<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.4 20241031//EN"
        "https://jats.nlm.nih.gov/publishing/1.4/JATS-journalpublishing1-4.dtd">
<article  article-type="research-article"        dtd-version="1.4">
            <front>

                <journal-meta>
                                                                <journal-id>j. res. pharm.</journal-id>
            <journal-title-group>
                                                                                    <journal-title>Journal of Research in Pharmacy</journal-title>
            </journal-title-group>
                                        <issn pub-type="epub">2630-6344</issn>
                                                                                            <publisher>
                    <publisher-name>Marmara University</publisher-name>
                </publisher>
                    </journal-meta>
                <article-meta>
                                        <article-id/>
                                                                <article-categories>
                                            <subj-group  xml:lang="en">
                                                            <subject>Pharmacognosy</subject>
                                                            <subject>Pharmaceutical Chemistry</subject>
                                                    </subj-group>
                                            <subj-group  xml:lang="tr">
                                                            <subject>Farmakognozi</subject>
                                                            <subject>Farmasotik Kimya</subject>
                                                    </subj-group>
                                    </article-categories>
                                                                                                                                                        <title-group>
                                                                                                                        <article-title>Investigation of total phenolic and flavonoid content of Salvia willeana (Holmboe) Hedge, an endemic plant of Cyprus, and screening of its antioxidant and cholinesterase inhibitory properties</article-title>
                                                                                                    </title-group>
            
                                                    <contrib-group content-type="authors">
                                                                        <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-7774-7266</contrib-id>
                                                                <name>
                                    <surname>Ercetin</surname>
                                    <given-names>Tugba</given-names>
                                </name>
                                                                    <aff>Department of Pharmacognosy, Faculty of Pharmacy, Eastern Mediterranean University</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0001-8102-284X</contrib-id>
                                                                <name>
                                    <surname>Safaei</surname>
                                    <given-names>Maryam</given-names>
                                </name>
                                                                    <aff>Department of Pharmacognosy, Faculty of Pharmacy, Eastern Mediterranean University, Famagusta</aff>
                                                            </contrib>
                                                    <contrib contrib-type="author">
                                                                    <contrib-id contrib-id-type="orcid">
                                        https://orcid.org/0000-0002-9503-5841</contrib-id>
                                                                <name>
                                    <surname>Gülcan</surname>
                                    <given-names>Hayrettin Ozan</given-names>
                                </name>
                                                                    <aff>YAKIN DOĞU ÜNİVERSİTESİ, ECZACILIK FAKÜLTESİ, FARMASOTİK KİMYA ANABİLİM DALI</aff>
                                                            </contrib>
                                                                                </contrib-group>
                        
                                        <pub-date pub-type="pub" iso-8601-date="20250628">
                    <day>06</day>
                    <month>28</month>
                    <year>2025</year>
                </pub-date>
                                        <volume>26</volume>
                                        <issue>2</issue>
                                        <fpage>263</fpage>
                                        <lpage>271</lpage>
                        
                        <history>
                                    <date date-type="received" iso-8601-date="20210603">
                        <day>06</day>
                        <month>03</month>
                        <year>2021</year>
                    </date>
                                                    <date date-type="accepted" iso-8601-date="20211231">
                        <day>12</day>
                        <month>31</month>
                        <year>2021</year>
                    </date>
                            </history>
                                        <permissions>
                    <copyright-statement>Copyright © 2010, Journal of Research in Pharmacy</copyright-statement>
                    <copyright-year>2010</copyright-year>
                    <copyright-holder>Journal of Research in Pharmacy</copyright-holder>
                </permissions>
            
                                                                                                <abstract><p>Salvia willeana (Holmboe) Hedge is an endemic plant of Cyprus island. There have been limited number of studies on the plant, beside some analytical studies on its chemical content. This study aimed to investigate total phenolic and flavonoid content of the plant concomitant to some pharmacological activity screening studies including antioxidant and cholinesterase inhibition. Following obtaining different organic solvent and aqueous extracts of the dried aerial parts of the plant, 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferric-reducing antioxidant power (FRAP), iron-chelation capacity assays, and modified Ellman’s method were employed for screening antioxidant and cholinesterase inhibition studies. S. willeana extracts displayed low to moderate activities in cholinesterase inhibition assays. The ethyl acetate extracts of the leaves and the methanol extracts of the stem part of the plant displayed the highest acetylcholinesterase inhibitory potential (i.e., 28.95 ± 0.035%, and 24.01 ± 0.007%, respectively), while the highest butyrylcholinesterase inhibitory potential was obtained in aqueous extracts of the stem at 0.5 mg/mL (i.e., 29.10 ± 0.005%). The methanol extracts of the leaves and flower of the plant provided the highest antioxidant activity in DPPH radical scavenging activity (67.94 ± 0.003%, and 45.07 ± 0.001%, respectively) at 0.5 mg/mL concentration. Ferrous iron chelating activity of the extracts were found weak in general. The plant was found rich in terms of its flavonoid and phenolic contents as shown in the ethyl acetate and methanol extracts of the leaves (i.e., 547.55 ± 3.12 mg/g, and 300.24 ± 1.23 mg/g extract, respectively).</p></abstract>
                                                            
            
                                                            <kwd-group>
                                                    <kwd>Salvia willeana</kwd>
                                                    <kwd>  antioxidant activity</kwd>
                                                    <kwd>  cholinesterase inhibitor</kwd>
                                                    <kwd>  Alzheimer’s Disease</kwd>
                                            </kwd-group>
                            
                                                                                                                        </article-meta>
    </front>
    <back>
                            <ref-list>
                                    <ref id="ref1">
                        <label>1</label>
                        <mixed-citation publication-type="journal">[1] Cragg GM, Newman DJ. Natural product drug discovery in the next millennium. Pharm Biol. 2001; 3: 8-17.
[CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref2">
                        <label>2</label>
                        <mixed-citation publication-type="journal">[2] Myers N, Mittermeier RA, Mittermeier CG, Da Fonseca GA, Kent J. Biodiversity hotspots for conservation priorities.
Nature. 2000; 403(6772): 853-858. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref3">
                        <label>3</label>
                        <mixed-citation publication-type="journal">[3] Francis PT, Palmer AM, Snape M, Wilcock GK. The cholinergic hypothesis of Alzheimer’s disease: a review of
progress. J Neurol Neurosurg Psychiatry. 1999; 66(2): 137-147. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref4">
                        <label>4</label>
                        <mixed-citation publication-type="journal">[4] Colović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase inhibitors: pharmacology
and toxicology. Curr Neuropharmacol. 2013; 11(3): 315-335. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref5">
                        <label>5</label>
                        <mixed-citation publication-type="journal">[5] Goh CW, Aw CC, Lee JH, Chen CP, Browne ER. Pharmacokinetic and pharmacodynamic properties of
cholinesterase inhibitors donepezil, tacrine, and galantamine in aged and young Lister hooded rats. Drug Metab
Dispos. 2011; 39(3): 402-411. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref6">
                        <label>6</label>
                        <mixed-citation publication-type="journal">[6] Mehta M, Adem A, Sabbagh M. New acetylcholinesterase inhibitors for Alzheimer&#039;s disease. Int J Alzheimers Dis.
2012: 1-8. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref7">
                        <label>7</label>
                        <mixed-citation publication-type="journal">[7] Lin H, Bhatia R, Lal R. Amyloid β protein forms ion channels: implications for Alzheimer’s disease
pathophysiology. FASEB J. 2001; 15(13): 2433-2444. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref8">
                        <label>8</label>
                        <mixed-citation publication-type="journal">[8] Meikle RD. Flora of Cyprus. Volume One, Kew: The Bentham-Moxon Trust Royal Botanic Gardens. 1977.
[9] Şenol FS, Orhan I, Celep F, Kahraman A, Doğan M, Yılmaz G, Şener B. Survey of 55 Salvia taxa for their
acetylcholinesterase inhibitory and antioxidant activities. Food Chem. 2010; 120: 34-43. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref9">
                        <label>9</label>
                        <mixed-citation publication-type="journal">[10] Orhan I, Kartal M, Naz Q, Ejaz A, Yılmaz G, Kan Y, Konuklugil B, Şener B, Choudhary MI. Antioxidant and
anticholinesterase evaluation of selected Turkish Salvia species. Food Chem. 2007; 103(4): 1247-1254.</mixed-citation>
                    </ref>
                                    <ref id="ref10">
                        <label>10</label>
                        <mixed-citation publication-type="journal">[11] Orhan IE, Şenol FS, Erçetin T, Kahraman A, Celep F, Akaydın G, Bilge Şener, Doğan M. Assessment of
anticholinesterase and antioxidant properties of selected sage (Salvia) species with their total phenol and flavonoid
contents. Ind Crops Prod. 2013; 41: 21-30. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref11">
                        <label>11</label>
                        <mixed-citation publication-type="journal">[12] Demirezer LÖ, Gürbüz P, Kelicen Uğur EP, Bodur M, Özenver N, Uz A, Güvenalp Z. Molecular docking and ex
vivo and in vitro anticholinesterase activity studies of Salvia sp. and highlighted rosmarinic acid. Turk J Med Sci.
2015; 45(5): 1141-1148. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref12">
                        <label>12</label>
                        <mixed-citation publication-type="journal">[13] Wu YB, Ni ZY, Shi QW, Dong M, Kiyota H, Gu YC, Cong B. Constituents from Salvia species and their biological
activities. Chem Rev. 2012; 112(11): 5967-6026. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref13">
                        <label>13</label>
                        <mixed-citation publication-type="journal">[14] Lopresti AL. Salvia (Sage): A review of its potential cognitive-enhancing and protective effects. Drugs R D. 2017;
17(1): 53-64. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref14">
                        <label>14</label>
                        <mixed-citation publication-type="journal">[15] Yen GC, Duh PD, Tsai HL. Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid. Food Chem.
2002; 79(3): 307-313. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref15">
                        <label>15</label>
                        <mixed-citation publication-type="journal">[16] Ellman GL, Courtney KD, Andres V Jr, Feather-stone RM. A new and rapid colorimetric determination of
acetylcholinesterase activity. Biochem Pharmacol. 1961; 7(2): 88–95. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref16">
                        <label>16</label>
                        <mixed-citation publication-type="journal">[17] Orhan I, Şenol FS, Koca U, Erçetin T, Toker G. Evaluation of the antioxidant and acetylcholinesterase inhibitory
activities of Arnebia densiflora Ledeb. Turk J Biol. 2011; 35(1): 111-115. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref17">
                        <label>17</label>
                        <mixed-citation publication-type="journal">[18] Noshadi B, Erçetin T, Luise C, Yüksel MY, Sippl W, Şahin MF, Gazi M, Gülcan HO. Synthesis, Characterization,
Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs. Chem Biodivers.
2020; 17(8): e2000197. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref18">
                        <label>18</label>
                        <mixed-citation publication-type="journal">[19] Gürdal EE, Turgutalp B, Gülcan HO, Erçetin T, Şahin MF, Durmaz I, Yarım M. Synthesis of Novel Benzothiazole-
Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic
Agents. Anticancer Agents Med Chem. 2017; 17(13): 1837-1845. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref19">
                        <label>19</label>
                        <mixed-citation publication-type="journal">[20] Norouzbahari M, Burgaz EV, Erçetin T, Fallah A, Foroumadi A, Firoozpour L, Gülcan HO. Design, synthesis and
characterization of novel urolithin derivatives as cholinesterase inhibitor agents. Lett Drug Des Discov. 2018; 15(11):
1131-1140. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref20">
                        <label>20</label>
                        <mixed-citation publication-type="journal">[21] Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958; 181: 1199-1200. [CrossRef]
[22] Sharopov F, Valiev A, Sobeh M, Arnold E, Winka M. Bioactivity of three Salvia species in relation to their total
phenolic and flavonoid contents. Pharm Chem J. 2018; 52(7): 596-600. [CrossRef]</mixed-citation>
                    </ref>
                                    <ref id="ref21">
                        <label>21</label>
                        <mixed-citation publication-type="journal">[23] Singleton VL, Rossi JA. Colorimetry of total phenolics with phosphomolybdic-phosphotungstic acid reagents. Am J
Enol Vitic. 1965; 16(3): 144-158.</mixed-citation>
                    </ref>
                                    <ref id="ref22">
                        <label>22</label>
                        <mixed-citation publication-type="journal">[24] Woisky RG, Salatino A. Analysis of propolis: some parameters and procedures for chemical quality control. J Apic
Res. 1998; 37(2): 99-105. [CrossRef]</mixed-citation>
                    </ref>
                            </ref-list>
                    </back>
    </article>
