# Phytochemical-Induced Metabolic Modulation: Dihydroartemisinin Regulates Cellular Metabolism in Madin-Darby Bovine Kidney Cells

## TL;DR

This study shows how dihydroartemisinin, a plant-based compound, changes metabolism in bovine kidney cells, suggesting it could help treat metabolic diseases.

## Contribution

The study reveals novel insights into how dihydroartemisinin modulates cellular metabolism, particularly through lipid and amino acid pathways.

## Key findings

- DHA treatment caused significant metabolic changes, with 67 baseline metabolites and 32-44 differentially abundant metabolites at low and high doses.
- Impairments in glycerophospholipid, amino acid, and nucleotide metabolism were observed, affecting membrane structure and bioenergetics.
- Lysophosphatidylcholine (18:0) and choline phosphate levels indicated lipid homeostasis changes, alongside imbalances in glutamic acid and proline.

## Abstract

Dihydroartemisinin (DHA) is a bioactive phytopharmaceutical with diverse pharmacological potential, predominantly because of its established antiplasmodial efficacy. Here, we investigated the effects of DHA on metabolic homeostasis in Madin-Darby bovine kidney cells in the context of dose-specific adaptation of metabolism and regulation of biochemistry pathway changes. According to our findings, extensive changes in metabolism were revealed by PCA, accounting for a variability of 59.4% to distinguish contrasting metabolic signatures from normal cells. Metabolomic characterization demonstrated 67 constituting metabolites of baseline cellular processes, while 32 and 44 metabolites have demonstrated differential abundance in low- and high-dose treatments, respectively. Impaired metabolism of glycerophospholipid, amino acid, and nucleotide biosynthesis was reported with implications such as regulation of membrane reorganization, nitrogen metabolism, and cellular bioenergetics. Bioindicators of high-volume lysophosphatidylcholine (18:0) and choline phosphate revealed a lipid homeostatic change, in addition to imbalances in glutamic acid and proline levels. Pathway regulation further modulated ABC transporters and arachidonic acid signaling as implications of systemic phytopharmaceutical-modulated reorganization of metabolism. Hence, the study gives mechanistic insight into DHA-initiated modulation of cellular metabolism in MDBK cells, elucidating its status as a cellular metabolism regulator. Findings confirm the potential of DHA as a phytopharmaceutical in modulating diseases of metabolism, further solidifying its relevance in evidence-based traditional herbal remedies and natural compound therapeutics.