In vitro and in vivo evaluation of enzymatic and antioxidant activity, cytotoxicity and genotoxicity of curcumin-loaded solid dispersions

Curcumin, the main bioactive polyphenolic compound in Curcuma longa L. rhizomes has a wide range of bioactive properties. Curcumin presents low solubility in water and thus limited bioavailability, which decreases its applicability. In this study, cytotoxic effects of curcumin solid dispersions (CurSD) were evaluated against tumor (breast adenocarcinoma and lung, cervical and hepatocellular carcinoma) and non-tumor (PLP2) cells, while cytotoxic and genotoxic effects were evaluated in Allium cepa. The effect of the CurSD on the acetylcholinesterase (AChE), butyrylcholinesterase (BChE), glutathione S-transferase (GST), andmonoamine oxidase (MAO A-B) enzymes was determined, as well as its capacity to inhibit the oxidative hemolysis (OxHLIA) and the formation of thiobarbituric acid reactive substances (TBARS). CurSD are constituted by nanoparticles that are readily dispersible in water, and inhibited 24% and 64% of the AChE and BChE activity at 100μM, respectively. GST activity was inhibited at 30μM while MAO-A and B activity were inhibited at 100μM. CurSD showed cytotoxicity against all the tested tumor cell lines without toxic effects for non-tumor cells. No cytotoxic and genotoxic potential was detected with the Allium cepa test.CurSD maintained the characteristics of free curcumin on the in vitro modulation of important enzymes without appreciable toxicity.The authors are grateful to the Foundation for Science and Technology (FCT, Portugal) and FEDER under Programme PT2020 for financial support to CIMO (strategic project UID/AGR/00690/2013) and the research contracts of J. Pinela (Project AllNatt, POCI-01-0145- FEDER-030463) and R. Calhelha. To the project POCI-01-0145-FEDER- 006984 – Associate Laboratory LSRE-LCM funded by FEDER through COMPETE2020 - Programa Operacional Competitividade e Internacionalização (POCI) – and by national funds through FCT. This work was also funded by the European Regional Development Fund through the Regional Operational Program North 2020, within the scope of Project NORTE-01-0145-FEDER-023289: DeCodE and Project Mobilizador Norte-01-0247-FEDER-024479: ValorNatural®.info:eu-repo/semantics/publishedVersio