Organ toxicity of Paris polyphylla in mice and the underlying hepatotoxic mechanism uncovered by an integrated network toxicology and transcriptomics.

Paris polyphylla is a traditional Chinese medicinal herb commonly used in herbal medicine formulations to treat pain, infections, snake bites, and injuries. While this plant has shown promising anti-tumor properties in recent research, scientists have discovered it may cause organ damage at certain doses. Researchers compared cultivated and wild varieties of two types of Paris polyphylla to understand their toxic effects on mice. They found that wild varieties contained higher levels of active compounds than cultivated ones. When mice received doses exceeding 1.95 g/kg body weight for extended periods, they showed signs of liver and heart damage, including increased liver enzyme levels and inflammation. Wild varieties caused more severe organ damage than cultivated varieties. The study focused particularly on liver toxicity, revealing that the herb disrupts normal liver cell function by damaging mitochondria (the cell's energy producers), triggering inflammation, and causing liver cells to die prematurely. These effects appear linked to specific molecular pathways involving proteins called STAT3 and BNIP3. The maximum safe single dose was found to be below 80 g/kg body weight. This research is important because it helps establish safety guidelines for using Paris polyphylla in herbal medicine. Patients using products containing this herb should be aware of potential liver and heart effects, especially with prolonged use or higher doses. If you're considering herbal medicine as part of your integrative treatment plan, consult with a qualified practitioner trained in traditional Chinese medicine safety protocols.

This toxicology study compared cultivated and wild varieties of Paris polyphylla Smith var. yunnanensis (PY) and var. chinensis (PC) using UPLC-MS/MS analysis, murine acute and subchronic toxicity models, network toxicology, and transcriptomics. Wild varieties demonstrated higher active compound concentrations than cultivated specimens. Maximum tolerated dose exceeded 80 g/kg body weight acutely; however, subchronic administration above 1.95 g/kg body weight produced significant hepatotoxicity and cardiotoxicity, evidenced by elevated liver enzymes and cardiac biomarkers with corresponding histopathological inflammation. Wild varieties induced more severe organ damage. Mechanistic investigation of cultivated PY revealed hepatotoxicity mediated through mitochondrial dysfunction, aberrant mitochondrial autophagy via STAT3/BNIP3 axis activation, hepatocyte apoptosis (Bcl-2 dysregulation), and inflammatory pathway stimulation. Findings were validated through Western blotting, TUNEL assay, and transmission electron microscopy. This integrated approach establishes safety parameters for clinical Paris polyphylla utilization and highlights potential herb-drug interactions requiring monitoring of hepatic function in patients receiving chronic therapy with PY-containing formulations.