Physiological Scrutiny to Appraise a Flavonol Versus Statins

Abstract

Because of the vast use of statins to control and treat hyperlipidemia, this study was set to compare the most common statins Atorvastatin and Simvastatin with the flavonol Kaempferol considering the unwilled collateral e ects of them. Sixty adult albino male rats were allocated into five groups of twelve members to each. It is obvious based on the results that Atorvastatin could cause significant declination in the hemoglobin, hematocrit, platelets and leukocytes while simvastatin could cause a significant declination in leukocytes and platelets, on the other side; the kaempferol could not a ect these values comparing with the control group. The lipid profile and the hepatic enzymes like Alanine aminotransferase (ALT), Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were significantly disturbed too in all groups and it was very clear that serum aminotransferases and alkaline phosphatase were significantly elevated in all groups except the Kaempferol comparing with control group at (P≤0.05). It is very obvious that kaempferol could ameliorate the lipid profile the antioxidant enzymes and the blood values in a manner which is better than those of statins. Keywords 1* 2 3 3 3 1 2 3 3/14/23, 11:56 AM Physiological Scrutiny to Appraise a Flavonol Versus Statins | Biomedical and Pharmacology Journal https://biomedpharmajournal.org/vol16no1/physiological-scrutiny-to-appraise-a-flavonol-versus-statins/ 2/14

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Biomedical & Pharmacology Journal, March 2023. Vol. 16(1), p. 289-293
Published by Oriental Scientific Publishing Company © 2023
This is an Open Access article licensed under a Creative Commons license: Attribution 4.0 International (CC-BY).
Physiological Scrutiny to Appraise a Flavonol Versus Statins
Wissam Sajid Hashim1*, Youssef Shakuri Yasin2, Azal Hamoody Jumaa3,
Marwan I. Al-Zuhairi3 and Ahmed Hazem Abdulkareem3
1Department of Physiology and medical Physics, College of Medicine, Al-Muthanna University, Iraq.
2Department of Nursing, Bilad Alrafidain University College, Diyala, 32001, Iraq.
3Faculty of Pharmacy, Bilad Alrafidain University College, Diyala, 32001, Iraq.
*Corresponding Author E-mail: dr.w80@mu.edu.iq
https://dx.doi.org/10.13005/bpj/2610
(Received: 21 December 2022; accepted: 24 January 2023)
Because of the vast use of statins to control and treat hyperlipidemia, this study
was set to compare the most common statins Atorvastatin and Simvastatin with the flavonol
Kaempferol considering the unwilled collateral effects of them. Sixty adult albino male rats
were allocated into five groups of twelve members to each. It is obvious based on the results
that Atorvastatin could cause significant declination in the hemoglobin, hematocrit, platelets
and leukocytes while simvastatin could cause a significant declination in leukocytes and
platelets, on the other side; the kaempferol could not affect these values comparing with the
control group. The lipid profile and the hepatic enzymes like Alanine aminotransferase (ALT),
Aspartate aminotransferase (AST) and Alkaline phosphatase (ALP) were significantly disturbed
too in all groups and it was very clear that serum aminotransferases and alkaline phosphatase
were significantly elevated in all groups except the Kaempferol comparing with control group
at (P=0.05). It is very obvious that kaempferol could ameliorate the lipid profile the antioxidant
enzymes and the blood values in a manner which is better than those of statins.
Keywords: Atorvastatin; Antioxidants; Flavonol; Kaempferol; Simvastatin; Statins.
Statins are a vast family of medicaments
which are used worldwide as remedies for the
elevated levels of blood lipids or the functional
disturbances of lipoproteins metabolism.1
Simvastatin and atorvastatin are members of
this family.2 It is true that statins could lower
blood lipids but at the same time they could
cause significant disturbances in other body
systems, for instance they cause a declination
in the hemoglobin, platelets, erythrocytes and
leukocytes with marked elevations of hepatic
enzymes.3,4 Hence, atorvastatin and simvastatin
are the subject of this study. On other side, the
avonol; kaempferol which is naturally presents in
vegetables and fruits particularly in grape,5 is the
subject of this study to be compared with statins.
Kaempferol was documented to be effective against
many diseases with strong antioxidant features. It
can be isolated from tea, broccoli, witch-hazel,
propslis, grapefruit, and other plant sources. The
pharmacological properties of kaempferol exhibit
antioxidant, anti-inflammatory, and anticancer
activity. Kaempferol also provides benets for the
treatment of atherosclerosis..6-8
MATERIALS AND METHODS
Animals of the experiment
Sixty adult male albino rats of 250-280
grams weights were adopted. The experiment has

290 HasHim et al., Biomed. & Pharmacol. J, Vol. 16(1), 289-293 (2023)
continued for two months after passing the period
of acclimatization of two months with a strict rules
considering the optimal conditions, the standard
diet and the special fat diet. The high fat diet was
introduced to the concerned groups to induce
hyperlipidemia.
Protocol of experiment
1. Control group (C group): Twelve male
rats were maintained on a standard diet.9
2. Cholesterol group (CHO group): Twelve
male rats were maintained on high fat diet-HFD
which consists of (lipids 41.5%, carbohydrates
40.2%, and proteins 18.3%).10
3. Atorvastatin group (ATST group): Twelve
male rats were maintained on HFD and they were
dosed once a day orally with atorvastatin 20 mg/
day by the use of oral gavage.
4. Simvastatin group (SVST group): Twelve
male rats were maintained on HFD and they were
dosed once a day orally with simvastatin 17 mg/day
by the use of oral gavage. The doses of atorvastatin
and simvastatin were depended based upon LD50
mentioned by.11,12
5. Kaempferol group (KMP group): Twelve
male rats were maintained on HFD and they
were injected once a day intraperitoneally with
kaempferol 2.5 mg/day. The dose of kaempferol
was depended upon a previous study.13
Parameters of the study
Dongi (Dongi 120 Italia) device was used
to obtain the required test exploiting the sera gained
from the animals of this study.
Statistical Analysis
ANOVA one way test was depended using
SPSS program version 21 to nd out the least
signicant differences among groups.
Ethical approval
This study was approved by the Ethics
Committee of the Scientic Research, College of
Medicine, Al-Muthanna University, Iraq (approval
no. 415/24.03.2022).
RESULTS
The erythrocytes count or the red blood
cells count R.B.C. was clearly affected and
signicantly elevated in the cholesterol or CHO
group while those values of the atorvastatin ATST,
simvastatin SVST and kaempferol KMP groups
were not affected comparing them with the control
Table 1. Comparison among kaempferol and statins effects on blood parameters of rats
Groups R.B.C× 106 cells/µl HBg/dl HCT% W.B.C.× 103 cells/µl PLT× 103 plt/µl
C 6.3 ± 0.53 b 11.4 ± 0.2 b 42.7 ± 1.11 b 8.3 ± 0.11 a 541.2 ± 33.66 a
CHO 8.3 ± 0.41 a 13.3 ± 0.34 a 51.2 ± 2.22 a 2.5 ± 0.23 b 433.2 ± 20.7 b
ATST 6.5 ± 0.44 b 10.3 ± 1.08 c 36.4 ± 2.12 c 3.1 ± 0.11 b 276.8 ± 8.77 c
SVST 6.7 ± 0.22 b 12 ± 0.3 b 40.3 ± 1.33 b 2.7 ± 0.15 b 311.3 ± 11.55 c
KMP 6.7 ± 0.21 b 12.1 ± 0.22 b 41.2 ± 4.14 b 8.4 ± 0.8 a 471.8 ± 42.11 b
LSD 1.6 1.1 6.3 5.2 69.4
Groups: C=Control, CHO=Cholesterol, ATST= Atorvastatin, SVST= Simvastatin, KMP= Kaempferol. LSD= Least Signicant
Difference. Similar small letters on number; a, b, c refer to presence of signicance or not among groups.
Table 2. Comparison among kaempferol and statins effects on differential leukocytes count of rats
Groups Neutrophil% Lymphocyte% Monocyte% Eosinophil% Basophil%
C 60.3 ± 1.01 c 22.8 ± 1.3 b 11 ± 1.2 a 0.4 ± 0.5 d 1 ± 0.1 c
CHO 72.2 ± 1.3 a 17.5 ± 1.2 c 6.7 ± 1.3 b 1 ± 0.1 a 1 ± 0.1 c
ATST 65.4 ± 1.11 b 20.6 ± 1.03 b 7.6 ± 1.4 b 0.2 ± 0.4 c 0.4 ± 0.5 d
SVST 41 ± 1.03 d 46.6 ± 2.6 a 6.4 ± 1.1 b 0.2 ± 0.4 c 1.6 ± 0.5 a
KMP 56.2 ±2.01 c 22.2 ± 1.02 b 12.3 ± 1.6 a 0.6 ± 0.5 b 1.2 ± 0.4 b
LSD 5.1 3.1 3.4 0.2 0.2
Groups: C=Control, CHO=Cholesterol, ATST= Atorvastatin, SVST= Simvastatin, KMP= Kaempferol. LSD= Least Signicant
Difference. Similar small letters on number; a, b, c refer to presence of signicance or not among groups.

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HasHim et al., Biomed. & Pharmacol. J, Vol. 16(1), 289-293 (2023)
Table 3. Comparison among kaempferol and statins effects on lipid prole of rats
Groups TC(mg/dl) TAGs (mg/dl) HDL (mg/dl) LDL (mg/dl) VLDL (mg/dl)
C 126 ± 3.3 c 68.4 ± 3.13 d 20.2 ± 1.1 a 90.4 ± 2 c 12.4 ± 1.2 d
CHO 161.8 ± 5.22 a 134.2 ± 2.7 a 10.2 ± 1.3 b 121.2 ± 2.1 a 26.2 ± 1.3 a
ATST 135 ± 5.11 b 124.6 ± 2.5 b 12.2 ± 1.4 b 100.2 ± 3.1 b 22.2 ± 1.7 b
SVST 136.6 ± 2.97 b 102.4 ± 2.2 c 12 ± 1.3 b 102 ± 3.2 b 20.2 ± 1.4 c
KMP 125 ± 1.11 c 64.2 ± 3.22 e 20 ± 3.2 a 91 ± 4.2 c 12 ± 2.1 d
LSD 10 4.2 7.8 9.2 2
Groups: C=Control, CHO=Cholesterol, ATST= Atorvastatin, SVST= Simvastatin, KMP= Kaempferol. LSD= Least Signicant
Difference. Similar small letters on number; a, b, c refer to presence of signicance or not among groups.
Table 4. Comparison among kaempferol and statins effects on hepatic enzymes and creatine of rats
Groups AST(U/L) ALT(U/L) ALP(U/L) Creatine(g/dl)
C 21 ± 1.13 d 34.6 ± 3.13 c 237 ± 6.12 b 1.7 ± 0.4 b
CHO 68 ± 4.12 b 58.8 ± 5.31 b 299.2 ± 10.14 a 2.8 ± 0.5 a
ATST 86.8 ± 7.3 a 52.8 ± 4.23 b 278.4 ± 10.21 a 1.5 ± 0.2 b
SVST 54.4 ± 9.13 c 90.8 ± 7 a 279.4 ± 10.1 a 1.6 ± 0.6 b
KMP 30.4 ± 2.21 d 43.6 ± 6.24 c 248.2 ± 9.91 b 1.4 ± 0.3 b
LSD 18.8 9.2 30.2 1.1
Groups: C=Control, CHO=Cholesterol, ATST= Atorvastatin, SVST= Simvastatin, KMP= Kaempferol. LSD= Least
Signicant Difference. Similar small letters on number; a, b, c refer to presence of signicance or not among groups.
group. The hemoglobin HB concentration and the
hematocrit HCT were signicantly elevated in the
CHO group and signicantly declined in the ATST
group comparing with the control and the other
groups. The leukocytes count or the total white
blood cells count W.B.C. and the platelets count
PLT were signicantly declined in all the groups
comparing with the control group at (Pd”0.05);
table 1. Considering the differential leukocytes
count, the neutrophils were signicantly elevated
in the CHO and ATST groups with signicant
declination in the SVST group comparing with the
control group. The lymphocytes were signicantly
declined in the CHO group with significant
elevation in the SVST group comparing with
the control group. The monocytes signicantly
declined in all treatment groups accept the KMP
group comparing with the control. The eosinophils
were signicantly declined in the ATST and SVST
groups with signicant elevation in the CHO and
KMP groups comparing with the control group.
The basophils were signicantly elevated in the
KMP and SVST groups with signicant declination
in the ATST group comparing with the control
group at (Pd”0.05); table 2. The lipid prole of
all the treatment groups was also affected as it is
seen in table 3, where the total serum cholesterol
TC was signicantly elevated in the CHO group
and it was signicantly less than the CHO group
considering the ATST and SVST groups but it was
also signicantly higher than the control group. The
same was true for the triacylglycerols TAGs, low
density lipoprotein LDL, and the very low density
lipoprotein VLDL and the KMP group was the
same as the control. The high density lipoprotein
HDL was signicantly declined in all treatment
groups except the KMP comparing with the
control at (Pd”0.05). The serum hepatic enzymes;
the alanine amino transferase ALT, the aspartate
aminotransferase AST and the alkaline phosphatase
ALP were all signicantly elevated in all treatment
groups accept the KMP group comparing with the
control group. The serum creatine was signicantly
elevated only in the CHO group comparing with
control group at (Pd”0.05); table 4.

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DISCUSSION
Flavonols including the kaempferol
were documented by researchers to be of high
antioxidant features and have the ability to protect
different body systems and to ameliorate bodily
functions.14,15 Our results of this study come as
a conrmation to previous studies which have
documented the sequelae of statins16-18 and the
advantages of avonols.19-21 The declination in
the erythrocytes count, leukocytes count elevation,
lipoproteins disturbances and hepatic enzymes
disturbances which were noticed in our studies
might be due the oxidative stress which is caused
by the statins and hence the related reactive species
of oxygen which were documented to be the major
cause of cellular membranes damages and lipids
peroxidation.22-24 On other hand, the amelioration
in the lipid profile, erythrocytes, hemoglobin,
leukocytes, platelets and hepatic enzymes which
were caused by kaempferol might be due to the
great feature of kaempferol as antioxidant which
render it to be affective protector to the cellular
membranes, good modulator to the immunity,
good modulator to the cellular pathways of healing
and apoptosis and others.25-27 Histological study
involving the effects of the statins Atorvastatin
and Simvastatin comparing with Kaempferol on
organs of rats such as liver, kidney and spleen is
recommended to support our ndings.
CONCLUSIONS
It is obvious based upon our results in this
study that Kaempferol is safer than Atorvastatin
and Simvastatin when it is used to alleviate the
hyperlipidemia; where it does not affect the
blood indices such as hemoglobin, erythrocytes,
leukocytes and others. Besides, kaempferol
does not affect the hepatic enzymes, alkaline
phosphatase and creatine. We can recommend
the Kaempferol to be used as antihyperlipidemic
medicine. Hyperlipidemia is a worldwide common
disorder, so the use of Kaempferol would be a good
choice considering its lacking the side effects which
are caused by Atorvastatin and Simvastatin.
Conict of interest
No conict of interest.
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