# Microalgae as Potential Sources of Bioactive Compounds for Functional Foods and Pharmaceuticals
## 4 Conclusions  
This study showed that several industrialy produced microalgal species contain compounds with antioxidant, calcium chelating, anti-inflammatory, and cytotoxic effects (on HepG cells) with possible pharmaceutical applications without any need for genetic engineering. Four species deserve some future attention, namely: _Phaedactylum tricornutum_ with significant antiproliferative effect on HepG2 cells; _Skeletonna_ sp. and _Porphyridium_ sp. with antioxidant effects coupled with metal chelating effect for iron, copper and calcium; and _Tetraselmis striata_ CTP4 with anti-inflammatory activity by decreasing the TNF-\(\alpha\) production in LPS stimulated Mac THP-1 cells. The chemical characterization of the hexane fractions of the ethanol extracts of _Porphyridium_ sp., _Skeletonna_ sp. and _Tetraselmis striata_ CTP4 and dichloromethane fraction from the ethanol extract of _Phaedactylum tricornutum_ showed compounds from different chemical classes, most of them of fatty acids, followed by long-chain aliphatic hydrocarbons (alkanes and alkenes), long-chain alcohols, esters, ethers and sterols. Most of these molecules have reported biological activities and could potentially be (at least partially) responsible for cytotoxicity effects against HepG2 cells, antioxidant, anti-inflammatory, and calcium chelating activities. Small variations in bioactivities of crude extracts were identified in between batches, so an optimization of culture conditions may be beneficial to improve the chemical composition of the algal biomass.  
Overall, we were successful in identifying prospective sources of biologically active compounds that could be used to counterbalance the effects of oxidative stress and inflammation, which are inevitably linked to many diseases that plague our modern-day societies, and therefore play an important role in health promotion. However, before considering human consumption, the in vivo effectiveness and the safety of these extracts should be assessed. Additional research is also required to isolate the active compound(s), and confirm their identity and structure. This would allow the study of the bioactive compounds' metabolism, providing clues for strain improvement via manipulation of microalgal cultivation conditions. This would allow the producers to increase the productivity of the bioactive compounds and enhance the bioactivity of the extracts.  
Conceptualization, C.S.B.V., D.C.S., K.N.G., J.V. and L.B.; methodology, C.S.B.V., D.C.S., K.N.G., J.V. and L.B.; formal analysis, M.S., F.K., S.T.U. and I.-M.K.; investigation, M.S., F.K., S.T.U., I.-M.K., C.S.B.V., D.C.S., K.N.G., J.V. and L.B.; resources, J.V. and L.B.; data curation, M.S., C.S.B.V., D.C.S., K.N.G., J.V. and L.B.; writing--original draft preparation, M.S., F.K., S.T.U. and I.-M.K.; writing--review and editing, M.S., C.S.B.V., D.C.S., J.V. and L.B.; supervision, C.S.B.V., D.C.S., K.N.G., J.V. and L.B.; project administration, C.S.B.V., D.C.S., J.V. and L.B.; funding acquisition, C.S.B.V., D.C.S., J.V. and L.B. All authors have read and agreed to the published version of the manuscript.  
The present work was funded by the Portuguese national budget and the UIDB/04326/2020, UIDP/04326/2020 and LA/P/0101/2020 grants, and the transitional provision DL57/2016/CP1361/CT0006 of the Foundation for Science and Technology (FCT). We would also like to acknowledge 055 ALGAKED + 05 INTERREG V-A--Espana-Portugal, ALGAE4 IBD project (grantAgreement/EC/H2020/101000501/EU) and AAC No. 41/ALG/2020--Project No. 072583--NUTRISAFE.  
Not applicable.  
To NECTON S.A. for the kind supply of the _Porphyridium_ sp., _Nannochloropsis_ sp., _Tisochrysis lutea, Phaedactylum tricornutum_, _Skeletonna_ sp., Spirulina, _Haematococcus_ _bluvialis_, and _Tetraselmis chui_ strain used in this study. To ALLMICROALGAE--Natural Products, S.A. for providing the biomass of _Tetraselmis striata_ CTP4.  
The authors declare no conflict of interest.