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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5264_Библиотеки_им_академика_М_И_Перельмана.pdf
64
Plant-based Foods and their Implications in Brain Health
Formulations
Spices
Raw/
Extract
Method of
extraction
Extracted
compositions Yield
AD
pathways
evaluated
Native
extract
Macro/ micro-
encapsulate Nano- vehicle
- - C Extracted powder - - - - - - EPR spectrum for
Methanolic extract - - C Extracted powder - - - - - - EPR spectrum for
- - D Pure saffron
powder in
physiological
saline
- - - - - - EPR spectrum for
Hydro-
alcoholioc extract
using a cold-
maceration
method
33.11 ± 3.25% C; D Extracted dried
powder
- - - - - - EPR spectrum for
Ethanolic extract - - D Extracted dry
powder
- - - - - - EPR spectrum for
TABLE 4.2 (Continued)
Spice compounds, their extracts and formulations: Mode of action in targeted pathways
of AD pathogenesis
65
Impact of Indian Herbs and Spices on Alzheimer’s Disease
Nasal
formulations
Characteristics of
the extract or the
formulations and
their pharmaceutical/
pharmacokinetic profiles
Preclinical/
Clinical study Remarks References
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
15.4 µM
(in vitro assays)
Target(s):
In vitro assays (amyloid
40 (1 mg/ mL)
Major nding(s)
reported:
formation and disrupted
amyloid aggregates
59
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Dose:
60 mg/ kg bw
Duration:
1 week
Route of
Administration:
Intraperitoneal
Subject:
Aged mice model
Target(s):
Major nding(s)
reported:
Saffron stigma constituents
inhibited aggregation
and deposition of
amyloids in the human
brain
60
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
30 mg/ kg bw
Duration:
21 days
Route of
administration:
Intraperitoneal
Subject:
Male Wistar rats (chronic
stress induced)
Target(s):
Chronic stress- induced
spatial learning and
memory impairments
and oxidative stress in
the hippocampus
Major nding(s)
reported:
Improved learning and
memory and repair
oxidative stress damage
to the hippocampus
induced by chronic
stress prominent in AD
61
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
50 mg/ kg/ day
Duration:
1 month
Route of
administration:
Oral
Subjects:
C57BL/ 6 wild- type mice
model
Target(s):
BBB function and integrity,
Major nding(s)
reported:
Effectively decreased
levels in 5XFAD rat-
brain hippocampus
62
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
Duration:
7 days
Route of administration:
Intrahippocampal
administration
Subjects:
Adult male Wistar rats
Target(s):
Learning and memory of
EB (ethidium bromide)-
demyelinated rats and
their oxidative status in
the hippocampus
Major nding(s)
reported:
Saffron alleviated
oxidative stress and
improved cognitive
6
(continued)
66
Plant-based Foods and their Implications in Brain Health
Formulations
Spices
Raw/
Extract
Method of
extraction
Extracted
compositions Yield
AD
pathways
evaluated
Native
extract
Macro/ micro-
encapsulate Nano- vehicle
Ethanolic extraction
(80%)
- - C - - Capsule
[containing
dried ethanolic
saffron extract
(15 mg),
magnesium
stearate
(lubricant), and
sodium starch
glycolate
(disintegrant)]
- - C - - - - - - - - EPR spectrum for
- - - - - - Saffrotin capsules
Impiran,
Tehran,
Iran, 15 mg
(containing
15 mg dried
extract of
saffron)
Homogenate
extraction
method
22.76 % - - - - - - - - - - - - - - - - 66
Solvent extraction - - E Crocin stock
(2 mg/ ml) was
prepared from
its powder
that was
dissolved in
piperazine-N,
ethanesulfonic
acid (PIPES)
buffer (pH 6.8)
- - - - - - EPR spectrum for
TABLE 4.2 (Continued)
Spice compounds, their extracts and formulations: Mode of action in targeted pathways
of AD pathogenesis
67
Impact of Indian Herbs and Spices on Alzheimer’s Disease
Nasal
formulations
Characteristics of
the extract or the
formulations and
their pharmaceutical/
pharmacokinetic profiles
Preclinical/
Clinical study Remarks References
- - - - EPR spectrum for
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
30mg/ day (15 mg
twice a day)
Duration:
22 weeks
Route of
administration:
Oral
Subjects:
Human
Target(s):
Double- blind study of
parallel groups of
patients with mild to
moderate AD through
ADAS- cog and CDR-
SB measures
Major nding(s)
reported:
Showed anti-
amyloidogenic activity
to donepezil
63
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
30mg/ day (15 mg
twice a day)
Duration:
16 weeks
Route of
administration:
Oral
Subjects:
Human
Target(s):
Psychometric measures
including the MMSE,
ADAS- cog, clinical
dementia rating
scale- sums of boxes
(CDR- SB)
Major nding(s)
reported:
Saffron showed effective
results in mild to
moderate AD
64
- - - - EPR spectrum for
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
30mg/ day (15 mg
twice a day)
Duration:
12 months
Route of
administration:
Oral
Subjects:
Human
Target(s):
Parallel- group, double-
blind randomized
clinical trial on outdoor
patients with dementia,
MMSE score
Major nding(s)
reported:
Reduced cognitive
decline in patients with
moderate to severe
AD comparable to
memantine
65
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
of crocin
(in vitro assays)
Target(s):
Inhibitory effect on
aggregation of
recombinant human tau
protein 1N/ 4R isoform
using biochemical
methods and cell culture
Major nding(s)
reported:
Crocin inhibited tau
aggregation with IC
50
of
100 µg/ ml
67
(continued)
68
Plant-based Foods and their Implications in Brain Health
Formulations
Spices
Raw/
Extract
Method of
extraction
Extracted
compositions Yield
AD
pathways
evaluated
Native
extract
Macro/ micro-
encapsulate Nano- vehicle
Methanol/ water
1:1 v/ v
- - A Methanolic
extract
- - - - - - EPR spectrum for
Extraction using
80% ethanol
- - C Crocin crystals - - - - - - EPR spectrum for
Black Cumin
seeds
Extract
(essential
oil)
Microwave- assisted
extraction (micro
distillation) and
hydro distillation
Thymoquinone 10.8%- 24.6 %
(MD) and
1.6 %- 21.8
% (HD)
- - - - - - - - - - - - - - - - 70
Hydro distillation 37.6 %;
18.4 %- 24 %
- - - - - - - - - - - - - - - - 71
Methanolic
extraction
followed by
fractionation in
hexane, ethyl
acetate and water
- - C Hexane and water
Fractions
- - - - - - EPR spectrum for
Solvent extraction
(methanol)
- - - - Oil obtained
after methanol
extraction
- - - - - - EPR spectrum for
(carbon dioxide)
77.2- 86.2 % C - - - - Nano-
TABLE 4.2 (Continued)
Spice compounds, their extracts and formulations: Mode of action in targeted pathways
of AD pathogenesis
69
Impact of Indian Herbs and Spices on Alzheimer’s Disease
Nasal
formulations
Characteristics of
the extract or the
formulations and
their pharmaceutical/
pharmacokinetic profiles
Preclinical/
Clinical study Remarks References
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico study
Concentration:
Various concentrations
used for in vitro
assays and docking
studies
Target(s):
Inhibitory effect on AChE
Major nding(s)
reported:
Extract showed moderate
AChE- inhibitory
activity (up to 30%)
68
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
50, 25 and 12.5 mg/
kg/ day
Duration:
2 weeks
Route of
administration:
Intraperitoneal
Subjects:
Male Wistar rat
Target(s):
In vivo inhibitory on
hyper- phosphorylated
Tau- tangles
Major nding(s)
reported:
Crocin showed reduction
of tau phosphorylation
69
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
1,10 & 100 µg/ ml
In vitro rat (Sprague
Dawley) cerebellar
granule (CGNs)
neuron cell culture
(in vitro assay)
Target(s):
in vitro rat
CGNs cell culture
Major nding(s)
reported:
Showed effective
1- 40- induced CGNs
toxicity
7
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
1 ml/ kg
Duration:
80 days
Route of
administration:
Oral (gavage)
Subjects:
Male Sprague Dawley rats
Target(s):
Effect on spatial
recognition
Major nding(s)
reported:
Helped to improve spatial
cognition in rats
challenged with chronic
cerebral hypoperfusion
72
emulsions
- - EPR spectrum for
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
1 mg/ kg bw
Duration:
3 months
Route of
administration:
Oral (gavage)
Subjects:
2- month- old Sprague
Dawley rats
Target(s):
other genes in HFCD
rat brains
Major nding(s)
reported:
Nanoemulsions effectively
rat brain
73, 74
(continued)
70
Plant-based Foods and their Implications in Brain Health
Formulations
Spices
Raw/
Extract
Method of
extraction
Extracted
compositions Yield
AD
pathways
evaluated
Native
extract
Macro/ micro-
encapsulate Nano- vehicle
Raw - - - - C - - - - - - - - EPR spectrum for
- - - - C - - - - - - - - EPR spectrum for
- - - - D - - - - - - - - EPR spectrum for
- - - - A - - - - - - - - EPR spectrum for
Bay
leaf
Extract Solvent extraction
(UAE in
methanol
followed by
liquid- liquid
extraction
obtaining three
fractions: CHCl
3
,
EtOAc, and
MeOH)
1,8- cineole 69.358%w/ w C - - - - - - - - EPR spectrum for
TABLE 4.2 (Continued)
Spice compounds, their extracts and formulations: Mode of action in targeted pathways
of AD pathogenesis
71
Impact of Indian Herbs and Spices on Alzheimer’s Disease
Nasal
formulations
Characteristics of
the extract or the
formulations and
their pharmaceutical/
pharmacokinetic profiles
Preclinical/
Clinical study Remarks References
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
Concentration:
0.1 and 1 µM
(in vitro assays)
Target(s):
Neuroprotective effects on
neurotoxicity
Major nding(s)
reported:
TQ pretreatment repressed
amyloid beta induced
apoptosis of cultured
cerebellar granule
neurons (CGNs)
75
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
0.78– 400 lM
(in vitro assays)
Target(s):
Neuroprotective effects of
TQ on neurotoxicity
Major nding(s)
reported:
TQ reduced Aß induced
neurotoxicity in vitro
model of undifferentiated
pheochromocytoma
rat cell line, PC- 12, by
inhibiting oxidative
stress
76
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
2.5- 40 µM
(in vitro assays)
Target(s):
Antioxidant effects on
microglial cells
Major nding(s)
reported:
Could effectively delay
neurodegeneration
induced by oxidative
stress in microglial cells
77
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentration:
5 and 10 mg/ kg; p. o.
(in vitro assays)
Target(s):
Role on L- Cys induced rats
Major nding(s)
reported:
TQ lowered stimulation of
AChE enzyme function
at the same dose level
of donepezil (10 mg/
kg; p. o)
78
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Concentrations:
mL
(in vitro assays)
Target(s):
In vitro assays on SH-
5YSY and SK- N- BE
(2)- C human neuronal
cell lines, as well as on
C6 mouse glial cell line
Major nding(s)
reported: Showed anti-
79
(continued)
72
Plant-based Foods and their Implications in Brain Health
Formulations
Spices
Raw/
Extract
Method of
extraction
Extracted
compositions Yield
AD
pathways
evaluated
Native
extract
Macro/ micro-
encapsulate Nano- vehicle
Hydrodistillation/
steam distillation
to obtain EO.
Also extracted
with ethanol
- - A Extracted oil
as well as
ethanolic
extract
- - - - - - EPR spectrum for
Aqueous extract - - A; B Aqueous extract - - - - - - EPR spectrum for
Incense - - A Bay leaf smoke - - - - - - EPR spectrum for
Coriander Extract
(volatile
oil)
Hydro distillation Linalool 76.33%- 87.53
%
- - Extracted oil - - - - - - - - - - - - 83
Ethanolic extract
(seeds)
- - - - Dried extract - - - - - - EPR spectrum for
- - A Dried extract - - - - - - EPR spectrum for
TABLE 4.2 (Continued)
Spice compounds, their extracts and formulations: Mode of action in targeted pathways
of AD pathogenesis
73
Impact of Indian Herbs and Spices on Alzheimer’s Disease
Nasal
formulations
Characteristics of
the extract or the
formulations and
their pharmaceutical/
pharmacokinetic profiles
Preclinical/
Clinical study Remarks References
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
In silico
Concentrations:
0.5 and 1 mg/ ml
(in vitro assays)
Target(s):
In vitro biochemical assays
Major nding(s)
reported: Showed good
AChE- inhibitory effects
80
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
Concentration:
0.3 µg/ ml
(in vitro assays)
Target(s):
In vitro study using brain
homogenate of male
Wister rats
Major nding(s)
reported:
Aqueous extracts showed
remarkably inhibited
effects of both AChE
and BChE
81
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: N.R
Release kinetics
In silico
Doses:
5 min before each test
Duration:
23 days
Route of
administration:
Olfactory
Subjects:
3- month- old male Wister
rats treated with
scopolamine
Target(s):
Potential effect of bay leaf
incense on memory
function and brain
antioxidant status
Major nding(s)
reported:
Tests suggested the
in effectively diminishing
and AChE activity
82
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: >5000 mg
Release kinetics
In silico
Dose:
100, 200 mg/ kg,
Duration:
15 days
Route of
administration:
Oral
Subjects:
Tacrine treated male
Wister rats
Target(s):
Cognitive behaviour
assessed by plus
maze learning
task, biochemical
assessments
Major nding(s)
reported:
Showed promising role in
ameliorating cognition
5, 84
validation of antioxidant
potency: N.R
SE value: N.R
LD
50
: >5000 mg
Release kinetics
In silico
Dose:
5, 10 and 15% w/ w of diet
Duration:
45 days
Route of
administration:
Oral
Subjects:
Scopolamine and
diazepam treated mice
model
Target(s):
Cognitive functions, total
serum cholesterol levels
and brain cholinesterase
activity
Major nding(s)
reported:
Had promising memory
improving capacities
5, 85
(continued)