Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics

Shoaib, Ambreen; Tasleem, Munazzah; Alabdallah, Nadiyah M.; Alam, Md. Jahoor; Asmar, Zeina El; Jamal, Qazi Mohammad Sajid; Bardakçı, Fevzi; Alqahtani, Saad S.; Ansari, Irfan Ahmad; Badraoui, Riadh

doi:10.3390/molecules26133996

Cited by 44 publications

(31 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MD simulations also suggest that shikonin could be a lead molecule for inhibiting PTP1B. The powerful inhibition of PTP1B by shikonin was determined experimentally (IC50 = 8.72 M), confirming the antidiabetic effects of the shikonin scaffold [ 160 ].…”

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 86%

“…The ability of shikonin, a natural naphthoquinone dying pigment, to inhibit PTP1B was evaluated through a complex approach involving in silico and in vitro methods [ 160 ]. Shikonin was docked at its putative binding site from 1AAX structure [ 161 ], which allowed the identification of crucial residues involved in the interaction.…”

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 99%

“…Shikonin and the 100 best docked compounds were filtered based on their ADMET and drug-likeness properties, which led to the identification of four additional possible ligands: ZINC31168041, ZINC31168045, ZINC31168041 and ZINC31168554. These compounds were also docked at PTP1B active sites, and ZINC31168045 presented the highest docking score [ 160 ]. MD simulations also suggest that shikonin could be a lead molecule for inhibiting PTP1B.…”

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 99%

See 2 more Smart Citations

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

et al. 2021

View full text Add to dashboard Cite

Diabetes represents a major health problem, involving a severe imbalance of blood sugar levels, which can disturb the nerves, eyes, kidneys, and other organs. Diabes management involves several synthetic drugs focused on improving insulin sensitivity, increasing insulin production, and decreasing blood glucose levels, but with unclear molecular mechanisms and severe side effects. Natural chemicals extracted from several plants such as Gymnema sylvestre, Momordica charantia or Ophiopogon planiscapus Niger have aroused great interest for their anti-diabetes activity, but also their hypolipidemic and anti-obesity activity. Here, we focused on the anti-diabetic activity of a few natural and synthetic compounds, in correlation with their pharmacokinetic/pharmacodynamic profiles, especially with their blood-brain barrier (BBB) permeability. We reviewed studies that used bioinformatics methods such as predicted BBB, molecular docking, molecular dynamics and quantitative structure-activity relationship (QSAR) to elucidate the proper action mechanisms of antidiabetic compounds. Currently, it is evident that BBB damage plays a significant role in diabetes disorders, but the molecular mechanisms are not clear. Here, we presented the efficacy of natural (gymnemic acids, quercetin, resveratrol) and synthetic (TAK-242, propofol, or APX3330) compounds in reducing diabetes symptoms and improving BBB dysfunctions. Bioinformatics tools can be helpful in the quest for chemical compounds with effective anti-diabetic activity that can enhance the druggability of molecular targets and provide a deeper understanding of diabetes mechanisms.

show abstract

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 86%

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 99%

Section: Molecular Docking and Molecular Dynamics Predicted Anti-diabetic Activitymentioning

confidence: 99%

See 1 more Smart Citation

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Moreover, in vivo S-treatment resulted in decreased weight gain and hepatic fat accumulation, enhanced glucose tolerance, augmented fatty acid oxidation-associated genes and ameliorated hepatic insulin signaling in mice ( Bettaieb et al, 2015 ; Gwon et al, 2015 ). The anti-diabetic potential of S has been further demonstrated in recent studies, which showed that S could act as a free fatty acid receptor 4 (FFA4) agonist in HT-29 cells and lower plasma glucose levels in diabetic mice ( Xu et al, 2021 ), whereas it suppressed protein tyrosine phosphate 1B (PTP1B), during in silico and in vitro experiments ( Saeed et al, 2021 ). At this point, it should be noted that, to the best of our knowledge, there has not been a related study on the effect of either the A enantiomer or the chirality of A/S on DM/obesity/glucose uptake.…”

Section: Introductionmentioning

confidence: 98%

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

et al. 2022

View full text Add to dashboard Cite

Alkannin, shikonin (A/S) and their derivatives are naturally occurring hydroxynaphthoquinones biosynthesized in some species of the Boraginaceae family. These natural compounds have been extensively investigated for their biological properties over the last 40 years, demonstrating a plethora of activities, such as wound healing, regenerative, anti-inflammatory, antitumor, antimicrobial and antioxidant. This study aims to extend the current knowledge by investigating the effects of various A/S compounds on two model systems, namely on 3T3-L1 pre-adipocytes and the nematode Caenorhabditis elegans. The former constitutes an established in vitro model for investigating anti-obesity and insulin-mimetic properties, while the latter has been widely used as a model organism for studying fat accumulation, lifespan and the anthelmintic potential. A set of chemically well-defined A/S derivatives were screened for their effect on pre-adipocytes to assess cell toxicity, cell morphology, and cell differentiation. The differentiation of pre-adipocytes into mature adipocytes was examined upon treatment with A/S compounds in the presence/absence of insulin, aiming to establish a structure-activity relationship. The majority of A/S compounds induced cell proliferation at sub-micromolar concentrations. The ester derivatives exhibited higher IC50 values, and thus, proved to be less toxic to 3T3-L1 cells. The parent molecules, A and S tested at 1 μM resulted in a truncated differentiation with a reduced number of forming lipids, whereas compounds lacking the side chain hydroxyl group projected higher populations of mature adipocytes. In C. elegans mutant strain SS104, A/S enriched extracts were not able to inhibit the fat accumulation but resulted in a drastic shortage of survival. Thus, the set of A/S compounds were tested at 15 and 60 μg/ml in the wild-type strain N2 for their nematocidal activity, which is of relevance for the discovery of anthelmintic drugs. The most pronounced nematocidal activity was observed for naphthazarin and β,β-dimethyl-acryl-shikonin, followed by isovaleryl-shikonin. The latter 2 A/S esters were identified as the most abundant constituents in the mixture of A/S derivatives isolated from Alkanna tinctoria (L.) Tausch. Taken together, the findings show that the structural variations in the moiety of A/S compounds significantly impact the modulation of their biological activities in both model systems investigated in this study.

show abstract

“…Diabetes is a well-known chronic disease that affects the ability of the human body to convert glucose into energy [1] [2]. In addition to causing blindness and kidney failure, diabetes is a leading cause of heart attacks, strokes, and lower-limb amputations, among other deadly diseases [3].…”

Section: Introductionmentioning

confidence: 99%

Elucidation and Prediction of Molecular Mechanisms and Associated Pathways of the Prostaglandin-endoperoxide Synthase-2 as a Common Key Gene for Diabetes and Cachexia: Bioinformatics Strategies

Saeed

2022

JPRI

View full text Add to dashboard Cite

Cachexia and diabetes both feature severe weight loss as a phenotype, and both diseases share several gene and protein abnormalities. This study investigates the PTGS2 gene as a common key gene for diabetes and cachexia. A variety of biological databases and enrichment approaches were used to explore this gene. Probable genes and substances that could be used to address disease symptoms were identified using STICH, a protein-protein, and protein-drug interactions. It was also established that PTGS2 is strongly linked to the pharmacology of the ibuprofen route of action. These findings and annotations will aid in further research into the therapeutic option of targeting the PTGS2 gene in the treatment of both disorders.

show abstract

Assessment of Antidiabetic Activity of the Shikonin by Allosteric Inhibition of Protein-Tyrosine Phosphatase 1B (PTP1B) Using State of Art: An In Silico and In Vitro Tactics

Cited by 44 publications

References 28 publications

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

Advanced Bioinformatics Tools in the Pharmacokinetic Profiles of Natural and Synthetic Compounds with Anti-Diabetic Activity

Expanding the Biological Properties of Alkannins and Shikonins: Their Impact on Adipogenesis and Life Expectancy in Nematodes

Elucidation and Prediction of Molecular Mechanisms and Associated Pathways of the Prostaglandin-endoperoxide Synthase-2 as a Common Key Gene for Diabetes and Cachexia: Bioinformatics Strategies

Contact Info

Product

Resources

About