ArticlePDF Available

CUMIN SEEDS: THE FUNCTIONAL FOOD WITH AN ABILITY TO INHIBIT THE DELETERIOUS PHENOMENON OF GLYCATION

Authors:

Abstract

Objective: Ageing is the natural process of getting old and involve deleterious phenomenon like glycation and oxidative stress. The quality of life can be improved and maintained for longer duration of time by inhibiting these harmful processes. In this regard, the dietary substances, especially spices hold tremendous potential. Methods: The present work was designed to assess the anti-ageing potential of five spices i.e. cumin seed, cinnamon, ginger, paprika and garlic, using anti-glycation and anti-oxidant assays along with HPLC fingerprint of the most potent extract. Results: Our data showed that among all spices, the ethanolic extract (70%) of cumin seeds showed the most significant inhibition of glycation (80%) and oxidative stress (95%) at the tested dose of 1mg/ml. The Venn diagram (set at a threshold of 50%) showed that among all tested extracts, only cumin seed was able to produce 50% inhibition in both assays. The HPLC fingerprint of cumin seed extract was also obtained as the crude reflection of the phytochemicals residing in it. Conclusion: Hence, the cumin seed presents itself as a promising functional food for the management of age-associated diseases and diabetic complications attributed to the deleterious phenomenon of glycation.
INTRODUCTION
Senescence or ageing is the natural phenomenon
of getting old, which is jeopardizing the human race
in an unprecedented manner. The world needs
balanced demography to run its machinery. How-
ever, the number of old age people shall surpass
youth by the year 2050; an event that is unprece-
dented in known human history (Suzman and
Beard, 2011). The scenario is alarming and stresses
upon the need to take appropriate measures to
increase quality of life over time. Several underlying
pathological mechanisms have been reported for
the process of ageing (Campisi et al., 2019). Among
which, one of them attributes senescence to the
buildup of garbage in the body (Sergiev et al., 2015)
such as Advance Glycation End products (AGEs)
(Ross, 2015) and oxidative stress (imbalance
between oxidants and antioxidants) (Pole et al.,
2016). Glycation (Maillard reaction) involves
interaction between carbohydrates; especially
reducing sugar and other bio-molecules i.e. nucleic
acids, proteins or lipids, which after a long process
produces AGEs (Goldin et al., 2006). The levels of
N(6)-carboxymethyl lysine (CML), the predominant
AGEs product, co-relates with the phenomenon of
ageing, age-linked diseases such as learning &
memory impairment (Southern et al., 2007, Igase
and Igase, 2018), kidney injury (Sun et al., 2016),
non-alcoholic fatty liver diseases (Leung et al., 2016)
and complications associated with diabetes melli-
tus (Ramasamy et al., 2005). The AGEs binds to its
receptor known as Receptor for Advanced Glyca-
tion End products (RAGE), thereby leading to
activation of Nuclear Factor-kappa B (NF-кB) (Hasl-
beck et al., 2005); the transcription factor famous
for oxidative stress. The stress in this case is specifical-
ly termed as glycative stress (Yonei et al., 2020).
In quest of impeding this deleterious phenomenon
of glycation, several inhibitors (natural and synthet-
ic) were reported (Reddy and Beyaz, 2006). Despite
of their significant effectiveness (e.g. aminoguani-
dine), they could not make it to the bed side due to
their potential to produce adverse effects (Thornal-
ley, 2003, Campbell, 1996). Under this milieu, the
field of nutritional pharmacology comes to rescue.
This is an emerging field in pharmacy, which uses
the concept of functional foods i.e. the food
resources which along with nutritional value also
offer medicinal value. This concept was formulated
by Hippocrates i.e. let food be thy medicine and
medicine be thy food (Hasler, 2002). The benefit of
using this concept is that it offers fast and inexpen-
sive solutions without needing detailed toxicologi-
cal assessments as part of drug development
process. Furthermore, this type of approach suits
well for the indications which grow insidiously.
Dietary spices hold promising potential as functional
food and need comprehensive investigations
(Dearlove et al., 2008). In this regard, cumin is the
famous spice used in folklore for the management
of tooth ache, gastrointestinal, inflammatory and
neurological disorders (Benelli et al., 2018). Other
biological actions attributed to cumin are antioxi-
dant, anticancer, stimulant and carminative (Shar-
ma et al., 2001). Cumin is actually the dried seed
obtained from Cuminum cyminum L., a medicinal
plant of Apiaceae family, which is native to the
Eastern Mediterranean and South Asia (Singh et al.,
2017, Zarandi et al., 2017).
Currently, there is no treatment option available in
the allopathic system of medicine for the manage-
ment of glycation. Keeping this in view, the present
study was designed to evaluate functional food i.e.
spices for their ability to inhibit the deleterious
phenomenon of glycation.
MATERIALS & METHODS
Selection of Spices
Five spices i.e. cumin seed, cinnamon, ginger,
paprika and garlic were selected for the present
study.
Preparation of plant extract
Briefly, 1 kg of each spice was separately soaked in
ethanol (70%, 3L) for three days at room tempera-
ture, followed by rotary evaporation to yield thick
extract, which was freeze dried and stored in refrig-
erator till further use.
Anti-glycation Assay
The in vitro AGE inhibition assay was performed by
incubating BSA (10 mg/ml) and fructose (50mM)
together for 24 hours at 60 ˚C. The spice extract was
used at the concentration of 1mg/ml. The AGEs
were detected using its innate fluorescence (Khan
et al., 2017). ) All results were tested in triplicate. The
percentage inhibition of AGEs was measured using
the following formula
% Inhibition = [1-(fluorescence of test)] / (fluores-
cence of control) x 100
Antioxidant Assay
Free radical scavenging activity of functional foods
was assessed by 1-1diphenyl-2-picryl-hydrazyl
(DPPH) as reported earlier (Shen et al., 2010). Briefly,
DPPH (0.1 mM in methanol) was added (100ul) to
spice extracts (1mg/ml, 300ul), vortexed and
allowed to stand at room temperature for 30
minutes. The absorbance was measured at 517nm
using UV spectrophotometer. Percent free radical
scavenging activity was calculated using the
following formula (Aiyegoro and Okoh, 2010):
DPPH Scavenging activity (%) = [(Abs control – Abs
sample) / Abs control] x 100
Venn Diagram
The Venn diagram was prepared at 50% threshold
to observe the effect of spice extracts on both
anti-glycation and anti-oxidant assays.
HPLC Fingerprint
The High Performance Liquid Chromatography
(HPLC) was used to obtain the fingerprint of the
extract. Following were the working conditions:
Extract Strength: 50µg/ml
Column: Hibar® 250-4, 6 LiChrospher® 100 RP-18e
(5um) column.
Detector: DAD (SPD-M20A) set at 250nm.
Mobile phase: Methanol (50%)
Flow rate: 0.5ml/min
Injection volume: 10µl
Data analysis
The data is shown as mean ± SEM of percent
change.
RESULTS
The results obtained in the present study are as
follows:
Anti-glycation Assay
Among the various spices, the cumin seeds extract
showed the most promising anti-glycation action
with the percent inhibition of 80% (Table-1). Cinna-
mon, ginger, paprika and garlic showed the
percent inhibition of 30%, 25%, 21% and 10% respec-
tively
ORIGINAL RESEARCH ARTICLE
CUMIN SEEDS: THE FUNCTIONAL FOOD WITH AN
ABILITY TO INHIBIT THE DELETERIOUS PHENOME-
NON OF GLYCATION
Muhammad Dawood Khan1, Uzair Nisar1, Hammad Ahmed1, Tayyaba Mumtaz2 and Ghulam Abbas1*
Affiliations
1Department of Pharmacology, Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan
2Department of Pharmacognosy, Faculty of Pharmacy, Ziauddin University, Karachi, Pakistan
Corresponding Author Email:
ghulam.abbas@zu.edu.pk
ghulam.abbas@hotmail.com
ABSTRACT
Objective: Ageing is the natural process of getting old and involve deleterious phenomenon like glycation
and oxidative stress. The quality of life can be improved and maintained for longer duration of time by inhib-
iting these harmful processes. In this regard, the dietary substances, especially spices hold tremendous
potential.
Methods: The present work was designed to assess the anti-ageing potential of five spices i.e. cumin seed,
cinnamon, ginger, paprika and garlic, using anti-glycation and anti-oxidant assays along with HPLC finger-
print of the most potent extract.
Results: Our data showed that among all spices, the ethanolic extract (70%) of cumin seeds showed the
most significant inhibition of glycation (80%) and oxidative stress (95%) at the tested dose of 1mg/ml. The
Venn diagram (set at a threshold of 50%) showed that among all tested extracts, only cumin seed was able
to produce 50% inhibition in both assays. The HPLC fingerprint of cumin seed extract was also obtained as
the crude reflection of the phytochemicals residing in it.
Conclusion: Hence, the cumin seed presents itself as a promising functional food for the management of
age-associated diseases and diabetic complications attributed to the deleterious phenomenon of glyca-
tion.
Keywords: Glycation; Oxidative stress; Cumin seeds; Functional food
62 ZIAUDDIN JOURNAL OF PHARMACEUTICAL RESEARCH 2021, VOL. 2(1)
INTRODUCTION
Senescence or ageing is the natural phenomenon
of getting old, which is jeopardizing the human race
in an unprecedented manner. The world needs
balanced demography to run its machinery. How-
ever, the number of old age people shall surpass
youth by the year 2050; an event that is unprece-
dented in known human history (Suzman and
Beard, 2011). The scenario is alarming and stresses
upon the need to take appropriate measures to
increase quality of life over time. Several underlying
pathological mechanisms have been reported for
the process of ageing (Campisi et al., 2019). Among
which, one of them attributes senescence to the
buildup of garbage in the body (Sergiev et al., 2015)
such as Advance Glycation End products (AGEs)
(Ross, 2015) and oxidative stress (imbalance
between oxidants and antioxidants) (Pole et al.,
2016). Glycation (Maillard reaction) involves
interaction between carbohydrates; especially
reducing sugar and other bio-molecules i.e. nucleic
acids, proteins or lipids, which after a long process
produces AGEs (Goldin et al., 2006). The levels of
N(6)-carboxymethyl lysine (CML), the predominant
AGEs product, co-relates with the phenomenon of
ageing, age-linked diseases such as learning &
memory impairment (Southern et al., 2007, Igase
and Igase, 2018), kidney injury (Sun et al., 2016),
non-alcoholic fatty liver diseases (Leung et al., 2016)
and complications associated with diabetes melli-
tus (Ramasamy et al., 2005). The AGEs binds to its
receptor known as Receptor for Advanced Glyca-
tion End products (RAGE), thereby leading to
activation of Nuclear Factor-kappa B (NF-кB) (Hasl-
beck et al., 2005); the transcription factor famous
for oxidative stress. The stress in this case is specifical-
ly termed as glycative stress (Yonei et al., 2020).
In quest of impeding this deleterious phenomenon
of glycation, several inhibitors (natural and synthet-
ic) were reported (Reddy and Beyaz, 2006). Despite
of their significant effectiveness (e.g. aminoguani-
dine), they could not make it to the bed side due to
their potential to produce adverse effects (Thornal-
ley, 2003, Campbell, 1996). Under this milieu, the
field of nutritional pharmacology comes to rescue.
This is an emerging field in pharmacy, which uses
the concept of functional foods i.e. the food
resources which along with nutritional value also
offer medicinal value. This concept was formulated
by Hippocrates i.e. let food be thy medicine and
medicine be thy food (Hasler, 2002). The benefit of
using this concept is that it offers fast and inexpen-
sive solutions without needing detailed toxicologi-
cal assessments as part of drug development
process. Furthermore, this type of approach suits
well for the indications which grow insidiously.
Dietary spices hold promising potential as functional
food and need comprehensive investigations
(Dearlove et al., 2008). In this regard, cumin is the
famous spice used in folklore for the management
of tooth ache, gastrointestinal, inflammatory and
neurological disorders (Benelli et al., 2018). Other
biological actions attributed to cumin are antioxi-
dant, anticancer, stimulant and carminative (Shar-
ma et al., 2001). Cumin is actually the dried seed
obtained from Cuminum cyminum L., a medicinal
plant of Apiaceae family, which is native to the
Eastern Mediterranean and South Asia (Singh et al.,
2017, Zarandi et al., 2017).
Currently, there is no treatment option available in
the allopathic system of medicine for the manage-
ment of glycation. Keeping this in view, the present
study was designed to evaluate functional food i.e.
spices for their ability to inhibit the deleterious
phenomenon of glycation.
MATERIALS & METHODS
Selection of Spices
Five spices i.e. cumin seed, cinnamon, ginger,
paprika and garlic were selected for the present
study.
Preparation of plant extract
Briefly, 1 kg of each spice was separately soaked in
ethanol (70%, 3L) for three days at room tempera-
ture, followed by rotary evaporation to yield thick
extract, which was freeze dried and stored in refrig-
erator till further use.
Anti-glycation Assay
The in vitro AGE inhibition assay was performed by
incubating BSA (10 mg/ml) and fructose (50mM)
together for 24 hours at 60 ˚C. The spice extract was
used at the concentration of 1mg/ml. The AGEs
were detected using its innate fluorescence (Khan
et al., 2017). ) All results were tested in triplicate. The
percentage inhibition of AGEs was measured using
the following formula
% Inhibition = [1-(fluorescence of test)] / (fluores-
cence of control) x 100
Antioxidant Assay
Free radical scavenging activity of functional foods
was assessed by 1-1diphenyl-2-picryl-hydrazyl
(DPPH) as reported earlier (Shen et al., 2010). Briefly,
DPPH (0.1 mM in methanol) was added (100ul) to
spice extracts (1mg/ml, 300ul), vortexed and
allowed to stand at room temperature for 30
minutes. The absorbance was measured at 517nm
using UV spectrophotometer. Percent free radical
scavenging activity was calculated using the
following formula (Aiyegoro and Okoh, 2010):
DPPH Scavenging activity (%) = [(Abs control – Abs
sample) / Abs control] x 100
Venn Diagram
The Venn diagram was prepared at 50% threshold
to observe the effect of spice extracts on both
anti-glycation and anti-oxidant assays.
HPLC Fingerprint
The High Performance Liquid Chromatography
(HPLC) was used to obtain the fingerprint of the
extract. Following were the working conditions:
Extract Strength: 50µg/ml
Column: Hibar® 250-4, 6 LiChrospher® 100 RP-18e
(5um) column.
Detector: DAD (SPD-M20A) set at 250nm.
Mobile phase: Methanol (50%)
Flow rate: 0.5ml/min
Injection volume: 10µl
Data analysis
The data is shown as mean ± SEM of percent
change.
RESULTS
The results obtained in the present study are as
follows:
Anti-glycation Assay
Among the various spices, the cumin seeds extract
showed the most promising anti-glycation action
with the percent inhibition of 80% (Table-1). Cinna-
mon, ginger, paprika and garlic showed the
percent inhibition of 30%, 25%, 21% and 10% respec-
tively
63 ZIAUDDIN JOURNAL OF PHARMACEUTICAL RESEARCH 2021, VOL. 2(1)
64 ZIAUDDIN JOURNAL OF PHARMACEUTICAL RESEARCH 2021, VOL. 2(1)
S. No. Functional Food Scientific Name Free Radical Scavenging (%)
1Cumin seed Cuminum cyminum 95
2Cinnamon Cinnamomum verum 87
3Ginger Zingiber officinale 80
4Paprika (red) Capsicum annum 85
5Garlic Allium sativum 41
Ascorbic acid 1 mM (positive control) 95
Antioxidant Assay
Among the various spices, the cumin seeds extract
showed the most promising anti-oxidant action with
the percent inhibition of 95% (Table-2). Cinnamon,
ginger, paprika and garlic showed the percent
inhibition of 87%, 80%, 85% and 41% respectively.
Table-1 Effect of Various Spice Extracts on Inhibition of Glycation
Table-2 Effect of Various Spice Extracts on Free Radical Scavenging
S. No. Functional Food Scientific Name Free Radical Scavenging (%)
1Cumin seed Cuminum cyminum 95
2Cinnamon Cinnamomum verum 87
3Ginger Zingiber officinale 80
4Paprika (red) Capsicum annum 85
5Garlic Allium sativum 41
Ascorbic acid 1 mM (positive control) 95
Venn Diagram
Among all tested extracts, only cumin seeds
showed 50% inhibition in both glycation and
anti-oxidant assays as shown in the Venn diagram
(Figure-1).
Figure-1 Venn diagram at Threshold of 50 percent
DISCUSSION
Ageing or senescence has been attributed to
capacity loss and emergence of diseases in living
beings. Both of which affect the quality of life. The
deleterious mechanism like glycation has been
reported to underlie the process of ageing and has
been the pharmacological target of anti-ageing
substances. In this regard, dietary interventions
especially through spices appear to be of medici-
nal value and their evaluation against the said
indication was the primary objective of the present
study.
Dietary modulation has always been an important
tool for the management of ailments, which are
either of chronic nature or develop insidiously. Nutri-
tionists often recommend use of specific constitu-
ents (Solfrizzi et al., 1999), diet (Berr et al., 2009) or
ask to follow specific dietary patterns (Yannakoulia
et al., 2015) to manage such situations. Furthermore,
the diet based interventions were found to have
greater patient compliance. In this context, the
dietary spices hold a promising position and their
consumption is negatively co-related with ageing
and associated ailments especially in our part of
the world, which is famous for spicy meals (Kannap-
pan et al., 2011). Keeping this in view, the five com-
monly used spices were selected (Cumin seed,
cinnamon, ginger, paprika and garlic) and their
ethanolic extracts (70%) were prepared followed by
assessment of their anti-glycation activity. Our data
showed that cumin seeds extract was most potent
in inhibiting the process of glycation with 80% inhibi-
tion (Table-1). Rest of the spices, did not produce a
significant inhibition i.e. cinnamon, ginger, paprika
and garlic showed the percent inhibition of 30%,
25%, 21% and 10% respectively. This is suggestive of
anti-ageing potential of cumin seeds. Search of
literature revealed that oxidative stress is also an
important factor responsible for deteriorating bodily
faculties with age. On similar lines, the spices were
reported to hold anti-oxidant potential as well (Srini-
vasan and nutrition, 2014). Keeping this in view, all
extracts were also tested for their ability to scav-
enge free radicals. It is of note that cumin seeds
were again found to be the most potent with inhibi-
tion of 95% (Table-2). With an exception of garlic,
the other spices i.e. cinnamon, ginger and paprika,
also showed promising results with the percent
inhibition of 87%, 80% and 85% respectively. The
Venn diagram, at threshold of 50% revealed that
among all tested extracts, only cumin seed was
able to produce more than 50% inhibition in both
assays. This suggests that along with inhibition of
deleterious phenomenon of glycation, the cumin
seeds extract additionally possesses anti-oxidant
potential, which shall add value to its medicinal
properties against ageing and associated diseases.
Additionally, the HPLC fingerprint of cumin seed was
also obtained for crude reflection of medicinal
constituents residing in it. This shall also be useful for
future comparisons in similar studies involving cumin
seeds extract.
In conclusion, our data demonstrates that the
cumin seed presents itself as the promising function-
al food for the management of age-associated
diseases and diabetic complications attributed to
the deleterious phenomenon of glycation.
65 ZIAUDDIN JOURNAL OF PHARMACEUTICAL RESEARCH 2021, VOL. 2(1)
HPLC Fingerprint
The HPLC finger print of cumin seed extract is shown in Figure-2
Figure-2 HPLC Fingerprint of Cumin Seed Extract
66 ZIAUDDIN JOURNAL OF PHARMACEUTICAL RESEARCH 2021, VOL. 2(1)
REFERENCES
AIYEGORO, O. A. & OKOH, A. I. 2010. Preliminary
phytochemical screening and in vitro antioxidant
activities of the aqueous extract of Helichrysum longi-
folium DC. BMC Complementary and Alternative
medicine, 10, 21.
BENELLI, G., PAVELA, R., PETRELLI, R., CAPPELLACCI, L.,
CANALE, A., SENTHIL-NATHAN, S. & MAGGI, F. 2018.
Not just popular spices! Essential oils from Cuminum
cyminum and Pimpinella anisum are toxic to insect
pests and vectors without affecting non-target inver-
tebrates. Industrial Crops and Products, 124, 236-243.
BERR, C., PORTET, F., CARRIERE, I., AKBARALY, T. N.,
FEART, C., GOURLET, V., COMBE, N., BARBERGER-GA-
TEAU, P. & RITCHIE, K. 2009. Olive oil and cognition:
results from the three-city study. Dementia and geriat-
ric cognitive disorders, 28, 357-364.
CAMPBELL, I. L. 1996. Exacerbation of lymphocytic
choriomeningitis in mice treated with the inducible
nitric oxide synthase inhibitor aminoguanidine. Journal
of neuroimmunology, 71, 31-36.
CAMPISI, J., KAPAHI, P., LITHGOW, G. J., MELOV, S.,
NEWMAN, J. C. & VERDIN, E. J. N. 2019. From discover-
ies in ageing research to therapeutics for healthy
ageing. 571, 183-192.
DEARLOVE, R. P., GREENSPAN, P., HARTLE, D. K., SWAN-
SON, R. B. & HARGROVE, J. L. J. J. O. M. F. 2008. Inhibi-
tion of protein glycation by extracts of culinary herbs
and spices. 11, 275-281.
GOLDIN, A., BECKMAN, J. A., SCHMIDT, A. M. & CREA-
GER, M. A. J. C. 2006. Advanced glycation end prod-
ucts: sparking the development of diabetic vascular
injury. 114, 597-605.
HASLBECK, K.-M., SCHLEICHER, E., BIERHAUS, A., NAW-
ROTH, P., HASLBECK, M., NEUNDÖRFER, B., HEUSS, D. J.
E., ENDOCRINOLOGY, C. & DIABETES 2005. The
AGE/RAGE/NF-κB pathway may contribute to the
pathogenesis of polyneuropathy in impaired glucose
tolerance (IGT). 113, 288-291.
HASLER, C. M. J. T. J. O. N. 2002. Functional foods:
benefits, concerns and challenges—a position paper
from the American Council on Science and Health.
132, 3772-3781.
IGASE, M. & IGASE, K. J. G. S. R. 2018. Cognitive impair-
ment and glycative stress. 5, 45-49.
KANNAPPAN, R., GUPTA, S. C., KIM, J. H., REUTER, S. &
AGGARWAL, B. B. 2011. Neuroprotection by spice-de-
rived nutraceuticals: you are what you eat! Molecular
neurobiology, 44, 142-159.
KHAN, S. A., HAIDER, A., MAHMOOD, W., ROOME, T. &
ABBAS, G. J. P. B. 2017. Gamma-linolenic acid amelio-
rated glycation-induced memory impairment in rats.
55, 1817-1823.
LEUNG, C., HERATH, C. B., JIA, Z., ANDRIKOPOULOS, S.,
BROWN, B. E., DAVIES, M. J., RIVERA, L. R., FURNESS, J.
B., FORBES, J. M. & ANGUS, P. W. J. W. J. O. G. 2016.
Dietary advanced glycation end-products aggra-
vate non-alcoholic fatty liver disease. 22, 8026.
POLE, A., DIMRI, M. & DIMRI, G. P. J. A. M. S. 2016.
Oxidative stress, cellular senescence and ageing. 3.
RAMASAMY, R., VANNUCCI, S. J., YAN, S. S. D.,
HEROLD, K., YAN, S. F. & SCHMIDT, A. M. J. G. 2005.
Advanced glycation end products and RAGE: a
common thread in aging, diabetes, neurodegenera-
tion, and inflammation. 15, 16R-28R.
REDDY, V. P. & BEYAZ, A. 2006. Inhibitors of the Maillard
reaction and AGE breakers as therapeutics for
multiple diseases. Drug discovery today, 11, 646-654.
ROSS, S. M. J. H. N. P. 2015. Sugar-induced aging: the
deleterious effects of excess dietary sugar intake. 29,
114-116.
SERGIEV, P., DONTSOVA, O. & BEREZKIN, G. J. A. N.
2015. Theories of aging: an ever-evolving field. 7.
SHARMA, P., YELNE, M. & DENNIS, T. 2001. Database on
medicinal plants used in Ayurveda, Central Council
for Research in Ayurveda and Sidda. New Delhi, 2,
538-549.
SHEN, Q., ZHANG, B., XU, R., WANG, Y., DING, X. & LI, P.
2010. Antioxidant activity in vitro of the selenium-con-
tained protein from the Se-enriched Bifidobacterium
animalis 01. Anaerobe, 16, 380-386.
SINGH, R. P., GANGADHARAPPA, H. & MRUTHUNJAYA,
K. 2017. Cuminum cyminum–A popular spice: An
updated review. Pharmacognosy Journal, 9.
SOLFRIZZI, V., PANZA, F., TORRES, F., MASTROIANNI, F.,
DEL PARIGI, A., VENEZIA, A. & CAPURSO, A. 1999. High
monounsaturated fatty acids intake protects against
age-related cognitive decline. Neurology, 52,
1563-1563.
SOUTHERN, L., WILLIAMS, J. & ESIRI, M. M. J. B. N. 2007.
Immunohistochemical study of N-epsilon-car-
boxymethyl lysine (CML) in human brain: relation to
vascular dementia. 7, 35.
SRINIVASAN, K. J. C. R. I. F. S. & NUTRITION 2014. Antioxi-
dant potential of spices and their active constituents.
54, 352-372.
SUN, H., YUAN, Y. & SUN, Z. J. B. R. I. 2016. Update on
mechanisms of renal tubule injury caused by
advanced glycation end products. 2016.
SUZMAN, R. & BEARD, J. J. W. H. O. 2011. Global health
and ageing. Bethesda, MD: US Department of Health
and Human Services.
THORNALLEY, P. J. 2003. Use of aminoguanidine (Pima-
gedine) to prevent the formation of advanced glyca-
tion endproducts. Archives of biochemistry and
biophysics, 419, 31-40.
YANNAKOULIA, M., KONTOGIANNI, M. & SCARMEAS,
N. 2015. Cognitive health and Mediterranean diet: just
diet or lifestyle pattern? Ageing research reviews, 20,
74-78.
YONEI, Y., YAGI, M. & TAKABE, W. J. G. S. R. 2020. Stop
the “Vicious Cycle” induced by Glycative Stress. 7,
13-21.
ZARANDI, M. H., ALLAHDADI, I., KHALAJ, H. & LABBAFI,
M. 2017. Cuminum cyminum L. Seed Science and
Technology, 6.
... Plant extracts exert anti-glycation potential by reducing the interaction of proteins and sugars by interfering with the lysine residues in the protein. A previous study reported 13.53% glycation inhibition via the aqueous extract [52], while the hydro-ethanolic extract exerted 80% inhibition at 1 mg/mL [53]. On the contrary, Carvacrol and Thymol displayed a frail anti-AGE activity compared to the methanolic plant extract [54]. ...
... The positive control (Phenol red) exhibited 76.42 ± 7.98% at 50 µM, similar to a previously reported value [23]. [52], while the hydro-ethanolic extract exerted 80% inhibition at 1 mg/mL [53]. contrary, Carvacrol and Thymol displayed a frail anti-AGE activity compared to th anolic plant extract [54]. ...
Article
Full-text available
Neurodegenerative diseases (NDs) are a large category of progressive neurological disorders with diverse clinical and pathological characteristics. Among the NDs, Alzheimer's disease (AD) is the most widespread disease, which affects more than 400 million people globally. Oxida-tive stress is evident in the pathophysiology of nearly all NDs by affecting several pathways in neurodegeneration. No single drug can manage multi-faceted diseases like NDs. Therefore, an alternative therapeutic strategy is required, which can affect several pathophysiological pathways at a time. To achieve this aim, hexane and ethyl acetate extract from Trachyspermum ammi (Carom) were prepared, and GC/MS identified the bioactive compounds. For the cell-based assays, ox-idative stress was induced in SH-SY5Y neuroblastoma cells using hydrogen peroxide to evaluate the neuroprotective potential of the Carom extracts/bioactives. The extracts/bioactives provided neuroprotection in the cells by modulating multiple pathways involved in neurodegeneration, such as alleviating oxidative stress and mitochondrial membrane potential. They were potent inhibitors of acetylcholine esterase enzymes and displayed competitive/mixed-type inhibition. Additionally, anti-Aβ 1-42 fibrilization/oligomerization and anti-glycation activities were also analyzed. The multi-faceted neuroprotection shown via Carom/Carvacrol makes it a prospective contender in drug development for NDs.
Article
Full-text available
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan. The milestones that mark the advances in ageing research, the medical, commercial and societal implications of ageing and the different ageing pathways and processes that are associated with ageing are discussed.
Article
Full-text available
Context: γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. Objective: The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. Materials and methods: GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 μM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. Results: Our data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 μM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. Conclusion: The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.
Article
Full-text available
AIM To determine if manipulation of dietary advanced glycation end product (AGE), intake affects non-alcoholic fatty liver disease (NAFLD) progression and whether these effects are mediated via RAGE. METHODS Male C57Bl6 mice were fed a high fat, high fructose, high cholesterol (HFHC) diet for 33 wk and compared with animals on normal chow. A third group were given a HFHC diet that was high in AGEs. Another group was given a HFHC diet that was marinated in vinegar to prevent the formation of AGEs. In a second experiment, RAGE KO animals were fed a HFHC diet or a high AGE HFHC diet and compared with wildtype controls. Hepatic biochemistry, histology, picrosirius red morphometry and hepatic mRNA were determined. RESULTS Long-term consumption of the HFHC diet generated significant steatohepatitis and fibrosis after 33 wk. In this model, hepatic 4-hydroxynonenal content (a marker of chronic oxidative stress), hepatocyte ballooning, picrosirius red staining, ?-smooth muscle actin and collagen type 1A gene expression were all significantly increased. Increasing the AGE content of the HFHC diet by baking further increased these markers of liver damage, but this was abrogated by pre-marination in acetic acid. In response to the HFHC diet, RAGE-/- animals developed NASH of similar severity to RAGE+/+ animals but were protected from the additional harmful effects of the high AGE containing diet. Studies in isolated Kupffer cells showed that AGEs increase cell proliferation and oxidative stress, providing a likely mechanism through which these compounds contribute to liver injury. CONCLUSION In the HFHC model of NAFLD, manipulation of dietary AGEs modulates liver injury, inflammation, and liver fibrosis via a RAGE dependent pathway. This suggests that pharmacological and dietary strategies targeting the AGE/RAGE pathway could slow the progression of NAFLD.
Article
Full-text available
Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether N ε -(carboxymethyl) lysine (CML, a member of the AGEs family) increases lipid accumulation in a human renal tubular epithelial cell line (HK-2) via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR), followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr) mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.
Article
Full-text available
Excessive free radical generation overbalancing the rate of their removal leads to oxidative stress. Oxidative stress has been implicated in the etiology of cardiovascular disease, inflammatory diseases, cancer, and other chronic diseases. Antioxidants are compounds that hinder the oxidative processes and thereby delay or suppress oxidative stress. There is a growing interest in natural antioxidants found in plants. Herbs and spices are most important targets to search for natural antioxidants from the point of view of safety. A wide variety of phenolic compounds present in spices that are extensively used as food adjuncts possess potent antioxidant, anti-inflammatory, antimutagenic, and cancer preventive activities. This paper reviews a host of spice compounds as exogenous antioxidants that are experimentally evidenced to control cellular oxidative stress, both in vitro and in vivo, and their beneficial role in preventing or ameliorating oxidative-stress-mediated diseases, from atherosclerosis to diabetes to cataract to cancer. The antioxidative effects of turmeric/curcumin, clove/eugenol, red pepper/capsaicin, black pepper/piperine, ginger/gingerol, garlic, onion, and fenugreek, which have been extensively studied and evidenced as potential antioxidants, are specifically reviewed in this treatise.
Article
Full-text available
Numerous lines of evidence indicate that chronic inflammation plays a major role in the development of various neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, brain tumor, and meningitis. Why these diseases are more common among people from some countries than others is not fully understood, but lifestyle factors have been linked to the development of neurodegenerative diseases. For example, the incidence of certain neurodegenerative diseases among people living in the Asian subcontinent, where people regularly consume spices, is much lower than in countries of the western world. Extensive research over the last 10 years has indicated that nutraceuticals derived from such spices as turmeric, red pepper, black pepper, licorice, clove, ginger, garlic, coriander, and cinnamon target inflammatory pathways, thereby may prevent neurodegenerative diseases. How these nutraceuticals modulate various pathways and how they exert neuroprotection are the focus of this review.
Article
Important portion of this production might be directed to the fabrication of green pesticides relying on the well-documented efficacy of many essential oils against insect pests as well as vectors, besides their safety for human health and the environment. In this regard, two popular spices of economic importance, such as cumin (Cuminum cyminum) and anise (Pimpinella anisum), which are not only cheap, readily available, generally recognized as safe (GRAS) but also produces larger amounts of essential oils, are gaining interest for botanical insecticide development. Herein, we evaluated the efficacy of the essential oils obtained from seeds of these two spices on two agricultural pests, i.e., the peach-potato aphid Myzus persicae and the tobacco cutworm Spodoptera littoralis, and on two insect vectors, i.e., the common housefly Musca domestica and the lymphatic filariasis and Zika virus vector Culex quinquefasciatus. Furthermore, their safety on beneficial organisms such as the earthworm Eisenia fetida and the aphid predator Harmonia axyridis was assessed. The two essential oils, characterized by γ-terpinen-7-al (35.3%), cumin aldehyde (21.8%), and α-terpinen-7-al (15.4%), and (E)-anethole (93.0%), respectively, showed noteworthy effects against all pest targets, with anise more effective on larvae of C. quinquefasciatus (LC⁠50=25.4 μl L⁠−1) and S. littoralis (LD⁠50=57.3 μg larva⁠−1), whereas cumin was more active on adults of M. persicae (LC⁠50=3.2 ml L⁠−1) and M. domestica (LD⁠50=31.8 μg adult⁠1). Moreover, when compared with the commercial insecticide α-cypermethrin, at sub-lethal doses they were definitely devoid of toxic effects on E. fetida and H. axyridis. These results represent a milestone to manufacture and commercialize green formulations to be used in crop protection and to combat insect vectors of public importance.
Article
Aminoguanidine (AG) is a prototype therapeutic agent for the prevention of formation of advanced glycation endproducts. It reacts rapidly with alpha,beta-dicarbonyl compounds such as methylglyoxal, glyoxal, and 3-deoxyglucosone to prevent the formation of advanced glycation endproducts (AGEs). The adducts formed are substituted 3-amino-1,2,4-triazine derivatives. Inhibition of disease mechanisms, particularly vascular complications in experimental diabetes, by AG has provided evidence that accumulation of AGEs is a risk factor for disease progression. AG has other pharmacological activities, inhibition of nitric oxide synthase and semicarbazide-sensitive amine oxidase (SSAO), at pharmacological concentrations achieved in vivo for which controls are required in anti-glycation studies. AG is a highly reactive nucleophilic reagent that reacts with many biological molecules (pyridoxal phosphate, pyruvate, glucose, malondialdehyde, and others). Use of high concentrations of AG in vitro brings these reactions and related effects into play. It is unadvisable to use concentrations of AG in excess of 500 microM if selective prevention of AGE formation is desired. The peak plasma concentration of AG in clinical therapy was ca. 50 microM. Clinical trial of AG to prevent progression of diabetic nephropathy was terminated early due to safety concerns and apparent lack of efficacy. Pharmacological scavenging of alpha-oxoaldehydes or stimulation of host alpha-oxoaldehyde detoxification remains a worthy therapeutic strategy to prevent diabetic complications and other AGE-related disorders.
Article
Several studies indicated that bifidobacteria possessed strong antioxidant activity. In present study, the antioxidant activities of Bifidobacterium animalis 01 proteins were evaluated using six assays, namely, linoleic acid preoxidation assay, erythrocyte hemolysis assay, 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, reducing power assay, hydroxyl (.OH) and superoxide radicals (.O(2)(-)) assays, in which the last two assays were measured by electron spin resonance (ESR). There were two kinds of B. animalis 01 proteins in this study, the regular B. animalis 01 protein (Pro-CK) and the B. animalis 01 selenium-contained protein (Pro-Se). Both Pro-CK and Pro-Se showed concentration dependent antioxidant activity in DPPH assay, reducing power assay and erythrocyte hemolysis assay. All results of six assays indicated that the antioxidant activity of the B. animalis 01 protein was improved remarkably after selenium was incorporated. The antioxidant activity of Pro-Se increased with the increase of selenium content in Pro-Se suggesting selenium played a positive role in enhancing the antioxidant activity of B. animalis 01 protein. Moreover, organic selenium was more effective than inorganic selenium on enhancing the hydroxyl radical scavenging ability of B. animalis 01 protein.