Hematological, Biochemical, Histopathological and ¹H-NMR Metabolomics Application in Acute Toxicity Evaluation of Clinacanthus nutans Water Leaf Extract

• Published in: Molecules (Basel, Switzerland) Switzerland), 2018-08, Vol.23 (9), p.2172
• Main Authors: Khoo, Leng Wei, Foong Kow, Audrey Siew, Maulidiani, M, Lee, Ming Tatt, Tan, Chin Ping, Shaari, Khozirah, Tham, Chau Ling, Abas, Faridah
• Format: Article
• Language: English
• Subjects: 1H-NMR metabolomics; Acanthaceae - chemistry; Acute toxicity; Animals; biochemical test; Blood Chemical Analysis; Carbohydrate Metabolism - drug effects; Chronic illnesses; Chronic toxicity; Clinacanthus nutans; Dose-Response Relationship, Drug; Drug dosages; Energy Metabolism - drug effects; Enzymes; Hematology; Herbal medicine; histopathology; Kidneys; Leaves; Liver; Male; medicinal plant; metabolic pathway; Metabolism; Metabolites; Metabolomics; Metabolomics - methods; NMR; Nuclear magnetic resonance; Oral administration; Physiology; Plant extracts; Plant Extracts - administration & dosage; Plant Extracts - chemistry; Plant Extracts - toxicity; Plant Leaves - chemistry; Proton Magnetic Resonance Spectroscopy; Rats; Rats, Sprague-Dawley; Studies; Toxicity; Toxicity testing; Toxicity Tests, Acute - methods; Toxicology; urinary metabolomics; Urine; Urine - chemistry; Water pollution effects
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules23092172

The present study aims for the first time to provide the in vivo acute toxicological profile of the highest dose of (Burm. f.) Lindau water leaf extract according to the Organization for economic co-operation and development (OECD) 423 guidelines through conventional toxicity and advanced proton nuclear magnetic resonance (¹H-NMR) serum and urinary metabolomics evaluation methods. A single dose of 5000 mg/kg bw of water extract was administered to Sprague Dawley rats, and they were observed for 14 days. Conventional toxicity evaluation methods (physical observation, body and organ weight, food and water consumption, hematology, biochemical testing and histopathological analysis) suggested no abnormal toxicity signs. Serum ¹H-NMR metabolome revealed no significant metabolic difference between untreated and treated groups. Urinary ¹H-NMR analysis, on the other hand, revealed alteration in carbohydrate metabolism, energy metabolism and amino acid metabolism in extract-treated rats after 2 h of extract administration, but the metabolic expression collected after 24 h and at Day 5, Day 10 and Day 15 indicated that the extract-treated rats did not accumulate any toxicity biomarkers. Importantly, the outcomes further suggest that single oral administration of up to 5000 mg/kg bw of water leaf extract is safe for consumption.