{"id":51936,"date":"2023-09-30T10:10:32","date_gmt":"2023-09-30T10:10:32","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=51936"},"modified":"2023-10-12T04:35:04","modified_gmt":"2023-10-12T04:35:04","slug":"anti-diabetic-effects-of-pomegranate-peel-extract-and-l-carnitine-on-streptozotocin-induced-diabetes-in-rats","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no3\/anti-diabetic-effects-of-pomegranate-peel-extract-and-l-carnitine-on-streptozotocin-induced-diabetes-in-rats\/","title":{"rendered":"Anti-Diabetic Effects of Pomegranate Peel Extract and L- Carnitine on Streptozotocin Induced Diabetes in Rats"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Diabetic mellitus (DM) <\/em>is a chronic endocrine condition that affects protein, lipid, and glucose metabolism.<\/strong>1<\/sup> All  forms of diabetes are characterized by decreased insulin levels in the blood (insulin deficit) and diminished ability of peripheral tissues to respond to (insulin resistance). The condition has pandemic proportions and poses a threat of spreading globally.<\/em>2<\/sup><\/p>\n\n\n\n

The World Health Organization (WHO) estimates that there were around 285 million cases of illness in the globe in 2010; by 2030, 438 million people are anticipated to use this number by 2025.3<\/sup> With the biggest number of diabetic people worldwide and a steadily rising incidence of diabetes, India has earned the unsavory title of “Diabetes Capital of the World”.4 <\/sup>Hyperglycemia, or elevated blood glucose levels, is caused by an inability to make or utilize insulin.5<\/sup> Long-term elevated glucose levels are linked to the body being harmed and a number of organs and tissues failing.6<\/sup> <\/em><\/p>\n\n\n\n

With different degrees of effectiveness, a wide variety of complementary and alternative therapies have been employed to treat DM.7<\/sup> Worldwide, medicinal plants continue to be very important in providing for people’s health .8<\/sup> <\/p>\n\n\n\n

Metformin is the drug of choice for treating type 2 diabetes T2DM and was originally regarded as complementary and alternative medicine.4<\/sup> Over 1200 plants and chemicals have been claimed to be treatments for the same disease, and over 400 have been tested for usage in type 2diabetic patients.9<\/sup> Hyperglycemia results in the constant production of reactive oxygen species (ROS), and research has shown that diabetes alters the activity of antioxidant enzymes in numerous organs.10<\/sup> Antioxidants are crucial for neutralizing free radicals and defending the organism against oxidative stress.11<\/sup><\/p>\n\n\n\n

Peel of pomegranate (PP) as a type of fruit, pomegranates are a Middle Eastern native plant that are now widely farmed and consumed on a global scale.12 <\/sup>The  (PP), which accounts for around 26% to 30% of the weight of the fruit, is distinguished by its high concentrations of antioxidants, such as phenolic chemicals and flavonoids compound and a range of minerals like potassium, magnesium, sodium, calcium, phosphorus, and complex sugars, it has been discovered that pomegranate peels may aid in promoting general health and treating specific diseases when consumed.13<\/sup> Therefore, supplements produced from Pomegranate Peel  Extract (PPE)will be more beneficial than pomegranate pulp extract alone. In order to maintain the body’s health and increase muscle mass, it is preferable to use pomegranate peels rather than other supplements since they are high in vitamin C, which is a crucial component of health.14<\/sup> <\/p>\n\n\n\n

 The physiologically active version of the non-essential amino acid carnitine is called L-carnitine .15<\/sup> Methionine and lysine, two amino acids, are used by your body to make carnitine, which is also present in foods like dairy, meat, and avocados. Carnitine, or L\u2010\u03b2\u2010hydroxy\u2010\u03b3\u2010N\u2010 trimethyl aminobutyric acid, is synthesized primarily in the liver and kidneys. There is experimental evidence that l-carnitine stimulates the activity of the pyruvate dehydrogenase complex by decreasing the intra-mitochondrial acetyl\u2010CoA\/CoA ratio through the trapping of acetyl groups .16<\/sup> The simultaneous reduction in acetyl\u2010CoA levels in the cytosol further contributes to activate the glycolytic pathway, that is why l-carnitine  covers a role in the glucose metabolism and assists in fuel sensing .17<\/sup> L-carnitine covers also an important role in lipid metabolism, acting as an obligatory cofactor for \u03b2-oxidation of fatty acids by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane as acylcarnitine esters. Its lack impairs the ability to use fat as fuel; this can result in an acute metabolic decompensation, most often early in life, with hepatic encephalopathy and hypoketotic hypoglycemia .18 <\/sup><\/p>\n\n\n\n

 The amino acid L-carnitine, which is a protein building block and aids in energy production, is also crucial for healthy heart and brain function, muscular movement, and a variety of other bodily functions .19<\/sup>  <\/p>\n\n\n\n

L-carnitine supplements can help those whose genetic condition causes their levels of natural l-carnitine to be too low. Having a medical procedure (hemodialysis for renal illness) or using some medications (such as valproic acid for seizures) that deplete the body’s L-carnitine levels .20<\/sup> Supplementation with L-carnitine under medical supervision may benefit diabetic patients, the effectiveness of the supplement as a replacement, however, requires further study, it is also given to dieters, severe vegetarians, and babies who are underweight or born prematurely. Certain fatty acids are transported into cells via L-carnitine, where they undergo oxidation.21<\/sup> Energy is released as a result of this process. L-carnitine supplements improve the body’s capacity to utilize fat as a source of energy, lower cholesterol and triglyceride levels, and may minimize the risk of health issues in diabetics who have impaired fat metabolism .15<\/sup> Since diabetes raises the chance of developing cardiac issues, L-carnitine has a preventive impact on the muscles and function of the heart. Review the pharmacological effects and clinical applications of L-carnitine as cardioprotective and antioxidant involving also the liver respiration chain activity, prevention and treatment of heart metabolic disturbances in cardiovascular, obese diabetic cardiomyopathy (considering the fibrosis, cardiac subcellular function, heart-rate variability, and cardiac autonomic function), hyperlipidemia, and dilated cardiomyopathy diseases.<\/p>\n\n\n\n

 Therefore the current study\naimed to evaluate\nthe anti-diabetic efficacy of pomegranate peel extract and L-carnitine on\nstreptozotocin-induced diabetes mellitus in rats.<\/p>\n\n\n\n

Materials and Procedures <\/strong><\/p>\n\n\n\n

Chemical<\/strong><\/p>\n\n\n\n

The Sigma Chemical Company provided L-carnitine and streptozotocin, as well as other high analytical grade chemicals and solvents.  <\/p>\n\n\n\n

Medicinal plants<\/strong><\/p>\n\n\n\n

Getting PPE produced and administered Fresh pomegranate fruit was purchased at the neighborhood market in Tanta, Egypt, and its peel was removed before being first dried in the shade for ten days. Using a grinder, the powdered dry plant ingredients were created. A total of 100 g of dried plant material that had been ground up was submerged in methanol for one day at room temperature before being filtered through Whatman filter paper. After the filtrate was centrifuged at 8000 rpm for 15 minutes, the methanol was evaporated at 45 o<\/sup>C under reduced pressure. 22<\/sup><\/p>\n\n\n\n

Animal<\/strong><\/p>\n\n\n\n

A total of 70 mature male albino wistar rats (297-350g) were purchased from the Egyptian Stock Holding Company for Biological Products of Vaccines, Sera, and Drugs (VACSERA, Alexandria, Egypt). Our study approved for animal care and use ethical committee by our university (IACUC-SCI-TU-0292). Before the trial began, rats were kept at our Faculty’s animal house for a week. They were kept in conventional circumstances with a standard rodent feed, unlimited access to water, a standard temperature of 25 \u00b0C, and a relative humidity of at least 40%.<\/p>\n\n\n\n

Experimental Induction of Diabetes  <\/strong><\/p>\n\n\n\n

After a 12-hour fast, high-fat diet rats were given a single, freshly-made intraperitoneal (ip) injection of streptozotocin (STZ), 55 mg\/kg body weight, which was promptly dissolved in 1 ml of sodium citrate buffer, pH 4.5.23<\/sup> To reverse drug-induced hypoglycemia, the STZ-treated rats were given access to 5% glucose solution overnight. On the third day following infusion of STZ, rats were declared diabetic if they had persistent glycosuria, hyperglycemia, and is it measured in blood levels greater than 250 mg\/dl.<\/p>\n\n\n\n

Design of Experiments<\/strong><\/p>\n\n\n\n

A total number of 70 rats were separated into seven groups, each made up of a maximum of ten rats: Group 1 normal rats were given a standard diet, Group 2 normal rats were given PPE 200mg\/kg per day over the course of 12 weeks 12<\/sup>, and Group 3 normal rats were given L-carnitine 100 mg\/kg per day over the course of 12 weeks 24<\/sup>; Group (4) diabetic control (rats were given a high-fat diet to induce hyperlipidemia, and rats were given STZ to induce T2DM; Group (5) diabetic rats received PPE 200mg\/kg orally every day for 12 weeks 12<\/sup>; Group (6) diabetic rats, which  received L-carnitine 100 mg\/kg orally every day for 12 weeks 24<\/sup>; and Group (7) diabetic rats, which received PPE 200mg\/kg and L-carnitine 100mg\/kg orally every day for 12 weeks, respectively. <\/p>\n\n\n\n

Methods   <\/strong><\/p>\n\n\n\n

Measurement of Body Weight<\/strong><\/p>\n\n\n\n

After a 12-week experiment, the weights for each rats in each group were recorded<\/p>\n\n\n\n

Preparing Blood  <\/strong><\/p>\n\n\n\n

After a 12-week treatment period, rats were fasted for 8 hours in preparation for blood serum analysis. Before taking blood samples from the orbital venous plexus, the rats were sedated with diethyl ether. For 10 minutes, blood serum was centrifuged at 2000 rpm while being chilled to measure the amounts of several biochemical markers..<\/p>\n\n\n\n

Blood Parameter Analysis<\/strong><\/p>\n\n\n\n

Serum glucose was performed using a kit purchased from human Diagnostics in Cairo City High density lipoprotein (HDL), and Low density lipoprotein (LDL) levels were assessed enzymatically using a kit purchased from human diagnostics, Cairo City, Egypt, in accordance with the method described by Burtis25<\/sup>.<\/p>\n\n\n\n

Tissue samples: Following scarification, the rats’ livers were instantly removed and cooled saline washed. Each slice of the ten liver from each group was homogenized individually with cooled glass-Teflon porter-Elvheim to estimate total Superoxide dismutase (SOD) , catalase (CAT), malondialdehyde (MDA)and nuclear factor erythroid related factor 2  (Nrf2) activity. <\/p>\n\n\n\n

Biochemical marker tests and antioxidantsenzyme activity:<\/strong><\/p>\n\n\n\n

SOD activity was measured using the Paoletti26<\/sup> method, CAT activity was measured using method Buege27<\/sup>,using a kit from Bio Diagnostics, (Cairo City, Egypt), MDA level was measured using  method Buege27<\/sup>,using a kit from Bio Diagnostics, (Cairo City, Egypt), and Nfe2 was measured. following a kit purchased from Bio Diagnostics (Cairo City, Egypt), the activity was assessed following the method Theodore.28<\/sup>  <\/p>\n\n\n\n

Statistical analysis<\/strong><\/p>\n\n\n\n

The statistical analysis of the data resulted in the presentation of means and standard deviations (SD). Using one-way analysis of variance (ANOVA), all data were statistically analyzed, and then all diabetic groups were compared using the Student’s t test utilizing computer software (Graphpad In State Software, Inc.). P-values less than p<\/em>= 0.05were considered as statistically significant.<\/p>\n\n\n\n

Results<\/strong><\/p>\n\n\n\n

Treatments’ impact on body weight<\/strong><\/p>\n\n\n\n

In contrast to normal animals,\ndiabetic animals had significantly lower body weights, which may have been\nimproved by better glycemic control after receiving PPE and L-carnitine\ntreatment. Table 1 shows that after the 12th week of treatment, there was a\nsubstantial rise in body weight across all groups (p<\/em>= 0.01). Biomedical analysis <\/p>\n\n\n\n

blood glucose levels <\/strong><\/p>\n\n\n\n

Table 2 demonstrates that there was no significant difference in serum glucose levels between the control group (G1) and group (G2) in any of the groups after the 12-week. The levels of serum glucose in the diabetic group (G4) are noticeably greater than those in the control group (G4). In contrast, diabetic rats treated with PPE + L-carnitine (G5, G6, and G7) groups demonstrated a significant (p0.01) decrease in serum glucose levels when compared to the diabetic group (G4); the decrease was more significant in the PPE and L-carnitine (G7) treatment than in the PPE (G5) or L-carnitine (G6) group.<\/p>\n\n\n\n

Changes in lipid profiles <\/strong><\/p>\n\n\n\n

Cholesterol and triglycerides levels in the control group (G1) and group (G6) did not significantly differ, as shown in Table 1 of the study. In comparison to the control group (G4), the diabetic group (G4) has significantly higher levels of HDL-C, triglycerides, and cholesterol. A significant (p0.01) reduction in cholesterol, triglycerides, and LDL-C levels was observed in diabetic rats treated with PPE or\/and L-carnitine (G5, G6, and G7) groups when compared to the diabetic group (G4); the reduction was more pronounced in the PPE + L-carnitine (G7) treatment group than in the PPE (G5) or L-carnitine (G6) groups.<\/p>\n\n\n\n

Antioxidative enzyme activity and the biomarker are affected by the treatment<\/strong><\/p>\n\n\n\n

According to Table 2, neither the control group (G3) nor the group (G6) had significantly different levels of SOD or CAT activity. In the diabetic group (G4) compared to the control group (G4), there is a discernible decline in the activity of (SOD and CAT). However, diabetic rats treated with PPE and L-carnitine (G5, G6, and G7) groups showed a significant (p= 0.01) increase in (SOD and CAT) activity when compared to the diabetic group (G4); the increase was more pronounced in the PPE + L-carnitine (G7) treatment than in the PPE (G5) or L-carnitine (G6) groups.<\/p>\n\n\n\n

 Malondialdehyde level in liver <\/strong><\/p>\n\n\n\n

The levels of MDA in the control group (G1) and group (G3) did not significantly differ, as shown in Table (2). Compared to the control group (G4), the levels of (MDA) are significantly higher in the diabetes group (G4). However, compared to the control group (G4), diabetic rats treated with PPE and L-carnitine (G5, G6, and G7) showed a significant (p0.01) decrease in MDA levels; the decrease was more pronounced in the PPE + L-carnitine (G7) treatment group than in the PPE (G5) or L-carnitine (G6) groups.<\/p>\n\n\n\n

liver\n(Nrf2<\/strong>  ) activity (ng\/mg protein)<\/strong><\/strong><\/p>\n\n\n\n

In the control group (G3) and group (G6), the levels of (Nrf2) did not significantly differ, as shown in Table 2. When compared to the control group (G4), the levels of (Nrf2) are significantly lower in the diabetes group (G4). In contrast, diabetic rats treated with PPE and L-carnitine (G5, G6, and G7) groups showed a significant (p0.01) increase in (Nrf2  )levels when compared to the diabetic group (G4); the increase was more pronounced in the PPE + L-carnitine (G7) treatment than in the PPE (G5) or L-carnitine (G6) groups.<\/p>\n\n\n\n

Table 1: The impact of PPE + L-carnitine’s on weightSerum glucose, lipid profile in different groups<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n
\n

 <\/strong><\/p>\n<\/td>\n

\n

G1<\/strong><\/p>\n<\/td>\n

\n

G2<\/strong><\/p>\n<\/td>\n

\n

G3<\/strong><\/p>\n<\/td>\n

\n

G4<\/strong><\/p>\n<\/td>\n

\n

G5<\/strong><\/p>\n<\/td>\n

\n

G6<\/strong><\/p>\n<\/td>\n

\n

G7<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Weight (g) <\/strong>after the 12th<\/sup><\/strong> week<\/strong><\/p>\n<\/td>\n

\n

361*\u00b15.4<\/p>\n<\/td>\n

\n

306\u00b12.1<\/p>\n<\/td>\n

\n

310*\u00b11.37<\/p>\n<\/td>\n

\n

297.0\u00b13.3<\/p>\n<\/td>\n

\n

318*\u00b14.1<\/p>\n<\/td>\n

\n

314.5*\u00b12.9<\/p>\n<\/td>\n

\n

324*\u00b12.5<\/p>\n<\/td>\n<\/tr>\n

\n

Glucose(mg\/d) <\/strong>after the 12th<\/sup><\/strong> week<\/strong><\/p>\n<\/td>\n

\n

88.5\u00b11.4<\/p>\n<\/td>\n

\n

80\u00b11.1<\/p>\n<\/td>\n

\n

83*\u00b11.45<\/p>\n<\/td>\n

\n

517\u00b122.4<\/p>\n<\/td>\n

\n

225.5*\u00b15.8<\/p>\n<\/td>\n

\n

226.5*\u00b18.7<\/p>\n<\/td>\n

\n

221*\u00b13.7<\/p>\n<\/td>\n<\/tr>\n

\n

Cholesterol (mg\/dl)<\/strong><\/p>\n<\/td>\n

\n

80.0\u00b16.2<\/p>\n<\/td>\n

\n

77\u00b14.2<\/p>\n<\/td>\n

\n

77.5*\u00b15.2<\/p>\n<\/td>\n

\n

87.5\u00b15.6<\/p>\n<\/td>\n

\n

75.0*\u00b12.4<\/p>\n<\/td>\n

\n

79.5*\u00b12.8<\/p>\n<\/td>\n

\n

72.5*\u00b11.9<\/p>\n<\/td>\n<\/tr>\n

\n

Triglycerides (mg\/dl)<\/strong><\/p>\n<\/td>\n

\n

80.5\u00b12.9<\/p>\n<\/td>\n

\n

74.5\u00b12.4<\/p>\n<\/td>\n

\n

78.5\u00b12.3<\/p>\n<\/td>\n

\n

97.5\u00b12.8<\/p>\n<\/td>\n

\n

74.0*<\/strong>\u00b10.9<\/p>\n<\/td>\n

\n

76.0*<\/strong>\u00b11.3<\/p>\n<\/td>\n

\n

72.5*<\/strong>\u00b12.9<\/p>\n<\/td>\n<\/tr>\n

\n

HDL-c (mg\/dl)<\/strong><\/p>\n<\/td>\n

\n

41.0*\u00b11.4<\/p>\n<\/td>\n

\n

37.5\u00b11.3<\/p>\n<\/td>\n

\n

40*\u00b13.4<\/p>\n<\/td>\n

\n

32.0\u00b11.4<\/p>\n<\/td>\n

\n

44.5*\u00b12.3<\/p>\n<\/td>\n

\n

42.5\u00b11.6<\/p>\n<\/td>\n

\n

47.0*\u00b11.5<\/p>\n<\/td>\n<\/tr>\n

\n

LDL-c (mg\/dl)<\/strong><\/p>\n<\/td>\n

\n

22.5*<\/strong>\u00b17.4<\/p>\n<\/td>\n

\n

23.5\u00b14.7<\/p>\n<\/td>\n

\n

23\u00b16.6<\/p>\n<\/td>\n

\n

37.5\u00b16.02<\/p>\n<\/td>\n

\n

16.0*<\/strong>\u00b13.4<\/p>\n<\/td>\n

\n

20.5\u00b13.4<\/p>\n<\/td>\n

\n

12.0*<\/strong>\u00b11.9<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Data were expressed as men\u00b1 SD of 10 rats per group. One-way ANOVA, which compares all diabetes group members, was used to determine the significance of the difference. As mean \u00b1SD, values are expressed. P 0.001 was the significance level for the one-way ANOVA. Where, G1 represents the normal Control group, G2 represents the normal Control treated with PPE, and G3 represents the normal Control treated with L-carnitine group. G4, the group with diabetes; G5, the group receiving PPE treatment; G6, the group receiving L-carnitine treatment; and G7, the group receiving PPE and L-carnitine treatment<\/p>\n\n\n\n

Table 2: The impact of PPE + L-carnitine’s on activity of (SOD, CAT, MDA and  Nrf2  ) (wet weight tissue) of liver in different groups<\/strong>.<\/p>\n\n\n\n\n\n\n\n\n\n
\n

 <\/strong><\/p>\n<\/td>\n

\n

G1<\/strong><\/p>\n<\/td>\n

\n

G2<\/strong><\/p>\n<\/td>\n

\n

G3<\/strong><\/p>\n<\/td>\n

\n

G4<\/strong><\/p>\n<\/td>\n

\n

G5<\/strong><\/p>\n<\/td>\n

\n

G6<\/strong><\/p>\n<\/td>\n

\n

G7<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

SOD <\/strong>(<\/strong>U\/gm\/wet weight tissue)<\/strong><\/p>\n<\/td>\n

\n

155.5*\u00b16.1<\/p>\n<\/td>\n

\n

163*<\/strong>\u00b12.7<\/p>\n<\/td>\n

\n

160\u00b12.9<\/p>\n<\/td>\n

\n

129\u00b11.9<\/p>\n<\/td>\n

\n

155*<\/strong>\u00b17.30<\/p>\n<\/td>\n

\n

140\u00b19.8<\/p>\n<\/td>\n

\n

174.5*<\/strong>\u00b15.0<\/p>\n<\/td>\n<\/tr>\n

\n

CAT<\/strong>(U\/gm\/wet weight tissue)<\/p>\n<\/td>\n

\n

2.07*<\/strong>\u00b10.2<\/p>\n<\/td>\n

\n

2.66*<\/strong>\u00b10.2<\/p>\n<\/td>\n

\n

2.1\u00b10.3<\/p>\n<\/td>\n

\n

1.82\u00b10.3<\/p>\n<\/td>\n

\n

2.14*<\/strong>\u00b10.4<\/p>\n<\/td>\n

\n

2.17\u00b10.1<\/p>\n<\/td>\n

\n

3.97*<\/strong>\u00b10.3<\/p>\n<\/td>\n<\/tr>\n

\n

MDA<\/strong>(nmol\/gm\/wet weight tissue)<\/p>\n<\/td>\n

\n

2.84\u00b10.13<\/p>\n<\/td>\n

\n

2.75*<\/strong>\u00b10.2<\/p>\n<\/td>\n

\n

2.8\u00b10.3<\/p>\n<\/td>\n

\n

3.74\u00b10.2<\/p>\n<\/td>\n

\n

3.03*<\/strong>\u00b10.3<\/p>\n<\/td>\n

\n

3.14\u00b10.2<\/p>\n<\/td>\n

\n

2.88*<\/strong>\u00b10.3<\/p>\n<\/td>\n<\/tr>\n

\n

Nrf2<\/strong>  (ng\/mg protein)<\/p>\n<\/td>\n

\n

116*<\/strong>\u00b14.5<\/p>\n<\/td>\n

\n

128*<\/strong>\u00b12.2<\/p>\n<\/td>\n

\n

124\u00b12.2<\/p>\n<\/td>\n

\n

107.5\u00b15.8<\/p>\n<\/td>\n

\n

126.5*<\/strong>\u00b12.3<\/p>\n<\/td>\n

\n

123.5*<\/strong>\u00b11.9<\/p>\n<\/td>\n

\n

145.5*\u00b15.5<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

Data were expressed as\nmen \u00b1 SD of 10 rats per group. By comparing all\ndiabetic group members, a one-way ANOVA was used to determine the significance\nof the difference. The formula for values is mean \u00b1 SD. P 0.001 was considered\nsignificant for one-way ANOVA. Where, G1, the untreated Control group; G2, the\nuntreated Control group treated with PPE; and G3, the untreated Control group\ntreated with L-carnitine; G4, the diabetic group; G5, the diabetic receiving\nPPE treatment; G6, the diabetic receiving L-carnitine treatment; and G7, the\ndiabetic receiving PPE plus L-carnitine treatment<\/p>\n\n\n\n

Discussion<\/strong><\/strong><\/p>\n\n\n\n

In diabetic humans, hyperglycemia was linked to a number of metabolic abnormalities. A key element of glucose balance is insulin’s capacity to control tissue glucose absorption. It is critical to switch out the currently used, side-effect-prone hypoglycemic drugs with innovative, highly effective, safe, and reasonably priced ones for the treatment of DM.29-31<\/sup> The goal of the current investigation was to determine how PPE and L-carnitine affected male albino wistar rats that had been given STZ to induce DM. The results showed that streptozotocin at a low dose and a high fat diet caused hyperglycemia in the experimental rats. In the current study, it was clear that rats with diabetes lost weight. While improvements were seen in the body weights of the diabetic group receiving PPE. PPE’s antidiabetic activity appears to be what gives it the ability to stop body weight loss.<\/p>\n\n\n\n

The current findings concur with earlier study <\/sup>.32<\/sup> According to the study, weight increased in the PPE and L-carnitine treated group compared to the diabetic group. Our findings agree with earlier research .33<\/sup> Due to the antidiabetic effect of L-carnitine, weight rose compared to the diabetes group; these findings are in line with the research .1,34<\/sup> PPE’s phenolic content is responsible for its anti-diabetic effects. PPE reduces lipid peroxidation and oxidative stress, which is one important mechanism by which it ameliorates the effects of diabetic problems. The neutralization of reactive oxygen species produced may have this impact.35,36<\/sup> <\/p>\n\n\n\n

In the results presented here, a rise in lipid peroxidation related with diabetes mellitus was noted. Lipid peroxidation was seen to diminish after PPE and L-carnitine were administered. This may be because it actively transports fatty acids for use in energy production18<\/sup> according to previous studies 18,37<\/sup>  and the current study, oral administration of L-carnitine for a 12-week period improves the improvement of several features of diabetes, such as body weight reduction and glycemic level after fasting. The results of the current study showed that the glucose level was elevated in the diabetic group, which is in line. 1,18<\/sup> The diabetic group’s glucose level rose in comparison to the control group. Compared to the diabetic group, the groups receiving PPE had lower glucose levels.12<\/sup> Earlier research is compatible with the findings of the current study. Because of L-Carnitine’s antidiabetic effect, glucose levels reduced in both those receiving treatment and those who were not, and these findings are in line with a study .35<\/sup> <\/p>\n\n\n\n

Numerous research have demonstrated the hypoglycemic and antioxidant benefits of PPE. The suppression of enzymes that break down carbohydrates is another benefit of pomegranate products. Punica granatum<\/em> (PG) flower and peel contain phenols, which may also have an antihyperglycemic effect. PPE likely regulates lipid metabolism by reducing oxidative and inflammatory damage and enhancing mitochondrial metabolism. 38,39<\/sup> <\/p>\n\n\n\n

The results of this investigation support PPE therapy. In this study, HDL-C decreased in the diabetes group compared to the normal control group, whereas lipid levels (TG, TC, and LDL-C) increased in the diabetic group. The findings from our study concur with those from 40<\/sup>. In agreement with 36,38<\/sup>, diabetics. Moreover L-carnitine is an important cofactor for the -oxidation of fatty acids and is involved in lipid metabolism. It accomplishes this by facilitating the passage of acylcarnitine esters, which are long-chain fatty acids, over the inner mitochondrial membrane. Its absence affects the body’s capacity to use fat as fuel, which can cause an abrupt metabolic decompensation, most frequently in infancy, characterized by hepatic encephalopathy and hypoketotic hypoglycemia 21,22<\/sup>. Increased ROS production and\/or a depleted antioxidant enzyme system, which includes SOD, catalase, and MDA, can also contribute to oxidative stress. These anti-oxidant enzymes guard cells against cytotoxic ROS.<\/p>\n\n\n\n

Additionally MDA, use glutathione’s capacity to decrease thiols to lessen ROS targets like oxidized lipids and proteins. Lipid peroxidation in the cellular and subcellular membranes is the unavoidable result of ROS injury under the situation of inactive antioxidant enzymes 41,42<\/sup>.We measured the concentrations of SOD, CAT, and MDA in liver homogenates. In the model group, elevated MDA levels coincided with a decline in SOD and CAT antioxidant levels. PPE and L-carnitine therapy raised SOD levels and lowered MDA levels. <\/p>\n\n\n\n

This study revealed that (SOD and CAT) were depleted in a diabetic group, and these results were consistent with Muhammad et al<\/em>., Cerda et al<\/em>., 43,44<\/sup> However, the current study also revealed that PPE increased the activity of antioxidant enzyme (SOD and CAT), and these results are consistent with studies .45.46<\/sup> In this study, PPE and L-carnitine both increased SOD and CAT activity. These results are consistent with studies .47<\/sup> On the other hand, the current study found that PPE decreased the activity of antioxidant enzyme activities MDA, these results being consistent with a study.46,47<\/sup> This investigation revealed that MDA was raised in a diabetic group, and these results are consistent.45<\/sup> PPE and L-carnitine had lower antioxidant enzyme activity MDA in this investigation. 48,43<\/sup><\/p>\n\n\n\n

Through Nrf2  controls the expression of detoxifying and antioxidant enzymes. Kelch-like ECH-associated protein 1(Keap1), an actin-binding repressor protein, locks down Nrf2 under normal circumstances and keeps it in the cytoplasm. Through this mechanism, Keap1 increases oxidative stress by inhibiting Nrf2 and ARE\/EpRE activation. Diabetes has been linked to decreased Nrf2 expression and increased oxidative stress .47,49<\/sup> Although the precise mechanism of Nrf2 downregulation is still unknown, increasing (Keap1) and phosphorylating ERK both lower Nrf2 levels. Additionally, Nrf2 transcription factor is activated in hepatic cells by PPE and L-carnitine. In the current work, PPE and L-carnitine prevented the hyperglycemia-induced downregulation of Nrf2, a downstream gene product of the Nrf2-Keap1 pathway. 50<\/sup> Therefore it is expected that regulating Nrf2 expression will be essential in preventing oxidative damage caused by hyperglycemia in diabetic rats by PPE and L-carnitine. On the one hand, the current study revealed that PPE boosted the activity of antioxidant enzyme activities (Nrf2); these results are compatible with a study Liu et al.<\/em>,.48<\/sup> This study shown that (Nrf2) was low in a diabetic group. L-Carnitine demonstrated higher antioxidant enzyme (Nrf2) activity in this study. 50,51<\/sup> In order to control the adaptive response to oxidants and electrophiles, Nrf2 performs as a xenobiotic-activated receptor. 52<\/sup><\/p>\n\n\n\n

   Conclusion<\/strong><\/strong><\/p>\n\n\n\n

The PPE and L-Carnitine are\neffective in preventing diabetes because they lower blood glucose, body weight, and elevated lipids caused by T2DM. Our\nresults show the efficacy of oral PPE and L-Carnitine in the management of type\n2 diabetes-related obesity. Also PPE and L-Carnitine play a significant\npart in functioning as a supplemental therapy in diabetes treatment protocols,\nwith the goal of reducing diabetes progression and fat gain in diabetics.<\/p>\n\n\n\n

Recommendation<\/strong><\/strong><\/p>\n\n\n\n

  <\/strong>Finally, we propose that PPE\nand L-Carnitine exhibit an intriguing anti-diabetic efficacy in this study and\nmay be of significant use a remedy for T2DM. These nutrients are also\ngood for lowering body weight, enhancing the lipid profile, and antioxidant\nenzymes.  <\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. Biolo G., Stulle M., Bianco F., Mengozzi G., Barazzoni R., Vasile A., Panzetta G., and   Guarnieri G. Insulin action on glucose and protein metabolism during L-carnitine supplementation in maintenance haemodialysis patients. Nephrol. Dial Transplant.<\/em>,2008;23(3):991-997
    CrossRef<\/a><\/li>
  2. Loai Aljerf and Iyad Alhaffar:Salivary Distinctiveness and Modifications in Males withDiabetes and Beh\u00e7et\u2019s Disease. Biochemistry Research International Volume<\/em> 2017, Article ID 9596202, 12 pages
    CrossRef <\/a><\/li>
  3. Liu Q., Wang S., Cai L. Diabetic cardiomyopathy and its mechanisms Role of oxidative stress and damage. J. of Diabetes Investig<\/em>; 2014,5:623-634.
     CrossRef <\/a><\/li>
  4. Ogurtsova  K, Rocha F. , Huang  Y., Linnenkamp  U., Guariguata L., Cho N.H. IDF diabetes atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res. Clin. Pract<\/em>., 2017  ;128:40-50.
     CrossRef <\/a><\/li>
  5. Elbandrawy MM, Sweef O, Elgamal D, Mohamed TM, Tousson E, Elgharabawy RM. Ellagic acid regulates hyperglycemic state through modulation of pancreatic IL-6 and TNF-\u03b1 immunoexpression. Saudi Journal of Biological Sciences<\/em>. May 1. 2022;29(5):3871-3880.
     CrossRef <\/a><\/li>
  6. Santo S. S., Sergio N., Luigi D. P., Giuseppe M., Margherita F., Gea O. C., Roberto F., Gabriella C., Giuseppe P., and Massimiliano A. Effect of PLC on functional parameters and oxidative profile in type 2 diabetes-associated PAD. Diabetes Res.Clin Pract.<\/em>, 2006;72(3):231-237.
    CrossRef <\/a><\/li>
  7. Chang C.L., Lin Y., Bartolome A.P., Chen Y.C., Chiu S.C., Yang W.C. Herbal therapies for type 2 diabetes mellitus: chemistry, biology, and potential application of selected plants and compounds. Evid Based Complement Alternat. Med<\/em>., 2013 ;2013:378657. 
     CrossRef <\/a><\/li>
  8. Abd Eldaim MA, Tousson E, Soliman MM, El Sayed IE, Abdel Aleem AA, Elsharkawy HN. Grape seed extract ameliorated Ehrlich solid tumor-induced hepatic tissue and DNA damage with reduction of PCNA and P53 protein expression in mice. Environmental Science and Pollution Research Aug<\/em>., 2021;28(32):44226-38.
    CrossRef <\/a><\/li>
  9. Aditi G., Kishore M., Puneet R., VijendraS., Dharam P. and Bansal U. Prevalence Of Anemia In Different Degrees Of Glycemic Control In Type Ii Diabetes Mellitus And Its Association With Crp . J. of  Molecular & Clinical Medicine<\/em>, 2022; Volume 9, Issue 08,  p 2738-2745<\/li>
  10. Tousson E, El Gharbawy DM. Impact of Saussurea lappa root extract against copper oxide nanoparticles induced oxidative stress and toxicity in rat cardiac tissues. Environmental Toxicology<\/em>, 26 October, 2022; https:\/\/doi.org\/10.1002\/tox.23688
    CrossRef <\/a> <\/li>
  11. Ahmed R. G. The physiological and biochemical effects of diabetes on the balance between oxidative stress and antioxidant defense system, Medical J. of the Islamic World Academy of Sciences<\/em>., 2005; vol. 15, pp. 31\u201342<\/li>
  12. Elsaid  F.G, Alsyaad K.M., Alqahtani  F.A. The role of olive leaves and  pomegranate peel extracts on diabetes mellitus induced in male rats. Egypt J. of  Hosp Med<\/em>., 2018;71:3079-3085.<\/li>
  13. Anna M. ,Miriana D.,Danilo M.,Monica D.C.,Riadh I., and Marcello S.L. Analysis of the Phytochemical Composition of Pomegranate Fruit Juices, Peels and Kernels: AComparative Study on Four Cultivars Grownin Southern Italy  Plants, 2021; 10,2521
     CrossRef <\/a><\/li>
  14. Kam A., Li K.M., Razmovski Naumovski V., Nammi S., Shi J.,Chan K. ,Ligq A. A Comparative Study on the Inhibitory Effects of Different Parts and Chemical Constituents of Pomegranate on \u03b1 Amylase and \u03b1 Glucosidase. Phytother Res<\/em>., 2013 ; 27: 1614-20.
    CrossRef <\/a><\/li>
  15. Tousson E, Hafez E, Zaki S, Gad A. The cardioprotective effects of L-carnitine on rat cardiac injury, apoptosis, and oxidative stress caused by amethopterin. Environmental Science and Pollution Research<\/em>., 2016; Oct 1;23(20):20600-8.
    CrossRef <\/a><\/li>
  16. Crentsil, V.:Mechanistic contribution of carnitine deficiency to geriatric frailty. Ageing Res. Rev.<\/em> 2010;9(3):265-26
    CrossRef <\/a><\/li>
  17. Broad E. M., Maughan R. J., and Galloway S. D.R.:Effects of exercise intensity and altered substrate availability on cardiovascular and metabolic responses to exercise after oral carnitine supplementation  in athletes. Int. J. of Sport Nutr.Exerc.Metab<\/em>. 2011;21 (5):385-397.
     CrossRef <\/a><\/li>
  18. Gonzalez O.M., Hernandez Gonzalez S. O., Hernandez Sa. E., and Martinez A: E. Effect of oral L-carnitine administration on insulin sensitivity and lipid profile in type 2 diabetes mellitus patients. Ann.Nutr.Metab<\/em>. 2008;52(4):335-338
     CrossRef <\/a><\/li>
  19. Essawy AE, El-Sayed SA, Tousson E, El-gawad A, Horeya S, Alhasani RH, Abd Elkader HT. Anti-kindling effect of Ginkgo biloba leaf extract and L-carnitine in the pentylenetetrazol model of epilepsy. Environmental Science and Pollution Research<\/em>., 2022; 29: 48573\u201348587.
     CrossRef <\/a><\/li>
  20. Danya S. , Zujaja H. H., Usama B. K., Haroon J. , Hassaan J. , Farooq U. A. establishing carnitine deficiency in patients of type-ii diabetes mellitus with early diabetic retinopathy  Pak J. of  Pathol<\/em>., 2021; Vol. 32 (4): 152-156.<\/li>
  21. Lee B.J., Lin J.S., Lin Y.C. and Lin P.T. Effects of L-carnitine supplementation on lipid profiles in patients with coronary artery disease. Lipids Health Dis<\/em>., 2016;15:107
     CrossRef <\/a><\/li>
  22. Ahmed A.T., Belal  S.K., Salem A.G. Protective effect of pomegranate peel extract against diabetic induced renal histopathological changes in albino rats. IOSR J. of  DMS<\/em>., 2014;13:94-105.
     CrossRef <\/a><\/li>
  23. Rajesh R., Sreekala A. Characterisation of streptozotocin induced diabetes mellitus in Wistar albino rats- A histological and haematological perspective.Med. Pulse Int. J. of  Anatomy<\/em>, 2020; 13 (2), 33\u201336.
     CrossRef <\/a><\/li>
  24. Heo Y.R., Lee Y., Cha Y.S. L-carnitine adminstration im-proves lipid metabolism in Streptozotocin-induced Diabetic rat. Nutr Sci<\/em>., 2002;5:3-8.<\/li>
  25. Burtis C., Ashwood E.R. and Bruns D,E. Tietz Textbook of clinical chemistry and Molecular Diagnostic,4th Ed.Elsevier Saunders Company , 2006; St Louis. pp. 1788-98 (Liver Function Tests ) , 938-57 ( lipid profile ),869-72(Glucose)<\/li>
  26. Paoletti F. and Mocali A. Determination of superoxide dismutase activity by purelychemical system based on NADPH oxidation. Methods Enzymol<\/em>., 1990, 186: 209-220.
    CrossRef <\/a><\/li>
  27. Buege J. A. and Aust S. D. (1978): Microsomal lipid peroxidation. Methods. Enzymol<\/em>. , 1997;52: 302\u2013310.
     CrossRef <\/a><\/li>
  28. Theodore M., Kawwai Y., Yang J., Kleshchenko Y., Reddy  S., and Villalte F. Multiple Nuclear Localization Signals Function in the Nuclear Import of the Transcription Factor Nrf2.  J. of  Biol. Chem<\/em>., 2008; 283(14): 8984-8994
    CrossRef<\/a><\/li>
  29. Atem Bethel AjongID, Bruno Kenfack, Innocent Mbulli AliID, Martin,Ndinakie Yakum, Loai AljerfIDPhelix Bruno Telefo : Hypocalcaemia and calcium intake in pregnancy: A research protocol for critical analysis of risk factors, maternofoetal outcomes and evaluation of diagnostic methods in a third-category health facility,Cameroon. PLOS ONE<\/em> ; 2020,15(11) November 5, , 13 pages
    CrossRef<\/a><\/li>
  30. Atem Bethel AjongID, Bruno Kenfack, Innocent Mbulli AliID,Martin Ndinakie Yakum, Ukaogo Prince Onydinma, Fulbert Nkwele Mangala Loai AljerfID, Phelix Bruno Telefo: Ionised and total hypocalcaemia in pregnancy: An analysis of prevalence and risk factors in a resource-limited setting, Cameroon. PLOS ONE<\/em>  2022, 17(5)\/ttps:\/\/doi.org\/10.1371\/journal.pone.0268643 May 18, , 19 pages
     CrossRef <\/a><\/li>
  31. Atem Bethel AjongID , Bruno KenfackID , Innocent Mbulli Ali, Martin Ndinakie Yakum, Prince Onydinma UkaogoID, Fulbert Nkwele Mangala ,Loai AljerfID, Phelix Bruno Telefo:Adverse maternofoetal outcomes associated with ionised calcaemia, total calcaemia, albuminaemia, and calcium supplementation in pregnancy: Analysis from a resourcelimited setting. PLOS ONE<\/em>, 2022,17(8) \/https:\/\/ doi.org\/ 10.1371\/ journal.pone.0271525 August 1 , 15 pages
    CrossRef <\/a><\/li>
  32. Mohammad Z.  <\/a>, Naseh P. , Mahlagha N.S.  <\/a>, Niloufar R.   <\/a>,  Omid A. , Farideh S.  <\/a>, Samira R.  The effects of L-carnitine supplementation on glycemic markers in adults.   J. of Nutr.<\/em>, 2023 Jan 10;9:p 3389-33100<\/li>
  33. Mihaela S.  , Alen A.  , Irena V.  , Oana E., Constantin G. and Natasa P. U. Extraction of Polyphenols and Valorization of Fibers from Istrian-Grown Pomegranate (Punica granatum L.). J. of  Foods<\/em>, 2022; 11(18), 2740-2756
     CrossRef <\/a><\/li>
  34. Yongzhen Z., Qiaoliang W., Mohammad H.R. Effect of L-Carnitine Supplementation during Exercises on Blood Fatigue and Energy Metabolism Factors . Progress in Nutrition<\/em>, 2022; Vol. 24, N. 3: 202-2021.<\/li>
  35. Thulsidhar H. , Bhuvaneshwari J.S., Chandrashekhar V. M. , and Reddy S. V. Evaluating Hypoglycaemic Activity of Pomegranate Peel Powder and Defatted Soybean Flour For  mulated Cookies in STZ Induced Diabetic Rats. J. of  Experimental Agriculture International<\/em>, 2022; 44 (11). p. 16-23.
     CrossRef <\/a> <\/li>
  36. Chen H.. ,Weimin Z., Jianke L., Lin D., Ou L, Shengjuan Z., and Jia L. Bene\ufb01cial Effects of Pomegranate on Lipid Metabolism in Metabolic Disorders . Mol. Nutr. Food Res<\/em>., 2019; 63, 1-12
     CrossRef <\/a><\/li>
  37. Yi Liu K. , Weng K., Ding T. W., Hong Yan L., Hua Bin L., Jia Rong Z. Pomegranate peel-derived punicalagin: Ultrasonic-assisted extraction, purification, and its \u03b1-glucosidase inhibitory mechanism. J. of Food Chemistry<\/em>, 2022;Volume 374,16 April, 1316-1335.
    CrossRef <\/a><\/li>
  38. Turgut S. S., Ayla S., and Fatma I. Effect of pomegranate peel extract on lipid and protein oxidation in beef meatballs during refrigerated storage. Meat science<\/em>., 2016; 116: 126-132.
     CrossRef <\/a><\/li>
  39. Salwe K.J, Sachdev D.O., Bahurupi Y., Kumarappan M. Evaluation of  antidiabetic, hypolipedimic and antioxidant activity of hydroalcoholic  extract of leaves and fruit peel of Punica granatum in male wistar albino  rats. J. of Nat Sci Biol Med<\/em>., 2015;6:56-62.
     CrossRef <\/a><\/li>
  40. Sohrab G., Roshan H., Ebrahimof S., Nikpayam O., Sotoudeh G., Siasi F. Effects of pomegranate juice consumption on blood pressure and lipid  profile in patients with type  2 diabetes: A  single-blind randomized  clinical trial. Clin. Nutr. ESPEN<\/em>., 2019;29:30-35.
     CrossRef <\/a><\/li>
  41. Saad. E.A., Hassanien.M.M, El-Hagrasy M.A,Radwan K.H.Antidiabetic, hypolipidemic and antioxidant activities and protective effects of  Punica granatum peels powder against pancreatic and hepatic tissues  injuries in streptozotocin induced IDDM in rats. Int . J. of Pharm Sci<\/em>., 2015 ;7:397-402<\/li>
  42. Wolters K., Medknow F.Effect of L-carnitine on the Lipid Profile, Glycemic Control,Oxidative Stress, and Anthropometric Indices of Individuals with Type 2 Diabetes. J. of Diabetology.,<\/em> 2022 ; p 199-209.
     CrossRef <\/a><\/li>
  43. Muhammad M. , Sultana B., Anwar F., Ahmad A., and Syed S.R. Enzyme-assisted supercritical fluid extraction of phenolic antioxidants from pomegranate peel. The J. of Supercritical Fluids.<\/em>, 2015; 104: 122-131.
     CrossRef <\/a><\/li>
  44. Cerda B. , Llorach R., Ceron J., Espin J.C., Tomas-Barberan F.A. Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice. Eu. J. of Nutr.,<\/em> 2003;42(1):18\u201328.
     CrossRef <\/a><\/li>
  45. Beatriz G., Manuela E.P., Juana F. L., Jos\u00e9 A. ,P\u00e9rez \u00c1. , Manuel V. M. Invitro gastrointestinal digestion of pomegranate peel (Punica granatum) \ufb02our  obtained from co-products :Changes in the Antioxidant potential and bioactive compounds stability J. of  Functional Foods<\/em>., 2015;19  617\u2013628
     CrossRef <\/a><\/li>
  46. Gil M.I., Tom\u00e1s B.F.A., Hess P. B., Holcroft D.M., Kader A.A.: Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J. of Agric Food Chem<\/em>. 2000;48:4581\u20139.
     CrossRef <\/a><\/li>
  47. Gomez A.L., MateA., Miguel C.J.L., Jimenez L., Jos A.,Camean, A. M., Revilla E.,and Vazquez C. M. L-carnitine attenuates oxidative stress in hypertensive rats. J. of Nutr. Biochem.<\/em>, 2007;18(8):533-540
     CrossRef <\/a><\/li>
  48. Li W., Khor T.O., Xu C., Shen G. and  Jeong W.S. Activation of Nrf2-antioxidant signaling attenuates NF\u03baB-inflammatory response and elicits apoptosis. Biochem. Pharmacol.<\/em>, 2008;76:1485\u201389.
    CrossRef <\/a><\/li>
  49. Hsu M. Y., Hsiao Y. P., Lin Y. T. Quercetin alleviates the accumulation of superoxide in sodium iodate-induced retinal autophagy by regulating mitochondrial reactive oxygen species homeostasis through enhanced deacetyl-SOD2 via the Nrf2-PGC-1\u03b1-Sirt1 pathway,. Antioxidants (Basel)., 2021; vol. 10, no. 7,p. 1125,
     CrossRef <\/a><\/li>
  50. Johnson D.A., Amirahmadi S., Ward C., Fabry Z., Johnson J.A.The absence of the pro-antioxidant transcription factor Nrf2 exacerbates experimental autoimmune encephalomyelitis. Toxicol. Sci.<\/em>, 2010;114:237\u201346.
     CrossRef <\/a><\/li>
  51. Klaassen C.D., Reisman S.A.Nrf2 the rescue: effects of the antioxidative \/ electrophilic response on the liver. Toxicol. Appl. Pharmacol<\/em>., 2010;244:57\u201365
    CrossRef <\/a><\/li>
  52. Zhang W. , Zhou J., Kang P., Shi Chao , and Qian S. Quercetin Inhibits Pyroptosis in Diabetic Cardiomyopathy through the Nrf2 Pathway. J. of Diabetes Research<\/em>., 2022 p.11
     CrossRef <\/a><\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

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