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\def\RunningAuthor{Mohd Kashif Husain et al.}
\firstPage{1009}
\articleType{Review Article}
\receivedDate{03 Jan 2021}
\acceptedDate{19 Feb 2021}
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\title{\textbf{Botany, Traditional Uses and Pharmacology of \textit{Bukkun Booti - Phyla nodiflora } (L\textit{.}) Greene: An Underexposed Botanical Drug of AYUSH-Unani System}}
\author{Mohd~Kashif~Husain\textsuperscript{*}\textsuperscript{1},  
            Goli~Penchala~Pratap\textsuperscript{1},  
            Mokhtar~Alam\textsuperscript{2},  
            Ghazala~Javed\textsuperscript{2}, 
            Munawwar~Husain~Kazmi\textsuperscript{1}~\\[5pt]{\textsuperscript{1}Survey of Medicinal Plants Unit (SMPU), National Research Institute of Unani Medicine for Skin Disorders (NRIUMSD), Hyderabad, Telangana, India}~\\{\textsuperscript{2}Central Council for Research in Unani Medicine (CCRUM), New Delhi, India}}

\begin{abstract}
\textit{Bukkun Booti} (\textit{Phyla nodiflora} (L.) Greene; Syn. \textit{Lippia nodiflora} (L.) Michx.), of Verbenaceae, is a fast-growing creeping perennial medicinal herb, has a very long history for human use as it is generally distributed throughout the world. The plant has been traditionally used and recorded in AYUSH-Ayurveda, Unani and Siddha systems of medicine. In the Unani System of Medicine (USM), the \textit{Bukkun Booti} is used for detoxification of the blood. It is useful in \textit{Baw{\selectfont\={a}}s\={\i}r} (bleeding piles), \textit{Ru`af} (epistaxis), \textit{Has{\selectfont\={a}}h al-Math{\selectfont\={a}}na} (cystolithiasis), \textit{Soz{\selectfont\={a}}k} (gonorrhea) \textit{`Usr al-Bawl} (dysuria) and \textit{Hummayat} (fevers). Ethno-medicinally, it has been widely used as a traditional folk medicine to treat and cure ailments by the local tribal and other communities. The entire plant is diuretic, febrifuge, stomachic and astringent; good for ulcers, wounds, asthma, bronchitis, knee-joints and to ladies after delivery. \textit{Bukkun Booti }is a rich source of antioxidants and secondary metabolites, and aerial parts are reported to contain phenolic compounds (flavonoids), which are found to have a broad array of reported pharmacological actions such as; antibacterial, anti-inflammatory, antioxidant, antidiabetic and hepatoprotective properties. The purpose of this review paper is to bring together the available information on the current status and therapeutic uses of \textit{Bukkun Booti} in the Unani System of Medicine and to discuss the botany and importance of the plant on the basis of folk uses, pharmacological activities and chemical constituents. The potential characteristics of \textit{P. nodiflora} could be utilized more efficiently by linking the bridge of traditional uses, pharmacology and phytochemistry through an integrated approach. 
\end{abstract}\def\keywordstitle{Keywords}

\begin{keywords}AYUSH-Unani,\newline Bukkum,\newline Bukkun Booti,\newline Folk-medicine,\newline Lippia nodiflora,\newline Pharmacology,\newline Unani therapeutics,\newline Verbenaceae
\end{keywords}
\twocolumn[ \maketitle {\printKwdAbsBox}]
\makeatletter{\raggedright\textsuperscript{*}Corresponding Author\par Name:\ Mohd~Kashif~Husain~\\ Phone:\ 73821-89745~\\  Email:\ kashifptc@gmail.com
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\section{Introduction}
Plant-based medicines have been used for ages in Indian traditional systems of medicine (AYUSH) for promoting healthiness and well-being. The World Health Organization \unskip~\citep{1014273:21491633} defines traditional medicine as ``the sum total of the knowledge, skills, and practices based on the theories, beliefs, and experiences indigenous to different cultures, whether explicable or not, used in the maintenance of health as well as in the prevention, diagnosis, improvement or treatment of physical and mental illness''. Unani System of Medicine (USM) is considered as one of the most age-old systems of medicine, which originated in Greece and stretched itself to Arab countries and finally to India \unskip~\citep{1014273:21491622}. The AYUSH systems, besides Ayurveda, Unani System also has a long history in the application of medicinal plants for a cure and therapeutic usages. There are several botanical drugs that are used in common between these two traditional systems for either the same or different therapeutic applications depend upon the formulations and method of preparations.

In USM, the botanical drug either can be used singly or in combinations. There are many botanical drugs that are very useful in Unani, Ayurveda and Siddha systems but little-known to the primary stakeholders. One of these known drugs is \textit{Bukkun} or \textit{Bukkum Booti}\unskip~\citep{1014273:21491624}, which is under-explored for protection, cultivation and sustainable utilization as a botanical drug at a commercial level.

\textit{Phyla nodiflora} (L.) Greene (Syn; \textit{Lippia nodiflora } (L.) Michx.) is a prostrate marshy herb of the Verbenaceae family, commonly known as \textit{Bukkun } or \textit{Bukkum Booti} in Unani System of Medicine (USM) and Jalapippali in Ayurveda. The herb is found in the tropical and sub-tropical region of the globe and Indian subcontinent. Its entire parts have been used as a traditional medicinal cure in Asian and African systems of medicine. The herb found in most of the states throughout India at lower elevations \unskip~\citep{1014273:21491629}, along lakes and dried water bodies. \textit{Bukkun Booti} grows in open and damp places near ponds, water streams, and paddy fields. Leaves are eatable. Traditionally (folk), the plant is used as a diuretic and febrifuge. A paste or poultice made from the whole fresh plant is used to treat swelled cervical glands, chronic sluggish ulcers and boils. In USM, the whole plant, leaves and roots are used for different actions \unskip~\citep{1014273:21491624}. The present review has been attempted to bring the relevant modern scientific evidence to one platform to understand the importance and usage of \textit{Bukkun Booti, } specifically in USM. The therapeutic applications and their current status related to pharmacological research and development, botany and important phytochemicals are also discussed in detail.

\textbf{Current Scientific Accepted Name }

\textbf{Authority }

\textit{Phyla nodiflora}

(L.) Greene

\textbf{Synonyms}

\textit{Lippia nodiflora} (L.) Michx.

\textit{Verbena nodiflora} L\textbf{.}

\textbf{Classification (Bentham and Hooker System)}

Kingdom: Plantae{\textendash} Plants 

Division: Tracheophyta 

Class: Magnoliopsida{\textendash} Dicotyledons 

Order: Lamiales 

Family: Verbenaceae(Verbena family)

Genus: \textit{Phyla} Lour. 

Species: \textit{Phyla nodiflora} (L.) Greene

\textbf{Classical Names}

Ayurvedic : Jalapippali, Shaaradi, Shakulaadani, Jalakarnaa

Unani : \textit{Bukkun} or \textit{Bukkum}/ \textit{BukanBooti}

Siddha : Paduthalai

\textbf{Vernaculars}

Arabic: Filfil Ma

English\textbf{: }Wild sage, frog fruit, turkey tangle

Hindi: Jal-Buti, Bakkan, Bhuiokra, Chota-okra, Jalapapil

Kannada: Neeruhippali, Neerupippali, Nelahippali,

Malayalam: ana-coluppa, katu-tippali

Marathi: Ratolia, Vakkan

Punjabi: Gorakhmundi

Tamil: Poduthalai, Talamputam

Sanskrit: Vasir Vasuka, Jalakarna

Telugu: Bokenaku, Gajapippala-kada, Mosalipappu, Neeru Pippali Kada

\textbf{Habitat and Ecology}

\textit{P. nodiflora }(\textit{Lippia}) species is found mostly on high-moisture holding clay to clay loam soils in wetland habitats; ranging from marshes to open, damp places near the streams, meadows, river backwaters, the margins of tarns and ditches, with some tolerance of brackish (salty) water. \textit{P. nodiflora} is well adapted to moist clay soils in riverine and floodplain surroundings \unskip~\citep{1014273:21491653}. It has been observed that the plant grow most profusely on the places which experience flooding of small duration \unskip~\citep{1014273:21491640}. To cope with the drier conditions, \textit{P. nodiflora} becomes inactive for a period of time. The plant is also capable of tolerating the occasional or regular flood.

\textbf{Conservation Status-Threats Information}

\textit{Phyla} species is assessed as Least Concern (LC) as it is prevalent with stable populations and does not face any major threats (Figure~\ref{f-a28da2c46ec2}). As per the available data, there are no known ongoing or future major threats to this species.


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\caption{\boldmath {Current status of the plant as per IUCN }}
\label{f-a28da2c46ec2}
\end{figure*}
\egroup

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\caption{\boldmath {A. Close view of the inflorescence with globose heads. B. Spathulate leaves along with elongated inflorescence. C. Whole plant with rooting at nodes}}
\label{f-25c83ce4e17f}
\end{figure*}
\egroup
Red List Category and Criteria; Least Concern (ver 3.1) Date Assessed;19 April 2018 Assessor/s: Lansdown, R.V. Reviewer/s: Sayer, C. Contributors: Molur, S., Patzelt, A., Knees, S.G., Bhat, G.K., Gupta, A.K. \& Sadasivaiah, B. \unskip~\citep{1014273:21491632}

Justification: \textit{Phyla nodiflora} is a common and widespread species with no known threats. Hence it is assessed as (LC) Least Concern \unskip~\citep{1014273:21491632,1014273:21491844}. Conservation Actions: No conservation action in place or needed.

\textbf{Botanical Description}

A creeping, small, perennial, much-branched herb with rooting at the stem nodes (Figure~\ref{f-25c83ce4e17f}C), subquadrangular, clothed with appressed white hairs, seems nearly glabrous.

Leaves opposite, subsessile, spathulate (Figure~\ref{f-25c83ce4e17f}B), obovate, 1-3 x 0.8-1.5cm, pubescent, base cuneate, apex rounded deeply fleshy, hairy, glabrescent to appressed pubescent and sharply serrate in the upper part \unskip~\citep{1014273:21491623}


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\caption{\boldmath {Part of \textit{P.} \textit{nodiflora} plant used as ethnomedicine}}
\label{f-2ccb15c1bc07}
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\caption{\boldmath {Form of ethnomedicine - \textit{P. nodiflora}}}
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\egroup

\bgroup
\fixFloatSize{images/35a62c41-8edb-4693-a2c0-4fa218d792ac-upicture5.png}
\begin{figure}[!htbp]
\centering \makeatletter\IfFileExists{images/35a62c41-8edb-4693-a2c0-4fa218d792ac-upicture5.png}{\includegraphics{images/35a62c41-8edb-4693-a2c0-4fa218d792ac-upicture5.png}}{}
\makeatother 
\caption{\boldmath {Ethnomedicinal uses of \textit{P. nodiflora} in different disease conditions}}
\label{f-4fcee01c4e1f}
\end{figure}
\egroup
Inflorescence with sessile flowers, densely packed in long-pedunculated axillary heads which are at first globose heads eventually elongate and becoming spicate and oblong fruits (Figure~\ref{f-25c83ce4e17f}A). Peduncles are 2.5-7.5 cm. long, usually produced from only one axil of each pair of the leaves (Figure~\ref{f-25c83ce4e17f}C). 

Calyx membranous, deeply two-lobed, compressed, glabrous on the back. Corolla pale pink, pushed off as a calyptra from ripening fruit. 2 lipped. Upper lip erect, bifid and lower lip 3 lobed. Drupes globose oblong, splitting into two, one-seeded glabrouspyrenes; seeds minute \unskip~\citep{1014273:21491610}. Flowering and fruiting (Fl. \& Fr) time; throughout the year

\textbf{Cultivation and Harvesting Details}

\textit{Phyla nodiflora }thrives in a diverse range of habitats from the subtropics to the tropics and is propagated by seed or division. Its cultivation flourishes in any well-drained moderately fertile soil of low fertility in sunlight. 

According to one report, the plant prefers ample moisture, while the other says that the well-grown plant is tolerant to drought. The plant makes a lot of vegetative growth when grown in the shade but does not flower well. 

The plant can carpet large areas as it spreads very fast by means of running stems. \textit{Bukkun} plant is capable of flowering and fruiting round the year.

\textit{P. nodiflora} is susceptible to the fungi \textit{Meliola durantae } and \textit{Cercospora lippiae}. It can be harvested whenever the need arises as leaves and flowers are in general present throughout the year. 

After harvesting the plant parts of \textit{Bukkun Booti} are usually used fresh but roots and above ground parts may well be dried for future use \unskip~\citep{1014273:21491625}. 

\textbf{Use and Trade Information}

Locally, the \textit{Bukkun} plant is collected from the wild for domestic medicinal use. It is sometimes grown as an ornamental plant and as a ground cover in tropical to warm temperate regions of the globe.

In India, the infusion of the dried leaves of \textit{P. nodiflora} species is mentioned as a remarkable remedy for a bronchial cough. Ethno-botanically the decoction of the plant, is used as a wash to boost weak babies to walk \unskip~\citep{1014273:21491649}. 

The plant is used as febrifuge and diuretic{\textemdash}poultice used as maturant for boils. An infusion of the leaves is given to the mother after delivery \unskip~\citep{1014273:21491624}.


\begin{table*}[!htbp]
\caption{\boldmath {Ethnomedicinal uses of \textit{Bukkun Booti }(\textit{Phyla nodiflora})} }
\label{tw-2ebc654c579b}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.07990000000000001\linewidth-2\tabcolsep}p{\dimexpr.28950000000000003\linewidth-2\tabcolsep}p{\dimexpr.35722500000000004\linewidth-2\tabcolsep}p{\dimexpr.273375\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack Plant Part Used / Form of  \mbox{}\protect\newline Ethnomedicine & \cAlignHack Ethnomedicinal Uses and Therapeutics & \cAlignHack References\\
\tblmidrule 
\cAlignHack 1. &
  Whole Plant (Pills) &
  Micturition, dysuria, \mbox{}\protect\newline bleeding piles &
  \unskip~\citep{1014273:21491611}\\
 &
   &
   &
  \\
\cAlignHack 2. &
  Leaf juice &
  Dandruff, leaf juice mixed and boiled with an equal volume of gingelly oil, is applied twice a week on the head. &
  \unskip~\citep{1014273:21491644}\\
 &
   &
   &
  \\
\cAlignHack 3. &
  Flowers, Leaves or Roots (Crude) &
  Oral thrush &
  \unskip~\citep{1014273:21491614}\\
 &
   &
   &
  \\
\cAlignHack 4. &
  Whole Plant \mbox{}\protect\newline (Crude) \mbox{}\protect\newline  &
  Nervous disorders, constipation, eczema, heatstroke, rheumatoid arthritis, gonorrhoea, pain, spasms. &
  \multicolumn{1}{p{\dimexpr(.273375\linewidth-2\tabcolsep)}}{\multirow{3}{\linewidth}{\unskip~\citep{1014273:21491646}}}\\
 &
  Leaf and Stem &
  Dizziness, headache, fever &
  \\
 &
  Stem Bark and Leaf \mbox{}\protect\newline (Crude) &
  Back Pain due to fall or \mbox{}\protect\newline Rheumatic pain &
  \\
 &
   &
   &
  \\
\cAlignHack 5. &
  Whole Plant \mbox{}\protect\newline (Crude) &
  Common cold &
  \unskip~\citep{1014273:21491605}\\
 &
   &
   &
  \\
\cAlignHack 6. &
  Whole Plant \mbox{}\protect\newline (Crude) &
  Jaundice &
  \unskip~\citep{1014273:21491635}\\
 &
   &
   &
  \\
\cAlignHack 7. &
  Whole plant \mbox{}\protect\newline (Paste and juice) &
  Paste for boils, swollen cervical glands, and chronic indolent ulcers. The juice is for bleeding gums. &
  \unskip~\citep{1014273:21493272}\\
 &
   &
   &
  \\
\cAlignHack 8. &
  Stem and Leaf (Paste) &
  Headache (Forehead)  &
  \multicolumn{1}{p{\dimexpr(.273375\linewidth-2\tabcolsep)}}{\multirow{2}{\linewidth}{\unskip~\citep{1014273:21491636}}}\\
 &
  Young Stem (Paste) &
  Broken bones &
  \\
 &
   &
   &
  \\
\cAlignHack 9. &
  Whole Plant (Decoction) &
  Skin rashes &
  \unskip~\citep{1014273:21491639}\\
 &
   &
   &
  \\
\cAlignHack 10. &
  Whole plant (Cooked) &
  Edible &
  \unskip~\citep{1014273:21491652}\\
 &
   &
   &
  \\
\cAlignHack 11. &
  Leaves and Roots \mbox{}\protect\newline (Extract) &
  Antibacterial &
  \unskip~\citep{1014273:21491650}\\
 &
   &
   &
  \\
\cAlignHack 12. &
  Whole Plant (Paste) &
  Cure ulcer, burning  \mbox{}\protect\newline Micturition and asthma. &
  \unskip~\citep{1014273:21491617}\\
 &
   &
   &
  \\
\cAlignHack 13. &
  Whole Plant, Tender stalks, Leaves, Fruits  \mbox{}\protect\newline (Crude and Paste) &
  Diuretic, fever, cold, maturation of boils, useful in children indigestion, piles (control irritation) \mbox{}\protect\newline  Fodder for sheep and goats (\textit{Capra hircus}) &
  \unskip~\citep{1014273:21491645}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}

\begingroup
\makeatletter\if@twocolumn\@ifundefined{theposttbl}{\gdef\TwoColDocument{true}\onecolumn\onecolumn}{}\fi\makeatother \setlength\LTcapwidth{\textwidth}
\begin{longtable}{p{\dimexpr.05889999999999999\linewidth-2\tabcolsep}p{\dimexpr.18912000000000003\linewidth-2\tabcolsep}p{\dimexpr.18026\linewidth-2\tabcolsep}p{\dimexpr.32824\linewidth-2\tabcolsep}p{\dimexpr.24348000000000003\linewidth-2\tabcolsep}}
\caption{\boldmath {Pharmacological studies on \textit{Phyla nodiflora}} }
\label{tw-bd1bf430e86e}
\def\arraystretch{1.1}\\\endfirsthead \hline \noalign{\vskip3pt} \noalign{\textit{Table \thetable\ continued}} \noalign{\vskip3pt} 
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack  Activity & \cAlignHack Part / Extract / Oil / Compound & \cAlignHack Experimental Studies \mbox{}\protect\newline Cell lines / Animal model / Microorganisms & \cAlignHack References\\
\tblmidrule \endhead \hline \noalign{\vskip3pt} \noalign{\textit{\hfill Continued on next page}} \noalign{\vskip3pt} \endfoot \endlastfoot 
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack  Activity & \cAlignHack Part / Extract / Oil / Compound & \cAlignHack Experimental Studies \mbox{}\protect\newline Cell lines / Animal model / Microorganisms & \cAlignHack References\\
\tblmidrule 
\cAlignHack 1. &
  Antibacterial &
  Methnolic \mbox{}\protect\newline extract \mbox{}\protect\newline  &
  Ethanol extract exhibited significant antibacterial activity against \textit{S. aureus, M. luteus, P. mirabalis} by the agar diffusion method. &
  \unskip~\citep{1014273:21491626} \mbox{}\protect\newline \\
\cAlignHack  &
   &
  Essential oil &
  Essential oil revealed good antibacterial activity against both grams positive and gram-negative bacteria. &
  \unskip~\citep{1014273:21491626}\\
\cAlignHack 2. &
  Anticancer &
  Leaf extract &
  Exhibited induced apoptosis in human lung cancer (NCI-H460) cells showed high antiproliferative activity. &
  \unskip~\citep{1014273:21491631} \mbox{}\protect\newline \\
\cAlignHack  &
   &
  Methanolic extract &
  Possessed antitumor activity in tumor bearing Swiss albino mice and significantly decreased the tumor volume and increased the life span. &
  \unskip~\citep{1014273:21491612}\\
\cAlignHack 3. &
  Antidandruff &
  Ethanolic extract and isolated compound &
  Dandruff causing organism (\textit{Malassezia furfur}) was found to be sensitive to all concentrations of the ethanolic extract and isolated compound. &
  \unskip~\citep{1014273:21491607}\\
\cAlignHack 4. &
  Antidiabetic &
  Methanol extract \mbox{}\protect\newline  &
  In streptozotocin-induced diabetic rats, a significant increase in the serum insulin level and decrease in fasting blood glucose, glycosylated haemoglobin levels and serum marker enzymes. &
  \unskip~\citep{1014273:21491608} \mbox{}\protect\newline \\
\cAlignHack  &
   &
  \ensuremath{\gamma }-sitosterol-isolated from \textit{L. nodiflora} &
  In streptozotocin (STZ) induced diabetic rats, \ensuremath{\gamma }-sitosterol significantly decreased the blood glucose level and glycosylated hemoglobin and increased the insulin secretion in response to glucose. &
  \unskip~\citep{1014273:21491606}\\
\cAlignHack 5. &
  Antifungal &
  Crude extracts (ethanol, methanol, ethyl acetate, chloroform) from the leaves and shoots  &
  The extract exhibited the most effective antifungal activities against; \textit{Aspergillus flavus, A. niger, Paecilomyces varioti, Microsporum gypseum } and \textit{Trichophyton rubrum}. &
  \unskip~\citep{1014273:21491637}\\
\cAlignHack 6. &
  Antihyperuricemic &
  Methanol Extract &
  Exhibited uric acid-lowering effect  &
  \unskip~\citep{1014273:21491648}\\
\cAlignHack 7. &
  Anti-inflammatory &
  Methanolic \mbox{}\protect\newline Extract of  \mbox{}\protect\newline Leaves \mbox{}\protect\newline  &
  The extract exhibited a significant anti-inflammatory and antinociceptive activity in acetic acid-induced writhing in white albino mice.  \mbox{}\protect\newline  &
  \unskip~\citep{1014273:21491657} \mbox{}\protect\newline \\
\cAlignHack  &
   &
  Cyclo-pentanophen \mbox{}\protect\newline anthrenol &
  The anti-inflammatory potential of cyclo-pentanophenanthrenol has been demonstrated on in vitro inflammation models.  &
  \unskip~\citep{1014273:21491616}\\
\cAlignHack 8. &
  Antioxidant &
  Methanolic extract &
  Exhibited concentration-dependent \textit{in vitro} antioxidant activity and scavenging activities.   &
  \unskip~\citep{1014273:21491651} \mbox{}\protect\newline \\
\cAlignHack  &
   &
   &
  The bioactive compound obtained through bioassay-guided, ethyl acetate fraction demonstrated excellent antioxidant activity \textit{in vitro}. &
  \unskip~\citep{1014273:21491634}\\
\cAlignHack 9. &
  Hepatoprotective &
  Methanolic \mbox{}\protect\newline extracts of  \mbox{}\protect\newline leaves \mbox{}\protect\newline  &
  Protected the liver cells against Lipopolysaccharides (LPS) induced toxicity on HepG2 cells and decreased the apoptotic gene expression. &
  \unskip~\citep{1014273:21491642}\\
\cAlignHack  &
   &
  Methanol Extract &
  Exhibited worthy hepatoprotective and antioxidant activity in acute experimental liver injury by paracetamol &
  \unskip~\citep{1014273:21491643}\\
\cAlignHack 10. &
  Hypotensive &
  Chloroform, ethyl \mbox{}\protect\newline acetate, methanol and water extracts \mbox{}\protect\newline  &
  Of all, the methanolic extract reduced the systolic blood pressure significantly in uninephrectomized DOCA-salt hypertensive rats. &
  \unskip~\citep{1014273:21491655}\\
\cAlignHack  &
   &
  Methanolic extract &
  The systolic pressure in DOCA-salt hypertensive wister rats significantly decreased. &
  \unskip~\citep{1014273:21491613}\\
\cAlignHack 11. &
  Neuro-pharmacological  &
  Petroleum, chloroform  \mbox{}\protect\newline and  \mbox{}\protect\newline ethanolic extracts  \mbox{}\protect\newline of aerial part &
  Ethanolic extract (due to the presence of flavonoids)produced anxiolytic, sedative(central inhibitory) and anticonvulsant effect in mice.  &
  \unskip~\citep{1014273:21491656}\\
\tblbottomrule 
\end{longtable}
\endgroup
\makeatletter\@ifundefined{TwoColDocument}{}{\twocolumn}\makeatother 

\begin{table*}[!htbp]
\caption{\boldmath {Phytochemicals of \textit{Phyla nodiflora}} }
\label{tw-8f57123a294f}
\def\arraystretch{1.1}
\ignorespaces 
\centering 
\begin{tabulary}{\linewidth}{p{\dimexpr.1152\linewidth-2\tabcolsep}p{\dimexpr.22765000000000004\linewidth-2\tabcolsep}p{\dimexpr.4254250000000001\linewidth-2\tabcolsep}p{\dimexpr.231725\linewidth-2\tabcolsep}}
\tbltoprule \rowcolor{kwdboxcolor}\cAlignHack S. No. & \cAlignHack Class  \mbox{}\protect\newline of Compounds & \cAlignHack Name of Chemical Constituent & \cAlignHack References\\
\tblmidrule 
\cAlignHack 1. &
  \cAlignHack Flavonoids &
  4'-hydroxywogonin; \mbox{}\protect\newline 3,7,4',5'-tetrahydroxy-3'- methoxyflavone;  \mbox{}\protect\newline 7,8,4'-tetrahydroxy-3'- methoxyflavone;  \mbox{}\protect\newline cirsiliol; larycitrin; onopordin \mbox{}\protect\newline 6-hydroxy-luteolin-6-sulfate;  \mbox{}\protect\newline hispidulin; hispidulin-7,4'-disulfate;  \mbox{}\protect\newline jaceosidin; jaceosidin-7-sulfate; jaceosidin-7,4'-disulfate; nepetin-3',4'-disulfate; nepetin-7-sulfate; nodifloretin-7-sulfate   &
  \unskip~\citep{1014273:21491618,1014273:21491621}\\
\cAlignHack 2. &
  \cAlignHack Triterpene &
  3\ensuremath{\beta }-19\ensuremath{\alpha }-dihydroxy-urs-1,20-(30)-diene \mbox{}\protect\newline Lippiacin; Pomolic acid; Ursolic acid &
  \unskip~\citep{1014273:21491638}\\
\cAlignHack 3. &
  \cAlignHack Phytosterol &
  \ensuremath{\beta }-sitosterol; \ensuremath{\beta }-sitosterolglucoside \mbox{}\protect\newline 4', 5' dimethoxybenzoloxystigmasterol; \mbox{}\protect\newline Stigmasterol; stigmasterolglucoside &
  \unskip~\citep{1014273:21491615,1014273:21491638}\\
\cAlignHack 4. &
  \cAlignHack Quinol &
  Benzofuranonerenglyolone (or halleridone); hallerone &
  \unskip~\citep{1014273:21491647}\\
\cAlignHack 5. &
  \cAlignHack Others &
  \ensuremath{\alpha }-ethyl-galactose; nodiflorin A; nodiflorin B; nodifloridin A; nodifloridin B ; cornoside &
  \unskip~\citep{1014273:21491609,1014273:21491638}\\
\tblbottomrule 
\end{tabulary}\par 
\end{table*}
\textbf{Description in Unani Classical Texts}

\textit{\textbf{Miz{\selectfont\={a}}j}} \textbf{ (temperament)}

Unani scholars and Vaidya have differed in the identification of its temperament \unskip~\citep{1014273:21491620,1014273:21491628};


  
  \begin{enumerate}
  \item \relax Hot and Dry
  \item \relax Hot and Dry in Second Degree
  \item \relax Cold 
  \end{enumerate}
  \textbf{Part Used}

Mostly Leaf / Whole Plant

\textbf{Dose}

One tola (10 g)\textbf{\space }

\textit{\textbf{Muzir}} \textbf{ (Adverse/Toxic Effect)}

Not suitable for persons with `Hot' temperament. It may cause or aggravate other diseases.

\textit{\textbf{Musleh}} \textbf{ (Corrective)}

Asl (honey) and mirch siyah (\textit{Piper nigrum}) is used to remove its adverse effects.

\textit{\textbf{Afa'al}} \textbf{ (Pharmacological Actions in Unani medicine)}

As per the Unani classical text \unskip~\citep{1014273:21491628}\textit{Bukkun Booti} is \textit{Mubarrid} (febrifuge), \textit{Musakkin Josh-e Khoon} (neutralize blood), \textit{Musaff\={\i}-i-Dam} (blood purifier), \textit{Dafi`a Fasad-i Safra} (neutralize bile), \textit{Munaffis Balgham} (expectorant), \textit{Dafe Zeequnnafas} (antiasthamatic), \textit{Dafe Jaraseem} (antimicrobial), \textit{Musakkin-e-Alam} (analgesic) and \textit{Muhallil Waram} (resolve inflammation).

\textit{Bukkun} is also \textit{Mudirr-i-Bawl} (diuretic) and \textit{Mufattite hasat} (lithotryptic). The infusion of the leaves is used in \textit{Sozish-e-Bawl} (burning micturition) \textit{Usr-e-Bawl} (difficulty in micturition) and \textit{Ehtebas-e-Bawl} (retention of urine). It is useful in \textit{Khafqane Har} (palpitation due to heat). It gives strength to the kidney and bladder (\textit{Hastae Gurda wa Masana}) \unskip~\citep{1014273:21491620,1014273:21491619}. 

\textit{\textbf{Istem'al}} \textbf{ (Therapeutic Indications in Unani medicine)}

\textit{Bukkun Booti} is useful in \textit{Baw{\selectfont\={a}}s\={\i}r} (bleeding piles/ hemorrhoid), \textit{Ru`af} (epistaxis) \textit{`Usr al-Bawl} (dysuria) and \textit{Has{\selectfont\={a}}h al-Math{\selectfont\={a}}na} (cystolithiasis) \textit{Hummayat} (fevers) due to \textit{Ufunat } (infection) and predominance of \textit{Balgham} (phlegm)and \textit{Qula} (stomatitis). A poultice of the fresh plant used externally as a paste to ripen boils and to cure inflammation (\textit{Muhallil Waram}). Also indicated in \textit{Su'al} (cough), which occurs due to \textit{Burudat} (cold), \textit{`Soz{\selectfont\={a}}k} (gonorrhoea) and used in various other conditions such as; asthma, bronchitis, knee joint pain, hepatitis, and infectious diseases \unskip~\citep{1014273:21491628,1014273:21491630}.

\textbf{Ethnomedicinal Uses}

\textit{P. nodiflora }plant is ethno-medicinally used as analgesic/anti-inflammatory/antipyretic diuretic, stomachic, febrifuge and astringent to the bowels; good for ulcers, wounds, asthma, bronchitis, ischury, knee-joints \unskip~\citep{1014273:21491654}. Usually, the plant is given to the women after delivery and kids suffering from indigestion. It is also useful in the treatment of menstrual disorders and respiratory diseases, reported having antimicrobial, antimalarial and antispasmodic action. A paste or poultice is further applied to cure swelling of cervical glands, to erysipelas, burns, and to old sluggish ulcers. It is said to be useful in constipation and the treatment of ischuria, blennorrhoea and lithiasis. An infusion is drunk as a post-partum tonic. An infusion of the whole fresh plant or the root is used in the treatment of fever. Some important information on ethnomedicinal uses has been summarized in Table~\ref{tw-2ebc654c579b}. A survey of the available ethnobotanical literature on \textit{P. nodiflora} showed that most of the workers had reported the use of the whole plant, followed by leaf (Figure~\ref{f-2ccb15c1bc07}), mostly in crude and paste form (Figure~\ref{f-8c5c1ae8c538}) of drugs (33 \%). Most of the workers reported its ethnomedicinal use for healing purpose (maximum) and to treat different disease conditions, including fever, piles, pain and bleeding gums, gonorrhoea, jaundice and nervous disorders (Figure~\ref{f-4fcee01c4e1f}).

\textbf{Pharmacological Evidence/ Experimental studies}

A number of studies showed that \textit{P. nodiflora} plant exhibited wide-ranging pharmacological properties, including; anti-inflammatory, antioxidant, anticancer, antihyperuricemic, hepatoprotective, antibacterial activity, and anti-fungal (Table~\ref{tw-bd1bf430e86e}).

\textbf{Phytochemicals of \textit{Phyla nodiflora}}

Of many chemical constituents, mostly flavonoids class of chemicals has been isolated from \textit{P. nodiflora} (Table~\ref{tw-8f57123a294f}). Phytochemical investigations have revealed the presence of numerous flavonoids from aerial parts, leaves and flower part of the plant. \textit{Phyla }also contain flavone glycosides-nodiflorins (A) and nodiflorins (B), lipiflorins (A) and lipiflorins ( B), in addition to flavones including; nepetin, nodifloretin and \ensuremath{\alpha }-hydroxyluteolin, and glucosides; \ensuremath{\beta }-sitosterol and stigmasterol \unskip~\citep{1014273:21491624}.
    
\section{Conclusion }
\textit{Bukkun Booti} (\textit{P. nodiflora}; Syn\textit{. L. nodiflora}) is a little-known but one of the most significant Unani medicinal plant. The current review deliberated the status, botany, therapeutic actions and uses available in classical Unani texts. Furthermore, a wide range of reported modern pharmacological actions and a reasonable amount of phytochemical data endorse the \textit{Bukkun Booti } (\textit{P. nodiflora}) as a promising medicinal plant, which could be utilized judiciously as healing-oriented medicine by adapting an integrative approach, especially to investigate the possible links between traditional uses, pharmacology and phytochemistry.  
\section*{Acknowledgement}The authors would like to thank Prof. Asim Ali Khan, Director General, Central Council for Research in Unani Medicine-CCRUM, Ministry of AYUSH, Government of India, for providing the necessary facilities. Dr Mohd Kashif Husain is thankful to CCRUM and the Ministry of AYUSH for the Young Scientist Award (YSA). We got no funding support for this study.

\textbf{Funding Support}

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

\textbf{Conflict of Interest}

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

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