Tannins present in Cichorium intybus enhance glucose uptake and inhibit adipogenesis in 3T3-L1 adipocytes through PTP1B inhibition (original) (raw)
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Selected Herbal Extracts Improve Diabetes Associated Factors in 3T3-L1 Adipocytes
Procedia - Social and Behavioral Sciences, 2013
Owing to the current worsening situation of the increasing burden of diabetes around the world including Malaysia it is worthwhile to discover non-pharmacological prevention or treatment for it. In order to have a useful explanation of the efficacy of herbs or nutrients for diabetes; it is desirable to know the effect on the balance between the adipogenesis, adipolysis and glucose uptake in the adipose tissues. Therefore, four herbs namely Orthosiphon stamineus (Cat whisker) (OS), Peronema canescens (Sungkai) (PC), Momordica charantia (Bitter gourd/bitter melon) (MC) and Pithecellobium jiringa (Jering) (PJ) were screened for their antidiabetic properties in in vitro model 3T3-L1 adipocytes. Water extracts of these herbs were prepared and evaluated for their effects on cell proliferation, adipogenesis, adipolysis and glucose uptake in 3T3-L1 preadipocytes cells. The aforementioned extracts promoted cell proliferation at a dose of 0.25mg/ml which showed more than 90% viability after 48 hours of treatment. The result of this study indicates that OS extracts significantly (P<0.001) increased adipogenesis whereas PC, MC and PJ extracts were not effective compared to control. The extracts from all four plants caused increased lipolysis compared to control. The Extract from OS and PJ significantly (P<0.05) stimulated glucose uptake in the cells whereas PC, MC were not effective. When the glucose consumption was compared to control it was significantly (P<0.001) increased for all extracts in the medium. The present study provides some important baseline data on the biochemical aspects of the effect induced by the herbs and suggestive of possessing antidiabetic properties which can be exploited for diabetes prevention and associated metabolic dysfunctions.
Pharmacognosy Magazine, 2017
Background: Adiantum philippense (AP) is a pteridophyte that shows antihyperglycemic activity in vivo diabetic model, but the mechanism of action is unknown. Objective: AP was found to play a pivotal role in minimizing the high blood glucose in alloxan-induced diabetic rats. Simultaneously, it was observed that it could maintain the normal lipid profile even in diabetic condition. To investigate its insulin-like activity along with its inhibitory role on adipocyte differentiation became the objective of our present study. Materials and Methods: Glucose uptake potential of this fern was done in isolated pancreatic islets and inhibition of adipocyte differentiation was assessed in 3T3-L1 cell line. Before this, the cytotoxic concentration was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on L929 cell line. To determine its role in lipid metabolism, the oil droplets produced in adipocytes were stained with Oil 'O' red staining, and triglyceride levels of various drug treatments were measured spectrophotometrically. Results: This fern extract was found to be actively utilizing glucose in the glucose uptake assay. Moreover, it was also involved in inhibiting differentiation of pro-adipocyte to adipocyte in the 3T3-L1 cell lines. The percentage inhibition as obtained from the absorbance showed that the ethanolic extract at the concentration of 200 µg/ml showed 32.48% inhibition. Conclusion: All the above-mentioned parameters when appraised indicated that this fern could be used as an alternative medicine in managing diabetes associated with obesity.
Journal of Ethnopharmacology, 2014
Ethnopharmacological relevance: Ibervillea sonorae (S. Watson) Greene (Cucurbitaceae), a plant used for the empirical treatment of type 2 diabetes in México, exerts antidiabetic effects on animal models but its mechanism of action remains unknown. The aim of this study is to investigate the antidiabetic mechanism of an Ibervillea sonorae aqueous extract (ISE). Materials and methods: Non-toxic ISE concentrations were assayed on the glucose uptake by insulinsensitive and insulin-resistant murine and human cultured adipocytes, both in the absence or the presence of insulin signaling pathway inhibitors, and on murine and human adipogenesis. Chemical composition of ISE was examined by spectrophotometric and HPLC techniques. Results: ISE stimulated the 2-NBDGlucose uptake by mature adipocytes in a concentration-dependent manner. ISE 50 mg/ml induced the 2-NBDG uptake in insulin-sensitive 3T3-F442A, 3T3-L1 and human adipocytes by 100%, 63% and 33%, compared to insulin control. Inhibitors for the insulin receptor, PI3K, AKT and GLUT4 blocked the 2-NBDG uptake in murine cells, but human adipocytes were insensitive to the PI3K inhibitor Wortmannin. ISE 50 mg/ml also stimulated the 2-NBDG uptake in insulin-resistant adipocytes by 117% (3T3-F442A), 83% (3T3-L1) and 48% (human). ISE induced 3T3-F442A adipogenesis but lacked proadipogenic effects on 3T3-L1 and human preadipocytes. Chemical analyses showed the presence of phenolics in ISE, mainly an appreciable concentration of gallic acid. Conclusion: Ibervillea sonorae exerts its antidiabetic properties by means of hydrosoluble compounds stimulating the glucose uptake in human preadipocytes by a PI3K-independant pathway and without proadipogenic effects.
Antidiabetic Screening of Commercial Botanical Products in 3T3-L1 Adipocytes and db=db Mice
Numerous botanicals are purported to improve glucose metabolism and diabetic risk factors with varying degrees of supportive evidence. We investigated 203 commercially available botanical products representing 90 unique botanical species for effects on lipogenic activity in differentiating 3T3-L1 adipocytes. Anti-inflammatory activity of 21 of these products was further assessed in tumor necrosis factor a (TNFa)-stimulated, mature 3T3-L1 adipocytes. From these results, rho-isoalpha acids, Acacia nilotica bark, fennel, and wasabi were tested in the db=db mouse model. Fifty-nine percent of the 90 unique botanicals increased adipogenesis as did the standard troglitazone relative to the solvent controls. Botanical species with the greatest percentage of positive products were Centella asiatica, Panax quinquefolius, and Phyllanthus amarus at 100%, Vitis vinifera at 80%, Humulus lupulus at 71%, Aloe barbadensis at 66%, and Momordica charantia, Phaseolus vulgaris, and Punica granatum at 60%. All 21 subset samples inhibited TNFa-stimulated free fatty acid release and attenuated TNFa inhibition of adiponectin secretion. Both rho-isoalpha acids and A. nilotica reduced nonfasting glucose in the db=db mouse model, whereas A. nilotica also decreased nonfasting insulin levels. A post hoc analysis of the screening results indicated that the positive predictive value of the lipogenesis assay alone was 72%, while adding the criterion of a positive response in the anti-inflammatory assays increased this figure to 82%. Moreover, this large-scale evaluation demonstrates that antidiabetic, in vitro efficacy of botanicals is more a function of manufacturing or quality control differences than the presence of marker compounds and further underscores the need to develop functional as well as analytical bases for standardization of dietary supplements.
Non-insulin-dependent diabetes mellitus is due to in large part to insulin resistance, a state where the target cells are no longer responding to ordinary levels of circulating insulin. A drug that promotes the initiation of insulin receptor (IR) signaling by enhancing IR phosphorylation should be useful in the treatment of Type 2 diabetes. To investigate a compound that is able to phosphorylate IR, a proanthocyanidin, cinnamtannin B1, has been isolated from the stem bark of Cinnamomum zeylanicum Blume (Lauraceae). The structure of the compound was established by spectroscopic methods. Cinnamtannin B1 (0.11 mM) activates the phosphorylation of insulin receptor β-subunit on 3T3-L1 adipocytes. Like insulin, cinnamtannin B1-stimulated phosphorylation of insulin receptor was inhibited by wortmannin, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K) and cytochalasin B, an inhibitor of the glucose transporter (GLUT4); otherwise the phosphorylation was enhanced by vanadate, a tyrosine phosphatase inhibitor. These results suggest that the activity of cinnamtannin B1 is specially mediated by phosphorylation of IR through activation of the PI3K.
NEW PHYTOCHEMICAL BASED COCKTAIL FOR IN VITRO ADIPOCYTES DIFFERENTIATION
Adipocyte (fat tissue) is commonly used in in vitro study of diabetes and many other areas in endocrinology. Prior to testing, preadipocytes (fat cells) culture will be differentiated to adipocytes using a mixture of three compounds, which are insulin, dexamethasone and isobutylmethylxanthine. The cocktail of these components is expensive. Furthermore, dexamethasone has been recently categorized as a restricted item in Malaysia. Therefore, in this work, an alternative component to replace these compounds is necessary. The first scope of the study is to replace insulin with suitable phytochemical based compound using Malaysian rich biodiversity. Based on the lead compound screening of phytochemicals for diabetes, cinnamon water extract has shown to have the ability to increase glucose uptake in adipocytes culture tested. The active component in the extract has been identified as Cinnamtannin B1 and the results indicates that this compound react similar to insulin in promoting preadipocytes differentiation to adipocytes tissue. First scope of the project has been achieved where Cinnamtannin B1 is found to be a potential candidate to replace insulin in currently used adipocytes differentiation cocktail. This finding is hoped to offer the possibility of using a non biological alternative to insulin in adipocytes differentiation.
Journal of Diabetes & Metabolic Disorders, 2021
Background Diabetes mellitus (DM) and obesity comorbidity signify a frequent metabolic disorder, representing a huge public health burden. Metformin, the most used anti-diabetic medication, is found to reduce body weight via growth differentiation factor 15 (GDF-15) signalling pathways. The medicinal herb Cichorium intybus L. (chicory or cichorium) has a promising pharmacological impact on energy homeostasis. On the other hands, little data is available on its role in DM and obesity. Despite its irrefutable effect, its exact mechanism of action has not completely elucidated; the present study evaluated the effect of chicory on DM, antioxidant status, inflammation, and GDF-15 level in comparison with the metformin effect. Material and methods Eighty albino mice were grouped as (control, obese diabetic group, metformin-treated, and Cichorium intybus L.-treated group). The study assessed blood glucose, lipid profile, inflammatory markers (IL-6, TNF-α), total antioxidant capacity (TAC) and caspase-3. Quantitative RT-PCR assessed GDF-15 and leptin relative mRNA expression. Results Cichorium intybus L. has significantly lowered inflammatory, apoptotic markers, and leptin levels compared with the diseased group. Likewise, the plant upregulated GDF-15 and TAC's levels. The study documented a non-significant difference between the Cichorium intybus L.-treated and the metformin-treated groups in all estimated markers. Conclusion The Cichorium intybus L. is a promising herbal supplement with anti-inflammatory, antioxidant, anti-diabetic, and weight reduction effects via affecting GDF-15 signalling pathways.
An insight into anti-adipogenic properties of an Oroxylum indicum (L.) Kurz extract
BMC Complementary Medicine and Therapies, 2020
BackgroundOroxylum indicumfruit extract (OIE) has been reported to inhibit the development of adipocytes. However, the exact mechanism of its metabolic activity is not clearly defined. This study attempted to investigate whether OIE was involved in disrupting the cell cycle, glucose metabolism, and mitochondrial function in 3 T3-L1 cells.MethodsThe effect of the OIE on cell cycle progression was measured by flow cytometry along with observing the expression of the cycle regulator by immunoblotting. The effect of the OIE on glucose metabolism was investigated. The amount of glucose uptake (2-NBDG) influenced by insulin was determined as well as the protein tyrosine phosphorylation (PY20), and glucose transporter4 (GLUT4) expression was determined by immunoblotting assay. Mitochondria are also essential to metabolic processes. This study investigated mitochondrial activity using fluorescent lipophilic carbocyanine dye (JC-1) and mitochondria mass by MitoTracker Green (MTG) staining fl...
Diabetology & Metabolic Syndrome, 2016
Background: Inflammation is an early event in the development of diabetes type 2 (T2D). Cichorium intybus L. (chicory) possesses anti-inflammatory action. We compared the anti-inflammatory aspect of aqueous chicory seed extract (CSE) in early and late stage T2D in rats. Methods: Wistar albino rats were divided into nine final groups (n = 6). Three main groups consisted of non-diabetic (Control), early stage diabetes (ET2D; niacinamide/streptozotocin, i.e., NIA/STZ), and late stage diabetes (LT2D; STZ). Within each main group, a subgroup was treated with CSE (125 mg/kg; i.p.); within each diabetic group (STZ and NIA/ STZ) a subgroup received metformin (100 mg/kg; i.p.); another subgroup in STZ group received aspirin (120 mg/kg; oral). After 21 days, fasting blood glucose (FBS), insulin, and TNF-α level were measured in serum; IKKβ and NF-κB (p65) mRNA and protein expression were evaluated by real time PCR and Western blotting; p65 DNA binding activity was determined by ELISA, in liver tissue. Results: The mRNA and protein expression levels of IKKβ, and P65 genes increased in both stages of T2D (p < 0.01); CSE decreased their expression (p < 0.001, mRNAs; p < 0.05, proteins). The increased DNA-binding capacity of NF-κB (p < 0.0001) in diabetes was lowered by CSE (p < 0.001). The effect of CSE was limited to ET2D requiring insulin. Conclusions: The anti-inflammatory action of CSE is due to a direct modulation of cytokine expression. The dependency of chicory action on the presence of insulin indicates its usefulness in the early stages of diabetes and for the purpose of preventing and delaying diabetes onset.
Journal of Experimental Pharmacology
Background: There would be over 600 million people living with diabetes by 2040 as predicted by the World Health Organization. Diabetes is characterized by raised blood sugar and insulin resistance. Insulin regulates the influx of glucose into the cell by upregulating the glucose transporter type 4 (GLUT4) expression on the plasma membrane. Besides, PPAR-γ also controls the metabolism of glucose in adipose tissues. Curcuma mangga Val., denoted as C. mangga, is a native Indonesian medicinal plant that has many beneficial effects, including an antidiabetic potential. Purpose: In this research, we aimed to disclose the hypoglycemic activity of ethanol extract of C. mangga (EECM) in 3T3-L1 fibroblasts-derived adipocyte cells in regulating glucose uptake as confirmed by the GLUT4 and PPAR-γ gene expression. Methods: The uptake of glucose was determined using radioactive glucose, while the gene expression of GLUT4, PPAR-γ, and β-actin was quantified using mRNA segregation and real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Results: We discovered that EECM interventions (200 and 50 μg/mL) increased glucose uptake in lipid-laden 3T3-L1 cells by 14.75 and 8.86 fold compared to the control noninsulin, respectively (p < 0.05). At the same doses, they also increased GLUT4 mRNA expression by 8.41 and 11.18 fold compared to the control non-insulin, respectively (p < 0.05). In contrast, EECM interventions (200 and 50 μg/mL) showed lower levels of PPAR-γ mRNA expression compared to the control metformin, indicating the anti-adipogenic potentials of EECM. Conclusion: EECM showed hypoglycemic activity in lipid-laden 3T3-L1 cells by improving glucose ingestion into the cells, which was mediated by increased GLUT4 expression and downregulated PPAR-γ expression.