Preclinical safety evaluation of the aqueous acetone extract of Chinese herbal formula Modified Huo Luo Xiao Ling Dan.

OBJECTIVE

To investigate the safety of oral administration of Modified Huo Luo Xiao Ling Dan (HLXLD), a compound traditional Chinese herbal medicine.

METHODS

The toxicological information of HLXLD and its individual constituent herbs was searched in cintcm or TCMlars (www.cintcm.com), PubMed (MEDLINE), Chinese Herbal Medicine (1999) and WHO Monographs on Selected Medicinal Plants (Vol. I- III). Single-dose acute toxicity was assessed by using the highest possible dosage. Motor function test was used to determine whether the herbal formula might cause motor impairment. Nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects, and 42-day chronic toxicity/adverse effects in rats were also assessed.

RESULTS

The literature searches showed that HLXLD and its eleven ingredient herbs had no side/adverse effects listed in the traditional Chinese medicine literature. Under the dosages proposed in the formula, the HLXLD formula had no side/adverse effects according to MEDLINE, Chinese Herbal Medicine and WHO Monographs on Selected Medicinal Plants. The studies in rats showed: (1) in single-dose acute toxicity assessment, the maximal feasible single oral dose, 9.20 g/kg HLXLD, showed no significant effect on clinical signs, or body weight and mortality over a 14-day period in rats; (2) during motor function test, nine-day repeat-dose of daily HLXLD treatment at 4.60 g/kg did not cause motor impairment; (3) in nine-day HLXLD repeat-dose sub-chronic toxicity/adverse effects assessment, there were no noticeable abnormal behavioral changes or obvious adverse reactions and signs in complete Freund's adjuvant inflamed rats (highest observed dosage: 4.60 g/kg), and no noticeable adverse effects were observed during, or 14 days after nine-day treatment at 4.60 g/kg in non-inflamed rats; (4) during 42-day chronic toxicity/adverse effects assessments, no noticeable abnormal behavioral changes, no obvious adverse reactions and signs were observed in normal rats administered with HLXLD at a dose of 2.30 g/kg and the values of serum biochemistry and histopathology were in normal range.

CONCLUSION

Both existing information and animal data support that Modified HLXLD is a safe herbal product for clinical application.