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

Diabetes mellitus is a multifactorial disease that affects both developing and developed countries and is a major public health concern. Many synthetic drugs are available in the market, which counteracts the associated pathologies. However, due to the propensity of side effects, there is an unmet need for the investigation of safe and effective drugs. This research aims to find a novel phytoconstituent having diminished action on blood glucose levels with the least side effects. Shikonin is a naturally occurring naphthoquinone dying pigment obtained by the roots of the Boraginaceae family. Besides its use as pigments, it can be used as an antimicrobial, anti-inflammatory, and anti-tumor agent. This research aimed to hypothesize the physicochemical and phytochemical properties of Shikonin’s in silico interaction with protein tyrosine phosphate 1B, as well as it’s in vitro studies, in order to determine its potential anti-diabetic impact. To do so, molecular docking experiments with target proteins were conducted to assess their anti-diabetic ability. Analyzing associations with corresponding amino acids revealed the significant molecular interactions between Shikonin and diabetes-related target proteins. In silico pharmacokinetics and toxicity profile of Shikonin using ADMET Descriptor, Toxicity Prediction, and Calculate Molecular Properties tools from Biovia Discovery Studio v4.5. Filter by Lipinski and Veber Rule’s module from Biovia Discovery Studio v4.5 was applied to assess the drug-likeness of Shikonin. The in vitro studies exposed that Shikonin shows an inhibitory potential against the PTP1B with an IC50 value of 15.51 µM. The kinetics studies revealed that it has a competitive inhibitory effect (Ki = 7.5 M) on the enzyme system, which could be useful in the production of preventive and therapeutic agents. The findings of this research suggested that the Shikonin could be used as an anti-diabetic agent and can be used as a novel source for drug delivery.

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Pengukuran Total Fenolik, Flavonoid, Aktivitas Antioksidan dan Antidiabetes Ekstrak Etil Asetat Daun Katemas (Euphorbia heterophylla, L.) Secara In Vitro dan In Silico Melalui Inhibisi Enzim α-Glukosidase

ALCHEMY Jurnal Penelitian Kimia ◽

10.20961/alchemy.16.2.40087.240-249 ◽

2020 ◽

Vol 16 (2) ◽

pp. 240

Author(s):

Rahmiwati Hilma ◽

Netti Gustina ◽

Jufrizal Syahri

Keyword(s):

Antioxidant Activity ◽

Molecular Docking ◽

Ethyl Acetate ◽

In Silico ◽

Ethyl Acetate Extract ◽

Dry Weight ◽

Antidiabetic Activity ◽

Total Phenolic ◽

Discovery Studio

Tujuan dari penelitian ini adalah untuk mengetahui aktivitas antioksidan dan antidiabetes ekstrak etil asetat daun katemas (Euphorbia heterophylla L.) secara in vitro dan in silico melalui inhibisi terhadap enzim α-glukosidase. Pada penelitian ini ekstraksi sampel dilakukan menggunakan maserasi bertingkat, dimulai dengan n-heksana, selanjutnya dengan etil asetat. Ekstrak etil asetat yang didapatkan dilakukan pengujian kuantitiatif total fenolik dan flavonoid. Uji aktivitas antioksidan terhadap ekstrak dilakukan menggunakan metode DPPH. Uji aktivitas antidiabetes terhadap ekstrak dilakukan secara in vitro dan in silico melalui inhibisi terhadap enzim α-glukosidase menggunakan akarbose sebagai standar. Uji aktivitas antidiabetes terhadap kandungan senyawa bioaktif ekstrak secara in silico atau molecular docking menggunakan software Discovery Studio 4.1. Hasil penelitian menunjukkan bahwa nilai total fenolik dari ekstrak adalah 4,24 mg GAE/g berat kering dan nilai flavonoid total adalah: 3,22 mg KE/g berat kering. Hasil uji aktivitas antioksidan ekstrak didapatkan nilai IC50 sebesar 37,56 µg/mL, digolongkan sebagai aktivitas antioksidan yang sangat kuat. Hasil uji aktivitas antidiabetes secara in vitro didapatkan nilai IC50 sebesar 138,63 µg/mL. Hasil molecular docking memperlihatkan bahwa senyawasenyawa aktif yang terdapat didalam ekstrak mampu membentuk ikatan hidrogen antara ligan dengan reseptor, tapi lebih sedikit jika dibandingkan dengan akarbose.Measurement of Total Phenolic, Flavonoids, Antioxidant and Antidiabetic Activity of Catemas Leaf Ethyl Acetate Extract (Euphorbia heterophylla L.) by In Vitro and In Silico through Enzim α-Glucosidase Inhibition. This study aims to determine the antidiabetic activity of katemas (Euphorbia heterophylla L.) ethyl acetate extract in vitro and in silico through inhibition of the αglucosidase enzyme. In this study, the sample extraction was carried out by multilevel maceration, starting with n-hexane, then with ethyl acetate. The ethyl acetate extract obtained was quantitatively tested by total phenolic and flavonoids. The antioxidant activity of the extract was tested using the DPPH method. The antidiabetic activity of the extract was examined through inhibiting the enzyme αglucosidase in vitro using a microplate reader and in silico (molecular docking) using Discovery Studio 4.1 software. The results showed that the total phenolic value of the extract was 4.24 mg GAE/g of dry weight, and the total flavonoid value was 3.22 mg KE/g of dry weight. Antioxidant activity test obtained IC50 of 37,56 µg/mL, classified as verry strong antioxidant. The in vitro antidiabetic test examined that IC50 is 138.63 µg/mL. The results of molecular docking showed that the active compounds in the extracts are able to form hydrogen bonds between ligand and receptor; however, the amount was less than the hydrogen bonds formed by acarbose.

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Role of 4-O Galloylchlorogenic Acid in Lung Cancer- An Insilico Approach

International Journal of Pharmaceutical and Clinical Research ◽

10.25258/ijpcr.v9i5.8595 ◽

2017 ◽

Vol 9 (5) ◽

Author(s):

Jaynthy C. ◽

N. Premjanu ◽

Abhinav Srivastava

Keyword(s):

Lung Cancer ◽

Cell Proliferation ◽

In Silico ◽

Computational Study ◽

Regulation Mechanism ◽

Down Regulation ◽

Fruit Extract ◽

In Vitro Techniques ◽

Discovery Studio

Cancer is a major disease with millions of patients diagnosed each year with high mortality around the world. Various studies are still going on to study the further mechanisms and pathways of the cancer cell proliferation. Fucosylation is one of the most important oligosaccharide modifications involved in cancer and inflammation. In cancer development increased core fucosylation by FUT8 play an important role in cell proliferation. Down regulation of FUT8 expression may help cure lung cancer. Therefore the computational study based on the down regulation mechanism of FUT8 was mechanised. Sapota fruit extract, containing 4-Ogalloylchlorogenic acid was used as the inhibitor against FUT-8 as target and docking was performed using in-silico tool, Accelrys Discovery Studio. There were several conformations of the docked result, and conformation 1 showed 80% dock score between the ligand and the target. Further the amino acids of the inhibitor involved in docking were studied using another tool, Ligplot. Thus, in-silico analysis based on drug designing parameters shows that the fruit extract can be studied further using in-vitro techniques to know its pharmacokinetics.

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