scholarly journals Methanol extract of Aruncus dioicus exerts antidiabetic effect via PCSK9/LDLR pathway

2021 ◽  
Vol 18 (3) ◽  
pp. 571-577
Author(s):  
Li Gong ◽  
Qing Yang ◽  
Yinluan Huang ◽  
Shaoyan Xie ◽  
Chao Zeng ◽  
...  

Purpose: To investigate the antidiabetic effect of methanol extract of Aruncus dioicus, and the underlying mechanism(s). Methods: Twenty-four adult female albino mice were randomly assigned to four groups of six mice each: normal control group, diabetic control group and two treatment groups. With the exception of normal control group, the diabetic control and treatment groups consisted of leptin receptor-deficient (db/db) type 2 diabetic mice. The diabetic control group was not treated, while the treatment groups received 200 or 400 mg/kg extract/day orally for 4 weeks. The effect of the extract on fasting blood glucose (FBG), proprotein convertase subtilisin/kexin type 9 (PCSK9), glycogen and lipid profiles were determined. The expressions of PCSK9, low-density lipoprotein receptor (LDL-R) and glucokinase (GCK) were determined in liver tissues using western blotting and real-time quantitative polymerase chain reaction (qRT-PCR). Results: Fasting blood glucose (FBG) was significantly and dose-dependently reduced in the treatment groups, relative to diabetic control group at different time-points (p < 0.05). Total cholesterol (TC), triacylglycerol (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were significantly higher in the diabetic control group than in normal control group (p < 0.05). However, treatment with methanol extract of A. dioicus significantly and dose-dependently reversed the changes in the levels of these parameters (p < 0.05). The expressions of LDLR and GCK were significantly down-regulated in diabetic control group, when compared with normal control group, but their expressions were significantly dose-dependently upregulated in the treatment groups (p < 0.05). Treatment with the extract significantly and dose-dependently down-regulated PCSK9 expression (p < 0.05). Liver injury characterized by large distended lipid droplets and fat accumulation was seen in diabetic mice, but treatment with methanol extract of A. dioicus significantly reversed the histopathological changes induced by DM. Conclusion: These results indicate that the antidiabetic effect of methanol extract of A. dioicus is exerted via a mechanism involving PCSK9/LDLR pathway.

Author(s):  
E. Eteng Ofem ◽  
Kenyoh Abam ◽  
Grace Ekpo ◽  
Savour Ufot ◽  
Joe Enobong ◽  
...  

The study was carried out to investigate the anti-diabetic effects of two medicinal plants Cataranthus roseus (C.R) and Nauclea latifolium (N.L) on some biochemical indices of streptozotocin induced diabetic albino wistar rats. Methods: Ethanolic leaf extracts of C.R. and N.L. were given at daily doses of 500 mg/kg body weight in two divided doses each for 14 days. Thirty albino wistar rats were divided into five (5) groups, consisting of 6 rats each viz: Group 1(normal control), Group 2 (diabetic control), Group 3 (insulin treated), Group 4 (received N.L) and Group 5 (received C.R.). Results: The results of the phytochemical screening contain flavonoids, polyphenols, and alkaloids were found to be present in appreciable amount in N.L while saponins and tannins were found in traceable concentration. Fasting blood glucose levels showed significant decrease (P<0.05) in all the test groups compared to diabetic control and closely related to the insulin treated groups. A significant increase (P<0.05) was observed in (TG) and (TC) concentration of all treated groups compared to the diabetic control group. The concentration of HDL was significantly increased while there was also a significant decreased (P<0.05) in VLDL and LDL in the diabetic control group and insulin group when compared to the normal control group, except for C.R treated group that shows a significant decrease compared with the diabetic control group. Enzymes activities were increased in insulin and diabetic groups. A significant reduction (P<0.05) was observed with the treated group of C.R. and N.L compared to the normal control group. Also, observed was a decrease in albumin level in groups treated with the extracts. Marked reduction in total protein level was observed in groups treated with extracts and insulin, compared to the normal control group. Serum concentrations of Na+, K+, Cl- in diabetic control groups showed a significant increase (P<0.05) compared to the normal control group. K+ concentration was observed to be significantly decreased (P<0.05) in all groups treated with extract and insulin compared to the normal control group. Conclusions: The results demonstrated that C. roseus and N. latifolium have anti-diabetic and antihepatotoxic properties and could be potential herbal remedy in treating and managing diabetic conditions.


Author(s):  
L. C. Chuku ◽  
N. C. Chinaka

The influenceof antioxidant supplementation on high fat diet-streptozotocin (HFD-STZ) induced type 2 diabetes mellitus in Wistar albino rats was investigated. Appropriate (RDA) proportions of some antioxidant rich substances which includes; vitamins (A, B3, B6, B12, C and E), minerals (calcium, selenium, chromium, magnesium, potassium and zinc), α-lipoic acid, cinnamon powder, curcumin (Meriva®), cordyceps, resveratrol, quercetin, D-ribose-L-cysteine were pulled together in corn oil and stored at 4°C for use. Serum glutathione (GSH) and malondialdehyde (MDA) levels, as well as activities of antioxidant enzymes: superoxide dismutases (SOD), catalase (CAT), glutathione-s-transferase (GST), glutathione peroxidise (GPx) and glutathione reductase (GR) were measured using standard methods. Data analysis was done with SPSS version 20.0 and significant level was set at P≤0.05. Results of in vitro oxidative stress indices and antioxidant enzyme activity indicate that after 4 weeks of treatment, there was no significant change (p≥0.05) in serum FBS levels of treated groups compared to the normal control group, but there was a significant decrease (p≤0.05) after 8 and 12 weeks of treatment when compared to the diabetic control group. There was no significant difference (p≥0.05) in the activities of antioxidant enzymes when compared to the normal control group, while in the diabetic control there was significant increase (p≤0.05) compared to the other groups. The results after 4, 8 and 12 weeks of treatment showed a significant increase (p≤0.05) in serum GSH level of normal and treated groups compared to diabetic control group, whereas there was a significant decline (p≤0.05) in serum MDA level of treated and normal control groups when compared to diabetic control. The results therefore suggest that the supplement may possess significant (p≤0.05) free radical scavenging potentials which could be beneficial to health.


Author(s):  
Khidir A. M. Hassan ◽  
Mahmoud M. E. Mudawi ◽  
Mansour I. Sulaiman

Metformin is now being recognized as the standard therapy in T2D patients who are overweight. Metformin has many drug-disease interactions that can increase the risk of metformin-associated lactic acidosis. Therefore this study was conducted to evaluate any possible pharmacodynamic interactions between metformin and drugs used to treat chronic diseases e.g. Hypertension. The rats were fasted overnight before inducing diabetes with streptozotocin. The rats were given an intraperitoneal injection of streptozotocin (50 mg kg−1) freshly prepared in 0.1M sodium citrate buffer. The diabetic state was confirmed 72 h after streptozotocin injection. Diabetic rats were grouped into seven groups each group of five rats and distributed among the normal control group diabetic control group and the treatment groups. The treatment continued for 10 days. Blood samples were taken before treatment and after 10 days and analyzed for serum glucose, cholesterol, HDL, LDL, and triglycerides. In the diabetic control group which was given STZ alone the blood glucose level decreased significantly (p &lt; 0.05) after 10 days but still above the hyperglycemic level (200mg/dl). The same was observed in the group treated with metformin. The group treated with nifedipine and aspirin showed significant reduction (p &lt; 0.01) in the glucose level below the hyperglycemic level (200mg/dl). While the groups treated with (Metformin + Nifedipine) and (Metformin +Aspirin) showed highly significant reduction (P&lt;0.001) in blood glucose level. These results conclude that the combination of (metformin +Nifedipine) and the combination of (Metformin + Aspirin) have highly significant hypoglycemic effect. It also showed that Nifedipine has promising role in reducing blood glucose level, lipid profile especially LDL-cholesterol, and body weight.


2021 ◽  
Vol 18 (5) ◽  
pp. 1083-1088
Author(s):  
Siddig I. Abdelwahab ◽  
Syam Mohan ◽  
Manal M.E. Taha ◽  
Waquar Ahsan ◽  
Mohammed Al Bratty ◽  
...  

Purpose: To investigate the antidepressant effect of methanol extract of smokeless tobacco and identify its bioactive compounds. Methods: Adult Wistar rats were randomly assigned to five groups of five rats each: normal control group, standard (reference) control group as well as 100, 200 and 500 mg/kg extract group. The extract, standard drug (imipramine) and normal saline were administered via the intraperitoneal (i.p.) route. The rats were subjected to forced swim test (FST) and tail suspension test (TST) to assess the antidepressant effect of methanol extract of smokeless tobacco. Gas chromatography–mass spectrometry (GC-MS) was used to identify the bioactive compounds of the extract. Results: The oral LD50 of the extract was > 2000 mg/kg. Significant decrease in immobility time was observed after single administration of imipramine (p < 0.05). The extract significantly and dosedependently decreased the immobility time, but increased climbing and swimming times, when compared with normal control group (p < 0.05). The immobility time of stressed rats regardless of sex was significantly and dose-dependently lowered, relative to normal control group (p < 0.05). Four major compounds were identified in the extract: nicotine (45.88 %); 1,5-dimethyl-2-pyrrolidinone (23.00 %), nhexadecanoic acid (11.31 %) and vitamin A aldehyde (9.38 %). Conclusion: These results demonstrate that the methanol extract of smokeless tobacco possesses antidepressant and mood-elevating effects in rats. However, its use should be discouraged since it contains a number of hazardous and carcinogenic components such as N-nitroso compounds and benzo(a)pyrene which are categorized as Class-I carcinogens.


2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Amir Abbas Momtazi-Borojeni ◽  
Mahmoud Reza Jaafari ◽  
Elham Abdollahi ◽  
Maciej Banach ◽  
Amirhossein Sahebkar

Background and Aim. The impact of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition on glycemic indices in diabetes mellitus remains far from clear. We explored the effects of PCSK9 inhibition on glycemic indices in the diabetes rat model. Methods. To prepare the anti-PCSK9 vaccine, a peptide construct called Immunogenic Fused PCSK9-Tetanus (IFPT) was linked to the surface of nanoliposome carriers. Healthy rats received four subcutaneous injections of the vaccine at biweekly intervals. Two weeks after the last vaccination, anti-PCSK9 antibody titers, PCSK9 targeting, and inhibition of PCSK9–low-density lipoprotein receptor (LDLR) interaction were evaluated. After verification of antibody generation, the immunized rats were intraperitoneally treated with a single dose (45 mg/kg) of streptozotocin (STZ) to induce diabetes mellitus. The levels of fasting blood glucose (FBG) were measured, and the oral glucose tolerance test (OGTT) as well as the insulin tolerance test (ITT) were carried out to assess glycemic status. At the end of the study, the total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglyceride, and high-density lipoprotein cholesterol concentrations were assayed. Histopathology examination of the liver and pancreas was also performed using the hematoxylin-eosin staining method. Results. The prepared nanoliposomal vaccine could strongly induce anti-PCSK9 antibodies in the vaccinated rats. Within one week following the STZ injection, the FBG level was lower in the vaccinated group vs. diabetic control group (49% ( − 171.7 ± 35   mg / dL , p < 0.001 )). In the OGTT, the injected rats showed improved glucose tolerance as reflected by the reduction of blood glucose levels over 180 min, compared with the diabetic controls. Moreover, the ITT demonstrated that, after the insulin injection, blood glucose concentration declined by 49.3% in the vaccinated group vs. diabetic control group. Expectedly, the vaccinated rats exhibited lower (-26.65%, p = 0.03 ) plasma LDL-C levels compared with the diabetic controls. Histopathology examination of pancreas tissue demonstrated that the pancreatic islets of the vaccinated rats had a slight decline in the population of β-cells and few α-cells. Normal liver histology was also observed in the vaccinated rats. Conclusion. PCSK9 inhibition through the liposomal IFPT vaccine can improve the glucose and insulin tolerance impairments as well as the lipid profile in diabetes.


2012 ◽  
Vol 5 (1) ◽  
pp. 161-170 ◽  
Author(s):  
R. Sharmin ◽  
M. R. I. Khan ◽  
Most. A. Akhtar ◽  
A. Alim ◽  
M. A. Islam ◽  
...  

Ethanolic extracts of some fruits of Cucurbitaceae family such as Cucumis sativus (cucumber), Lagenaria siceraria (white pumpkin), Luffa acutangula (ridge gourd), Benincasa hispida (ash gourd), Citrullus lanatus (sweet melon) and Cucarbita maxima (pumpkin) have been studied for their hypoglycemic effects on alloxan induced diabetic rats (AIDRs). Screening results suggested that among the tested fruits the hypoglycemic potency follows: cucumber > white pumpkin > ridge gourd. These three fruit-extracts were further investigated for their hypoglycemic, hypolipidemic and glycogenesis effects. Cucumber, white pumpkin and ridge gourd extracts reduced blood glucose level by 67, 65 and 51%, respectively at 12 hours after single intraperitoneal injection; while reduced the low density lipoprotein (LDL) level to 13, 28 and 86%, respectively in AIDRs. The maximum reduction 87% was observed by cucumber extract. Cucumber, white pumpkin and ridge gourd extracts reduced total cholesterol level to 29, 15 and 38%, respectively comparing with the diabetic control group. Here the maximum reduction of 85% was observed by white pumpkin extract. Cucumber, white pumpkin and ridge gourd also reduced triglyceride levels to 72, 68 and 80%, respectively. Maximum reduction of 32% was observed by white pumpkin. Significant improvement of glycogenesis was also observed by ridge gourd extracts in AIDRs.© 2013 JSR Publications. ISSN: 2070-0237 (Print); 2070-0245 (Online). All rights reserved.doi: http://dx.doi.org/10.3329/jsr.v5i1.10252        J. Sci. Res. 5 (1), 161-170 (2013)


2020 ◽  
Vol 19 (1) ◽  
pp. 71-76
Author(s):  
Li Dong ◽  
Lixia Yang ◽  
Fengsui Liu ◽  
Haitao Zhan ◽  
Xinwei Chen

Purpose: To investigate the effect of farrerol on diabetic hepatopathy in a rat model of type 2 diabetes mellitus (T2DM).Methods: Adult male Wistar rats (n = 40) were randomly assigned to four groups of ten rats each: normal control, diabetic control, farrerol control and treatment groups. With the exception of normal control and farrerol control groups, the rats were fed high-fat diet (HFD) for four weeks, and thereafter injected streptozotocin (STZ) at a dose of 30 mg/kg body weight intraperitoneally (i.p.) for induction of T2DM. Rats in farrerol control and treatment groups received 50 mg/kg farrerol orally/day. Serum levels of triacylglycerol (TG), total cholesterol (TC), high-density lipoprotein  cholesterol (HDL-C) and lowdensity lipoprotein cholesterol (LDL-C) were determined. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were assessed in liver homogenate while mRNA and protein expressions of glucose transporter 2 (GLUT2) were assayed in liver using real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting, respectively. Expression levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also determined using qRT-PCR.Results: Diabetes mellitus (DM) led to significant reductions in rat body weight and SOD activity, while increasing fasting blood glucose (FBG) and MDA levels (p < 0.05). However, treatment with farrerol significantly reversed the effect of DM on these parameters (p < 0.05). The mRNA expressions of TNF-α and IL-1β were significantly higher in diabetic control group than in normal control group, but were significantly reduced after farrerol treatment (p < 0.05). Treatment with farrerol also significantly reversed the effect of DM on rat lipid profile (p < 0.05). The expression of GLUT2 protein was significantly downregulated in the liver of diabetic control rats, when compared with normal control rats, but was significantly upregulated after treatment with farrerol (p < 0.05).Conclusion: The results of this study show that farrerol alleviates STZ-induced hyperglycemia and dyslipidemia via reduction in oxidative stress and inflammation, and upregulation of GLUT2 protein expression. Thus, farrerol has antidiabetic and hepatoprotective potentials for clinical use in  humans. Keywords: Diabetes mellitus, Dyslipidemia, Farrerol, Hepatopathy, High-fat diet


Author(s):  
Hamİt Uslu ◽  
GÖzde Atİla Uslu

Objective: In this study, we aimed to determine the effects of chromium picolinate (CrPic) on diabetes, one of the most common and fatal diseases in the world, and its associated oxidative damages.Methods: CrPic (100 μg/kg) and metformin (1000 mg/kg) were orally administered for 21 days in rats with nicotinamide + streptozotocin-induced Type 2 diabetes.Results: Significant decreases in fasting blood glucose levels were observed 14 days after initial administration in both CrPic (p<0.01) and metformin (p<0.001) groups compared with a diabetic control group (DC). Malondialdehyde (MDA) levels of all tissues were significantly higher in the DC group than in a normoglycemic control group (p<0.001). MDA levels of the CrPic group significantly decreased in heart (p<0.05) and liver (p<0.01) tissues. Glutathione (GSH) and catalase (CAT) levels in heart, kidney, and liver tissues increased in CrPic group (GSH p<0.001, p<0.05, and p<0.01; CAT p<0.001, p<0.001, and p<0.05, respectively). Superoxide dismutase enzyme levels significantly increased in CrPic group in the liver tissue (p>0.001), but no such changes were observed in heart and kidney tissues (p>0.05).Conclusion: The results obtained from this study indicate that CrPic may be effective in alleviating hyperglycemia and its consequent oxidative damage in experimental Type 2 diabetes.


Author(s):  
Kayode A. Arowora ◽  
Chinedu Imo ◽  
Chukwuma S. Ezeonu ◽  
Zuhairah I. Muhammad

<p class="abstract"><strong>Background:</strong> This study was carried out to investigate the effects of <em>Datura metel (</em>leaf, seed and fruit<em>)</em> on blood lipid profile of male albino rats.</p><p class="abstract"><strong>Methods:</strong> Thirty-five albino rats (8 weeks old) weighing between 66g and 84g were purchased and randomly allotted into 7 groups. The normal control (group 1) received normal saline, while groups 2 to 7 received extracts of <em>Datura metel</em> at low (300 mg/kg body weight) and high doses (600 mg/kg body weight). The extracts were administered orally for seven consecutive days, while the animals were sacrificed on the 8th day; blood samples were collected, allowed to stand for fifteen minutes and then centrifuged.  </p><p class="abstract"><strong>Results:</strong> There was a general decreasing trend in the mean values of low density lipoprotein levels across  the groups, however, group 7 (with lowest value) was found to be significantly lower (p &lt;0.05) than other groups when compared with the normal control. Also, there was a general decreasing trend in the values of high density lipoprotein compared with normal control group, however lowest value was recorded to be 1.35±0.06 mmol/l for group 5. There were no significant differences (p &gt;0.05) in triglyceride levels across the groups, while total cholesterol in groups 5 and 6 had significant differences with values of 2.05±0.06 mmol/l and 2.13±0.10 mmol/l respectively when compared with the normal control.</p><p><strong>Conclusions:</strong> This study suggests that ethanolic extracts of<em> Datura metel </em>have active ingredients that are capable of improving blood lipid profile and this might be useful in the management of cardiovascular diseases. </p>


2020 ◽  
Vol 5 (3) ◽  
pp. 7-15
Author(s):  
Agbor Cyril Abang ◽  
Anyanwu G. E

Local Nigerian men have been using AuriculariaPolytricha as a treatment for sexual dysfunction without supporting evidence from scientific experiments. This study was to investigate the effect of ethanolic extract of A. Polytricha on testicular DNA expression and some oxidative stress markers using STZ-Induced diabetic rats as a model. The experiment included six groups, Group A (Normal Control, treated with normal saline), Group B (treated with 65mg/kg.bw of STZ), Groups C, D, and E (treated with 250mg/kg.bw, 500mg/kg.bw, 1000mg/kg.bw AP after inducing diabetics), and Group F (treated with 40mg/kg.bw metformin after inducing diabetics). The experiment lasted for 35 days. After termination of the experiment, Fuelgen nuclear reaction was used for DNA demonstration to assess testicular DNA distribution while serum Superoxide Dimutase (SOD), Catalase and Melondialdehyde where evaluated using reagent based antioxidant enzyme assay. Results reveals that SOD and Melondialdehyde activities were remarkably (p<0.05) higher in diabetic control animals when compared with the normal control group. Values in Groups C, D and F that were administered with 250, 500mg/kg.bw A. polytricha and metformin respectively were also significantly (p<0.05) increased when compared with the normal control group. However, diabetic animals placed on 1000mg/kg.bw A. polytrichadid not show any statistical significance in comparison with normal control group but was remarkably (p<0.01) decreased when compared to the diabetic group that received low dose A. polytricha, an indication that the reversal is dose dependent. Catalase concentration in diabetic control animals was remarkably (p<0.05) higher when compared to the normal control but was not significantly (p<0.05) different in groups D (DM+500mg/kg.bw A. polytricha) and E (DM+1000mg/kg.bw A. polytricha) when compared with the normal control group. Diabetic control animals showed reduced magenta colour intensity of DNA and increased clustering and cross linking of DNA strands when compared with the normal control. However the degree of cross link in DNA strands was reduced in the diabetic animals placed on 1000mg/kg.bw A. polytrichawhen compared with the diabetic control group. Reversal in DNA damage and values of serum oxidative stress markers following administration of graded doses of A. polytricha could be attributed to essential phytochemical and therapeutic constituents in A. polytricha like polyphenol and flavonoid which can be found useful in prevention and treatment of diabetes induced testicular dysfunction. In summary, AP can contribute to a reversal in DNA damage and levels of serum oxidative stress markers in treating diabetes-induced testicular dysfunction.


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