Abstract: OBJECTIVE: To investigate sub-chronic toxicity of polyphenol and polysaccharide extracts from Areca catechu in Wistar rats. METHODS: A total of 100 Wistar rats were randomly divided into control group,and Areca polysaccharide polyphenols-treated groups:0.28,0.83 and 2.5 g/kg. From the 0.28 and 0.83 g/kg groups,20 in each group,were killed after 90 days of exposure. From the 2.50 g/kg and control groups (30 in each group),20 were killed after 90 days of exposure,and treatments were stopped for the remaining 10 which received normal feeding for the subsequent 28 days. Each treated rat received 10 mL/kg volume of continuous intragastric administration for 90 days,once a day,and the control rats received equal volume of distilled water. Changes of body weight, food availability, hematology, biochemical parameters, urinalysis, main organ coefficient and histopathological examination were detected. RESULTS: Total weight gain of the 2.50 g/kg group was lower than that of the control group during the treatment period. There were no significant differences in the food utilization rates between groups except that the male rats in the first week of 2.50 g/kg group was lower than that in the control group. Five male and five female rats in the 2.50 g/kg group showed symptoms of poor spirit,rough coat and sluggish reaction after 3 weeks of treatment. Two male and two female rats died during the treatment period. Flatulence and thinning of gastrointestinal wall were observed in naked rats,but no obvious abnormalities were found in the histopathological examination of major organs. There were no obvious abnormalities in other dose groups compared with the control group during the exposure and the recovery periods. Although there were statistical differences in hematology,blood biochemistry and individual urine indexes between the control and the other dose groups,they were all within the range of normal test values in our laboratory, and had no biological significance. The organ coefficient and histopathological examination of the main organs showed no obvious abnormalities. It was considered that the death of rats might have been caused by gastrointestinal flatulence due to intestinal fermentation of a large amount of polysaccharide. Under the conditions of this study,90-day oral treatment with 0.83 g/kg areca polysaccharide polyphenols was considered to be at the no observed adverse effect level (NOAEL). CONCLUSION: Oral administration of 2.50 g/kg areca polysaccharides polyphenols for 90 days caused lethargy and flatulence in Wistar rats. Although this symptom was reversible,excessive dosage caused mortality. Therefore,development and utilization of areca polysaccharides polyphenols should be controlled within the safe dose range.

Key words: polyphenol and polysaccharide extract from Areca catechu, rats, sub-chronic toxicity, no observed adverse effect level