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Serum levels of (a) aspartate transaminase (AST U/l), (b) alanine transaminase (ALT, U/l), and (c) alkaline phosphatase (ALP U/l) of control group fed on standard diet and treated with 1 ml/day distilled water (C‐SD), high‐fat high‐sucrose‐fed group treated with distilled water (C‐HFHS), high‐fat high‐sucrose‐fed group treated with 100 mg kg⁻¹ day⁻¹ metformin (Met‐HFHS), high‐fat high‐sucrose‐fed group treated with 200 mg kg⁻¹ day⁻¹ hydroalcoholic extract of Stevia (S200‐HFHS), and high‐fat high‐sucrose‐fed group treated with 400 mg kg⁻¹ day⁻¹ extract of Stevia (S400‐HFHS) and 10 rats in each group. * and Δ symbols indicate significant difference (p < .05) from C‐SD and C‐HFHS groups, respectively, analyzed with one‐way ANOVA test
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The beneficial effects of Stevia on metabolic indices have been studied in recent years. However, controversial results emphasize the need for further investigation. We aimed to examine and compare the effects of Stevia’s hydroalcoholic extract with two dosages (200, 400 mg/kg) with those of metformin (100 mg/kg) on metabolic syndrome (MetS) indice...
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Frozen yogurt is known as ice cream with some properties of yogurt. Frozen yogurts are a rich source of sucrose levels between 15% and 28% of total ingredients. Consumers suffering from lactose intolerance and metabolic syndrome are looking for sugar-free products. The current study investigates the sugar replacements by using sweeteners (stevia, s...
Citations
... Our results are controversial to similar study done by Ranjbar et al 27 . They studied the effects of stevial extract in high fat diet induced metabolic syndrome rats. ...
... Ranjbar et al also concluded that their regime dosage differences did not affect the amelioration of high fat liver changes. 27 The effect of different doses of stevia extract on LFTs was also compared by Elanga et al 29 by giving 25, 250, 500 and 100 mg/Kg/day dosage to female rats in groups. Their treatment with stevia extract showed comparable declension effects of liver enzymes by 500 and 1,000 mg dosage, while we used just 250 mg/Kg regime and got similar hepatoprotective effects. ...
Background: Obesity is a prevalent issue affecting a growing number of individuals globally. It is a systemic disorder with complications and co-morbidities. Non-alcoholic fatty liver disease (NAFLD) is a disastrous outcome of metabolic syndrome induced by obesity. Objective of this study was to find the effect of Stevia leaves in restoration of liver function tests (ALT, AST, ALP, and Bilirubin) in obese Sprague Dawley rats. Methods: This animal experimental study was carried out in the Physiology Department, in collaboration with the Pathology Department of Islamabad Medical and Dental College, and National Institute of Health, Islamabad on 90 healthy male Sprague Dawley rats over a period of 14 weeks. The animals were divided randomly into three groups of 30 rats each. Group 1 was given normal diet while Groups 2 and Group 3 were given high fat diet. Stevia leaves were further added for six weeks in the diet of Group 3. Results: High fat diet induced NAFLD in rats was ameliorated significantly on treatment with stevia. On comparison of liver function tests in obese control with stevia treated group, the values of ALT and AST were significantly decreased (p<0.05). However, ALP and bilirubin were not decreased significantly. Conclusion: Stevia rebaudiana exerts hepatoprotective effect in restoring liver damage due to high fat diet induced NAFLD in Sprague Dawley rats.
... Steviosides improve pancreas beta cell function for diabetes patients (Philippaert et al., 2017). Rats studying research have proven that adding stevia extract to their diet and substituting fructose with it lead to the fact that the researched animals developed better metabolic, oxidative, and histopathological indicators (Ranjbar et al., 2020). Clinical researches prove that stevia and its separate combinations have therapeutic and pharmacological effects and do not harm human health. ...
Diabetes is a metabolic disease whose prevalence in the world is increasing every year. To improve the life quality of diabetes patients and achieve better treatment results, adjusted food products with lower carbohydrate quantities are necessary. Primarily fructose is used in products for diabetes patients, but fructose increases obesity risk. The aim of the study is to evaluate available scientific articles on potential natural sweeteners for the substitution of fructose in food products for people with diabetes. Natural sweeteners could be a good alternative to fructose, they decrease product glycemic index and positively influence the health of diabetes patients. Stevia is a plant used in food production for obtaining sweet taste. Glycosides extracted from stevia are food additives, i.e. sweeteners. Stevia decreases sugar levels and improves insulin secretion, it has antibacterial and antioxidative features. The use of stevia in food production causes a bitter aftertaste of products. To disguise the bitter aftertaste, other natural sweeteners are added to stevia. Thaumatin is a sweet protein used in food production. To improve product taste, polyols and other natural sweeteners are added. Polyols are a good alternative for fructose substitution because they slightly influence sugar levels in the blood and they have high chemical thermal stability. Products containing different combinations of several natural sweeteners possess the best sensory features. The research results show that stevioside, rebaudioside, thaumatin, and polyols are good alternatives for fructose substitution in products. To clarify how sweeteners, influence food product features additional researches are necessary.
... The diabetic group rats (6 diabetic rats) were given 2 mL of distilled water orally. The Stevia group rats (6 diabetic rats) receive dissolved Stevia extract in distilled water in a dose of 400 mg/kg via oral gavage for 8 weeks 22 . The Stevia leaves were purchased from Agro-industry Product (SICAP), Cairo, Egypt, and the extract was prepared following the procedure described by El-Mesallamy et al 23 . ...
Objective:
Diabetes mellitus (DM) has been considered a major problem because of its related complications and growing incidence worldwide. Testicular dysfunction has become a predominant diabetic complication characterized by impaired reproductive function and testicular damage. Stevia rebaudiana Bertoni has been known for its antioxidant effect on diabetes, inflammation, and obesity. The current study investigates the protective effect of Stevia on diabetic-induced testicular injury.
Materials and methods:
Sprague Dawley adult male rats were divided into three groups: the control group, the diabetic group, and the diabetic + Stevia group, type 2 diabetes is induced by a high-fat diet (HFD) and a single dose of 35 mg/kg streptozotocin injection. The effects of Stevia were evaluated regarding biochemical, oxidative stress, histopathological and ultrastructural changes, and immunohistochemical expression of vascular endothelial growth factor (VEGF), vascular cell adhesion molecule-1 (VCAM-1), receptor-interacting serine/threonine-protein kinase 1 (RIPK 1), and caspase 3.
Results:
Stevia extract attenuated the diabetic-induced oxidative stress, restored the testicular architecture, and decreased testicular damage, inflammation, necroptosis, and apoptosis by upregulating VEGF and downregulating VCAM 1, RIPK 1, and caspase 3.
Conclusions:
The current study highlights the importance of Stevia as an antioxidant anti-inflammatory that ameliorates diabetic-induced testicular injury by modulating oxidative stress, inflammation, necroptosis, and apoptosis.
... Metformin is a standard drug used for the treatment type 2 diabetes through its ability to reduce hepatic gluconeogenesis and oppose the action of glucagon 52 . These results are supported by several publications that a metformin dose of 100 mg/kg can resolve MS in rats 53,54 . Furthermore, metformin can suppress Ang II-induced cardiovascular remodeling by reducing AT 1 R expression in cardiovascular cells 55 . ...
This study is aimed to investigate whether tuna protein hydrolysate (TPH) supplementation could alleviate cardiovascular complications induced by a high-fat diet (HFD) in rats. Rats were fed a HFD for 16 weeks and given TPH (100 mg/kg, 300 mg/kg, or 500 mg/kg) or metformin (100 mg/kg) (n = 8) for the last four weeks. TPH had the following effects: resolved their impaired glucose tolerance, hyperglycemia, dyslipidemia, obesity, and hypertension (p < 0.05); alleviated left ventricular dysfunction and hypertrophy (p < 0.05), and vascular dysfunction and hypertrophy (p < 0.05); adipocyte hypertrophy; increases in circulating leptin and tumor necrosis factor (TNF-α) were mitigated (p < 0.05); increased renin-angiotensin system (RAS), oxidative stress, and decreased nitric oxide metabolites were modulated (p < 0.05). TPH restored the expression of angiotensin II receptor type 1 (AT1R)/NADPH oxidase 2 (NOX2), endothelial nitric oxide synthase (eNOS), nuclear factor erythroid 2-related factor (Nrf2)/heme oxygenase-1 (HO-1), and peroxisome proliferator-activated receptor γ (PPARγ)/the nuclear factor kappa B (NF-κB) protein in cardiovascular tissue (p < 0.05). In metabolic syndrome (MS) rats, metformin and TPH had comparable effects. In conclusion, TPH alleviated cardiovascular complications related to MS. It suppressed RAS, oxidative stress, and inflammation that were associated with modulation of AT1R/NOX2, eNOS, Nrf2/HO-1, and PPARγ/NF-κB expression.
... This assay can be performed using various methods and, in the studies included herein, it was measured colorimetrically. The ferric reducing antioxidant power (FRAP) assay [40] is based on the ability of antioxidants to reduce ferric ion Fe +3 to ferrous ion Fe +2 in a redox reaction, the Fe +2 then reacts with the colorimetric reagent TPTZ (2,4,6-tripyridyl-s-triazine, and iron(III) chloride hexahydrate) to produce a complex which can be measured spectrophotometrically at 593 nm. In one study [41], TAC was indirectly measured by determining the residual H 2 O 2 through the conversion of 3,5, dichloro dicloro-2-hydroxy benzensulphonate to a colored product. ...
Stevia (Stevia rebaudiana Bertoni) is an aromatic plant known for its high sweetening power ascribed to its glycosides. Stevia also contains several bioactive compounds showing antioxidant, antiproliferative, antimicrobial, and anti-inflammatory activities. Since inflammation and oxidative stress play critical roles in the pathogenesis of many diseases, stevia emerges as a promising natural product that could support human health. In this study we set out to investigate the way stevia affects oxidative stress markers (e.g., SOD, CAT, GPx, GSH, MDA) in diseased rats administered stevia leaf extracts or glycosides. To this end, we performed an inclusive literature search, following PRISMA guidelines, and recruited multivariate meta-analysis and meta-regression to synthesize all available data on experimental animal models encountering (a) healthy, (b) diseased, and (c) stevia-treated diseased rats. From the 184 articles initially retrieved, 24 satisfied the eligibility criteria, containing 104 studies. Our results demonstrate that regardless of the assay employed, stevia leaf extracts restored all oxidative stress markers to a higher extent compared to pure glycosides. Meta-regression analysis revealed that results from SOD, CAT, GSH, and TAC assays are not statistically significantly different (p = 0.184) and can be combined in meta-analysis. Organic extracts from stevia leaves showed more robust antioxidant properties compared to aqueous or hydroalcoholic ones. The restoration of oxidative markers ranged from 65% to 85% and was exhibited in all tested tissues. Rats with diabetes mellitus were found to have the highest restorative response to stevia leaf extract administration. Our results suggest that stevia leaf extract can act protectively against various diseases through its antioxidant properties. However, which of each of the multitude of stevia compounds contribute to this effect, and to what extent, awaits further investigation.
... S. rebaudiana hydromethanolic extract (SRHME) of plant leaves was prepared as reported earlier [20]. About 400 g of fnely ground Stevia leaves was immersed in solution containing 80 methanol : 20 distilled water for 72 h with constant shaking, and the resulting mixture was fltered to remove the extract-containing solvent from the crushed leaves. ...
... Additionally, Stevia may assist in lowering blood sugar, depriving tumor cells of a crucial source of energy. Consequently, tumor models in vivo and cancer cells showed cytotoxic and antiproliferative activities by Stevia plant derivatives [20]. Te anticancer efectiveness of the methanol Stevia extract against MCF7 cells was previously reported, with an IC 50 value of 228 µg/ml [91]. ...
... Extract against SKVO3 Cells. Cell cycle arrest caused by the control of essential proliferating proteins and stimulation of the apoptotic process are the two basic mechanisms underlying Stevia's cytotoxicity [20]. As a result, in this study, the following potential apoptotic ...
The phenolic and flavonoid content of the Stevia rebaudiana hydromethanolic extract (SRHME) was examined, and phytochemical identification using GC-mass spectrometry was achieved. Also, the antioxidant, antihemolytic, and antilipid peroxidation capabilities of the extract were assessed. The extract’s potential to induce apoptosis, inhibit cell proliferation, and reduce metastasis in SKVO3 cells was also checked. The findings of the GC-MS chromatogram demonstrated the existence of bioactive antioxidants and anticancer components in SRHME. Moreover, the extract demonstrated protection against cellular oxidative damage in human erythrocytes by preventing lipid peroxidation and hemolysis. Besides, SRHME demonstrated a selective cytotoxic effect with a strong IC50 value (17.5 µg/ml) on SKVO3 cells without any harmful effects on normal WI-38 cells using the MTT and LDH tests. Additionally, according to assays for wound healing and transwell chamber, the studied extract suppressed the ability of SKOV3 cells from migrating and invading, respectively. Also, the extract-treated SKVO3 cells showed rise in the percentage of apoptotic cells with a prominent comet nucleus, according to apoptotic assays in comparison to untreated cells. Furthermore, a flow cytometry analysis of SRHME-treated SKVO3 cells showed a halt in the S phase and an increase in sub-G1 apoptotic cells (25.44%). Also, the tested extract significantly decreased the levels of ROS in the treated cells, indicating that ROS was involved in the production of SKVO3 apoptosis. Lastly, SRHME strongly impacted the expression levels of proteins related to apoptosis, S-phase cell cycle arrest, and antimetastatic capacity in the treated SKVO3 cells.
... ST decreased epididymal adipocyte size but did not significantly reduce epididymal fat (Park et al., 2022). Animal experiments also indicated SG potential to improve the lipid profile and other health indices associated with excess body weight (Khan et al., 2021;Kurek et al., 2020;Ranjbar et al., 2020). Oral administration of SG combined with green tea saponins (RASE1 formulation) reduced mouse body and body fat pad weight and blood cholesterol, TG, glucose and insulin levels. ...
Stevia rebaudiana Bertoni is famous for sweetness due to the content of steviol glycosides (SG). This study aimed to determine the effect of SG (stevioside, rebaudioside A) and steviol on adipogenesis and lipogenesis in the 3T3-L1 model. Test compounds were also analysed for their ability to affect glucose uptake in hypertrophied insulin-resistant 3T3-L1 adipocytes. The most active compound in modulating adipogenesis, lipogenesis and insulin resistance was steviol, SG metabolism product. Steviol (10 μM, 100 μM) significantly down-regulated the expression of adipogenic transcription factors (PPARγ, C/EBPα, SREBP1) and lipogenic genes (FAS, aP2, LPL), which caused decreased lipid accumulation and triglyceride content in adipocytes. Treatment of insulin-resistant adipocytes with steviol (1 μM) and stevioside (1 μM, 10 μM) increased GLUT-4 transcript level and improved glucose uptake. Steviol also lowered resistin gene expression, which may mitigate insulin resistance in hyper-trophied adipocytes. This study promotes SG as potential health-promoting ingredients in low-calorie functional foods.
... Some researchers have reported that Stevia (and its derivatives) can decrease the blood glucose levels by stimulating insulin secretion 25 , reducing protein and gene expression levels of phosphoenolpyruvate carboxykinase (PEPCK) 26 and decreasing insulin resistance 27 , decreasing the activity of gluconeogenic enzymes (glucose-6-phosphatase and fructose1,6-bisphosphatase) and glycogenesis or increasing glycolysis enzyme (hexokinase and glucose-6phosphate dehydrogenase) in STZ-NA induced diabetic rats 28 . ...
... Noteworthy, the lipid-lowering effect of stevioside was abolished by silencing PPARa (Jia et al. 2019), suggesting that its effects were mediated by activation of PPARa. Very recently, the effects of Stevia's hydroalcoholic extract (200 and 400 mg/kg) on metabolic syndrome indices were compared with those of 100 mg/kg metformin, in rats fed with a highfat, high-sucrose diet (Ranjbar et al. 2020). Both treatments suppressed the adverse effects of the high fat and high sugar diet on the lipid profile, liver enzymes, antioxidant capacity, and histopathologic factors. ...
The application of stevia glycosides in the food industry has grown steadily in the last two decades. Besides the use of its constituents as natural sweeteners, increasing attention has been given to their potential health benefits and therapeutic applications. Whereas in some cases clinical studies have been realized (prominently, to investigate its hypoglycemic and antihypertensive activity) many of them have failed to cover the expectations from preclinical investigations. Here, we review current knowledge on stevia constituents’ pharmacokinetics (both in rodents and in humans) and some of the most profusely investigated potential medical/health-related applications: i.e. diabetes and metabolic syndrome, hypertension, antimicrobial and anticancer activity. The outcome of available clinical studies and the perspectives of Stevia therapeutic uses are discussed in connection with pharmacokinetics knowledge.
... Metabolic syndrome is characterized by hyperglycemia, hyperlipidemia and central obesity, which increases the risk of various diseases including cardiovascular disease, diabetes, non-alcoholic fatty liver and cancer (Lent-Schochet et al., 2019). Latest epidemiological data show that the global prevalence of metabolic syndrome exceeds 20% (Tahereh et al., 2020). Due to the lack of potent pharmacotherapy, the rising prevalence of metabolic syndrome poses a huge threat to human health worldwide. ...
Background: Metabolic syndrome is characterized by central obesity, hyperglycemia and hyperlipidemia. Insulin resistance is the leading risk factor for metabolic syndrome. Kun-Dan decoction (KD), a traditional Chinese medicine, has been applied to treat patients with metabolic syndrome for over ten years. It is increasingly recognized that autophagy deficiency is the key cause of metabolic syndrome. Therefore, we aimed to explore whether KD can activate autophagy to improve metabolic syndrome.
Methods: Network pharmacology was used to explore the underlying mechanism of KD in the treatment of metabolic syndrome. The high-fat diet-fed rats and oleic acid-induced LO2 cells were employed in our study. Oral glucose tolerance test and insulin tolerance test, obesity and histological examination, serum cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity in high-fat diet-fed rats were analyzed. Furthermore, the protein expressions of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), phospho-AMPK, mammalian target of rapamycin (mTOR), phospho-mTOR, p62, autophagy related protein (Atg) 5, Atg7, Atg12, Atg13, Atg16L1 and microtubule-associated protein 1A/1B-light chain 3 (LC3)-Ⅱ/Ⅰ were examined in rats and LO2 cells. Moreover, autophagy activator rapamycin and inhibitor 3-methyladenine, and small interfering RNA against Atg7 were utilized to verify the role of autophagy in the treatment of metabolic syndrome by KD in oleic acid-induced LO2 cells.
Results: Results from network pharmacology indicated that targeted insulin resistance might be the critical mechanism of KD in the treatment of metabolic syndrome. We found that KD significantly suppressed obesity, serum cholesterol, triglyceride and LDL-C levels and increased serum HDL-C level in high-fat diet-fed rats. Furthermore, KD enhanced insulin sensitivity and attenuated HOMA-IR in high-fat diet-fed rats. Western blot showed that KD could enhance autophagy to increase the insulin sensitivity of high-fat diet-fed rats and oleic acid-induced LO2 cells. Furthermore, 3-methyladenine and small interfering RNA against Atg7 could reverse the protective effect of KD on LO2 cells. However, rapamycin could cooperate with KD to enhance autophagic activation to increase insulin sensitivity in LO2 cells.
Conclusion: The induction of autophagy may be the major mechanism for KD to improve insulin resistance and metabolic syndrome.
