Lycopene Improves the Metformin Effects on Blood Glucose and Neutrophil Counts in Type 2 Diabetic Rats Medina Sianturi1.
Neni Susilaningsih2.
Heri Nugroho3,4.
Maria Suryani1 Department of Nursing.
STIKes Elisabeth.
Semarang.
Central Java.
Indonesia Department of Histology.
Faculty of Medicine.
Diponegoro University.
Semarang.
Central Java.
Indonesia Department of Internal Medicine.
Faculty of Medicine.
Diponegoro University.
Semarang.
Central Java.
Indonesia Department of Interbnal Medicine.
Kariadi Teaching Hospital.
Semarang.
Central Java.
Indonesia Correspondence:
Medina Sianturi.
STIKes Elisabeth.
Kawi Street 11.
Semarang.
Indonesia Zip Code: 50252 Email: challenia@gmail.
Received: February 5, 2023 Revised: March 6, 2023 Accepted: April 20, 2023 Published: April 29, 2023 DOI: 10.
33086/ijmlst.
Abstract In patients with type 2 diabetes mellitus (T2DM), both innate and acquired immunity are weakened by Lycopene is one of the hydrocarbon carotenoids that has been widely studied for its powerful antioxidant and anti-inflammatory properties, furthermore act as hypoglycemic and immunomodulator.
Herein, we investigated the effect of lycopene and metformin combination on fasting blood glucose (FBG) and neutrophil The rats were divided randomly into six groups, each containing five rats.
Group 1 consisted of normal rats (N) and group 2.
T2DM (DM) rats, which were administered 0.
mL of coconut oil.
group 3 T2DM rats were administered 250 mg/kg of metformin in 0.
5 mL of coconut oil.
4,5 and 6 rats were administered a combination of metformin 250 mg/kg with 10 mg/kg (DML-.
, 20 mg/kg (DML-.
and 40 mg/kg (DML-.
of lycopene in 0.
5 mL of coconut oil, respectively.
Treatment was administered every day for 28 days.
A model of T2DM rats was induced by a high-fat diet for two weeks combined with streptozotocinAenicotinamide.
Data were analyzed with a one-way ANOVA test followed by the least significant difference (LSD) test.
There were significant differences in FBG levels and the number of neutrophils in all groups.
Lycopene combined with metformin had lower FBG concentrations and higher neutrophil counts compared to metformin monotherapy .
<0.
, and these observations were dose-dependent.
Lycopene combined with metformin can improve blood glucose and neutrophil counts in rats with diabetes.
The highest effect was observed in combination with lycopene at a dose of 40 mg/kg and metformin at a dose of 250 mg/kg.
Keywords Blood Glucose.
Lycopene.
Metformin.
Neutrophil.
T2DM.
Citation: Sianturi M.
Susilaningsih N.
Nugroho H.
Suryani M.
Lycopene Improves the Metformin Effects on Blood Glucose and Neutrophil Counts in Type 2 Diabetic Rats.
Indones J Med Lab Sci Technol.
:80Ae9.
DOI: 10.
33086/ijmlst.
This is an open access article distributed under the Creative Commons Attribution-ShareAlike 4.
0 International License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
A2023 by author.
Medina Sianturi, et al.
Lycopene was also able to reduce the INTRODUCTION Patients with type 2 diabetes mellitus neutrophil counts, although this was not (T2DM) experience disorders of blood significant, and the neutrophil-lymphocyte glucose metabolism that affect immunity.
has been found that diabetes mellitus (DM) Lycopene is a carotenoid (C40H.
found patients experience disturbances in the in red fruits and vegetables, including number and function of neutrophils .
Ae.
Research on neutrophil counts in DM patients watermelon, that has been made into an is still controversial.
A previous study showed an increase in the number of nutraceutical has been widely studied.
neutrophils in T2DM patients.
It was found Lycopene treatment is given either in single that the number of neutrophils with DM was doses or in combination with other therapies 25 times higher than that of those without such as metformin and statins.
The results DM .
The number of neutrophils was showed that lycopene is very beneficial for found to be higher in females .
, which diabetic patients who are intolerant to statins differed from the study by Eze et al.
The combination of metformin with low which reported a decrease in neutrophil doses of lycopene can reduce fasting blood counts in DM .
No correlation was found glucose levels after two weeks of intervention between fasting blood glucose and neutrophil .
, while high doses of 45 mg/kg can counts .
Neutrophils are cells of the innate reduce blood glucose by 50%, and the results immune system that are the first to arrive at are the same as with single or combined doses the site of infection and primarily kill of metformin and lycopene .
Treatment microorganisms .
Neutrophil count is with lycopene can reduce neutrophil counts, but it is no different from treatment with a The different dose of lycopene .
This is the first increases the risk of infection and thus the study to evaluate the effects of combination morbidity and mortality of DM patients .
therapy with lycopene and metformin on The results of studies that have been neutrophil counts in rats with T2DM at conducted so far suggest that the use of different doses of lycopene.
The aim of this lycopene as a single therapy can improve study was to evaluate the synergy of lycopene glycemic status by reducing fasting blood with metformin and its effects on blood glucose by 30 - 40% .
and HbA1c by glucose levels and rat immunity against type 41% .
, improving insulin resistance 2 DM induced by a combination of a high-fat levels, and increasing insulin sensitivity .
diet, streptozotocin, and nicotinamide.
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MATERIALS AND METHODS
performed in accordance with the principles Materials expressed in the Declaration of Helsinki.
All Thirty male albinos Wistar rats 6 weeks subjects were cared for according to the old and weighing approximately 160Ae200 g animal laboratory guidelines of the CNFS, was purchased from the Laboratory Animals Gadjah Mada University.
of the Center for Food and Nutrition Studies Experimental Design This study used a completely randomized Yogyakarta.
Indonesia.
They were housed in experimental design.
Wistar rats were an animal room with a 12-hour lightAedark randomly divided into a normal control group cycle, a temperature of 24AC A 2AC, and a (N group, n = .
and a type 2 diabetic ratsAo relative humidity of 5060%.
The rats were group .
= .
, which were fed a high-fat diet housed in individual stainless-steel cages and (Comfeed had ad libitum access to water and food, in Cholesterol 2%.
Folic Acid 0.
2%, and Lard accordance with the animal laboratory 10%).
After two weeks, the type 2 diabetic guidelines of the CNFS (Center for Natural ratsAo Sciences and Fisherie.
at Gadjah Mada StreptozotocinAeNicotinamide University.
Tesque.
Japa.
at 45 mg/kg/BW and 110
(CNFS),
Gadjah Mada University Metformin in the form of metformin Flour (Nacalai mg/kg, respectively, in citrate buffer .
H 4.
Tbk.
After 72 h, fasting blood Indonesi.
and tomato extract powder glucose Ou 200 mg/dl was determined in type containing 98% lycopene from Sigma- 2 diabetic rats .
PAR-s .
(Phapros Aldrich (St.
Louis.
MO.
USA) were used.
All In total, thirty Wistar rats were divided groups of rats with and without diabetes were into six groups for treatment with a treated with a single dose by gavage daily for 28 days.
Doses of lycopene and metformin The first and second groups were were chosen according to Eze et al.
and normal (N) and type 2 diabetic rats (DM) Figueiredo et al.
, respectively.
given 1 mL of coconut oil (CNFS).
The third The research was carried out in AugustAe group was type 2 diabetic rats treated with a September 2022 in the Laboratory Animals combination of metformin 250 mg/kg of CNFS.
Gadjah Mada University.
The in coconut oil (DMe.
The four groups were experimental procedures approved by the local ethics committee of the Medical Faculty combination of metformin and lycopene with of Diponegoro University .
pproval no.
a dose of 10 mg/kg lycopene in 1 mL of 28/EC/H/FK-UNDIP/IV/2.
coconut oil (DML-.
The fifth group were Ina.
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Statistical analysis combination of metformin and lycopene with Results were expressed as the mean A a dose of 20 mg/kg lycopene in 1 mL of standard deviation.
Differences between coconut oil (DML-.
The sixth group were groups were analyzed using one-way analysis of variance followed by the Least Significant combination of metformin and lycopene at a Difference (LSD) test.
Statistical analyzes dose of 40 mg/kg lycopene in 1 mL of were performed with SPSS version 23.
coconut oil (DML-.
All treatments Significant differences between mean values were considered at p < 0.
28 days through an oral feeding tube.
Coconut the bioavailability of lycopene but does not RESULTS Fasting Blood Glucose influence blood glucose concentration .
Biochemical Assays Figure 1A shows the levels of fasting After 28 days of final intervention and experimental groups after 28 days of overnight fasting, all experimental animals There were euthanized under ketamine anesthesia.
<0.
Blood samples were collected from the retro-
orbital flexure using a glass capillary, placed effect of the combination of metformin in a tube containing EDTA for neutrophil
with lycopene activity at doses of 20
and 40 mg/kg compared to metformin Serum
FBG
Blood
FBG
The mean differences were There was 3,500 rpm .
,000 .
for 10 minutes for the mg/dL, concentration was determined by the glucose oxidase method using a Dyasis reagent kit (Holzheim, in the metformin monotherapy group, with a German.
manufacturerAos Neutrophil mg/kg .
mean difference of -16.
25 (Figure 1B).
There manufacturerAos manual for Hematology Analyzer Sysmex FBG concentration and neutrophil counts (Figure .
XP-100 .
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Figure 1.
FBG concentration and neutrophil counts in rats with T2DM.
Values are expressed in terms of the mean A standard error of the mean.
Differences between groups were analyzed using a one-way analysis of variance followed by the least significant difference (LSD) test, *p<0,001, **p<0,05 compared to aN group.
compared to bDM group: compared to cDMet group.
compared to dDML-10 group.
compared to dDML-20 group.
and compared to dDML-40 group.
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differences were 0.
19 and -0.
34 x 106/AAL.
Neutrophil Counts The number of neutrophils in the Neutrophil count levels in the experimental groups after 28 days of combination of metformin and lycopene treatment is shown in Figure 1.
There was a dosed at 10 mg/kg were higher than those in significant difference in the number of the metformin monotherapy group, with a neutrophils between all groups .
< 0.
mean difference of 0.
19 x 106/AAL (Fiure 1B).
The combination of metformin and lycopene There was a significant and strong negative activity had a greater significant effect at relationship between FBG concentration and doses of 20 and 40 mg/kg compared to neutrophil count (Figure .
The Figure 2.
Correlation of FBG and neutrophil counts in rats with T2DM decrease in blood glucose and an increase in DISCUSSION The findings indicate that the induction neutrophil counts, indicating that these of T2DM in rats leads to disruptions in glucose metabolism and immune function, as control and immune function in T2DM rats.
evidenced by increased blood glucose and Metformin is the first-line therapy as an However.
T2DM .
Treatment with metformin monotherapy has combination with lycopene resulted in a been able to reduce blood glucose levels.
Metformin Ina.
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inhibiting glycogenesis in the liver, which This is the first study to evaluate the results in the reduction of hepatic glucose and effects of combination therapy with lycopene an increase in the hepatic cytosolic redox and metformin on neutrophil counts in rats state .
Administration of metformin and with T2DM.
This study showed that lycopene combination therapy with different treatment with a combination of lycopene and doses resulted in a better lowering of blood metformin increased neutrophil counts by 53 glucose when compared to metformin Ae 67,6%.
This result is different from the studies of Bathia at al.
, .
and Maldovan et accordance with the research of Haribabau et ,.
which found a decrease in neutrophil , .
Figueiredo, et al.
, .
Yin et al.
count by administering a single dose of .
and Zheng, et al.
, .
which stated that lycopene to patients with hepatocellular lycopene, as an antioxidant, can act as an These anti-diabetic.
Lycopene, as an antidiabetic, by Eze et al.
, .
which showed that giving preventing insulin resistance, inflammation, lycopene monotherapy to diabetic rats could and fat accumulation .
It increases insulin increase the number of neutrophils, although sensitivity through lycopene, and increases it was not significantly higher when insulin sensitivity through upregulation of compared to this study.
The results of this insulin receptors and IGF-1 receptors.
PI3K, study prove that the combination of lycopene and metformin is effective in increasing Akt phosphorylated in the hippocampus and cerebral cortex of insulin-resistant rats.
Treatment These results are consistent with research neutrophil counts in T2DM rats.
The mechanism of action of lycopene can improve the immune status of patients with lycopene and metformin resulted in a DM, because lycopene is immunomodulatory decrease in fasting blood glucose that was 13- and increases the number of neutrophils 27% higher than a single dose of lycopene .
Neutrophils can improve immunity by .
The addition of lycopene at doses of reducing infections, which are common in 20 mg/kg and 40 mg/kg in metformin therapy patients with T2DM.
provided better blood glucose reduction The combination of metformin and results than the Figueiredo .
study, where lycopene can improve the mechanism of the addition of 45 mg/kg lycopene had the same blood glucose reduction results as causing the number of neutrophils to be metformin monotherapy.
higher than with metformin treatment This improvement occurs Ina.
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through the mechanism of action of lycopene was founding to lower blood glucose through non-oxidative pathways that can improve immune status .
In contrast to Additionally, lycopene was founding the study by Huang et al.
, .
reducing FGD to improve the performance of metformin in increased the number of neutrophils, proving lowering blood glucose concentrations and a relationship between blood glucose levels increasing neutrophil counts.
The dose- and the immunity of T2DM patients.
This dependent effect of the lycopene and suggests that with a decrease in fasting blood metformin combination was observed.
The glucose concentration, there is an increase in combination of lycopene at a dose of 40 neutrophil counts.
mg/kg and metformin at a dose of 250 mg/kg The increasing doses of lycopene that has the highest effect.
improved blood glucose and neutrophil count monotherapy were 20 and 40 mg/kg.
This AUTHOR CONTRIBUTIONS Medina Sianturi:
indicates that the best doses to improve blood methodology, validation, formal analysis, sugar and immunity start at 20 mg/kg, which investigation, data curation, writing original is consistent with the study by Imran et al.
draft, writing review and editing, and project Neni Susilaningsih:
recommended dose is 20 mg/kg.
The results conceptualization, methodology, validation, of this observation prove that lycopene formal analysis, review, and editing.
Heri synergizes with metformin in decreasing Nugroho: conceptualization, methodology, blood glucose and improving the immune validation, review, and editing.
Maria system by increasing neutrophil counts in Suryani: conceptualization, review, and DM rats, and is expected to help type 2 DM patients .
The results of this study can be antioxidants, especially lycopene, in patients ACKNOWLEDGEMENTS We would like to thank the Ministry of with type 2 diabetes and be considered when Education.
Technology for providing funding for this Culture.
Research.
CONCLUSIONS
CONFLICT OF INTEREST
the combination of lycopene and metformin Ina.
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Medina Sianturi, et al.
REFERENCES