scholarly journals Biochemical and Oxidative Changes in High Fat Diet/Streptozotocin-induced Diabetic Rats Treated with Metformin and the Polyherbal Diawell

Author(s):  
O. N. Briggs ◽  
E. O. Nwachuku ◽  
D. Tamuno-Emine ◽  
N. Nsirim ◽  
K. N. Elechi-Amadi

Diabetes mellitus is an epidemic, with a huge disease burden on the patients. This has led to an increase in the use of herbal remedies and combination therapies to reduce this burden. Aim: This study evaluates the biochemical and oxidative changes in type 2 diabetic rats, treated with metformin and the polyherbal drug diawell. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis was also done on the herbal tablet. Results: Mean FPG levels were significantly lower (p˂0.05) in all groups, except the group administered diawell, which was not significantly different (p>0.05), compared to the diabetic control. Mean FPG levels were significantly higher (p˂0.05) in the metformin group, diawell group, but showed no significant difference (p>0.05) in the combination group, compared to the negative control. HOMA-IR was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The metformin and diawell groups had significantly higher (p˂0.05) HOMA-IR values, whereas the combination (metformin + diawell) showed no significant difference (p>0.05) when compared to the negative control. TOS was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The metformin and diawell groups had significantly higher (p˂0.05) TOS values, whereas the combination (metformin + diawell) showed no significant difference (p>0.05) when compared to the negative control. There was significantly lower (p˂0.05) TAS levels in the diabetic and treatment groups, compared to the negative control. OSI values were significantly lower (p˂0.05) in all groups when compared to the diabetic control. Also, OSI values were significantly higher (p˂0.05) in the treatment groups compared to the negative control. Conclusion: There was depletion of antioxidant parameters and an increase in oxidative stress in the diabetic rats. Administration of metformin and the polyherbal tablet diawell individually, were not effective in correcting the pathological and biochemical changes associated with diabetes. However, the combination treatment produced a better glycaemic response and attenuated the oxidant status in the rats. Antioxidant therapy should be incorporated in diabetes management, and anti-diabetic herbals properly evaluated.

Author(s):  
Ojoye N. Briggs ◽  
Kemzi N. Elechi-amadi ◽  
Justice C. Ohaka ◽  
Edna O. Nwachuku ◽  
Bartimaeus S. Ebirien-agana

Aim: This study evaluated the effects of metformin in combination with a herbal capsule (glucoblock) on insulin resistance and oxidative stress index in type 2 diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment for insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis on the herbal capsule was done using classical methods. Results: The results revealed the presence of alkaloids (100.31μg/mg), flavonoids (131.45μg/mg), cardiac glycosides (55.93μg/mg) and saponins (61.47μg/mg) in the herbal drug glucoblock. The results showed significantly lower FPG levels in the treatment groups when compared to the diabetic control. Group 3 administered metformin had significantly higher FPG levels compared to the negative control. Group 4 administered the herbal drug glucoblock and group 5 administered a combination of metformin and glucoblock, showed no significant differences in FPG levels when compared to the negative control. The diabetic control had significantly higher FPI levels compared to the negative control and treatment groups. The treatment groups showed no significant differences in FPI levels when compared to the negative control. HOMA-IR was significantly higher in the diabetic control compared to the negative control and treatment groups. Also, HOMA-IR values in the treatment groups showed no significant difference compared to the negative control except for group 3 (metformin), that was significantly higher than the negative control. SOD was significantly lower in the diabetic control, compared to the negative control and treatment groups. There were no significant differences in SOD levels in the treatment groups compared to the negative control. TOS levels in the negative control group and treatment groups were significantly lower, compared to the diabetic control. TAS was significantly lower in the diabetic control and treatment groups compared to the negative control. OSI in the diabetic control was significantly higher, compared to the negative control and treatment groups. Also, the treatment groups had significantly higher OSI compared to the negative control. Conclusion: High fat diet and streptozotocin induction produced significant insulin resistance and oxidative stress in the diabetic rats. Glucoblock was more effective in reducing insulin resistance compared to metformin. The combination showed synergistic drug-herb reaction as glucoblock potentiated the actions of metformin. Both showed antioxidant potential but were not effective in lowering oxidative stress to normal levels. There is need to incorporate antioxidant therapy in the treatment protocol for diabetes mellitus.


Author(s):  
O. N. Briggs ◽  
E. O. Nwachuku ◽  
E. S. Bartimaeus ◽  
D. Tamuno-Emine ◽  
K. N. Elechi-Amadi ◽  
...  

The increased prevalence of diabetes, and the huge disease burden on patients has led to an increase in the use of complementary and alternative medicine in diabetes treatment and management. Aim: This study evaluates the antidiabetic and antioxidant effects of the polyherbal capsule glucoblock and glibenclamide in type 2 diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body Wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Fasting plasma insulin (FPI), total oxidant status (TOS), total antioxidant status (TAS) and superoxide dismutase (SOD) levels were quantitatively determined by a rat-specific sandwich-enzyme linked immunosorbent assay (ELISA) method. Insulin resistance (IR) was determined using the homeostatic model assessment of insulin resistance (HOMA-IR) method. Oxidative stress index (OSI) was determined by the ratio of TOS to TAS. Phytochemical analysis was also done on the herbal capsule. Results: Mean FPG levels were significantly lower (p˂0.05) in all groups, compared to the diabetic control. Mean FPG level was significantly higher (p˂0.05) in the combination group, but showed no significant difference (p>0.05) in the glibenclamide group, and glucoblock group, compared to the negative control. HOMA-IR was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The combination group had significantly higher (p˂0.05) HOMA-IR values, whereas the individual treatment groups showed no significant difference (p>0.05) when compared to the negative control. TOS was significantly higher (p<0.05) in the diabetic control compared to the negative control and treatment groups. The treatment groups showed no significant difference (p>0.05) in TOS, compared to the negative control. There was significantly lower (p˂0.05) TAS levels in the diabetic and treatment groups, compared to the negative control. OSI values were significantly lower (p˂0.05) in all groups when compared to the diabetic control. Also, OSI values were significantly higher (p˂0.05) in the treatment groups compared to the negative control. SOD was significantly lower (p<0.05) in the diabetic control compared to the negative control and treatment groups. The treatment groups showed no significant difference (p>0.05) in SOD levels, compared to the negative control. Conclusion: Increase in total oxidant status and oxidative stress depleted antioxidant parameters. The polyherbal capsule glucoblock was effective when used alone and produced equipotent effect to the treatment with glibenclamide. However, the combination treatment did not fare better. Antioxidant therapy should be used together with antidiabetics in the management of diabetes, and care should be taken in the use herb-drug combinations.


Author(s):  
O. N. Briggs ◽  
K. N. Elechi-Amadi ◽  
F. C. Ezeiruaku ◽  
R. E. Teme

The scourge of diabetes has led to an increase in the use of complementary and alternative medicine. The lack of regulation and control leads to the indiscriminate use of these herbals, with potential risk to patients. Aim: This study evaluates the lipidaemic and hepatic status of type 2 diabetic rats treated with the polyherbal capsule glucoblock. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Total Cholesterol (TC), Triglyceride (TG) and High Density Lipoprotein Cholesterol (HDL-C) were determined using enzymatic methods. Low Density Lipoprotein Cholesterol (LDL-C) was calculated using the Friedewald’s equation. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) were determined using Reitman-Frankel method, while alkaline phosphatase (ALP) was determined using the colorimetric phenolphthalein method. Liver sections were stained using haematoxylin and eosin (H&E) staining technique, and phytochemical analysis was also done on the herbal capsule. Results: The results show no significant differences in TC levels in all groups compared to the negative control. TG level was significantly higher in the diabetic control group when compared to the negative control. TG level in the singular treatment groups were significantly lower, but the combination group (glibenclamide + glucoblock) showed no significant difference compared to the diabetic control. The negative control had significantly higher HDL-C compared to the diabetic control and treatment groups. There were no significant differences in HDL-C levels in all the treatment groups, when compared to the diabetic control. The negative control had significantly lower LDL-C compared to the diabetic control and treatment groups. There were no significant differences in LDL-C levels in all the treatment groups, when compared to the diabetic control. ALT, AST and ALP levels were significantly higher in the diabetic control, but was significantly reduced to normal levels by the treatments. Liver sections of the negative control showed normal histoarchitecture. The diabetic control showed inflammation and fatty deposition. The treatment groups showed a nearly normal histoarchitecture, with fatty deposits. Conclusion: High fat diet in combination with a sub-diabetic dose of streptozotocin produced significant diabetes in the Wistar rats with dyslipidaemia and elevated liver enzyme levels. The anti-diabetic treatments, glibenclamide and glucoblock did not correct the dyslipidaema caused by diabetes. However, the treatments had equipotent hepatoprotective effect and restored liver enzyme levels to normal as well as improving liver histology.


All Life ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 310-320
Author(s):  
Rahul Gopalakrishnan ◽  
Nandhakumar Elumalai ◽  
Renuka Alagirisamy

Author(s):  
O. N. Briggs ◽  
E. O. Nwachuku ◽  
H. Brown ◽  
K. N. Elechi-Amadi

Type 2 diabetes is one of the most important diseases worldwide. It affects several organ systems including the liver and lipid metabolism. Many herbal formulations have shown anti-diabetic potential, however, their safety and efficacy remain a debate in the medical community. Aim: This study evaluates the therapeutic effects of the anti-diabetic polyherbal drug diawell in combination with metformin on liver enzyme and lipid profile in type 2 diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-220 g were used for this study. The rats were placed on high fat diet, and diabetes was induced by a single intraperitoneal injection of freshly prepared streptozotocin (STZ) (45 mg/kg body wt). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Total Cholesterol (TC), Triglyceride (TG) and High density lipoprotein cholesterol (HDL-C) were determined using enzymatic methods. Low density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald equation. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using Reitman-Frankel method, while alkaline phosphatase (ALP) was determined using the colorimetric phenolphthalein method. Liver sections were stained using haematoxylin and eosin (H&E) staining technique, and phytochemical analysis was also done on the herbal tablet. Results: The results show no significant differences in mean TC levels in all groups. TG level was significantly higher in the diabetic control when compared to the negative control. There were no significant differences in TG levels in the metformin group, and diawell group when compared to the diabetic control. TG levels in the combination group (metformin + diawell) was significantly lower versus the diabetic control, and showed no significant difference compared to the negative control. HDL-C was significantly higher in the negative control when compared to the diabetic control and the treatment groups. There were no significant differences in HDL-C levels in all the treatment groups, when compared to the diabetic control. LDL-C levels were significantly lower in the negative control compared to the diabetic control and treatment groups. There were no significant differences in LDL-C levels in all the treatment groups, when compared to the diabetic control. The diabetic control had significantly higher ALT, AST and ALP levels compared to the negative control and treatment groups. All the treatment groups showed no significant differences in ALT and AST levels compared to the negative control. Liver sections of the negative control showed normal histoarchitecture. The diabetic control showed inflammation and fatty deposition. The treatment groups showed a nearly normal histoarchitecture, with fatty deposits. Conclusion: High fat diet in combination with 45 mg/kg of STZ produced significant diabetes in the Wistar rats with dyslipidaemia and elevated liver enzyme levels. Metformin and the polyherbal tablet diawell had no impact on the lipid levels as it did not correct the dyslipidaema, however, the treatments showed hepatoprotective potentials and restored liver enzyme levels to normal. Lipid lowering drugs should be included in the management of type 2 diabetes, and there should be proper evaluation of anti-diabetic herbal products.


Author(s):  
Ojoye N. Briggs ◽  
Kemzi N. Elechi-Amadi ◽  
Chrissie Okobia ◽  
Ferdinand C. Ezeiruaku

Aim: This study evaluates the anti-hyperglycaemic, anti-dyslipidaemic and hepatoprotective effects of the polyherbal mixture diarth, in alloxan-induced diabetic rats. Methodology: A total of 35 male Wistar albino rats weighing between 120-140 g were used for this study. Diabetes was induced by a single intraperitoneal injection of freshly prepared alloxan-monohydrate (140 mg/kg body weight). Fasting plasma glucose (FPG) was determined using the glucose oxidase method. Total Cholesterol (TC), Triglyceride (TG) and High density lipoprotein cholesterol (HDL-C) were determined using enzymatic methods. Low density lipoprotein cholesterol (LDL-C) was calculated using the Friedewald’s equation. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using Reitman-Frankel method, while alkaline phosphatase (ALP) was determined using the colorimetric phenolphthalein method. Phytochemical analysis was done on the herbal mixture, using classical methods. Results: The results revealed the presence of the phytochemicals saponins, alkaloids, cardiac glycosides, flavonoids and tannins in the polyherbal mixture diarth. The results revealed significantly lower FPG levels in the negative control and treatment groups compared to the diabetic control. FPG level was significantly higher in the glibenclamide treated group, but showed no significant differences in the diarth group and the combination group (glibenclamide + diarth), compared to negative control. TC levels in the diabetic control was significantly higher compared to the negative control and treatment groups. There were no significant differences in TC levels in the negative control and the treatment groups. The diabetic control had significantly higher TG level compared to the negative control. TG level in the glibenclamide treated group was not significantly different from that of the diabetic control. TG level in the diarth treated group was significantly lower than the diabetic control, but also significantly higher than that of the negative control. TG levels in the combination group (diarth + glibenclamide) was significantly lower than the diabetic control, and showed no significant difference compared to the negative control. The negative control and treatment groups had significantly higher HDL-C levels compared to the diabetic control. The treatment groups showed no significant difference in HDL-C levels, compared to the negative control. The negative control and treatment groups had significantly lower LDL-C levels compared to the diabetic control. The treatment groups showed no significant difference in LDL-C levels, compared to the negative control. The results show significantly elevated ALT, AST and ALP in the diabetic rats compared to the negative control and treatment groups. The treatment groups showed no significant differences in ALT and AST levels compared to the negative control. Conclusion: 140 mg/kg body weight of alloxan produced significant diabetes in the Wistar rats with dyslipidaemia and elevated liver enzyme levels. Treatment with the polyherbal mixture diarth showed anti-hyperglycaemic, anti-dyslipidaemic and hepatoprotective effects. The effects were equipotent compared to treatment with glibenclamide, thus could be incorporated in the management of diabetes.


2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.


2013 ◽  
Vol 41 (03) ◽  
pp. 487-502 ◽  
Author(s):  
Wei-Xi Cui ◽  
Jie Yang ◽  
Xiao-Qing Chen ◽  
Qian Mao ◽  
Xiang-Lan Wei ◽  
...  

Non-alcoholic fatty liver disease (NAFLD) has become a major challenge to the healthcare system. This study was designed to evaluate the effect of the triterpenoid-rich fraction (TF) from Ilex hainanensis Merr. on NAFLD. Male Sprague-Dawley (SD) rats were fed a normal diet (control) or high fat diet (NAFLD model). After four weeks, the high fat diet group was orally administrated TF (250 mg/kg) for another two weeks. High fat diet fed rats displayed hyperlipidemia and a decline in liver function compared with control. However, administration with TF could effectively improve these symptoms, as demonstrated by decreasing the plasma levels of triglyceride (p <0.05), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), alanine transaminase (p < 0.05), aspartate aminotransferase (p < 0.01), liver index (p < 0.05) and insulin resistance index (p < 0.05) while increasing the high-density lipoprotein cholesterol (p < 0.05). Meanwhile, histopathological examination of livers also showed that TF could reduce the incidence of liver lesions induced by high fat diet. Furthermore, TF could alleviate oxidative stress and inflammation status indicated by the decline malondialdehyde and superoxide dismutase levels (p < 0.01, both) and levels of interleukin 6 and tumor necrosis factor-α (p < 0.05). In addition, immunohistochemistry showed TF evidently elevated the peroxisome proliferator-activated receptor (PPARα) expression (p < 0.01), while it diminished the Cytochrome P450 2E1 (CYP2E1) expression (p < 0.01) in liver. These results demonstrate that TF has potential ability to protect liver against NAFLD by regulating lipids metabolism and alleviating insulin resistance, inflammation and oxidative stress. This effect might be associated with regulating PPARα and CYP2E1 expression.


Author(s):  
Rizka Veni ◽  
Awal Prasetyo ◽  
Muflihatul Muniroh

This study aims to analyze the effect of combination of motor vehicle particular matter exposure and high-fat diet in kidney histopathology, creatinine levels, and MDA levels in Wistar rats. This study used a posttest-only control group design. Eighteen healthy male Wistar rats were divided into three groups. The intervention groups received motor vehicle fume exposure for 100 s with normal diet (X1) or high-fat diet (X2), and the control group received no exposure (C). Data analysis was processed with a SPSS 25.0 computer program by using the one-way ANOVA test followed by post hoc LSD. The degree of kidney histopathological damage showed significant differences between the X1 and X2 groups when compared with the control group (p < 0.05). The results of the creatinine level examination found a significant difference between the X2 and C groups (p < 0.05) and the treatment groups X1 and X2 (p < 0.05). The results of kidney MDA level examination showed a significant difference between the treatment groups (X1 and X2) and the control group (p < 0.05). The combination of particular matter of motor vehicle fumes exposure and high-fat diet could induce kidney damage through histopathological change and increased creatinine levels and kidney MDA levels in Wistar rats.


2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Wannachai Sakuludomkan ◽  
Ranchana Yeewa ◽  
Subhawat Subhawa ◽  
Chakkrit Khanaree ◽  
Arisa Imsumran Bonness ◽  
...  

Houttuynia cordata Thunb. (plukaow in Thai language) exhibits several biological properties, and many products of H. cordata are therefore commercially available for human consumption, such as fermented juice or tablets as food supplements. This study aimed to investigate the antidiabetic effects of fermented H. cordata (HC) in high-fat diets and streptozotocin-induced diabetic rats. Oral administration of HC at a dose of 100 mg/kg.bw not only maintained bodyweight, food intake, and water consumption but also reduced blood glucose levels and improved glucose tolerance ability in the diabetic rats. Moreover, HC also decreased oxidative stress markers in serum and inflammatory-related mediators in pancreas tissues, indicating the improvement of pancreatic beta-cell function in the diabetic rats. In order to clarify the mechanism of HC, the effects of ethanolic extract of HC (HCE) on insulin resistance were determined in 3T3-L1 adipocytes. FHE could recover glucose uptake and decrease lipolysis in palmitate-treated 3T3-L1 adipocytes. Taken together, these results demonstrate that HC can improve diabetic symptoms by enhancing insulin sensitivity, reducing oxidative stress, and suppressing inflammation.


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