\documentclass[twocolumn,twoside]{article}
\makeatletter\if@twocolumn\PassOptionsToPackage{switch}{lineno}\else\fi\makeatother

\usepackage{amsfonts,amssymb,amsbsy,latexsym,amsmath,tabulary,graphicx,times,xcolor}

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
% Following additional macros are required to function some 
% functions which are not available in the class used.
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
\usepackage{url,multirow,morefloats,floatflt,cancel,tfrupee}
\makeatletter


\AtBeginDocument{\@ifpackageloaded{textcomp}{}{\usepackage{textcomp}}}
\makeatother
\usepackage{colortbl}
\usepackage{xcolor}
\usepackage{pifont}
\usepackage[nointegrals]{wasysym}
\urlstyle{rm}
\makeatletter

%%%For Table column width calculation.
\def\mcWidth#1{\csname TY@F#1\endcsname+\tabcolsep}

%%Hacking center and right align for table
\def\cAlignHack{\rightskip\@flushglue\leftskip\@flushglue\parindent\z@\parfillskip\z@skip}
\def\rAlignHack{\rightskip\z@skip\leftskip\@flushglue \parindent\z@\parfillskip\z@skip}

%Etal definition in references
\@ifundefined{etal}{\def\etal{\textit{et~al}}}{}


%\if@twocolumn\usepackage{dblfloatfix}\fi
\usepackage{ifxetex}
\ifxetex\else\if@twocolumn\@ifpackageloaded{stfloats}{}{\usepackage{dblfloatfix}}\fi\fi

\AtBeginDocument{
\expandafter\ifx\csname eqalign\endcsname\relax
\def\eqalign#1{\null\vcenter{\def\\{\cr}\openup\jot\m@th
  \ialign{\strut$\displaystyle{##}$\hfil&$\displaystyle{{}##}$\hfil
      \crcr#1\crcr}}\,}
\fi
}

%For fixing hardfail when unicode letters appear inside table with endfloat
\AtBeginDocument{%
  \@ifpackageloaded{endfloat}%
   {\renewcommand\efloat@iwrite[1]{\immediate\expandafter\protected@write\csname efloat@post#1\endcsname{}}}{\newif\ifefloat@tables}%
}%

\def\BreakURLText#1{\@tfor\brk@tempa:=#1\do{\brk@tempa\hskip0pt}}
\let\lt=<
\let\gt=>
\def\processVert{\ifmmode|\else\textbar\fi}
\let\processvert\processVert

\@ifundefined{subparagraph}{
\def\subparagraph{\@startsection{paragraph}{5}{2\parindent}{0ex plus 0.1ex minus 0.1ex}%
{0ex}{\normalfont\small\itshape}}%
}{}

% These are now gobbled, so won't appear in the PDF.
\newcommand\role[1]{\unskip}
\newcommand\aucollab[1]{\unskip}
  
\@ifundefined{tsGraphicsScaleX}{\gdef\tsGraphicsScaleX{1}}{}
\@ifundefined{tsGraphicsScaleY}{\gdef\tsGraphicsScaleY{.9}}{}
% To automatically resize figures to fit inside the text area
\def\checkGraphicsWidth{\ifdim\Gin@nat@width>\linewidth
	\tsGraphicsScaleX\linewidth\else\Gin@nat@width\fi}

\def\checkGraphicsHeight{\ifdim\Gin@nat@height>.9\textheight
	\tsGraphicsScaleY\textheight\else\Gin@nat@height\fi}

\def\fixFloatSize#1{}%\@ifundefined{processdelayedfloats}{\setbox0=\hbox{\includegraphics{#1}}\ifnum\wd0<\columnwidth\relax\renewenvironment{figure*}{\begin{figure}}{\end{figure}}\fi}{}}
\let\ts@includegraphics\includegraphics

\def\inlinegraphic[#1]#2{{\edef\@tempa{#1}\edef\baseline@shift{\ifx\@tempa\@empty0\else#1\fi}\edef\tempZ{\the\numexpr(\numexpr(\baseline@shift*\f@size/100))}\protect\raisebox{\tempZ pt}{\ts@includegraphics{#2}}}}

%\renewcommand{\includegraphics}[1]{\ts@includegraphics[width=\checkGraphicsWidth]{#1}}
\AtBeginDocument{\def\includegraphics{\@ifnextchar[{\ts@includegraphics}{\ts@includegraphics[width=\checkGraphicsWidth,height=\checkGraphicsHeight,keepaspectratio]}}}

\DeclareMathAlphabet{\mathpzc}{OT1}{pzc}{m}{it}

\def\URL#1#2{\@ifundefined{href}{#2}{\href{#1}{#2}}}

%%For url break
\def\UrlOrds{\do\*\do\-\do\~\do\'\do\"\do\-}%
\g@addto@macro{\UrlBreaks}{\UrlOrds}



\edef\fntEncoding{\f@encoding}
\def\EUoneEnc{EU1}
\makeatother
\def\floatpagefraction{0.8} 
\def\dblfloatpagefraction{0.8}
\def\style#1#2{#2}
\def\xxxguillemotleft{\fontencoding{T1}\selectfont\guillemotleft}
\def\xxxguillemotright{\fontencoding{T1}\selectfont\guillemotright}

\newif\ifmultipleabstract\multipleabstractfalse%
\newenvironment{typesetAbstractGroup}{}{}%

%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

\usepackage[authoryear]{natbib}



\newif\ifnokeywords\nokeywordsfalse

\makeatletter\input{size10-pointfive.clo}\makeatother%
\definecolor{kwdboxcolor}{RGB}{242,242,242}
\usepackage[hidelinks,colorlinks=true,allcolors=blue]{hyperref}
\linespread{1}                 
\def\floatpagefraction{0.8}

\usepackage[paperheight=11.69in,paperwidth=8.26in,top=1in,bottom=1in,left=1in,right=.75in,headsep=24pt]{geometry}

\usepackage{multirow-custom}

\makeatletter

\def\hlinewd#1{%
  \noalign{\ifnum0=`}\fi\hrule \@height #1%
  \futurelet\reserved@a\@xhline}
\def\tbltoprule{\hlinewd{1pt}\\[-14pt]}
\def\tblbottomrule{\noalign{\vspace*{6pt}}\hline\noalign{\vspace*{2pt}}}
\def\tblmidrule{\hline\noalign{\vspace*{2pt}}}



\let\@articleType\@empty
\let\@journalDoi\@empty
\let\@journalVolume\@empty
\let\@journalIssue\@empty
\let\@crossMarkLink\@empty
\let\@receivedDate\@empty
\let\@acceptedDate\@empty
\let\@revisedDate\@empty
\let\@publishedDate\@empty
\let\@copyrightYear\@empty
\let\@firstPage\@empty
\def\articleType#1{\gdef\@articleType{#1}}
\def\journalDoi#1{\gdef\@journalDoi{#1}}
\def\crossMarkLink#1{\gdef\@crossMarkLink{#1}}
\def\receivedDate#1{\gdef\@receivedDate{#1}}
\def\acceptedDate#1{\gdef\@acceptedDate{#1}}
\def\revisedDate#1{\gdef\@revisedDate{#1}}
\def\publishedDate#1{\gdef\@publishedDate{#1}}
\def\copyrightYear#1{\gdef\@copyrightYear{#1}}
\def\journalVolume#1{\gdef\@journalVolume{#1}}
\def\journalIssue#1{\gdef\@journalIssue{#1}}
\def\firstPage#1{\gdef\@firstPage{#1}}
\let\@issuelogo\@empty%
\let\@issuelogoex\@empty%
\def\issuelogo#1{\gdef\@issuelogo{#1}}
\def\issuelogoex#1{\gdef\@issuelogoex{#1}}


\def\author#1{%
  \gdef\@author{%
    \hskip-\dimexpr(\tabcolsep)\hskip5pt%
    \parbox{\dimexpr\textwidth-1pt}%
    {\fontsize{11}{13}\selectfont\raggedright #1}%
  }%
}


\usepackage{pharmascope-abs}
\usepackage{caption}
\usepackage{lastpage}
\usepackage{fancyhdr}
\usepackage[noindentafter,explicit]{titlesec}
\usepackage{fontspec}

\setmainfont[%
BoldFont=cambriab.ttf,%
ItalicFont=CAMBRIAI.TTF,%
BoldItalicFont=CAMBRIAZ.TTF]{Cambria.ttf}
\lefthyphenmin = 3

\def\title#1{%
  \gdef\@title{%
      \vspace*{-40pt}%
       \ifx\@articleType\@empty\else{\fontsize{10}{12}\scshape\selectfont\hspace{8pt}\@articleType\hfill\mbox{}\par\vspace{2pt}}\fi%
       \minipage{\linewidth}
         \hrulefill\\[-0.7pt]%%{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}\hfill
         \mbox{~}\hspace{5pt}\parbox{.1\linewidth}{\IfFileExists{images/\@issuelogo.\@issuelogoex}{\includegraphics[width=79pt,height=61pt]{images/\@issuelogo.\@issuelogoex}}{\includegraphics[width=75pt,height=50pt]{ijrps_logo.png}}}\hfill
         \fcolorbox{kwdboxcolor}{kwdboxcolor}{\parbox{.792\linewidth}{%
          \begin{center}\fontsize{17}{17}\selectfont\scshape\vskip-7pt International Journal of Research in Pharmaceutical Sciences\hfill\end{center}%
          \vspace*{-10pt}\hspace*{4pt}{\fontsize{8}{9}\selectfont Published by JK Welfare \& Pharmascope Foundation\hfill  Journal Home Page: \href{www.ijrps.com}{\color{blue}\underline{\smash{www.ijrps.com}}}}\hspace*{4pt}\mbox{}}}%
       \par\vspace*{-1pt}\rule{\linewidth}{1.3pt}%
       \endminipage%
    \par\vspace*{9.2pt}\parbox{.98\linewidth}{\linespread{.9}\raggedright\fontsize{14}{17}\selectfont #1}%
    \vspace*{-8pt}%
  }
}


\setlength{\parindent}{0pt}
\setlength{\parskip}{0.4pc plus 1pt minus 1pt}

\def\abbrvJournalTitle{Int. J. Res. Pharm. Sci.}

\fancypagestyle{headings}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
}\pagestyle{headings}

                                                         
\fancypagestyle{plain}{%
  \renewcommand{\headrulewidth}{0pt}%
  \renewcommand{\footrulewidth}{0.3pt}%
  \fancyhf{}%
  \fancyhead[R]{%
    \fontsize{9.12}{11}\selectfont\RunningAuthor,\ \abbrvJournalTitle,\ \ifx\@journalVolume\@empty X\else\@journalVolume\fi%
    \ifx\@journalIssue\@empty\else(\@journalIssue)\fi%
    ,\ \ifx\@firstPage\@empty 1\else\@firstPage\fi-\pageref*{LastPage}%
  }%
  \fancyfoot[LO,RE]{\fontsize{9.12}{11}\selectfont\textcopyright\ International Journal of Research in Pharmaceutical Sciences}%
  \fancyfoot[RO,LE]{\fontsize{9.12}{11}\selectfont\thepage}
  \ifx\@firstPage\@empty\else\setcounter{page}{\@firstPage}\fi
}


\def\NormalBaseline{\def\baselinestretch{1.1}}
\usepackage{textcase}
\setcounter{secnumdepth}{0}

\titleformat{\section}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{13}\selectfont}
{\thesection}
{6pt}
{\MakeTextUppercase{#1}}
[]
\titleformat{\subsection}[block]{\bfseries\boldmath\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsection}
{6pt}
{#1}
[]
\titleformat{\subsubsection}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubsubsection}
{6pt}
{#1}
[]
\titleformat{\paragraph}[block]{\NormalBaseline\filright\fontsize{10.5}{10}\selectfont}
{\theparagraph}
{6pt}
{#1}
[]
\titleformat{\subparagraph}[block]{\NormalBaseline\filright\fontsize{10.5}{12}\selectfont}
{\thesubparagraph}
{6pt}
{#1}
[]

\titlespacing{\section}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subsubsection}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\paragraph}{0pt}{.5\baselineskip}{.5\baselineskip}  
\titlespacing{\subparagraph}{0pt}{.5\baselineskip}{.5\baselineskip}

\captionsetup[figure]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}
\captionsetup[table]{skip=1.4pt,font=bf,labelsep=colon,justification=raggedright,singlelinecheck=false}

\def\bibyear#1{#1}
%\def\bibjtitle#1{#1}   %%Publisher request
\def\bibauand{}
\setlength\bibsep{3pt}
\setlength\bibhang{8pt}

\makeatother
\date{}


\usepackage[flushleft]{threeparttablex}

\usepackage{float}

\begin{document}


\def\RunningAuthor{Pratiwi S N E et al.}
\firstPage{1462}
\articleType{Review Article}
\receivedDate{20 Mar 2021}
\acceptedDate{26 Apr 2021}
\revisedDate{25 Apr 2021}
\journalVolume{2021, 12}
\journalIssue{2}
\journalDoi{ijrps.v12i2.4716}
\copyrightYear{2021}
\def\authorCount{3}
\def\affCount{1}

\def\journalTitle{International Journal of Research in Pharmaceutical Sciences}

\title{A review of the phytochemical compounds and pharmacological activities of \textit{Eurycoma longifolia}}
\author{Insanu~M,  
            Pratiwi~S~N~E\textsuperscript{*}, 
            Fidrianny~I~\\[5pt]{Department of Pharmaceutical Biology, School of Pharmacy, Bandung Institute of Technology, Bandung-40132, Indonesia}}

\begin{abstract}
\textit{Eurycoma longifolia} belongs to Simaroubaceae family. It is a tall tree and has different local name from many countries and this review consisted of their traditional usage, phytochemical compounds and pharmacological activity. A systematic review was conducted to study the scientific work of \textit{E. longifolia} which published in the last 10 years and minimum 20 articles that published in the last 2 years, published in Pubmed, Scopus etc. also has a digital object identifier (DOI). \textit{E. longifolia} was a popular traditional medicine. The leaves wasused as supplement for giving birth, its bark as anthelmintic and its roots as antimalaria, laxative, antidiabetic etc.Due to high demand of this plant there are various formula of \textit{E. longifolia} available in health food market. Many studies have been performed to determine the active constituents and pharmacology activities of \textit{E. longifolia}.  Alkaloid, quassinoid, polyphenols, flavonoid, polysaccharide, triterpenoid were found in \textit{E. longifolia}.  Quassinoids is a major phytochemical compound in \textit{E. longifolia} which has various types like eurycumanone, eurycomanol, eurycomadilactone and eurylactone. Quassinoids has bitter taste and often found in Simaroubaceae family.Pharmacological activities of \textit{E. longifolia} such as anti-inflammatory, analgesic, antioxidant, antimicrobial, antidiabetic, anti-osteoporotic activities. The literature review results showed that \textit{E. longifolia} can be considered as medicinal plant for human. In the future, further studies on mechanism of pharmacology activity of \textit{E. longifolia} are warranted.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Eurycoma Longifolia,\newline Traditional Usage,\newline Phytochemical Compound,\newline Pharmacology Activity
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Pratiwi~S~N~E~\\ Phone:\ +62-82218747914~\\  Email:\ sausanpratiwi17@gmail.com
        \par}\vspace*{-11pt}\hrulefill\par{\fontsize{12}{14}\selectfont ISSN: 0975-7538}\par% 
        \textsc{DOI:}\ \href{https://doi.org/10.26452/\@journalDoi}{\textcolor{blue}{\underline{\smash{https://doi.org/10.26452/\@journalDoi}}}}\par%
        \vspace*{-11pt}\hrulefill\\{\fontsize{9.12}{10.12}\selectfont Production and Hosted by}\par{IJRPS |~\href{www.ijrps.com}{www.ijrps.com}}\par%
        \vspace*{-2pt}{\fontsize{9.12}{10.12}\selectfont\textcopyright\ \@copyrightYear\ $|$ All rights reserved.}\par%
        \vspace*{-11pt}\rule{\linewidth}{1.2pt}
        \makeatother
        
    
\section{Introduction}
\textit{Eurycoma longifolia} is one of the species in Eurycoma genus and belong to Simaroubaceae family. This plant is originated from the Southeast Asia so can be found in Malaysia, Laos, Cambodia, Myanmar, Indonesia, Vietnam and Thailand. \textit{E. longifolia} also called as bidaralaut and pasakbumi (Indonesia), tongkatali, lempedupahit, bedaramerah (Malaysia), Ian-don, piak and tung saw (Thailand), Cay babenh and bbabinh (Vietnam), tho nan (Laotian) \unskip~\citep{1086301:22080276}. \textit{E. longifolia} is a slender, shrubby, tall and slow-growing tree andwell known as herbal medicine \unskip~\citep{1086301:22080304}. Since old time, \textit{E. longifolia} has been used as traditional medicine and nowadays this plant has been sold in the market with various form. Their leaves, barks and roots have been used as traditional medicine for different diseases. 

Many studies have been performed to determine the active constituents and pharmacology activities of \textit{E. longifolia}. Several parts of \textit{E. longifolia} have been used to treat some diseases.The most commonly used part is the roots because it has many active constituents. The extract also has been studied and proved that contain many active substances to treat various diseases \unskip~\citep{1086301:22080292}. Active substances such as quassinoids, alkaloids, squalene derivatives, triterpenes were found in \textit{E. longifolia}. The major active substance of \textit{E. longifolia }was quassinoids with various type and biological activities.Quassinoids has bitter taste and often found in Simaroubaceae family \unskip~\citep{1086301:22080273}. Eurycomanone is the most bioactive of quassinoids found in \textit{E. longifolia}\unskip~\citep{1086301:22080299}. Some of pharmacological activities of \textit{E. longifolia }were antimicrobial, antidiabetic, cytotoxicity against cancerous cells, drug for sexual insufficiency, immunomodulator, anti-inflammation, etc.\unskip~\citep{1086301:22080321}. In this article review, we aimed to examine the chemical substances and pharmacological activities of \textit{E. longifolia}.
    
\section{Materials and Methods}
The article review was conducted by collecting the scientific work about chemical compound, and pharmacology activity of \textit{E. longifolia} which published in the last 10 years and minimum 20 articles that published in the last 2 years, published in Pubmed, Scopus etc., also has a DOI. The scientific work search by using keyword ``\textit{Eurycoma longifolia}''. 
    
\section{Results and Discussion}
\textbf{Traditional Uses}

In Malaysia, decoction of \textit{E. longifolia} have been used to treat depression, high blood pressure, malaria and fatigue \unskip~\citep{1086301:22080280}.  Based on cultural beliefs, the traditional uses of \textit{E. longifolia} have been passed from generation to generations. The taste of the decoction is bitter and it is assumed more bitter give better efficacy \unskip~\citep{1086301:22080314}. 


\begin{table*}[!htbp]
\caption{\boldmath {Anti-inflammatory activity of isolated compound} }
\label{tw-8ffd89e5573a}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.487\linewidth-2\tabcolsep}p{\dimexpr.25130000000000006\linewidth-2\tabcolsep}p{\dimexpr.26169999999999998\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack Compound & \cAlignHack IC\ensuremath{_{50}} (\ensuremath{\mu}M) & \cAlignHack Ci\ensuremath{_{95}}(\ensuremath{\mu}M)\\
\tblmidrule 
\cAlignHack Eurycomalide C &
  \cAlignHack 18.4 &
  \cAlignHack 16.9\ensuremath{-}20.1 \\
\cAlignHack Eurycomalactone &
  \cAlignHack 0.5 &
  \cAlignHack 0.3\ensuremath{-}0.7\\
\cAlignHack 7\ensuremath{\alpha }-hydroxyeurycomalactone  &
  \cAlignHack 1.5 &
  \cAlignHack 1.3\ensuremath{-}1.6\\
\cAlignHack 5,6-dehydroeurycomalactone  &
  \cAlignHack 6.2 &
  \cAlignHack 5.3\ensuremath{-}7.4\\
\cAlignHack Eurycolactone E &
  \cAlignHack 3.8 &
  \cAlignHack 3.2\ensuremath{-}4.5\\
\cAlignHack Longilactone &
  \cAlignHack 4.7 &
  \cAlignHack 3.7\ensuremath{-}5.9\\
\cAlignHack 14,15\ensuremath{\beta }-dihydroxyklaieanone &
  \cAlignHack 1.0 &
  \cAlignHack 0.8\ensuremath{-}1.2\\
\cAlignHack 11-dehydroklaieanone  &
  \cAlignHack 1.9 &
  \cAlignHack 1.8\ensuremath{-}2.1\\
\cAlignHack Eurycomanone  &
  \cAlignHack 2.4 &
  \cAlignHack 2.0\ensuremath{-}2.9\\
\cAlignHack 13,21-dehydroeurycomanone &
  \cAlignHack 0.7 &
  \cAlignHack 0.6\ensuremath{-}0.9\\
\cAlignHack 1-methoxycarbonyl-\ensuremath{\beta }-carboline  &
  \cAlignHack 29.3 &
  \cAlignHack 20.3\ensuremath{-}42.4\\
\cAlignHack 9-hydroxycanthin-6-one  &
  \cAlignHack 3.8 &
  \cAlignHack 3.3\ensuremath{-}4.4\\
\cAlignHack 9-methoxycanthin-6-one  &
  \cAlignHack 7.4 &
  \cAlignHack 6.6\ensuremath{-}8.2\\
\cAlignHack 9,10-dimethoxycanthin-6-one  &
  \cAlignHack 19.5 &
  \cAlignHack 13.0\ensuremath{-}29.4\\
\cAlignHack 3,5,6,7,8,3\ensuremath{'},4\ensuremath{'}-heptamethoxyflavone  &
  \cAlignHack 23.3 &
  \cAlignHack 18.4\ensuremath{-}29.4\\
\cAlignHack Parthenolide (positive control) &
  \cAlignHack 1.5 &
  \cAlignHack 1.3\ensuremath{-}1.8\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begin{table*}[!htbp]
\caption{\boldmath {Antimicrobial activity of \textit{E. longifolia}} }
\label{tw-334d484d7bf8}
\centering 
\begin{threeparttable}

\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.12120000000000001\linewidth-2\tabcolsep}p{\dimexpr.0823\linewidth-2\tabcolsep}p{\dimexpr.0745\linewidth-2\tabcolsep}p{\dimexpr.082\linewidth-2\tabcolsep}p{\dimexpr.09\linewidth-2\tabcolsep}p{\dimexpr.09\linewidth-2\tabcolsep}p{\dimexpr.09\linewidth-2\tabcolsep}p{\dimexpr.09\linewidth-2\tabcolsep}p{\dimexpr.1078\linewidth-2\tabcolsep}p{\dimexpr.08020000000000001\linewidth-2\tabcolsep}p{\dimexpr.092\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Microorganism & \multicolumn{2}{p{\dimexpr(.1568\linewidth-2\tabcolsep)}}{\cAlignHack Methanol extract} & \multicolumn{2}{p{\dimexpr(.172\linewidth-2\tabcolsep)}}{\cAlignHack Acetone extract} & \multicolumn{2}{p{\dimexpr(.18\linewidth-2\tabcolsep)}}{\cAlignHack Ethyl acetate extract} & \multicolumn{2}{p{\dimexpr(.1978\linewidth-2\tabcolsep)}}{\cAlignHack Chloroform extract} & \multicolumn{2}{p{\dimexpr(.1722\linewidth-2\tabcolsep)}}{\cAlignHack Petroleum ether extract}\\
\rowcolor{kwdboxcolor} & \cAlignHack Stem & \cAlignHack Root & \cAlignHack Stem & \cAlignHack Root & \cAlignHack Stem & \cAlignHack Root & \cAlignHack Stem & \cAlignHack Root & \cAlignHack Stem & \cAlignHack Root\\
\tblmidrule 
\textit{E. coli} &
  \cAlignHack + &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack -\\
\textit{P. aeruginosa} &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack + &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack -\\
\textit{S. Virchow} &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack -\\
\textit{B. cereus} &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack +\\
\textit{S. aureus} &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack + &
  \cAlignHack +\\
\textit{A. A. niger} &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack + &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack - &
  \cAlignHack -\\
\tblbottomrule 
\end{tabulary}\par 
\begin{tablenotes}\footnotesize 
    
\item{Note: + = present; - = absent}
\end{tablenotes}
\end{threeparttable}

\end{table*}

\bgroup
\fixFloatSize{images/df713e8e-ce11-47eb-868a-97d6e851f5f1-upicture1.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/df713e8e-ce11-47eb-868a-97d6e851f5f1-upicture1.png}{\includegraphics{images/df713e8e-ce11-47eb-868a-97d6e851f5f1-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Structure of chemical compounds in \textit{E. longifolia}}}
\label{f-3f0cc5e9781e}
\end{figure*}
\egroup
It has been commonly used in traditional medicine to treat dysentery and glandular swelling \unskip~\citep{1086301:22080320}. The leaves of \textit{E. longifolia} was used as herbal supplement for following child-birth and prevent gum disease \unskip~\citep{1086301:22080278}. Mostly the bark of \textit{E. longifolia} is used as anthelmintic. Its roots extract was used as traditional medicine for malaria, aging, aches, constipation, fever, enhancing energy, osteoporosis, diabetes, anxiety, syphilis, stress, etc. \unskip~\citep{1086301:22080279}.\textit{ E. longifolia} is also popular for its aphrodisiac effect that can enhancing libido due to its ability to stimulate the production of androgen hormones \unskip~\citep{1086301:22080286}.

Due to high demand of this plant there are various formula of \textit{E. longifolia} are available in health food market, in crude drug powder form or capsules which contain crude drug powder or \textit{E. longifolia} extract \unskip~\citep{1086301:22080296}. It can be found as health supplements in capsules, tablets and beverages \unskip~\citep{1086301:22080318}. Nowadays, root extract of\textit{ E. longifolia} used as pre-mixed in tea, coffee and carbonated drink which sales in commercial market \unskip~\citep{1086301:22080277}. 

\textbf{Phytochemical Compounds}

Several major phytochemical compounds have been determined in \textit{E. longifolia} such as quassinoid, squalene-type triterpenes, canthin-6-one alkaloids, and tirucallane-type triterpenes \unskip~\citep{1086301:22080291}. Quassinoidswas the most phytochemical compound identified in\textit{ E. longifolia}, mostly C18-C22 quassinoids \unskip~\citep{1086301:22080287}. Besides that, polyphenols, high molecular weight polysaccharides and glycoprotein were also founded in root of \textit{E. longifolia}\unskip~\citep{1086301:22080281}. Polar to semi-polar saponins have been founded in \textit{E. longifolia} roots \unskip~\citep{1086301:22080311}. 

Flavonoids was discovered in ethyl acetate, chloroform, methanol and acetone extracts of stem and root of \textit{E. longifolia}. Alkaloids was only detected in chloroform, ethyl acetate and petroleum ether extracts of the stem. Terpenoids was observed in all the extracts except acetone extract. All the extracts of \textit{E. longifolia} stem except petroleum ether and chloroform have been discovered the presence of protein \unskip~\citep{1086301:22080275}. Eurylophenolosides A and B, eurylolignanosides A and B which were four new phenolic acid along with 12 known isolates were detected from 70\% ethanol extract of the roots \unskip~\citep{1086301:22080303}.

Quassinoid has many various types with biological activity. Phytochemical studies of this \textit{E. longifolia} have led to the discovery of quassinoids type which promising various biological activities \unskip~\citep{1086301:22080294}. Five quassinoids, eurycomanone, 13\ensuremath{\alpha }(21)-epoxyeurycomanone, eurycomanol, eurycomanol-2-O-\ensuremath{\beta }-d-glucopyranoside and 13,21-dihydroeurycomanone were observed using electrospray ionization (ESI) and atmospheric pressure chemical (APCI) in positive and negative ion modes \unskip~\citep{1086301:22080300}. Other five new quassinoids, eurylactone E, eurylactone F, eurylactone G, eurycomalide D, and eurycomalide E were identified along with 10 known quassinoids \unskip~\citep{1086301:22080274}. Meanwhile study by \unskip~\cite{1086301:22080310}  exposed that \ensuremath{\Delta }4,5,14-hydroxyglaucarubo, 5-iso-eurycomadilactone, eurycomadilactone, 13-epi-eurycomadilactone was found as four new quassinoids. The structure of chemical compounds in \textit{E. longifolia }was shown in Figure~\ref{f-3f0cc5e9781e}.

\textbf{Pharmacological Activities}

\textit{E. longifolia} had many pharmacological activities. The activities were described below:

\textbf{Antioxidant Activity}

Administration of 70\% ethanol extract of \textit{E. longifolia} root proved increase SOD (Super Oxidant Dismutase) levels and reducing MDA (Malondialdehyde) levels. \textit{E. longifolia} contained flavonoid, alkaloid, phenols and glycoside which were known to have antioxidant activity \unskip~\citep{1086301:22080306}. Flavonoid has a role as free radical scavenger and stimulating antioxidant enzymes. Alkaloid has a role as scavenger of superoxide radical. The activity of antioxidant and SOD enzymes would increase but superoxide anion level decrease \unskip~\citep{1086301:22080309}.

The other research by \unskip~\cite{1086301:22080289}  presented that \textit{E. longifolia }inhibited PDE-5, arginase and angiotensin-converting enzyme(ACE) as pro-oxidant-induced lipid peroxidation in a concentration dependent. The inhibitory activity showed with half maximum inhibitory concentration (IC\ensuremath{_{50}}). The result on PDE-5 (IC\ensuremath{_{50\ }} = 251.8 \ensuremath{\mu}g/ml), ACE (IC\ensuremath{_{50}} = 96.07 \ensuremath{\mu}g/ml) and arginase (IC\ensuremath{_{50\ }} = 48.28 \ensuremath{\mu}g/ml).

\textbf{Anti-inflammatory and Analgesic Activity}

All of the alkaloids from \textit{E. longifolia} roots displayed potential nitric oxide(NO) inhibitory activities on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Many compounds such as 4,9-dimethoxy-5-hydroxycanthin-6-one, 1-hydroxy-canthin-6-one, 4-methoxycanthin-6-one, 5-methoxy-canthin-6-one, 8-hydroxy9-methoxyycanthin-6-one, 4,9-dimethoxycanthin-6-one, 5,9-dimethoxycanthin-6-one and 9,10-dimethoxycanthin-6-one inhibited NO release from LPS-stimulated RAW264.7 \unskip~\citep{1086301:22080312}.

Some of quassinoids and alkaloids showed the most potent NF-\ensuremath{\kappa }B inhibitory effect with IC\ensuremath{_{50\ }} displayed in the Table~\ref{tw-8ffd89e5573a}\unskip~\citep{1086301:22080302}. Recent study was identified new anti-inflammatory \ensuremath{\beta }-carboline, 7-methoxy-(9H\ensuremath{\beta }-carbolin-1-il)-(E)-1-propenoic acid from \textit{E. longifolia} hairy roots which had strong inhibitory effect on NO release and decrease cyclooxygenase-2 (COX-2) expression induced by LPS RAW264.7 \unskip~\citep{1086301:22080293}.

\textit{E. longifolia} extract discovered anti-inflammatory activity on carrageenan-induced paw edema. It inhibits the expression of COX-2 induced by LPS through blocking the NF-\ensuremath{\kappa }B translocation. The extract also showed analgesic effect on heat-induced (hot plate test) and chemical-induced pain (acetic acid induced writhing). The analgesic effects were time and dose dependent and the analgesic activity of 400 mg/kg \textit{E. longifolia} was higher than aspirin at 2 and 3 h after administration in heat-induced pain but lesser at 1 h. Thus, the onset time of \textit{E. longifolia} is slower than aspirin \unskip~\citep{1086301:22080305}. 

\textbf{Immunomodulatory and Cytotoxic Activity}

Polysaccharide from \textit{E. longifolia} roots could activate macrophages by improving pinocytic and phagocytic abilities in concentrations {\textless}250 \ensuremath{\mu}g/ml, promote NO and cytokine secretion. The polysaccharide containeduronic acid and its backbone composed of \ensuremath{\beta }-1,4-xylose which enhanced its immunomodulatory activity \unskip~\citep{1086301:22080297}. sd

The compounds TAF273, F3 and F4 from methanolic extract of E. longifolia roots found had cytotoxic activity at IC\ensuremath{_{50\ }} 19\ensuremath{\pm}3, IC\ensuremath{_{50\ }} 55\ensuremath{\pm}2 and IC\ensuremath{_{50\ }} 62\ensuremath{\pm}7\ensuremath{\mu}g/ml.The TAF273, F3 and F4 were tested on K-562 cells \unskip~\citep{1086301:22080316}. The extract have been reported able to increase immunological parameters such as T cells, CD4\ensuremath{^{+}} T cells and lymphocytes \unskip~\citep{1086301:22080315}.

\textbf{Antitumor Activity}

Extract of \textit{E. longifolia} root enhanced the apoptotic level of adenocarcinoma cells. Thehigher the dose of \textit{E. longifolia} extract showed the higher the apoptotic level of adenocarcinoma cells. After 24 h given the extract, the percentage of DNA damaged cells increased 39,4\% and 43,5\% after 48 h with highest concentration (100 \ensuremath{\mu}g/ml) \unskip~\citep{1086301:22080295}.

The treatment with TAF273 compound induced apoptotic in K-562 cells in dose and time dependent. The TAF273 compound at concentration 25 and 50 \ensuremath{\mu}g/ml enhanced apoptotic index (AI) from 10\% (untreated) to 30 and 41\%. Eurycomanone at concentration of 6 and 12 \ensuremath{\mu}g/ml also enhanced the apoptotic index to approximately 28 and 39\%. The apoptotic index were calculated from the mean from at least three experiments \unskip~\citep{1086301:22080316}.

\textbf{Anti-osteoporotic}

\unskip~\cite{1086301:22080298}  revealed that \textit{E. longifolia} had a potential in treating androgen deficient osteoporosis in men by alternative agent to testosterone replacement. Based on histomorphometry, quassinoids in \textit{E. longifolia} extract effective as testosterone in the ORX + EL25, DGX + EL50, and DGX + EL100 groups to reduce degenerative changes of bone structure by enhancing bone volume and trabecular number. The extract also reduced percentage of osteoclast and increased percentage of osteoblast \unskip~\citep{1086301:22080319}. Other than that \textit{E. longifolia} suppressed the high of C-terminal telopeptide of type I~collagen to prevent the enhancement of bone resorption rate after orchiectomy \unskip~\citep{1086301:22080313}. Based on recent study, \textit{E. longifolia} showed anti-osteoporotic effect in six samples which improved fracture bones by increasing bone volume \unskip~\citep{1086301:22080310}.

\textbf{Sexuality Drug for Men}

\unskip~\cite{1086301:22080288}  demonstrated that \textit{E. longifolia} was detected to increase male sexual libido, male fertility, penile erection and testosterone level. The conventional way to treat TDS (testosterone deficiency syndrome) is TRT (testosterone replacement therapy). \textit{E. longifolia} showed improving sexual health by restoring testosterone levels and naturally used as TRT \unskip~\citep{1086301:22080308}. 

Studies showed eurypeptides activate CYP17(17 \ensuremath{\alpha }-hydroxylase/17,20 lyase), an enzyme that enhancing the conversion of pregnolone and 17-OH-pregnolone to produce more dehydroepiandrosterone and the metabolism of pregnolone and 17-OH-pregnolone to testosterone and 4-androstenedione \unskip~\citep{1086301:22080324}. Aqueous extract of \textit{E. longifolia} found to inhibit ROCK-II which has a role for inhibiting smooth muscle contraction.Trans-coniferyl aldehyde, eurycomanone and scopoletin exhibited maximum inhibition of ROCK-II at 82.1\ensuremath{\pm}0.63, 78.3\ensuremath{\pm}0.38 and 77.1\ensuremath{\pm}0.11 \% \unskip~\citep{1086301:22080290}.

\textbf{Anticancer and Antiproliferative}

Eurycomanone had ability to affect the expression of cellular protein that have multifunctional roles in proliferation and associated with cancer development. This compound will affect cell replication that involving in p53 tumor suppressor gene, cancer cells with hnRNP A2/B1 markers, annexin I, prohibitin and inhibit lung cancer proliferation \unskip~\citep{1086301:22080272}. SQ40 contain 40\% of the total quassinoids showed inhibitory activity against LNaP human prostate cancer cells. SQ40 detected to inhibit LNCaP cell growth at IC\ensuremath{_{50\ }} 5.97 \ensuremath{\mu}g/ml. In lower dose, SQ40 inhibited LNCaP cell growth and in higher dose SQ40 can cause cleavage in LNCaP cells \unskip~\citep{1086301:22080317}.

\textbf{Antimicrobial activity}

Methanol, acetone, ethyl acetate, chloroform and petroleum ether extract of E. longifolia roots were found active against Gram positive bacteria but inactive against Gram negative bacteria. The chloroform extract of the root exhibited highest activity among Gram positive bacteria with inhibition zone of 11.67 \ensuremath{\pm} 1.53 mm against S. aureus followed by acetone extract with inhibition zone of 11.00 \ensuremath{\pm} 1.00 mm at 200 \ensuremath{\mu}g/ml.

Stem extracts were found active against Gram positive bacteria and showed low to moderate activity against Gram negative bacteria with inhibition zone of 9.33 \ensuremath{\pm} 0.58 mm against P\textit{. aeruginosa} and 3.33 \ensuremath{\pm} 5.77 mm against \textit{E. coli}. The ethyl acetate exposed the highest activity among all tested extracts with inhibition zone of 11.00 \ensuremath{\pm} 1.73 mm against \textit{Aspergillusniger} at 200 \ensuremath{\mu}g/ml \unskip~\citep{1086301:22080275}. The antimicrobial activity of \textit{E. longifolia} root and stem were presented in Table~\ref{tw-334d484d7bf8}.

Research by \unskip~\cite{1086301:22080322}  study regarding influence of \textit{E. longifolia} against tuberculosis. Treatment tuberculosis with \textit{E. longifolia} and rifampicin found increasing in TNF-\ensuremath{\alpha } production by promoting autophagy through ERK1/2 and NF-Kb signal to suppress intracellular \textit{Mycobacterium tuberculosis} growth. Pasakbumin play a role in this activity. It was also enhanced levels of pro-inflammatory cytokine and NO via ERK1/2 and NF-Kb.

\textbf{Antidiabetic}

\textit{E. longifolia} root was capable in modulating glucose and lipid metabolism. It enhanced insulin sensitivity and suppressed lipid production in 3T3-L1 adipocytes simultaneously. Also increase uptake glucose up to more than 200\% with a dose of 50 \ensuremath{\mu}g/mL \unskip~\citep{1086301:22080323}. 

As said above, \textit{E. longifolia} has been used to treat erectile dysfunction that one of the compilations cause by diabetes. More than half men having diabetic also experiencing erectile dysfunction led to impotency \unskip~\citep{1086301:22080285}. \textit{E. longifolia }800 mg/kg showed reducing in omentum fat weight and body weight of 31,9\% and 5,7\%. Opponently the serum testosterone concentration increased by 30.2\% \unskip~\citep{1086301:22080282}.

\textbf{Anti-obesogenic}

\textit{E. longifolia} root expressed strong potential lipolysis enhancement but low pancreatic lipase inhibitory and reduced lipid accumulation in 3T3-l1 adipocytes. The roots containedeurycomanone and 13\ensuremath{\beta },21-epoxyeurycomanone which increased lipolysis with EC\ensuremath{_{50}} of 14.6 and 8.6 \ensuremath{\mu}M \unskip~\citep{1086301:22080301}. The standardized quassinoid and eurycomanone fractionwas found affected in 3Y3-L1 preadipocyte cells. Both compounds decreased body weight, epididymal and perianal fat. Besides that, standardized quassinoids-enriched fraction (SQEL) also increased glucose clearance, reduced elevated total cholesterol and serum triglycerides levels \unskip~\citep{1086301:22080284}.

\textbf{Antigout}

Quassinoids in \textit{E. longifolia} hadhuman urate transporter 1 (URAT1) inhibition activity by reducing blood uric acid levels in induced hyperuricemia animal model \unskip~\citep{1086301:22080283}. Study by \unskip~\cite{1086301:22080307}  presented that \textit{E. longifolia }reduced ankle swelling caused by gout in low and medium doses which indicated that \textit{E. longifolia} has anti-gout effect.
    
\section{Conclusion}
This review summarized the traditional usage, phytochemical compound and pharmacology activity. Based on the literature review was reported the most compound that gave pharmacology activity on \textit{E. longifolia} were quassinoids especially euricumanone. This review showed \textit{E. longifolia} has potential as medicinal plant which can be developed into traditional medicine for human. In the future, further study about mechanism of pharmacology activity of \textit{E. longifolia} is needed. 
    
\section{Acknowledgement}
The authors are thankful to Department of Pharmaceutical Biology, School of Pharmacy, Bandung Institute of Technology, Bandung, Indonesia, for providing the facilities. 

\textbf{Conflict of Interest}

The authors declare that there is no conflict of interest for this study.

\textbf{Funding Support}

The authors declare that they have no funding support for this study.
    

\bibliographystyle{pharmascope_apa-custom}

\bibliography{\jobname}
\end{document}
