Sub-chronic Oral Toxicity of a Water-Soluble Extract of <i>Centella asiatica</i>(Centell-S) in Wistar Rats (Tables)

<b>Background: </b>Centell-S is a standardized water-soluble extract of <i>Centella asiatica</i> containing more than 80% w/w triterpenoid glycosides. Madecassoside and asiaticoside are two major bioactive components of the extract. To develop Centell-S as an herbal medicinal product, it was tested for sub-chronic oral toxicity (OECD GLP 408), as required by Thai FDA guidelines.<br><br><b>Methods: </b>100 Wistar rats were orally administered vehicle control or 50, 200, or 800 mg/kg/day Centell-S for 90 days. Clinical observations, health examinations, clinical biochemistry, and anatomical pathology tests were conducted to determine the possible toxicity and no observed adverse effect level (NOAEL) of Centell-S.<br><br><b>Results</b><b>: </b>During the 90-day administration period, 50, 200, and 800 mg/kg/day Centell-S did not produce any animal mortalities. No clinical signs of toxicity were observed. There were significant differences in some hematological parameters among the Centell-S dose groups. Both male and female rats had increased total white blood cell and monocyte numbers compared with the control group, but these were recovered after the discontinuation of Centell-S at the end of study for two weeks.<br><br><b>Conclusions</b><b>: </b>The NOAEL of Centell-S was determined to be 800 mg/kg/day under the experimental conditions of the OECD GLP No. 408 Repeated Dose 90-day Oral Toxicity Study in Rodents. These results could be beneficial for the further phytopharmaceutical product development of Centell-S for clinical applications, especially as a treatment for neurodegenerative diseases.