How does wormwood affect mice? - briefly
Administration of wormwood extracts to laboratory mice produces dose‑dependent reductions in body weight and food intake, accompanied by hepatic stress indicated by elevated ALT and AST enzymes. High doses also trigger neurobehavioral alterations, such as decreased locomotor activity and increased mortality.
How does wormwood affect mice? - in detail
Wormwood (Artemisia absinthium) exerts a range of physiological and behavioral effects when administered to laboratory mice. Acute exposure to doses of 200–500 mg kg⁻¹ produces rapid onset of tremors, hyperactivity, and ataxia, reflecting central nervous system stimulation by the sesquiterpene lactone absinthin and the monoterpene thujone. Higher concentrations (>600 mg kg⁻¹) lead to convulsions, respiratory depression, and mortality within 30–90 minutes, indicating dose‑dependent neurotoxicity.
Chronic administration (daily oral gavage of 50–150 mg kg⁻¹ for 4–8 weeks) alters metabolic parameters. Studies report:
- Reduced body‑weight gain despite unchanged food intake, suggesting increased basal metabolic rate.
- Elevation of hepatic enzymes (ALT, AST) and histopathological signs of mild steatosis, implicating hepatotoxic stress.
- Decrease in circulating glucose levels and enhanced insulin sensitivity, possibly mediated by flavonoid‑induced activation of AMP‑activated protein kinase.
- Modulation of gut microbiota composition, with increased abundance of Lactobacillus spp. and reduction of Firmicutes, correlating with observed changes in lipid absorption.
Immunological assessments show suppressed splenic lymphocyte proliferation and lowered cytokine production (IL‑2, IFN‑γ) after prolonged exposure, indicating immunosuppressive potential. Conversely, low‑dose treatment (≤25 mg kg⁻¹) has been linked to increased antioxidant enzyme activity (SOD, catalase) and reduced lipid peroxidation in brain tissue, suggesting a hormetic effect at sub‑toxic levels.
Behavioral testing reveals anxiolytic‑like outcomes in elevated plus‑maze trials after 2‑week administration of 30 mg kg⁻¹, whereas higher doses produce anxiogenic responses and impaired spatial memory in Morris water‑maze tasks. These divergent effects align with thujone’s biphasic interaction with GABA_A receptors.
Pharmacokinetic data indicate rapid absorption from the gastrointestinal tract, peak plasma concentrations at 45 minutes, and extensive hepatic metabolism via cytochrome P450 isoforms CYP2C9 and CYP3A4. Elimination half‑life ranges from 1.5 to 2.5 hours, with primary excretion in urine as glucuronide conjugates.
Overall, wormwood demonstrates dose‑dependent neuro‑ and hepatotoxicity, metabolic modulation, immunosuppression at chronic high doses, and potential antioxidant and anxiolytic benefits at low concentrations. Experimental design must therefore balance therapeutic windows against toxicity thresholds to avoid adverse outcomes in murine models.