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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">The significant ways to improve the quality of the preconception phase are to improve nutritional status&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">1</span></a> Nutrition is associated with increasing the cortisol hormone as a physiological response to stress that is secreted by the adrenal cortex&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">2&#8211;4</span></a> Working women&#44; during menstruation&#44; pregnancy&#44; childbirth&#44; postpartum&#44; and menopause&#44; are more likely to experience stress up to two times more than men&#46;<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">2&#44;5&#44;6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Glutathione hormone is related to oxidative stress&#46; It is a state of imbalance between reactive oxygen species &#40;ROS&#41; and the ability of biological systems to reduce ROS levels&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">7</span></a> These conditions can cause several reproductive diseases such as endometriosis&#44; PCOS&#44; decreased oocyte quality&#44; infertility&#44; miscarriage&#44; preeclampsia&#44; IUGR&#44; and premature birth <a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">8&#44;9</span></a> occurrence of Polycystic Ovarian Syndrome &#40;PCOS&#41; associated with reproductive and metabolic diseases&#44; and this condition is characterized by irregular menstruation&#44; oligomenorrhea or amenorrhea&#44; anovulation&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">10</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The state of oxidative stress at the cellular level can affect the quality of the women&#39;s and men&#39;s reproductive organs&#44; decrease fertility&#44; and increase the risk of abortion&#44; and fetal growth is inhibited due to excessive exposure to glucocorticoid hormones&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">11</span></a> Oxidative stress has been linked to many patterns of disease&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">12</span></a> The body&#39;s main antioxidant&#44; glutathione&#44; has an important role in preventing cell damage caused by oxidative stress <a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">13</span></a> and is able to maintain vitamin C and vitamin E&#44; which also acts as exogenous antioxidants&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">14</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Low levels of estrogen and stressful conditions also trigger women to be vulnerable to oxidative stress&#46; Previous studies in experimental animals have suggested that high corticosterone levels are associated with low estradiol and have a negative effect on mood&#44;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">15</span></a> low estrogen levels leading to amenorrhea and irregular menstruation&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a> Young women and menopausal women who experience decreased estrogen are more at risk for autoimmune disease&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">17</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The provision of ginger containing antioxidants can reduce oxidation activity&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">18</span></a> and the ethanol content of ginger increases enzymatic antioxidant activity&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">19</span></a> Ginger can also replace the role of mefenamic acid &#40;NSAIDs&#41; in reducing menstrual pain in women&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Honey with antioxidant content such as flavonoids&#44; phenolic acids&#44; enzymes&#44; vitamins &#40;A&#44; E&#44; C&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> and a minor mineral &#40;copper and iron&#41;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">22</span></a> can prevent cancer&#44; heart disease&#44; infectious diseases&#44; decreased neurological function&#44; inflammation&#44; and aging&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">21</span></a> Honey administration to 2 months mice affects brain development and memory and reduces these mice&#39;s anxiety level&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">23</span></a> Administration of Tualang honey in induced stress mice can reduce ACTH and corticosterone levels&#44; reduce MDA&#44; and increase antioxidant activity in the brain&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">20</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">It takes innovations to helps humans reduce stress in the preconception phase to effort a healthy reproduction&#46; Therefore&#44; we need an intervention with minimal side effects on the body&#59; one of the alternatives is those derived from natural ingredients or food&#46; Honey and ginger are two natural ingredients whose acceptance for consumption is very easy for people&#46; This study is expected to contribute as primary research for preconception problems&#44; especially in subjects with mild stress&#46; It is also expected to strengthen the use of inexpensive natural ingredients to solve health problems and impact local honey entrepreneurs by increasing sales&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">This study strengthens previous research conducted by the team because it needs to check the reliability of the previous study&#44; except that the previous study used two doses and examined each hormone separately&#46; The study was repeated using the highest dose and evaluating the hormone simultaneously&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">24&#8722;27</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="par0045" class="elsevierStylePara elsevierViewall">This research was an in vivo laboratory research and is carried out in the Biopharmacy Laboratory and the Microbiology Laboratory of the Teaching Hospital of Hasanuddin University with a pretest&#8211;posttest control group research design&#46; Honey and ginger were local products from south Sulawesi&#44; Indonesia&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The sample of this study was female Balb&#47;c mice aged 2&#8211;3 months&#44; divided into 2 groups &#40;5 of each group&#41;&#46; Group 1 as a control group&#41; is given standard feed&#44; and group 2 as ginger honey as much as 42<span class="elsevierStyleHsp" style=""></span>mg&#47;20<span class="elsevierStyleHsp" style=""></span>g BW is given by oral sonde and standard feed for 14 days&#46; Before administering the intervention&#44; the mice were given swimming treatment for 15<span class="elsevierStyleHsp" style=""></span>min to increase the stress state&#46; The examination of cortisol hormone levels&#44; glutathione levels&#44; and estrogen hormone levels is carried out using the ELISA method on the 15<span class="elsevierStyleSup">th</span> day&#46; 2&#46; This research was approved by The Ethics Committee of Faculty of Medicine&#44; Hasanuddin University&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Result</span><p id="par0055" class="elsevierStylePara elsevierViewall">The analysis results showed that ginger honey increased 1&#46;892<span class="elsevierStyleHsp" style=""></span>ng&#47;ml of the hormone cortisol&#44; although this increase was not significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;165&#41;&#46; However&#44; this increase was still lower than the control group&#44; which increased its cortisol hormone to 3&#46;450<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; although it was also not significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;064&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that ginger honey significantly increased glutathione hormone levels by 2&#46;438<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; while the control group showed a decrease in glutathione levels by 0&#46;148<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;554&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows a significant increase in estrogen levels of 22&#46;754<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; compared to the control group&#44; which increased by 3&#46;598<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;134&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Based on the data of <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#44; in the Intervention group&#44; ginger honey had the most significant effect on increasing estrogen level hormone by 22&#46;754<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">As much as 42<span class="elsevierStyleHsp" style=""></span>mg&#47;20<span class="elsevierStyleHsp" style=""></span>g BW in female Balb&#47;c mice&#44; Ginger honey can increase glutathione and estrogen levels that handle oxidative stress and increase cortisol levels insignificantly&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Glutathione exists in almost all body cells that act as antioxidants&#44; hydrogen donors&#44; to free radicals to prevent oxidative stress&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">29&#44;30</span></a> Oxidative stress is a trigger for PCO disease&#44; oocyte damage&#44; and infertility&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">31</span></a> A mixture of ginger and gelam honey can overcome oxidative stress conditions in diabetes mellitus patients by decreasing ROS production by increasing Glutathione levels in the blood&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">32</span></a> Our research shows that the administration of ginger honey supplements can significantly increase glutathione levels by 0&#46;447<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; In a previous study on 12 Sprague Dawley rats given Gelam honey as much as 2&#46;5<span class="elsevierStyleHsp" style=""></span>ml&#47;kg BW&#44; which is equivalent to 1 tsp for adults in 8 months&#44; can reduce levels of MDA and levels of DNA damage&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">33</span></a> Previous research also states that Rambutan Honey contains flavonoids and phenolic as a natural antioxidant which plays a role in reducing lipid peroxide and free radicals&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">9</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">The existence of stressful conditions can suppress the circulation of gonadotropins and steroid hormones&#44; which will result in the disruption of the menstrual cycle&#46; The decrease in GnRH is due to the increased secretion of CRH&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">16</span></a> On the other hand&#44; an increase in LH&#44; testosterone due to metabolic disorders in the body can cause infertility due to ovulation abnormalities&#46; The provision of ginger in mice with ovulation abnormalities can improve and be effective in balancing the hormones LH&#44; FSH&#44; estrogen&#44; and progesterone&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">28</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusion</span><p id="par0090" class="elsevierStylePara elsevierViewall">Ginger honey affects reducing cortisol levels&#44; increasing glutathione and estrogen levels&#46; Therefore&#44; ginger honey supplements are the potential to use as complementary therapies&#46; The limitation of this study is that it only tested one dose and did not compare it with positive controls given anti-depressants&#46; Future studies can test this product on humans with preconception subjects who experience mild stress&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflict of interest</span><p id="par0095" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "identificador" => "xpalclavsec1456623"
          "titulo" => "Keywords"
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        2 => array:2 [
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          "titulo" => "Introduction"
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          "identificador" => "sec0010"
          "titulo" => "Methods"
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        6 => array:2 [
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          "titulo" => "Conclusion"
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        7 => array:2 [
          "identificador" => "sec0030"
          "titulo" => "Conflict of interest"
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        8 => array:1 [
          "titulo" => "References"
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    ]
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    "fechaRecibido" => "2021-06-28"
    "fechaAceptado" => "2021-07-30"
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        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1456623"
          "palabras" => array:5 [
            0 => "Cortisol"
            1 => "<span class="elsevierStyleItalic">Ginger Honey</span>"
            2 => "Glutathione"
            3 => "Estrogen"
            4 => "Stress"
          ]
        ]
      ]
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This study was aimed to determine the effect of ginger honey supplementation on cortisol&#44; glutathione&#44; and estrogen levels&#46; The study was conducted on mice that had not yet experienced conception&#44; and prior stress induction was carried out so that they could be continued for human trials at the preconception stage and subjects who experienced mild stress&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">It was an in vivo study&#44; pretest&#8211;posttest control group design&#46; The sample of this study was 2&#8211;3 months female Balb&#47;c mice&#44; divided into negative control and ginger honey intervention as much as 28<span class="elsevierStyleHsp" style=""></span>mg&#47;20<span class="elsevierStyleHsp" style=""></span>g BW for 14 days&#8212;the ELISA method used to examine cortisol hormone&#44; glutathione levels&#44; and estrogen levels&#46; The mice chosen were those that had never experienced conception&#44; and before the intervention&#44; swimming activities were carried out on the mice until they showed symptoms of stress&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Results show 42<span class="elsevierStyleHsp" style=""></span>mg&#47;20<span class="elsevierStyleHsp" style=""></span>g BW of ginger honey administration for 14 days increased 1&#46;892 ng&#47;dl of cortisol &#40;<span class="elsevierStyleItalic">p</span> &#61; 0&#46;165&#41;&#44; increased 2&#46;438 ng&#47;dl of glutathione &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;002&#41;&#44; and also increased 22&#46;754<span class="elsevierStyleHsp" style=""></span>ng&#47;ml estrogen levels in induced stress Balb&#47;c female mice &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Ginger honey did not affect reducing cortisol levels but increasing glutathione and estrogen levels significantly&#46; Ginger honey supplements are the potential to use as complementary therapies&#46;</p></span>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleItalic">Pre</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">8&#46;041<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;218&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttable-entry\n
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                      "doi" => "10.1186/s12875-014-0212-7"
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