# Hepatic Sinusoidal Obstruction Syndrome Induced by Pyrrolizidine Alkaloids from Gynura segetum: Mechanisms and Therapeutic Advances

## TL;DR

This review explores how a toxic compound in Gynura segetum causes liver damage and outlines new diagnostic and treatment strategies for the condition.

## Contribution

The paper provides a systematic review of mechanisms, diagnostics, and therapies for pyrrolizidine alkaloid-induced liver injury.

## Key findings

- Pyrrolizidine alkaloids cause liver injury through pyrrole-protein adducts and endothelial cell damage.
- New diagnostic tools like the Nanjing Criteria and Gd-EOB-DTPA MRI improve HSOS detection and prognosis.
- Therapies now include anticoagulation, TIPS, and autophagy modulation, moving beyond supportive care.

## Abstract

The traditional Chinese medicinal herb Gynura segetum is increasingly recognized for its hepatotoxic potential, primarily attributed to its pyrrolizidine alkaloid (PA) content. PAs are a leading cause of herb-induced liver injury (HILI) in China and are strongly linked to hepatic sinusoidal obstruction syndrome (HSOS). This review systematically summarizes the pathogenesis, diagnostic advancements, and therapeutic strategies for PA-induced HSOS. Molecular mechanisms of PA metabolism are detailed, encompassing cytochrome P450-mediated bioactivation and the subsequent formation of pyrrole-protein adducts, which trigger sinusoidal endothelial cell injury and hepatocyte apoptosis. Advances in diagnostic criteria, including the Nanjing Criteria and the Roussel Uclaf Causality Assessment Method (RUCAM)-integrated Drum Tower Severity Scoring System, are discussed. Furthermore, emerging biomarkers, such as circulating microRNAs and pyrrole-protein adducts, are examined. Imaging modalities, such as contrast-enhanced computed tomography (CT) and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) magnetic resonance imaging (MRI), have evolved from descriptive tools into quantitative and prognostic instruments. Therapeutic approaches have evolved from supportive care to precision interventions, including anticoagulation, transjugular intrahepatic portosystemic shunt (TIPS), and autophagy-modulating agents. A comprehensive literature review, utilizing databases such as PubMed and Web of Science, was conducted to summarize progress since the introduction of the “Nanjing Guidelines”. Ultimately, this review underscores the critical need for integrated diagnostic and therapeutic frameworks, alongside enhanced public awareness and regulatory oversight, to effectively mitigate PA-related liver injury.