Diabetes mellitus is a chronic metabolic disease and its prevalence is increasing worldwide (Guariguata et al. 2014).Curcumin is a natural polyphenol with various pharmacological activities such as anti-inflammation, anti-cancer and anti-oxidation (Hussain et al. 2017). Studies have also pointed out the therapeutic potential of curcumin against neurodegenerative diseases (Reddy et al. 2016). Alzheimer's disease is one of the most important complications of diabetes and is the most common type of dementia in the elderly population (Rocchi et al. 2003). AD is characterized by progressive decline in cognitive functions and accumulation of Aβ that forms senile plaques in the brain (Price et al. 1995). Studies suggest that curcumin crosses the blood-brain barrier and reaches the brain. Curcumin has been shown to bind to amyloid plaques in the brain and reverse existing amyloid pathology (Garcia-Alloza et al. 2007).
At the beginning of the study, the mean body weight of the rats was approximately 265 ± 10 g. At the end of the study, it was determined that the body weight gain in Group 2 and Group 4, in which experimental diabetes was induced by STZ, was significantly lower than the control group (Group 1) (P > 0.05), while it decreased slightly in the other groups (P > 0.05).When curcumin (100 mg/kg) was given to rats who developed diabetes by applying low-dose streptozotocin along with a high-energy diet for eight weeks, there was an increase in body weight, increase in body mass index and thickening in the waist circumference in the control group and diabetes curcumin (DC) groups at the end of 8 weeks. It was determined that the weight gain was 49.12% in the DC group, and 48.02% in the DC group (Yang et al. 2018).
In our study, it was determined that there was a 14.13% decrease in live weight in Group 4 (DC).In the study by Kuhad and Chopra (2007), male wistar albino rats were given 65 mg/kg STZ to induce diabetes, while 60 mg/kg was given to the diabetes curcumin (DC) group by oral gavage for ten weeks for treatment.At the end of the study, it was observed that there was an 8.1% decrease in body weight in the DC group, and an 11.40% increase in body weight in the curcumin group at the end of the study.In our study, it was determined that there was a 5% increase in body weight in Group 3 (curcumin). In another study, STZ (60 mg/kg) was given to male rats and diabetes was formed, and curcumin (150 mg/kg/day) was given by oral gavage for twelve weeks for treatment, and the control group (C), the diabetic group (D) and the diabetes were additionally administered. The body weight gain of the curcumin (DC) group was compared and it was determined that this increase was higher in the DC group than in the D group (Huang et al. 2013).In our study, it was seen that the effect of curcumin on body weight gain in rats with experimental diabetes was compatible with the literature.
There are studies showing that curcumin administration to diabetic rats regulates blood glucose levels (Nishiyama et al. 2005; Huang et al. 2013; Mustafa, 2016; Rahimi et al. 2016).In a study conducted in parallel with our study, three-month-old male rats were given diabetes (D) by STZ (35 mg/kg) and diabetes (DC) group was given curcumin (100 mg/kg) for eight weeks by oral gavage, and group D was given at the end of the study. When blood glucose levels were compared between the DC group and the blood glucose level, it was reported that there was no significant difference (Suryanarayana et al. 2005).Sprague-Dawley male rats were administered STZ (55 mg/kg) and rats with diabetes (D) were given 200 mg/kg curcumin to the diabetes curcumin (DC) group by oral gavage for twelve weeks. At the end of the study, group D and DC group blood glucose levels were determined as 498 (mg/dl), 478 (mg/dl), respectively, and it was reported that the effect of curcumin on reducing hyperglycemia was not significant (Majithiya and Balaraman 2005). In another study, Sprague Dawley rats with STZ (45 mg/kg) were administered curcumin 200 mg/kg/day by oral gavage for 14 days, and it was reported that the effect of curcumin administration on serum glucose concentration was not significant at the end of the study (Nishizono et al. 2000). The results of our study showed that, at the end of the experiment, the blood glucose levels of Groups 2 (D), 4 (DC), and 5 (CD) with diabetes were significantly higher than those of the control group (Group 1), and that, although not statistically significantly, the blood glucose levels of the groups with diabetes who received curcumin treatment were slightly higher.
Alanineaminotransferase (ALT) and aspartataminotransferase (AST) activities are liver enzymes commonly used for liver function tests. At the end of the study, it was determined that ALT and AST enzyme activity increased in experimental diabetic rats. These results are supported by studies showing that DM is associated with elevated hepatic enzyme activity, which may be a result of liver cell destruction or changes in membrane permeability indicating severe hepatocellular damage.In a study, 60 mg/kg curcumin was administered to adult male Wistar Albino rats for whom diabetes was induced with STZ (60 mg/kg) for 30 days by oral gavage, and it was reported that the effect of curcumin on serum AST level was not significant, but it significantly decreased ALT level (Palma et al. 2014). In another study, diabetes was induced by STZ (50 mg/kg) injection in rats and curcumin was given 80 mg/kg/day by oral gavage for 60 days. It was reported that ALT and AST enzyme activity decreased significantly (Mustafa 2016). In our study, it was observed that curcumin administration had a positive effect on reducing the liver enzymes ALT and AST in experimental diabetes-induced rats, which was consistent with the literature.
Hyperlipidemia is a complication of DM. Significant changes in the lipid profile can be seen depending on the induction of DM. In a study, after inducing diabetes with STZ (65 mg/kg) in rats, curcumin was administered at a dose of 10 mg/kg for 45 days. It has been reported that the water-soluble form of curcumin lowers total cholesterol and improves the lipid profile (Abdel Aziz et al. 2012). In another study, DM was induced by intravenous injection of 40 mg/kg STZ in rats. The rats were given 90 mg/kg curcumin with yogurt at 1.0 mL per day per rat by oral gavage for 35 days.At the end of the study, it was reported that total cholesterol levels were 21% higher in the diabetes (D) group and 22% higher in the diabetes curcumin (DC) group compared to the control (C) group (Gutierres et al. 2012).In another study, 120 mg/kg of alloxan monohydrate was administered intraperitoneally to Sprague Dawley rats to induce diabetes. Rats were administered 200 mg/kg of turmeric extract by oral gavage for 56 days. At the end of the study, it was reported that the total cholesterol levels were 24% higher in the diabetes (D) group compared to the control (C) group, and it approached the control group in the group in which diabetes was formed and turmeric extract was given (El-Hadary and Sitohy 2021).In our study, it was determined that the total cholesterol level was higher in the diabetic groups (Groups 2, 4 and 5) compared to the control group.
It was suggested that urea, creatinine and uric acid levels, which are indicators of kidney function parameters, were affected in rats with diabetes, and that the administration of curcumin derivatives to diabetic rats may protect kidney function (Wu et al. 2014; Xu et al. 2018; El-Hadary and Sitohy, 2021) .In a study investigating the effect of stevia and turmeric extracts on hypoglycemia in rats, it was reported that turmeric extracts significantly decreased the elevated urea, creatinine and uric acid levels in rats with diabetes and had a protective effect on kidney functions (El-Hadary and Sitohy 2021). In our study, it was determined that there was an increase in urea and creatinine levels in the groups with diabetes (Group 2 and Group 4) compared to the control (Group 1) group, but this increase was not statistically significant. In the group with diabetes on the 28th day (Group 5), it was determined that the urea and creatinine levels were not affected and were close to the control group.It was observed that the uric acid level was increased in Group 2 and 5 compared to the control group (P > 0.05) in the diabetes-induced groups, while this increase was the highest in Group 4 (P < 0.05).In another study, 15 and 30 mg/kg curcumin were administered to diabetic rats induced by 65 mg/kg STZ for 2 weeks, and at the end of the study, polyuria, increased urinary albumin excretion, increased serum creatinine, and increased blood urea nitrogen were detected in diabetic rats. It was reported that as a result of curcumin treatment of 15 and 30 mg/kg per day in diabetic rats, it effectively reduced diabetic proteinuria, polyuria, and increased serum creatinine and blood urea nitrogen. It was reported that creatinine and urea clearance were also significantly reduced following the administration of curcumin to diabetic rats compared to untreated diabetic rats, and it had a healing effect on renal dysfunction by reducing oxidative stress (Sharma et al., 2006). In our study, it was determined that urea and creatinine levels were higher in Group 2 (D) and Group 4 (DC) compared to the control (Group 1) group, and Group 5 approached the control group.
In one study, diabetes was induced by injection of STZ (50 mg/kg) in rats and curcumin (80 mg/kg/day) was given by oral gavage for 60 days.At the end of the study, it was determined that there was a significant decrease in albumin and total protein levels in the diabetic group compared to the control group, and a significant increase in these parameters in the diabetic group treated with curcumin (Mustafa 2016). In another study, experimental T2DM was induced in adult rats and treated with curcumin (80 mg/kg) by oral gavage for eight weeks.At the end of the study, it was reported that the total protein level decreased significantly in the diabetes (D) group compared to the control (C) group, and there was a significant increase in the curcumin-treated diabetes curcumin (DC) group (Al-Saud, 2020).In our study, it was determined that the total protein level among the groups decreased in the diabetes-induced groups compared to the control group (P > 0.05), and this decrease was observed the most in Group 5 (P < 0.05).Among the groups, Group 5 had the highest amount of albumin and the lowest amount of globulin (P < 0.05).
Insulin resistance (IR) is a condition in which defects in the action of insulin do not function as normal insulin levels as signals for glucose uptake. Insulin resistance is also an important risk factor for related chronic diseases such as type 2 diabetes, atherosclerosis and cardiovascular disease. Insulin resistance is an important component of the metabolic syndrome, which consists of a number of risk factors such as abdominal obesity, hypertension and dyslipidemia (Hekmatdoost et al. 2011). Regarding the pathophysiology of diabetes, there are studies investigating the therapeutic effect of curcumin in cases of insulin action, insulin secretion malfunction, β-cell dysfunction, insulin secretion reductions, and insulin resistance (IR) (Kim et al. 2016; Zheng et al. 2018; Lee et al. 2020;Al-Saud, 2020). In a study, after induction of experimental T2DM in adult rats, curcumin (80 mg/kg) was administered by oral gavage for eight weeks, and it was reported that glucose level and insulin resistance (HOMA-IR) decreased after curcumin treatment in diabetes (D) groups at the end of the study (Al-Saud, 2020). In another study, high-fat diet-induced diabetic Sprague Dawley rats were given 80 mg/kg curcumin for 15 days, and it was reported that curcumin exhibited an anti-hyperglycemic effect and improved insulin sensitivity at the end of the study (El-Moselhy et al. 2011). An experimental T2DM model was established in Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats and treated for forty weeks by administering curcumin (100 mg/kg).At the end of the study, it was reported that there was no difference in HOMA-IR values between the control (C), diabetes (D) and diabetes curcumin (DC) groups (Kim et al., 2016). In our study, it was determined that Group 2 (D), Group 4 (DC) and Group 5 (CD) HOMA-IR scores in Group 2 (D), Group 4 (DC) and Group 5 (CD) diabetes at the end of the trial were ≥ 2.5 and insulin resistance was formed.
Alzheimer's disease (AD) is a progressive, neurodegenerative disease characterized by extracellular amyloid beta (Aβ) protein deposits and intracellular neurofibrillary tangles of hyperphosphorylated tau protein (Patil et al. 2013; Chen, 2018). Curcumin is a component of turmeric, a spice used in many types of cooking. Epidemiological evidence showing that populations that consume foods containing significant amounts of curcumin have a lower risk of Alzheimer's disease (AD) suggest that this compound may have a neuroprotective effect. Curcumin also protects against toxicity when β-amyloid is applied to produce animal models of AD, and curcumin reduces the formation of β-amyloid from amyloid precursor protein; It has been reported to inhibit the aggregation of β-amyloid in layers. The neuroprotective effect of curcumin has been reported in several in vitro studies in transgenic mice with excessive β-amyloid production (Liu et al. 2010; Zhang et al. 2010; Huang et al. 2012; Potter, 2013). In the in vitro study investigating the protective effect of curcumin against amyloid-β (Aβ)-induced neuronal damage, rat cortical neurons were cultured with different Aβ and curcumin treatments to evaluate neuronal morphologies, viability, and damage.At the end of the study, it was reported that curcumin protected cell viability and Aβ-induced neuronal damage by Aβ, and decreased oxidative stress markers and reactive oxygen species levels (Huang et al., 2012).In a study investigating the effects of curcumin mixture and different curcuminoids on Aβ 42, APP and BACE1, it was reported that curcumin had a reducing effect on β-amyloid protein level, inhibited β-amyloid 1–42 production in cultured cells, and also decreased APP protein level (Liu et al. 2010). In a study investigating Aβ levels and APP levels of curcumin in mouse primary cortical neurons by various in vitro methods, it was reported that curcumin strongly reduced Aβ levels by reducing the maturation of APP in the secretory pathway, and had an effect on alleviating amyloid-β pathology (Zhang et al. 2010).It was reported that the addition of curcumin not only had antioxidant and anti-inflammatory effects in experimental mice with transgenetic APP plaque formation, but also reduced amyloid plaque formation and Aβ accumulation (Lim et al. 2001).At the end of our study, it was observed that there was a significant difference between Group 2 (D) and Group 4 (DC) in terms of brain β-amyloid protein levels, and the decrease was higher in the group given curcumin.After feeding a high-fat diet for eight weeks, rats induced T2DM by 35 mg/kg STZ were given curcumin and curcumin nanoparticles (CURNP) by oral gavage for six weeks.At the end of the study, serum insulin levels, brain and hippocampus Aβ-42 protein, and tau protein levels were significantly higher in the diabetes (D) group than in the control (C) group. reported to be low.In conclusion, the findings of this study show that curcumin and CURNP inhibit amyloidogenesis and hyperphosphorylation of tau proteins in the brain hippocampus of rats (Abdulmalek et al., 2021).At the end of our study, it was observed that the levels of Total Beta Amyloid protein and Tau protein in the serum and brain tissue of Group 2 (D) were higher compared to the control group, and treatment with curcumin in Group 5 had a positive effect on the reduction.
Antioxidants play an important role in the prevention and improvement of diabetic complications (Rahimi et al. 2005).Curcumin, a powerful antioxidant, protects neurons from oxidative damage by regulating mitochondrial membrane potential and inhibiting intracellular ROS production.Accordingly, many studies have shown that curcumin reduces diabetes and diabetes-related symptoms (Suryanarayana et al. 2007; Aggarwal and Harikumar, 2009;Acar et al. 2012).In the study investigating the effect of STZ-induced diabetic rats on the oxidant/antioxidant balance in the sciatic nerve and brain tissue, it was observed that TOS and OSI levels in the brain tissue of diabetic rats increased significantly compared to control rats, and TAS levels decreased significantly compared to the control.It was reported that TOS and OSI levels in brain tissue decreased in diabetic rats treated with curcumin, while TAS level increased, and curcumin has the ability to reduce oxidative damage in the brain tissue of diabetic rats (Acar et al. 2012).In our study, it was determined that the level of TOS increased in Group 2 and Group 5 with diabetes compared to the control group (Group 1), and the level of TAS activity in this tissue decreased significantly compared to the control group.It was determined that TOS level in the brain tissue was highest in Group 2 with diabetes, and with curcumin treatment, TOS level decreased and TAS level increased in Group 4.
In one study, diabetes was induced in rats with 55 mg/kg of STZ, and 50 mg/kg to 150 mg/kg of curcumin was given to the groups by oral gavage for 42 days to treat it. The activities of enzymes involved in the antioxidant defense system were investigated. At the end of this study, although the TAS level of diabetic rats did not change with curcumin treatment, a significant increase was observed in TOS, OSI and MDA levels in rats in the diabetic group (D). At the end of the treatment of diabetic rats with curcumin, it was observed that the oxidative stress parameters returned to the normal range.At the end of the study, it was reported that curcumin exhibits potent antioxidant properties and therefore may be beneficial in ameliorating the oxidative stress caused by diabetes and improving the cardiac damage caused by diabetes in the heart tissue (Naghdi et al. 2022). In our study, it was determined that the TAS level in the serum was lower in Group 2 compared to the control group (Group 1), and Group 4 returned to normal levels with curcumin treatment.It was predicted that TOS activities in the serum were significantly higher in Group 2 with diabetes compared to the control (Group 1) group, and in Group 4, it approached the control group with curcumin treatment, and it was predicted that curcumin could improve the complications of diabetes by increasing the oxidative stress caused by diabetes, increasing the antioxidant activity.
In a study conducted in parallel with our study, diabetes was induced by injection of 50 mg/kg STZ in adult rats and curcumin (100 mg/kg) was administered to rats by oral gavage for 42 days for treatment.At the end of the study, it was reported that curcumin reduced testicular damage by reducing oxidative stress in diabetic rats (Kanter et al. 2013).In a study, it was reported that the application of curcumin and turmeric improved oxidative stress in streptozotocin-induced diabetes, but did not completely prevent it (Suryanarayana et al. 2007).It has been reported that the administration of curcumin to STZ-induced diabetic rats has an inhibitory effect on oxidative stress and modulation of antioxidant enzymes and lipid peroxidation (Palma et al. 2014). In a study investigating the role of curcumin in the pancreatic tissue of diabetes through cellular stress induced by STZ in Wistar Albino male rats, it was shown that curcumin can reduce oxidative stress, ER stress and related inflammation, and protect pancreatic beta cells from apoptotic damage under hyperglycemic conditions (Rashid and Sil, 2015).In another study investigating oxidative damage and mitochondrial dysfunction in diabetic rat brain, curcuminoids showed protective effects against oxidative damage and mitochondrial dysfunction in diabetic rat brain (Rastogi et al. 2008).In our study, it was determined that the level of brain tissue and blood serum TOS activity was higher in Group 2 with diabetes compared to the control (Group 1) group, and significantly decreased in Group 4 with curcumin treatment. It was observed that the level of TAS activity in serum and brain tissue decreased in Group 2 compared to the control (Group 1) group, and approached the control group in Group 4. Curcumin has an effect of reducing oxidative stress, which increases with diabetes, and increasing antioxidant activity.
Curcumin can improve the complications of diabetes by increasing the antioxidant activity of oxidative stress caused by diabetes and that curcumin can be recommended as a supportive treatment in addition to diabetes treatment, but experimental studies with a longer trial period are needed to better demonstrate the efficacy of curcumin.