## 3 Results and Discussion
### Cytotoxicity of Fermented CF Leaf Methanolic Extract  
An increasing CF extract concentration may produce toxic components (e.g., saponin, alkaloids, or phytic acid) and cause cytotoxicity [12]. Regardless of the potency of the physiological activity of the fermented CF leaf extract, it cannot be used if it causes cytotoxicity. Therefore, we examined the cytotoxic effect of the fermented CF leaf extract on HaCaT and  
\begin{table}
\begin{tabular}{c c c c c c c} \hline  & \multicolumn{4}{c}{**Phenolic Yield**} & \multicolumn{4}{c}{**Antiaging Activity (IC\({}_{\text{50}}\), mg/L)**} \\ \hline
**TPC** & **TFC** & **Collagenase** & **Elastase Activity** & **Hyaluronidase** & **MMP-1 Activity** \\
**(mg-GAE/g-DW)** & **(mg-QE/g-DW)** & **Activity** & **Elastase Activity** & **Hyaluronidase** & **Adtivity** & **MMP-1 Activity** \\ \hline Leaf extract & 162.5 \(\pm\) 6.7 & 87.1 \(\pm\) 2.8 & 113.5 \(\pm\) 9.2 & 137.4 \(\pm\) 16.2 & 106 \(\pm\) 7.6 & 176.4 \(\pm\) 13.8 \\ \hline \end{tabular}
\end{table}
Table 1: TPC, TFC, and antiaging activity of the methanolic extract of _C. formosanum_ leaves fermented with _A. oryzae_.  
\begin{table}
\begin{tabular}{c c c c c c c} \hline  & \multicolumn{4}{c}{**Antimicrobial Activity**} \\ \hline  & \multicolumn{4}{c}{**MIC (mg/L)**} & \multicolumn{4}{c}{**MFC (mg/mL)**} \\ \hline  & _E. coli_ & _S. aureus_ & _P. aeruginosa_ & _C. acnes_ & _C. albicans_ & _A. brasiliensis_ \\ \hline Leaf extract & 150 \(\pm\) 12 & 180 \(\pm\) 14 & 140 \(\pm\) 9 & 120 \(\pm\) 5 & 230 \(\pm\) 26 & 280 \(\pm\) 21 \\ \hline \end{tabular}
\end{table}
Table 2: Antimicrobial activity of the methanolic extract of _C. formosanum_ leaves fermented by _A. oryzae_.  
Raw 264.7 cells as well as the effects of both unfermented and fermented extracts on HEMn cell survival. Figure 3 presents the cytotoxic effects of these extracts on HEMn, HaCaT, and Raw 264.7 cells. All concentrations of the fermented CF leaf extract were nontoxic (viability \(\geq\) 92.7%) for all tested cells. The viability of HaCaT cells was >94.6% \(\pm\) 0.5% compared with that of control cells when the concentration of the fermented extract was \(\leq\)400 mg/L, implying that it is potentially safe for skin treatment. [PERSON] et al. (2016) reported that the CF seed extract at concentrations of \(\leq\)150 mg/L did not affect HaCaT cell viability [3]. Moreover, the viability of LPS-stimulated RAW 264.7 cells was 92.7% \(\pm\) 1.6% at \(\leq\)400 mg/L. This suggests that a dose of \(\leq\)400 mg/L of the fermented CF leaf extract is suitable for anti-inflammatory studies. The results also revealed that the fermented CF leaf extract had a considerably lower cytotoxicity in HEMn cells, whereas the unfermented extract, even at 250 mg/L, exhibited significant cytotoxicity (\(p\) < 0.05) compared with the control. Moreover, the viability of HEMn cells at 400 mg/L of unfermented and fermented extracts was 78.2% \(\pm\) 1.4% and 92.8% \(\pm\) 2.5%, respectively. Thus, the fermented extract at 400 mg/L was considered safe for all the three cell lines and may therefore be safe and effective for use in antioxidative, antiaging, antimicrobial, and skin-whitening products (Tables 1 and 2).