scholarly journals Anti-Obesity and Lipid Lowering Activity of Bauhiniastatin-1 is Mediated Through PPAR-γ/AMPK Expressions in Diet-Induced Obese Rat Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Reddy Sankaran Karunakaran ◽  
Oruganti Lokanatha ◽  
Ganjayi Muni Swamy ◽  
Chintha Venkataramaiah ◽  
Muppuru Muni Kesavulu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
High Fat Diet ◽  
Docking Studies ◽  
Lipid Lowering ◽  
High Fat ◽  
Down Regulation ◽  
Binding Interactions ◽  
Molecular Docking Studies ◽  
Ppar Γ ◽  
Group I

Objective: To evaluate the therapeutic efficacy and underlying molecular mechanisms of Bauhiniastatin-1 (BSTN1) to alleviate adiposity in diet-induced obese rodent model and in 3T3-L1 cells.Methods: BSTN1 was purified and confirmed through HPLC. In-vitro experiments such as MTT assay, Oil Red-O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis were performed in 3T3-L1 cells in the presence and absence of BSTN1. In animal experiments, rats were divided into Group-I: normal pellet diet-fed, Group-II: HFD-fed, Groups-III, IV and V: HFD-fed BSTN1 (1.25, 2.5, and 5 mg/kg.b.wt./day/rat)-treated and Group-VI: HFD-fed Orlistat-treated. The rats were fed either normal diet or high fat diet (HFD) for 18 weeks and water ad-libitum. BSTN1 was orally administered from 13th week onwards to the selected HFD-fed groups. Body composition parameters, biochemical assays, histopathology examination and western blot analysis were performed to identify the predicted targets related to obesity. Molecular docking studies threw light on the binding interactions of BSTN1 against PPAR-γ, FAS and AMPK.Results: BSTN1 at 20 μM significantly (p < 0.001) inhibited adipocyte differentiation and lipid accumulation in 3T3-L1 cells. A conspicuous down-regulation in the mRNA expression levels of PPAR-γ, FAS and SREBP1 was observed but AMPK expression remained unchanged in BSTN1 treated 3T3-L1 cells. A substantial decrease in body weight gain, fat percent, total body fat, serum and liver lipid profile (except high-density lipoprotein), glucose, insulin and insulin resistance in BSTN1 treated rats was noticed in a dose dependent manner. In BSTN1 (5 mg/kg.b.wt.)-treated groups significantly (p < 0.01) elevated plasma adiponectin level but reduced leptin level as well as fall in serum AST and ALT were noticed. Further, the disturbed structural integrity and architecture of adipose and hepatic tissues due to high fat diet feeding were considerably recovered with BSTN1 treatment. Down-regulation in the protein expression level of PPAR-γ and activation of AMPK through phosphorylation was observed in BSTN1 treated rats than the untreated. Molecular docking studies revealed strong binding interactions of BSTN1 against PPAR-γ and AMPK and thus supported the experimental results.Conclusion: Taken together, the results suggest that BSTN1 could be a promising pharmacological molecule in the treatment of obesity and dyslipidemia.

Hypoglycemic activity of 6-bromoembelin and vilangin in high-fat diet fed-streptozotocin-induced type 2 diabetic rats and molecular docking studies

Life Sciences ◽  
2016 ◽  
Vol 153 ◽  
pp. 100-117 ◽  
Author(s):  
Antony Stalin ◽  
Santiagu Stephen Irudayaraj ◽  
Gopalsamy Rajiv Gandhi ◽  
Kedike Balakrishna ◽  
Savarimuthu Ignacimuthu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
High Fat Diet ◽  
Docking Studies ◽  
Diabetic Rats ◽  
Hypoglycemic Activity ◽  
High Fat ◽  
Molecular Docking Studies ◽  
Type 2 Diabetic

scholarly journals Synthesis of a 1,2,3-bistriazole derivative of embelin and evaluation of its effect on high-fat diet fed-streptozotocin-induced type 2 diabetes in rats and molecular docking studies

2020 ◽  
Vol 96 ◽  
pp. 103579 ◽  
Author(s):  
Antony Stalin ◽  
Subramani Kandhasamy ◽  
Balakrishnan Senthamarai Kannan ◽  
Rama Shanker Verma ◽  
Savarimuthu Ignacimuthu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Molecular Docking ◽  
High Fat Diet ◽  
Docking Studies ◽  
High Fat ◽  
Molecular Docking Studies

scholarly journals Binding Efficacy and Thermogenic Efficiency of Pungent and Nonpungent Analogs of Capsaicin

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3198 ◽  
Author(s):  
Padmamalini Baskaran ◽  
Kyle Covington ◽  
Jane Bennis ◽  
Adithya Mohandass ◽  
Teresa Lehmann ◽  
...  
Keyword(s):  
Hydrogen Bond ◽  
Molecular Docking ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Docking Studies ◽  
Transient Receptor Potential Vanilloid ◽  
Metabolic Dysfunction ◽  
High Fat

(1) Background: Capsaicin, a chief ingredient of natural chili peppers, enhances metabolism and energy expenditure and stimulates the browning of white adipose tissue (WAT) and brown fat activation to counter diet-induced obesity. Although capsaicin and its nonpungent analogs are shown to enhance energy expenditure, their efficiency to bind to and activate their receptor—transient receptor potential vanilloid subfamily 1 (TRPV1)—to mediate thermogenic effects remains unclear. (2) Methods: We analyzed the binding efficiency of capsaicin analogs by molecular docking. We fed wild type mice a normal chow or high fat diet (± 0.01% pungent or nonpungent capsaicin analog) and isolated inguinal WAT to analyze the expression of thermogenic genes and proteins. (3) Results: Capsaicin, but not its nonpungent analogs, efficiently binds to TRPV1, prevents high fat diet-induced weight gain, and upregulates thermogenic protein expression in WAT. Molecular docking studies indicate that capsaicin exhibits the highest binding efficacy to TRPV1 because it has a hydrogen bond that anchors it to TRPV1. Capsiate, which lacks the hydrogen bond, and therefore, does not anchor to TRPV1. (4) Conclusions: Long-term activation of TRPV1 is imminent for the anti-obesity effect of capsaicin. Efforts to decrease the pungency of capsaicin will help in advancing it to mitigate obesity and metabolic dysfunction in humans.

scholarly journals Crude extract and isolated bioactive compounds from Notholirion thomsonianum (Royale) Stapf as multitargets antidiabetic agents: in-vitro and molecular docking approaches

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mater H. Mahnashi ◽  
Yahya S. Alqahtani ◽  
Ali O. Alqarni ◽  
Bandar A. Alyami ◽  
Muhammad Saeed Jan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Research Work ◽  
Docking Studies ◽  
Common Disease ◽  
World Population ◽  
Binding Interactions ◽  
Molecular Docking Studies ◽  
Crude Extracts

Abstract Background Diabetes mellitus is a common disease effecting the lifestyles of majority world population. In this research work, we have embarked the potential role of crude extracts and isolated compounds of Notholirion thomsonianum for the management diabetes mellitus. Methods The crude extracts of N. thomsonianum were initially evaluated for α-glucosidase, α-amylase and antioxidant activities. The compounds were isolated from the activity based potent solvent fraction. The structures of isolated compounds were confirmed with NMR and MS analyses. The isolated compounds were tested for α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and DPPH activities. The molecular docking studies were carried out to find the binding interactions of isolated compounds for α-glucosidase, α-amylase and PTP1B. Results Initially, we screened out crude extracts and subfractions of N. thomsonianum against different in-vitro targets. Among all, Nt.EtAc was observed a potent fraction among all giving IC50 values of 67, 70, < 0.1, 89 and 16 μg/mL against α-glucosidase, α-amylase, DPPH, ABTS and H2O2 respectively. Three compounds (Nt01, Nt02 and Nt03) were isolated from Nt.EtAc of N. thomsonianum. The isolated compounds Nt01, Nt02 and Nt03 exhibited IC50 values of 58.93, 114.93 and 19.54 μM against α-glucosidase, while 56.25, 96.54 and 24.39 μM against α-amylase respectively. Comparatively, the standard acarbose observed IC50 values were 10.60 and 12.71 μM against α-glucosidase, α-amylase respectively. In PTP1B assay, the compounds Nt01, Nt02 and Nt03 demonstrated IC50 values of 12.96, 36.22 and 3.57 μM in comparison to the standard ursolic acid (IC50 of 3.63 μM). The isolated compounds also gave overwhelming results in DPPH assay. Molecular docking based binding interactions for α-glucosidase, α-amylase and PTP1B were also encouraging. Conclusions In the light of current results, it is obvious that N. thomsonianum is potential medicinal plant for the treatment of hyperglycemia. Overall, Nt.EtAc was dominant fraction in all in-vitro activities. Three compounds Nt01, Nt02 and Nt03 were isolated from ethyl acetate fraction. The Nt03 specifically was most potent in all in-vitro assays. The molecular docking studies supported our in-vitro results. It is concluded that N. thomsonianum is a rich source of bioactive antidiabetic compounds which can be further extended to in-vivo based experiments.

Exploration of Diosmin to control diabitis and its complications-an in vitro and in silico approach

2020 ◽  
Vol 16 ◽  
Author(s):  
Kushagra Dubey ◽  
Raghvendra Dubey ◽  
Revathi Gupta ◽  
Arun Gupta
Keyword(s):  
Molecular Docking ◽  
Aldose Reductase ◽  
Inhibitory Activity ◽  
Blood Lipid ◽  
Docking Studies ◽  
Alpha Amylase ◽  
Lipid Lowering ◽  
Molecular Docking Studies ◽  
Alpha Glucosidase

Background: Diosmin is a flavonoid obtained from the citrus fruits of the plants. Diosmin has blood lipid lowering activities, antioxidant activity, enhances venous tone and microcirculation, protects capillaries, mainly by reducing systemic oxidative stress. Objective: The present study demonstrates the potential of Diosmin against the enzymes aldose reductase, α-glucosidase, and α-amylase involved in diabetes and its complications by in vitro evaluation and reverse molecular docking studies. Method: The assay of aldose reductase was performed by using NADPH as starting material and DL-Glyceraldehyde as a substrate. DNS method was used for alpha amylase inhibition and in alpha glucosidase inhibitory activity p-nitrophenyl glucopyranoside (pNPG) was used as substrate. The reverse molecular docking studies was performed by using Molegro software (MVD) with grid resolution of 30 Å. Result: Diosmin shows potent inhibitory effect against aldose reductase (IC50:333.88±0.04 µg/mL), α-glucosidase (IC50:410.3±0.01 µg/mL) and α-amylase (IC50: 404.22±0.02 µg/mL) respectively. The standard drugs shows moderate inhibitory activity for enzymes. The MolDock Score of Diosmin was -224.127 against aldose reductase, -168.17 against α-glucosidase and -176.013 against α-amylase respectively, which was much higher than standard drugs. Conclusion: From the result it was concluded that diosmin was a potentially inhibitor of aldose reductase, alpha amylase and alpha glucosidase enzymes then the standard drugs and it will be helpful in the management of diabetes and its complications. This will also be benevolent to decrease the socio economical burden on the middle class family of the society.

scholarly journals In silico molecular docking studies of some phytochemicals against peroxisome-proliferator activated receptor gamma (PPAR-γ)

2018 ◽  
Vol 5 (2) ◽  
pp. 001-005
Author(s):  
H. A. Ahmed ◽  
I. Y. Alkali
Keyword(s):  
Molecular Docking ◽  
Insulin Sensitivity ◽  
Binding Affinity ◽  
Docking Studies ◽  
Peroxisome Proliferator ◽  
Autodock Vina ◽  
Peroxisome Proliferator Activated Receptor ◽  
Standard Drug ◽  
Molecular Docking Studies ◽  
Ppar Γ

Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily that regulate the gene expression of proteins involved in glucose, lipid metabolism, adipocyte proliferation and differentiation and insulin sensitivity. Thiazolidinediones (TZDs) are one important class of synthetic agonists of PPAR-γ. TZDs are antidiabetic agents that target adipose tissue and improve insulin sensitivity, and they are currently being used in the treatment of type 2 diabetes. The study was carried out in order to discover new phytochemicals that have the ability to stimulate the PPAR-γ using molecular docking studies. AutoDock vina was used as molecular-docking tool in order to carry out the docking simulations. Nine phytochemicals namely plumbagin, quercetin, isovitexin, mangiferin, syringin, lupe-20-ene-3-one, purine 2, 6-dione, diosmetin and β sitosterol and pioglitazone a standard drug were docked against PPAR-γ using AutoDock vina and the results were analyzed using binding affinity. The results revealed that the compounds have significant binding affinity towards the PPAR-γ comparable to pioglitazone the standard drug. Based on the findings of this study these phytochemicals can serve as source of antidiabetic drugs via the mechanism of inhibition of PPAR-γ.

scholarly journals Design and synthesis of novel heterocyclic compounds as a PPAR-γ agonist

2020 ◽  
Vol 11 (2) ◽  
pp. 2063-2069
Author(s):  
Zambare Y. B. ◽  
Bhole R. P. ◽  
Chitlange S. S.
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Docking ◽  
Docking Studies ◽  
Binding Energies ◽  
Oral Glucose ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Docking Studies ◽  
Discovery Studio ◽  
Ppar Γ

The multifarious metabolic syndrome, diabetes mellitus (DM), is a diseaseof concern all over the world and is approximate to affect 400 million individuals by the 2020. Several classes of drugs at the moment are available to lessen hyperglycemia in diabetes mellitus especially in Type-II. These drugs mostly have dangerous side effects and thus incisive for a new class of compounds is necessary to conquer this inconvenience. A series of 6 novel 5-nitrobenzofuran-2yl-carbamides derivatives were synthesized and molecular docking studies were performed on PPAR-γ target using (PDB code-4rfm).The preparation of5-nitro-1-benzofuran-2-carbohydrazide(4) on action with acetic acid, 1, 4-diaxone and sodium nitrite resulted in 5-nitro-1-benzofuran-2-carbonyl azide (5).The related compound (5) on action with substituted aromatic substituted amines undergoes Curtis type of rearrangement to give 5-nitro-N-(sub. carbamoyl)-1-benzofuran-2-carboxamide.The characterization and identification of prepared compounds were identified on the basis of NMR, IR, Mass and elemental analysis. Docking study of targeted compounds were done using software Autodock Tools 1.5.6 and visualisation done by Discovery Studio 3.5 software (Accelrys Inc. San Diego, CA USA). Molecular docking studies, the binding energies are determined to be in the range of –5.90 to –9.80 kcal/mol, with peroxisome proliferator activated receptor γ (PPAR-γ) receptors (PDB ID: 4RFM). The prepared compounds have been studied for their oral glucose tolerance test to distinguish the effect on plasma glucose level.

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