Wan Iryani Wan Ismail

Potential Roles of Stevia rebaudiana Bertoni in Abrogating Insulin Resistance and Diabetes: A Review.

Insulin resistance is a key factor in metabolic disorders like hyperglycemia and hyperinsulinemia, which are promoted by obesity and may later lead to Type II diabetes mellitus. In recent years, researchers have identified links between insulin resistance and many noncommunicable illnesses other than diabetes. Hence, studying insulin resistance is of particular importance in unravelling the pathways employed by such diseases. In this review, mechanisms involving free fatty acids, adipocytokines such as TNFα and PPARγ and serine kinases like JNK and IKKβ, asserted to be responsible in the development of insulin resistance, will be discussed. Suggested mechanisms for actions in normal and disrupted states were also visualised in several manually constructed diagrams to capture an overall view of the insulin-signalling pathway and its related components. The underlying constituents of medicinal significance found in the Stevia rebaudiana Bertoni plant (among other plants that potentiate antihyperglycemic activities) were explored in further depth. Understanding these factors and their mechanisms may be essential for comprehending the progression of insulin resistance towards the development of diabetes mellitus.

Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p < 0.001) in normal conditions and up to 4.4 times (p < 0.001) in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet.

Anti-proliferative effect of Tinaspora crispa (L.) Hook. F. & Thompson and Gelam (Melaleuca sp.) honey on several cancer cell lines

Tinaspora crispa and Gelam (Melaleuca sp.) honey were identified as potential anti-proliferative agents due to presence of high antioxidant activity. In this research, human breast adenocarcinoma (MCF-7), human colorectal carcinoma (HCT116), human hepatocellular carcinoma (HepG2) and adenocarcinoma human alveolar basal epithelial (A549) cell lines were treated with both extracts and further diagnosed the viability using 3- (4,5 - dimethylthiazol-2-y) - 5 - (3-carboxymetaxyphenyl) 2- (4- sulphophenyl) - 2H - tetrazolium (MTS) assay. T.crispa and Gelam honey have showed anti-proliferative effects to selected cancer cell lines. The maximal effect of T. crispa and Gelam honey were demonstrated on HepG2 (IC50 = 9.13 µg/ml) and HCT116 (IC50 = 3.98 %, v/v) accordingly. In addition, we revealed that Gelam honey exhibited anti-proliferative effect on MCF-7. While the finest preparation of T.crispa crude extract revealed a potential result compared to previous studies. Total phenolic content may play the major role in demonstrating anti-proliferative effect, which was measured parallel as the main source of antioxidant activity.

Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

Mechanism of apoptosis induced in hepatoma G2 (HepG2) cell lines by Tinospora crispa: Targeting signalling of the insulin-like growth factor (IGF) system and the insulin signalling (IS) pathway

Abstract Introduction Hepatoma G2 (HepG2) cell line proliferation is controlled by insulin-like growth factor (IGF) signalling system. It is affected by exaggeration of self-producing IGF-1 ligand and disruption of the insulin signalling (IS) pathway which are later inhibit apoptotic activity. Tinospora crispa, a local herbal plant used as folklore medicine, contains natural insulin enhancer and possesses antiproliferative effects. The plant will be used in the study to observe its effect in restoring physiological function of the IS pathway, subsequently inducing apoptosis. Objective To evaluate the mechanism of T. crispa in compensating insulin resistance thus inducing apoptosis in HepG2 cancer cell line. Methods The protein expression of the IGF and IS pathways was investigated by the Western blotting method in order to track the compensatory mechanism. Results & Discussion IGF-1R overexpression in HepG2 impaired insulin-induced AKT phosphorylation thus inactivated glucose intake through GLUT4. After treated with T. crispa crude methanolic extract, IGF-1R function of the cells was downregulated (p 0.32). The extract permitted the function of the IS pathway of HepG2 by enhancing insulin-induced autophosphorylation (PY20) on the s – insulin receptor (IR-β) (p Conclusion Tinospora crispa has the potential as an anti-cancer agent via targeting insulin-like growth factor system and insulin signalling pathway in HepG2 cancer cell line.

Corrigendum to “Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes”

[This corrects the article DOI: 10.1155/2013/938081.].