Evaluation of the glycemic effect ofCeratonia siliquapods (Carob) on a streptozotocin-nicotinamide induced diabetic rat model

Abstract

BackgroundCeratonia siliqua pods (carob) have been nominated to control the high blood glucose of diabetics. In Yemen, however, its antihyperglycemic activity has not been yet assessed. Thus, this study evaluated the in vitro inhibitory effect of the methanolic extract of carob pods against α-amylase and α-glucosidase and the in vivo glycemic effect of such extract in streptozotocin-nicotinamide induced diabetic rats.Methods2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric reducing antioxidant power assay (FRAP) were applied to evaluate the antioxidant activity of carob. In vitro cytotoxicity of carob was conducted on human hepatocytes (WRL68) and rat pancreatic β-cells (RIN-5F). Acute oral toxicity of carob was conducted on a total of 18 male and 18 female Sprague-Dawley (SD) rats, which were subdivided into three groups (n = 6), namely: high and low dose carob-treated (CS5000 and CS2000, respectively) as well as the normal control (NC) receiving a single oral dose of 5,000 mg kg−1 carob, 2,000 mg kg−1 carob and 5 mL kg−1 distilled water for 14 days, respectively. Alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, total bilirubin, creatinine and urea were assessed. Livers and kidneys were harvested for histopathology. In vitro inhibitory effect against α-amylase and α-glucosidase was evaluated. In vivo glycemic activity was conducted on 24 male SD rats which were previously intraperitoneally injected with 55 mg kg−1 streptozotocin (STZ) followed by 210 mg kg−1nicotinamide to induce type 2 diabetes mellitus. An extra non-injected group (n = 6) was added as a normal control (NC). The injected-rats were divided into four groups (n = 6), namely: diabetic control (D0), 5 mg kg−1glibenclamide-treated diabetic (GD), 500 mg kg−1 carob-treated diabetic (CS500) and 1,000 mg kg−1 carob-treated diabetic (CS1000). All groups received a single oral daily dose of their treatment for 4 weeks. Body weight, fasting blood glucose (FBG), oral glucose tolerance test, biochemistry, insulin and hemostatic model assessment were assessed. Pancreases was harvested for histopathology.ResultsCarob demonstrated a FRAP value of 3191.67 ± 54.34 µmoL Fe++ and IC50 of DPPH of 11.23 ± 0.47 µg mL−1. In vitro, carob was non-toxic on hepatocytes and pancreatic β-cells. In acute oral toxicity, liver and kidney functions and their histological sections showed no abnormalities. Carob exerted an in vitro inhibitory effect against α-amylase and α-glucosidase with IC50 of 92.99 ± 0.22 and 97.13 ± 4.11 µg mL−1, respectively. In diabetic induced rats, FBG of CS1000 was significantly less than diabetic control. Histological pancreatic sections of CS1000 showed less destruction of β-cells than CS500 and diabetic control.ConclusionCarob pod did not cause acute systemic toxicity and showed in vitro antioxidant effects. On the other hand, inhibiting α-amylase and α-glucosidase was evident. Interestingly, a high dose of carob exhibits an in vivo antihyperglycemic activity and warrants further in-depth study to identify the potential carob ...

Supplementation with a Carob (Ceratonia siliqua L.) Fruit Extract Attenuates the Cardiometabolic Alterations Associated with Metabolic Syndrome in Mice

“…An important finding is that supplementation with CSAT+ ® decreases the glycemic status and the HOMA-IR, suggesting improved insulin sensitivity. These results are in agreement with previous studies that report increased insulin sensitivity in response to carob treatment both in experimental animals [20] and in humans [18,19,46]. However, other authors have reported that carob consumption in combination with a glucose load increases plasma glucose and serum insulin responses in humans [47].…”

“…However, other authors have reported that carob consumption in combination with a glucose load increases plasma glucose and serum insulin responses in humans [47]. In diabetic rats, the insulin sensitizing effect is mediated by a decrease in the activity of the α-amylase and α-glucosidase and through a lower destruction of pancreatic β-cells that leads to improved insulin synthesis and secretion [20]. In our model, the beneficial effect on the glycemic status seems to be mediated by a reduction in MetS-induced insulin resistance in skeletal muscle and visceral adipose tissue, since we found a significant activation of the PI3K/Akt pathway in response to insulin in both visceral adipose tissue and gastrocnemius muscle explants from chow and CSAT+ ® -treated mice but not in explants from mice fed with the HFHS diet alone.…”

“…Among them the fruit of carob tree, (Ceratonia siliqua L.), may be a good candidate since several studies have reported that it exerts beneficial effects improving the glycemic status [18][19][20][21], the lipid profile [22][23][24][25][26], and attenuating the cardiovascular alterations associated with MetS [23,27,28]. Its therapeutic effects are attributed to several bioactive compounds that are present not only in the pulp but also in the pod and the seeds of the carob fruit.…”

Carob pod polyphenols suppress the differentiation of adipocytes through posttranscriptional regulation of C/EBPβ

“…reported that carob pod polyphenols (CPPs) had stronger antioxidant effects against the discoloration of β-carotene than catechins and procyanidins [ 3 ]. Furthermore, several in vivo models have demonstrated that carob pods have hepatoprotective effects against carbon tetrachloride-induced toxicity [ 4 ] or ethanol-induced liver injury [ 5 ], gastroprotective effects against ethanol-induced oxidative stress [ 6 ], and antidiabetic effects against alloxan-induced diabetes [ 7 ] or streptozotocin-nicotinamide-induced diabetes [ 8 ]. However, the anti-obesity effect and its mechanism of action have not been clarified.…”

Cathinone: An alkaloid of Catha edulis (Khat) exacerbated hyperglycemia in diabetes-induced rats

“…According to Qasem et al (2018) , 20 µl of 250, 125, 62.5, 31.25 or 15.625 µg/ml of cathinone and α-acarbose were pipetted separately in triplicates into their specified wells of 96-wells plate, which was followed by pipetting 50 µl of the porcine pancreatic α-amylase into each well. After that, the plate was incubated at 28 °C for 10 min.…”