Metabolic exploration of the developmental abnormalities and neurotoxicity of Esculentoside B, the main toxic factor in Phytolaccae radix.

P: radix is a perennial herb, and its extracts have various biological properties that make it a potential candidate for the treatment of tumors, edema, and lymphatic stasis. However, the main factor contributing to its toxicity are not clear. Here, we used a zebrafish toxicological model to study the main toxicity factor of P. radix and explore the potential mechanisms involved. The results revealed that Esculentoside B was the major toxic factor of P. radix. Exposure of zebrafish larvae to Esculentoside B caused developmental abnormalities, neurotoxicity and altered locomotor behavior. The combination of AChE activity and the expression levels of genes relevant to CNS development demonstrated that Esculentoside B is neurotoxic to zebrafish larvae, impairs their CNS development, and that AChE may be a toxic target of Esculentoside B. Metabolomic analysis has revealed that Esculentoside B exposure can disrupt D-Amino acid metabolism, protein export, autophagy, and mTOR signaling pathways in zebrafish larvae. These findings provide insights into the molecular mechanisms underlying EsB-induced neurotoxicity in zebrafish, which can facilitate further research and development of P. radix for safe consumption.

Metabolomic navigated Citrus waste repurposing to restore amino acids disorder in neural lesion.

The fruit juice food industry produces huge waste annually, mainly Citrus peel and seeds. We investigated their chemical composition using hydrophilic interaction chromatography (HILIC-) and reverse phase liquid chromatography tandem mass spectrometry (RPLC-MS/MS), revealing 277 compounds, mainly containing flavonoids and limonoids. As the primary representative component in Citrus waste, limonin was selected to be explored new bio-functions. We applied Zebrafish larvae to study the metabolomic response invoked by limonin. The differential metabolites (DMs) varied depending on the exposing concentration of limonin. Enrichment analysis indicated that the identified DMs related to inflammation and neurologic disorders, including epilepsy which were newly discovered for limonoids and Citrus waste. Limonin was found to restore amino acids disorder to take neuroprotection against epilepsy. Our findings provided a new bio-function and purpose for Citrus waste and limonoids. Also, we demonstrated a concise case to repurpose food waste for new applications under metabolome investigation.

Metabolomics Mechanism and Lignin Response to Laxogenin C, a Natural Regulator of Plants Growth.

Laxogenin C (LGC) is a natural spirostanol deriving from plant hormone which has shown growing regulation similar to those of brassinosteroids. In the present study, LGC showed a promoting effect on tomato seed germination and seedling growth in a dose-dependent manner. We applied LC-MS/MS to investigate metabolome variations in the tomato treated with LGC, which revealed 10 differential metabolites (DMs) related to KEGG metabolites, associated with low and high doses of LGC. Enrichment and pathway mapping based on the KEGG database indicated that LGC regulated expressions of 2-hydroxycinnamic acid and l-phenylalanine to interfere with phenylalanine metabolism and phenylpropanoids biosynthesis. The two pathways are closely related to plant growth and lignin formation. In our further phenotypic verification, LGC was confirmed to affect seedling lignification and related phenylpropanoids, trans-ferulic acid and l-phenylalanine levels. These findings provided a metabolomic aspect on the plant hormone derivates and revealed the affected metabolites. Elucidating their regulation mechanisms can contribute to the development of sustainable agriculture. Further studies on agrichemical development would provide eco-friendly and efficient regulators for plant growth control and quality improvement.