In vitro enzyme inhibitory and anti-oxidant properties, cytotoxicity and chemical composition of the halophyte Malcolmia littorea (L.) R.Br. (Brassicaceae)

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Natural Product Research

Formerly Natural Product Letters

ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20

In vitro

enzyme inhibitory and anti-oxidant

properties, cytotoxicity and chemical composition

of the halophyte Malcolmia littorea (L.) R.Br.

(Brassicaceae)

Viana Castañeda-Loaiza, Chloé Placines, Maria João Rodrigues, Catarina G.

Pereira, Gokhan Zengin, Nuno R. Neng, José M. F. Nogueira & Luísa Custódio

vitro enzyme inhibitory and anti-oxidant properties, cytotoxicity and chemical composition of

the halophyte Malcolmia�littorea (L.) R.Br. (Brassicaceae), Natural Product Research, DOI: 10.1080/14786419.2020.1719484

To link to this article: https://doi.org/10.1080/14786419.2020.1719484

View supplementary material Published online: 04 Feb 2020.

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SHORT COMMUNICATION

In vitro enzyme inhibitory and anti-oxidant properties,

cytotoxicity and chemical composition of the halophyte

Malcolmia littorea (L.) R.Br. (Brassicaceae)

Viana Casta~neda-Loaizaa_{, Chloe Placines}a_{, Maria Jo~ao Rodrigues}a

, Catarina G. Pereiraa, Gokhan Zenginb , Nuno R. Nengc , Jose M. F. Nogueirac

and Luısa Custodioa

a

Faculty of Sciences and Technology, Centre of Marine Sciences, University of Algarve, Faro, Portugal;bScience Faculty, Department of Biology, Selcuk University, Konya, Turkey;cCentre of Chemistry and Biochemistry/Department of Chemistry and Biochemistry, Faculty of Sciences of the University of Lisbon, Lisbon, Portugal

ABSTRACT

This work reports for the first time the in vitro anti-oxidant (towards DPPH, ABTS, copper and iron), enzymatic inhibitory (on AChE, BuChE, a-glucosidase, a-amylase and tyrosinase), cytotox-icity (towards HepG2 and HEK 293 cells), and metabolomics (by HPLC-MS) of extracts from organs of Malcolmia littorea (L.) R.Br. Extracts were constituted mainly by phenolic acids and flavonoids, and main compounds were salicylic acid and luteolin-7-O-gluco-side. Samples showed reduced radical scavenging and metal chelating capacity, and only the methanol extracts reduced iron. The root’s ethanol and methanol extracts, and the aerial organ’s ethanol extract exhibited the highest AChE inhibition. The root’s ethanol extract displayed dual anti-cholinesterase activity. Samples showed a low capacity to inhibita-amylase, but a high a-glucosidase inhibition was obtained with the root’s and flower’s ethanol extracts, and flower’s methanol extract. Overall, samples displayed a high inhibition against tyrosinase, reduced HepG2 cellular viability and were less toxic towards HEK 293 cells.

List of abbreviations: ABTS: 2,20 -Azino-bis(3-ethylbenzothiazo-line-6-sulfonic acid) diammonium salt; AD: Alzheimers disease; AChE: Acetylcholinesterase; BHT: butylated hydroxytoluene; BuChE: Butyrylcholinesterase; DPPH: 2,2-diphenyl-1-picrylhydrazyl;

ARTICLE HISTORY Received 21 October 2019 Accepted 11 January 2020 KEYWORDS Phytochemicals; tyrosinase inhibitors; cholinesterase inhibitors; salt tolerant plants

CONTACTLuısa Custodio lcustodio@ualg.pt

Supplemental data for this article can be accessed athttps://doi.org/10.1080/14786419.2020.1719484.

ß 2020 Informa UK Limited, trading as Taylor & Francis Group

FRAP: ferric reduction activity power; HPLC-MS: High-performance liquid chromatography-mass spectrometry; IC50: Half maximal inhibitory concentration; RSA: radical scavenging activity

1. Introduction

Halophyte plants can survive in adverse stressful conditions (e.g. high salinity and intense UV radiation), in part due to the production of bioactive secondary metabolites, including phenolic compounds and alkaloids. These compounds have protective role for the plant and display important bioactivities (e.g. anti-oxidant, anti-inflammatory), which may explain the several ethnomedicinal and veterinary uses of different species, as, for example Chrithmum maritimum L. and Pistacia lentiscus L. (Ksouri et al. 2012; Pereira et al.2017). Halophytes are therefore considered a very promising reservoir of natural bioactive products with a high-added value in different commercial segments, such as food, cosmetics and pharmaceutical.

The halophyte Malcolmia littorea (L.) R.Br. grows along coastal sand-dunes of the west Mediterranean area. Despite the biological properties and medicinal uses of someMalcolmia species (e.g. M. africana, Bokhari et al.2014), to the best of our know-ledge there is no available related information onM. littorea. Aiming at its valorisation, in this work, extracts were prepared from different organs and assessed for in vitro anti-oxidant and enzymatic inhibitory properties, cytotoxicity and chemical contents by high-performance liquid chromatography coupled to mass spectrometry (HPLC-MS).

2. Results and discussion

The phenolic profile of the extracts is summarised in Table S1. Methanol extracts showed higher contents of compounds, followed by water and ethanol extracts. Flowers’ extracts displayed higher abundance of identified molecules, followed by roots and aerial organs. Thirty two molecules were identified (mainly phenolic acids and flavonoids). Some were present in all samples (e.g. vanillic acid), while others were specific to a particular extract or organ (e.g. coumarin, detected only in roots’ water extracts). Major compounds were salicylic acid (SA) and luteolin-7-O-glucoside. SA shows a key role in plant resistance towards salinity, is common in halophytes and displays several bioactivities (e.g. anti-oxidant, Gharbi et al. 2017). Luteolin-7-O-glucoside (flavonoid) also exhibits important biological activities (e.g. anti-oxidant, Luo et al. 2017). Samples displayed reduced radical scavenging activity (RSA) and metal chelation properties (Table S2). Methanol extracts showed a high capacity to reduce iron (FRAP), which may be related with its higher phenolics content.

Extracts were more active against AChE than BChE, and the highest AChE inhibition was observed for roots’ ethanol and methanol extracts, and aerial organs’ ethanol extracts (Table S3). Roots’ ethanol extract also displayed a relevant activity towards BChE (Table S3). AChE inhibition is considered a relevant strategy for the management of Alzheimer’s disease (AD) symptoms, and dual activity against AChE and BChE may be appropriate in patients at a moderate stage of AD (Jiang et al. 2017). Roots and flowers ethanol extracts, and flowers methanol extracts displayed relevant activity

towards a-glycosidase, but low a-amylase inhibition. In the management of early Type 2 diabetes, excessive amylase inhibition causes gastrointestinal disorders, and therefore, products more active towards a-glucosidase than a-amylase are usually preferred (Zengin et al. 2018; Mahomoodally et al. 2019). Samples showed generally high tyrosinase inhibitory capacity, a pivotal enzyme in melanogenesis, cuticle formation in insects, and foodstuffs enzymatic browning processes (Zolghadri et al.

2019). Tyrosinase inhibitors have multiple applications as, for example, depigmentation agents, in food preservation, and in insect pest control (Zolghadri et al. 2019). Aerial organs’ water extract showed the highest cytotoxicity towards HepG2 cells (38.3%), was non-cytotoxic on HEK 293 cells (93.1%), and displayed the highest selectivity index (SI ¼ 2.31) (data not shown). Cytotoxicity of organic extracts on human blood erythrocytes was previously reported forM. africana extracts (Bokhari et al. 2014).

3. Conclusion

M. littorea’s extracts were mainly constituted of phenolic acids and flavonoids, displayed reduced anti-oxidant properties, but methanol extracts showed high FRAP. Roots’ ethanol extract had dual anti-cholinesterase activity. Roots and flowers ethanol extracts and flowers methanol extracts exhibited relevant activity towards a-glucosidase and low a-amylase inhibition. Samples displayed high tyrosinase inhibitory capacity. All extracts reduced HepG2 cellular viability and were less toxic towards HEK 293 cells. Our results suggestM. littorea as a candidate for further studies aiming its exploitation as a source of bioactive natural products.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

Work funded by the Foundation for Science and Technology (FCT) and the Portuguese National Budget (CCMAR/Multi/04326/2019, UID/DTP/04138/2019, ALG-01-0145-FEDER-028876 projects). M.J.R. and L.C. acknowledge FCT for SFRH/BD/116604/2016 and CEECIND/00425/2017.

ORCID

Gokhan Zengin http://orcid.org/0000-0002-5165-6013

Nuno R. Neng http://orcid.org/0000-0001-9879-1565

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