# Elucidation of Sulforaphane‐Mediated Effects on the Cellular Human Metabolome Using Metabolic Profiling

**Authors:** Nadine Bieß, Hans‐Ulrich Humpf, Matthias Behrens, Andrea Gerdemann

PMC · DOI: 10.1002/mnfr.70373 · 2026-01-16

## TL;DR

This study explores how sulforaphane, a compound from broccoli, affects human cell metabolism, revealing its impact on key metabolic pathways and antioxidant activity.

## Contribution

The paper provides a comprehensive metabolic profiling of sulforaphane's effects on primary metabolic pathways in human cells.

## Key findings

- Sulforaphane affects the tricarboxylic acid cycle, urea cycle, and related amino acids.
- It influences glycolysis, the pentose phosphate pathway, and increases glutathione levels.
- The compound shows a broad impact on primary metabolic pathways, highlighting its bioactive potential.

## Abstract

Sulforaphane (SFN) is an isothiocyanate derived from glucoraphanin, which occurs in broccoli. Several human health‐promoting effects are attributed to the consumption of cruciferous vegetables or food supplements containing SFN. Its described cancer‐preventive, chemoprotective, and antioxidant properties made SFN an increasingly important research topic. The antioxidant properties have previously been connected to stimulation of the Nuclear factor erythroid‐2‐related factor 2 (Nrf2)/Kelch‐like ECH‐associated protein 1 (Keap1) signaling pathway. However, the global effects of SFN on the primary metabolic pathways have yet to be fully unraveled. Therefore metabolic profiling was used to elucidate the effects of SFN on the cellular metabolome. For this purpose, human hepatoblastoma cells (HepG2) were incubated with SFN and the changes of primary metabolite levels were determined by targeted hydrophilic interaction liquid chromatography tandem mass spectrometry (HILIC‐MS/MS) analysis. Metabolic profiling revealed that SFN affects the tricarboxylic acid cycle, the urea cycle and their related amino acids. Furthermore, effects on glycolysis, pentose phosphate pathway and glutathione (GSH) levels were observed. This profound impact on nearly all primary metabolic pathways indicates a high bioactive potential of this natural compound. Especially elevated GSH levels underline the commonly described antioxidant potential of SFN.

Sulforaphane (SFN) is an isothiocyanate derived from broccoli and is related to various health‐promoting effects. By using metabolic profiling on the hepatoblastoma cell line HepG2 several effects on pathways such as TCA cycle, urea cycle and redox metabolism through SFN were identified.

## Linked entities

- **Proteins:** GABPA (GA binding protein transcription factor subunit alpha), KEAP1 (kelch like ECH associated protein 1)
- **Chemicals:** Sulforaphane (PubChem CID 5350), glucoraphanin (PubChem CID 9548634), glutathione (PubChem CID 124886), doxorubicin (PubChem CID 31703)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** KEAP1 (kelch like ECH associated protein 1) [NCBI Gene 9817] {aka INrf2, KLHL19}, NFE2L2 (NFE2 like bZIP transcription factor 2) [NCBI Gene 4780] {aka IMDDHH, NRF2, Nrf-2}
- **Diseases:** hepatoblastoma (MESH:D018197), cancer (MESH:D009369)
- **Chemicals:** pentose phosphate (MESH:D010428), urea (MESH:D014508), tricarboxylic acid (MESH:D014233), isothiocyanate (MESH:C037152), GSH (MESH:D005978), SFN (MESH:C016766), amino acids (MESH:D000596), glucoraphanin (MESH:C119494)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12810221/full.md

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Source: https://tomesphere.com/paper/PMC12810221