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Integrated network pharmacology approach shows a potential role of Ginseng catechins and ginsenosides in modulating protein aggregation in Amyotrophic Lateral Sclerosis

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Abstract

Amyotrophic lateral Sclerosis is an incurable, progressive neurodegenerative motor neuron disease. The disease is characterized by protein aggregates. The symptoms include weakness, denervation of muscles, atrophy and progressive paralysis of bulbar and respiratory muscles and dysphagia. Various secondary metabolites are evaluated for their ability to improve symptoms in ALS. Ginseng has been traditionally used for treating several neurodegenerative diseases. Several studies using model systems have shown a potential role of Ginseng catechins and Ginsenosides in clearing protein aggregation associated with ALS. We focus on Network pharmacology approach to understand the effect of Ginseng catechins or ginsenosides on protein aggregation associated with ALS. A catechin/ginsenoside-protein interaction network was generated and the pathways obtained were compared with those obtained from transcriptomic datasets of ALS from GEO database. Knock out of MAPK14, AKT and GSK from Catechin and BACE 1 from ginsenoside modulated pathways inhibited protein aggregation. Catechins and ginsenosides have potential as therapeutic agents in the management of ALS.

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Abbreviations

ALS:

Amyotrophic lateral sclerosis

GEO:

Gene expression omnibus

MAPK14:

Mitogen-activated protein kinase 14

GSK:

Glycogen synthase kinase

BACE1:

Beta-secretase 1

SNP:

Single nucleotide polymorphism

SOD1:

Super oxide dismutase 1

C9orf72:

Chromosome 9 open reading frame 72

FUS:

Fused in sarcoma

TDP-43:

Tar DNA binding protein 43

HAT:

Histone acetyltransferase

HADC:

Histone deacetylases

HD:

Huntington’s disease

PD:

Parkinson’s disease

DMSO:

Dimethyl sulfoxide

GREIN:

GEO RNA-seq experiments interactive navigator

GSEA:

Gene set enrichment analysis

STITCH:

Search tool for interactions of chemicals

E-YFP:

Enhanced yellow florescent protein

URA-YNB:

Uracil–yeast nitrogen base

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Acknowledgements

A sincere thanks to Sri Sathya Sai Institute of Higher Learning for providing free and valuable education. We acknowledge the grant support from the Department of Biotechnology-Basic Research in Modern Biology DBT (BRB): BT/PR8226/BRB/10/1224/2013, Department of Science and Technology-The Science and Engineering Research Board–Extra Mural Research DST-SERB-EMR: EMR/2017/005381, Department of Biotechnology- Bioinformatics Infrastructure facility DBT-BIF: BT/BI/25/063/2012, Department of Science and Technology- Fund for improvement of Science and Technology Infrastructure in Higher Educational Institutions (DST-FIST): SR/FST/LSI-616/2014, University Grants Commission-Special Assistance Program (UGC-SAP III): F.3-19 /2018/DRS-III(SAP-II) for infrastructure funding.

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  1. Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute of Higher Learning, Prasanthi Nilayam, Anantapur, Andhra Pradesh, 515134, India

    R. Sai Swaroop, Sai Sanwid Pradhan, V. M. Datta Darshan, Kanikaram Sai Phalguna & Venketesh Sivaramakrishnan

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Contributions

The study was contributed by S.S.R. S.S.P helped in standardizing and processing several bio-informatic pipelines used for the study. D.D.V.M and K.S.P assisted in performing the yeast experiments. S.V conceptualized the entire idea, interpreted the results, and played a major role in the preparation of the manuscript.

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Correspondence to R. Sai Swaroop or Venketesh Sivaramakrishnan.

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Swaroop, R.S., Pradhan, S.S., Darshan, V.M.D. et al. Integrated network pharmacology approach shows a potential role of Ginseng catechins and ginsenosides in modulating protein aggregation in Amyotrophic Lateral Sclerosis. 3 Biotech 12, 333 (2022). https://doi.org/10.1007/s13205-022-03401-1

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