International Journal of PharmTech Research

CODEN (USA): IJPRIF ISSN : 0974-4304

Vol.2, No.2, pp 1298-1310, April-June 2010

Pharmacological and Therapeutic Activity of Cissus

quadrangularis: An Overview
Garima Mishra1*, Saurabh Srivastava2, B.P.Nagori3
*1
Swami Vivekanand College of Pharmacy, Chandigarh Patiala Highway, Sector-8, Banur
(Ramnagar), Teh. Rajpura, Patiala. INDIA.
2
University Institute of Pharmaceutical Sciences, Panjab University,
Chandigarh-160014. INDIA.
3
Lachoo Memorial College of Science and Technology, Jodhpur-3420003.
Rajasthan. INDIA.
*
Corres.author: [email protected], Ph: 09780580180

ABSTRACT: Since ancient ages plants have served human beings as a natural source of treatments and therapies,
amongst them medicinal herbs have gain attention because of its wide use and less side effects. In current scenario focus
on plant research has increased throughout the world and a huge amount of evidences have been collected to show
immense potential of medicinal plants used in various traditional systems. More than 15000 plants have been studied
during the last 5 year period. Recently scientists are using these renewable resources to produce a new generation of
therapeutic solutions. Inspite of many synthetic compounds, the most efficient drugs available are directly or indirectly
related with the plant kingdom. Many of the plant extracts have proven to posses pharmacological actions. Production
and cost advantages of plant-made pharmaceuticals can allow more capital to be invested in research and development
of new therapeutics, giving patients access to new drugs faster. This review highlights some of the phytochemical and
pharmacological aspects of Cissus quadrangularis Linn. Cissus quadrangularis, a perennial climber widely used in
traditional medicinal systems of India has been reported to posses bone fracture healing, antibacterial, antifungal,
antioxidant, anthelmintic, antihemorrhoidal and analgesic activities. Cissus quadrangularis Linn. Has been recognized
as a rich source of carotenoids, triterpenoids and ascorbic acid and is proved to have potential for medical effects,
including “Gastroprotective activity” in conjugation with NSAID therapy and in “Lipid metabolism and oxidative
stress”. Needless to say that versatile uses and various therapeutic activities has made the plant a valuable medicinal
herb.
KEYWORDS: Cissus quadrangularis, phytochemical constituents, Hadjod, Phytochemistry, Pharmacological activities.

INTRODUCTION It requires warm tropical climate and propagated by

Cissus quadrangularis (Linn) has been used by stem cuttings in months of June and July. It is a
common man in India for promotion of fracture climbing herb, tendrils simple, opposite to the leaves,
healing and well known as “Hadjod”. It is also known leafless when old. Leaves simple or lobed, cordate,
as Vitis quadrangularis Wall. Which belongs to family broadly ovate or reniform, serrate, dentate, sometimes
Vitaceae. It is a common perennial climber, which is 3-foliate and glabrous. Flowers small, greenish white,
distributed throughout India particularly in tropical bisexual, tetramerous, in umbellate cymes, opposite to
regions. The plant is commonly known as Vajravalli in the leaves. Calyx is cup shaped. Fruit globose or
Sanskrit, Hadjod in Hindi, Kandvel in Marathi, obovoid fleshy berries, succulent, very acrid, dark
Haddjor in Punjabi, Hadbhanga in Oria, Vedhari in purple to black, one seeded; seeds ellipsoid or
Gujrati, Perandi in Tamil, Nalleru in Telugu and pyriform. Stem is buff colored with greenish ting,
Veldgrap, Edible Stemmed Vine in English.
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1299

dichotomously branched, sub- angular, glabrous, It has been investigated that methanolic extract of
fibrous and smooth. [1, 2] Cissus quadrangularis possesses antiulcer and
It has been prescribed in Ayurveda as an alternative, cytoprotective property in indomethacin induced
anthelmintic, dyspeptic, digestive, tonic, analgesic in gastric mucosal injury. The aqueous extract also shows
eye and ear diseases, and in the treatment of irregular acetylcholine like activity on isolated ileum of rabbit
menstruation and asthma. In some parts of world, the and uterus of rat. The action on dog blood pressure is
whole plant is used in oral re-hydration, while the leaf, analogous to muscarinic and nicotinic actions of
stem, and root extracts of this plant are important in acetylcholine. Ethyl acetate fractions of both fresh and
the management of various ailments. Some other dry stem extracts show antioxidant activity. The ethyl
reports on Cissus quadrangularis justifies its acetate extract and methanol extract of both fresh and
effectiveness in management of obesity and dry stem further exhibit antimicrobial activity against
complications associated with metabolic disorders [3], gram-positive bacteria including Bacillus subtilis,
as well as its antioxidant and free radical scavenging Bacillus cereus, Staphylococcus aureus and
activity in vitro.[4, 5] In current scenario formulations Streptococcus species. Due to its widespread and
now contain extracts of Cissus quadrangularis in versatile therapeutic uses as well as pharmacological
combination with other active ingredients, used for the actions, the present study highlighted the health
purpose of management of overweight and obesity, as promoting and therapeutic properties of Cissus
well as complications resulting from these conditions, quadrangularis. [9, 10, 11, 12]
specifically metabolic syndrome (syndrome X).
Phytochemical screening of Cissus quadrangularis PHYTOCHEMISTRY:
revealed high contents of ascorbic acid, carotene, Phytochemical studies of Cissus quadrangularis have
anabolic steroidal substances, and calcium. The stem shown the presence of various versatile constituents
contains two asymmetric tetracyclic triterpenoids, and such as flavanoids, triterpenoids, Vitamin C, stilbene
two steroidal principles. The presence of β-sitosterol, derivatives and many others, e.g. resveratrol,
δ-amyrin, δ-amyrone, and flavanoids (quercetin) piceatannol, pallidol perthenocissin and phytosterols.
having different potential metabolic and physiological Out of which ascorbic acid, triterpene, β-sitosterol,
effects has also been reported. [6, 7] ketosteroid, two asymmetrical tetracyclic triterpenoids
and calcium were identified as major constituents of
CLASSIFICATION: [2, 20] this plant. [7, 11, 13, 14]
Kingdom : Plantae The Cissus quadrangularis contains high amount of
Division : Magnoliophyta Carotene A, anabolic steroidal substances and
Class : Magnoliopsida Calcium. The plant contains ascorbic acid, 479 mg and
Order : Vitales carotene, 267 mg per 100 g freshly prepared paste, in
Family : Vitaceae addition to calcium oxalate. The stem of the plant
Genus : Cissus contains two asymmetric tetracyclic triterpenoids,
Species : quadrangularis onocer – 7 ene 3 α, 21 β diol (Fig. 1) (C30H52O2 m.p.
200 – 202 °C) and onocer - 7 ene – 3 β, 21 α diol (Fig.
THERAPEUTIC USES: 2) (C30H52O2, m.p. 233 – 234 °C). It also contains two
The stout, fleshy quadrangular stem is traditionally steroidal principles –
used for the treatment of gastritis, bone fractures, skin 1. C27H45 O, melting point 249-252 °C
infections, constipations, eye diseases, piles, anemia, 2. C23H41 O, melting point 136-138 °C
asthma, irregular menstruation, burns and wounds. The Presence of β-sitosterol (Fig.3), δ amyrin and δ-
leaves and young shoots are powerful alteratives. amyrone is also reported. The aerial parts of Cissus
Powder is administered in treatment of hemorrhoids quadrangularis is found to contain a new asymmetric
and certain bowl infections. The juice of stem is useful tetracyclic triterpenoid, 7-Oxo-Onocer-8-ene-3 β 21 α
in scurvy and in irregular menstruation whereas the diol (Fig 1) (C30H50 O3 , m.p. 235-237 °C). [15, 16, 17, 18, 19]
stem paste boiled in lime water is given in asthma. It is Seven new compounds are also reported which are 4-
also used as a powerful stomachic. Cissus hydroxy 2 methyl-tricos-2 ene -22- one, 9-methyl-
quadrangularis Linn. has potent fracture healing octadec-9-ene, heptadecyl- octadecanoate, icosanyl-
property and antimicrobial, antiulcer, antioxidative, icosanoate, 31-methyl tritiacontan-1-ol, 7- hydroxy-
antiosteoporotic, gastroprotective, cholinergic activity 20- oxo- docosanyl cyclohexane and 31-methyl
as well as beneficial effects on cardiovascular diseases. tritiacontanoic acid. Small amount of taraxeryl acetate,
[8]
friedelan-3-one, taraxerol and isopentacosanoic acid is
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1300

also present. Presence of 3, 3’, 4, 4’- TOXICITY STUDY:

tetrahydroxybiphenyl is also reported. [20, 21, 22] Toxicity study was conducted to evaluate the three-
Analysis of the air-dried Cissus quadrangularis plant month sub chronic toxicity of Cissus quadrangularis
reported to contain moisture 13.1, protein 12.8, wax powder in five groups of 12 Wistar rats of each sex.
1.0, fiber 15.6, carbohydrate 36.6, mucilage and pectin Water control group received orally 10 ml of water/kg
1.2 and ash 18.2%. The root powder also contain a rich BW/day. The dried stems powder was given orally to
source of mineral elements (mg/100g dry matter): the four treatment groups at the doses of 0.03, 0.3, 3.0
potassium 67.5, calcium 39.5, zinc 3.0, sodium 22.5, and 30 g/kg BW/day, which were equivalent to 1,10,
iron 7.5, lead 3.5, cadmium 0.25, copper 0.5 and 100 and 1000 fold of the therapeutic dose in human
magnesium 1.15. [23, 24, 25, 26] respectively, the last group was the recovery group. No
Analysis of the toxicants also revealed the presence of difference of initial or final body weights between
oxalate, tannin, phytate, saponin contents (135, 0.3, 20, Cissus quadrangularis treated and control groups was
0.16 mg/100g of dry matter) respectively. The ash detected.
formed from the Cissus quadrangularis contains It was found that Cissus quadrangularis did not
mostly carbonates and to a smaller extent phosphates produce any significant dose-related changes of
of sodium, potassium, magnesium and calcium. hematological parameters of serum clinical chemistry
Presence of potassium tartarate is also reported. [27, 28] and no histopathological lesion of any internal organ
The Cissus quadrangularis stem is also reported to that could be due to the toxic effect of Cissus
contain a water-soluble glycoside, which produces a quadrangularis was observed. The result indicated that
fall in blood pressure in anaesthetized cats. Fresh Cissus quadrangularis at the doses given did not
stems of Cissus quadrangularis produces irritating produce any toxicity in the rats during the
action on the skin, which may be attributed to the administration period of 3 months. [34]
presence of calcium oxalate and 31 methyl
tritiacontanoic acid along with taraxeryl acetate, PHARMACOLOGICAL ACTIVITY:
taraxerol and iso-pentacosanoic acid. [29, 30] Bone fracture healing activity:
Recently three new stilbene derivatives, Cissus quadrangularis (Vitaceae), a rambling shrub,
quadrangularins A, B and C were isolated from Cissus characterized by a thick quadrangular fleshy stout
quadrangularis together with resveratrol, piceatannol, stem, Commonly known as the “Bone Setter,” the
pallidol and parthenocissine A. The stem extract of plant is referred to as “Asthisamdhani” in Sanskrit and
Cissus quadrangularis plant contains a high “Hadjod” in Hindi because of its ability to join bones.
percentage of calcium ions (4% by weight) and A phytogenic isolated steroid is believed to be the
phosphorous. Recently a study has been undertaken main constituent in Cissus quadrangularis. Studies on
which showed that the plant extract when reacted with fracture healing suggest that this unidentified anabolic
CO2, leads to formation of calcite crystals of highly steroid may act on estrogenic receptors of the bone.
irregular morphology, indicating that bioorganic Efficacy of Cissus quadrangularis on early ossification
molecules present in the extract modulate the crystal and remodeling of bones have been reported and it has
morphology.[31, 32, 33] been observed that Cissus quadrangularis acts by
stimulation of metabolism and increased uptake of the
STRENGTH AS PER AYURVEDIC minerals calcium, sulpher and strontium by the
PHARMACOPOEIA OF INDIA: [1, 2, 16, 19] osteoblasts in fracture healing. [35, 36]
Foreign Matter: NMT 1% W/W
Total Ash: NMT 5% W/W Cissus quadrangularis is found to contain vitamins
Acid insoluble ash: NMT 1% W/W and steroids, which are found to have specific effect on
Alcohol soluble extractive: NLT 3% W/W bone fracture healing. The anabolic steroidal principles
Water soluble extractive: NLT 23% W/W from Cissus quadrangularis showed a marked
Fixed oil: NLT 3% W/W influence in the rate of fracture healing by influencing
Sulphated Ash content: NMT 5% W/W early regeneration of all connective tissues involved in
Arsenic: NMT 1 ppm the healing and quicker mineralization of callus. [37, 38]
Lead: NMT 5 ppm Systemic use of Cissus quadrangularis in rats caused
Total bacterial count: NMT 800 CFU/g complete restoration of normal composition of bone,
Total fungal count: NMT 500 CFU/g after fracture in four weeks while the controls required
Moisture content: NMT 5% W/W six weeks. There was a shortening of about two weeks
in the bone healing duration. The total weight of the
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1301

fractured bone also came down towards normal much rabbits caused a significant increase in
earlier than the controls indicating quickest bone mucopolysaccharides level and also caused
remodeling. All the events namely fibroblastic phase proliferation of osteoblastic, chondroblastic and
(first week), collagen phase (second week) and cartilage proliferation. It also led to increased
osteochondroital phase (third and fourth weeks) were mineralization in the callus. Thus the parenteral
hastened by about 10 to 14 days in the treated group. administration of the total extract of Cissus
This hastening in the fracture healing was attributed to quadrangularis not only neutralized the anti-anabolic
the stimulation of all the cells of mesenchyma origin, effect of cortisone in healing of fractures but also
namely the fibroblasts, the chondroblasts and enhances the mineralization of the callus. This effect
osteoblasts by Cissus quadrangularis. It has greater was much greater than that of anabolic hormone
impact on osteoblastic proliferation than other cellular Durabolin a drug of choice for the neutralization of
responses. In both the models the mucopolysaccharide cortisone possibly due to its vitamin contents. [47, 48]
and collagen levels of the bones in the treated group A clinical study was planned to evaluate the effect of
came down to normal at the end of only four weeks the Cissus quadrangularis in the healing of fractures.
while the control required 6 weeks as confirmed with All the sixteen patients with various types of fractures
histological and histochemical observations. [39, 40, 41] were treated with external application of the paste
Radioactive calcium (Ca45) studies indicated that prepared from the Cissus quadrangularis. This
Cissus quadrangularis causes less lowering of calcium treatment was given in addition to the standard
(Ca45) uptake in the treated animals while in the treatment of fractures, e.g. complete immobilization.
control animals there was a greater decrease in the As per radiological observations the results were
calcium (Ca45) uptake in the first week followed by a excellent in 6 cases with the 40% reduction in the
gradual increase in the subsequent weeks which healing time, good in 8 cases with 53% reduction in
reached its maximum in the 4th weeks the calcium the healing time and poor in 1 case with 7% reduction
(Ca45) uptake in the treated group came to normal at in healing time. Clinically in about 80% of the cases,
the end of 5th week as compared to 6 - 8 weeks in excellent results were observed and in the remaining
controls. Thus it was concluded that Cissus 14% of the cases the results were good. Only in one
quadrangularis caused less amount of tissue reaction case there was no demonstrable effect. In few of the
in the fractured region leading to optimum treated cases although radiologically only an early
decalcification in the early stage with minimum of callus formation was observed but clinically the
callus formations. Hence deposition of calcium was symptoms of fracture such as pain, tenderness and
just enough to join the two broken segments of bones swelling were significantly absent. It was also
so that it’s remodeling takes much faster in the treated observed that the injured bones surrounded by muscles
group as compared with controls. This early showed a greater beneficial effect of this herb than
completion of calcification process and earlier those that are subcutaneous. It was hypothesized that
remodeling phenomenon lead to early recovery of Cissus quadrangularis helps in the earlier formation of
animals. The tensile strength studies indicated much collagen fibers leading to earlier calcification and
early gain in the tensile strength in Cissus callus formation. [49, 50, 51, 52]
quadrangularis treated group, leading to 90 percent of
gain of its normal strength at the end of 6th week in A study was undertaken to evaluate the effect of
comparison to 60 percent of gain in strength in the Cissus quadrangularis extract on the healing process
controls. Thus Cissus quadrangularis builds up the of experimentally fractured radius-ulna of dog.
chemical composition of the fractured bone namely its Histopathological and radiological investigations on
mucopolysaccharides, collagen, calcium, phosphorus 11th day revealed faster initiation of the healing process
and others as well as its functional efficiency. [42, 43, 44, and a greater decrease in serum calcium level in the
45, 46]
treated group than the control group. On 11th day, the
treated group exhibited initiation of osteogenesis,
Healing of the fractured bone is delayed considerably which was absent in the control group. Fracture was
by the administration of Cortisone. The periosteal completely healed in 21 days in the treated group and
reaction is reduced and the amount and density of remained incomplete in the control group. Radiograph
callus is lowered. The mortality rate of the treated of the treated group revealed almost complete bridging
subjects is very high due to severe body wasting, of the fractured ends with extensive bony deposition
atrophy of muscles and gastric perforation. Cissus and peristoneal reaction compared to that of control
quadrangularis treatment in these cortisone treated group. The treated group also revealed replacement of
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1302

cartilaginous cells by osteoblastic cells and union of process takes place at the site of fracture during the
the fractured gap at several places with the formation latter half of the third week. This is accompanied with
of new bony trabeculae whereas bony trabeculae were the fall of mucopolysaccharides in the region. In
absent in the control group. [53, 54] animals treated with Cissus quadrangularis such a
Alkaline phosphates are involved in bone formation mineralization process takes place much earlier,
and healing of fractures. The enzyme, secreted by the roughly in the second half of the second week. Not
osteoblasts accelerates the process of mineralization only the healing has been faster but also the quality of
either by increasing the local concentration of the callus seems to be better in terms of the enormous
inorganic phosphate or activating the collagen fibers to deposition of the minerals at the end of the second
induce deposition of calcium salts. Cissus week only. This is followed by early demineralization
quadrangularis has caused an increase in alkaline so that the callus becomes remodeled to take a normal
phosphate levels during fracture healing in adult dogs. shape of the bone. These findings further confirmed
A study was conducted using albino rats to explore that the Cissus quadrangularis has favourable action in
whether the beneficial effect of Cissus quadrangularis the rate of healing of fracture in experimental animals.
[57, 58]
in the healing of fractures is due to its vitamin C
content. The animals receiving Cissus quadrangularis Analgesic activity:
showed rapid accumulation of larger quantity of The analgesic effect of the drug as observed by
mucopolysaccharides in the first week followed by Haffner’s tail flip and Eddy’s hot plate methods were
more rapid fall and its earlier disappearance from the dose related. There was increase in reaction time even
fractured area and both of these actions have beneficial with such small dose as 1/40 th of the LD50 . The effect
effect on the healing of the fractures. At the end of the lasted for about 4 hrs. Cissus quadrangularis exhibited
third week the Skiagram showed greater amount of significant analgesic activity compared to that of
calcification in the Cissus quadrangularis treated Aspirin when tested using Haffner’s clip and Eddy’s
group in which one could hardly see a gap at the site of hot plate methods. The extract was found to be
the fracture, while the control and vitamin C treated effective by both oral and i.p. routes significantly
group showed some gap. At the end of 5th week the (P<0.001) and reaction time was found to be increased
union at the fractured site was more firm in the Cissus by both methods. The duration of analgesic activity
quadrangularis treated group than the others. Earlier was from 2 to 4 hr and optimum effect was observed at
disappearance of mucopolysaccharides from the 1/20th-1/10th of LD50 dose. The extract compared well
fractured area is associated with the earlier with Acetylsalicylic acid. [59, 60]
calcification and firmer callus formation. The analgesic effect of this plant when used in bone
Mucopolysaccharides play an important role in the fractures may be of great value in relief of pain which
healing by supplying raw materials for repairs. is a constant feature in these cases. As it compared
Therefore, it seems that in the early period the greater well with acetyl salicylic acid in its analgesic response
the accumulation of these materials more rapid will be the nature of its chemically active constituents needs to
the rate of healing. In the later period when the be explored. [61]
mucopolysaccharides content decline in the fractured
area is an indicative of rapid utilization of these raw Antiosteoporotic activity:
materials leading to earlier completion of healing Osteoporosis, a silent epidemic, has become a major
process. This effect of the Cissus quadrangularis is not health hazard in the recent years afflicting over 2000
due to its vitamin C content alone, since the million people worldwide. It is a chronic, progressive
administration of the vitamin C to normal animals did condition associated with micro-architectural
not produce such a beneficial effect. Its action is more deterioration of bone tissue that results in low bone
systemic, which is responsible for the greater mass. The leading cause of osteoporosis is the lack of
mobilization of mucopolysaccharides from the tissues certain hormones, particularly estrogen in women and
in to the blood and earlier utilization of the substances androgen in men as well as Imbalance in the activities
required in the healing process. [55, 56] of osteoblasts and osteoclasts cells lead to osteoporosis
in postmenopausal women. In osteoporosis the bones
Phosphorus (P 32) is a useful isotope to study the rate of begin to deteriorate due to calcium deficiency. In
mineralization during healing of fractures since it is menopause, the decrease in hormones affects the
readily incorporated in the area where the calcium body’s ability to maintain calcium levels resulting in
phosphate complex is deposited during the latter part an increased loss of minerals from the bone.
of healing. In control animals, such a mineralization Postmenopausal women are at particular risk to
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1303

osteoporosis because the loss of estrogen associated Thus, Cissus quadrangularis has potential usefulness
with the menopause leads to bone loss of much greater for treatment of peptic ulcer disease. [71-79]
magnitude than expected on the basis of age alone.
Treatment focuses on slowing down or stopping the Antioxidant activity:
mineral loss thereby preventing bone fractures and Extracts of Cissus quadrangularis Linn were tested for
controlling the pain associated with the disease. Many antioxidant activity by β-carotene linoleic acid model
synthetic agents such as estrogens in hormone and also by 1, 1-diphenyl-2-picrylhydrazyl model. The
replacement therapy, selective estrogen receptor ethyl acetate fraction of both fresh and dry stem
modulators like raloxifen and droloxifen, extracts at a concentration of 100 ppm showed 64.8%
bisphosphonates and calcitonin have been developed antioxidant activity in the β-carotene linoleic acid
to treat osteoporosis but each one of them is associated system and 61.6% in the 1, 1-diphenyl-2-
with side effects such as hypercalcemia, picrylhydrazyl systems. [80]
hypercalciurea, increased risk of endometrial and Another study was performed to evaluate the effect of
breast cancer, breast tenderness, menstruation, the methanolic extract of Cissus quadrangularis
thromboembolic events, vaginal bleeding and hot against free radical damage. The test extract exhibited
flushes. [46, 47, 48, 49] significant inhibition in DPPH free radical formation,
superoxide radical production and lipid peroxide
Cissus quadrangularis significantly inhibits production in erythrocytes. The activities of liver
antianabolic effects and exerts some beneficial effects marker enzymes and antioxidant defense enzymes in
on recovery of bone mineral density in rat liver homogenate were assessed in control and
postmenopausal osteoporosis. A study was conducted experimental animals. [81, 82, 83, 84]
in which ethanol extract of Cissus quadrangularis was Carbon tetrachloride (CCl4) caused a significant
evaluated for its anti-osteoporotic activity in increase in aspartate aminotransaminase (AST) and
ovariectomized rat model of osteoporosis at two alanine aminotransaminase (ALT), alkaline
different dose levels of 500 and 750mg/kg per day. phosphatase (ALP) and decrease in superoxide
Healthy female albino rats were divided into five dismutase (SOD), catalase (CAT), glutathione
groups of six animals each. [50, 52, 53, 54] peroxidase (GPx) and reduced glutathione (GSH),
The first group served as control. All the remaining which was reverted by Cissus quadrangularis
groups were ovariectomized. Group 2 was fed with pretreatment. The results obtained suggest that Cissus
equivolume of saline and served as ovariectomized showed inhibition of lipid peroxidation, free radical
control. Group 3-5 were orally treated with Raloxifen production and increase in antioxidant enzymes
(5.4mg/kg) and ethanol extract of Cissus activities, which reveal its antioxidant property. It can
quadrangularis (500 and 750mg/kg), respectively. The be concluded that the free radical scavenging activity
findings assessed on the basis of biomechanical, of the plant extract may be responsible for the
biochemical and histopathological parameters showed therapeutic action against tissue damage. [85, 86, 87, 88]
that the ethanol extract of the plant had a definite The stem part of Cissus quadrangularis contains
Antiosteoporotic effect. [55, 56, 57, 62] vitamin C, carotenoids, calcium, steroidal and these
are known to be excellent antioxidants and numerous
Antiulcer activity: studies suggest that dietary intake of plant polyphenol
Cissus quadrangularis is an indigenous plant antioxidants may have positive effects in oxidative-
commonly mentioned in Ayurveda for treatment of stress related pathologies. These antioxidative
gastric ulcers. The ulcer-protective effect of a constituents present in Cissus might be responsible for
methanolic extract of Cissus quadrangularis was the free radical scavenging activity, antilipid
comparable to that of the reference drug sucralfate. [63, peroxidative and antisuperoxide formation. [89, 90, 91, 92]
64, 65]
Further, gastric juice and mucosal studies showed
that Cissus at a dose of 500 mg/kg given for 10 days Parasympathomimetic activity
significantly increased the mucosal defensive factors Aqueous extract showed acetylcholine like activity on
like mucin secretion, mucosal cell proliferation, isolated ileum of rabbit and rat, uterus of rat, dog
glycoproteins and life span of cells. [66-70] The present tracheal muscle and ileum in situ of dog. The
investigation suggests that Cissus not only strengthens responses on dog blood pressure were analogous to
mucosal resistance against ulcerogens but also Muscarinic and Nicotinic actions of Acetylcholine. It
promotes healing by inducing cellular proliferation. was ineffective on frog rectus muscle.
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1304

Anabolic and Androgenic activity: in relieving pain, reduction of swelling and promoting
In addition to speeding the remodeling process of the the process of healing of the simple fractures as well as
bone, Cissus also leads to a much faster increase in in curing the allied disorders associated with fractures.
bone tensile strength. In clinical trials Cissus has led to It acts by preventing the conversion of arachidonic
a fracture healing time in the order of 55 to 33 percent acid to inflammatory prostaglandins. [96, 97, 98]
of that of controls. Cissus exerts antiglucocorticoid Recently anti-inflammatory activity assay of Cissus
properties is suggested by a number of studies where extract was performed. Cyclooxygenase is a key
bones were weakened by treatment with Cortisol and enzyme in the prostaglandin biosynthetic pathway,
upon administration of Cissus extract the Cortisol which is important in the inflammatory process. The
induced weakening was halted and the healing process ability to inhibit the COX-1 activity was used to
begun. [93] evaluate the anti-inflammatory activity of Cissus
Endogenous Glucorticoids including the body’s extract. The anti-inflammatory activity of the extract
endogenous hormone Cortisol activate pathways that was expressed as the percentage of inhibition of
degrade not only bone, but skeletal muscle tissue as prostaglandin synthesis using a COX-1 assay. The
well. Glucocorticoids induce muscle breakdown. They amount of (14C)-labelled prostaglandin synthesized
activate the so-called Ubiquitin-Proteasome pathway was measured using a scintillation counter after
of proteolysis. This pathway of tissue breakdown is removing the unmetabolized (14C)-Arachidonic acid
important for removing damaged and non-functional substrate by column chromatography. The percent
proteins. inhibition of prostaglandin synthesis was calculated.
[99, 100]
By exerting an anabolic, antiglucorticoid effect Cissus
preserve muscle tissue during times of physical and
emotional stress, which is of more interest to the Antihemorrhoidal Activity:
average bodybuilder or athlete. [94] As the combination of flavonoids (90% diosmin and
10% hesperidin) used clinically for the treatment of
Anti-inflammatory activity: hemorrhoid was reported to have anti-inflammatory
Studies have revealed that oral administration of and analgesic activities as well as venotonic effect
phenidone produced marked inhibition of the paw which is not reported previously. Phytochemical study
edematous response induced by arachidonic acid of C. quadrangularis revealed that its major
injection. CQ exerted inhibitory effect on the edema compounds are flavonoids. The bioflavonoids,
formation in this animal model. It has been observed particularly diosmin, hesperidin and oligomeric
that flavanoids, several flavones, flavonols, flavanols proanthocyanidin complexes have demonstrated
and flavanonols are inhibitors of lipoxygenase, potential in the treatment of hemorrhoids and varicose
especially luteolin which is one of the compounds veins. [101] These bioflavonoids exhibit phlebotonic
found in C. quadrangularis. In this regard, it has been activity, vasculoprotective effects and antagonistic
previously shown that at least flavonoid, one of the effect on the biochemical mediators of inflammation.
major components of C. quadrangularis, inhibits the The anti-inflammatory effect which is already been
inflammatory process. Furthermore the anti- observed from the crude extract of C. quadrangularis
inflammatory activity of β sitosterol was also could be produced by the flavonoids especially
demonstrated which is another active constituent of C. luteolin, and by β-sitosterol. The venotonic effect of C.
quadrangularis. The result of the study confirmed the quadrangularis may also be postulated to be due to the
finding that C. quadrangularis have an inhibitory effect of flavonoids present in the extract which act in
effect on edema induced by both carrageenin and the same way as that of diosmin and hesperidin. As
arachidonic acid. Taken together, it is evident that both diosmin and hesperidin are used in combination
cyclooxygenase and lipoxygenase pathways of (Daflon®) to treat hemorrhoid, the extract which
arachidonic acid metabolism are inhibited by C. produced the same activities (anti-inflammatory and
quadrangularis. It is therefore suggested that C. venotonic) can also be used as antihemorrhoidal drug.
quadrangularis is a dual inhibitor of arachidonic acid Besides these effects, C. quadrangularis also
metabolism. [95] possesses analgesic effect, which can be very useful in
Cissus also posses anti-inflammatory activity on a mg painful hemorrhoid. The present study proved the
per mg basis comparable to aspirin or ibuprofen. traditional use of C. quadrangularis as an
Cissus quadrangularis constitutes one of the antihemorrhoidal drug in Thai folk medicine. [102, 103]
ingredients of an Ayurvedic preparation, ‘Laksha
Gogglu’, which has been proved to be highly effective
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1305

Gastroprotective Activity:
Cissus quadrangularis is well known for the treatment attenuation of the oxidative mechanism and neutrophil
of gastric disorders in traditional medicine, owing to infiltration. Triterpenoids and β-sitosterols present in
its rich source of carotenoids, triterpenoids and Cissus quadrangularis possess antilipidperoxidative
ascorbic acid, and has received considerable attention effect and have a pivotal role in the gastroprotective
regarding its role in human nutrition. A number of effect of CQE. [76, 79]
studies have analysed and revealed the effect against
gastric toxicity and the gastroprotective effect of Miscellaneous:
Cissus quadrangularis extract (CQE) along with its Stem paste of the plant may also be useful for
mechanism underlying the therapeutic action against muscular pains, burns, wounds, bites of poisonous
the gastric mucosal damage induced by aspirin. [63, 64, insects and for saddle sores of horses and camels. The
67]
The studies have investigated the effect of CQE on powder of dry shoots is given in digestive troubles. A
the course of experimentally induced gastric ulcer by decoction of the shoots with dry ginger and black
analyzing the levels of tumor necrosis factor-α (TNF- pepper is given for body pains. The infusion of the
α), interleukines, microvascular permeability, activity plant is anthelmintic. The plant extracts also exhibit
of nitric oxide synthase-2 (NOS-2), mitochondrial cardiotonic property. Young shoots are used in
antioxidants, lipid peroxidation and DNA damage. The dyspepsia and indigestion. The powdered stem is
investigational findings have shown significant mixed with pulses and fried in sesame oil, used as a
increase in vascular permeability, NOS-2 activity. remedy for several vata diseases. It is also used in skin
Levels of TNF-α and interleukines were monitored and diseases Leprosy, Cough, Epilepsy and Convulsions.
oxidative damage were noted in aspirin administered FORMULATION AND DOSAGE: [1, 2, 4, 5]
rats. The optimum protective dose of 500 mg/kg of Decoction of dried stalks: 10-30 ml bid
extract was given for the pretreatment of gastric ulcers Ø Juice: 10-20 ml bid
with different doses of CQE (250, 500 and 750 mg/kg) Ø Powder: 3-6 g bid
for 7 days which significantly attenuated these AYURVEDIC PREPARATIONS:
biochemical changes caused by aspirin in rats. [69, 70] Ø Flexi-Muv Oil (Anti-inflammatory, Anti-
The results showed ulcer protection by 40, 71.2 and arthritic)
72.6%, respectively, as compared to ranitidine (RTD) Ø Boneforte Capsule (Calcium supplement)
(30 mg/kg) by 71.9% in the aspirin model. In addition, Ø Laksha Gogglu (Analgesic, anti-
the findings of the studies have shown that inflammatory)
administration of aspirin increases lipid peroxidation
status, xanthine oxidase (XO), myeloperoxidase and CONCLUSION
decrease in superoxide dismutase (SOD), catalase Traditional recipes for treatment of physical and
(CAT) and selenium–glutathione peroxidase activities mental ailments exist in all major ancient civilizations
in the gastric mucosa, resulting in mucosal damage at of the world. Needless to mention that the root and
both cellular and subcellular level which were reversed stem extracts of the plant Cissus quadrangularis have
by CQE. [71] In addition, CQE prevents oxidative therapeutic efficacy and are known to possess
damage of DNA by reducing DNA fragmentation antioxidant, antimicrobial activity, and are routinely
indicating its block on cell death. Pretreatment with used to accelerate the process of bone fracture healing.
CQE ameliorated the observed effect significantly in The plant is considered as a versatile medicinal plant
the gastric mucosa of ulcerated rats. Ulcer protection in both Ayurvedic and modern drug development areas
in CQE treated rats was also confirmed by for its valuable medicinal uses. It is a very rich source
histoarchitecture, which was comprised of reduced size of some minerals, which are necessary for proper
of ulcer crater and restoration of mucosal epithelium. functioning of human body. In the present overview
These findings suggest that the gastroprotective the Emphasis has been laid on the phytochemical
activity of CQE could be mediated possibly through its constituents and pharmacological activity of the plant
antioxidant, antiapoptotic effects as well as by the Cissus quadrangularis Linn.
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1306

OH

OH H3C CH3
H3C CH3
CH3 CH3
CH3 CH3
CH3 CH3
CH3 HO
CH3 O
H3C CH3
HO
H3C CH3

Fig. 1 Onocer-7-ene, 3-a, 21-b diol Fig 2. 7-oxo-onocer-8-ene.3-b. 21-a diol

H3C CH3

CH3 Et CH3

CH3

HO

Fig. 3 b-sitosterol

REFERENCES Linn and their quantitation by HPTLC and HPLC.

1. www.pioneerherbs.com. Phytochem Anal, 2001, 12, 91-105.
2. Rastogi RP, Mehrotra BN. Compendium of Indian 6. Jakikasem S, Limsiriwong P, Kajsongkarm T,
Medicinal Plants, Part I, Publication and Sontorntanasart T., Phytochemical study of cissus
information directorate 1995, 104. quadrangularis. Thai J Pharm Sci, 2000, 24, 25.
3. Oben J, Kuate D, Agbor G, Momo C, Talla X., 7. Jainu M., Devi CS., “Effect of Cissus
The use of a cissus quadrangularis formulation in quadrangularis on gastric mucosal defensive
the management of weight loss and metabolic factors in experimentally induced gastric ulcer- a
syndrome. Lipids in Health and Disease, 2006, 5, comparative study with Sucralfate”. Journal of
24. medicinal food, 2004, 7(3), 372-376.
4. Mallika J, Shyamala CSD, In vitro and In vivo 8. Jainu M., Devi CS., Potent Antiulcerogenic
evaluation of free radical scavenging potential of activity of Cissus quadrangularis on Aspirin
Cissus quadrangularis. Afri J of Biomed Res, 2005, induced gastric ulcer by its antioxidative
8, 95-99. mechanism. Journal of Clinical Biochemical
5. Mehta M, Kaur N, Bhutani K., Determination of Nutrition, 2003, 34, 43-47.
marker constituents from Cissus quadrangularis 9. Jainu, M., Devi, C.S.S., Potent antiulcerogenic
activity of methanolic extract of Cissus
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1307

quadrangularis by antioxidative mechanism. 24. Khan S.S., Singh M.P., Chaghtai S.A.,
Journal of Clinical Biochemistry and Nutrition, Ethnomedicobotany of Cissus quadrangularis
2003, 34, 43–47. Linn. Oriental Journal of Chemistry, 1991, 7,
10. Aslokar LV., Kakkar KK., Chakre OJ., Glossary 170–172.
of Indian Medicinal Plants with active principles; 25. Kumbhojkar M.S., Kulkarni D.K., Upadhye A.S.,
CSIR publication, 1997, 145-150. Ethnobotany of Cissus quadrangularis L. from
11. Enechi OC., Odonwodo I., An assessment of the India. Ethnobotany, 1991, 3, 21–25.
Phytochemical and Nutrient composition of the 26. Udupa KN., Chaturvedi GN., Tripathi SN.,
pulverized root of Cissus quadrangularis. Bio- Advances in research in Indian medicine, Varnasi:
Research, 2003, 1(1), 63-68. Banaras Hindu University. 1970, 12, 165–96.
12. Mehta M., Kaur N., Bhutani KK., Determination 27. Kritikar KR., Basu BD., In: Basu LM., editor.
of Marker Constituents from Cissus Indian Medicinal Plants, (Third revised and
quadrangularis and their quantitation by HPTLC enlarged ed.). India: Allahabad, 2000, 841–3.
and HPLC. Phytochemical Analysis, 2001, 12(2), 28. Austin A., Kannan R., Jagadeesan M.,
91-5. Pharmacognostical studies on Cissus
13. Enechi, O. C., and Odonwodo, I., An assessment quadrangularis L. variant I and II. Ancient Sci Life,
of the phytochemical and nutrient composition of 2004, 33–47.
the pulverized root of Cissus quadrangularis. Bio- 29. Pluemaj T., Saifah E., Constituents of Cissus
Research, 2003, 1, 63–68. quadrangularis Linn. J Pharm Sci., 1986, 11, 205–
14. Shirley D. A., Sen SP., High-resolution X-ray 11.
photoemission Studies on the active constituents of 30. Prajapati ND., Purohit SS., Sharma AK., A Hand
Cissus quadrangularis. Current Sci., 1966, 35, 317. Book of Medicinal plants. Agrobios publication
15. Sen SP., Studies on active constituents of Cissus 2003, 145.
quadrangularis. Indian J. Pharm., 1966, 315-317. 31. Rastogi RP., Mehrotra BN., Compendium of
16. Bhutani K.K., Kapoor R., Atal C.K., Two Indian Medicinal plants Vol.3, CDRI Lucknow
unsymmetric tetracyclic triterpenoids from Cissus and PID New Delhi 1995, 173-174.
quadrangularis. Phytochemistry, 1984, 23(2), 407– 32. Attawish A., Chivapat S., Chuthaputti A. and
410. Punyamong S., Sub chronic Toxicity of Cissus
17. Saburi A., Adesanya R., Marie TN., Najeh M., quadrangularis linn. Sangkalarin J. Science
Alain BM., Mary P., Stilbene derivatives from Technology, 2002, 24(1), 39-42.
Cissus quadrangularis. J. Nat. Prod., 1999, 62, 33. Udupa K.N., Arinkar J.H., and Singh L.M.,
1694-1695. Experimental studies of the use of cissus
18. Ambasta SP. The Useful Plants of India, CSIR quadrangularis in healing of fractures, Ind. J. Med.
publication, 1992, 127. SC., 1961, 15, 551-557.
19. Chopra RN., Nayar SN., Chopra IC., Glossary of 34. Prasad G.C., Udupa K.N., Effect of Cissus
Indian Medicinal Plants, CSIR publication, 1999, quadrangularis on the healing of cortisone treated
66-67. fracture, Indian Journal of Medical Research,
20. Chopra N.N., Chopra I.C., Handa K.L., Kapur 1963, 51, 667.
L.D., Cissus quadranglularis. Indigenous Drugs of 35. Prasad G.C., Udupa K.N., Pathways and site of
India, 1958, 669–670. action of a phytogenic steroid from Cissus
21. Gupta M.M., Verma R.K., Lipid constituents of quadrangularis, Journal of Research in Indian
Cissus quadrangularis. Phytochemistry, 1991, Medicine, 1972, 4, 132.
30(3), 875–878. 36. Udupa K.N., Prasad G.C., Sen S.P., The effect of
22. Pluemjai T., Saifah E., Constituents of Cissus phytogenic steroid in the accleration of fracture
quadrangularis Linn. Thai Journal of repair, Life Science, 1965, 4, 317.
Pharmaceutical Sciences, 1986, 11(4), 205–211. 37. Udupa K.N., and Prasad G., Biochemical and
23. Somova L.I., Shode F.O., Ramananan P., Nadar calcium 45 studies on the effect of cissus
A., Antihypertensive, antiatherosclerotic and quadrangularis in fracture repair, lndian J. Med.
antioxidant activity of triterpenoids isolated from Res., 1964, 52, (5) 480-487.
Olea europaea, subspecies africana leaves. Journal 38. Udupa K. N., and Prasad G. C., Further studies on
of Ethnopharmacology, 2003, 84, 299–305. the effect of Cissus quadrangularis in accelerating
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1308

fracture healing, Indian J. Med. Res., 1964, 52, 51. Lu J. X., Descamps M., Dejou J., Koubi G.,
26–35. Hardouin P., Lemaitre J. and Proust J.P., The
39. Singh L.M., and Udupa K.N., Studies of C. biodegradation mechanism of calcium phosphate
quadrangularis in fracture by using phosphorus, biomaterials in bone, J. Biomed. Mater. Res.,
Ind. j. Med. Sci., 1962, 76, 926-931. 2002, 4, 408–412.
40. Sen S.P., Udupa, K.N., Prasad, G., Studies on the 52. Soliman FA., Hassan SYS., Serum calcium and
active constituents. 10 Further studies on the effect phosphorus in rabbits during fracture healing with
of Cissus quadrangularis in accelerating fracture reference to parathyroid activity, Nature, 1964,
healing, Indian Journal of Medical Research 1966, 204, 693-4.
52, 26. 53. Cohen J., Matetskov CJ., Marshall JM., William
41. Kausch A.P., Horner H.T., A comparison of JW., Radioactive calcium tracer studies in bone
calcium oxalate crystals isolated from callus grafts, J Bone Jt Surg, 1957, 39A, 561-77.
cultures and their explant sources, Scanning 54. Gaillard PJ., Proc. Kon., Ned. Akad., Westenchap.
Electron Microscopy. 1982, 1, 199–211. Ser., In: Bourne GH, ed. Biochemistry and
42. Chopra S.S., Patel M.R., Awadhiya R.P., Studies physiology of bone, New York and London:
of Cissus quadrangularis in experimental fracture Academic Press. 1972, 337.
repair: a histopathological study, Indian Journal of 55. Singh L.M., and Udupa K.N., Studies of C.
Medical Research, 1976, 64(9), 1365–1368. quadrangularis in fracture by using phosphorus,
43. Chopra SS., Patel MR., Gupta LP., Datta IC., Ind. j. Med. Sci., 1962, 76, 926-931.
Studies on Cissus quadrangularis in experimental 56. Chopra S.S., Patel M.R., Awadhiya R.P., Studies
fracture Repair: Effect on Chemical Parameters in of Cissus quadrangularis in experimental fracture
Blood, Ind J Med Res, 1975, 63, 6. repair: a histopathological study, Indian Journal of
44. Canalis H., McCarthy T., Centrella M., Growth Medical Research, 1976, 64 (9), 1365–1368.
factors and the regulation on bone remodeling, 57. Singh SP., Mishra N., Dixit KS., Singh N., Kohli
Journal of Clinical Investigation, 1998, 81, 277– RP., “An experimental study of Analgesic Activity
281. of Cissus quadrangularis”, Indian Journal of
45. Genant H.K., Bay link D.J., Gallagher J.C., Pharmacology, 16(3), 1984, 162-63.
Estrogens in the prevention of osteoporosis in post 58. Ferreira S.H., Moncada S., Vane J.R.,
menopausal women, American Journal of Prostaglandins and the mechanism of analgesia
Obsteterics and Gynaecology, 1998, 161, 1842– produced by aspirin-like drugs, British Journal of
1846. Pharmacology, 1973, 49, 86–97.
46. Ogey A., Bayraktar F., Sevin G., A comparative 59. Viswanatha SAHM, Thippeswam MDV,
study of Raloxifen and estrogen on bone strength Mahendra KCB., Some neuropharmacological
and cholesterol levels in ovariectomized rats, effects of methanolic root extract of Cissus
Endocrine Abstracts, 2001, 3, 10. quadrangularis in mice, Afr. J. Biomed. Res. 2006,
47. Peng Z., Tuukkanen J., Zhang H., The mechanical 9, 64-75.
strength of bone in different rat models of 60. Shirwaikar A., Khan S., Malini S.,
experimental osteoporosis, Bone, 1994, 15, 523– Antiosteoporotic effect of ethanol extract of Cissus
532. quadrangularis Linn. on ovariectomized rat,
48. Sanyal A., Ahmad A., Sastry M., Calcite growth in Journal of Ethonopharmacology, 2003, 89, 245–
Cissus quadrangularis plant extract, Current 250.
Science, 2005, 89(10), 1742-1745. 61. Jainu M., Devi CSS., Attenuation of neutrophil
49. Deka DK., Lahon LC., Saikia J., Mukit A., Effect infiltration and proinflammatory cytokines by
of “Cissus quadrangularis in accelerating healing Cissus quadrangularis: a possible prevention
process of experimentally fractured radius-ulna of against gastric ulcerogenesis, J Herbal
dog”, Indian Journal of Pharmacology, 1994, Pharmacother 2005, 5, 33-42.
26(1), 44-45. 62. Austin A., Jagdeesan M., Gastric and duodenal
50. Shirwaikar A., Khan S., Malini S., antiulcer and cytoprotective effects of Cissus
Antiosteoporotic effect of ethanol extract of Cissus quadrangularis Linn. variant II in rats, Nig J Nat
quadrangularis, Journal of Ethnopharmacology, Prod Med, 2002, 6, 1-7.
2003, 89(2), 245-250. 63. Szabo S., Trier J.S., Brown A., Schoor J., Early
vascular injury and increased permeability in
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1309

gastric mucosal injury caused by ethanol in rat. 76. Hatazawa R., Tanaka A., Tanigami M., Amagase
Gastroenterology 1985, 88, 228–236. K., Kato S., Ashida Y., et al. Cyclooxygenase-
64. Jainu M., Devi CSS., Potent antiulcerogenic 2/prostaglandin E2 accelerates the healing of
activity of methanol extract of Cissus gastric ulcers via EP4 receptors, Am J Physiol
quadrangularis by antioxidative mechanism, J. Gastrointest Liver Physiol, 2007, 293, 788–97.
Clin. Biochem. Nutr. 2003, 34, 43–47. 77. Pohle T., Brozozowski T., Becker JC., Vander
65. Jainu M., Devi CSS., Effect of Cissus VIR., Markmann A., Konturek SJ., et al. Role of
quadrangularis on gastric mucosal defensive reactive oxygen metabolites in aspirin induced
factors in experimentally induced gastric ulcer—a gastric damage in humans, gastroprotection by
comparative study with sucralfate, J. Med. Food, ascorbic acid, Ali Pharm Ther, 2001, 15, 677–87.
2004, 7, 372–376. 78. Singleton VL., Orthofer R., Lamuela-Raventòs
66. Jainu M., Devi CSS., Vijaimohan K., Protective RM., Analysis of total phenols and other oxidation
effect of Cissus quadrangularis on neutrophil substrates and antioxidants by means of Folin-
mediated tissue injury induced by aspirin in rats, J. Ciocalteu reagent Methods, Enzymol, 1999, 299,
Ethnopharmacol, 2006, 104, 302–305. 152-178.
67. Anoop A., Jagdeesan M., Gastric and duodenal 79. Matsuzawa Y., Funahashi T., Nakamura T.,
antiulcer and cytoprotective effect of Cissus Molecular mechanism of metabolic syndrome X:
quadrangularis Linn. variant II in rats, Nigerian Contribution of adipocytokines adipocyte derived
Journal of Natural Products and Medicine, 2002, bioactive substances, Ann N Y Acad Sci, 1999,
6, 1–7. 892, 146-154.
68. Wallace J.L., Whittle B.J.R., Role of mucus in the 80. Furukawa S., Fujita T., Shimabukuro M., Iwaki
repair of gastric epithelial damage in the rat, M., Yamada Y., Nakajima Y., Nakayama O.,
Gastroenterology, 1986, 91, 603–611. Makishima M., Matsuda M., Shimomura I.,
69. Sanchez-Fidalgo S., Martin-Lacave I., Illanes M., Increased oxidative stress in obesity and its impact
Motilva V., Angiogenesis, cell proliferation and on metabolic syndrome, J Clin Invest, 2004, 114,
apoptosis in gastric ulcer healing. Effect of a 1752-1761.
selective COX-2 inhibitor, Eur J Pharm, 2004, 81. Brown RK., Kelly FG., Evidence for increased
505, 187–94. oxidative damage in patients with cystic fibrosis,
70. Soldato Ma L., Wallace PD., Divergent effects of Paediatric Res, 1994, 36, 487-93.
new cyclooxygenase inhibitors on gastric ulcer 82. Gutteridge JM., Swain J., Lipoprotein oxidation:
healing: shifting the angiogenic balance, Proc Natl the 'fruit and vegetable gradient' and heart disease,
Acad Sci, 2002, 99, 13243–7. Br J Biomed Sci, 1993, 50, 284-8.
71. Levi S., Goodlad RA., Lee CY., Inhibitory effect 83. Mustafa A., David E., Ksonen Laa, Diabetes,
of NSAIDs on mucosal cell proliferation oxidative stress and physical exercise, Journal
associated with gastric ulcer healing, Lancet, 1990, sports Sc Med, 2002, 1, 1-14.
336, 840–3. 84. Ngondi JL., Oben J., Musoro FD., Etame SLH,
72. Mallika J., Shyamala Devi CS., Potent Mbanya D., The effect of different combination
antiulcerogenic activity of methanol extract of therapies on oxidative stress markers in HIV
Cissus quadrangularis by antioxidative infected patients in Cameroon, Aids Research and
mechanism, J Clin Biochem Nutr, 2003, 34, 43–7. Therapy, 2006, 3, 19.
73. Szabo S., Vincze A., Growth factors in ulcer 85. Gabriel Agbor A., Oben Julius E., Ngogang
healing: lessons from recent studies, J Physiol Jeanne Y., Xinxing Cai, Vinson Joe A.,
Paris, 2000, 94, 77–81. Antioxidant Capacity of Some Herbs/spices from
74. Bernard JA., Beauchamp RD., Russell WF., Cameroon. A Comparative study of two Methods,
Dabosis RN., Coffey RJ., Epidermal growth J Agri and Food Chem, 2005, 53, 6819-6824.
factor-b related peptides and their relevance to 86. Murthy K. N. C., Vanitha A., Swami M. M. and
gastrointestinal pathophysiology, Ravishankar G. A., Antioxidant and antimicrobial
Gastroenterology, 1995, 108, 564–80. activity of Cissus quadrangularis L., J. Med. Food,
75. Yetkin G., Celebi N., Ozer C., Gonul B., Ozoul C., 2003, 6, 99–105.
The healing effect of TGF-a on gastric ulcer 87. Chidambara Murthy KN., Vanitha A., Mahadeva
induced by acetyl salicylic acid in rats, Int J Swamy M., Ravishankar GA., Antioxidant activity
Pharm, 2004, 277, 163–72.
Garima Mishra et al /Int.J. PharmTech Res.2010,2(2) 1310

of Cissus quadrangularis linn, Journal of 94. Ferrandiz M.L., Alcaraz M.J., Anti-inflammatory
Medicinal Food, 2003, 6(2), 99-105. activity and inhibition of arachidonic acid
88. Patarapanich C., Thiangtham J., Saifah E., metabolism by flavonoids, Agents and Actions,
Laungchonlatan S., Janthasoot W., Determination 1991, 32 (3–4), 283–288.
of antioxidant constituents in the herb Cissus 95. Dela Pureta R., Martinez-Dominguez E., Ruiz-
quadrangularis Linn., Ind. J. Pharm. Res., 2004, 2, Gutierrez V., Effect of minor components of virgin
77. olive oil on topical anti-inflammatory assays,
89. Pratt DE., Natural antioxidants from plant Zetschrift Fur Naturforschong, 2000, 55, 814–819.
material. In: Huang IMT, Ho CT, Lee CY, editors. 96. Mallika J., Shyamala Devi CS., Gastroprotective
Phenolic compounds in food and their effects on action of Cissus quadrangularis extract against
health. New York, American Chemical Society, NSAID induced gastric ulcer: role of
1992, 54–72. proinflammatory cytokines and oxidative damage,
90. Spiegelman BM., Flier JS., Obesity and the Biol Interact, 2006, 161, 262–70.
regulation of energy balance. Cell, 2001, 104, 531- 97. Hatazawa R., Tanigami M., Izumi N., Kamei K.,
543. Tanaka A., Takeuchi K., Prostaglandin E2
91. Kahn BB., Flier JS., Obesity and insulin stimulates VEGF expression in primary rat gastric
resistance, J Clin Invest, 2000, 106, 473-481. fibroblasts through EP4 receptors,
92. Jainu M., Devi CS., “Invitro and Invivo Evaluation Inflammopharmacology, 2007, 15, 214–7.
of free radical scavenging potential of Cissus 98. Cospite M., Double-blind, placebo-controlled
quadrangularis”, African Journal of Biomedical evaluation of clinical activity and safety of
Research, 2005, 8(2), 95-99. Daflon® 500 mg in the treatment of acute
93. Lin J., Opoku AR., Hutchings AD., Jager AK., haemorrhoids, Angiology, 1994, 45, 566–573.
Staden JV., “Preliminary screening of some 99. Diana G., Catanzaro M., Ferrara A., Ferrari P.,
traditional Zulu medicinal plant for Anti- Activity of diosmin in the treatment of
inflammatory and Anti-microbial activity”, hemorrhoids, Clinica Terapeutica, 2000, 151(5),
Journal of Ethno- pharmacology, 1999, 68, 267- 341–344.
274. 100. Lyseng-Williamson K.A., Perry C.M.,
Micronised purified flavonoid fraction: a review of
its use in chronic venous insufficiency, venous
ulcers and hemorrhoids, Drugs, 2003, 63(1), 71–
100.

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