## 3 Results  
### Characterization of Flavonoids in Plebeian Sage and Its Extract  
Plebeian sage leaf contains 77.8 mg of flavonoids, and its extract (PS) contains 365.5 mg, flavonoids per each dry matter (g). Six representative compounds consisting of flavone (5) and flavanone (1) derivatives were tentatively identified from the leaf and PS through positive ionized mass fragmentation using UPLC-DAD-QToF/MS analysis (Table 3). The current positive ionized pattern of these compounds provides additional sodium (Na\({}^{+}\), \(m/z\) 23) and potassium (K\({}^{+}\), \(m/z\) 39) adduct ions with basic protonated molecules [M+H]\({}^{+}\) that can help to determine the parent ion. The conjugations with glucose moiety (162 Da) were the 7-OH position of their corresponding aglycones ([M+H-glucose]\({}^{+}\)) such as 6-hydroxyluteolin (\(m/z\) 303), 5,7,3\({}^{\prime}\),\({}^{\prime}\),\({}^{\prime}\)-tetrahydro-6-methoxyflavanone (\(m/z\) 319), luteolin (\(m/z\) 287), nepetin (\(m/z\) 317) and hispidulin (\(m/z\) 301).  
Among these glycosides (mg/g dry matter of leaf), 6-hydroxyluteolin 7-O-glucose (13.5 g), cymaroside (11.3 g), nepirtin (23.5 g) and homoplantaginin (19.5 g) were found as major constituents. Especially, 5,7,3\({}^{\prime}\),\({}^{\prime}\)-tetrahydroxy-6-methoxyflavanone 7-O-glucose is a new flavanone glycoside (naasanone, 9.4 g). In the PS, most flavonoids increased by more than three times compared to those in the Plebeian sage leaf. PS contains 6-hydroxyluteolin 7-O-glucose (65.9 g), naasanone (53.4 g), cymaroside (62.8 g), nepirtin (78.3 g) and homoplantaginin (104.8 g) as major constituents of flavonoids.  
\begin{table}
\begin{tabular}{c c c} \hline
**Gene Symbol** & **Catalog Number** & **Detected Transcript(s)** & **Amplicon Length** \\ \hline GAPDH & QT00199633 & NM\_017008 & 149 bp \\ IL-6 & QT00182896 & NM\_012589 & 128 bp \\ IL-18 & QT02459506 & XM\_001070641 & 105 bp \\ MMP-2 & QT00996254 & NM\_031054 & 103 bp \\ MMP-3 & QT00189308 & NM\_133523 & 82 bp \\ MMP-9 & QT00178290 & NM\_031055 & 149 bp \\ \hline \end{tabular}
\end{table}
Table 2: Primer information for gene expression in qPCR experiment.  
\begin{table}
\begin{tabular}{c c c c} \hline
**Compounds** & \multicolumn{2}{c}{**ESI(+)-QToF/MS**} & \multicolumn{2}{c}{**Contents (mg/g Dry Matters)**} \\ \cline{2-4}  & **Fragmentation of [M+H]\({}^{+}\) (\(m/z\))** & **Leaf** & **PS** \\ \hline
6-hydroxyluteolin 7-O-glucose & 487, **465**, 303 & 13.5 \(\pm\) 0.4 & 65.9 \(\pm\) 4.6 \\
5,7,3\({}^{\prime}\),\({}^{\prime}\),\({}^{\prime}\)-tetrahydroxy-6-methoxyflavanone & 503, **481**, 319 & 9.4 \(\pm\) 0.2 & 53.4 \(\pm\) 1.3 \\
7-O-glucose (naasanone) & 471, **449**, 287 & 11.3 \(\pm\) 0.4 & 62.8 \(\pm\) 1.3 \\ luteolin 7-O-glucose (nepirtin) & 501, **479**, 317 & 22.5 \(\pm\) 0.6 & 78.3 \(\pm\) 1.9 \\ hispidulin 7-O-glucose (homoplantaginin) & 485, **463**, 301 & 19.5 \(\pm\) 0.4 & 104.8 \(\pm\) 2.4 \\ hispidulin & 339, 323, **301** & 0.6 \(\pm\) 0.1 & 1.3 \(\pm\) 0.1 \\ \hline Total & & 77.8 \(\pm\) 1.9 & 365.5 \(\pm\) 9.1 \\ \hline \end{tabular}
\end{table}
Table 3: Characterization of isolated flavone and flavanone derivatives from Plebeian sage leaf and its extract (PS).