Evaluation of the chronic oral toxicity of the classical ancient prescription Kai-Xin-San.

ETHNOPHARMACOLOGICAL RELEVANCE

The Kai-Xin-San (KXS), as an ancient classic prescription, has been used for the treatment of amnesia for thousands of years. Modern clinical and non-clinical pharmacological studies have found that it has significant therapeutic effects on dementia and depression, but there are relatively few studies on its safety.

AIM OF THE STUDY

Subacute and chronic toxicity studies were conducted to investigate the symptoms, severity, target organs, development and recovery of toxic reactions, as well as the toxic dose. These studies provide technical data for ensuring the safety of KXS.

MATERIALS AND METHODS

In the sub-acute toxicity study, rats were orally administered KXS at doses of 0.80, 1.61, 3.22, and 6.43 g/kg body weight for a duration of 4 weeks. In the chronic toxicity study, rats were orally administered KXS at doses of 0.27, 0.81, and 2.43 g/kg body weight for a duration of 26 weeks, and a withdrawal study was conducted for a period of 4 weeks after the treatment.The rats were observed daily for clinical signs and mortality. Changes in body weight, food consumption, and water consumption were periodically monitored. Additionally, urinalysis results, hematological and biochemical parameters, relative organ weights, and pathology were monitored at specific observation time points.

RESULTS

In the sub-acute toxicity study, necropsy of dead and moribund rats revealed evident distension and swelling of the gastrointestinal tract, as well as thinning of the intestinal wall. The main adverse reactions observed included flatulence, piloerection, abnormal breathing sounds, and emaciation. Doses of 1.61 g/kg and below did not cause animal death. The gastrointestinal system is the main target organ of toxicity. In the chronic toxicity study, the no-observed-adverse-effect-level (NOAEL) of KXS was 0.27 g/kg, and its toxic effects were primarily concentrated in the gastrointestinal system. This led to secondary pathological changes in the immune system, hematopoietic system, and heart, suggesting that relevant indicators should be monitored when large doses are used clinically for an extended period of time.

CONCLUSIONS

During the rodent toxicity evaluation, severe gastrointestinal damage was observed when KXS, powdered with crude drugs, was administered. The NOAEL for rats was found to be 0.27 g/kg/day.