Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study – Analysis of Centella asiatica Extract Associates Di-Caffeoylquinic Acids with Protection against Amyloid-β Toxicity in an MC65 cell model

Armando Alcazar-Magana
ORCID logo ,
Ashish Vaswani
,
Kevin S. Brown
ORCID logo ,
Yuan Jiang
ORCID logo ,
Md Nure Alam
,
Maya Caruso
,
Parnian Lak
,
Paul Cheong
,
Nora E. Gray
,
Joseph F. Quinn
ORCID logo ,
Amala Soumyanath
ORCID logo ,
Jan F. Stevens
ORCID logo ,
Claudia S. Maier
*
Version 1 : Received: 3 January 2024 / Approved: 3 January 2024 / Online: 3 January 2024 (09:30:22 CET)

A peer-reviewed article of this Preprint also exists.

Alcázar Magaña, A.; Vaswani, A.; Brown, K.S.; Jiang, Y.; Alam, M.N.; Caruso, M.; Lak, P.; Cheong, P.; Gray, N.E.; Quinn, J.F.; Soumyanath, A.; Stevens, J.F.; Maier, C.S. Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of C. asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-β Toxicity. Molecules 2024, 29, 838. Alcázar Magaña, A.; Vaswani, A.; Brown, K.S.; Jiang, Y.; Alam, M.N.; Caruso, M.; Lak, P.; Cheong, P.; Gray, N.E.; Quinn, J.F.; Soumyanath, A.; Stevens, J.F.; Maier, C.S. Integrating High-Resolution Mass Spectral Data, Bioassays and Computational Models to Annotate Bioactives in Botanical Extracts: Case Study Analysis of C. asiatica Extract Associates Dicaffeoylquinic Acids with Protection against Amyloid-β Toxicity. Molecules 2024, 29, 838.

Abstract

Rapid screening of botanical extracts for the discovery of bioactive natural products was performed using a fractionation approach in conjunction with flow-injection high-resolution mass spectrometry for obtaining chemical fingerprints of each fraction, enabling the correlation of the relative abundance of molecular features (representing individual phytochemicals) with the read-outs of bioassays. We applied this strategy for discovering and identifying constituents of Centella asiatica (C. asiatica) that protect against Aβ cytotoxicity in vitro. C. asiatica has been associated with improving mental health and cognitive function, with potential use in Alzheimer’s disease. Human neuroblastoma MC65 cells were exposed to subfractions of an aqueous extract of C. asiatica to evaluate the protective benefit derived from these subfractions against amyloid β-cytotoxicity. The % viability score of the cells exposed to each subfraction was used in conjunction with the intensity of the molecular features in two computational models, namely Elastic Net and selectivity ratio, to determine the relationship of the peak intensity of molecular features and % viability. Finally, the correlation of mass spectral features with MC65 protection and their abundance in different sub-fractions were visualized using GNPS molecular networking. Both computational methods unequivocally identified dicaffeoylquinic acids as providing strong protection against Aβ-toxicity in MC65 cells, in agreement with the protective effects observed for these compounds in previous preclinical model studies.

Keywords

Centella asiatica; bioactives; bioassays; computational methods; Elastic Net; spectral networks; GNPS

Subject

Biology and Life Sciences, Life Sciences

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.