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\def\RunningAuthor{Alfred Maroyi}
\firstPage{5596}
\articleType{Review Article}
\receivedDate{21 May 2020}
\acceptedDate{06 Aug 2020}
\revisedDate{19 Jun 2020}
\journalVolume{2020, 11}
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\title{\textbf{Review of phytochemistry, biological activities and therapeutic potential of \textit{Cleistochlamys kirkii}}}
\author{Alfred~Maroyi\textsuperscript{*}~\\[5pt]{Department of Botany, University of Fort Hare, Private Bag X1314, Alice 5700, South Africa}}

\begin{abstract}
\textit{Cleistochlamys kirkii} (Benth.) Oliv is a shrub or small tree widely used as a traditional medicine in the east and central Africa. \textit{Cleistochlamys kirkii} is indigenous to Malawi, Mozambique, Tanzania, Zambia and Zimbabwe. This study is aimed at evaluating the phytochemistry, biological activities and therapeutic potential of \textit{C. kirkii}. Results of the current study are based on data derived from several online databases such as Scopus, Google Scholar, PubMed and Science Direct, and pre-electronic sources such as scientific publications, books, dissertations, book chapters and journal articles. This study revealed that the leaf and root infusion, maceration and decoction of \textit{C. kirkii } are mainly used as traditional medicines for haemorrhoid wounds, rheumatism and tuberculosis. Phytochemical compounds identified from the species include \ensuremath{\alpha },\ensuremath{\beta }-unsaturated lactone, acetogenin, benzyl benzoate derivatives, c-benzylated flavanone, heptanolide, an indole alkaloid, phenolics, polyoxygenated cyclohexene and derivatives, sesquiterpene and tetracyclic triterpenes. \textit{In vitro} studies have confirmed the biological activities of \textit{C. kirkii } crude extracts and compounds isolated from the species which include antibacterial, antifungal, antiplasmodial and cytotoxicity. Documentation of the medicinal uses, phytochemistry and pharmacological properties of \textit{C. kirkii } is essential as this information provides baseline data required for future research and development of health-promoting and pharmaceutical products. \textit{Cleistochlamys kirkii} should be subjected to detailed ethnopharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological properties.
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}Annonaceae,\newline Cleistochlamys kirkii,\newline indigenous pharmacopeia,\newline traditional medicine,\newline tropical Africa
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Alfred~Maroyi~\\ Phone:\ +27406022322 ~\\  Email:\ amaroyi@ufh.ac.za
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\section{Introduction}
\textit{Cleistochlamys kirkii} (Benth.) Oliv is a shrub or small tree belonging to the Annonaceae, commonly known as the custard apple family. Annonaceae is one of the most diverse and primitive plant families consisting of about 108 genera and 2400 species worldwide \unskip~\citep{844184:19928712,844184:19928704} argued that members of the Annonaceae family are used throughout the world as sources of traditional medicines used against arthritis, gastrointestinal problems, hypertension, inflammation, respiratory infections, rheumatism, skin infections, snake bites, sores and wounds. The extracts and phytochemical compounds isolated from Annonaceae species are characterized by analgesic, anthelmintic, antidia-


\begin{table*}[!htbp]
\caption{\boldmath {Medicinal uses of Cleistochlamys kirkii } }
\label{tw-e3e0ee5516ab}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.32230000000000004\linewidth-2\tabcolsep}p{\dimexpr.33769999999999996\linewidth-2\tabcolsep}p{\dimexpr.34\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}Medicinal uses & Plant part used & Reference\\
\tblmidrule 
Cough &
  Leaf and root decoction taken orally &
  \unskip~\citep{844184:19928722}\\
General weakness &
  Leaf and root decoction taken orally  &
  \unskip~\citep{844184:19928722}\\
Haemorrhoid wounds &
  Leaf decoction applied topically &
  \unskip~\citep{844184:19928703,844184:19928716}\\
Hernia &
  Leaf and root decoction taken orally &
  \unskip~\citep{844184:19928705,844184:19928701}\\
Muscular pains &
  Leaf and root maceration taken orally &
  \unskip~\citep{844184:19928722,844184:19928701}\\
Purgative &
  Leaf and root decoction taken orally &
  \unskip~\citep{844184:19928722}\\
Rheumatism &
  Leaf decoction applied topically &
  \unskip~\citep{844184:19928709,844184:19928700}\\
Stomach ache &
  Leaf and root maceration taken orally &
  \unskip~\citep{844184:19928722,844184:19928701}\\
Tuberculosis &
  Leaf infusion and/or decoction taken orally &
  \unskip~\citep{844184:19928709,844184:19928715}\\
Venereal diseases &
  Leaf and root decoction taken orally &
  \unskip~\citep{844184:19928722,844184:19928701}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
betic, anti-inflammatory, antimicrobial, antioxidant, antipyretic, antiulcer, antinociceptive, antimalarial, antiprotozoal, antileishmanial, cytotoxicity and hepatoprotective properties \unskip~\citep{844184:19928713,844184:19928698}. The genus \textit{Cleistochlamys }Oliver is a monotypic genus confined to east and central tropical Africa \unskip~\citep{844184:19928708,844184:19928710}. The genus name ``\textit{Cleistochlamys}'' is a contraction of two Greek words ``\textit{kleistos}'' or ``\textit{klistos}'' meaning ``closed'' and ``\textit{chlamys}'' or ``\textit{chlamydos}'' meaning ``cloak'' \unskip~\citep{844184:19928702}. The specific name ``\textit{kirkii}'' honours Sir John Kirk (1832 {\textendash} 1922), a Scottish physician, naturalist and companion of the explorer David Livingstone, a British administrator in Zanzibar who recorded and collected the tree species in Sena district of Mozambique \unskip~\citep{844184:19928725}.

\textit{Cleistochlamys kirkii }(Figure~\ref{f-24376a49c361}) is a much-branched shrub or small straggling tree, seldom taller than 10 metres \unskip~\citep{844184:19928699}. The bark of \textit{C. kirkii } is smooth, tough, pale grey to light brown in colour and flaking. The leaves are simple, alternate, narrowly oblong to obovate and thinly textured \unskip~\citep{844184:19928723}. The leaves are dark to bright shiny green above, blue-green and slightly paler below, apex rounded, often notched with a broadly tapering to the rounded base with entire and waxy margins \unskip~\citep{844184:19928721}. The flowers are axillary, sessile, with a heavy sweet scent, creamy-white with reddish-brown bracts below, appearing when trees are leafless. The fruit is a cluster of fleshy oval berries which are purple-black when ripe (Figure~\ref{f-24376a49c361}). \textit{Cleistochlamys kirkii} has been recorded in alluvium soils in hot and dry bushveld, thickets and river valleys in Malawi, Mozambique, Tanzania, Zambia and Zimbabwe up to an altitude of 900 m above sea level \unskip~\citep{844184:19928718,844184:19928719}. The fruit of \textit{C. kirkii} is eaten fresh or left to stand in water to make a pleasant fruit drink \unskip~\citep{844184:19928707,844184:19928724}. \textit{Cleistochlamys kirkii} is\textit{\space } an important medicinal plant species in southern Africa \unskip~\citep{844184:19928709,844184:19928722}. Thus, this review aims to provide an integrated and detailed appraisal of the existing knowledge on the phytochemistry, biological activities and therapeutic potential of \textit{C. kirkii}.

\textbf{Medicinal uses of } \textit{\textbf{Cleistochlamys kirkii }} \textbf{\space }

The leaf and root infusion, maceration and decoction of \textit{C. kirkii } are mainly used as traditional medicines for haemorrhoid wounds, rheumatism and tuberculosis \unskip~\citep{844184:19928715,844184:19928717} (Table~\ref{tw-e3e0ee5516ab}). 

Other medicinal applications of \textit{C. kirkii} supported by at least two literature records include the use of leaf and root decoction against hernia, muscular pains, stomach ache and venereal diseases \unskip~\citep{844184:19928722,844184:19928701}.


\begingroup
\makeatletter\if@twocolumn\@ifundefined{theposttbl}{\gdef\TwoColDocument{true}\onecolumn\onecolumn}{}\fi\makeatother \setlength\LTcapwidth{\textwidth}
\begin{longtable}{p{\dimexpr.3319\linewidth-2\tabcolsep}p{\dimexpr.3013\linewidth-2\tabcolsep}p{\dimexpr.3668\linewidth-2\tabcolsep}}
\caption{\boldmath {Phytochemical composition of Cleistochlamys kirkii } }
\label{tw-36eaccf07776}
\def\arraystretch{1.1}\\\endfirsthead \hline \noalign{\vskip3pt} \noalign{\textit{Table \thetable\ continued}} \noalign{\vskip3pt} \hline \endhead \hline \noalign{\vskip3pt} \noalign{\textit{\hfill Continued on next page}} \noalign{\vskip3pt} \endfoot \endlastfoot 
\tbltoprule \rowcolor{kwdboxcolor}Phytochemical compound & Plant part & Reference\\
\tblmidrule 
(-)-1,6-desoxy-\ensuremath{\beta }-senepoxide &
  Fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715}\\
(1S,4S,5S,6R)-5-[(benzyloxy)- methyl]-5,6-dihydroxycyclohex-2-ene-1,4-diyl diacetate &
  Leaves &
  \unskip~\citep{844184:19928703}\\
2-Methoxybenzylbenzoate &
  Root bark &
  \unskip~\citep{844184:19928700}\\
3-hydroxybenzaldehyde &
  Leaves &
  \unskip~\citep{844184:19928703}\\
7-Methoxyisochamanetin &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Acetylmelodorinol &
  Bark, fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715,844184:19928717}\\
(E)-Acetylmelodorinol &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Benzophenone  &
  Root bark &
  \unskip~\citep{844184:19928717}\\
Benzoylmelodorinol &
  Fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715}\\
Benzylbenzoate &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Butenolide cleistanolate &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Chamanetin  &
  Root bark &
  \unskip~\citep{844184:19928717,844184:19928700}\\
cis-solamin &
  Root bark &
  \unskip~\citep{844184:19928717}\\
Cleistonol &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Cleistenonal  &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Cleistenolide  &
  Bark, fruits, leaves, roots and stems &
  \unskip~\citep{844184:19928715,844184:19928717}\\
Cleistodienol  &
  Fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715}\\
Cleistodiendiol  &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Cleistenediols A - F &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Cleistenechlorohydrins A - B &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Cleistophenolide &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Cleistodienol A - B &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Dichamanetin &
  Root bark &
  \unskip~\citep{844184:19928717,844184:19928700}\\
Echinulin &
  Root bark &
  \unskip~\citep{844184:19928717}\\
ent-subglain C &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Guaiol &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Iso-acetyl melodorinol &
  Fruits, leaves roots and stems  &
  \unskip~\citep{844184:19928715}\\
Isochamanetin &
  Root bark &
  \unskip~\citep{844184:19928717,844184:19928700}\\
Melodorinol  &
  Fruits, leaves roots and stems  &
  \unskip~\citep{844184:19928715}\\
Pinocembrin  &
  Bark, fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715,844184:19928700}\\
Pinostrobin &
  Root bark &
  \unskip~\citep{844184:19928700}\\
Polycarpol  &
  Bark, fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928717,844184:19928700}\\
Sootepenol B &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Tetramethylscutellarein  &
  Leaves &
  \unskip~\citep{844184:19928703}\\
(Z)-(+)-5-(2,3-dihydroxy-propylidene)-5H-furan-2-one &
  Fruits, leaves, roots and stems  &
  \unskip~\citep{844184:19928715}\\
Z-acetylmelodorinol  &
  Leaves &
  \unskip~\citep{844184:19928703}\\
Z-melodorinol &
  Leaves &
  \unskip~\citep{844184:19928703}\\
\tblbottomrule 
\end{longtable}
\endgroup
\makeatletter\@ifundefined{TwoColDocument}{}{\twocolumn}\makeatother 

\bgroup
\fixFloatSize{images/78fce020-e7e1-4390-a2e1-b34fd30b94e0-upicture1.png}
\begin{figure*}[!htbp]
\centering \makeatletter\IfFileExists{images/78fce020-e7e1-4390-a2e1-b34fd30b94e0-upicture1.png}{\includegraphics{images/78fce020-e7e1-4390-a2e1-b34fd30b94e0-upicture1.png}}{}
\makeatother 
\caption{\boldmath {Cleistochlamys kirkii: (A) branch showingleaves and fruits and (B) branch showingflower buds (photo: WT Wursten)}}
\label{f-24376a49c361}
\end{figure*}
\egroup
\textbf{Phytochemical composition and pharmacological properties of \textit{Cleistochlamys kirkii }}

Phytochemical compounds such as \ensuremath{\alpha },\ensuremath{\beta }-unsaturated lactone, acetogenin, benzyl benzoate derivatives, c-benzylated flavanone, heptanolide, an indole alkaloid, phenolics, polyoxygenated cyclohexene and derivatives, sesquiterpene and tetracyclic triterpenes have been identified from the bark, fruits, leaves, roots and stems of \textit{C. kirkii } (Table~\ref{tw-36eaccf07776}). The following pharmacological activities have been documented from the crude extracts and phytochemical compounds isolated from \textit{C. kirkii}: antibacterial, antifungal, antiplasmodial and cytotoxicity.

\textbf{Antibacterial activities }

\unskip~\citet{844184:19928714} evaluated the antibacterial activities of crude dichloromethane extract of \textit{C. kirkii} stem bark and the compounds cleistenolide and pinocembrin isolated from the stem bark of the species against \textit{Pseudomonas phaseolicola} and \textit{Staphyloccocus aureus} using the disc method. The crude extract exhibited activities at all concentrations, while the compounds showed moderate to weak activities at concentrations above 200.0 ppm \unskip~\citep{844184:19928720}. Similarly, \unskip~\cite{844184:19928714} evaluated the antibacterial activities of crude dichloromethane extract of \textit{C. kirkii} stem bark and the compounds cleistenolide and pinocembrin isolated from the stem bark of the species against \textit{Pseudomonas syringae} PV. \textit{phaseolicola} using the disc method with streptomycin as a positive control. The crude extract and the compounds exhibited activities against the tested pathogen with a diameter of inhibition zones ranging from 5.3 mm to 15.0 mm in comparison to the width of inhibition zone of 17.5 mm exhibited by the positive control \unskip~\citet{844184:19928720,844184:19928715} evaluated the antibacterial activities of the compounds cleistenolide, cleistodienol, (Z)-(+)-5-(2,3-dihydroxy-propylidene)-5H-furan-2-one, melodorinol, acetyl melodorinol, iso-acetyl melodorinol and benzoyl melodorinol isolated from the fruits, leaves, roots and stems of \textit{C. kirkii} against \textit{Staphylococcus aureus} and \textit{Bacillus anthracis} using the hole plate method with chloramphenicol (10.0 \ensuremath{\mu }g/mL) as a positive control. The compounds exhibited activities \unskip~\citet{844184:19928715,844184:19928706,844184:19928711} evaluated the antibacterial activities of n-hexane, dichloromethane, ethyl acetate and methanol extracts and fractions of \textit{C. kirkii} root bark and the compounds chamanetin, isochamanetin, dichamanetin, echinulin, cis-solamin, cleistenolide, acetylmelodorinol, polycarpol and benzophenone isolated from the species against \textit{Salmonella typhymurium, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus subtilis} and \textit{Staphylococcus aureus} using broth microdilution method with amoxicillin, oxacillin and vancomycin as positive controls. The authors also evaluated the type of interaction of the compounds with the \ensuremath{\beta }-lactam antibiotics amoxicillin and oxacillin using a chemosensitization assay performed on the checkerboard method against \textit{Staphylococcus aureus} resistant and susceptible strains. The best results were obtained for apolar and polar extracts with minimum inhibitory concentration (MIC) values of 7.5 \ensuremath{\mu}g/mL to 62.\ensuremath{\mu}g/mL against Gram-positive strains.  The compounds chamanetin, isochamanetin, dichamanetin and cleistenolide exhibited activities against the tested pathogens. The compound polycarpol, in combination with antibiotics, exhibited substantial synergistic activities \unskip~\citet{844184:19928706,844184:19928717,844184:19928716} evaluated the antibacterial activities of the compounds polycarpol, chamanetin, isochamanetin, dichamanetin and acetylmelodorinol isolated from the root bark of \textit{C. kirkii} against \textit{Staphylococcus aureus, Escherichia coli, Chromobacterium violaceum} and \textit{Enterobacter cloaceae} using the microdilution method. The authors also assessed the combined effects of antibiotics ciprofloxacin and tetracycline and the compounds chamanetin and dichamanetin by using the checkerboard microdilution method in \textit{Staphylococcus aureus} strains. The compounds chamanetin and dichamanetin exhibited activities against \textit{Staphylococcus aureus} with MIC values ranging from 0.8 \ensuremath{\mu }M to 25 \ensuremath{\mu }M. The combined effect of the antibiotics and the compounds chamanetin and dichamanetin on \textit{Staphylococcus aureus} resulted in synergism \unskip~\citep{844184:19928716} .

\textbf{Antifungal activities}

\unskip~\citet{844184:19928714} evaluated the antifungal activities of crude dichloromethane extract of \textit{C. kirkii} stem bark and the compounds cleistenolide and pinocembrin isolated from the stem bark of the species against \textit{Fusarium solani, Botryodiploida theobromae, Aspergillus niger} and \textit{Aspergillus flavus} using the disc method with benomyl as a positive control. The crude extract and the compounds exhibited activities against \textit{Botryodiploida theobromae, Aspergillus niger} and \textit{Aspergillus flavus} with a diameter of inhibition zones ranging from 10.0\% to 48.5\% in comparison to the diameter of inhibition zone of 100\% exhibited by the positive control \unskip~\citep{844184:19928714}. Similarly, \unskip~\citet{844184:19928715} evaluated the antifungal activities of the compounds cleistenolide, cleistodienol, (Z)-(+)-5-(2,3-dihydroxy-propylidene)-5H-furan-2-one, melodorinol, acetyl melodorinol, iso-acetyl melodorinol and benzoyl melodorinol isolated from the fruits, leaves, roots and stems of \textit{C. kirkii} against \textit{Candida albicans} using the disk diffusion method with ketoconazole as a positive control. The compounds exhibited activities against the tested pathogen \unskip~\citep{844184:19928715}. 

\textbf{Antiplasmodial activities}

\unskip~\citet{844184:19928703} evaluated the antiplasmodial activities of the ethanolic crude extract of \textit{C. kirkii} leaves. The compounds cleistodienediol, cleistodienol A, cleistodienol B, cleistenechlorohydrin A, cleistenechlorohydrin B, cleistenediol F, cleistenonal, cleistophenolide, ent-subglain C, melodorinol, acetylmelodorinol, tetramethylscutellarein and 2-hydroxybenzaldehyde isolated from the species against the chloroquine-sensitive strain of \textit{Plasmodium falciparum} 3D7 and Dd2 using an imaging-based assay method. The compounds cleistodienediol, cleistodienol A, cleistodienol B and acetylmelodorinol exhibited activities against both 3D7 and Dd2 with half-maximal inhibitory concentration (IC\ensuremath{_{50}}) values ranging from 0.2 \ensuremath{\mu}M to 40.0 \ensuremath{\mu}M \unskip~\citep{844184:19928703}. Similarly, \unskip~\citet{844184:19928700} evaluated the antiplasmodial activities of ethanolic crude extract of \textit{C. kirkii} root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7-methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the chloroquine-sensitive strain of \textit{Plasmodium falciparum} 3D7 using an imaging-based assay method with artesunate as the reference drug. The crude extract gave 72.0\% inhibition against the 3D7 strain at 0.01 \ensuremath{\mu}g/mL, while the compounds dichamanetin, (E)-acetylmelodorinol and cleistenolide exhibited IC\ensuremath{_{50}} values of 9.3 \ensuremath{\mu}M, 7.6 \ensuremath{\mu}M and 15.2 \ensuremath{\mu}M, respectively, against 3D7 \unskip~\citep{844184:19928700}. 

\textbf{Cytotoxicity activities}

\unskip~\citet{844184:19928715} evaluated the cytotoxicity activities of the compounds cleistodienol, (Z)-(+)-5-(2,3-dihydroxy-propylidene)-5H-furan-2-one, melodorinol, acetyl melodorinol, iso-acetyl melodorinol and benzoyl melodorinol isolated from the fruits, leaves, roots and stems of \textit{C. kirkii} using the brine shrimp assay. The compounds exhibited activities with half-maximal lethal dose (LD\ensuremath{_{50}}) value of 0.09 \ensuremath{\mu }g/mL \unskip~\citep{844184:19928715}. Similarly, \unskip~\citet{844184:19928703} evaluated the cytotoxicity activities of the ethanolic crude extract of \textit{C. kirkii} leaves. The compounds cleistodienediol, cleistodienol A, cleistodienol B, cleistenechlorohydrin A, cleistenechlorohydrin B, cleistenediol F, cleistenonal, cleistophenolide, ent-subglain C, melodorinol, acetylmelodorinol, tetramethylscutellarein and 2-hydroxybenzaldehyde isolated from the species against HEK-293 cells and MDA-MB-231, triple-negative, aggressive breast cancer cell line. All the compounds exhibited activities with IC\ensuremath{_{50}} values ranging from 0.03 \ensuremath{\mu}M to 8.2 \ensuremath{\mu}M \unskip~\citep{844184:19928700}. \unskip~\citet{844184:19928700} also evaluated the cytotoxicity activities of ethanolic crude extract of \textit{C. kirkii} root bark and the compounds cleistonol, chamanetin, isochamanetin, dichamanetin, 7-methoxyisochamanetin, pinostrobin, pinocembrin, benzyl benzoate, 2-methoxybenzyl benzoate, guaiol, polycarpol, (E)-acetylmelodorinol and cleistenolide isolated from the species against the triple-negative aggressive breast cancer cell line MDA-MB-231 using Alamar Blue assay with lupeol as the reference drug. The crude extract exhibited activities with an IC\ensuremath{_{50}} value of 42.0 \ensuremath{\mu}g/mL. In contrast, the compounds chamanetin, isochamanetin, dichamanetin, pinocembrin, (E)-acetylmelodorinol and cleistenolide exhibited activities with IC\ensuremath{_{50}} values ranging from 9.6 \ensuremath{\mu}M to 30.7 \ensuremath{\mu}M \unskip~\citep{844184:19928700}.
    
\section{Conclusions}
The current scientific evidence, as illustrated by biological activities demonstrated by \textit{C. kirkii}, indicates its potential as traditional medicine. The biological activities exhibited by the extracts and compounds isolated from the species directly or indirectly support a wide range of physiological processes, which offers protection against the growth of undesirable microbes and cytotoxicity properties which could trigger antitumor activities. The present study showed that there are still some research gaps in the phytochemistry, pharmacological and toxicological properties of the species. Therefore, further rigorous research is required aimed at evaluating the phytochemical properties of the different plant parts used as sources of traditional medicines as well as clinical trials and in vivo experiments.
    
\section{Acknowledgement}
I am grateful to the reviewers who kindly commented on my manuscript.

\textbf{Conflict of Interest}

The authors declare that they have no conflict of interest for this study.

\textbf{Funding Support}

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

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