Acute and subchronic toxicity studies of polysaccharide components from Trametes robiniophila Murr (Huaier) in Sprague-Dawley rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Trametes robiniophila Murr (Huaier) is a traditional Chinese medicine (TCM) with potent immunomodulatory effects. Clinically validated for anti-hepatocellular carcinoma activity, Huaier granules are the mainstream proprietary preparation derived from this fungus. In recent years, polysaccharide components from natural medicinal herbs have attracted extensive research attention owing to their prominent biological activities. Although Huaier has been applied in clinical practice for decades, systematic toxicological investigations focusing on its purified polysaccharides remain unreported to date.

AIM OF THE STUDY: This study represents the first systematic toxicological investigation of Huaier polysaccharide (HEP). The acute and subchronic toxicity of HEP was evaluated in Sprague-Dawley (SD) rats, aiming to lay a theoretical foundation for the further development and rational clinical application of this bioactive polysaccharide.

MATERIALS AND METHODS: Acute toxicity was evaluated via a single oral administration of HEP at doses of 2500, 5000, and 10 000 mg/kg in rats; general toxic symptoms and mortality were continuously observed for 13 days thereafter. For the subchronic toxicity study, daily oral gavage of HEP (250, 500, and 1000 mg/kg) was performed for 90 consecutive days. At the scheduled termination of both acute and subchronic experiments, blood samples were collected for hematological and serum biochemical analyses. Furthermore, major vital organs including the heart, liver, kidney, lung, and spleen were harvested for histopathological examination to identify potential tissue lesions. Meanwhile, routine organ injury biomarkers, such as hepatic enzymes, creatinine, urea, bilirubin, creatine kinase and lactate dehydrogenase, were determined to quantitatively assess the degree of visceral organ damage.

RESULTS: The acute toxicity results demonstrated that HEP exhibited no overt toxic effects in rats; neither mortality nor remarkable body weight alterations were observed throughout the experiment. The estimated oral LD50 of HEP was higher than 10 000 mg/kg. Hematological analysis showed no statistically significant differences between the HEP-treated groups and the control group. Regarding serum biochemistry, the high-dose HEP induced significant changes in ALP and UA in male rats, as well as variations in GLB and GLU in female rats, while the medium-dose HEP only significantly affected the UA level in male rats. Notably, these abnormal biochemical fluctuations were not detected in the 90-day subchronic toxicity test. Moreover, subchronic administration of HEP exerted no obvious influences on body growth or routine hematological indices of rats. In addition, histopathological examination of major vital organs revealed no detectable pathological lesions in either acute or subchronic toxicity studies.

CONCLUSION: Acute toxicity studies have shown that HEP affects levels of ALP, UA, GLB, and GLU in rats. However, these changes were not observed following long-term oral administration of HEP. Furthermore, histopathological staining of organ tissues revealed no substantial damage, and the slight fluctuations in serum biochemical parameters were redefined as physiological, non-adverse general changes rather than signs of actual organ toxicity or pathological damage. Additionally, no other toxic effects were observed in either acute or subacute toxicity tests, indicating that HEP possesses a high level of safety.