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Untargeted metabolomics reveals alterations in metabolites of lipid metabolism and immune pathways in the serum of rats after long-term oral administration of Amalaki rasayana

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Abstract

Amalaki rasayana, a traditional preparation, is widely used by Ayurvedic physicians for the treatment of inflammatory conditions, cardiovascular diseases, and cancer. Metabolic alterations induced by Amalaki rasayana intervention are unknown. We investigated the modulations in serum metabolomic profiles in Wistar rats following long-term oral administration of Amalaki rasayana. Global metabolic profiling was performed of the serum of rats administered with either Amalaki rasayana (AR) or ghee + honey (GH) for 18 months and control animals which were left untreated. Amalaki rasayana components were confirmed from AR extract using HR-LCMS analysis. Significant reductions in prostaglandin J2, 11-dehydrothromboxane B2, and higher levels of reduced glutathione and glycitein metabolites were observed in the serum of AR administered rats compared to the control groups. Eleven different metabolites classified as phospholipids, glycerophospholipids, glucoside derivatives, organic acids, and glycosphingolipid were exclusively observed in the AR administered rats. Pathway analysis suggests that altered metabolites in AR administered rats are those associated with different biochemical pathways of arachidonic acid metabolism, fatty acid metabolism, leukotriene metabolism, G-protein mediated events, phospholipid metabolism, and the immune system. Targeted metabolomics confirmed the presence of gallic acid, ellagic acid, and arachidonic acid components in the AR extract. The known activities of these components can be correlated with the altered metabolic profile following long-term AR administration. AR also activates IGF1R-Akt-Foxo3 signaling axis in heart tissues of rats administered with AR. Our study identifies AR components that induce alterations in lipid metabolism and immune pathways in animals which consume AR for an extended period.

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Data availability

Metabolomic data were submitted to the software MetaboLights and can be accessed by anyone using the study ID- MTBLS867.

Abbreviations

AR:

Amalaki rasayana

GH:

Ghee + Honey

HR-LCMS:

High resolution liquid chromatography mass spectrometry

UPLC:

Ultra-performance liquid chromatography

Q-TOF:

Quadrupole-time of flight

HILIC:

Hydrophilic interaction chromatography

RPLC:

Reversed-phase liquid chromatography

ESI:

Electrospray ionization

MW:

Molecular weight

QC:

Quality control

RT:

Retention time

PCA:

Principal component analysis

HMDB:

Human metabolome database

RP-Pos:

Reverse phase-positive

RP-Neg:

Reverse phase-negative

LysoPC:

Lysophosphatidylcholine

12-HHT:

12-Hydroxyheptadecatrienoic acid

CE:

Ceramide

LPA:

Lysophosphatidic acid

PS:

Phosphatidylserine

PGP:

Phosphatidylglycerolphosphate

PPARɣ:

Peroxisome proliferator-activated receptor gamma

GA:

Gallic acid

EA:

Ellagic acid

AA:

Arachidonic acid

TXB2:

11-Dehydrothromboxane B2

GSH:

Glutathione

PDGF:

Platelet-derived growth factor

SMC:

Smooth muscle cell

LTB4:

Leukotriene B4

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Acknowledgements

We thank Director, Rajiv Gandhi Center for Biotechnology for providing the facilities and funding this study.

Funding

We thank Rajiv Gandhi Center for Biotechnology, Trivandrum for funding this study.

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Author notes

  1. Vikas Kumar and A. Aneesh Kumar contributed equally to this work.

Authors and Affiliations

  1. Cardiovascular Diseases and Diabetes Biology, Rajiv Gandhi Centre for Biotechnology (RGCB), Trivandrum, 695014, Kerala, India

    Vikas Kumar, A. Aneesh Kumar, Abdul Jaleel, T. R. Santhosh Kumar & Chandrasekharan C. Kartha

  2. NCIM Research Centre, National Chemical Laboratory (NCL), Pune, Maharashtra, India

    Vinod Joseph

  3. Jawaharlal Nehru Tropical Botanic Garden and Research Institute, Trivandrum, Kerala, India

    Vipin Mohan Dan

  4. Cancer Research Program, Rajiv Gandhi Centre for Biotechnology (RGCB), Trivandrum, Kerala, India

    T. R. Santhosh Kumar

  5. Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India

    Vikas Kumar, A. Aneesh Kumar, Abdul Jaleel & T. R. Santhosh Kumar

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  1. Vikas Kumar
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Contributions

VK, TRSK, and CCK designed and directed the overall project and interpreted the results. VK, AKA, VMD, and VJ performed all the experiments. VK analyzed and drafted the manuscript. CCK revised and edited the manuscript.

Corresponding author

Correspondence to Chandrasekharan C. Kartha.

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All authors declare that there is no conflict of interest.

Ethical approval

All animal experiments were carried out with the approval of the Institutional animal ethics committee (IAEC) in Rajiv Gandhi Center for Biotechnology (RGCB) under the protocol no. IAEC/150/CCK/2012. Animal experiments were conducted by strictly following the rules and regulations of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), Government of India.

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Chemical compound studied in this article

Gallic acid (PubChem CID): 370; Ellagic acid (PubChem CID): 5281855; Arachidonic acid (PubChem CID): 444899.

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Kumar, V., Kumar, A.A., Joseph, V. et al. Untargeted metabolomics reveals alterations in metabolites of lipid metabolism and immune pathways in the serum of rats after long-term oral administration of Amalaki rasayana. Mol Cell Biochem 463, 147–160 (2020). https://doi.org/10.1007/s11010-019-03637-1

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