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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)
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