20 MAP kinase T3 MAP kinase
(
15
.)
- III
Salvia officinalis
1
Salvia officinalis(
101
( )
103
)
2
Salvia officinalis20
-30
2 4(
155
)
13(
99
()
100
.)
(
99
)
3
taxonomie
200
3000
Salvia900
(
81
)
Phylogénic Classification
Order : lamiales
Familly : lamiaceae
Classic classification :
(
155
)
ةكلمم
Kingdom : plantae
ةكلمم تحت
Subkingdom : Tracheobionta
عرف
Embrenchement : spermatophytes
عرف تحت
Subembrenchement : Angiospermes
مسق
Division : Magnoliopsides
فنص
Class : Magnoliopidae
فنص تحت
Subclass : Asteridae
ةبتر
Order : Lamiliales
ةلئاع
Familly : Lamiliacea (Labiées)
سنج
Genre : Salvia
عون
Espece : Officinalis
15
4
Salvia officinalis(
84
)
salviol ، cineol ، borneol ، thuyone(
101
( )
85
( )
88
( )
83
)
(6)
6
gallic acid ، 3-ocaffeoylquinic ، 5-o-caffeoylquinic acid ، caffeic acid rosmarinic acid(
95
( )
88
( )
92
)
. hesperetin ، apigenin ، genkwanin, hispidulin ، cirsimaritin(
11
)
quercetin ، luteolin(
90
)
kaempferol ، chrysin ، chricin galangin 109.4 ùg 589.8 g 100 honey(
86
)
(
82
).
carnosic acid ، rosmadial(
186
( )
86
( )
85
)
methylcarnosate ، epirosmanol ethylether ، epirosmanol methyl ether ، carnosol epirosmanol(
95
)
.
(
102
)
tanins résine saponine asparagine œstrogène vitamines sels(
95
)
ىلس لوذجنا
-7
-
تٍنىٍُ فنا ثبَىكً نا
(
غهي ضهخخسًنا
/
غهك
)
ضهخخسً هن
ىنىَبثًٍ نا
SOME
ىئبًنا ضهخخسً ناو
SOI
.
(
81
)
5
Salvia officinalis
Salvia
officinalis
(100)
6
Salvia officinalis(101)
.
7
Salvia salvare(
88
)
ٲ
(
102
)
؟
(
137
. )
8
Salvia officinalis700
(
99
.)
9
Salvia officinalis(
155
)
بًك
(
88
)
rosmarinic(
95
)
thujone Estrogen(
102
)
غ ً د ٗ هػ تًٛ ٚ شًنا ٖ ٕ خذ ح بًك
rosmarinic(
103
)
(
155
)
(
103
()
100
)
(
91
)
(
97
)
(
155
)
(
102
)
(
155
)
(
83
)
Azathioprine (AZP) , } { 6-(1-methyl-4-nito-5-imidazolyl) thiopurine(
93
( )
94
)
GSH GST(
87
)
acetyl choline esterase
(
84
)
(
95
( )
98
( )
96
)
(
155
).
-
IV
desfantaines Phlomis bovie De Noé sub sp(bovie) synPhlomis samia
1
Phlomis samia desfantaines 100
(
149
)
250 60 URSS 54 45 4 Phlomis herba-venti Phlomis bovei،
Phlomis caballeroiP. crinita
(
140
)
Phlomis samia desfantaines
50
80
(
155
)
141
1
/
8
(
155
)
Phlomis bovie De Noé
Phlomis samia desfantaines
P. bovei maroccana Maire
139
Phlomis samia(
155
).
jerusalem sage sticky jerusalem sage139
Phlomis sp – 20(
142
( )
139
)
.
مكشنا
16
:
ثببُن تٍفاشغىحىف سىط
Phlomis samia
.
2
لا
فٍ ُ ظ ح
(
155
)
:
ةكلمم
Kingdom : plantae
ةكلمم تحت
Subkingdom : Tracheobionta
عرف
Embrenchement : spermatophytes
عرف تحت
Subembrenchement : Angiospermes
مسق
Division : Magnoliopsides
فنص
Class : Magnoliopidae
فنص تحت
Subclass : Asteridae
ةبتر
Order : Lamiliales
ةلئاع
Familly : Lamiliacea (Labiées)
سنج
Genre : Phlomis
عون
عون تحت
Espece : samia
Sub sp : desfantaines
3
iridoid glucoside(
149
( )
134
( )
144
)
loganin aucubin verbenalin(
138
)
phenylethanoid glycosides(
140
)
(
149
( )
151
)
martynosid17
1 4oacetylmartynoside17
2)
samioside17
3(
143
)
مكش
17
:
ثببُن تٍئبًٍ كنا ثبَىكً نا غ ؼب
Phlomis samia
.
lignaneٔ
monomeric phenylpropanoid1
( 18 ) glucoside, 2,6-dimethoxy-4-hydroxyphenol-1-O-D-glucopyranoside 2 megastigmaneglucoside phlomuroside (=3hydroxy-5,6-epoxyionol-9O-Dglucopyranoside) 3uridine
(
144
)
.
مكش
18
:
ثبَىكً نا غ ؼبن تٍئبًكنا غٍ ظ نا
.
chrysoeriol apiginine luteolin(
152
( )
140
)
iriodictyol،
naringenin،
flavanones(
152
( )
148
)
(
148
)
8
P. bovei D germacrene 21.45139
146
β-caryophyllene %8.43 thymol %7.05(
139
( )
154
)
hexahydrofarnesyl acetone %5.84(
139
)
(
154
( )
139
( )
151
)
(
139
)
4
Enterotoxins Escherichia coli Staphylococcus pyogenes Salmonella Yersinia Clostridium phlomis(
149
)
phlomis iridoid flavonoid phenylpropanoid phenylthanoid(
156
)
phlomis(
147
)
(
149
)
(
158
)
(
150
)
(
138
)
(
163
)
(158)(160)
(
138
)
phenylpropanoides(
158
( )
141
)
(
162
()
164
)
(
165
( )
149
)
(
164
)
iridoid sedative purgative(138)
(
153
)
(
145
)
SOD ، CAT ، GPx(
145
)
(
138
()
162
)
مً ؼنا قشطو داىً نا
:
Salvia officinalis
Phlomis samia
I
II
III
Phlomis samia
Salvia officinalis
DPPH
V
Phlomis samia
Salvia officinalis
β-carotene /linoleic acid
IV
Salvia officinalis
Phlomis samia
I
II
Salvia officinalis
Phlomis samia
Salvia officinalis
Phlomis samia
1
Body weight, thyroid and relative thyroid weight.
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
1
free triiodothyronine(T3)
2
free thyroxine(T4)
.
V
1
Glucose
2
3
Triglycerides
4
Cholesterole
5
Creatinine
6
HDL
7
LDL
VI
Salvia officinalis Phlomis samiaVI
1
1
TBARS
1
1
TBARS
Determination of hepatic total thiobarbituric reactive substances (TBARS)
1
2
TBARS
Determination of heart total thiobarbituric reactive substances (TBARS)
1
3
TBARS
Determination of kidney total thiobarbituric reactive substances (TBARS)
2
sulfahydryl
2
1
sulfahydryl
Hepatic nom protein sulfahydryl (NPSH) reactivity.
2
2
sulfahydryl
heart nom protein sulfahydryl (NPSH) reactivity.
2
3
sulfahydryl
kidney nom protein sulfahydryl (NPSH) reactivity.
VI
2
Enzymatic antioxydant
1
Determination of hepatic catalase
(CAT)
2
Determination of kedny catalase activety
3
Determination of heart catalase activity
wistar albino rats
43
140
200
6
7
200
20
10
Salvia officinalis Phlomis samia200
NaCL 0.9 %10
83
0.3
L-thyroxineip
(114)
Gastric tupe8
4
3
7
10
0.9%
7
0.3mg /kg L-thyroxine Experimental hyperthyroidism7
0.3mg /kg L- thyroxine200
Phlomis samia7
200mg/kg Phlomis samia7
200
Salvia officinalis7
200
Salvia officinalisPhlomis samia
19
2008
3
Salvia officinalis2
2008
retary evaporator37
20
Salvia officinalis
Phlomis samia
wistar albinos
15
gestante21
21
28
140
200
6
7
10
200
chemicals
(1)KCL :
1.15
100
(2) GN()
(3) ellma’s reagent (5,5’dithio-bis-(2-nitrobenzoic acid) DTNB ; 3-carboxy - 5-nitrophyl disulfide)
20
5
phosphate buffer PH sulfahydryl(NPSH)
20
40
saline1
1
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)
600
thiobarbituric acid
100
10
TBBARs(9) trichloro acetic acid (TCA) (poreac) :
1
TCA
100 % 10 SH) (10) TSH reagent kit :
(11) T3 reagent kit ;
T3
(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:
125
50
(20) methanol:
(21) ALCL3:
3
150
(22) B-caroteine :
B-caroteine0.5
1
(23) chlorophorme :
B-carotene (24) BHT
2
1
(25) linolieque acid :
25
(26) tween :
(27) DPPH :
40
10
(28) K3Fe(CN) 6:
25
100
(30) gumme arabique 1% : 1
gumme arabique100
(31) acid phosphorique 84%:bufer and solution
phosphate buffer solution (ph 7.4 PH8) 0.1M 13.6 (potassium dihydrogen-phosphate 1000 1 PH 14.98 K2HPO4 1000 PH PH 7.4 PH 8
. sulfahydryl (NPSH)
قشطنا
:
Salvia officinalis
Phlomis samia
I
83
Salvia officinalis Phlomis samia macération1
rotary evaporator20
19
.
هُ حط ىث هفٍفجح و ههسغ هخٍمُ ح ثببُنا غً ج Macération لىهحً نا ىف تٍحببُنا ةسدىبنا شًغ ىنىحك (methanol 90%) ةذً ن 7 وبٌا ىلس ٌ بًثاو قسو ىث ٍ طمنبب حٍ ششخنا 1 ىهػ مظ حَ و حشاشنا 1 و 2 و 3 غً منا ىف تٍلببنا تٍحببُنا ةسذبنا تثنبث و تٍَ بث ةشي بهحٍ ششح دبؼٌ ةدبػا تٍهً ػ تٍَ بث شًغ تثنبثو صبهجب فٍ فجح rotary evaporator 37 ىهػ تجحبُنا ةدبًنا ظفح ةساشح تجسد -20 ° و تهيبؼًنا ىخحII
1
trichlorure ( 172 ) d’aluminium .
1- quercetine 50ùg /1 ml
2- rutine
3- AlCl
3(2 %, dans le méthanol).
4- methanol
quercetine
rutine 0 40 μg/ml quercetine rutine1
AlCl3 (2 %, dans le méthanol).10
430
3
1
1
AlCl3430
10
quercetine rutine quercetine rutine1
(mg EQ / g E) (mg ER / g E). .y = 0,0393x + 0,0223 R2 = 0,9985 y = 0,0179x + 0,0319 R2 = 0,994 0 0,2 0,4 0,6 0,8 1 1,2 1,4 1,6 1,8 0 10 20 30 40 50 ug/ml زيكرتلا ى ئو ض لا ص بص تم لاا ة دش quercetine rutine
20
quercetine
rutine
.2
bleu de Prusse 1977(
170
)
Graham 1992(
171
)
. ferricyanide de potassium (K3Fe[CN]6)
ions ferreux (Fe2+)
chlorure de fer (FeCl3)
700 nm .
1- K
3Fe(CN)
6(0.016 M)0.5%
2- FeCl
3(0.02 M, dans le HCl 0.1N)
3- solution stabilisante :
3-1 gamme arabique 1%
3-2 acide phosphorique 85%
3-3 eaux distillées 180 ml
0.1
(
extract
)
3
1
K3Fe(CN)6 (0.016 M) (, ( 0.02 M ) FeCl3 HCl 0.1N15
5
30 ml phosphoric acid 85 %, 90 ml 30 ml Gomme Arabic 1%700
acid gallic acide gallique (500ùg /ml )700
y = 0,0046x + 0,0331 R2 = 0,9979 0 0,2 0,4 0,6 0,8 1 1,2 0 50 100 150 200 250 )لم/مارغوركم( كيلبغلا ضمح زيكرت21
:
gallic acid (mg EAG / g E).
III
Phlomis samia
Salvia officinalis
DPPH
:
أذبًنا
:
Phlomis samia Salvia officinalis in vitro DPPHDPPH
(2,2'-diphenyl-1-picrylhydrazyl) 2,2'-diphenyl-1-picrylhydrazine (Cuendet et al., 1997; Burits and Bucar, 2000)
517
nm(
168
)
(
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
5
DPPH 0.004 %30
517
nm BHT
(I %) DPPH : I % = [(AC – AE) / AC] × 100AC : ( ) . AE %50 DPPH (IC50) µg / ml BHT . y = 479,78x + 34,709 R2 = 0,9354 0 10 20 30 40 50 60 70 80 90 0 0,02 0,04 0,06 0,08 0,1 0,12 ) µg/ml) BHT ـلا زيكرت )% ( ظ يب ثت لا تب س ن
22
BHT
.
IV
Phlomis samia
Salvia officinalis
β-carotene / linoleic acid
Phlomis samia Salvia officinalis
β-carotene / acid linoleic diene hydroperoxydes linoleic
(
167
. )
0.5
B-caroteine1
25
linoleic acid tween200
retaryevaporation100
(100 ml / min / 30 min)
μl350
(extract)
2.5
490
6
24
48
3
1
BHT2
350
μl3
2
3
490 nm1
2
3
4
5
6
24
48
.
(AA %) AA % = (AE / AC) × 100A
E : . AC BHT (AA %)24
V
1
GN9
25
2
3
1
5
discs4
37
24
48
inhibition zones Aspergillus sp Pseudomonas sp gram (-) Staphylococcus sp gram (+) Klebsiella sp gram (-) Esherichia coli gram (-) CondidaSalvia officinalis
Phlomis samia
I
140
200
NaCL 0.9%0.3
L- thyroxine L- thyroxine0.3
200
10
Phlomis samia Salvia officinalis20
200
Phlomis samia Salvia officinalis50
%
:
Preliminary LD 50 test
8
S officinalis 200 400 500 1000 2000 4000 5000 Nacl % 0.9 P samia 150 300 500 1000 2000 4000 500072
II
Salvia officinalis
Phlomis samia
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
III
Thyroid morphological and histological study
10% Neutral buffred formalin
10
%
24
l’éclaircissement le xylène Embadded in paraffin) microtome5
37
l’éosine-ématoxilne Hematoxylin
l’éosine
IV
Thyroid hormones assay
6000 15 -20 T3 T4 TSH
commercially available kit
V
auto analyseur (Technicon RA et Opera systems № de ref. T01-2801-56)
1
glucoseىٚضَإ غي
glucose-oxydase .
glucose-oxydaseذغكؤٚ
glucoseٗ نإ
gluconique l’acideٔ
(H2O2) hydrogène peroxydeجحبُنا
م بق ٍ ي م بقخغٚ
phénol-aminophenazoneىٚضَا دٕ جٔ ٗ ف
peroxydase (POD)ٗ حلاا م ػبفخنا بغد
:
GOD
β-Glucose + O2 + H2O Acide Gluconique + H2O2
POD
H2O2 + Phénol + Aminophenazone Quinone + H2O
تجٕ ي لٕ ؿ ٗ هػ ط بقح تجحبُنا ٍ ٛ ُ ٛ كنا تػٕ ً جً ن تٛئٕؼنا تفبثكنا ةذش
505
ِ زْ لذحٔ شخيٕ َ بَ
م ظ ً نا ٗ ف شكغنا ضٛكشح ٗ هػ تفبثكنا
(
91
( )
92
)
2
ىهكنا لوشخسهكنا ضٍكشح شٌذمح
:
93
Trinder Boehring Mannhein
Cholestérol estéraseCholestérol estérifié + H2
o
Cholestérol + acide gras.Cholestérol
o
xydaseCholestérol +
O
2 ∆- 4Cholesténone + H2O2.H2O2 + phénol + chromogène (amino 4 phénazone) Peroxydase Quinone imine 500 nm
3
-
مظ ً نا ً ف تٍثلاثنا ثاذٌ شسٍهغنا تًٍ ك شٌذمح
:
تَٛ ٕ ن تًٛ ٚ ضَإ تقٚشـ ن بؼبح تٛثلاثنا ثاذٚ شغٛ هـ نا شٚذقح ىح
.
أذبًنا
:
ثاذٛ بٛهنا وذْ ىٚضَإ م ؼف تجٛ خَ سشذ خًنا لٔشغٛ هـ نا شٚذقح ٗ هػ م ػبفخنا أذبي ذً خؼٚ
enzym lipase . LipaseGlycerol Kinase
Glycerol + ATP Glycerol 3 phosphate + ADP Glycerol 3 phosphate
Oxydase
Glycerol 3 phosphate Dihydroxyacétone phosphate + H2O2
Peroxydase
2H2O2 +Phénol +amino-4-phénézone Quinone imine + 4 H2O
nm 500