INVESTIGATION OF CHRONIC TOXICITY PROPERTIES IN THE AQUEOUS AND ALCOHOLIC EXTRACTS OF FERULA MOSCHATA

Abstract

Background: Children Background: Ferula moschata (Reinsch.) Koso-Pol., known locally as "moshk koren" or "sumbul," is a perennial herb endemic to Central Asia, traditionally used in Uzbek and Tibetan medicine for its purported neurotonic, sedative, and antispasmodic properties. Despite its long-standing ethnobotanical use, a systematic toxicological profile, particularly concerning its long-term administration, is lacking. This study aims to evaluate the chronic toxicity of standardized aqueous and alcoholic extracts of Ferula moschata roots in a laboratory animal model.

Methods: A 90-day subchronic oral toxicity study was conducted in accordance with OECD Guideline 408. Wistar rats (n=120, equal sexes) were divided into four groups: Control (distilled water), Low-Dose (100 mg/kg), Medium-Dose (300 mg/kg), and High-Dose (1000 mg/kg) for both aqueous and alcoholic extracts. Body weight, feed, and water consumption were monitored weekly. Hematological parameters (complete blood count), biochemical parameters (ALT, AST, ALP, creatinine, urea, total protein, albumin), and urinalysis were assessed at 30, 60, and 90 days. At termination, gross pathological examination and histopathological evaluation of major organs (liver, kidneys, heart, spleen, lungs, brain) were performed.

Results: No mortality was observed in any group. The alcoholic extract at 1000 mg/kg caused a statistically significant (p<0.05) reduction in body weight gain and a transient increase in ALT and AST levels at the 60-day mark, which normalized by day 90, suggesting adaptive hepatocyte response. Histopathological analysis revealed mild hepatic centrilobular congestion and minimal hydropic degeneration in the high-dose alcoholic group. The aqueous extract showed no significant adverse effects on hematological, biochemical, or histopathological parameters at all doses tested. The No-Observed-Adverse-Effect-Level (NOAEL) was determined to be 300 mg/kg/day for the alcoholic extract and greater than 1000 mg/kg/day for the aqueous extract.

Conclusion: The aqueous extract of Ferula moschata demonstrates a wide margin of safety under the conditions of this study, supporting its traditional use. The alcoholic extract, while showing higher bioactivity, also presents a potential for mild, reversible hepatotoxicity at very high doses. Further investigation into the specific hepatotoxic compounds within the alcoholic fraction is warranted.

KEYWORDS:

Ferula moschata, Chronic Toxicity, Sumbul, Uzbek Medicinal Plants, Hepatotoxicity, NOAEL, OECD Guideline 408, Phytopharmacology.