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Cell-Based Assays in Natural Product-Based Drug Discovery

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Evidence Based Validation of Traditional Medicines

Abstract

Natural products have been crucial and bounteous sources for the discovery of lead compounds and drugs for various therapeutic indications. The intrinsic complexity of the natural products poses several obstacles in the HTS programs. Besides, drug screening in animals is a long-drawn, costly process with many hurdles and low productivity. Cell-based HTS assays on the other hand are excellent means for preliminary screening of drugs of natural origin for numerous therapeutic indications as they help in designing more relevant in vivo pharmacological models to study drugs and thus expedite drug discovery process. In this book chapter, we have discussed a plethora of cell-based HTS assays for drug discovery, employing optical and electrochemical methods of detection and for quantification of cells and information on their proliferation rate, biomarker production, and activation of various signaling pathways. Also, the potential applications of these cell-based assays are discussed briefly for screening of natural products for their anti-inflammatory, anti-diabetic, anti-obesity/hypolipidemic, anti-microbial, anti-mycobacterial, anti-cancer, and anti-viral activities.

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Abbreviations

2DG :

2-deoxy-d-[14C] glucose or 2-deoxy-d- [3H] glucose

2-NBDG :

2-[N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)amino]-2-deoxy-d-glucose

3-O-MG :

3-O-methyl glucose

ABC1 :

ATP-binding cassette transporter A1

AK :

Adenylate kinase

AMPK :

5′-adenosine monophosphate-activated protein kinase

BLV :

Bovine leukemia virus

CAM :

Calcein acetoxymethyl

CFU :

Colony-forming units

CHIKV :

Chikungunya virus

CPE :

Cytopathic effect

FITC :

Fluorescein 5(6)-isothiocyanate

GFPs :

Green fluorescent proteins

GLP-1 :

Glucagon-like peptide-1

GLUT-4 :

Glucose transporter type 4

HCS :

High-content screening

HEK 293 cells :

Human embryonic kidney 293 cells

HTS :

High-throughput screening

IL :

Interleukin

LDH :

Lactate dehydrogenase

MIC :

Minimum inhibitory concentration

MTBH :

Mycobacterium tuberculosis H37Rv

Nrf2 :

Nuclear factor erythroid 2-related factor 2

PPAR γ :

Peroxisome proliferator-activated receptor γ

Rluc :

Renilla luciferase

SGLT2 :

Sodium/glucose cotransporter 2

SREBP1 :

Sterol regulatory element-binding protein 1

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Correspondence to Alka Mukne .

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Mukne, A., Momin, M., Betkar, P., Rane, T., Valecha, S. (2021). Cell-Based Assays in Natural Product-Based Drug Discovery. In: Mandal, S.C., Chakraborty, R., Sen, S. (eds) Evidence Based Validation of Traditional Medicines. Springer, Singapore. https://doi.org/10.1007/978-981-15-8127-4_11

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