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Ziziphus rugosa is one of the wild plant belongs to the family Rhamnaceae. This plant is traditionally used for the treatment of Diarrhoea, Menorrhagia, Ulcer, Skin disease, Cough, Hypotension. The phytochemical analysis showed the presence of tannins, quinines, phenols, flavonoids, alkaloids, terpenoids, saponins, glycosides, protein, fibre, carbohydrates. Some active chemical constituents isolated and evaluated for their medicinal use. The pharmacological studies revealed that Ziziphus rugosa possess antidiabetic, antioxidant, anti-inflammatory, analgesic, anti-cancer, CNS depressant, antimicrobial, antiparasitic, dermatological and many other effects. The results of this exploration showed that, traditional use of Ziziphus rugosa plant is to treat various ailments in their area is based on the knowledge of tribal people reside in those regions. The current review will discuss the traditional uses, chemical constituents, pharmacological effects and therapeutic importance of Ziziphus rugosa.
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Int. J. Pharm. Sci. Rev. Res., 62(2), May - June 2020; Article No. 08, Pages: 40-44 ISSN 0976 044X
International Journal of Pharmaceutical Sciences Review and Research
International Journal of Pharmaceutical Sciences Review and Research
Available online at www.globalresearchonline.net
©Copyright protected. Unauthorised republication, reproduction, distribution, disseminatio n and copying of this document in whole or in part is strictly prohibited.
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40
Manjunatha E*1,2, Murugan Vedigounder1, Geetha K M1, R Nandeesh2, M N Palaksha3
1 College of Pharmaceutical Sciences, Dayananda Sagar University, Bangalore, Karnataka, India.
2 Sree Siddaganga College of Pharmacy, B H Road, Tumkur, Karnataka, India.
3 Bharathi College of Pharmacy, Mandya, Karnataka, India.
*Corresponding author’s E-mail: manjupharma@gmail.com
Received: 08-03-2020; Revised: 16-05-2020; Accepted: 25-05-2020.
ABSTRACT
Ziziphus rugosa is one of the wild plant belongs to the family Rhamnaceae. This plant is traditionally used for the treatment of
Diarrhoea, Menorrhagia, Ulcer, Skin disease, Cough, Hypotension. The phytochemical analysis showed the presence of tannins,
quinines, phenols, flavonoids, alkaloids, terpenoids, saponins, glycosides, protein, fibre, carbohydrates. Some active chemical
constituents isolated and evaluated for their medicinal use. The pharmacological studies revealed that Ziziphus rugosa possess
antidiabetic, antioxidant, anti-inflammatory, analgesic, anti-cancer, CNS depressant, antimicrobial, antiparasitic, dermatological and
many other effects. The results of this exploration showed that, traditional use of Ziziphus rugosa plant is to treat various ailments in
their area is based on the knowledge of tribal people reside in those regions. The current review will discuss the traditional uses,
chemical constituents, pharmacological effects and therapeutic importance of Ziziphus rugosa.
Keywords: Ziziphus rugosa, Anti-diabetic, Antioxidant, Anti-inflammatory and cytotoxic.
INTRODUCTION
he world health organization (WHO) estimates that
4 billion people, 80 percent of world population
presently use herbal medicine for some aspect of
primary health care. WHO notes that 119 plants derived
pharmaceutical medicines correlated directly with their
traditional uses as plant medicines by native cultures.1The
plant kingdom still holds many species of plant containing
substances of medicinal value which have yet to be
discovered and large numbers of plants are constantly
being screened for their pharmacological value in addition
to the already exploited plants. As a result of modern
isolation techniques and pharmacological screening
procedures new plant drugs usually find their place in
modern medicine.2 Since the time immemorial, our
traditional system of medicine and folklore claiming those
medicinal plants as whole or their parts are being used in
all types of skin diseases successfully including bacterial
and fungal. The most of the medicinal preparations now a
day’s available in the market are either not effective up to
the mark or has developed resistance resulting in
reoccurrence again. Plant derived drug serve as prototype
to develop more effective and less toxic medicines.3,4
Ziziphus rugosa is one of the wild plants belongs to the
family Rhamnaceae. This is a large family of flowering
plants, mostly trees, shrubs, and some vines, commonly
called as buckthorn family, included in the order Rosales.
Ziziphus rugosa Lam. chiefly found in dry deciduous
forests. It is a large straggling thorny evergreen straggling
spiny shrub or small tree, 3-6 m tall, Leaves are alternate,
dark-green, broadly ovate or broadly elliptic, serrate,
oblique or subcordate or rounded at the base. The wood
of the tree is reddish in color and moderately hard,5 fruits
orange to black, obovoid-globose or subglobose fruit is 9 -
12mm long and 8-10mm wide.6-7 The Kodava community
in the Kodagu region of the Western Ghats eats the raw
and ripened fruit for nutritional source traditionally.8 This
plant is host for Laccifer lacca, a parasitic scale insect9 and
is food for various wild animals like Elephant and Deer.10
Figure 1: Ziziphus rugosa plant and its inflorescence.
Review on A Wild Medicinal Plant: Ziziphus rugosa
T
Review Article
Int. J. Pharm. Sci. Rev. Res., 62(2), May - June 2020; Article No. 08, Pages: 40-44 ISSN 0976 044X
International Journal of Pharmaceutical Sciences Review and Research
International Journal of Pharmaceutical Sciences Review and Research
Available online at www.globalresearchonline.net
©Copyright protected. Unauthorised republication, reproduction, distribution, disseminatio n and copying of this document in whole or in part is strictly prohibited.
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41
Table 1: Some of the selected species of genus Ziziphus are11-13
Z. apetala Hook.f. ex
Z. attopensis Pierre
Z. cotinifolia Reissek
Z. fungii Merr
Z. hutchinsonii
Z. incurva Roxb.
Z. mexicana Rose.
Z. mistol Griseb.
Z. mucronata Willd.
Z. platyphylla Reissek
Z. rugosa,
Z. saeri Pittier
Common names of Ziziphus rugosa13
Hindi: churna Kannada: Bilichurimullu, Kottemullu
Malayalam: Malamtutali Marathi: Churan, Sanskrit:
Ghonta Tamil: Totari Telugu: Gottikampa pindu parighamu
Tulu: Kottemullu.
Classification: 14
Kingdom: Plantae
Division: Tracheophytes
Subdivision: Angiosperms
Order: Rosales
Family: Rhamnaceae
Genus: Ziziphus
Species: Ziziphus rugosa
TRADITIONAL USES
From ethnobotonical and traditional claims the plant parts
used by the natives for various ailments. Bark, fruit, leaves,
flower and root are used in the preparation of Herbal
formulations. In some parts of South India natives use dried
stem bark as Astringent, for Mouth ulcer and Diarrhoea,
Flower is uses for Menorrhagia15. Traditionally natives of
Thalamalai Hills, Namakkal District, Tamilnadu16,
Gopalswamy hills of Karnataka, Western Ghats and
Coimbatore district of Tamilnadu, used the bark of this
plant for the treatment of Ulcer, Skin disease, Cough,
diarrhoea, hypotension. 17
Z. rugosa fruit is commonly known as famine edible and
even sold by locals. Natives prepare dosa by grinding the
ripe fruit. The fruit is described as demulcent in the
treatment of throat and broncho-pulmonary irritation and
powdered dried fruit and leaves are applied topically in the
treatment of boils.18. The fruit was also used as coolant and
to keep body hydrated used by villages of upper-Ghat
(Salkani and Killara) and two of the coastal zone (Murur and
Kallabbe) in the central Western Ghats, Karnataka, India.
The fruit is used by the rural communities of Tiruchirappalli
District, Tamilnadu, South India for wounds and diarrhea.19
PHYTOCHEMICAL INVESTIGATION
Preliminary phytochemical investigations reported the
presence of various phytoconstituents and the results are
given in the table 2.
Isolated Phytochemicals
Phytochemical investigations reported the presence of
various isolated phytoconstituents and the results are given
in the table 3.
Table 2: The preliminary phytochemical studies.
Fruit
Bark
Leaves
Root
Alkaloids, saponins, flavonoids and glycosides,
fibre protein and carbohydrates 20
Macronutrients: Nitrogen, potassium, calcium
and magnesium Micronutrients: Zinc, copper,
manganese and iron21
Terpenoids, alkaloids,
steroids, flavonoids,
glycosides and saponins 23
carbohydrates
(monosaccharides,
reducing and mixed-
reducing sugars),
alkaloid, glycosides,
steroids, tannins and
saponin22
Tannins, alkaloids,
steroids, saponins,
flavonoids, coumarin
and terpenoids25
Table 3: Isolated compounds reported.
Fruit
Bark
Root
Triterpeniod: Betulinic
acid 20
Cyclopeptide alkaloids: Nummularine-P, Sativanine-H
and Rugosanine-B
Triterpinoids: Lupeol and Betunilic acid.
Lignan glycosides, (6 S,7 R,8 R)-7a-[(b-
glucopyranosyl)oxy] lyoniresinol and (þ)-lyoniresinol-3a-
O-b-D-glucopyranoside.
Flavonoid glycosides: Kaempferol-3-O-a-L-
rhamnopyranosyl-(1!2)-a-L-rhamnopyranoside and
Horridin33
Triterpeniods: Lupeol, betulin, betulinic
aldehyde, betulinic acid, alphitolic acid,
euscaphic acid, zizyberenalic acid, and
β−sitosterol.
Coumarin: Scopoletin
Flavonoids: Kaempferol, afzelin, quercitrin,
and (+)-catechin.24
Int. J. Pharm. Sci. Rev. Res., 62(2), May - June 2020; Article No. 08, Pages: 40-44 ISSN 0976 044X
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International Journal of Pharmaceutical Sciences Review and Research
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42
PHARMACOLOGICAL ACTIVITIES
Cytotoxic and anticancer activity
The methanolic extract of Pericarp and seed has proved as
good anticancer agent and when tested against human
melanoma cells.20 Pericarp and Seed Extract of Zizyphus
rugosa Lam. was evaluated for Cytotoxic Activity in terms of
lethal effect on the brine shrimp Artemia nauplii assay.
Degree of lethality was directly proportional to the
concentration of the extract. Seed extract showed potent
cytotoxicity (LC50 of 564.73μg/ml) and thus it was toxic
compared to pericarp (LC50 of 1000μg/ml) the extracts have
shown bioactivity in terms of causing mortality of brine
shrimps.22 The ethanolic extract was found to have good
toxicity to Brine Shrimp Artemia nauplii compared with the
reference anticancer drug vincristine sulphate.22
Antimicrobial and insecticidal activity
Methanol extract of Z. rugosa fruit pericarp was evaluated
for antibacterial activity. The extract exhibited dose
dependent inhibition of test bacteria using well plate
method. Among bacteria, E. coli was found to be more
susceptible to extract than S. aureus as revealed by wider
zones of inhibition.26 From another study it is inferred that
the aqueous pericarp extract of Z. rugosa exhibited efficient
antibacterial activity against both gram positive and gram
negative organisms. The ethanolic extract possesses
highest antifungal activity followed by aqueous and hexane
against A. niger. and C. albican.27
Ethanolic extract of Ziziphus rugosa leaves also exhibited
antimicrobial activity, where showed moderate activity
against only one bacterium (Shiggla sonni) while the
standard drug Chloramphenicol showed very good zone of
inhibition against all five types (Salmonella typhi,
Staphylococcus aureus, Shiggla sonni, Salmonella
paratyphi, Salmonella grb) of bacteria18. Chloroform extract
of bark as antimicrobial agent showed significant inhibition
against Staphylococcus aureus but good inhibition against
Streptococcus pyogens, Pseudomonas aerogenes and
Salmonella typhi.28
The seed methanolic extract was evaluated for Insecticidal
activity in terms of Larvicidal effect.on second instar larvae
of A. aegypti. The larvicidal effect of extract was
determined after 24 hours. Dead larvae were identified
when they failed to move after probing with a needle in
siphon or cervical region. Concentration of 50 mg/ml was
effective and produced 100% mortality.29
Antioxidant activity
The free radical scavenging activity of methanol seed
extract was evaluated. The extract exhibited concentration
dependent radical scavenging activity i.e., higher the
concentration, more scavenging potential on DPPH
method. The extract was able to reduce the stable free
radical DPPH to the yellow colored diphenylpicrylhydrazine
with an IC50 value of 61.88 μg/ml. The scavenging activity
was compared with ascorbic acid.30
The Ethanolic extract of leaves In DPPH and NO radical
scavenging methods for evaluation of its antioxidant
activity, IC50 was moderately was found satisfactory
(179.713µg/ml) compared with the reference ascorbic acid
(15.707µg/ml). In LPO (Lipid peroxidation) assay the Leaf
fraction extract showed moderate inhibition potential (IC50
402.835µg/ml) in comparison to standard drug BHT (IC50
32.94µg/ml).22 Active compounds (16) were isolated from
bark shown in table 3, were evaluated for antioxidant
(DPPH) activities, there compound 6 showed the most
potent antioxidant activity.33
In vivo analgesic activity
The analgesic activity of the methanolic extract of
Z. rugosa leaves was evaluated using acetic acid-induced
writhing method in rat. The extract significantly reduced the
number of writhing movements induced by intraperitoneal
administration of acetic acid solution. The dose-dependent
inhibition of abdominal constrictions by the methanol
extract indicates anti-nociceptive potential. The exerted
inhibition of writhing was close to the standard non-
narcotic analgesic drug, Indomethacin.30
Anti-inflammatory activity
The anti-inflammatory activity of aqueous and methanolic
extract of Z. rugosa on carrageenan-induced paw edema
was determined using Wistar rats. The aqueous and
Methanolic extracts of root and bark showed significant
anti-inflammatory effect in the acute phase of the
inflammation process.31
CNS Depressant Activity
Methanolic extract of Z. rugosa leaves exerted CNS
Depressant activity in Open field test and Hole cross test
using rats. In open field test the extract was evaluated for
decreasing capability of CNS-locomotor activity. The extract
significantly decreased the locomotor activity in a dose
dependent manner and this effect was evident from the
initial observation (0 min) period and continued up to 5th
observation period (120min). In Hole cross test the extract
showed a decrease in locomotionin the test animals. The
number of crossing hole from one chamber to another by
rat of the control group remained almost steady to slight
decrease from 0 minute to 120 minutes. The extract
displayed dose dependent activity and Depression
produced was found to be close to that of standard drug,
Diazepam.31
Anti-diabetic activity:
In vivo alloxan induced diabetic rat model and invitro alpha
amylase inhibition assay of Ziziphus rugosa Lam. bark was
selected for determination of its anti-diabetic potential.
Two doses of the petroleum ether extract and standard
drug Glibenclamide were administered to the diabetic rats.
Treated diabetic groups showed statistically significant
decrease in blood glucose level which indicates the
antidiabetic potential. There was significant decrease in α-
amylase, urea and creatinine levels which showed the
improvement in pancreas and kidney functions. It also
Int. J. Pharm. Sci. Rev. Res., 62(2), May - June 2020; Article No. 08, Pages: 40-44 ISSN 0976 044X
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International Journal of Pharmaceutical Sciences Review and Research
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43
showed increase in total protein level which maintains the
body weight.
In invitro method Alpha amylase inhibition assay was
performed to assess the antidiabetic property of Ziziphus
rugosa Lam. bark. It was also found that the IC50 value of
the benzene fraction was much closer to the IC50 value of
acarbose compared to the other fractions, which indicates
that the benzene fraction possesses good antidiabetic
property.32
The α-glucosidase inhibition of crude ethanol extract
obtained from the bark of Z. rugosa was assayed and
molecular docking studies has been carried out for its anti
diabetic activity. Betunilic acid showed the most powerful
yeast α-glucosidase inhibitory activity. The molecular
docking results highlighted the role of the carboxyl moiety
of 2 for yeast a-glucosidase inhibition through H-bonding,
and concluded that Lupeol and Betunilic acid emerged as
promising molecules for anti-diabetic therapy32.
CONCLUSION
Plants are natural sources of bioactive compounds to treat
various life-threatening diseases. The present review is the
first review work on Ziziphus rugosa plant to explain the
traditional uses, chemical constituents and reported
pharmacological activities of this plant.
The review shows the activity of various parts of the plant
and its pharmacognostic profile. Extracts and
Phytoconstituents isolated from this plant have shown to
produce different pharmacological response, which
includes antidiabetic, antioxidant, anti-inflammatory,
analgesic, cytotoxic, anti-cancer, CNS depressant,
antimicrobial, antiparasitic, dermatological and many other
effects.
The reported pharmacological activities show that Ziziphus
rugosa is a promising medicinal plant, could be utilized and
further studied for several medical applications because of
its effectiveness and safety. Considering all the above
medicinal importance of Ziziphus rugosa, it can be
concluded that further studies on this plant may helpful for
future researchers to explore more medicinal uses.
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Source of Support: Nil, Conflict of Interest: None.
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Eighteen species of Rhamnaceae were collected from different geographical regions of Pakistan to resolve its controversial phylogenetic position using morphological and molecular analysis. The phylogenetic tree based on 71 different micro and macro-morphological characters using Paleontological and statistical software (PAST) with Dice’s coefficient showed an overall genetic diversity of 32%. Further, in each species the atpβ gene promoter was amplified, purified, sequenced and the dendrogram was constructed using Molecular evolutionary genetic analysis (MEGA7) tool which divided the sequences into two main clades showing a narrow genetic diversity of 0.05% with well supported bootstrap’s values (95-100 %). Pairwise’s distance ranged from 0.12 to 0.73 with a mean value of 0.396. The phylogenetic study confirmed the work done by earlier phylogeneticist with additional reports of some new species, Berchemia pakistanica, Berchemia edgworthii, Berchemia floribunda, Helinus lanceolatus and Rhamnella gilgitica which are indigenous to Pakistan. The analysis of Cis-regulatory elements and its mapping via Plant cis-acting regulatory DNA element (PLACE) and Domain graph (DOG) revealed numerous elements including 50 common and 28 unique, showing variation in copy numbers and locations. It was observed that Berchemia pakistanica and Berchemia edgworthii have the unique features possessing diverse cis-regulatory elements with diverse functions.
Book
Continuing the high standards set by the widely acclaimed first and second volumes of Medicinal Plants of the World: Chemical Constituents, Traditional and Modern Medicinal Uses, Ivan A. Ross now comprehensively documents in Volume 3 the medicinal value of 16 major plant species widely used around the world in medical formulations. The plants for this volume are Camellia sinenis, Cannabis sativa, Cocos nucifera, Coffea arabica, Daucus carota, Ferula assafoetida, Hordeum vulgare, Larrea tridentata, Nicotiana tabacum, Olea europaea, Oryza sativa, Plantago ovata, Saccharum officinarum, Serenoa repens, Sesamum indicum, and Zingiber officinale. The author's exhaustive summary of available scientific data for each plant provides detailed information on how the plant is used in different countries, describing its traditional therapeutic applications and what is known from its use in clinical trials. Additional material presented includes a botanical description with a color photo of each plant for identification, the common names used for the plant throughout the world, and a listing of the plant's known chemical constituents. A comprehensive bibliography cites the literature available from a wide range of disciplines. Medicinal Plants of the World: Chemical Constituents, Traditional and Modern Medicinal Uses, Volume 3, offers a unique collection of vital scientific information for pharmacologists, herbal medicine practitioners, drug developers, phytochemists, medicinal chemists, phytologists, toxicologists, and researchers who want to explore the many uses of plant materials for medicinal and related purposes. Its wealth of significant information will reveal little-known facts about these plants and open new horizons of application for the many novel drugs and drug candidates found in them.
Article
The present investigation was designed to evaluate the analgesic and central nervous system (CNS) depressant activities of the methanolic extract of Ziziphus rugosa Lam. in rat model. The analgesic activity of the extract was examined using acetic acid-induced writhing test (chemically induced pain) at the doses of 200 and 300 mg/kg body weight. Further, the CNS depressant activity of the plant extract was evaluated by open field and hole cross tests at the doses of 300 and 500 mg/kg body weight. In the analgesic activity test, the methanolic extract of Z. rugosa showed significant (p < 0.01) antinociceptive activity in a dose dependent manner. The extract at the dose of 300 mg/kg exhibited 51.87% inhibition of writhing response which was comparable to the reference drug Indomethacin (55.20%). On the other hand, the plant extract also demonstrated significant (p < 0.01) dose-dependent reduction of locomotor and exploratory activities in the open field and hole cross tests. This analgesic and CNS-depressant activity of the extract might be due to the presence of biologically important chemical compounds.
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Now in its third edition, this classic reference is the one-stop-shop for information on the foundations of medicinal chemistry for pharmaceutical researchers who are involved in drug development & discovery but who do not have a background in medicinal chemistry. Wermuth aids pharmaceutical researchers and chemists in making faster, more accurate identifications of the active substances that could potentially treat the disorder they are researching. New chapters on Drug Absorption & Transport give pharmaceutical scientists information on how potential drugs can move through the drug discovery/development phases more quickly. This third edition still stands as the only source for practical aspects of medicinal chemistry by focusing on the daily problems met by the medicinal chemist in drug discovery. NEW TO THIS EDITION: * Focus on chemoinformatics and drug discovery * Enhanced pedagogical features * New chapters including: - Drug absorption and transport - Multi-target drugs * Updates on hot new areas: NEW! Drug discovery and the latest techniques NEW! How potential drugs can move through the drug discovery/ development phases more quickly NEW! Chemoinformatics.
Article
An attempt has been made to determine proximates, nutritive value, elemental composition and heavy metal content of the ripe, unripe pulp and seeds of Ziziphus rugosa Lamk. for two years (2009 and 2010). The edible parts of the pulp and seeds were separately analyzed with reference to their unripe and ripe conditions. The macronutrients studies of pulp reveal that nitrogen was the highest which was followed by potassium, calcium, sodium, magnesium and Phosphorus in case of unripe pulp, whereas in case of ripe pulp nitrogen was followed by potassium, magnesium, sodium, calcium and Phosphorus. Among the micronutrients iron was the dominant element which was followed by manganese, zinc and copper both in ripe and unripe pulp, respectively. The heavy metals, lead and cadmium were recorded only during 2009 and the lead was highest and values of cadmium were low not only in ripe pulp but also in unripe pulp. Among the components of nutritive value the moisture was the highest which is followed by carbohydrates, ash, fat, fibre and proteins, in case of unripe pulp, whereas in case of ripe pulp, the moisture was followed by carbohydrates, protein, fibre, fat and ash contents. In seeds, among the macronutrients nitrogen, was again the dominant and which was followed by potassium, magnesium, phosphorus and calcium in case of ripe seeds and nitrogen was followed by potassium, phosphorus, magnesium, sodium and calcium in unripe seeds, respectively. In case of micronutrients, iron was the dominant metals which was followed by manganese, zinc and copper both in unripe and ripe seeds. The lead was the dominant heavy metal not only in ripe seeds but also in unripe seeds. Among the proximates, the carbohydrates was the dominate proximate which was followed by moisture, fat, fibre, ash and protein in case of ripe seed and carbohydrates was followed by moisture, protein, ash, fat and fibre in case of unripe seeds. Between the pulp and the seeds, the seeds have more nutritive value than that of pulp and again the unripe seeds are more nutritious than the ripe seeds. The variation of macronutrients and proximates between unripe and the ripe components in pulp and seeds is statistically significant (P=0.00032 for pulp and P=0.00052 for seeds and P=0.000158 for pulp and P=0.0032 for seeds, respectively). At the same time variation of micronutrients between pulp and seeds is not significant (P=1.426 for pulp and 4.227 for seeds, respectively). The average values of proximate, nutritive values and elemental components of pulp of Z. rugosa are compared with Recommended Dietary Allowances (RDA) values and discussed. Further, the uses of pulp of fruits to establish cottage industries to improve economic and social condition of local people are appended.