## 4 Conclusions and Perspectives  
Natural products and their derivatives have been recognized for many years as a source of therapeutic agents that can be less toxic and more effective. It has been estimated that nearly 75,000 species of higher plants exist on the earth, and only 10% have been used in traditional medicine. Only 1 to 5% have been studied scientifically and are known to have therapeutic value. \begin{table}
\begin{tabular}{c c c c} \hline \hline \multirow{2}{*}{**Group**} & **TNF-\(\alpha\)** & **IL-6** & **IL-10** \\  & **(pg/mL)** & **(pg/mL)** & **(pg/mL)** \\ \hline Negative Control & \(168.5\pm 42.2\) & \(109.9\pm 1.2\) & \(11.4\pm 1.6\) \\ Positive Control & \(95.0\pm 9.6\) & \(95.3\pm 9.0\) & \(28.8\pm 6.7\) \\ Free Extract & \(133.3\pm 26.5\) & \(106.9\pm 7.7\) & \(10.7\pm 1.2\) \\ Extract-loaded PLGA NPs & \(117.6\pm 15.1\) & \(96.3\pm 7.6\) & \(27.3\pm 10.9\) \\ Extract-loaded PCL NPs & \(123.4\pm 17.3\) & \(114.6\pm 16.1\) & \(18.8\pm 2.9\) \\ \hline \hline \end{tabular}
\end{table} 
Table 4: Status of the different parameters evaluated in the plasma of the rats for each group (mean \(\pm\) S.D.). For the first time, the current study provides a scientific evidence of AIA and Coll inhibition properties of a methanolic extract obtained from _S. nigra_ L. flowers. This effect was even more noticeable after encapsulation in PLGA NPs. Both in vitro and in vivo methodologies supported the potential topical use of methanolic extract of _S. nigra_ L. obtained from flowers. Comparing the two polymers used as carriers, PLGA NPs displayed a higher value of in vivo AIAby topical route, reaching a mean value of 61% of inhibition of oedema. Similar values of IL-6 and IL-10 were observed bewteen extract-loaded PLGA NPs and the positive control, a commercial formulation of diclofenac. This polymeric carrier also showed a high Coll inhibition activity. On the other hand, PLGA NPs did not cause cytotoxicity in HaCaT and HFF cell lines. More detailed studies of the AIA should be performed to identify the exact mechanism associated to this biological activity, as well as to verify if the developed system in this work can be applied in a chronic model of inflammation. Overall, the obtained results could certainly attract interest in extract-loaded PLGA NPs as a potential nanoproduct in a very near future. Conceptualization, C.P.R. ; A.J.A. methodology, A.H.M., N.D., A.T.S., A.F., L.C., M.M.G., S.S., P.R., L.A., J.C., P.F., R.P., A.S.V., P.K., C.P.R. ; software, A.H.M. ; validation, M.R.B., formal analysis, A.H.M., investigation, writing--original draft preparation, A.H.M., N.D., M.M.G., S.S., L.A., A.S.V., P.K., A.J.A., C.P.R. ; writing--review and editing, N.D., M.M.G., S.S., L.A., P.K., A.J.A., C.P.R., supervision, C.P.R. ; A.J.A. ; project administration, C.P.R. ; A.J.A. ; funding acquisition, C.P.R. All authors have read and agreed to the published version of the manuscript. Authors also gratefully acknowledge the Regiertulas and Fundacao para a Ciencia e a Tecnologia (FCT) (UIDB/04138/2020, UIDB/00100/2020, UIDP/50017/2020+UIDB/50017/2020) and Portugal 2020 to the Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125) for financial support. Furthermore, the authors are also grateful to the work supported by the FCT and the Portuguese National and Regional Budget, through CCMAR/Multi/04326/2019 project. Finally, [PERSON] was supported by the FCT Scientific Employment Stimulus (CEECIND/00425/2017). The authors are grateful to the Center for Neurosciences and Cell Biology, University of Coimbra, Portugal, for the kind gift of the RAW264.7 cells.