Safety assessment of Lindera obtusiloba leaf extract (LOLE) by cytotoxicity and mutagenicity assays. (A) The percentage of cell viability was determined by MTT assay. RAW 264.7 cells were treated with LOLE at various concentrations, and formazan absorbance was measured at 570 nm. The relative cell viability was compared to the control treated with DMSO. (B,C) Evaluation of LOLE by Ames test with strains TA98 and TA100, without (S9+) and with metabolic activation (S9+). The positive controls (PC) employed for (S9+) were 4-NQO (4-nitroquinoline 1-oxide, 15 μg per plate) and for (S9+), 2-AA (2-aminoanthracene, 5 μg per plate), respectively. Phosphate-buffered saline (PBS)-treated samples were used as negative controls for the test without metabolic activation. The white bars represent the control groups, whereas the gray bars represent the intervention groups. Results are expressed as the percentage of neutralized virus compared to control (mean ± SEM; n = 3). **** p < 0.0001 *** p < 0.001, * p < 0.05 vs. negative control.