## 3 Results
### Expression of Cannabinoid Receptors in OA Synoial Membrane  
The presence of CB1 and CB2 receptors and PI-PLC \(\beta\)2 and \(\beta\)3 was detected by immunohistochemistry in synovial membranes isolated both from non-OA and OA patients. CB1 receptors were expressed in both normal and pathological tissues but with different scores; they were moderately present in non-OA patients (score 1+), while strongly present in OA patients (score 3+) (Figure 1, left-upper panel). CB2 receptors were detected only in non-OA tissue (score 2+) (Figure 1, \begin{table}
\begin{tabular}{c c c c c c} \hline \hline \multirow{2}{*}{**Compounds**} & \multirow{2}{*}{**HPEDMSO**} & \multirow{2}{*}{**HPEEDOH100**} & \multirow{2}{*}{**HPEEOH50**} & \multirow{2}{*}{**HPEEHO100**} \\ \cline{2-2} \cline{6-6}  & & & & & \(\mu\)g/mg of Dry Extract (Mean \(\pm\) SE) & \\ \hline Polyphenols (TAE) & 99.6 \(\pm\) 0.05 ***5 & 69.6 \(\pm\) 0.05 & 97.9 \(\pm\) 0.01 ***5 & 84.2 \(\pm\) 0.04 ** \\ Tannins (TAE) & 14.2 \(\pm\) 0.02 ** & 9.2 \(\pm\) 0.04 & 9.2 \(\pm\) 0.02 & 17.9 \(\pm\) 0.03 *** \\ Flavonoids (QE) & 113.0\(\pm\) 5.1 ***5 & 71.3 \(\pm\) 6.6 ***5 & 75.1 \(\pm\) 6.1 ***5 & 37.6 \(\pm\) 4.3 \\ Flavonols (QE) & 43.8 \(\pm\) 2.4 ***5 & 27.6 \(\pm\) 3.2 & 30.1 \(\pm\) 2.0 5 & 25.1 \(\pm\) 2.0 \\ \hline \hline \end{tabular}  
* TAE—tamic acid equivalent. QE—quercetin equivalent. **\(p<\) 0.01 and ***\(p<\) 0.01 significantly higher than HPEEDOH100 (ANOVA followed by [PERSON]’s multiple comparison post hoc test). 5 \(p<\) 0.05 and 58 \(p<\) 0.01 significantly higher than HPEEDO (ANOVA followed by [PERSON]’s multiple comparison post hoc test).  
\end{table} 
Table 2: Amounts of total polyphenols, tannins, flavonoids, and flavonoids in the extract from _Harpagophytum proumbens_ root (HPE) dissolved in DMSO (HPEDMSO), 100% _v/v_ EtOH (HPEEDOH100), 50% _v/v_ EtOH (HPEEOH50), and deionized water (HPEH2O). Data are the mean \(\pm\) SE of at least three independent experiments with three replicates for each experiment (n = 9). \begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline \multirow{2}{*}{**No. 1**} & \multirow{2}{*}{**Component 2**} & \multirow{2}{*}{**LRI 3**} & \multirow{2}{*}{**LRI 4**} & \multirow{2}{*}{**MS 5**} & \multirow{2}{*}{**HPEDMSO**} & \multirow{2}{*}{**HPEEDOH100**} & \multirow{2}{*}{**HPEEDOH50**} & \multirow{2}{*}{**HPEEHO**} \\  & & & & & & **(\%)** & **(\%)** & **(\%)** \\ \hline
1 & \(\beta\)-pinene & 978 & 974 & + & - & - & 5.1 & - \\
2 & thymol & 1308 & 1310 & + & 0.8 & - & - & - \\
3 & eugenol & 1339 & 1344 & + & 6.0 & 14.6 & 51.6 & - \\
4 & \(\alpha\)-copaene & 1381 & 1387 & + & - & 6.3 & 3.7 & - \\
5 & \(\beta\)-carophyllene & 1412 & 1416 & + & 77.4 & 77.1 & 38.6 & - \\
6 & isoeugenol & 1432 & 1439 & + & - & - & 1.0 & - \\
7 & \(\alpha\)-humulene & 1450 & 1454 & + & 10.0 & 0.8 & - & - \\
8 & \(\delta\)-cadinene & 1528 & 1530\({}^{+}\) & + & 5.8 & 1.3 & - & - \\  & Total (\%) & & & 100.0 & 100.0 & 100.0 & \\ \hline \hline \end{tabular}  
* Compound identification number; 2 compounds are reported according their elution order on column; 3 linear retention indices measured on apolar columns; 4 linear retention indices from literature; \({}^{+}\) normal alkane RJ; \({}^{5}\) identification by MS spectra, tr \(<\) 0.1%.  
\end{table} 
Table 3: Volatile compounds (relative percentage in the volatile fraction) detected in _Harpagophytum proumbens_ root extract (HPE) dissolved in DMSO (HPEDMSO), 100% _v/v_ EtOH (HPEETOH100), 50% _v/v_ EtOH (HPEETOH50), and deionized water (HPEH2O). left-bottom panel). Regarding the presence of PI-PLC \(\beta\)2 and \(\beta\)3, we found that the expression of PI-PLC \(\beta\)2 showed a lesser staining in non-OA (score 2+) than OA tissue (score 3+), and it was localized in the cytoplasm of both tissues (Figure 1, right-upper panel). PI-PLC \(\beta\)3 was equally expressed in tissues from non-OA (score 3+) and OA patients (score 3+) (Figure 1, right-bottom panel).