Integration of in silico, in vitro and ex vivo pharmacology to decode the anti-diabetic action of Ficus benghalensis L. bark

Abstract

Background

Traditionally, Ficus benghalensis L. is used to treat metabolic disorders and is also recorded in the Ayurvedic pharmacopeia of India. The present study aimed to evaluate the anti-diabetic property of hydroalcoholic extract/fraction(s) of F. benghalensis L. bark via in silico, in vitro, and ex vivo approach.

Methods

Enzyme inhibitory activity, glucose uptake in rat hemidiaphragm, and glucose permeability, and adsorption assays were performed using in vitro and ex vivo methods as applicable. Further, the PASS was used to identify the probable lead enzyme inhibitors. The presence of predicted enzyme inhibitors was confirmed via the LC-MS. Similarly, the docking of ligands with respective targets was performed using autodock4.0.

Results

Flavonoids rich fraction possessed the highest α-amylase, and α-glucosidase inhibitory activity followed by maximum efficacy for glucose uptake in rat hemidiaphragm. Similarly, the hydroalcoholic extract showed the highest efficacy to inhibit glucose diffusion. Likewise, 3,4-dihydroxybenzoic acid was predicted for the highest pharmacological activity for α-amylase, ursolic acid for PTP1B, and apigenin for α-glucosidase inhibition respectively. The LC-MS analysis also identified the presence of the above hit molecules in the hydroalcoholic extract.

Conclusion

The analogs of 3,4-dihydroxybenzoic acid, apigenin, and ursolic acid could be the choice of lead hits as the α-amylase, α-glucosidase, and PTP1B inhibitors respectively. Additionally, the majority of secondary metabolites from the hydroalcoholic extract of F. benghalensis may be involved in enhancing the glucose uptake to support the process of glycogenesis.

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Data availability

Data will be provided in case of a request.

Abbreviations

AUC:

area under the curves

DNS:

Dinitrosalicylic acid

EC50:

Effective concentration 50

GLUT:

Glucose transporter

IAEC:

Institutional Animal Ethics committee

ICMR-NITM:

Indian Council of Medical Research - National Institute of Traditional Medicine

LC-MS:

Liquid chromatography-mass spectrometry

MF:

Molecular formula

MW:

Molecular weight

Pa:

Pharmacological activity

PASS:

Prediction of Activity Spectra for Substances

Pi:

Pharmacological inactivity

p-NPG:

4-Nitrophenyl-β-D- glucopyranoside

PTP1B:

Protein Tyrosine Phosphatase 1B

RCSB:

Research Collaboratory for Structural Bioinformatics

SMILES:

Simplified molecular-input line-entry system

WHO:

World Health Organization

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Acknowledgments

The authors are thankful to Principal KLE College of Pharmacy Belagavi for providing necessary facilities to complete the work. Pukar Khanal is thankful to Ms. Taaza Duyu (Department of Pharmacology and Toxicology, KLE College of Pharmacy Belagavi) for her assistance during the enzyme inhibitory activity, Rohini S. Kavalapure (Department of Pharmaceutical Chemistry, KLE College of Pharmacy Belagavi) for interpreting LC-MS data, Dr. Manish Wanjari (Regional Ayurveda Research Institute for Drug Development Gwalior-474009, Madhya Pradesh, India) for his suggestion for glucose permeability assay and Dr. Yadu Nandan Dey for his suggestion for drafting this manuscript.

Funding

This work has not received any funds from national and international agencies.

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Correspondence to Pukar Khanal or B. M. Patil.

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Ethical statement

Glucose uptake and permeability assayes were performed after receiving ethical clearance from Institutional animal ethical clearance (IAEC) at KLE College of Pharmacy, Belagavi (resolution no. KLECOP/CPCSEA-Reg, No.221/Po/Re/S/2000/CPCSEA, Res.28–12/10/2019).

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Khanal, P., Patil, B.M. Integration of in silico, in vitro and ex vivo pharmacology to decode the anti-diabetic action of Ficus benghalensis L. bark. J Diabetes Metab Disord (2020). https://doi.org/10.1007/s40200-020-00651-9

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Keywords

  • Apigenin
  • Diabetes mellitus
  • Ficus benghalensis
  • Postprandial hyperglycemia