Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i>
<b>Background:</b> A water extract of the Ayurvedic plant <i>Centella asiatica</i> (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer’s disease and affects dendritic arborization, mitochondrial activity, and oxidative stress...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-12-01
|
| Series: | Pharmaceuticals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1424-8247/18/1/19 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832587709229563904 |
|---|---|
| author | Steven R. Chamberlin Jonathan A. Zweig Cody J. Neff Luke Marney Jaewoo Choi Liping Yang Claudia S. Maier Amala Soumyanath Shannon McWeeney Nora E. Gray |
| author_facet | Steven R. Chamberlin Jonathan A. Zweig Cody J. Neff Luke Marney Jaewoo Choi Liping Yang Claudia S. Maier Amala Soumyanath Shannon McWeeney Nora E. Gray |
| author_sort | Steven R. Chamberlin |
| collection | DOAJ |
| description | <b>Background:</b> A water extract of the Ayurvedic plant <i>Centella asiatica</i> (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer’s disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant’s therapeutic benefit. <b>Methods:</b> Mouse primary cortical neurons were treated with CAW or equivalent concentrations of four TT combined, eight CQA combined, or these twelve compounds combined (TTCQA). Treatment effects on the cell transcriptome (18,491 genes) and metabolome (192 metabolites) relative to vehicle control were evaluated using RNAseq and metabolomic analyses, respectively. <b>Results:</b> Extensive differentially expressed genes (DEGs) were seen with all treatments, as well as evidence of interactions between compounds. Notably, many DEGs seen with TT treatment were not observed in the TTCQA condition, possibly suggesting CQA reduced the effects of TT. Moreover, additional gene activity seen with CAW as compared to TTCQA indicates the presence of additional compounds in CAW that further modulate TTCQA interactions. Weighted Gene Correlation Network Analysis (WGCNA) identified 4 gene co-expression modules altered by treatments that were associated with extracellular matrix organization, fatty acid metabolism, cellular response to stress and stimuli, and immune function. Compound interaction patterns were seen at the eigengene level in these modules. Interestingly, in metabolomics analysis, the TTCQA treatment saw the highest number of changes in individual metabolites (20), followed by CQA (15), then TT (8), and finally CAW (3). WGCNA analysis found two metabolomics modules with significant eigenmetabolite differences for TT and CQA and possible compound interactions at this level. <b>Conclusions:</b> Four gene expression modules and two metabolite modules were altered by the four treatment types applied. This methodology demonstrated the existence of both negative and positive interactions between TT, CQA, and additional compounds found in CAW on the transcriptome and metabolome of mouse primary cortical neurons. |
| format | Article |
| id | doaj-art-5aefe7de557340dd823debb745176d36 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj-art-5aefe7de557340dd823debb745176d362025-01-24T13:45:01ZengMDPI AGPharmaceuticals1424-82472024-12-011811910.3390/ph18010019Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i>Steven R. Chamberlin0Jonathan A. Zweig1Cody J. Neff2Luke Marney3Jaewoo Choi4Liping Yang5Claudia S. Maier6Amala Soumyanath7Shannon McWeeney8Nora E. Gray9Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Neurology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Neurology, Oregon Health & Science University, Portland, OR 97239, USABENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USABENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USABENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USABENFRA Botanical Dietary Supplements Research Center, Oregon Health & Science University, Portland, OR 97239, USADepartment of Neurology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Medical Informatics and Clinical Epidemiology, Oregon Health & Science University, Portland, OR 97239, USADepartment of Neurology, Oregon Health & Science University, Portland, OR 97239, USA<b>Background:</b> A water extract of the Ayurvedic plant <i>Centella asiatica</i> (L.) Urban, family Apiaceae (CAW), improves cognitive function in mouse models of aging and Alzheimer’s disease and affects dendritic arborization, mitochondrial activity, and oxidative stress in mouse primary neurons. Triterpenes (TT) and caffeoylquinic acids (CQA) are constituents associated with these bioactivities of CAW, although little is known about how interactions between these compounds contribute to the plant’s therapeutic benefit. <b>Methods:</b> Mouse primary cortical neurons were treated with CAW or equivalent concentrations of four TT combined, eight CQA combined, or these twelve compounds combined (TTCQA). Treatment effects on the cell transcriptome (18,491 genes) and metabolome (192 metabolites) relative to vehicle control were evaluated using RNAseq and metabolomic analyses, respectively. <b>Results:</b> Extensive differentially expressed genes (DEGs) were seen with all treatments, as well as evidence of interactions between compounds. Notably, many DEGs seen with TT treatment were not observed in the TTCQA condition, possibly suggesting CQA reduced the effects of TT. Moreover, additional gene activity seen with CAW as compared to TTCQA indicates the presence of additional compounds in CAW that further modulate TTCQA interactions. Weighted Gene Correlation Network Analysis (WGCNA) identified 4 gene co-expression modules altered by treatments that were associated with extracellular matrix organization, fatty acid metabolism, cellular response to stress and stimuli, and immune function. Compound interaction patterns were seen at the eigengene level in these modules. Interestingly, in metabolomics analysis, the TTCQA treatment saw the highest number of changes in individual metabolites (20), followed by CQA (15), then TT (8), and finally CAW (3). WGCNA analysis found two metabolomics modules with significant eigenmetabolite differences for TT and CQA and possible compound interactions at this level. <b>Conclusions:</b> Four gene expression modules and two metabolite modules were altered by the four treatment types applied. This methodology demonstrated the existence of both negative and positive interactions between TT, CQA, and additional compounds found in CAW on the transcriptome and metabolome of mouse primary cortical neurons.https://www.mdpi.com/1424-8247/18/1/19<i>Centella asiatica</i>triterpenescaffeoylquinic acidsmouse primary cortical neuronstranscriptomemetabolome |
| spellingShingle | Steven R. Chamberlin Jonathan A. Zweig Cody J. Neff Luke Marney Jaewoo Choi Liping Yang Claudia S. Maier Amala Soumyanath Shannon McWeeney Nora E. Gray Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> Pharmaceuticals <i>Centella asiatica</i> triterpenes caffeoylquinic acids mouse primary cortical neurons transcriptome metabolome |
| title | Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> |
| title_full | Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> |
| title_fullStr | Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> |
| title_full_unstemmed | Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> |
| title_short | Multi-Omics Analysis in Mouse Primary Cortical Neurons Reveals Complex Positive and Negative Biological Interactions Between Constituent Compounds of <i>Centella asiatica</i> |
| title_sort | multi omics analysis in mouse primary cortical neurons reveals complex positive and negative biological interactions between constituent compounds of i centella asiatica i |
| topic | <i>Centella asiatica</i> triterpenes caffeoylquinic acids mouse primary cortical neurons transcriptome metabolome |
| url | https://www.mdpi.com/1424-8247/18/1/19 |
| work_keys_str_mv | AT stevenrchamberlin multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT jonathanazweig multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT codyjneff multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT lukemarney multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT jaewoochoi multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT lipingyang multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT claudiasmaier multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT amalasoumyanath multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT shannonmcweeney multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai AT noraegray multiomicsanalysisinmouseprimarycorticalneuronsrevealscomplexpositiveandnegativebiologicalinteractionsbetweenconstituentcompoundsoficentellaasiaticai |