Analysis of the mechanism of curcumin against osteoarthritis using metabolomics and transcriptomics

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Abstract

Curcumin, a polyphenolic compound derived from the turmeric plant ( Curcuma longa), has been extensively studied for its anti-inflammatory and anti-proliferative properties. The safety and efficacy of curcumin have been thoroughly validated. Nevertheless, the underlying mechanism for treating osteoarthritis remains ambiguous. This study aims to reveal the potential mechanism of curcumin in treating osteoarthritis by using metabolomics and transcriptomics. Firstly, we validated the effect of curcumin on inflammatory factors in human articular chondrocytes. Secondly, we explored the cellular metabolism mechanism of curcumin against osteoarthritis using cell metabolomics. Thirdly, we assessed the differences in gene expression of human articular chondrocytes through transcriptomics. Lastly, to evaluate the essential targets and elucidate the potential mechanism underlying the therapeutic effects of curcumin in osteoarthritis, we conducted a screening of the proteins within the shared pathway of metabolomics and transcriptomics. Our results demonstrated that curcumin significantly decreased the levels of inflammatory markers, such as IL-β, IL-6, and TNF-α, in human articular chondrocytes. Cell metabolomics identified 106 differential metabolites, including beta-aminopropionitrile, 3-amino-2-piperidone, pyrrole-2-carboxaldehyde, and various other components. The transcriptomic analysis yielded 1050 differential mRNAs. Enrichment analysis showed that the differential metabolites and mRNAs were significantly enriched in seven pathways, including glycine, serine, and threonine metabolism; pentose and glucuronate interconversions; glycerolipid metabolism; histidine metabolism; mucin-type o-glycan biosynthesis; inositol phosphate metabolism; and cysteine and methionine metabolism. A total of 23 key targets were identified to be involved in these pathways. We speculate that curcumin may alleviate osteoarthritis by targeting key proteins involved in glycine, serine, and threonine metabolism; inhibiting pyruvate production; and modulating glycolysis.

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edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

Mark Robinson, Davis J. McCarthy, Gordon K. Smyth (2009)

Summary: It is expected that emerging digital gene expression (DGE) technologies will overtake microarray technologies in the near future for many functional genomics applications. One of the fundamental data analysis tasks, especially for gene expression studies, involves determining whether there is evidence that counts for a transcript or exon are significantly different across experimental conditions. edgeR is a Bioconductor software package for examining differential expression of replicated count data. An overdispersed Poisson model is used to account for both biological and technical variability. Empirical Bayes methods are used to moderate the degree of overdispersion across transcripts, improving the reliability of inference. The methodology can be used even with the most minimal levels of replication, provided at least one phenotype or experimental condition is replicated. The software may have other applications beyond sequencing data, such as proteome peptide count data. Availability: The package is freely available under the LGPL licence from the Bioconductor web site (http://bioconductor.org). Contact: mrobinson@wehi.edu.au

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StringTie enables improved reconstruction of a transcriptome from RNA-seq reads.

Mihaela Pertea, Geo M Pertea, Corina M Antonescu … (2016)

Methods used to sequence the transcriptome often produce more than 200 million short sequences. We introduce StringTie, a computational method that applies a network flow algorithm originally developed in optimization theory, together with optional de novo assembly, to assemble these complex data sets into transcripts. When used to analyze both simulated and real data sets, StringTie produces more complete and accurate reconstructions of genes and better estimates of expression levels, compared with other leading transcript assembly programs including Cufflinks, IsoLasso, Scripture and Traph. For example, on 90 million reads from human blood, StringTie correctly assembled 10,990 transcripts, whereas the next best assembly was of 7,187 transcripts by Cufflinks, which is a 53% increase in transcripts assembled. On a simulated data set, StringTie correctly assembled 7,559 transcripts, which is 20% more than the 6,310 assembled by Cufflinks. As well as producing a more complete transcriptome assembly, StringTie runs faster on all data sets tested to date compared with other assembly software, including Cufflinks.

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MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights

Zhiqiang Pang, Jasmine Chong, Guangyan Zhou … (2021)

Since its first release over a decade ago, the MetaboAnalyst web-based platform has become widely used for comprehensive metabolomics data analysis and interpretation. Here we introduce MetaboAnalyst version 5.0, aiming to narrow the gap from raw data to functional insights for global metabolomics based on high-resolution mass spectrometry (HRMS). Three modules have been developed to help achieve this goal, including: (i) a LC–MS Spectra Processing module which offers an easy-to-use pipeline that can perform automated parameter optimization and resumable analysis to significantly lower the barriers to LC-MS1 spectra processing; (ii) a Functional Analysis module which expands the previous MS Peaks to Pathways module to allow users to intuitively select any peak groups of interest and evaluate their enrichment of potential functions as defined by metabolic pathways and metabolite sets; (iii) a Functional Meta-Analysis module to combine multiple global metabolomics datasets obtained under complementary conditions or from similar studies to arrive at comprehensive functional insights. There are many other new functions including weighted joint-pathway analysis, data-driven network analysis, batch effect correction, merging technical replicates, improved compound name matching, etc. The web interface, graphics and underlying codebase have also been refactored to improve performance and user experience. At the end of an analysis session, users can now easily switch to other compatible modules for a more streamlined data analysis. MetaboAnalyst 5.0 is freely available at https://www.metaboanalyst.ca . Graphical Abstract From raw data to statistical and functional insights using MetaboAnalyst 5.0.

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Author and article information

Contributors

Qinghu He: hqh19651111@dingtalk.com , hqh19651111@163.com

Journal

Journal ID (nlm-ta): Naunyn Schmiedebergs Arch Pharmacol

Journal ID (iso-abbrev): Naunyn Schmiedebergs Arch Pharmacol

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0028-1298

ISSN (Electronic): 1432-1912

Publication date (Electronic): 8 November 2023

Publication date PMC-release: 8 November 2023

Publication date (Print): 2024

Volume: 397

Issue: 5

Pages: 3313-3329

Affiliations

[1 ]Department of Rehabilitation and Healthcare, Hunan University of Medicine, ( https://ror.org/05htk5m33) Huaihua, 418000 Hunan China

[2 ]College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, ( https://ror.org/02my3bx32) Changsha, 410208 Hunan China

Article

Publisher ID: 2785

DOI: 10.1007/s00210-023-02785-y

PMC ID: 11074044

PubMed ID: 37938371

SO-VID: eab1e2f4-6a4e-43f4-bd2f-8a2c1e0731f0

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 August 2023

Date accepted : 12 October 2023

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: curcumin,osteoarthritis,uplc-q-tof/ms,transcriptomics,metabolomics

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ScienceOpen disciplines: Pharmacology & Pharmaceutical medicine

Keywords: curcumin, osteoarthritis, uplc-q-tof/ms, transcriptomics, metabolomics

Analysis of the mechanism of curcumin against osteoarthritis using metabolomics and transcriptomics

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RNA drug delivery

Most cited references 83

edgeR: a Bioconductor package for differential expression analysis of digital gene expression data

StringTie enables improved reconstruction of a transcriptome from RNA-seq reads.

MetaboAnalyst 5.0: narrowing the gap between raw spectra and functional insights

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