Acute and subchronic toxicological evaluation of Ganoderma lucidum spore powder in mice
Tingting Zhang, Zheng Zhang, Zhechao An, Shoulin Yin, Jianyong Tang, Wei Wu, Xiaojuan Wang, Wenhui Xu, Ying Su, Yingzhe Liu, Shuqin Duan, Jingwei Liu, Fengda Li, Ziyun Zhong, Yanan Liu, Liangliang Li, Yuan Li, Lei Yang, Yunhe Liu, Baofeng Yang, Fan YangAbstract
Objective
Ganoderma lucidum spore powder (GLSP) consists of small, ovoid reproductive cells released during the later stage of Ganoderma lucidum ( G. lucidum ) development. Its bioactive constituents are enclosed within a resistant outer wall and become more bioavailable following wall disruption. Although GLSP is widely recognized for its medicinal potential, its safety profile has not been systematically characterized. This study evaluated the acute and subchronic toxicity of GLSP derived from G. lucidum cultivated in Northeast China.
Methods
Acute toxicity was assessed in male and female mice following a single oral administration of GLSP at the maximum feasible dose of 16 g/kg. For the subchronic toxicity study, mice were randomly assigned, with equal numbers of males and females, to a control group (CTL) or to low-, medium-, and high-dose GLSP groups receiving 1.075, 2.15, and 4.3 g/kg/day, respectively. GLSP was administered by oral gavage for 13 consecutive weeks, followed by a 4-week recovery period. Clinical condition, behavior, body weight, and food consumption were monitored throughout the study. Cardiac function was evaluated using electrocardiography and echocardiography, and blood pressure was measured noninvasively. Anti-fatigue and hypoxia-tolerance capacities were evaluated using forced-swimming and hypoxia tolerance tests. Bone mass and microarchitecture were assessed by micro-computed tomography (microCT). At the end of the dosing and recovery periods, serum biochemical parameters, relative organ weights, and histopathological findings were comprehensively evaluated.
Results
In the acute toxicity study, no mortality or abnormal behavior, or other signs of toxicity were observed during the 14-day observation period following a single oral dose of GLSP at 16 g/kg. In the subchronic toxicity study, daily GLSP administration for 13 weeks produced no treatment-related changes in clinical appearance, behavior, body weight, food consumption, serum biochemical parameters, relative organ weights, or histopathological findings at any tested dose. Cardiac function, blood pressure, anti-fatigue capacity, and hypoxia tolerance were not adversely affected. GLSP administration also had no significant effect on bone mass or microarchitecture. Findings after the 4-week recovery period were consistent with those observed at the end of the dosing period.
Conclusions
GLSP produced no observable acute or subchronic toxicity in mice under the conditions of this study. The no-observed-adverse-effect level was therefore considered to be at least 4.3 g/kg/day following 13 weeks of repeated oral administration. These findings support a favorable preclinical safety profile for the further development and application of GLSP.