Table of Contents  
ORIGINAL ARTICLE
Year : 2019  |  Volume : 18  |  Issue : 4  |  Page : 296-303

Effect of lemon balm (Melissa officinalis) aqueous extract on streptozotocin-induced diabetic rats


1 Department of Medical Physiology, National Research Centre, Giza, Egypt
2 Department of Pharmacology, National Research Centre, Giza, Egypt

Date of Submission02-Mar-2019
Date of Acceptance31-Mar-2019
Date of Web Publication28-Jan-2020

Correspondence Address:
Ph.D Mahitab I EL-Kassaby
Medical Physiology Department, National Research Centre, Dokki, 12311 Giza
Egypt
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/epj.epj_14_19

Rights and Permissions
  Abstract 

Background Lemon balm (Melissa officinalis) has a significant role in curing diseases and maintaining health through its antioxidant capacity. The aim of this study was to evaluate antidiabetic effect of lemon balm aqueous extract (LBAE) on streptozotocin (STZ)-induced diabetic rats.
Materials and methods The extract was administered to STZ-induced diabetic rats in low and high doses (200 and 400 mg/kg body weight/day, respectively) for 4 weeks. Serum insulin, glucose, lipid profiles, alkaline phosphatase, serum alanine aminotransferase, aspartate transaminase, creatinine and urea levels were determined, whereas total antioxidant capacity, malondialdehyde, nitric oxide, Na+/K+ ATPase activity (ATPase), tumor necrosis factor-α, and cluster of differentiation 4 levels were evaluated in liver and kidney tissue homogenates.
Results and conclusion Oral administration of LBAE significantly decreased glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, malondialdehyde, nitric oxide, tumor necrosis factor-α, and cluster of differentiation 4 levels. However, insulin, high-density lipoprotein cholesterol, and total antioxidant capacity levels significantly increased with respect to diabetic control group. These findings revealed that LBAE possesses antihyperglycemic and antihyperlipidemic effects against STZ-induced disorders in diabetic rats. Hence, it can be used in the management of diabetes mellitus.

Keywords: diabetes, Melissa officinalis, rats, streptozotocin


How to cite this article:
EL-Kassaby MI, Salama AA, Mourad HH, Abdel-Wahhab KG. Effect of lemon balm (Melissa officinalis) aqueous extract on streptozotocin-induced diabetic rats. Egypt Pharmaceut J 2019;18:296-303

How to cite this URL:
EL-Kassaby MI, Salama AA, Mourad HH, Abdel-Wahhab KG. Effect of lemon balm (Melissa officinalis) aqueous extract on streptozotocin-induced diabetic rats. Egypt Pharmaceut J [serial online] 2019 [cited 2020 Oct 30];18:296-303. Available from: http://www.epj.eg.net/text.asp?2019/18/4/296/272268


  Introduction Top


The occurrence of diabetes mellitus elevated annually all over the world. Number of diabetic patients will increase to 592 million in 2035 [1]. Insulin-dependent patients are the majority, whereas noninsulin-dependent patients are small proportions (7–10%) of diabetic patients [2]. Type 1 diabetes (T1D), a chronic disease, is produced via pancreas autoimmune destruction of β-cells leading to hyperglycemia and insulin deficiency [3]. Thus, disturbances may be generated in glucose and lipid homeostasis resulting in dyslipidemia and hyperglycemia [4] causing increased production of oxygen free radicals (FRs) as a result of autoxidation of glucose [5] and glycosylation of protein [6] leading to oxidative stress, which is associated with several health complications, including antipathies, cardiovascular disorders, blindness, renal failure, neuropathies, and cancers [7].

Streptozotocin (STZ) is an antibiotic, used experimentally owing to its ability to induce insulin-dependent diabetes mellitus following multiple low-dose (30–50 mg/kg) injection. STZ-treated rats developed clinical features and signs that are similar to those found in T1D mellitus [8].

Plants provide a natural way for treating diverse complex disorders [9]. Edible biomaterial extracts have become a major focus of nutritional research to develop healthy and safe nutraceutical functional foods [10]. Recently, drug formulation from natural herbs attracted the attention of many researchers [11].

Lemon balm, Lamiacea family, has beneficial and flavouring properties in food and cosmetics cultivated not only for its characteristic lemon-scented leaves but also for several purposes. Balm has therapeutic properties in nervous agitation and gastrointestinal complaints [12]. Rosmarinic acid which is the main phenolic acid compound found in the leaves is responsible for the antioxidative and antiviral activities of plant extract [13]. This study aimed to investigate the antidiabetic effects of lemon balm aqueous extract (LBAE) on STZ-induced diabetic rats.


  Materials and methods Top


Animals

Forty Wistar rats were used. The animals were 6–10 weeks old (150–200 g). Animals were kept in clean plastic cages and housed in the animal holdings of the National Research Centre, Egypt. The animals were exposed to 12-h light, 12-h darkness cycle at room temperature. They were maintained on animal feeds and allowed free access to water and feeds. All animal methods are in accordance with the recommendations stated by ethics committee of the National Research Centre approval on animal care [14].

Drugs and chemicals

STZ was purchased from Sigma-Aldrich Corporation is an American chemical, life science and biotechnology company (St. Louis, Missouri, United States).

Glimepiride (Amaryl) was purchased from Sanofi-Aventis (Cairo, Egypt) El Sawah El Amiriya.

Plant extraction

Overall, 100 g of the powdered herb material was placed in a 1000-ml round-bottom quick-fit flask, and 400 ml distilled water was added. The mixture was left for 24 h. Water fractions were combined and filtered through qualitative no. 1 Whatman filter paper (Whatman International Ltd, Maidstone, UK). In Aroma and Flavoring Department, National Research Centre, the filtrate was subjected to lypholyzation process through freeze drier (Snijders Scientific, Tilburg, Holland) under pressure 0.1–0.5 mbar and temperature −35 to −41°C conditions. The dry extract was stored at −20°C until used.

Induction of diabetes

Diabetes was induced in overnight fasted rats by a single intraperitoneal injection of a freshly buffered (0.1 mol/l citrate, pH 4.5) solution of STZ at a dosage of 50 mg/kg body weight [15]. After 72 h of STZ administration, the tail vein blood was collected to determine fasting blood glucose level with an Accu Chek sensor comfort glucometer (China). Only rats with hyperglycemia (glucose over 250 mg/dl) were considered as diabetic and included in the experiment [16].

Experimental design

Rats were divided randomly into five groups (n=8) and treated orally for the experimental period of 4 weeks as follows: group 1, normal control animals; group 2, diabetic group that received STZ only; group 3, diabetic group that received Amaryl (0.1 mg/kg body weight/day) orally [17]; and groups 4 and 5, diabetic groups that received LBAE (200 and 400 mg/kg body weight/day) orally [18].

Serum and tissue biochemical analysis

At the end of the experiment, overnight fasting animals were Ether anesthetized. Venous retro orbital blood samples were collected using a glass capillary without anticoagulant. Serum was separated by centrifugation at 3000 rpm/min for 15 min. The resulting samples were stored at −20°C until assayed. Serum was used for estimation of glucose, insulin, lipid profiles, alanine aminotransferase, aspartate transferase, alkaline phosphatase, urea, and creatinine using specific diagnostic kits (Biodiagnostic, Dokki, Giza, Egypt).

Livers and kidneys were removed and washed in ice-cold saline solution immediately, and then each organ was homogenized in 0.1 mol/l potassium phosphate buffer (pH 7.4) using Tissue master TM125 (Omni International, Kennesaw United States). After centrifugation at 3000 r/min for 10 min, the clear supernatant was stored at −80°C to be used for estimation of total antioxidant capacity (TAC), malondialdehyde (MDA), nitric oxide (NO), Na+-K+-ATPase using specific diagnostic kits (Biodiagnostic), tumor necrosis factor-α (TNF-α), and cluster of differentiation 4 (CD4) levels using Elabscience Biotechnology Inc. Houston, Texas, United States.

Statistical analysis

All the values are presented as mean±SE. Comparisons between different groups were carried out using one-way analysis of variance followed by least significant difference (LSD) test for multiple comparisons. GraphPad Prism software, version 5 (GraphPad Software Inc., San Diego, California, USA), was used to carry out these statistical tests. The difference was considered significant when P less than 0.05.


  Results Top


Effect of Melissa officinalis aqueous extract on serum glucose and insulin levels

The glucose level was increased whereas insulin level was decreased in diabetic rats compared with normal rats. These results were reversed in diabetic group that received Amaryl when compared with diabetic rats. However, treatment with both doses of LBAE reduced the increased level of blood glucose and increased level of serum insulin when compared with diabetic rats) [Table 1]).
Table 1 Serum insulin and blood glucose levels in normal, streptozotocin-induced diabetic Amaryl-treated and streptozotocin-induced diabetic lemon balm aqueous extract-treated rats

Click here to view


Effect of Melissa officinalis aqueous extract on serum lipid profile

[Table 2] shows that rats in diabetic group displayed significantly elevated triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL) levels in comparison with normal group. However, serum high-density lipoprotein (HDL) level of diabetic rats was significantly lower than that of normal ones. In contrast, diabetic rats received Amaryl as well as those treated with LBAE in both low and high doses, showed significant decreases in TG, TC, and LDL levels and a significant increase in HDL level when compared with diabetic rats.
Table 2 Serum lipid profiles in normal, streptozotocin-induced diabetic Amaryl-treated and streptozotocin-induced diabetic lemon balm aqueous extract-treated rats

Click here to view


Effect of Melissa officinalis aqueous extract on liver and kidney functions

[Table 3] represents liver and kidney biochemical parameters. Significant alterations in these parameters were noticed in STZ diabetic rats as compared with normal rats. In contrary, STZ diabetic rats that received Amaryl reduced these elevations. The treatment with LBAE significantly improved the levels of these biochemical markers toward the normal values.
Table 3 Serum liver and kidney functions in normal, streptozotocin-induced diabetic Amaryl-treated, and streptozotocin-induced diabetic lemon balm aqueous extract-treated rats

Click here to view


Effect of Melissa officinalis aqueous extract on oxidative stress markers of liver and kidney

[Table 4] reveals that diabetic animals exhibited significant increases in MDA and NO levels concomitant with significant decreases in TAC level in both liver and kidney homogenates when were compared with normal control. On the contrary, administration of Amaryl and LBEA to diabetic rats succeeded to decreases in MDA and NO levels in concomitant with significant increases in TAC level in both liver and kidney homogenates as compared with diabetic rats.
Table 4 Oxidative stress markers of liver and kidney in normal, streptozotocin-induced diabetic Amaryl-treated, and streptozotocin-induced diabetic lemon balm aqueous extract-treated rats

Click here to view


Effect of Melissa officinalis aqueous extract on cluster of differentiation 4 and tumor necrosis factor-α levels

Liver and kidney CD4 levels were lower, whereas TNF-α levels were higher in diabetic rats compared with normal rats. However, treatment of diabetes rats with Amaryl as well as both doses of LBAE reduced TNF-α contents, whereas Amaryl and high-dose of LBAE only elevated CD4 contents when compared with diabetic rats ([Figure 1] and [Figure 2]).
Figure 1 Effect of lemon balm aqueous extract on the level of cluster of differentiation 4 (pg/g) in liver and kidney of normal and diabetic rats. (a) Significant from normal control at P<0.05. (b) Significant from diabetic control at P<0.05.

Click here to view
Figure 2 Effect of lemon balm aqueous extract on the level of tumor necrosis factor-α (pg/g) in liver and kidney of normal and diabetic rats. (a) Significant from normal control at P<0.05. (b) Significant from diabetic control at P<0.05.

Click here to view


Histopathological results

The light microscopical examination of the pancreatic section from the control rats revealed normal size of β-cells of islets of Langerhans ([Figure 3]a). In contrast, pancreatic section from diabetic control group showed small-size, atrophic pancreatic islets of Langerhans ([Figure 3]b). Pancreatic section from Amaryl (0.1 mg/kg) group showed pancreatic islets of Langerhans were shaped regularly and arranged evenly ([Figure 3]c). Pancreatic section from low-dose (200 mg/kg) and from high-dose (400 mg/kg) treated groups showed that pancreatic islets of Langerhans were shaped regularly and arranged evenly ([Figure 3]d and e, respectively).
Figure 3 (a) Pancreatic section from normal control group showed normal size of β-cells of islets of Langerhans shown by arrow (H&E, ×400), (b) pancreatic section from diabetic control group showed small-size, atrophic pancreatic islets of Langerhans, which were shown by arrow (H&E, ×400), (c) pancreatic section from Amaryl (0.1 mg/kg) group showed pancreatic islets of Langerhans, which were shaped regularly and arranged evenly shown by arrow (H&E, ×400), (d) pancreatic section from low-dose (200 mg/kg) treated group showed pancreatic islets of Langerhans, which were shaped regularly and arranged evenly shown by arrow (H&E, ×400), (e) Pancreatic section from high-dose (400 mg/kg) treated group showed pancreatic islets of Langerhans, which were shaped regularly and arranged evenly shown by arrow (H&E, ×400).

Click here to view



  Discussion Top


Diabetes mellitus is a syndrome of metabolic disorder of carbohydrate, protein, and fat [19]. Plants that have antidiabetic activity and proven long-term safety should be used in lipid metabolic disorders and cardiovascular diseases [20],[21]. The current study was carried out to show the effect of LBAE on STZ diabetic rats.

Blood glucose level was increased whereas level of serum insulin was decreased in diabetic rats compared with normal rats. These are in line with Adaramoye et al. [22] who used STZ in inducing hyperglycemia in rats. Using STZ is accepted in animal models of diabetes mellitus because it resembles human diabetes mellitus [23] which may eventually leads to renal damage and hepatotoxicity [24].

In this study, LBAE caused a reduction and an elevation in levels of blood glucose and serum insulin, respectively, when compared with diabetic rats. The essential oil of M. officinalis has antidiabetic effect evidenced by adjusting hepatic gluconeogenesis. The study carried out by Chung et al. [21] showed the hypoglycemic effect of plant extract at low doses via regulating glucose uptake as well as suppressing gluconeogenesis [21].

Oxidative stress is the main cause of diabetes complications [25]. These complications may originate from high blood glucose levels, where the production of reactive oxygen species and FRs exceed the capacity of the organism to defend leading to disruption of cellular reduction–oxidation balance [26],[27],[28].

The administration of STZ-induced β-cells destruction through NO and inhibition of enzymatic FR scavenging activity in pancreatic tissue [29]. The present study showed that LBAE produced regeneration of the pancreatic β-cells that is evidenced by the elevation of TAC and the reduction of NO level as compared with STZ-induced diabetic group. After damage, pancreatic β-cells replenish the lost cells owing to their proliferating capacity [30]. Our histopathological results showed that the LBAE was responsible for the proliferation of pancreatic β-cells and its normal morphology. Aqueous extract of M. officinalis has antioxidant effect owing to its total polyphenolic and flavonoid constituents [31]. Previous study showed the pharmacological effects of volatile terpenoids of M. officinalis oils [32].

This study exhibited the hepatoprotective, renoprotective, and pancreatoprotective activities that are highly associated with its antioxidant activity [33],[34].

In diabetic condition, elevated TC and TG levels along with decreased HDL level are confirmed [35]. Administration of STZ in the current study changed lipid profiles through increased levels of TC, TG, LDL, and LDL and reduced HDL level when compared with normal control rats. These findings also happened in high-fat-diet diabetic rats [36].

Daily drinking of M. officinalis tea can regulate TG and cholesterol in humans [29]. In addition, the potential effect of M. officinalis may suppress hypercholesterolemia, hyperlipidemia, and lipid peroxidation in the liver of rats [30]. The study of Changizi-Ashtiyani et al. [37] on hypercholesterolemic rats has shown that M. officinalis reduced serum cholesterol, LDL, and triglyceride. These results may be related to M. officinalis antioxidant properties which increase the level of thyroid hormone or the quercetin compounds in the plant, which possess inhibitory effect on lipid peroxidation [38].

Zarei et al. [39] found that liver enzymes levels were reduced when receiving M. officinalis in hypercholesterolemic group. Accumulation of lipids in the liver stimulates hepatic dysfunction leading to the increases in liver enzymes levels, particularly alanine aminotransferase [40]. On the contrary, increase in lipid levels in liver hyperlipidemia induces the liberation of FRs [41].

The hepatoprotective effect of M. officinalis extract may be owing to antioxidant properties of its phenolic compounds that possess FR scavenging capacity through inhibition of cytochrome system and flavonoids that increase the antioxidant enzymes capacity, protecting the cells against glutathione depletion [21].

In this study, serum levels of creatinine and urea were elevated in the STZ-diabetic rats. These results are consistent with the previous studies of Alderson et al. [42] and Adisa et al. [43]. Elevated levels of serum urea produced nephrosclerosis, glomerulonephritis, and even tubular necrosis [44]. Our data indicated that LBAE caused reduction in serum levels of creatinine and urea in STZ-diabetic rats, indicating its protective effects against diabetes-induced renal dysfunction [45].

Our STZ diabetic model induced inflammation as it increased liver and kidney contents of TNF-α that endorsed by changes in immune cell function, as it decreased liver and kidney CD4 contents as compared with normal rats. In type 2 diabetes; inflammation is in correlation with T-cell subset imbalance [46],[47]. Immunosuppressant effect of STZ may be related to its action on bone marrow and important T cells [48],[49]. STZ produced defection of insulin action and β-cell apoptosis leading to immune responses. The proper protein synthesis and normal T-cell functions are related to appropriate uptake of glucose [50]. Zhang et al. [51] declared that CD3 and CD4 levels were reduced in patients with diabetes.

In this study, the anti-inflammatory effects of LBAE, which has been shown to decrease liver and kidney TNF-α levels and increase CD4 level as compared with diabetic rats, may be attributed to its bioactive phenolic contents especially flavonoids and rosmarinic acid with their hepatoprotective and anti-inflammatory actions that suppress many enzymes included in the inflammatory activity [52],[53].


  Conclusion Top


This study asserts antihyperlipidemic and antidiabetic effects of LBAE in STZ-induced diabetic rats and this will encourage its use as antidiabetic agent. In addition, its beneficial effects on reducing both kidney and liver functions, as well as TNF-α, and enhancing CD4 expression of diabetic rats suggest the possible ameliorating role of the plant extract against secondary complications of diabetes. Further studies are needed to determine active components of LBAE, which have more therapeutic effects.

Acknowledgements

This research was funded by the National Research Center (NRC), Giza, Egypt (project no. P100523). The authors acknowledge the NRC technical and financial support.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
International Diabetes Federation. IDF diabetes atlas. 6th edition. Brussels, Belgium: International Diabetes Federation; 2013.  Back to cited text no. 1
    
2.
Rochette L, Zeller M, Cottin Y, Vergely C. Diabetes, oxidative stress and therapeutic strategies. Biochim Biophys Acta 2014; 1840:2709–2729.  Back to cited text no. 2
    
3.
Hagar HM, Mahitab IE, Enas AE, Reham SE, Fathia AM, Khaled GA. Role of soy protein concentrate on oxidative stress and DNA fragmentation in streptozotocin-induced diabetic rats. J Innov Pharm Biol Sci 2017; 4:16–25.  Back to cited text no. 3
    
4.
Newairy ASA, Mansour HA, Yousef MI, Sheweita SA. Alterations of lipid profile in plasma and liver of diabetic rats: effect of hypoglycemic herbs. J Environ Sci Health 2002; 37:475–484.  Back to cited text no. 4
    
5.
Hunt JV, Smith CCT, Wolff SP. Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 1990; 39:1420–1424.  Back to cited text no. 5
    
6.
Wolff SP, Dean RT. Glucose autoxidation and protein modification: the potential role of ‘autoxidative glycosylation’ in diabetes. Biochem J 1987; 245:243–250.  Back to cited text no. 6
    
7.
Mansour HA, Newairy ASA, Yousef MI, Sheweita SA. Biochemical study on the effects of some Egyptian herbs in alloxan-induced diabetic rats. Toxicology 2002; 170:221–228.  Back to cited text no. 7
    
8.
Park JH, Jung JH, Yang JY, Kim HS. Olive leaf down-regulates the oxidative stress and immune dysregulation in streptozotocin-induced diabetic mice. Nutr Res 2013; 33:942–951.  Back to cited text no. 8
    
9.
Weidner C, Wowro SJ, Freiwald A, Kodelja V, Abdel-Aziz H, Kelber O, Sauer S. Lemon balm extract causes potent antihyperglycemic and antihyperlipidemic effects in insulin-resistant obese mice. Mol Nutr Food Res 2014; 58:903–907.  Back to cited text no. 9
    
10.
Muller M, Kersten S. Nutrigenomics: goalsandstrategies. Nat Rev Genet 2003; 4:315–322.  Back to cited text no. 10
    
11.
Sheweita SA, Newairy AA, Mansour HA, Yousef MI. Effect of some hypoglycemic herbs on the activity of phase I and II drug-metabolizing enzymes in alloxan-induced diabetic rats. Toxicology 2002; 174:131–139.  Back to cited text no. 11
    
12.
Herodez SS, Hadolin M, Skergeta M, Kneza Z. Solvent extraction study of antioxidants from Balm (Melissa officinalis L.) leaves. Food Chem 2003; 80:275–282.  Back to cited text no. 12
    
13.
Wang H, Provan GJ, Helliwell K. Determination of rosmarinic acid and caffeic acid in aromatic herbs by HPLC. Food Chem 2004; 87:307–311.  Back to cited text no. 13
    
14.
National Research Council (Washington, USA). Guide for the Care and Use of Laboratory Animals: Eighth Edition Committee for the Update of the Guide for the Care and Use of Laboratory Animals; National Research Council. 2010. 248. National Academies Press at: http://www.nap.edu/catalog/12910.html  Back to cited text no. 14
    
15.
Salama AAA, Ibrahim BMM, Yassin NA, Mahmoud SS, Gamal El-Din AA, Shaffie NA. Regulatory effects of Morus alba aqueous leaf extract in streptozotocin-induced diabetic nephropathy. Der Pharma Chem 2017; 9:46–52.  Back to cited text no. 15
    
16.
Sharafeldin K, Raza Rizvi M. Effect of traditional plant medicines (Cinnamomum zeylanicum and Syzygium cumini) on oxidative stress and insulin resistance in streptozotocin induced diabetic rat. J Basic Appl Zool 2015; 72:126–134.  Back to cited text no. 16
    
17.
Yassin MM, Mwafy SN. Protective potential of Glimepiride and Nerium oleander extract on lipid profile, body growth rate, and renal function in streptozotocin-induced diabetic rats. Turk J Biol 2007; 31:95–102.  Back to cited text no. 17
    
18.
Saberi A, Abbasloo E, Sepehri G, Yazdanpanah M, Mirkamandari E, Sheibani V, Safi Z. The effects of methanolic extract of Melissa officinalis on experimental gastric ulcers in rats. Iran Red Crescent Med J 2016; 18:24–27.  Back to cited text no. 18
    
19.
Weidner C, Wowro SJ, Freiwald A, Kawamoto K. Amorfrutin B is an efficient natural peroxisome proliferator activated receptor gamma (PPARgamma) agonist with potent glucose-lowering properties. Diabetologia 2013; 56:1802–1812.  Back to cited text no. 19
    
20.
Ulbricht C, Brendler T, Gruenwald J, Kligler B. Lemon balm (Melissa officinalis L.): an evidence-based systematic review by the Natural Standard Research Collaboration. J Herb Pharmacother 2005; 5:71–114.  Back to cited text no. 20
    
21.
Chung MJ, Cho SY, Bhuiyan MJ, Kim KH, Lee SJ. Anti-diabetic effects of lemon balm (Melissa officinalis) essential oil on glucose- and lipid-regulating enzymes in type 2 diabetic mice. Br J Nutr 2010; 104:180–188.  Back to cited text no. 21
    
22.
Adaramoye O, Amanlou M, Habibi-Rezaei M, Pasalar P, Ali MM. Methanolic extract of African mistletoe (Viscum album) improves carbohydrate metabolism and hyperlipidemia in streptozotocin-induced diabetic rats. Asian Pac J Trop Med 2012; 5:427–433.  Back to cited text no. 22
    
23.
Usuki S, Tsai YY, Morikawa K, Nonaka S, Okuhara Y, Kise M. IGF-1 induction by acylated steryl-glucosides found in a pre-germinated brown rice diet reduces oxidative stress in streptozotocin-induced diabetes. PLoS One 2011; 6:286–293.  Back to cited text no. 23
    
24.
Maric-Bilkan C, Flynn ER, Chade AR. Microvascular disease precedes the decline in renal function in the streptozotocin-induced diabetic rat. Am J Physiol Renal Physiol 2012; 302:308–315.  Back to cited text no. 24
    
25.
Maritim A, Sanders R, Watkins JB. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 2003; 17:24–38.  Back to cited text no. 25
    
26.
Dowling DK, Simmons LW. Reactive oxygen species as universal constraints in life-history evolution. Proc Biol Sci 2009; 276:1737–1745.  Back to cited text no. 26
    
27.
Cansian RL, Kubiak GB, Borsatti L, Mielniczki-Pereira AA, Roman SS, Paroul N et al. Antioxidant and genotoxic properties of Maytenus dasyclada: a comparative study in relation to Maytenus reference species. Braz J Biol 2015; 75:471–476.  Back to cited text no. 27
    
28.
Takao LK, Imatomi M, Gualtieri SC. Antioxidant activity and phenolic content of leaf infusions of Myrtaceae species from Cerrado (Brazilian Savanna). Braz J Biol 2015; 75:948–952.  Back to cited text no. 28
    
29.
Jun HJ, Lee JH, Jia Y, Hoang MH. Melissa officinalis essential oil reduces plasma triglycerides in human apolipoprotein E2 transgenic mice by inhibiting sterol regulatory element-binding protein-1c-dependent fatty acid synthesis. J Nutr 2012; 142:432–440.  Back to cited text no. 29
    
30.
Bolkent S, Yanardag R, Karabulut-Bulan O, Yesilyaprak B. Protective role of Melissa officinalis L. extract on liver of hyperlipidemic rats: a morphological and biochemical study. J Ethnopharmacol 2005; 99:391–398.  Back to cited text no. 30
    
31.
Martins EN, Pessano NTC, Leal L, Roos DH, Folmer V, Puntel GO. Protective effect of Melissa officinalis aqueous extract against Mn-induced oxidative stress in chronically exposed mice. Brain Res Bull 2012; 87:74–79.  Back to cited text no. 31
    
32.
Carnat AP, Carnat A, Fraisse D, Lamaison JL. The aromatic and polyphenolic composition of lemon balm (Melissa officinalis L. subsp. officinalis) tea. Pharm Acta Helv 1998; 72:301–305.  Back to cited text no. 32
    
33.
Dastmalchi K, Damien Dorman HJ, Oinonen PP, Darwis Y, Laakso I, Hiltunen R. Chemical composition and in vitro antioxidative activity of a lemon balm (Melissa officinalis L.) extract. Food Sci Technol 2008; 41:391–400.  Back to cited text no. 33
    
34.
Cabrera AC, Prieto JM. Application of artificial neural networks to the prediction of the antioxidant activity of essential oils in two experimental in vitro models. Food Chem 2010; 118:141–146.  Back to cited text no. 34
    
35.
Howard BV, Robbins DC, Sievers ML, Lee ET, Rhoades D, Devereux RB et al. LDL cholesterol as a strong predictor of coronary heart disease in diabetic individuals with insulin resistance and low LDL: the Strong Heart Study. Arterioscler Thromb Vasc Biol 2000; 20:830–835.  Back to cited text no. 35
    
36.
Sharma AK, Bharti S, Kumar R, Krishnamurthy B, Bhatia J, Kumari S, Arya DS. Syzygium cumini ameliorates insulin resistance and beta-cell dysfunction via modulation of PPAR, dyslipidemia, oxidative stress, and TNF-alpha in type 2 diabetic rats. J Pharmacol Sci 2012; 119:205–213.  Back to cited text no. 36
    
37.
Changizi-Ashtiyani S, Zarei A, Taheri S. A comparative study of hypolipidemic activities of the extracts of Melissa officinalis and Berberis vulgaris in rats. J Med Plants 2013; 12:38–47.  Back to cited text no. 37
    
38.
Dolatabadi F, Abdolghaffari AH, Farzaei MH, Baeeri M, Ziarani FS, Eslami M et al. The protective effect of Melissa officinalis L. in visceral hypersensitivity in rat using 2 models of acid-induced colitis and stress-induced irritable bowel syndrome: a possible role of nitric oxide pathway. J Neurogastroenterol Motil 2018; 24:490–501.  Back to cited text no. 38
    
39.
Zarei A, Changizi-Ashtiyani S, Taheri S. Comparison between effects of different doses of Melissa officinalis and atorvastatin on the activity of liver enzymes in hypercholesterolemia rats. Avicenna J Phytomed 2013; 4:15–23.  Back to cited text no. 39
    
40.
Murray RK, Rodwell VW, Bender D, editors. Harpersillustrated biochemistry. 29th ed. USA: McGrawHill Press; 2012. pp. 260–286.  Back to cited text no. 40
    
41.
Nazari A, Delfan B, Shahsavari G. The effect of Satureja khuzestanica on triglyceride, glucose, creatinine and alkaline phosphatase activity in rat. Persian J Shahrekord Univ Med Sci 2005; 7:1–8.  Back to cited text no. 41
    
42.
Alderson NL, Chachich ME, Frizzell N, Canning P, Metz TO, Januszewski AS. Effect of antioxidants and ACE inhibition on chemical modification of proteins and progression of nephropathy in streptozotocin diabetic rat. Diabetologia 2004; 47:1385–1395.  Back to cited text no. 42
    
43.
Adisa RA, Choudhary MI, Olorunsogo OO. Hypoglycemic activity of Buchholzia coriacea (Capparaceae) seeds in streptozotocin induced diabetic rats and mice. Exp Toxicol Pathol 2011; 63:619–625.  Back to cited text no. 43
    
44.
Sief MM, Khalil FA, Abou-Arab AAK, Abou Donia MA, El-Sherbiny AM, Mohamed SR. Ameliorative role of Melissa officinalis against hepatorenal toxicities of organophosphorus malathion in male rats. MOJ Toxicol 2015; 1:2–8.  Back to cited text no. 44
    
45.
Zarei A. The effects of hydroalcoholic extract of Melissa officinalis.L on the level of renal function and liver enzymes in diabetic rats. Iran J Endocrinol Metabol 2016; 17:353–361.  Back to cited text no. 45
    
46.
King GL. The role of inflammatory cytokines in diabetes and its complications. J Periodontal 2008; 79:1527–1534.  Back to cited text no. 46
    
47.
Navarro-González JF, Mora-Fernández C. The role of inflammatory cytokines in diabetic nephropathy. J Am Soc Nephrol 2008; 19:433–442.  Back to cited text no. 47
    
48.
Zhen Y, Sun L, Liu H, Duan K, Zeng C, Zhang L et al. Alterations of peripheral CD4+CD25+Foxp3+ T regulatory cells in mice with STZ-induced diabetes. Cell Mol Immunol 2012; 9:75–85.  Back to cited text no. 48
    
49.
Abdullah CS, Li Z, Wang X, Jin ZQ. Depletion of T lymphocytes ameliorates cardiac fibrosis in streptozotocin-induced diabetic cardiomyopathy. Int Immunopharmacol 2016; 39:251–264.  Back to cited text no. 49
    
50.
DeFuria J, Belkina AC, Jagannathan-Bogdan M, Snyder-Cappione J, Carr JD, Nersesova YR et al. B cells promote inflammation in obesity and type 2 diabetes through regulation of T-cell function and an inflammatory cytokine profile. Proc Natl Acad Sci USA 2013; 110:5133–5138.  Back to cited text no. 50
    
51.
Zhang X, Saaddine JB, Chou CF, Coteh MF, Cheng YJ, Geiss LS et al. Prevalence of diabetic retinopathy in the United States. JAMA 2010; 304:649–656.  Back to cited text no. 51
    
52.
Denise PM, Adroaldo L, Carlos EL, Rodrigo MF, Vasyl CS, Carlos LR et al. Nephroprotective and anti-inflammatory effects of aqueous extract of Melissa officinalisL. on acetaminophen-induced and pleurisy-induced lesions in rats. Braz. arch. biol. technol. 2013; 56:383–392.  Back to cited text no. 52
    
53.
Mahmoodi M, Koohpeyma F, Saki F, Maleksabet A, Zare MA. The protective effect of Zataria multiflora Boiss. hydroalcoholic extract on TNF-α production, oxidative stress, and insulin level in streptozotocin-induced diabetic rats. Avicenna J Phytomed 2019; 9:72–83.  Back to cited text no. 53
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  Materials and me...
  In this article
Abstract
Introduction
Results
Discussion
Conclusion
References
Article Figures
Article Tables

 Article Access Statistics
    Viewed982    
    Printed73    
    Emailed0    
    PDF Downloaded147    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]