Table of Content

Pharse Page No
1 Introduction
1.1Salvadora persica
1.2. Common names
1.3 Plant profile
1.4 Botanical classification
1.5 Distribution
1.6 Morphology
1.7 Cultivation
1.8 Plant Uses
1.8.1 Traditional uses
1.8.2 Nutritional uses
1.8.3 Medicinal uses
1.8.4 Pharmacological effects
1.8.5 Antimicrobial effects
1.8.6Antiparasitic insecticidal and antiscorpion effects
1.8.7 Antioxidant effects
1.8.8 Antidiabetic effects
1.8.9 Anticancer effects
1.8.10 Antiinflammatory and analgesic effects
1.8.11 zGastrointestinal
effects
1.8.12 Antilipidemic activity
1.8.13 Side effects and toxicity
2 Chemical
composition
2.1 Amino Acids
2.2 Minerals Content
3 Phytochemistry
3.1 Cucurbitacins
3.2 Glycosides, phenolic acids and flavonoids
3.3 Fatty Acids and tocopherols
3.4 Alkaloids
3.5 Volatile Compounds
4 Salvadora persica seeds oil
4.1 Yield percentage and physicochemical properties
4.2 Salvadora persica seeds oil as potential biodiesel

1.10 USE AND PHYTOCHEMICALS

1.11 PHARMACOLOGIC ACTIVITIES

1.11.1 Hypolipidemic activity

1.11.2 Antiulcer activity

1.11.3Anticonvulsant activity

1.11.4Antifertility activity

1. 11.5Antibacterial activity

1. 11.6 Antimycotic activity

1.11.7Analgesic effect
 1. 11.8 Cytotoxicity

1.12 Side effects and toxicity

1.2 Chemical composition
1.2.1 Amino Acids
1.2.2 Minerals Content
1.3 Phytochemistry
1.3.1 Cucurbitacins
1.3.2 Glycosides, phenolic acids and flavonoids
1.3.3 Fatty Acids and tocopherols
1.3.4 Alkaloids
1.3.5 Volatile Compounds
1.4 Salvadora persica seeds oil
1.4.1 Yield percentage and physicochemical properties
1.4.2 Salvadora persica seeds oil as potential biodiesel

Chemicals profile of salvadora persica (leaves , stem ,roots)

Chapter one
Introduction
 Chapter one

1.Introduction

1.1Salvadora persica

Salvadora persica L., most commonly known as Arak (in Arabic)

and Peelu (in Urdu), belong to the family Salvadoraceae. In 1749, the term
Salvadora, was set forth by Dr Laurent Garcin, in honour of an apothecary
of Barcelona, Juan Salvadory Bosca (1598–1681). The term persica is used
to indicate Persia while the standard author abbreviation L. indicates the
father of modern taxonomy.

The common names of S. persica used by various countries are

summarised in paragraph (1.2). Morphologically, S. persica is a large well-
branched evergreen tree with soft whitish yellow wood, leaves (3.8–

6.3 by 2–3.2 cm), greenish yellow flowers, and red fruit when ripe.

S. persica can survive in extreme conditions and is capable of tolerating

very dry environments to highly saline soils. It is found in arid, coastal
regions, saline lands, desert flood plains, and grassy savannahs.

In addition, it shows preference to clays but is also present on loam,

sand, and black soils. In different countries, the plant displays some
variations in its distributional behavior, which may be due to changes in
water resources, edaphic variables, climatic factors, and anthropogenic
pressures along the elevation gradient.
S.persica is commonly known as miswak tree since it is the most
common source of miswak and extensively used among the 182 species of
plants used as chewing sticks across the world.
Miswak is an Arabic word, also known as miswaak, miswaki,
meswak, misswak, mswaki, siwaki, sewak, and siwak in different Arabic
dialects and countries, which means tooth cleaning stick. In English,
miswak has been referred to as the “natural toothbrush”. Miswak is
trimmed at one of the tip forming an exposed end which is then chewed to
form a brush (Fig. 1). In geographical areas where S. persica tree grows,
miswak is prepared from that plant itself while in regions where S. persica
is absent, miswak can be made from other plants, such as Azadirachta
indica A.Juss. (Neem), Olea europaea L. (Zaitoon), Capparis aphylla Roth
(Khiran), Acacia arabica (Lam.) Willd. (Kikar), and others.
The World Health Organisation (WHO) has also recommened and
encouraged the use of these sticks for oral hygiene . Historically, chewing
sticks were firstly used by the Babylonians some 7000 years ago and
eventually used by Greek and Roman empires. Even now it is used in many
parts of the world mainly in Africa and the Middle East.
Recently, there have been considerable interest in exploring the
medicinal properties of S. persica. Several studies have probed into the
biological profile of this plant and a wealth of literature has emerged and
published. Nonetheless, there is currently a dearth of updated compilation
of available data on itstraditional uses, phytochemistry, pharmacological
properties, and potential bioapplication in various fields. In this context, we
aimed to provide an up-to-date detailed description of the traditional uses
of S. persica across the world, and a critical analysis of its phytochemical
composition and pharmacological properties. The potential bio-application
of S. persica in food preservation, functional food development, animal
feed, and nanotechnology have also been systematically reviewed. Lastly,
possible future directions of research and priority are also discussed.
(Aumeeruddy et al,2018)
 Fig. [1.1] Salvadora persica - miswak.

1.2 Common names:

English mustard tree, saltbush, tooth-brush bush, toothbrush tree

Arabic arak, miswak, siwak India arak, aranmakapicam,
aranmakapicamaram, badapilu, bhaara gaangu, brihatpilu, cakantititam,
cakuntititam, camarankari, camaratam, cankiciyam,cevvuka,
chekkerachettu, chhota-pilu, chhotapilu, chinnavaragogu, China
varagogu, chirukalarva, chota-pilu, ciru kalarva, cittuva, cittuvila,
cumirtam,darakht-i-misvak, darakht-i-miswak, darakhtemisvak, dhalu,
gauli, geya, ghooria, ghunia, gogu, gone, goni, goni chakke, goni-mara,
gonia, gonimara, goniya, gonni, gudaphala, gunia, irak,
irattakampilucaramakki, irattaputpam, jal, jar, jhai, jhak, jhal,
juttueerugamma chettu, kaarugogu, kabbar,kakavallapam, kakham,
kalarva, kalawa, kallivira, kankhina, kantacakikam, kantacakikamaram,
kareegoni, kargol, kargoli, kari goni mara, karkol,karugogu, khabhar,
khakheen, khakhin, kharajal, khari jar, kharjal, kharijal, kharijar, kickin,
kickni, kireegoni, kirgonji, kiri gonee mara, kirigoni mara,kodumaavali,
 kotumavali, kotungo, koyya, kunni, langhupilu, madhupilu,
mahaphala, mahapilu, mahavriksha, meeraj, meerajoli, miraj, mirajoli,
miriga,mitha jal, mithi-pilu, motijalya, nettuka, nettukamaram, nilavukay,
ooghai puttay, opa, pancatipika, paviyam, pedda gogu, peddavara
goki,peddavaragogu,peddavaragoki,peddavarajuvenki,peddawaragowenk,
peddawaraguwenki, peelu, pelu, pennavaragogu, perungoli, pilu, pilu ka
pala,piludi, piluh, piluka, pilva, pilvu, pinna-veragogu, pinnavaragogu,
piravalapalam, rajapilu, rhakhan, rokacamani, shiru-kalarva, sittuvila,
sramsi,surugalarva, tanuka, tanukamaram, tanukonam, thorapeelu,
thorapilu, thuraka gogu, tiksna-vrksatphalani, tiksnataru, tiksnavrksa,
titcanapalai, titcanapalaimaram, toboto, uba, uga, ughaiputtai, uka, ukai,
ukamaram, ukattekku, ukaver, upa, uvay, vagai, varagogu, varagoja,
varagoki, varagu, varakari, veda, vedha, velvigai, veragogu,
vikkinapalam, virutcanam, vivay, wara gogu, waragogu, waraguwenki,
warangu-wenki East Africa esekon, mswaki, ol-remit Kenya aadde, adde,
ade, adhe, adhei, akhai, ashokonyon, asiokon, asiokonion, barsute, cadei,
chokow‟o, esekon, esokon, hayay, huda, iremito, mjungumoto,mswaki,
muezamoyo, mukayau, muswaki, nyaa, nyedhe, olremit, oremit,
sogotaiwa, sokotei, sokotu Namibia kerriebos (Afrikaans); ozongambu
(fruit), otjingambu (Herero); khoris (Nama/Damara); okatunguya,
omumkavu (Ndonga); enghadu (Kwanyama); omungavo, omungavu
(Mbalantu); omunkavu (Kwambi, Nkolonkadhi, Ngandjera); omgavo,
omungavu (Eunda); omungavu (Kwaluudhi) Nigeria asawaki, kighir
Somalia Caday Southern Africa omungambu (Herero) Tanzania
chigombo, iremito, mkayo, mkung‟uni, mkunghuni, modee, msaki,
mswake, mswaki, mtele, muche, muléwa, muwiga, mwiga, olremit,
oremit. (Aumeeruddy et el,2018)
1.3 Religious Aspects

The use of miswak dates back to ancient times however its importance
was highlighted by Prophet Muhammad (Peace be Upon Him [PBUH])
during the early days of Islam. The religion Islam has stressed on the
importance of maintaining good overall body as well as oral hygiene. It has
been advised to the followers to keep in practice the use of chewing stick
(miswak) for keeping the oral cavity clean and minimizing halitosis. The
Prophet Muhammad (PBUH) preached Islam not just by his words but also
through his actions by showing and observing practically. The sayings of
the Holy Prophet Muhammad PBUH described and stressed on the
importance of various plant species amongst which miswak tops the
list.[14] Following are some hadiths in which The Prophet Muhammad
(PBUH) emphasized on the use of Miswak; Jabbir Bin Abdullah (RA)
relates that prophet Muhammad (PBUH) said “The black colored Kapas
(fruit of Salvadora) is the finest one.”[15] Hazrat Aaisha (RA) narrates that
Muhammad (PBUH) said “Miswak purifies the mouth and is a cause of
Allah's pleasure.”[15] Furthermore, Abu-Hizat-us-Sabahi (RA) described
that Muhammad (PBUH) gave him a twig of Salvadora and said, “Use it as
miswak.”( Niazi et al ,2016)
Miswak as oral health cleaning tool as stated in the Prophetic narrations
Hadith is the second authentic reference source after the
Qur‟an. There are number of ahadith of the Prophet (s.a.w) which
encourages people to practice siwak in their daily life. According to these
narrations, the Prophet (s.a.w.) gave keen interest to siwak as the oral
cleaning tool. The following tables are comparative classifications of
ahadith of miswak that are mentioned in the Six Authentic Books of hadith
collections; there are some repeated hadith mentions in those
books.(Nordin Et el,2012)
1.4 Botanic Describtion:-

Salvadora persica is an evergreen shrub or small tree to 6-7 m; main

trunk erect or trailing with profusely branched, wide crown of crooked,
straggling and drooping branches; young branches green in colour; bark
slightly rough, greyish-brown on main stem, paler elsewhere. ( pilu et al
,2009) ( Figure 2).

Leaves oblong-elliptic to almost circular, 3 x 7 cm, light to dark

green,rather fleshy, sometimes with wartlike glandular dots and dense,
rather loose hairs; apex broadly tapering to rounded, sharp-tipped; base
broadly tapering; margin entire; petiole up to 10 mm long; leaves in
opposite pairs. . ( pilu et al ,2009)(Figure 3)

Flowers greenish to yellowish, very small, in loose, slender-branched

axillary or terminal panicles, up to 10 cm long. . ( pilu et al ,2009)

Fruit spherical, fleshy, 5-10 mm in diameter, pink to scarlet when

mature,single seeded; seeds turn from pink to purple-red and are
semitransparent when mature. . ( pilu et al ,2009)( Figure 4)

The generic name was given in 1749 in honour of an apothecary of

Barcelona, Juan Salvador y Bosca (1598-1681), by Dr Laurent Garcin,
botanist, traveller and plant collector. The true specimen of this species
came, as the specific name indicates, from Persia. ( pilu et al ,2009)
 Fig [1.2] Salvadora persica tree .(Khatak et al, ,2010)

Fig [1.3] Salvadora persica leaves .(Khatak et al, ,2010)

 Fig [1.4] Salvadora persica fruits. (Khatak et al, ,2010)

1.5 Distribution:

S. persica has a wide geographic distribution ranging from Rajasthan

(India), Nepal, and Malaysia in the east through Pakistan, Iran, Iraq, Saudi
Arabia, and Egypt to Mauritania in the west, and from North Africa
through Sudan, Ethiopia, and Central Africa to southwestern Africa.
(Khatak et al, ,2010)

It belongs to the family Salvadoraceae and has a wide geographic

distribution, ranging from Rajasthan, Nepal and Malaysia in the east
through Pakistan, Iran, Iraq, Saudi Arabia and Egypt to Mauritania in the
West, and from North Africa through Sudan, Ethiopia, and Central Africa
to Southwestern Africa. (Khatak et al, ,2010)

It is widely scattered in the poor savanna areas in Western Sudan as

a range crop having immense medicinal value with numerous uses.( Mariod
et al , J Am Oil Chem Soc, 2009) t is widely distributed in the arid regions
of India and often on saline soils.(Khatak et al, ,2010)

1.6 Planting

The agroclimatic zoning Every plant is sensible to weather

conditions. In order to satisfy its physiological requirements, each plant has
a minimum as well as a maximum demand from the climate. Beyond such
limits, it is negatively affected. The range between these two values
represents the energetic level the plant needs for its physiological complex
to work efficiently. This range is called “ideal temperature” (Ometto,
1981). Agroclimatic zoning consists in the division of an area of land into
climatic resources units and identifies areas with different potential yields,
according to the environmental conditions. These units have a unique
combination of climatic characteristics, which in turn specify the potentials
and constraints for land use. Then, agroclimatic zoning can be understood
as the division of an area according to the favorability for agriculture. To
establish the siwak-growing zones, the identification of its requirements,
limits and bio-meteorological tolerance and conditions is fundamental. The
climatological characteristics of native areas and the regions of successful
cultivation around the world were first taken into consideration.
Afterwards, the resulting bioclimatic indicators were extrapolated to the
Argentine territory. Growth aspects, such as development and death
chances by excess or deficiency, were examined. Geographical location,
mean annual rainfall and temperature records area available (for the period
1981–2010) from meteorological and agrometeorological stations within
the study area were also taken into account. The bioclimatic variables
studied were average annual temperature, absolute minimum temperature
and annual rainfall. These were obtained by interpolating the data collected
in the 125 meteorological stations around the country that belong to the
National Meteorological Service. From the available database,
geographical limits were mapped for the different variables that define
different aptitude classes: optimal, very suitable, suitable, marginal and
non-suitable zones. To analyze the thermal regime, the average of the
annual temperatures was considered. When the average was lower than 12
°C, the area was rated as non-suitable and in the 12 to 15 °C range it was
labeled as suitable, while temperatures ranging from 15 to 30 °C qualified
it as an optimal area. Although Argentine territory extends towards the
Tropic of Capricorn (23°27′S), it lacks tropical climates. Therefore, when
tropical species are exploited, special care must be taken to avoid damage
by frost. The absolute minimum temperature, which is by definition the
lowest recorded temperature that occurs at least once every 30 years, was
mapped independently. The area was considered non-suitable when the
absolute minimum temperature was lower than −10 °C, because the frost
not only inhibits fructification, but it is also lethal to the species. In order to
analyze the moisture regime, the isohyets that corresponded to the annual
rainfall were considered. Optimal areas were the ones receiving rainfalls in
the 300–700 mm range. The areas with values below 300 mm were rated
non-suitable and those above 700 mm, suitable. Finally, the agro-climatic
zoning (obtained overlaying the cited maps above) shows the areas in the
country where this species may be grown with success probability under
rainfed conditions. Five classes of agroclimatic suitability areas were
defined: optimal, very suitable, suitable, marginal and non-suitable. Table 1
shows the agroclimatic indices that define each class of agroclimatic
suitability. It is important to highlight that the non suitable areas present
two or more of the constraints indicated in Table 1. To obtain the maps, a
series of previously interpolated bioclimatic variables were used, which
were processed afterwards with the Geographic Information System (GIS)
tool of the Arc-GIS 9.3 program. Climatic interpolations were made using
the “Interpolate to Raster” tool, within the “3D Analyst” extension of the
same program, following the Ordinary Kriging interpolation method.(
Falasca et al ,2015)
1.7 Morphology:

The surface morphology of Miswaks powder was investigated by

scanning electron microscope (SEM) at magnification of 1500. The SEM
images of Miswak are shown. The microstructure of Miswaks image
showed that the surface could be seen to contain amounts of small pores
indicating that this material has good characteristics to be employed as a
natural adsorbent for dye uptake (Fig. 3). The microstructure of Miswaks
showed that the cells are nearly spherical and irregular in size and
distribution. The cell size of Miswak-3 is found to be bigger than that of
Miswak-1 and Miswak-2. It is believed that these pores provide ready
access and large surface area for the sorption of dyes on the binding sites.(
Moawed ,2013)

1.8 Traditional Uses

1.8.1 Leaves

The leaves are eaten as a vegetable in the eastern tropical Africa and
are used in the preparation of a sauce, and tender shoots and leaves are
eaten as salad. Leaves are bitter in taste, corrective, deobstruent, astringent
to the bowels, tonic to the liver, diuretic, analgesic, anthelmintic, useful in
ozoena and other nose troubles, piles, scabies, leukoderma, lessening
inflammation, and strengthening the teeth. Leaves are pungent and are
considered in Punjab as an antidote to poison of all sorts and in south of
Bombay as an external application in rheumatism. The juice of the leaves is
also used in scurvy. (Khatak et al,2010)
1. 8.2 Fruits

Fruits are sweet and edible. A fermented drink is reported to be made

from the fruits. Fruits possess deobstruent, carminative, diuretic,
lithontriptic, and stomachic properties and are used in biliousness and
rheumatism. In Sind, it is believed that fruits have a good effect on snake
bite. (Khatak et al,2010)

1. 8.3 Root bark

Root bark is used as a vesicant and is employed as an ingredient of

snuff. A paste of the roots is applied as a substitute for mustard plaster and
their decoction is used against gonorrhea and vesical catarrh. A decoction
of the bark is used as a tonic in amenorrhea and the dose of the decoction is
half a teacupful twice daily and as a stimulant in low fevers and as an
emmenagogue. (Khatak et al,2010)

1. 8.4 Stem bark

Stem bark is used as an ascarifuge and also in gastric troubles.

(Khatak et al,2010)

1. 8.5 Seeds

Seeds have bitter and sharp taste. They are used as purgative,
diuretic and tonic seed oil is applied on the skin in rheumatism. (Khatak
et al,2010)
 Table [1.1] Explain Agroclimatic conditions and suitability of
plant growth

Annual rainfall Annual Absolute

(mm) temperature minimum
(°C) temperature
(°C)
Optimal area 300–700 15.0–30.0 <10
Very suitable >700 15.0–30.0 <10
Suitable area >700 12.0–15.0 <10
Marginal area >300 >12.0 <10
Non suitable area
< 300 <12.0 <10

Is important to highlight that the non suitable areas present two or

more of the constraints indicated in Table 1. To obtain the maps, a series of
previously interpolated bioclimatic variables were used, which were
processed afterwards with the Geographic Information System (GIS) tool
of the Arc-GIS 9.3 program. Climatic interpolations were made using the
“Interpolate to Raster” tool, within the “3D Analyst” extension of the same
program, following the Ordinary Kriging interpolation method. (Falasca et
al ,2015)

1.9therpeutic Applications

1.9.1tooth Paste:

Miswak can be used as mouthwash as it reduces plaque. But no such

preparation presently exists in the market. ( Khatak et al,2010).
Some of the known commercial toothpastes produced from Salvadora
persica plant are as follows: Sarkan toothpaste (UK), Quali-miswak
toothpaste (Switzerland), Epident toothpaste (Egypt), Siwak-F toothpaste
(Indonesia), Fluroswak miswak (Pakistan), Dentacare Miswak plus (Saudi
Arabia) ( Khatak et al,2010).

1.9.2Endodontic irrigation solution

Although the antimicrobial activity of miswak has been reported, its

toxicity must be considered. In addition, no report has been yet made on
the utilization of the extract as an irrigant solution in endodontic practice.
Samh et al. evaluated, in vitro, the effect of different concentrations of
miswak extract on L929 cell line in tissue culture and compared the results
with sodium hypochlorite (NaOCl). They found a concentrationdependent
morphologic change of L929 cell line when exposed to miswak extract and
NaOCl. They suspect recovery of the cells after a 4-h exposure period to
different miswak extract concentrations. ( Khatak et al,2010)

1.10 Use And Phytochemicals

In Middle Eastern, some Asian and African cultures chewing sticks

are prepared from the roots and twigs of S. persica. To prepare this type of
sticks the stings or roots are cut into pieces of 10-to 25-cm long. The sticks
of Miswak can usually be used 3–10 times daily considered as an
inexpensive and an effi cient oral hygiene. (Sharma et al ,2018)

The Primary Health Care Approach (PHCA) principles entirely

consider the use of Miswak. (Sharma et al ,2018)

The use of chewing sticks as an oral hygiene tool like Miswak, where it is
traditionally grown is encouraged and recommended by the World Health
Organization (WHO). (Sharma et al ,2018)
In addition, Miswak is also recommended for the teeth whitening, the
memory improving tool, the breath freshener, calming the bile, drying up
the phlegm, the gums strengthening, sharpening the vision and increasing
the appetite. (Sharma et al ,2018)
Antimicrobial substances such as sulfur can be extracted from its roots and
stems, moreover Trimethylamine, benzyl isothiocyanate, Salvadorine, beta
cholesterol, tannins, saponines, sodium chloride, potassium chloride,
vitamin C, flavonoids and sterols are associated with anti-bacterial effects.
Besides this, the significant amounts of added silica can help to remove
plaque mechanically. (Sharma et al ,2018)

In this plant fluoride is also found in measurable quantities, which is easily

dissolved and released in water. (Sharma et al ,2018)

1.11 Pharmacologic Activities

1.11.1 Hypolipidemic Activity

The stems of Salvadora persica are widely used as tooth cleaning

sticks in Arabic countries and decoctions show hypocholesterolemic
properties. The effects of prolonged administration of a lyophilized stem
decoction of Salvadora persica were evaluated in diet induced rat
hypercholesterolemic. The preparation was administered for 15 and 30
days and cholesterol, HDL, LDL, and triglycerides plasma levels were
assayed. The results showed that the Salvadora persica decoction
significantly lowered cholesterol and LDL plasma levels in the rats,
proving to be more active at 30 days of treatment. The systemic
administration of Triton resulted in a rise in plasma cholesterol and
triglyceride levels. The results showed that Salvadora persica decoction
was inactive at 18 h after treatment, whereas at 27 h it was able to reduce
cholesterol and LDL plasma levels; in all the experiments HDL and
triglycerides were unchanged. (Khatak et al,2010).

1. 11.2Antiulcer activity

Salvadora persica possessed significant protective action against ethanol

and stress-induced ulcers. This study was designed to confirm the antiulcer
activity of Salvadora persica decoction using optical microscopy. The
elements of gastric mucosa tended to be reestablished normally in tested
rats. (Khatak et al,2010).

1.11.3Anticonvulsant activity

The effect of Salvadora persica as an anticonvulsant was identified by

using stem extracts. The stem extracts show the potentiation of sodium
pentobarbital activity and on generalized tonic-clonic seizure produced by
pentylentertazol (PTZ) on the rat is reported. The extracts of Salvadora
persica Linn. extended sleeping-time and decreased induction-time induced
by sodium pentobarbital, in addition it showed protection against PTZ-
induced convulsion by increasing the latency period and diminishing the
death rate. (Khatak et al,2010).

1.11.4Antifertility activity

Miswak extract did not have much effect on female mouse fertility,
although it caused a significant decrease in the relative weights of the ovary
and an increase in the uterine weights. Exposure of male mice to miswak
resulted in a 72% reduction in pregnancies in untreated females
impregnated by test males. The relative weights of the testes and preputial
glands were significantly increased and that of the seminal vesicles was
significantly decreased in test males. The results indicate that miswak has
adverse effects on male and female reproduction systems and fertility.
(Khatak et al,2010).

1. 11.5Antibacterial activity

Salvadora persica contain substances that possess plaque inhibiting and

antibacterial properties against several types of cariogenic bacteria, which
are frequently found in the oral cavity. The growth and acid production of
these bacteria is thus inhibited.A comparison of alcohol and aqueous
extract of miswak was also made. It was found that alcoholic extract is
more effective than aqueous extract for antibacterial activity. In another
study, miswak pieces were standardized by size and weight and tested
against Streptococcus mutans, Lactobacillus acidophilus, Aggregatibacter
actinomycetemcomitans, Porphyromonas gingivalis, and Haemophilus
influenzae. Results found that the strong antibacterial effects against all
bacteria tested is due to the presence of a volatile active antibacterial
compounds. (Khatak et al,2010)

The effects of the extracts of Salvadora persica and derum were examined
on the proliferation of Balb/C 3T3 of fibroblast and viability of
carcinogenic bacteria. For this, aqueous extracts of miswak and derum
were prepared and their effects investigated on the growth of Balb/C 3T3
mouse fibroblast by measuring the mitochondrial dehydrogenase activity.
Also the effect on the viability of various cariogenic bacteria was also
determined. From the obtained results, it is concluded that miswak and
derum have adverse effects on the growth of cariogenic microorganisms,
with derum as more active than miswak; they show cell proliferation by
156% and 255%, respectively.(Khatak et al,2010).
1. 11.6 Antimycotic activity

Aqueous extracts of miswak could be used to reduce the growth of

Candida albicans. Such inhibition lasts for up to 36 h at concentrations of
15% and above.(Khatak et al,2010).

1.11.7Analgesic effect

Mansour et al. studied the analgesic effect of miswak decoction when

injected into mice. They found that miswak was more effective against
thermal stimuli than against chemical stimuli and also acts as an analgesic.
(Khatak et al,2010)

1. 11.8 Cytotoxicity

Mohammad et al. investigated the cytotoxic potential of Salvadora

persica on gingival and other periodontal structures, using the agar overlay
method. Results showed no cytotoxic effect by a freshly cut and freshly
used miswak. However, the same plant used after 24 h does contain
harmful components. Based on these findings they recommend cutting the
used portion of the miswak after it has been used for one day and preparing
a fresh part. The cytotoxicity in this study became evident only after 24 h
because the agar overlay method depends on the diffusion of the
medicament to the agar material.( Khatak et al,2010)

1.12 Side effects and toxicity

Acute oral toxicity The acute oral toxicity of extract of S. persica

was determined in mice (Loomis, 1978). Mice (25-30g) fasted for 12h were
randomly divided into groups comprising of six animals per group. Graded
doses of the extract dissolved in normal saline (500-5000 mg/kg p.o.) were
separately administered to the mice while control group received normal
saline only in the same quantity by means of feeding cannula. All animals
were then allowed free access to food and water and observed over a period
of first six hours and then for the period of 72 hours for signs of acute
toxicity. Daily observation on general health, growth, gross physical and
behavioral activities and also the morbidity and mortality if any was noted
and recorde.(Ahmed et al ,2011)

2. Chemical composition

Chemical analysis of S. persica miswak has demonstrated the

presence of b-sitosterol and m-anisic acid (Ezmirly et al., 1979; Ray et al.,
1975); chlorides, salvadourea, and gypsum; organic compounds, such as
pyrrolidine, pyrrole, and piperidine derivatives (Galletti et al., 1993);
glycosides, such as salvadoside and salvadoraside (Kamel et al., 1992); and
flavonoids, including kaempferol, quercetin, quercetin rutin, and a
quercetin glucoside (Abdel-Wahab et al., 1990). The roots and bark of the
S. persica tree are composed of 27% ash; a high ratio of alkaloids, such as
salvadorine and trimethylamine; chlorides and fluorides; moderate
concentrations of silica, sulfur, and vitamin C; and small quantities of
tannins, saponins, flavonoids, and sterols (Akhtar and Ajmal, 1981; Al Lafi
and Ababneh, 1995; Farooqi and Srivastava, 1968). High amounts of
sodium chloride and potassium chloride were noted, along with other
sulfur-containing organic substances (salvadourea and salvadorine)
(Dorner, 1981). S. persica miswak contains nearly 1.0 lg/g of total fluoride
and was found to release significant amounts of calcium and phosphorus
into water (Char et al., 1987). Repeated chewing of S. persica miswak was
found to release fresh sap, which may have an anticariogenic effect (Almas
and al-Lafi, 1995).However, another study noted that a negligible amount
(0.07 lg/ml) of fluoride was released when S. persica miswak was soaked
in water (Hattab, 1997). Farooqi and
Srivastava(1968) isolated benzylisothiocyanate (BITC) from S. persica
roots, and Ezmirly and El-Nasr (1981) demonstrated that BITC is an
endproduct derived from the enzymatic hydrolysis of the glucosinolate
present in the plant. BITC is a chemopreventive agent that is thought to
prevent cariogenic and other genotoxic compounds from reaching or
reacting with target sites on the treated tissue (Al-Dosari et al., 1992;
Benson and Barretto, 1985; Benson et al., 1980; Wattenberg, 1977). At a
concentration of 133.3 lg/ml, BITC was found to have virucidal activity
against Herpes simplex virus 1 (al-Bagieh, 1992). In addition, BITC has
exhibited broad-spectrum bactericidal activity (Pulverer, 1969) and was
found to inhibit the growth and acid production of Streptococcus mutans
(Al-Bagieh and Weinberg, 1988). Other components of S. persica also have
beneficial effects on oral health. The sulfur content in the ash of S. persica
roots was found to be as high as 4.73% (Galletti et al., 1993). Sulfur has a
bactericidal effect (Abo Al-Samh, 1995) and vitamin C was found to help
in tissue healing and repair (Almas, 1993). Silica acts as an abrasive and
was found to help in removing stains from tooth surfaces (Al Lafi and
Ababneh, 1995; Khoory, 1983). The astringent effect of tannins may help
to reduce clinically detectable gingivitis. Tannins were found to inhibit the
action of glucosyltransferase, thereby reducing plaque and gingivitis (Gazi
et al., 1992). Resins may form a layer on enamel that protects against
dental caries (Al Lafi and Ababneh, 1995). Salvadorine, an alkaloid present
in S. persica miswak, may exert a bactericidal effect and stimulate the
gingiva (Almas, 1993). The mildly bitter taste of the essential oils in S.
persica miswak stimulates the flow of saliva, which acts as 64 H.S.
Halawany a buffering agent. High concentrations of chloride inhibit the
formation of calculus (Akhtar and Ajmal, 1981) and aid in removing stains
from tooth surfaces (Almas, 1993). Saturation of calcium in saliva due to
the use of chewing sticks was found to promote enamel
remineralization.(Halawany,2012).
Flavonoids

Flavonoids are secondary metabolites with polyphenolic structure

and synthesized in plants, through poly propanoid pathway (Ali, 2011).
Flavonoids form part of the largest category of phytochemicals, the
phenolic phytochemicals. The term „phenol‟ encompasses a variety of plant
compounds containing an aromatic ring with one or more hydroxyl groups.
Many phenolic occur in nature with a sugar group attached a thesis, making
them water soluble Flavonoidsare present as shown by the formation of
magenta red solution. Dietary flavonoids represent a diverse range of
polyphenolic compounds that occur naturally in plant foods. The range and
structural complexity of flavonoids has led to their sub flavones,
flavanones, flavan-3-ols (and their ,classification as flavanols
proanthocyanidins), isoflavones and anthocyanins. They are,oligomers
present in significant amounts in many commonly consumed fruits,
vegetables, grains, herbs and drinks, these structurally diverse compounds
exhibit a range of biological activities in vitro which may explain their
potential cardio protective and anti-cancer properties, including
antioxidant, anti-inflammatory, apoptotic activity and improvement of
endothelial function, as well as inhibition of angiogenesis and cell
proliferation activities.( Anthoney Swamy T* et al ,2015). Table 2 show
chemical composition of salvadora persica (Abhary et al ,2015).
2.1 Minerals content

The minerals content profile of Miswak showed high levels of

chloride in the water extract (71 mg/g) and lower levels in the ethanol
extract (6.21 mg/g). Metals and trace metals were also found in high
concentrations in the dried powder of Miswak as illustrated in Table 3.
(Abhary et al ,2015)

(Abhary et al ,2015)
2.2 Free radicals

Free radicals are highly reactive particles also highly reactive by

products with an unpaired electrons, produced when cells are exposed to
stress(s). They initiate chain reactions which lead to disintegration of cell
membranes and cell compounds, including lipids, proteins, and nucleic
acids (Leong and Shui, 2002). Free radical oxidative stress has been
,implicated in the pathogenesis of a wide variety of clinical disorders
autoimmune ,such as cancer, cardiovascular disease, Alzheimer‟s disease
disease, diabetes, multiple sclerosis and arthritis (Halliwell and Gutteridge,
1999).
Biological systems protect themselves against the damaging effects
of activated specie by several means (e.g. Such as production of
Antioxidants are substances that markedly delay or prevent.antioxidants)
the oxidation of oxidizable substrate when present in foods or body at low
concentrations.

There are two types of antioxidants, (1) Enzymatic antioxidants (e.g.,

ascorbic peroxidase, polyphenoloxidase and ,superoxide dismutase
catalase) and (2) Non-enzymatic antioxidants (e.g., ascorbic acid ) a-
tocopherol (vitamin E), glutathione, carotenoids, and flavonoids)
(Krishnaiah et al., 2011). Antioxidants may help the body to protect itself
against various types of oxidative damage caused by reactive oxygen
species, which are linked to a variety of diseases including cardiovascular
diseases, cancers (Gerber et al., 2002), neurodegenerative diseases and
Alzheimer‟s disease (Di Matteo and Esposito, 2003). plant antioxidants
can therefore serve as a type of preventive The natural medicine. Some
researchers suggest that two-thirds of the world‟s plant species have
medicinal value; in particular, many medicinal plants have great
antioxidant potential (Krishnaiah et al., 2011). If human disease is believed
to be due to the it is possible to limit oxidative tissue damage and hence
prevent disease progression by antioxidant defense
supplements(Bhattacharya et al., 1999).

In other words, if the balances ways in the direction of pro-oxidants,

oxidative stress can arise, which under normal circumstances is controlled
by a broad range of antioxidant enzymes, proteins and antioxidants
provided by the diet The protection offered by fruits and vegetables
against oxidative stress in several diseases has been attributed to various
antioxidants and vitamins.
Dietary phenolic compounds and flavonoids have generally been
considered, as non-nutrients and their possible beneficial effect on human
health has only recently been recognized. Flavonoids are known to posses
,anti-inflammatory, antioxidant, antiallergic, hepatoprotective
antithrombotic, neuroprotective, and anticarcinogenic activities (Araceli et
al., 2003). Therefore, the search for natural antioxidants of plant origin has
gained momentum in recent years.
`The phenolic compounds may contribute directly to the antioxidant
action due to the presence of hydroxyl functional groups around the nuclear
structure that are potent hydrogen donators. These phenolic compounds of
plant origin show their antioxidant effect by various mechanisms including
their ability to scavenge free radicals, chelate metal ions that serve as the
catalysts for production of free radicals or activate various antioxidant
enzymes and inhibit oxidases (Ibrahim et al,2015).
2.3 Organic compounds

Chemical analysis of S. persica root extracts demonstrated the

presence of β-sitosterol, m-anisic acid, salvadourea and high content of
gypsum have been found in the stem.[4] Organic components identified in
S.persica included pyrrolidine, pyrrole and piperidine derivatives;
glycosides such as salvadoraside; flavonoids such kaempferol, rutin, and a
quercetin glucoside; and sugar terpenoids, alkaloids, esters of fatty acids
and of aromatic acids, and fats.[5,6,7] An indole alkaloid being a urea
derivative, salvadoricine, from the leaves, salvadourea and glucotropaeolin,
from the roots, 1-triacontanol and 1-octacosanol from the stems and
trimethylamine from the root bark have been isolated and characterised by
chemical and spectral data. [8, 9] In these studies myristic, lauric and
palmitic acids have been identified as the major components of the seeds.
Trimethylamine was also isolated from the leaves and the bark and the
presence of alkaloids has been reported. Dried seeds contain 30% to 40 %
non-edible oil, with 30% lauric and 50% myristic acid which is used as a
substitute for coconut oil in soap-making and detergentpreparation.[10, 11,
12] Various Indian companies like Godrej Soaps Ltd, Bombay, Tata Oil
Mills, Hindustan Lever Ltd, Aegis Chemicals, Lauric Oils/Seeds and
Seedlings, and KVIC, Bombay are exploiting the oil of Salvadora spp. Five
glycosides from the stem have been isolated. Two of them were new and
identified as sodium 1-Obenzyl- -D-glucopyranoside- 2-sulphate
(salvadoside) and 5,5 dimethoxylariciresinol, 4´-4-bisO- -D-
glucopyranoside (salvadoraside), in addition to syringin, liriodendrin and
sistosterol 3-Oglucopyranoside. This represents the first report of syringin
and lignan glycosides from the family Salvadoraceace. The leaves contain a
flavonoid quercetin and many phenolic acids like vanillic, syringic, ferulic,
p-hydroxybenzoic and salicylic acid. (Darout,2015)
Resins in small amount, tannins (tannic acid), alkaloids in large
amounts, flavonoids, sterols, -sitosterol, m-anisic acid, salvadourea 1,3-
Bis-(3methyoxy-benzyl)urea , essential volatile oils, e.g. mustard oil,
vitamin C, and steam-distillable compound of 10% benzyl nitrate and 90%
benzylisothiocyante have all been reported from the roots. Another studies
showed that in addition to some of the above mentioned compounds, the
root contains 27 % ash, large amounts of chlorine, trimethylamine, but
negligible amount of tannins and saponins. It is believed that some of these
components are useful in tooth cleaning. (Darout,2015).
2.4 Phytochemistry

Salvadora persica L. commonly known as Miswak and have immense

medicinal value as anti-microbial and in prevention of tooth decay. Present
study deals with phytochemical and antioxidant evaluation of S. persica
twig and stem. Chloroform and ethanolic extracts from S. persica twig and
stem are screened for antioxidant activity using, DPPH free radical
scavenging activity. Methanolic extract has been studied through HPTLC.
In S. persica twig, IC50 of chloroform extract and ethanolic extract was
found to be 181.33 ± 1.15 µg/ml and 197.00 ± 1.73 µg/ml respectively,
however in stem, IC50 of chloroform extract and ethanolic extract was
found to be 187.33 ± 0.57 µg/ml and 235.66 ± 1.52 µg/ml respectively.
Ascorbic acid is used as standard which showed IC50 2.03 ± 0.06 µg/ml. In
HPTLC studies the ferulic acid content was found to be 0.026% and
0.082% in S. persica stem and twig respectively. All the extracts showed
significant in vitro antioxidant activity, chloroform extract showed the most
potent activity followed by ethanolic extract. Ferulic acid, a potential
antioxidant present in this species, has been studied through HPTLC. The
presence of ferulic acid has not yet been reported and quantified in this
species which may be utilized for the proper standardization of the
drug.(Gupta Et El ,2015).
2.5 Volatile Compounds

This study is the first to report the presence of oleic, linolic and
stearic acids in this plant. This work has led to the identification of a
variety of low molecular weight compounds most of which are simple
secondary metabolites. Among the compounds identified are esters of fatty
acids and of aromatic acids, and some terpenoids. Storage of S. persica
twigs for two years prior to extraction did not seem to affect the result of
the chemical analysis greatly(AbdELRahman1 Et El,2003)
Salvadora persica seeds oil.

`Oil Content, Fatty Acid, Tocopherol and Sterol Composition The oil
content of Salvadora seeds collected from Kordofan (sandy soil) and Gezira
(heavy clay soil) states, Sudan, was found as 41.4 and 42.8% (Table 1),
respectively, is comparable with that reported by FAO [4] which, reported less
oil in the seeds (40%), and Reddy et al. [20] which showed high oil content
44.78–45.50% for seeds grown in alkali soils, and 43.28–44.36% for seed
grown in saline soils. The oil content we showed in this study is less than the
oil content reported by Tripathi and Rathore [21]. The oil content of the two
samples was significantly different at P\0.05. On the whole, the oil content of
S. persica seeds is very high in comparison to common oil sources found in
Sudan such as groundnut, sesame, cotton seed, and caster bean with oil
contents between 20 and 45% [22, 23]. Therefore, from an economical point of
view, production of industrial oil from seeds of S. persica could be interesting.
The results for fatty acid composition, total saturated fatty acids (SFA),
monounsaturated fatty acids (MUFA) of crude S. persica seed oil. The major
fatty acids were myristic acid (C14:0) followed by palmitic acid (C16:0) and
oleic acid (C18:1), representing 45.5, 35.1 and 10.2%, respectively, in oil
extracted from the Kordofan sample, and 45.5, 34.4 and 10.6 in the Gezira
sample. Besides these three main fatty acids, five more were identified and
quantified in both samples. SFA was the main group of fatty acids,
representing 85.9 and 84.0% in Kordofan and Gezira samples respectively,
followed by MUFA 14.0 and 15.9%, respectively. The ratios of
saturated/unsaturated acid are 6.1 and 5.2 respectively, which is very high
because of the high level of saturated fatty acid such as C14, and C16. The
fatty acid profile of S. persica oil is consistent with results published by other
workers As further important criteria for the assessment of seed oils, the
contents and composition of tocopherols, tocotrienols, and plastochromanol-8
(P-8) were determined; these data are presented in Table 2. The tocopherol
content of S. persica seed oil showed a medium amount of tocopherols 46.3
and 45.7 mg/100 g in Kordofan and Gezira samples respectively, which was
higher than the tocopherol amount of groundnuts oil (27.9 mg/100 g), and
lower than the tocopherol amount of other common oils studied by Mariod et
al(Mariod Et Al,2009)