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Review article https://doi.org/10.12980/jclm.4.2016J6-163 ©2016 by the Journal of Coastal Life Medicine. All rights reserved.
A review of therapeutic potential of Ajuga bracteosa: A critically endangered plant from Himalaya
Mubashir Hussain1*, Yamin Bibi1, Naveed Iqbal Raja1, Muhammad Iqbal1, Sumaira Aslam1, Nida Tahir1, Muhammad Imran1, Anam Iftikhar2
1Department of Botany, PMAS Arid Agriculture University, Rawalpindi, Pakistan
2Department of Fisheries and Aquaculture, University of Veterinary and Animal Sciences, Lahore, Pakistan
Journal of Coastal Life Medicine 2016; 4(11): 918-924
Journal of Coastal Life Medicine
*Corresponding author: Mubashir Hussain, Department of Botany, PMAS Arid
Agriculture University, Rawalpindi, Pakistan.
Tel: +923417871162
E-mail: mubashirhussain_22@hotmail.com
The journal implements double-blind peer review practiced by specially invited
international editorial board members.
1. Introduction
From the ancient times the people are relying on medicinal
plants for curing their ailments. History of medicinal plants is as
old as human history. From centuries the history of pharmacy and
pharmacognosy is interlinked. Herbal drugs are utilized worldwide
for treatment of wide range of diseases, so medicinal plants play
a crucial role in world health. Despite of great advancement in
modern medicines, people are still dependent on plants for health
care. It is approximated that directly or indirectly almost 25% of
entire modern medicines are derived from plants. Medicinal plants
show distribution worldwide but they are more abundant in tropics.
According to World Health Organization, 60%–80% population
of developing countries depends on plants for their primary health
care. From the last decades the use of medicinal plants become so
popular that many important plants are at risk of extinction due to
over exploitation.
Genus Ajuga of family Lamiaceae has numerous
pharmacologically vital groups of flowering plants. These species
are rich in the territory of Western Himalaya and upper Gangetic
plans[1,2]. Ajuga bracteosa (A. bracteosa) is an important
medicinal plant of Himalaya region. It has tremendous medicinal
potential because of the presence of active ingredients. As for
as conservation status is concerned, A. bracteosa is indexed
into critically endangered category[3]. There is possibility of
extinction of this highly medicinal plant. So there is need of
multidimensional approach to conserve this plant species through
better management practices like ex-situ conservation as well
as multiplication both through biotechnological as well as
conventional methods that could provide the possible solution to
the existing problem.
ARTICLE INFO ABSTRACT
Medicinal plants are the nature’s gift for the humanity to treat various ailments and to spend
a prosperous healthy life. There are almost 300 species of Ajuga. Among them, Ajuga
bracteosa Wall. ex Benth (A. bracteosa) is an important medicinal plant of Himalaya regions.
Its medicinal potential is due to the presence of various pharmacologically active compounds
such as neo-clerodane diterpenoids, flavonol glycosides, iridoid glycosides, ergosterol-5,8-
endoperoxide and phytoecdysones. The aim of this review article was to gather information
about A. bracteosa which is currently scattered in form of various publications. This review
article tried to attract the attention from people for therapeutic potential of A. bracteosa.
The present review comprises upto date information of botanical aspects, active ingredients,
traditional uses, and pharmacological activities such as antitumor, antimicrobial, antimalarial,
anti-inflammatory, cardiotonic activity, antiarthritic activity, antioxidant activity and in vitro
production of secondary metabolites for pharmaceuticals. Due to remarkable medicinal
potential and commercialization, this species is indexed into critically endangered category
and it is facing extremely high risk of extinction. Conservation practices and management
techniques should be carried out to protect this important species from extinction. Recent
biotechnological approaches will be quite helpful for its conservation.
Article history:
Received 26 Aug 2016
Received in revised form 8 Sep 2016
Accepted 14 Sep 2016
Available online
Keywords:
Ajuga bracteosa
Critically endangered
Pharmacology
Antitumor
Himalaya
journal homepage: www.jclmm.com
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924 919
2. Geographic distribution
A. bracteosa is commonly known as kauri booti and it belongs
to family Lamiaceae[4]. It is a perennial herb growing wild in
the Punjab plains, upper Gangetic plains and from Kashmir to
Nepal in Western Himalaya[2]. A. bracteosa is a prised medicinal,
aromatic, villous, soft and decumbent herb which is about 10–30
cm in height[5]. It is established on grassland, exposed slopes and
open field in temperate and subtropical region of the world[6] at an
elevation of 1 300 to 2 400 m[7].
3. Taxonomic hierarchy and vernacular names
A. bracteosa belongs to kingdom plantae, division Tracheophyta,
class Magnoliopsida, order Lamiales and family Lamiaceae.
A. bracteosa is known from different vernacular names. It is
commonly called “Bungle” in English, “Nilkanthi” in Sanskrit
and “Jan-i-adam” in Kashmiri. It is well distributed in the northern
areas of Pakistan, where it is called as kauri booti due to its vicious
taste[8].
4. Morphological description
It is a perennial prolixly branched evergreen herb (Figure 1)
that remains flattened to the pulverised. Its yellowish flowers are
congested in axillary spirals. A. bracteosa has usually woodier
rootstock, leaves often larger up to 9.0 cm × 3.5 cm but usually
much less with a more crenate to lobed margin, calyces 3.0–4.5
mm, corollas 10 mm, stamens usually exserted, and nutlets clearly
longer and broader (eflora of Pakistan).
Figure 1. A. bracteosa.
5. Active ingredients
Phytochemically, A. bracteosa contains various compounds
such as neo-clerodane diterpenoids, flavonol glycosides, iridoid
glycosides, ergosterol-5,8-endoperoxide and phytoecdysones[2,9-
11]. These chemical compounds were either synthesized or
isolated from the plant. Cytotoxicity level was evaluated using
skin carcinoma cell line and it was found that ergosterol-5,8-
endoperoxide and neo-clerodane diterpenoids were not cytotoxic at
higher concentration used for antiplasmodial activity.
6. Biological properties
A. bracteosa is utilized in medicine since ancient times and
has various applications. In ethno medicine its use is reported
as anthelmintic, astringent, antibacterial, antifungal, anti-
inflammatory, hypoglycemic and it also remediates intestinal
ailments[2]. This plant is traditionally used to treat phlegm
and fever in China[12]. It is recommended in Ayurveda to treat
rheumatism, amenorrhea, gout and palsy[13]. A. bracteosa contains
diverse important compounds such as neo-clerodane diterpenoids,
withanolides, iridoid glycosides and phytoecdysteroids[2]. Previous
investigations of A. bracteosa have reported the inhibition of
lipoxygenase, acetylcholinesterase and butyrylcholinesterase[11,14],
cancer chemopreventive[15] and antispasmodic actions[7]. It is
known that most of the plant derived compounds have substantial
analgesic properties. Based on this, compounds which are derived
from medicinal plants have very little side effects[16].
7. Pharmacology
7.1. Antitumor activity
Cancer is still one of the most devastating disease throughout
the world including Pakistan. The risk prevalence and differences
in the comparative risk were explained by various factors, mainly
dietary factors[17]. Hartwell[18] listed more than 3 000 plant species
that have reportedly been used in the treatment of cancer, but in
many instances, the “cancer” is undefined, or reference is made to
conditions such as hard swellings, abscesses, calluses, corns, warts,
polyps, or tumors, to name a few. Plants have served as important
sources of effective anticancer agents and over 60% currently used
anticancer agents were isolated from natural sources, including
plants, marine organisms and microorganisms are related to
them[19,20]. Mothan et al.[21] reported in vitro anti-proliferative
activities (IC50 values in mg/mL ± SEM) of the crude methanolic
extracts tested against three human cancer cell lines by using
methanolic extract of A. bracteosa. The phytochemicals which are
screened include essential oil, terpenoids, flavonoids, and iridoid.
7.2. Antimicrobial activity
During early and in established contagion, ethanolic extract
of leaves of A. bracteosa (250, 500 and 750 mg/kg per day)
established a dose-dependent chemosuppression along with
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924
920
significant (P < 0.05) repository activity. Among various
concentrations, concentration of 750 mg/kg per day showed
maximum 68.8% chemosuppression in respiratory tract and 77.7%
chemosuppression during early contagion were found. ED50 of
ELEAB was 300 mg/kg body weight of mice[22].
The elevated problematic issue in recent years is the Plasmodium
resistance to the traditional antimalarial drugs pressures the
necessity to look for novel and newer antiplasmodial constituents
with new mode of action and efficacy. The medicinally important
A. bracteosa has been curtained for its antiplasmodial effectiveness
and it was found that the extract possess significant in vitro
antiplasmodial efficacy with an IC50 of 10.0 μg/mL[23].
7.3. Antimalarial activity
Malaria is another most devastating disease and various plants
are currently being employed to treat and control of malaria have
become tougher due to spread of insecticides resistant mosquito
vectors and drug resistant parasites. In an attempt to find advance
antimalarial drugs, various resources such as ethnopharmacological
should attain more attention. More extensively studies are required
for the safety issues of traditional herbal medicines along with their
potential role of active ingredients are vital steps for accessible
and properly standardize herbal medicines. Phytochemical
characterization assist as base for the development of new
compounds. Various phytochemicals were tested and it was found
that they have the therapeutic potential for malaria[22].
7.4. Anti-inflammatory activity
Seventy percent ethanolic extract of A. bracteosa possesses
promising and significant anti-inflammatory activity. The
mechanism of anti-inflammatory is supposed to be facilitated
through the inhibition of COX-1 and COX-2. The study also
indicates that isolated active ingredients (lupulin A, ajugarin I,
deoxyharpagide withaferin A and reptoside) could be accountable
for COX inhibitory and anti-inflammatory activity. The study
confirms traditional use of A. bracteosa for the treatment of
rheumatism and some other inflammatory disorders[24].
7.5. Cardiotonic activity
An alkaloidal fraction from A. bracteosa showed the cardiostimulant
action on frog heart and rat ventricle. The activity was antagonized by
dichloroisoprenaline, did not occur in hearts from reserpine-treated
animals, and may result from liberation of catecholamine stores in
the heart[25].
7.6. Antiarthritic activity
The substantial and promising antiarthritic activity of ELEAB is
possibly facilitated through the inhibition of COX-1 and COX-2.
The isolated active ingredients i.e. 6-deoxyharpagide, withaferin
A, lupulin A, reptoside and ajugarin I, could be responsible for
inducing the antiarthritic activity. The current opinion is the first
trial providing the scientific evidence to support and rationalize
traditional use of A. bracteosa for the treatment of rheumatism[13].
7.7. Antioxidant activity
Reactive oxygen species eagerly assault and persuade oxidative
damage to various biomolecules such as DNA, proteins, lipids
and lipoprotein. This damage is considered to be vital factor in
different chronic diseases of human such as diabetes mellitus,
cerebrovascular diseases, rheumatism, cancer and cardiovascular
diseases[26]. The existing therapeutic approaches often have
severe side effects such as strong host immune response and
cytotoxicity to normal cells. Therefore, there is requirement
of useful antioxidants to protect against chronic diseases.
Antioxidants are considered as chemical substances that lessen
and prevent oxidation. Antioxidants have the ability to protect
from the damaging effects of radicals in tissue. They are supposed
to counteract against heart disease, tumor, arteriosclerosis,
cerebrovascular diseases and various other diseases[27]. Various
antioxidant compounds have been found in different medicinal
species, which are well known for their free radical scavenging
assay.
Phenolic compounds may have direct contribution in the
antioxidant activity. A strong relationship exists between
antioxidant activities and phenolic compounds which have been
produced in various plants in vitro[28]. The presence of phenolic
compounds in various medicinal plants has been known to possess
antioxidant potential.
The antioxidant activity of essential oil, plant extract or isolated
compounds has grown due to the circumstance that antioxidants
can scavenge the reactive oxygen species and hence may be
beneficial in the prophylaxis and treatment of various diseases such
as Alzheimer’s disease, stroke diabetes, cancer, inflammation and
arteriosclerosis[29-33]. The potential antioxidant activity of the oils
was determined on the basis of scavenging activity of the stable
free radical 2,2-Diphenyl-1-picrylhydrazl. Antioxidant activity
was reported only from the oil of A. bracteosa and it showed 78%
radical scavenging activity which is more as compared to high
antioxidant activity of ascorbic acid[21]. This elevated antioxidant
activity could be linked with high amount of oxygenated
monoterpenes in the A. bracteosa essential oil[32].
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924 921
7.8. In vitro production of secondary metabolites for
pharmaceutical
Plant secondary metabolites are recognized as unique sources
for pharmaceuticals, flavors, food additives and other industrial
materials either as a raw material or as a part of final product.
Among various classes of secondary metabolites, polyphenols
comprise the major group of innate antioxidants[34]. Flavonoids
and phenolics possess biological properties like anti-carcinogen,
anti-aging, antioxidant and protection from brain dysfunctions,
viz. Huntington’s diseases, Parkinson’s, Alzheimer’s immune/
autoimmune and cardiovascular diseases[35].
Secondary metabolites from plants have important biological
and pharmacological activities, such as anti-oxidative and anti-
carcinogenic. The biological activities of phenolic compounds and
flavonoids are associated to their antioxidant potential.
Callus culture and cell suspension cultures are the effective
ways for the production of secondary metabolites which have
various therapeutic potential. To study the production and growth
kinetics, cell suspension cultures are proposed to be simple system
to implement and evaluate the most favorable scheme for the
production of medicinal compounds in good quantities[36]. Light
regimes play a significant role in all the fundamental process of
plant and fundamental building blocks like primary and secondary
metabolism, growth and development[37]. By optimizing in vitro
conditions like light regime, production of secondary metabolites
can be proficiently stimulated. Various stimulatory effects of light
regime have been observed for the accumulation of secondary
metabolites such as artemisinin, anthocyanins, derivatives
and flavonoids[38]. Light is very crucial as the inhibitory and
stimulatory effects for the production of secondary metabolites.
The antioxidant and antimicrobial activities and contents of total
phenolics and flavonoids of Ajuga chamaepitys (L.) Schreb. subsp.
chamaepitys (Lamiaceae) were investigated. The total phenolic
content was determined spectrophotometrically using the Folin-
Ciocalteu reagent and expressed as the gallic acid equivalent (GAE)
(mg GAE/g of extract). The highest value was obtained in the ethyl
acetate extract (57.02 mg GAE/g)[39].
8. Traditional uses
A. bracteosa is highly medicinal plant and it is the most valuable
species among all the species of genus Ajuga. A. bracteosa is
traditionally used to treat fever and phlegm in China[12]. It is
recommended in Ayurveda to treat gout, palsy, amenorrhea and
rheumatism[13]. Leaves of A. bracteosa are stimulant, diuretic and
locally used to treat malaria[40,41]. A. bracteosa is regarded an
alternative to cinchona[42] (Table 1).
Table 1
Traditional methods of applications of A. bracteosa.
Conditions Methods of applications
Headache Paste of the leaves is applied to cure headache[43]
Abdominal pain Powder of the whole plant is given to treat abdominal pain[43]
Indigestion Powder of whole plant is also used to treat indigestion[43]
Astringent Whole plant is used as astringent[3]
Tonic Whole plant is also used as tonic[3]
Internal colic Whole plant is used to treat internal colic[44]
Pimples Barks juice is used to treat pimples[44]
Jaundice Leaves extracts are used to treat jaundice[45]
Hypertension Whole plant is used to treat hypertension[45]
Sore throat Whole plant is used to sore throat[45]
Cold Decoction of root is taken[44]
Leprosy Root powder is ingested[44]
Blood purification Leaves extract is used for blood purification[46]
Diabetes Decoction of leaves is used to treat the diabetes
Fever Decoction of leaves is used to treat the fever
Swollen wounds Plant extract is used is used to cure swollen wounds[47]
Bites of insects Plant extract is used is used to cure bites of insects[47]
Eye trouble Plant extract is used is used to cure eye trouble[47]
Bladder disease Plant extract is used is used to treat bladder disease[47]
9. Conservation status
Conservation status, viz., critically endangered, endangered,
vulnerable and least concern are recorded on the basis of density
in accordance with International Union for Conservation of Nature
Red List Database. Alam and Ali[48] revealed several threats
to Pakistan’s biodiversity including habitat loss, deforestation,
grazing, invasive species, illegal trade, industrial pollution, growing
demand for natural resources and the lack of adequate training.
Medicinally important species like A. bracteosa is critically
endangered not only locally, but also in the whole region[49].
Looking at the broad spectrum of A. bracteosa for various purposes
particularly in pharmacology, it is useful to cultivate this plant
at large scale. A. bracteosa is indexed in critically endangered
category, so consistent efforts should be made to protect this plant
species to become extinct. A multidimensional approach is required
to maintain and includes selection of better quality genotype and
ex-situ as well in-situ conservation followed by multiplication both
by conventional as well as biotechnological methods that could
provide solution to the existing problem.
10. Threats towards its extinction
Wild plants have been collected from decades[50]. For many
years, ex-situ management has been ignored of wild plants. The
time of collection and lack of awareness about its part used lead to
be the mismanagement of the species. Currently various obstacles
exist for gathering, sustainable cultivation and use of medicinal
plants. These include lack of clear resource and custodianship,
little understanding of sustainable management parameter and
knowledge of market requirement[51]. Tali et al.[52] assessed the
threatened status of A. bracteosa in accordance with International
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924
922
Union For Conservation Of Nature guideline. The population size,
area of occupancy, extent of occurrence and various other threats of
this species were recorded. The most common operative threats are
landslides and overexploitation for the local use.
11. Biotechnological methods
Tissue culture is a method of growing and multiplication of plant
cells, tissues, organs, seeds or other plant parts in a sterile environment
on a defined solid or liquid nutrient medium[53,54]. Plant tissue culture is
a form of vegetative propagation used for the large-scale production of
plants known as micropropagation[53]. Plant tissue culture technology
offers the possible for proficiently propagating genetically uniform,
disease-free and enormous amounts of plants since its notion[55]. The
formation of synthetic seeds through somatic embryogenesis is an
emerging trend to conserve the medicinally important plants and some
other plants whose seeds are not viable like Citrus reticulata L.[56].
The role of tissue culture in genetic engineering and biotechnology
was first time exemplified by Kanta and Maheshwari in 1962. Plant
tissue culture has become an important tool in the study of basic areas
of plant biology and biochemistry[54]. Biotechnological advancement
not only provides alternative methods for in vitro preservation of
tropical fruits and recalcitrant seeds but also provides tools for disease
free germplasm conservation, lower labor cost and limiting disease-
transfer[57,58].
Jan et al.[8] reported callus induction from various explants of A.
bracteosa viz., leaf, petiole and leaf nodes. Maximum callus induction
response was obtained when Murashige and Skoog medium was
supplemented with 6-Benzyl amino purine after 19 days of inoculation.
Callus derived from leaf explants showed maximum response for
regeneration. Maximum multiple shoot regenerated on Murashige and
Skoog medium when supplemented with 5 mg/L BAP after 28 days
of inoculation. The results of Jan et al.[8] are in contrast with Srivastav
et al.[59] who reported maximum callus induction when Murashige
and Skoog medium was supplemented with combination of BAP and
Indole-3-acetic acid after 10 days of inoculation. Another technique
of conservation is cyto-storage or normal storage of important plant
species under in vitro condition to preserve germplasm. Another
common technique of in vitro storage is utilization of alginate
encapsulation of explants to produce synthetic seeds[60].
12. Challenges in conservation, sustainable use and way
to forward
A. bracteosa was considered as highly medicinal plant. Due to high
demand, most of natural population of A. bracteosa is under severe
pressure at the present scenario. Due to excessive exploiting of this
species, it is declining day by day. Due to the various known uses
of this herb, there is a high demand at local and international level
pharmaceutical industry. During the last decade, this species has
attained a considerable attention because it is critically endangered and
will be extinct in upcoming years if exploited at the same rate. So there
is need of sustainable use of this highly medicinal species.
A multidimensional approach is required to maintain and includes
selection of better quality genotype and ex-situ as well in-situ
conservation followed by multiplication both by conventional as
well as biotechnological methods that could provide solution to the
existing problem. The importance of any medicinal plant depends
on its active ingredients which is present in that species. It would be
desirable to carry out cultivation of elite clones. The superior clones
can be approved by the use of various molecular markers techniques
and chemo-profiling. The conventional methods of propagation as well
as plant tissue culture techniques can be used to multiply and raising
the commercial plantation for conservation. Tissue culture can be
employed as substitute to conservative methods in vitro propagation
with the purpose of increasing the developmental rate of preferred
genotypes and commercial micropropagation[61]. Gene transfer,
selection and regeneration of transformants is now a day’s employed by
the plant tissue culture techniques[62]. This technique is helpful in the
production of millions of healthy, vigorous and disease free plants in
less time, space, labor and with less cost. Besides in vitro propagation,
cell suspension culture is useful for the large scale production of
secondary metabolites.
Post-harvest handling is another factor upon which the quality of
plants is dependent. The collectors of herbal material pay less attention
to quality of material during harvesting, handling and storage. It
has been found that herbal drugs samples which are stored harbor
mycotoxin producing fungi. Cultivation practices also need to be
addressed. Due to genetic and environmental differences wild harvested
plants vary in consistency and quality. Regional environmental
conditions also influence the efficacy of medicinal plants. Some of
the factors such as temperature, photoperiod, soil characteristics and
rain fall have severe effects on the production of active constituents.
Therefore, consistent efforts should be taken for the sustainable
management of medicinal plants such as A. bracteosa at community
level.
13. Conclusion
A. bracteosa is highly medicinal plant of Himalaya region but it is
indexed in the critically endangered category. This plant has immense
potential because of its efficacy towards various diseases. Some
progress has been made, but still consistent efforts are required to
explore the individual compounds isolated from A. bracteosa to validate
and understand its traditional uses and clinical practices. It is also
important plant species with respect to its ethnomedicinal importance,
so this importance exert significant pressure on plant regarding its
use. This pressure posed serious threat towards its extinction. So there
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924 923
is urgent need to conserve this species and sustainable harvesting is
usually required. A multidimensional approach is usually required
to maintain and includes selection of better quality genotype and ex-
situ as well in-situ conservation followed by multiplication both by
conventional as well as biotechnological methods that could provide
possible solution to the existing problem.
Conflict of interest statement
We declare that we have no conflict of interest.
References
[1] Singh N, Mahmood U, Kaul VK, Jirovetz L. A new phthalic acid ester from
Ajuga bracteosa. Nat Prod Res 2006; 20(6): 593-7.
[2] Israili ZH, Lyoussi B. Ethanopharmacology of plants of genus Ajuga. Pak J
Pharm Sci 2009; 22: 425-62.
[3] Ahmad KS, Kayani WK, Hameed M, Ahmad F, Nawaz T. Floristic
diversity and ethnobotany of senhsa, district Kotli, Azad Jammu & Kashmir
(Pakistan). Pak J Bot 2012; 44: 195-201.
[4] Qureshi RA, Ghufran MA, Gilani SA, Yousaf Z, Abbas G, Batool A.
Indigenous medicinal plants used by local women in southern Himalayan
regions of Pakistan. Pak J Bot 2009; 41: 19-25.
[5] Hedge I, Nasir Y, Ali S. Flora of Pakistan, Karachi: University of Karachi,
Department of Botany; 1990, p. 192. [Online] Available from: http://www.
efloras.org/florataxon.aspx?flora_id=5&taxon_id=200019466 [Accessed
on 21st August, 2016]
[6] Gupta AK, Tandon N. Reviews on the Indian medicinal plants. New Delhi:
Indian council of medicinal research; 2004.
[7] Chandel S, Bagai U. Antiplasmodial activity of Ajuga bracteosa against
Plasmodium berghei infected BALB/c mice. Indian J Med Res 2010; 131:
440-4.
[8] Jan M, Singh S, Kaloo ZA, Maqbool F. Medicinal importance of Ajuga
bracteosa Wall ex Benth. -a review. Int J Adv Res 2014; 2(1): 389-94.
[9] Kayani WK, Rani R, Ihsan-ul-Haq, Mirza B. Seasonal and geographical
impact on the morphology and 20-hydroxyecdysone content in different tissue
types of wild Ajuga bracteosa Wall. ex Benth. Steriods 2014; 87: 12-20.
[10] Rahman K, Nisar M, Jan AU, Suliman M, Iqbal A, Ahmad A, Ghaffar R.
Antibacterial activity of important medicinal plants on human pathogenic
bacteria. Int J Agronmy Agric Res 2015; 6(6): 106-11.
[11] Castro A, Coll J, Arfan M. neo-Clerodane diterpenoids from Ajuga
bracteosa. J Nat Prod 2011; 74(5): 1036-41.
[12] Shen XY, Isogai A, Furihata K, Sun HG, Suzuki A. Two neo-clerodane
diterpenoids from Ajuga macrosperma. Phytochemistry 1993; 33: 887-9.
[13] Kaithwas G, Gautam R, Jachak SM, Saklani A. Antiarthritic effects of
Ajuga bracteosa Wall ex Benth. in acute and chronic models of arthritis in
albino rats. Asian Pac J Trop Biomed 2012; 2(3): 185-8.
[14] Riaz N, Malik A, Aziz-ur-Rehman, Nawaz SA, Muhammad P, Choudhary
MI. Cholinesterase-inhibiting withanolides from Ajuga bracteosa. Chem
Biodivers 2004; 1: 1289-95.
[15] Ghufran MA, Qureshi RA, Batool A, Kondratyuk TP, Guilford JM, Marler
IE, et al. Evaluation of selected indigenous medicinal plants from the
western Himalayas for cytotoxicity and as potential cancer chemopreventive
agents. Pharmaceut Biol 2009; 47: 533-8.
[16] Verpoorte R. Exploration of nature’s chemodiversity: the role of secondary
metabolites as leads in drug development. Drug Discovery Today 1999; 3:
232-8.
[17] Pal A, Toppo FA, Chaurasiya PK, Singour PK, Pawar RS. In-vitro
cytotoxicity study of methanolic fraction from Ajuga Bracteosa wall ex.
benth on MCF-7 breast adenocarcinoma and hep-2 larynx carcinoma cell
lines. Pharamcognosy Res 2014; 6(1): 87-91.
[18] Hartwell JL. Plants used against cancer. A survey. Lawrence: Quarterman
Publications; 1982.
[19] Cragg GM, Kingston DGI, Newman DJ. Anticancer agents from natural
products. Boca Raton: CRC Press; 2005.
[20] Newman DJ, Cragg GM, Snader KM. Natural products as sources of new
drugs over the period 1981-2002. J Nat Prod 2003; 66: 1022-37.
[21] Mothan RA, Gruenert R, Bednarski PJ, Lindequist U. Evaluation of the in
vitro anticancer, antimicrobial and antioxidant activities of some Yemeni
plants used in folk medicine. Pharmazie 2009; 64: 260-8.
[22] Chandel S, Bagai U. Antiplasmodial activity of Ajuga bracteosa against
Plasmodium berghei infected BALB/c mice. Indian J Med Res 2010; 131:
440-4.
[23] Chandel S, Bagai U. Screening of antiplasmodial efficacy of Ajuga
bracteosa Wall ex. Benth. Parasitol Res 2011; 108: 801-5.
[24] Gautam R, Jachak SM, Saklani A. Anti-inflammatory effect of Ajuga
bracteosa Wall Ex Benth. mediated through cyclooxygenase (COX)
inhibition. J Ethnopharmacol 2011; 133: 928-30.
[25] Patel DG, Gulati OD, Gokhale SD. Positive inotropic action of an alkaloidal
fraction from Ajuga bracteosa Well ex Benth. Indian J Physiol Pharmacol
1962; 6: 224-30.
[26] Yang QM, Pan XH, Kong WB, Yang H, Su Y, Zhang L, et al. Antioxidant
activities of malt extract from barley (Hordeum vulgare L.) toward various
oxidative stress in vitro and in vivo. Food Chem 2010; 118: 84-9.
[27] Verma AR, Vijayakumar M, Rao CV, Mathela CS. In vitro and in vivo
antioxidant properties and DNA damage protective activity of green fruit of
Ficus glomerata. Food Chem Toxicol 2010; 48: 704-9.
[28] Al Khateeb W, Hussein E, Qouta L, Alu’datt M, Al-Shara B, Abu-zaiton
A. In vitro propagation and characterization of phenolic content along with
antioxidant and antimicrobial activities of Cichorium pumilum Jacq. Plant
Cell Tissue Org Culture 2012; 110: 103-10.
[29] da Silva NA, da Silva JK, Andrade EH, Carreira LM, Sousa PJ, Maia
JG. Essential oil composition and antioxidant capacity of Lippia
schomburgkiana. Nat Prod Commun 2009; 4: 1281-6.
[30] Kumar G, Kanaujia N, Bafana A. Functional and phylogenetic diversity of
root-associated bacteria of Ajuga bracteosa in Kangra valley. Microbiol Res
2012; 167(4): 220-5.
[31] Lee SE, Hwang HJ, Ha JS, Jeong HS, Kim JH. Screening of medicinal
Mubashir Hussain et al./Journal of Coastal Life Medicine 2016; 4(11): 918-924
924
plant extracts for antioxidant activity. Life Sci 2003; 73: 167-79.
[32] Rehman NU, Begum N, Ali L, Al-Hassari, Abbas G, Ahmad S, et al.
Lipid peroxidation, antiglycation, cytotoxic, phytotoxic, antioxidant,
antiplatelet and antimicrobial activities of Ajuga bracteosa against
various pathogens. Pak J Bot 2015; 47(3): 1195-7.
[33] Ganaie HA, Ali MN, Ganai BA, Kaur J, Ahmad M. GC-MS analysis
and evaluation of mutagenic and antimutagenic activity of ethyl acetate
extract of Ajuga bracteosa Wall ex. Benth: an endemic medicinal plant
of Kashmir Himalaya, India. J Clin Toxicol 2016; 6(2): 1-9.
[34] Cieśla L, Kowalska I, Oleszek W, Stochmal A. Free radical scavenging
activities of polyphenolic compounds isolated from Medicago sativa and
Medicago truncatula assessed by means of thin-layer chromatography
DPPH˙ rapid test. Phytochem Anal 2013; 24(1): 47-52.
[35] Zaka M, Abbasi BH, Rahman LU, Shah A, Zia M. Synthesis and
characterisation of metal nanoparticles and their effects on seed
germination and seedling growth in commercially important Eruca
sativa. IET Nanobiotechnol 2016; 10(3): 134-40.
[36] Fang HY, Zhu H, Ding HM, Han HR, Liu XL, Hao LJ, Li MH.
[Research progress on effect factors of secondary metabolites content in
callus]. Zhongguo Zhong Yao Za Zhi 2014; 39(15): 2846-50. Chinese.
[37] Srivastava P, Sisodia V, Chaturvedi R. Effect of culture conditions on
synthesis of triterpenoids in suspension cultures of Lantana camara L.
Bioprocess Biosyst Eng 2011; 34: 75-80.
[38] Khan T, Abbasi BH, Khan MA, Shinwari ZK. Differential effects of
thidiazuron on production of anticancer phenolic compounds in callus
cultures of Fagonia indica. Appl Biochem Biotechnol 2016; 179(1): 46-58.
[39] JakovljevićDZ, VasićSM, StankovićMS, ČomićLR, Topuzovi MD.
Secondary metabolite content and in vitro biological effects of Ajuga
chamaepitys (L.) schreb. subsp. Chamaepitys. Arch Biol Sci 2015; 67(4):
1195-202.
[40] Al-Musayeib NM, Mothana RA, Matheeussen A, Cos P, Maes I. In
vitro antiplasmodial, antileishmanial and antitrypanosomal activities
of selected medicinal plants used in the traditional Arabian Peninsular
region. BMC Complement Altern Med 2012; 12: 49.
[41] Pavela R. Larvicidal effects of various Euro-Asiatic plants against Culex
quinquefasciatus Say larvae (Diptera: Culicidae). Parasit Res 2008; 102:
555-9.
[42] Pal A, Pawar RS. A study on Ajuga bracteosa Wall ex. Benth for
analgesic activity. Int J Curr Biol Med Sci 2011; 1: 12-4.
[43] Ahmad KS, Habib S. Indigenous knowledge of some medicinal plants of
Himalaya Region, Dawarian Village, Neelum Valley, Azad Jammu and
Kashmir, Pakistan. Univ J Plant Sci 2014; 2(2): 40-7.
[44] Hamayun M, Khan SA, Sohn EY, Lee IJ. Folk medicinal knowledge and
conservation status of some economically valued medicinal plants of
District Swat, Pakistan. Lyonia 2006; 11(2): 101-13.
[45] Sher H, Khan ZD. Resource utilization for economic development and
folk medicine among the tribal people. Observation from the northern
part of the Pakistan. Pak J Plant Sci 2006; 12(2): 149-62.
[46] Ahmad I, Ahmad MSA, Hussain M, Hameed M, Ashraf MY, Koukab S.
Spatio-temporal effects on species classification of medicinal plants in
Soone valley of Pakistan. Int J Agric Biol 2009; 11(1): 64-8.
[47] Sher H, Al-yemeni M. Economically and ecologically important plant
communities in high altitude coniferous forest of Malam Jabba, Swat,
Pakistan. Saudi J Biol Sci 2011; 18(1): 53-61.
[48] Alam J, Ali SI. Conservation Status of Astragalus gilgitensis Ali
(Fabaceae): a critically endangered species in the Gilgit District,
Pakistan. Phyton 2009; 48: 211-23.
[49] Ahmad KS, Qureshi R, Hameed M, Ahmad F, Nawa T. Conservation
assessment and medicinal importance of some plants resources from
Sharda, Neelum Valley, Azad Jammu and Kashmir, Pakistan. Int J Agric
Biol 2012; 6: 997-1000.
[50] Khan M. Report of participatory rural appraisal on agriculture at Bayun,
Kalam, Swat. A joint Pak/Swiss-Govt: venture. 1985, p. 11-20
[51] Chen SL, Yu H, Luo HM, Wu Q, Li CF, Steinmetz A. Conservation and
sustainable use of medicinal plants: problems, progress, and prospects.
Chin Med 2016; 11: 37.
[52] Tali BA, Ganie AH, Nawchoo IA. Conservation status of Ajuga
bracteosa Wall ex Benth: an important medicinal plant species of
Kashmir Himalaya. Int J Ecol Ecosolution 2016; 3(1): 1-6.
[53] Ahloowalia BS, Maluszynsk M, Nichterlein K. Global impact of
mutation-derived varities. Euphytica 2004; 135: 187-240.
[54] Shaban NZ, Hegazy WA, Abdel-Rahman SM, Awed OM, Khalil SA.
Potential effect of Olea europea leaves, Sonchus oleraceus leaves and
Mangifera indica peel extracts on aromatase activity in human placental
microsomes and CYP19A1 expression in MCF-7 cell line: comparative
study. Cell Mol Biol (Noisy-le-grand) 2016; 62(9): 11-9.
[55] Honda H, Liu C, Kobayashi T. Large-scale plant micropropagation. Adv
Biochem Eng Biotechnol 2001; 72: 157-82.
[56] Hussain M, Raja NI, Iqbal M, Iftikhar A, Sadaf HM, Sabir S, et al.
Plantlets regeneration via somatic embryogenesis from the nucellus
tissues of Kinnow Mandarin (Citrus reticulata L.). Am J Plant Sci 2016;
7(6): 798-805.
[57] Kaul S, Das S, Srivastava PS. Micropropagation of Ajuga bracteosa, a
medicinal herb. Physiol Mol Biol Plant 2013; 19(2): 289-96.
[58] Alves SAO, Lemos OFD, Santos Filho BG, Silva ALLD. In vitro
embryo rescue of interspecific hybrids of oil palm (Elaeis oleifera x
Elaeis guineensis). J Biotechnol Biodivers 2011; 2: 1-6.
[59] Kaul S, Das S, Srivastava PS. Micropropagation of Ajuga bracteosa, a
medicinal herb. Physiol Mol Biol Plants 2013; 19: 289-96.
[60] Mishra J, Singh M, Palni LMS, Nandi SK. Assessment of genetic
fidelity of encapsulated microshoots of Picrorhiza kurrooa. Plant Cell
Tissue Org Culture 2011; 104: 181-6.
[61] Helal NAS. The green revolution via synthetic (artificial) seeds: a
review. Res J Agric Biol Sci 2011; 7(6): 464-77.
[62] Hsie BS, Brito JZ, Vila Nova MX, Borges-Paluch LR, Silva MV, Donato
VMST. Determining the genetic stability of micropropagated sugarcane
using inter-simple sequence repeat markers. Genet Mol Res 2015; 14(4):
17651-9.
