World Journal of Pharmaceutical research

Baby Joseph et al.

World Journal of Pharmaceutical Research

Volume 2, Issue 3, 596-605.

Research Article

ISSN 2277 7105

CISSUS QUADRANGULARIS IN THE TREATMENT OF

OSTEOPOROSIS
Baby Joseph*, Jency George and Jeevitha Mohan
Interdisciplinary Research Centre, Department of Biotechnology, Malankara Catholic
College, Mariagiri, Kaliakkavilai,Tamil Nadu, India.
Article Received on
11 March 2013,
Revised on 10 April 2013,
Accepted on 28 April 2013

ABSTRACT
Cissus quadrangularis belongs to the taxonomic group Magnoliopsida
and family Vitaceae. Cissus quadrangularis is an ancient medicinal
plant native to the hotter parts of Ceylon and India. It has been used by
common folk in India for promoting the fracture healing process. It

*Correspondence for
Author:
Dr. Fr. Baby Joseph

was prescribed in the ancient Ayurvedic texts as a general tonic and

analgesic, with specific bone fracture healing properties. This review

Interdisciplinary Research

gives a brief idea about its botanical description, phytochemistry,

Centre, Department of

Osteoblastogenesis activity and its molecular healing mechanisms in

Biotechnology, Malankara

osteoporosis.

Catholic College, Mariagiri,

Keywords:

Antiosteoporosis

activity,

Osteoblastogenesis,

Kaliakkavilai,Tamil Nadu,

Phytochemistry, Cissus quadrangularis

India
petercmiscientist@yahoo.c
o.in

1. INTRODUCTION
Medicinal plants have been used as traditional treatments for numerous

human diseases for thousands of years and in many parts of the world. More than 30% of the
entire plant species, at one time or other was used for medicinal purposes. The herbal
products today symbolise safety in contrast to the synthetics that are regarded as unsafe to
human and environment. Medical plants play an important role in the management of
diseases in developing countries where resources are meager. Herbal medicine is based on the
premise that plants contain natural substances that can promote health and alleviate illness [1,
2]

. The most important of these biologically active constituents of plants are alkaloids,

flavonoids, tannins and phenolic compounds.

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The Cissus quadrangularis, invites attention of the researchers worldwide for its
pharmacological activities such as analgesic
radical scavenging activity

[5]

[3]

, anti-inflammatory

[4]

, antioxidant and free

, anti-osteoporosis activity and bone healing activity

[6]

. The

purpose of this article is to review the botanical description, phytochemistry,

Osteoblastogenesis activity of Cissus quadrangularis and its molecular healing mechanisms
in osteoporosis.
2. Osteoporosis and its symptoms
2.1 Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture [7]. Osteoporosis
is a silent epidemic disease. It has become a major health hazard in the recent years afflicting
over 2000 million people worldwide. It is a chronic, progressive condition associated with
micro-architectural deterioration of bone tissue that results in low bone mass. The most
common sites of osteoporosis fracture are the wrist, spine, shoulder and hip. Over 80% of all
fractures in people 50 are caused by osteoporosis. Osteoporosis causes 70-90% of 30,000 hip
fractures annually. Twenty-eight per cent of women and 37% of men who suffer a hip
fracture will die within the following year.
2.2. Symptoms
Osteoporosis itself has no symptoms. Its main consequence is the increased risk of bone
fractures. Osteoporosis fractures occur in situations where healthy people would not normally
break a bone. Therefore it is regarded as fragility fractures. Typical fragility fractures occur in
the vertebral column, rib, hip and wrist [8].
3. Cissus quadrangularis
Cissus quadrangularis is a perennial plant of the grape family. It is commonly known as
Veldt Grape or Devil's Backbone. The plant commonly known as bone setter- it is referred
to as Asthisandhani in Sanskrit and Hodjod in Hindi because of its ability to join bones.
Cissus quadrangularis is used as a medicinal plant. In siddha medicine it is considered as
tonic and analgesic. It is also used to heal broken bones, injured ligaments and tendons, thus
its name asthisamharaka (that which prevents the destruction of bones)[9]. The fresh stem and
leaves of Cissus quadrangularis (CQ) are used for the treatment of hemorrhoids, menstrual
disorders, scurvy and flatulence [10].

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3.1. Scientific classification

Kingdom

Plantae

Division

Magnoliophyta

Class

Magnoliopsida

Order

Vitales

Family

Vitaceae

Genus

Cissus

Species

quadrangularis

3.2. Distribution
Cissus quadrangularis, a vine that belongs to the family Vitaceae. It is one of the most
frequently used medicinal plants in India. This is an edible plant found in the warmer regions
of India, Sri Lanka, Malaysia, Java and West Africa. It is probably native to India or Sri
Lanka, but is also found in Africa, Arabia, and Southeast Asia. It has been imported to
Brazil and the southern United States [10].
3.3. Botanical description
Cissus quadrangularis L. is commonly known as Asthisamhari is a succulent plant of family
Vitaceae commonly found throughout the hotter parts of India [11]. Plant flowers in the month
of June-December. Plant material occurs as pieces of varying lengths, stem quadrangular, 4winged, internodes 4-15cm long and 1-2cm thick. The surface is smooth, glabrous, buff
colored with greenish tinge, angular portion reddish-brown; no taste and odour. Leaves are
simple 2.5-5cm long, broadly ovate or reniform, sometimes 3-7 lobed, denticulate, glabrous,
cordate, rounded, truncate or cuneate at the base; petioles 6-12mm long; stipules small
broadly ovate, obtuse. Flowers are in shortly peduncle cymes with spreading umbellate
branches. Calyx is cup shaped, truncate or very obscurely lobed. Petals are 4, ovate-oblong,
short, stout. Berry is obovoid or globose, scarcely 6mm, long apiculate, red when ripe, 1(very rarely 2) seeded [12]. The whole plant including all parts such as stems, leaves, roots are
documented to possess medicinal properties in ethnobotanical surveys conducted by
ethnobotanists in traditional system of medicine Table 1.

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Table: 1 Botanical description of Cissus quadrangularis

Characters

Cissus quadrangularis

Plant

Quadrangular-sectioned branches with internodes

Leaves

Simple 2.5-5cm long, broadly ovate or reniform, denticulate, glabrous,

cordate, rounded, truncate or cuneate at the base, stipules small broadly
ovate, obtuse.

Flowers

Small white, yellowish, or greenish flowers, shortly peduncle cymes

with spreading umbellate branches

Calyx

Cup shaped, truncate or very obscurely lobed

Petals

Petals are 4, ovate-oblong, short, stout.

Stem

Quadrangular, 4-winged, internodes 4-15cm long and 1-2cm thick

Seed

Globular berries are red when ripe, obovoid or globose

Flowering

and June-December in Indian conditions

Fruiting time
3.4. Principal Constituents of Cissus quadrangularis
Cissus quadrangularis have numerous bioactive compounds such as alkaloids, resveratrol,
piceatannol, pallidol, parthenocissin, quadrangularins, ascorbic acid, carotene, phytosterol
substances, calcium, flavinoids, vitamins, enzymes, nicotinic acid, tyrosin, and triterpenoids.
Cissus quadranguaris contains a variety of terpenoid components, such as the balsam ketone,
amyrin, onocer 7 ene 3 a 21diol, taraxerol, acetyl taraxerol, friedelin ketone. The main
chemical constituents are tetracyclic triterpenoids, onocer-7-ene-3alpha, 21 beta-diol and
onocer-7-ene-3beta, 21 alpha-diol and two steriodal principles I and II, alpha-sitosterol, deltaamyrin. The stem contains two asymmetric tetracyclic triterpenoids, and two steroidal
principles. The presence of -sitosterol, - amyrin, -amyrone, and flavanoids (quercetin)
having different potential metabolic and physiological effects has also been reported [13] and
the stem has revealed unique stilbene derivatives, which are termed quadrangularins A, B
and C10. Other lipids and several phytosterols like heptadecyl octadecanoate, icosanyl
icosanoate, 4-Hydroxy-2-methyltricos-2-en-22- one, 9-methyl-octadec-9-ene, -amyrin, amyrone taraxeryl acetate, friedelan-3-one, taraxerol, P-sitosterol and isopentacosanoic acid
are identified in this plant. Cissus quadrangularis is rich in vitamin C and beta-carotene.

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Analysis showed that Cissus contained Ascorbic acid at a concentration of 479 mg, and
carotene 267 units per 100g of freshly prepared paste, in addition to calcium oxalate [14].
3.5. Traditional uses
The roots and stems are most useful for healing of fracture of the bones. The stem is bitter. It
is given internally and applied topically in broken bones. It is also used in complaints of the
back and spine. A paste of stem is useful for muscular pains. The plant has been documented
in Ayurveda for the treatment of osteoarthritis, rheumatoid arthritis and osteoporosis

[15, 16]

The stem juice of plant is used to treat scurvy, menstrual disorders, otorrhoea and epistaxis.
The use of sap with tamarind has been reported in East Africa for the treatment of gonorrhoea
[17]

.The herb is fed to cattle to induce flow of milk. The ash of plant is useful as a substitute

for baking powder. A paste of stem is given in asthma, burns and wounds, bites of poisonous
insects and for saddle sores of horses and camels [18]. Decoction of shoots with dry ginger and
black pepper is given for body pain the infusion of plant is anthelmintic. Leaves and young
shoots are powerful alternatives, dried and powdered. They are administering in certain
bowel infections connected with indigestion. The plant is useful in helminthiasis, anorexia,
dyspepsia, colic, flatulence, skin diseases, leprosy, hemorrhage, epilepsy, convulsion,
haemoptysis, tumors, chronic ulcers, swellings. The stout fleshy quadrangular stem is
traditionally used for treatment of gastritis constipation, eye diseases, piles and anemia. The
stem boiled in limewater it forms a preserve useful as a stomachic. The Rongas of east Africa
apply the pounded stem to wounds [11].
3.6. Anti-osteoporosis activity of Cissus quadrangularis
Ethanol extract was evaluated for its antiosteoporotic activity in ovariectomized rat model of
osteoporosis at two different dose levels of 500 and 750 mg/kg per day. The rats were divided
into five groups. First group served as control. All the remaining groups were
ovariectomized. Group 2 was fed with saline and served as ovariectomized control. Groups
35 were orally treated with Raloxifen (5.4 mg/kg) and ethanol extract of Cissus
quadrangularis (500 and 750 mg/kg), respectively. The biomechanical, biochemical and
histopathological parameters showed that the ethanol extract had a definite antiosteoporotic
effect [6].

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4. Cissus quadrangularis mechanism for osteoporosis treatment

4.1. Enhances Bone Marrow Mesenchymal Stem Cell Proliferation and Facilitates
Osteoblastogenesis
Human bone is composed of a mineralized organic matrix and bone cells. Osteoblasts are
active mature bone cells that synthesize the organic matrix and regulate the mineralization
process. Osteogenesis begins with osteoblast formation and secretion of type I collagen,
which makes up about 90% of the organic bone matrix, or the osteoid

[19]

. Once osteoblasts

are active, they begin to produce large amounts of alkaline phosphatase, a phosphate-splitting
enzyme that is released into the osteoid to initiate the deposition of minerals. Calcium
hydroxyapatite, which comprises 70% of the bone mass, crystallizes along the cavities in the
three-dimensional collagen network. After mineralization, the complete bone becomes hard
and rigid with the mechanical properties necessary to withstand external forces, support the
body and protect the internal organs. The proliferation rate and biological activity of the
osteoblasts controls the rate of bone formation, and accelerated osteoblast growth is the key
factor for efficient bone repair. The reduction in bone mass in osteoporosis is due to an
imbalance between bone resorption and bone formation in which the rate of resorption
exceeds that of formation. The most important risk factor for osteoporosis is advanced age, in
both men and women. In women, estrogen deficiency following menopause is correlated with
a rapid reduction in BMD (bone mineral density). In men, a decrease in testosterone levels
has similar but less pronounced effects. Other causes of osteoporosis include tobaccosmoking, low body mass index, malnutrition, alcoholism, insufficient physical activity and
exposure to heavy metals like cadmium [10].
Bone marrow mesenchymal stem cells (MSCs) have recently received widespread attention
due to their potential use in tissue engineering applications. MSCs are defined as selfrenewable, multipotent progenitor cells with the capacity to differentiate into several distinct
mesenchymal lineages and are thus excellent candidates for tissue engineering.Bone marrow
mesenchymal stem cells are the source of bone-forming osteoblasts [18]. The petroleum ether
extract of Cissus quadrangularis can stimulate the differentiation of mesenchymal stem cells
into osteoblasts in a dose-dependent manner even in the absence of osteogenic conditioning
media. This activity of the plant extract is increased further in the presence of osteogenic
media. The plant extract also facilitated extracellular matrix mineralization, which was more
pronounced in the presence of osteogenic media. Finally, the presence of plant extract in the
control and osteogenic media stimulated the proliferation rate of MSCs [10].

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Bhagath Kumar Potu et al [10], examined that the CQ plant extract enhances the proliferation
and differentiation ability of MSCs into osteoblasts. ALP activity, the most widely
recognized biomarker for osteoblast activity [20], was enhanced by a short treatment with CQ.
In vivo experiments that have demonstrated that CQ promotes ALP activity and enhances
collagen synthesis in the fracture-healing process

[6]

. Bhagath Kumar Potu et al

[10]

, suggest

that the petroleum ether fraction may contain active constituents that stimulate osteoblast
differentiation and its bioactivity. The phytogenic steroids found in CQ may be involved in
stimulating osteoblastogenesis and may act on estrogen receptors of bone cells. In vitro and
in vivo data suggest that CQ can be effectively used to treat various bone disorders and can
also be used as a preventive measure for disorders that lead to decreased bone mineral
density.
4.2. Molecular Mechanism of Cissus quadrangularis for osteogenesis
The exact molecular mechanism involved in Cissus quadrangularis (CQ), which promoted
osteogenesis. Wnt signaling pathway has been shown to play a significant role in the control
of osteoblastogenesis and bone formation

[10]

. The Wnt signaling pathway is a network of

proteins that passes signals from receptors on the surface of the cell to DNA expression in the
nucleus. It controls cell-cell communication in the embryo and adult [21, 22]. Mutations in these
signaling molecules are strongly associated with changes in bone mineral density and
fractures. Loss-of-function mutations in LRP5 (low-density lipoprotein receptorrelated
protein) receptors cause osteoporosis-pseudoglioma syndrome, while gain-of-function
mutations in the same group lead to high bone mass phenotypes. Using knockout and
transgenic mouse models for Wnt pathway components, it has been established that this
signaling pathway regulates many aspects of osteoblast physiology including commitment,
differentiation, bone matrix formation/mineralization and apoptosis as well as its coupling
with osteoclastogenesis and bone resorption [23]. Therefore, it is reasonable to suggest that the
active constituents of CQ may stimulate the proliferation and differentiation of MSCs and
promote new bone formation through the WntLRP5-catenin signaling pathway for preosteoblast formation. Furthermore, the role of CQ in RANK-RANKL expression and
osteoclast differentiation and activity needs to be identified. Recently, it has been shown that
the CQ-mediated increase in osteoblast activity may be mediated through a MAPKdependent pathway [24].

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5. CONCLUSION
The whole plant is used in India for the treatment of various diseases. Ayurveda mentions it
as a tonic and analgesic, and prescribes its use to help heal broken bones, thus its name
asthisamharaka. It is used in the treatment of osteoporosis, asthma, cough, hemorrhoids, and
gonorrhea. Cissus may be useful not only in building up bones but in improving functional
efficiency. Cissus quadrangularis is rich in vitamin C and betacarotene. The extract also
neutralizes the antianabolic effect of cortisone in healing of fractures, possibly due to its high
vitamin C content. The antioxidant potential of the extracts can be assessed by employing
different in vitro assays. More Clinical and Pathological studies should be conducted to
investigate the active potentials of bioactive compounds present in this plant.
Conflict of interest statement
We declare that we have no conflict of interest.
ACKNOWLEDGEMENTS
The authors are grateful to the Staff Members of Biotechnology Department, Malankara
Catholic

College,

Mariagiri,

Kanyakumari,

Tamilnadu,

India

for

their

constant

encouragement and support.

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