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                    SYNOPSIS FOR
                M.PHARM DISSERTATION

                   SUBMITTED TO

                    M. PHARM PART-I



1.   Name of the candidate and            VISHWESHWAR MAHISHANKAR
     address(in block letters)
                                          NARGUND COLLEGE OF PHARMACY,
                                          DATTATREYA NAGAR, II MAIN, 100FEET
                                          RING ROAD, BSK III STAGE,

2.   Name of the institution              NARGUND COLLEGE OF PHARMACY,
                                          DATTATREYA NAGAR, II MAIN, 100FEET
                                          RING ROAD, BSK III STAGE,

3.   Course of study and subject          MASTER OF PHARMACY IN

4.   Date of the admission                8th JUNE, 2009

5.   Title of the topic:



             Obesity is abnormal or excessive fat accumulation that presents risk to health. The body
     mass index (BMI) of a person is 25-30 kg/m2 indicates overweight and above 30 kg/m2 represents
     obesity. World Health Organization (WHO) assigns obesity as global epidemic. WHO’s latest
     study indicate that globally in 2005, approximately 1.6 billion adults (15+) were overweight and at
     least 400 million adults were obese. Further WHO projects that by 2015 approximately 2.3 billion
     people will be overweight and more than 700 million will be obese1. Once it was considered that
     obesity was only in high income countries. But now a day, it is spread dramatically in medium and
     low income countries1.
             The epidemic of obesity is on the rise and this is probably due to increasingly sedentary
     lifestyles combined with easy availability of palatable, high fat foods. Its prevalence has shown a
     startling Increase in allage groups and in all the countries of the world during past 19 years. In
     1980, a Department of health Survey in U.K. showed that 6% of men and 8% of women were
     obese, as defined by a BMI >30 kg/m2. In 1995, 15% of men and 16.5% of women were
     obese and more than half of the adult population is now either overweight or obese. It has been
     predicted that if this trend continues to the year 2005, the prevalence of obesity among men and
     women would by then be 18 and 24% - exactly three times the target figure. There has also been
     an increase in comorbid risk factors like coronary heart disease, hypertension, various cancers
     (e.g., endometrium, ovaries, breast, colon), gall bladder disease, NIDDM, arthritis, respiratory
     disease, pregnancy complications, menstrual difficulties, varicose veins, psychological
     problems (poor self-esteem, depression, poor employment prospects).2-3
            The successful management of obesity is possible through lifestyle changes in diet and
     physical activity. But this requires extreme efforts. The market for safe and efficacious drug is
     therefore potentially huge, but currently available therapies are not having potential and these are
     associated with lot of side effects. Currently FDA approved only two drugs in US for long-term
     treatment for obesity. These are orlistat and sibutramine4.
                 Obesity is often associated with whole-body low-grade pro-inflammatory state,
     insulin resistance and a number of metabolic disturbances together defined as the metabolic

syndrome. In the search for mechanisms that help explain the link between obesity, insulin
resistance, and metabolic complications, it has been suggested that endocrine substances produced
by adipose tissue (adipocytokines) might play a role. Adiponectin is a 30 kDa plasma protein
secreted by mature adipocytes5 representing 0.01% of total plasma proteins6. Plasma adiponectin
levels have been shown to be reduced in type 2 diabetic patients7, insulin-resistant subjects8, obese
individuals6, as well as in coronary heart disease patients7. These findings suggest that adiponectin
has insulin-sensitizing and anti-atherosclerotic effects9. In human plasma, adiponectin circulates in
distinct multimeric complexes forming trimeric low molecular weight (LMW), hexameric medium
molecular weight (MMW), and oligomeric high molecular weight (HMW) complexes. However,
using different analytical methods, some authors distinguished only two adiponectin isoforms:
LMW and HMW8,10,12,13,2 . Adiponectin cellsurface receptors (AdipoR1, AdipoR2) are expressed
in muscle, liver, and adipose tissue14,15. In mouse myocytes and hepatocytes, adiponectin
stimulates phosphorylation and the activation of 50-AMP-activated protein kinase16, a key
regulatory enzyme in glucose and lipid metabolism, inducing glucose uptake and fatty acid
oxidation in muscle16, 17 and reducing hepatic gluconeogenesis18. Activation of different cellular
transduction pathways seems to be specific for different multimeric complexes in different
organs19, 20. Previous investigations revealed that plasma HMW adiponectin levels are positively
associated with insulin sensitivity indices12,21,13,22,23 and plasma highdensity lipoprotein cholesterol
(HDL C), while negatively associated with body mass index (BMI) and central body fat mass (11).
Mutations in the adiponectin gene associated with impaired formation of HMW complexes have
been phenotypically connected with hypoadiponectinemia and type 2 diabetes in humans20.
       . Adiponectin is 30 kDa plasma protein secreted by mature adipocytes. Plasma adiponectin
level are decreased in type 2 diabetes mellitus patients, obese individuals, and in coronary heart
disease patients. This suggest that adiponectin – insulin sensitizing and antiatherosclerotic effects.
Plasma adiponectin levels are positively associated with insulin sensitivity indices and plasma
high density lipoproteins (HDL), and plasma high density lipoprotein cholesterol (HDLC), while
negatively associated with body mass index and central body fat mass. Mutation associated with
adiponectin gene may lead impaired formation high molecular weight adiponectin and individual
suffer from type 2 diabetes mellitus10.
         From the literature survey it can be understood that an explorative investigation is
necessary to treat obesity and the obesity related metabolic syndrome such as diabetes mellitus.

Cyperous rotundus tuber extracts are suggested to be effective in reducing the body weight.Hence
an explorative investigation of aqueous extracts of C.rotundus on obesity and glucose tolerance
and the present study is envisaged.
Plant description:
     In the traditional system, it was used both in its fresh and dry form. It is also mentioned in
literature pertaining to Arabian and Persian medicines. It was known to heal ulcers and sores.
Dioscorides mentions its use as a diuretic in the treatment of ulcers, as an emmenagogue and an
ingredient in warm plasters. It was used as a perfume and an aromatic. It grows throughout

Scientific name: Cyoerus rotundus
Family : Cyperaceae
Genus : Cyperus
Species : rotundus
Synonyms : Musta

Botanical Description:
This grass like herb is found in South India. It has tubers roots or rhizomes that are fragment. It
has been mentioned in “Sahasrayoga”, prennial herb with long rhizomes, sometimes tuberous
,culms up to 60 cm tall; leaves 2-6 cm wide; spikes ovate, on rays to 6 cm long; spikletes linear,
1-2 cm long, 12-30 flowered, the rachilla winged; scales purplish, carinate, obtuse; achene sub-
obvoid, trigonal, 1.5 mm long, black, minutely papillate36.

Plant chemicals:
The C. rotundus have been reported to contain oils, alkaloids, glycosides, saponins, flavonoids,
tannins, starch and carbohydrates. It also contains proteins and traces of Mg, V, Cr, Mn and Co.
The rhizome oils of C. rotundus from India were reported to have α-copaene (11.4-12.1%),
cyperene (8.4-11.7%), valerenal (8.7-9.8%), caryophyllene oxide (7.8-9.7%) and trans-
pinocarveol (5.2-7.4%), some of which were absent in the species from other countries. The
essential oil of C. rotundus from Germany, and found the oil to be dominated by cyprotene, α-

copaene, cyperene, α-selinene, rotundene, cadalene and nootkatene, among others35.
         Ngamrojanavanich et al.,(2006)           reported the inhibitory effect of hexane extract of
cyperus rotundus and other medicinal on Na+K+ ATPase pump.The hexane extract of C.rotundus
and Orthosiphon aristatus showed high potent inhibitory activity on crud e enzyme Na+,k+-
ATPase from rat brain.41
         Uddin et al ,(2006) observed the antidiarrhoeal activity of C.rotundus.The methanol
extract of c.rotundus rhizome ,given orally at the doses of 250 and 500 mg/kg body weigh,showed
significant antidiarrhoeal activity in castor oil induced diarrhoea in mice.among the fractions
,tested at 250mg/kg ,the petroleum ether fraction and residuai methano fraction were found to
retain the activity,the lattrr being more active as compared to the control.The ethyl acetate fraction
did not show any antidiarrhoeal activity.42
         Natarajan et al.(2006) reported the antioxidant activity of C.rotundus and other medicinal
plant against free radical induction.A combination of speacies (piper nigram,p.longum and
zingiber officinale) herbs(C.rotundus and plumbago zeylanicam) and salts makes up Amrita bindu
. These result reveal that Amrita bindu , a salt –spice-herbal mixture exerts a promising antioxidant
potential againsts free radical induced oxidative damage.43
         Duarte et al.,(2005) reported the anti-candida activity of C.rotundus .44           .
         Jagtap et al.,(2004) observed the effect of polyherbal formulation containing C.rotundus
on experimental models of inflammatory bowel disease. The formulation showed significant
inhibitory activity against inflammatory bowl disease induced in these experimental animal
models. The activity was comparable with the standard drug prednisolone. The results obtained
established the efficacy of this poly herbal formulation against inflammatory bowel diseases.45
         Haung and Peng(2003) observed the advances in the study of chemical constituents and
pharmacology of C.rotundus L.46
         Bamgbose et al. (2003) studied the utilization of tigernut ( C. rotundus, L.) meal in diets
for cockerel starters. The effect of feeding graded levels of tigernut meal (TGN) as a replacement
for the maize in the diets of cockerel starters on carcass characteristics and economics of feed
conversion was assessed for 70 days. Tigernut replaced maize at 0 %, 33.33%, 66.67% and 100%
levels. A total of 120 day-old chicks were randomly allotted to four experimental diets such that
each dietary treatment had three replicates of ten birds. Inclusion of TGN at 33.33% in cockerel
diets supported better carcass yield in terms of high plucked, eviscerated, drumstick, thigh, neck,

wings, heads, shanks, livers, hearts and lungs weights without significance differences (P>0.05) in
values obtained. However, there were significant difference (P<0.05) in values obtained. However,
there were significant difference (P<0.05) in back, breast, abdominal fat, gizzard, spleen, kidney
and intestinal weights and lengths. Inclusion of        TGN 100% level significantly depressed
parameters assessed. The optimum replacement level of maize with TGN was 33.33% as this gave
no significant reduction in carcass yield of the birds but a significant reduction in the cost of feed
consumed. It required a feed cost of 0.31 US dollars to produce one kilogram weight gain on diet 2
(33.33%). Inclusion of TGN in the diet resulted in feed cost saving of 4.88% (D2), 8.17 (D3) and
8.90% (D4) respectively.47
        Ha et al. (2002) studied the four sesquiterpenes, beta-selinene, isocurcumenol, mootkatone
and aristolone and one triterpene, oleanolic acid were isolated from the ethyl acetate fraction of the
rhizomes of C. rotundus      and tested for their ability to modulate gamma- aminobutyric acid
(GABA(A)-benzodiazepine receptor function by radioligand binding assays using rat cerebro
cortical membranes. Among these compounds, only isocurunenol, one of the newly identified
constituents of this plants, was found to inhibit (3H)Ro15-1788 binding and enhance
(3H)flunitrazepam binding in the presence of GABA. These results suggest that isocurcunenol
may serve as a benzodiazepine receptor agonist and allosterically modulate               GABAargic
neurotransimission via enhansiment of endegenous receptor ligand binding.48
         Seo et al. (2001) studied that rhizomes of C. rotundus have been used in oriental
traditional medicines for the treatment of stomach and bowel disorders, and inflammatory
diseases. Nitric oxide and super oxide are are important mediators in the pathogenesis
inflammatory diseases. This study was undertaken to addresses weather the methanol extracts of
rhizomes of C. rotundus could modulate NO and O-2 productions by murine macrophsge cell line,
RAW 264.7 cells. The MeOH extract of rhizomes of C. rotundus showed the inhibition of NO
production in a dose-dependent manner by RAW 264.7 cells stimulated with interferon-gama plus
lipopolysaccharides. The inhibition ofNO production by the extract was due to the suppresssion of
iNOS protein, as well as iNOS mRNA expression, determined by western and northen blotting
analysis, respectively. In addition the MeO Of O2- by phorbol ester-stimulated RAW 264.7 cells in
dose- and time – dependent manners. Collectively, these results suggested that the MeOH extract
of rhizomes of C. rotundus could be developed as anti-inflammatory candidate for the treatment of
inflammatory diseases mediated by overproduction of NO and O2-.49

          Hsieh et al. (2000) investigated the ameliorating effects of the cognitive-enhancing
Chinese herbs administrated orally for 1 week-panax ginseng (pg), panax notoginseng (PNG),
Dioscorea opposite (DO). Gastrodia elata (GF), salvia miltiorrhiza (SM), acorus gramineus (AG),
coptis chinensis (CC), Polygonum multiflorum(pm), cyperus rotundus (CR) and psoralea
corylifolia(PC)-on the scopolamine(SCOP)-induced amnesia by using passive avoidance task in
rats.Often Chinese herbs,only PG,PNG,GE and CC prolonged SCOP-shortened step-through
latency(STL).these results revealed that PG,PNG,GE and CC administered orally for 1 week
improved the SCOP-induced learning and memory deficit in rats.50
          Jeong et al.(2000) observed Rotendines A(1),B(2),and C(3) the novel sesquiterpene
alkaloids with an unpresident carbon skeleton, were isolated from the rhizomes of C.rotendes. the
structure of 1-3 were elucidated by spectral and chemical methods.51
          Bamgbos et al(1997)observed the effect of feeding tagenut(C.rotundus L)meal on the
performance of rabbits.52
          Thebtaranonth et     al.(1995) performed activity –guided investigation of C.rotendus
tubers led to the isolation of pactchoulenone,cariyophyllene-alpha-oxide,10,12-paraoxycalamene
and 4,7-di methyl-1-tetralone.The anti-malarial activity of these compounds are in the range of
EC50 10(-4)-10(-6) M,with the novel edoperoxide sesquiterpene ,10,12-peroxy calamenene,
exhibiting the strongest effect at EC50 2.33 10(-6) M.53
          Xue    et   al.(1994)   reported   the   effect   of   the   combination   of   Astragalus
membranaceus(fisch) Bge. (AM), Angelica sinensis (oliv.) Diels (TAS) , Cyperus rotundus L,
(CR), Ligusticum chuangxiong hort (LC) and peaonia veitchii Lynch (PV) on the
hemorrhcological changes in “blood stagnating” rats.54
          Xue et al.(1994) built the “blood stagnating” rat model with adrenalin and cold
stimulation. Its hemorrhcological character was an increase in the viscosity , thickness of blood
and its liability to coagulate . the experimental result showed that AM and TAS could decrease the
whole blood specific viscosity, but at the same time increase the plasma specific viscosity. the Qi-
regulating drug CR and two blood activating drug LC and PV could improve the hemorrhcological
changes in “blood stagnated” rats .the combination of qi- regulating drugs and blood-activating
drugs had more favorable effect.55
        Study on analgesic effect of C.stoloniferus Retz, was reported by VU and Mai (1994). The
decocts of rhizomes of C.rotundus and C.stoloniferus and total alkaloids and essential oil from C.

stoloniferus showed analgesic effect in the acetic acid writhing test . the oral LD50 of essential oil
of C.stoloniferus in mice was 12.1 ml./Kg.56
        Shinde et al.1988 reported the effect of Nagarmotha (C rotundus Linn) on reserpine
induced emesis in pigeons.57
       Biologically active substances in subterranean parts of purple nutssedge is reported by
Friedman and Horowitz 1971 as the growth of barley( hordeum disichon var eszperanza) seedlings
in nutrient solution was reduced by purple nutsedge (cyperus otundus) plants growing in
connected vials and by addition of ethanol extract of purple nutsedge, aqueous and ethanol extract
from subterranean parts of purple nutsedge red seed the germination and root elongation of barley.
Stimulations of barley root elongation were obtained with diluted aqueous extract the germination
of barley, mustard( brassica nigra var Alsace,) and cotton (Gossypium hirsutum var acala 1517)
was reduced in soil which had been infested previously with purple nutsedge. Radical elongation
of barley was inhibited by ethanol extract of soil previously infested. Chromatographic studies
indicated that the inhibitors are phenolic substances.58
     Gupta et al.(1971) performed pharmacological studies to isolate the active constituents from
c. rotundus possessing anti inflammatory, antipyretic and analgesic activities.59
       Lee et al.(1970) characterized ferredoxin from nutsedge, c.rotundus L, and other species
with a high photosynthetic capacity. Singh et al.(1970) investigated pharmacological activites of
       Akperoekova and abdullaev (1966) reported the diuretic effect of drug from and galenicals
from the roots of cyperus rotundus growing in azerbaidzhan. The chemical composition of dry
roots was as follows: alkaloids 0.21-0.24, heart glycosides 0.62-0.74 flavonoids 1.25, polyphenolic
compounds 1.62, saccharides before hydrolysis 13.22, saccharides after hydrolysis 14.4, starch
9.2, pectins 3.72, ethereal oils 1.06, lipid compounds 2.98, resins 4.21, total acidity expressed as
malic acid3.25% and vitamin c 8.8mg%. the water extract were nontoxic for white mice; the LD50
of the alcohol extract (2:1) was determined as 90g/kg. both the drug form and galenicals increased
diuresis was induced by administration of resins, alkaloids(39.6) polyphenolic compounds,
flavonoids and ethereal oils and glycosides(11.6%) list and horhammer,(1969-1979).61
        Indira et al. (1956) reported the occurrence of estrogenic substance in plants. L. estrogenic
activity of cyperus rotundus. The oil of c. rotundus exhibits low order estrogenic activity. The
hydrocarbon fraction is more active than other fractional distillates, but none of the components

was found as active as the oil. The probability of these compounds being proestrogens is indicated
by the ratio of systemically active to locally effective concentration. No correlation exists between
antibacterial activity and estrogenic potency of the oil and its fraction.62

1. Preparation of cyperus rotundus aqueous extracts
2. To evaluate the effect of aqueous extracts of C.rotundus on pancreatic lipase activity.
3. To induce Cafeteria diet / High fat diet fed obesity in Wistar rats of either sex and evaluate the
   effect of aqueous extracts of C.rotundus against weight gain / loss and effects of the extracts
   on adipositic fat deposition.
4. To evaluate the effect of aqueous extracts of C.rotundus on glucose tolerance levels in obese
   wistar rats.
5. To evaluate the effect of aqueous extracts of C.rotundus on the Adepokine ie., Adiponectin
   levels in obese diabetic rats.


7.1 Source Of Data :
       Whole work is planned to generate data from laboratory studies i.e. experiments are
performed as described in references. Experimental studies in journals and in text books available
with college and various institutions.
Web sites: http://




Measurement of pancreatic lipase activity.
Lipase activity is determined by measuring the rate of release of oleic acid from triolein. Briefly, a
suspension of triolein (80 mg), phosphatidylcholine (10 mg) and taurocholic acid (5 mg) in 9 mL
of 0.1 mol/L N-tris (hydroxymethyl) methyl-2-aminoethanesulfonic acid buffer (pH 7.0)
containing 0.1 mol/L NaCl was sonicated for 5 min. This sonicated substrate suspension (0.1 mL)
was incubated with 0.05 mL (10 U) of pancreatic lipase and 0.1 mL of various concentrations of
sample solutions for 30 min at 37°C in a final volume of 0.25 mL. The amount of oleic acid
released was determined by the method of Zapf et al. (1981) with a slight modification (Tsujita
and Okuda 1983). The incubation mixture was added to 3.0-mL aliquots of a 1:1 (v/v) mixture of
chloroform and n-heptane containing 2% (v/v) methanol and extracted by shaking the tubes
horizontally for 10 min in a shaker. The mixture was centrifuged at 2000 3 g for 10 min, and the
upper aqueous phase was removed by suction. Copper reagent (1.0 mL) was then added to the
lower organic phase. The tube was shaken for 10 min, the mixture was centrifuged at 2000 3 g for
10 min and 0.5 mL of the upper organic phase, which contained copper salts of the extracted free
fatty acids, was treated with 0.5 mL of 1 g/L bathocuproine in chloroform containing 0.5 g/L
hydroxyanisole. The absorbance was then measured at 480 nm. Lipase activity was expressed as
moles of oleic acid released per liter of reaction mixture per hour.63

Animals: Either sex Wistar rats (80 to 120 g)
No of animals: 30
Housing: 5 / cage, 12 hrs light/dark cycle
Temperature: 22±20c
Food: pellet chow and water.
I1.Diet induced obesity
Following groups will be made
Group 01: control
Group 02: Cyperus rotundus

Group 03: cafeteria diet
Group 04: cafeteria diet + Cyperus rotundus extract
Group 05: cafeteria diet + streptozocin
Group 06: cafeteria diet + streptozocin + C. rotundus

Parameters tested with procedure:
1. Body weight: The body weight (g) was recorded on day 1 and then on alternate days for 40
days in each group.
2. Body temperature: The body temperature was recorded on day 39 using rectal telethermometer
before and after drug administration at 30, 60, 90, 120 and 180 min with a contact time of 1
3. Locomotor activity: It was recorded on day 40 using open field behaviour test apparatus and
30 min after drug administration to treatment groups. The apparatus consisted of a circular
wooden arena of 75 cm diameter and wall with a height of 25 cm. Open field test was performed
by placing the rat in the center circle and recording the ambulatory activity, the frequency of
rearing and grooming for a 5 min test period.
4. Organ weight: The animals were sacrificed by cervical dislocation and then different organs
(kidney, liver, heart, spleen) and fat pads (mesenteric, left and right perirenal and uterine fat pads)
were removed and weighed.
5. Biochemical parameters:
Glucose, Total cholesterol, Triglyceride level, LDL, HDL, Glucose tolerance test. Adeponectin by

The mean values ±SEM will be calculated for each parameter. The data was analyzed using one-
way analysis of variance (ANOVA).

7.4 Does the study require any investigation to be conducted on patients or other humans or
animals? If so please describe briefly.
Yes, The above study requires investigation on animals. The study may involve sacrifice of
animals at the end of the studies to measure end point indicators.

7.5 Has ethical clearance been obtained from your institution in case of 7.3?
Application has been submitted to “Institutional Animal Ethics Committee” Nargund College of
Pharmacy, Bangalore. Clearance certificate as and when granted by the IAEC will be submitted to
the university.


  2. Mason P. Obesity - new insights into a growing problem. Pharmaceu J 1997;258:800-2.
  3. 5. Bjorntop P. Obesity. Lancet 1997;350:423-6.
  4. Dunstan Cooke, Steve Bloom; The obesity pipeline: Current strategies on the development
     of ant-obesity drugs; Nature reviews drug discovery 2006 November; 5: 919-931.
  5. Scherer PE,Williams S, FoglianoM, Baldini G & LodishHFM.Anovel serum protein
     similar to C1q, produced exclusively in adipocytes. Journal of Biological Chemistry 1995
     270 26746–26749.
  6. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I,
     Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K,
     Muraguchi M, Ohmoto Y, Funahashi T & Matsuzawa Y. Paradoxical decrease of an
     adipose-specific protein, adiponectin, in obesity. Biochemical and Biophysical Research
     Communications 1999 257 79–83.
  7. Hotta K, Funahashi T,AritaY, TakahashiM,MatsudaM, OkamotoY, Iwahashi H, Kuriyama
     H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K,
     Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T & Matsuzawa Y.
     Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic
     patients. Arteriosclerosis, Thrombosis, and Vascular Biology 2000 20 1595–1599.
  8. Abbasi F, Chu JW, Lamendola C, McLaughlin T, Hayden J, Reaven GM & Reaven PD.
     Discrimination between obesity and insulin resistance in the relationship with adiponectin.
     Diabetes 2004 53 585–590.
  9. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M,
     Kuriyama H, Kishida K, Nishizawa H, Hotta K, MuraguchiM,OhmotoY, Yamashita S,
     Funahashi T &MatsuzawaY. Adipocyte-derived plasma protein, adiponectin, suppresses
     lipid accumulation and class A scavenger receptor expression in human monocyte-
     derivedmacrophages. Circulation 2001 103 1057–1063.
  10. Bobbert T, Rochlitz H,Wegewitz U, Akpulat S, Mai K,Weickert MO, Mohlig M, Pfeiffer
     AF & Spranger J. Changes of adiponectin oligomer composition by moderate weight
     reduction. Diabetes 2005 54 2712–2719.

11. Korner A, Wabitsch M, Seidel B, Fischer-Posovszky P, Berthold A, Stumvoll M, Bluher
   M, Kratzsch J & Kiess W. Adiponectin expression in humans is dependent on
   differentiation of adipocytes and down-regulated by humoral serum components of high
   molecular weight. Biochemical and Biophysical Research Communications 2005 337 540–
12. Lara-Castro C, Luo N, Wallace P, Klein RL & Garvey WT. Adiponectin multimeric
   complexes and the metabolic syndrome trait cluster. Diabetes 2006 55 249–259.
13. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP, Wagner JA, Wu
   M, Knopps A, Xiang AH, Utzschneider KM, Kahn SE, Olefsky JM, Buchanan TA &
   Scherer PE. Complex distribution, not absolute amount of adiponectin, correlates with
   thiazolidinedione-mediated improvement in insulin sensitivity. Journal of Biological
   Chemistry 2004 279 12152–12162.
14. Fu Y, Luo N, Klein RL & Garvey WT. Adiponectin promotes adipocyte differentiation,
   insulin sensitivity, and lipid accumulation. Journal of Lipid Research 2005 46 1369–1379.
15. Yamauchi T, Kamon J, Ito Y, Tsuchida A, Yokomizo T, Kita S, Sugiyama T, Miyagishi
   M, Hara K, Tsunoda M, Murakami K, Ohteki T, Uchida S, Takekawa S, Waki H, Tsuno
   NH, Shibata Y, Terauchi Y, Froguel P, Tobe K, Koyasu S, Taira K, Kitamura T, Shimizu
   T, Nagai R & Kadowaki T. Cloning of adiponectin receptors that mediate antidiabetic
   metabolic effects. Nature 2003 423 762–769.
16. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S, Yamashita S, Noda M,
   Kita S, Ueki K, Eto K, Akanuma Y, Froguel P, Foufelle F, Ferre P, Carling D, Kimura S,
   Nagai R, Kahn BB & Kadowaki T. Adiponectin stimulates glucose utilization and
   fattyacid oxidation by activating AMP-activated protein kinase. Nature Medicine 2002 8
17. Winder WW & Hardie DG. AMP-activated protein kinase, a metabolic master switch:
   possible roles in type 2 diabetes. American Journal of Physiology 1999 277 E1–E10.
18. Lochhead PA, Salt IP, Walker KS, Hardie DG & Sutherland C. 5-Aminoimidazole-4-
   carboxamide riboside mimics the effects of insulin on the expression of the 2 key
   gluconeogenic genes PEPCK and glucose-6-phosphatase. Diabetes 2000 49 896–903.
19. Tsao TS, Tomas E, Murrey HE, Hug C, Lee DH, Ruderman NB, Heuser JE & Lodish HF.
   Role of disulfide bonds in Acrp30/adiponectin structure and signaling specificity. Different

   oligomers activate different signal transduction pathways. Journal of Biological Chemistry
   2003 278 50810–50817.
20. Waki H, Yamauchi T, Kamon J, Ito Y, Uchida S, Kita S, Hara K, Hada Y, Vasseur F,
   Froguel P, Kimura S, Nagai R & Kadowaki T. Impaired multimerization of human
   adiponectin mutants associated with diabetes. Molecular structure and multimer formation
   of adiponectin. Journal of Biological Chemistry 2003 278 40352–40363.
21. Matsubara M, Katayose S & Maruoka S. Decreased plasma adiponectin concentrations in
   nondiabetic women with elevated homeostasis model assessment ratios. European Journal
   of Endocrinology 2003 148 343–350.
22. Tschritter O, Fritsche A, Thamer C, Haap M, Shirkavand F, Rahe S, Staiger H, Maerker E,
   Haring H & Stumvoll M. Plasma adiponectin concentrations predict insulin sensitivity of
   both glucose and lipid metabolism. Diabetes 2003 52 239–243.
23. von Eynatten M, Hamann A, Twardella D, Nawroth PP, Brenner H & Rothenbacher D.
   Relationship of adiponectin with markers of systemic inflammation, atherogenic
   dyslipidemia, and heart failure in patients with coronary heart disease. Clinical Chemistry
   2006 52 853–859
24. Gurpreet Kaur, Kulkarni SK; Antiobesity effect of polyherbal formulation OB-200G in
   female rats fed on cafeteria and atherogenic diets; Indian Journal Pharmacology; 2000; 32:
25. Nishikant A. Raut, Naresh J. Gaikwad, Antidiabetic activity of hydro-ethanolic extract of
   Cyperus rotundus in alloxan induced diabetes in rats, Fitoterapia , 2006; 77:585–88.
26. Soumaya K, Ribai BA, In`es B, Afef A, Nawel H, Amor M, Kamel G, Leila C G ,
   Investigation of extracts from (Tunisian) Cyperus rotundus as antimutagens and radical
   scavengers, Environmental Toxicology and Pharmacology 2005; 20:478–484.
27. Wei XH, Chenga XM, Shen JS, Wang ZT; Antidepressant effect of Yueju-Wan ethanol
   extract and its fractions in mice models of despair, Journal of Ethnopharmacology 2008;
28. Kavithalakshmi SN, Madhusudhanan N, Shanmugasundaram RK, Shanmugasundaram
   ERB, Antioxidant activity of a salt–spice–herbal mixture against free radical induction,
   Journal of Ethnopharmacology 2006; 105:76–83
29. Puratchikody A., NithyaDevi C., Nagalakshmi G, Wound healing activity of Cyperus

   rotundus Linn., Indian Journal of Pharmaceutical Sciences 2006; 68 (1):97-101.
30. Polak J, Kovacova Z, Holst C, Verdich C, Astrup A, Blaak E, Patel K, Oppert J M, Langin
   D, Martinez JA, Sørensen TI A and Stich V, Total adiponectin and adiponectin multimeric
   complexes in relation to weight loss-induced improvements in insulin sensitivity in obese
   women: the NUGENOB study, European Journal of Endocrinology 2008; 158:533–541
31. Pharmacological investigations of certain medicinal plants and compounds formulations
   used in Ayurveda and Siddha, Central council for research in Ayurveda and Siddha,
   Departmant of Indian systems of medicine and homeopathy, Ministry of Health and family
   welfare, Govt. of India, New Delhi, 1st edition,1996, 236-239.
32. Sharma R, Gupta R, Cyperus rotundus extract inhibits acetylcholinesterase activity from
   animal and plants as well as inhibits germination and seedling growth in wheat and tomato,
   Life Sciences 2007; 80:2389–2392.
34. Dilip KP, Determination of brain biogenic amines in Cynodon dactylon pers. And Cyperus
   rotundus l. Treated mice, Indian journal of Pharmacy and Pharmaceutical Sciences, 2009;
35. Oladipupo A. Lawal and Adebola O. Oyedeji, Chemical Composition of the Essential Oils
   of Cyperus rotundus L. from South Africa, Molecules 2009; 14: 2909-2917
36. Stone B. The flora of Guam; 1970; 6:167
37. Hson-Mon-Chang, Pui P, But H. Pharmacology and application of Chinese Materia
   medica, 1987; 2:893-895.
38. Dhawan BN, Dubey MP, Malhotra BN, Rastogi RP, Tandon JS, Screening of Indian plants
   for biological activity, Indian Journal of Experimental Biology, 1980; 18:594-606.
39. Chang IM, Yun HS, Plants with liver protective activities, Pharmacologyand toxicology of
   aucubin, Advances in Chinese Medicinal Materials Research World Scientific Press,
   Philadelphia, pp 269-285.
40. Shinde S., Phadke S, Bhagwat AW, Effect of Nagarmotha (Cyperus rotundus) on reserpine
   –induced emesis in pigeons, Indian Journal of Physiol. Pharmacol. 1988; 32(3):229-30.
41. Ngamrojanavanich N, Manakit S, Pompakakul S , Petsom A Inhibitory effects of selected
   Thai medicinal plants on Na+ K+ ATPase . Fitoterapia,. 2006; 77(6): 481-3
42. Uddin SJ, Mondal K, Shilpi JA, Rahman MT Antidiarrheoel activity of Cyperus rotundus.

   Fitoterapia 1972; 77(2):134-6.
43. Natarajan KS, Narasimhan M, Shanmugasundaram KR, Shamugasundaram ER,
   Antioxidant acivity of salt-spice-herbal mixture against free radical induction. J.
   Ethamopharmacol. 2006; 105(1-2):76-83.
44. Duarte J, Torres AJ, Zarzuelo A Cardiovascular effects of visnogen on rats. Plant Medica.
   2000; 66:35-39.
45. Jagtap AG, Shirke SS, Phadke AS Effectsof polyherbal formulation on experimental
   models of inflammatory bowel diseases. J. Ethmopharmacol. 2004; 90(3):195-204.
46. Huang X, Peng G Advances in the study of chemical constituients and pharmacology
   Cyperus rotundus. Zhong Yao Cai. 2003; 26(1):65-8.
47. Bamgbose AM, Nwokoro SO, Kudi AC, Bogoro S, Egbo ML, Kushwaha S Effect of
   feeding tagernut (Cyperus rotundus) meal on the performance of rabbits. Trop. Anim.
   Health Prod. 1997; 19(1):60-2
48. Ha JH, Lee KY, Choi HC, Cho J, Kang BS, Lim JC, Lee DU Modulation of radioligand
   binding to the GABA(A)-benzodiazepine receptor complex by a new component from
   Cyperus rotundus. Biol. Pharm. Bull., 2002; 25(1):128-130.
49. Seo WG, Pae HO, Oh GS, Chai KY, Kwon TO, Yun YG, Kim NY, Chaung HT Inhibitory
   effects of methanol extracts of Cyperus rotundus Rhizomes on nitric oxide and superoxide
   productions by murine macrophage cell line, RAW 264.7 cells. J. Ethmopharmacol., 2001;
   76(1): 59-64.
50. Hsieh MT, Peng WH, Wu CR, Wang WH The ameliorating effects of the cognitive-
   enhancing Chinese herbs on scopolamine-induced amnesia in rats. Phytother. Res., 2000;
   14(5): 375-7.
51. Jeong SJ, Miyamoto T, Inagaki M Kim YC, Higuchi R Rotundines A-C, three novel
   sesquiterpene alkaloids from Cyperus rotundus. J. Nat. Prod. 2000; 63(5):673-675.
52. Bamgbose AM, Nwokoro SO, Kudi AC, Bogoro S, Egbo ML, Kushwaha S Effect of
   feeding tagernut (Cyperus rotundus) meal on the performance of rabbits. Trop. Anim.
   Health Prod. 1997; 19(1):60-2
53. Thebtaranonth C, Thebtaranonth Y, Wanauppathamkul S, Yuthavong Y Antimalarial
   sesquiterpenes from tubers of Cyperus rotundus : Structure of 10, 12-peroxycalamene, a
   sesquiterpene endoperoxide. Phytochemistry, 1995; 40(1): 125-128.

54. Xue JX, Yan YQ, Jiang Y Effects of combination of Astragalus membranaceus
   (Fisch.)Bge. (AM) Angelica Sinesis (Oliv.) Diels (TAS) Cyperus rotundus (CR)
   Ligusticum chuangxiong Hort (LC) and Peaonia veitchii lynch (PV) on the
   haemorrheological changes in normal rats. Zhongguo Zhong YAo Za Zhi 1994; 19(2):108-
   10, 128.
55. Xue JX, Yan YQ, Jiang Y Effects of combination of Astragalus membranaceus
   (Fisch.)Bge. (AM) Angelica Sinesis (Oliv.) Diels (TAS) Cyperus rotundus (CR)
   Ligusticum chuangxiong Hort (LC) and Peaonia veitchii lynch (PV) on the
   haemorrheological changes in normal rats. Zhongguo Zhong YAo Za Zhi 1994; 19(2):108-
   10, 128.
56. Vu VD, Mai TT Study on analgesic effects of Cyperus stoloniferus Retz.(Ha Noi
   Pharmaceutical M Vietnam) Tap Chi Duoc Hoc. 1994; 1:16-17.
57. Shinde S, Phadke S, Bhagwat AW Effects of Nagamotha (Cyperus rotundus) on reserpine
   induced emesis in pigeons. Indian J. Physiol. Pharmacol. 1988; 32(3):229-230
58. Friedman T, Horowitz M Boilogically active substances in subterranean parts of purple
   nutsedge. (volcani Inst. Agric Res., Bet Dasgan, Israel) Weed Sci., 1971; 19(4): 398-401
59. Gupta S, Yadava JNS, Tandon JS Antisecretory (antidiarrheal) acivity of Indian medicinal
   plant? Against Escherichia coli rnterotoxin induced secretion in Rabbit and Guinea pig
   ileal lop models. Inst. J. Pharmacog. 31(3): 198-204.
60. Lee SS, Travis J, Black CC Jr. Characterization of ferredoxin from nutsedge, Cyperus
   rotundus and other species with a high photosynthetic capacity. Arch. Biochem. Biophys.
   1970; 141(2):676-89.
61. Akperbekova BA, Abdullaev RA Diuretic effects of drug from and galenicals from the
   roots of Cyperus rotundus growing in Azerbaidzhan. Izv. Akad. Nauk. Azerb. SSR, Ser.
   Biol. Nauk, 1966; 4:98-105.
62. Indira M, Sirsi M, Randomir S and Dev S Occurrence of estrogenic substances in plants I.
   Estrogenic activity of Cyperus rotundus. J. Sci. Ind. Res. 1956; 15C:202-4.
63. Li-Kun Han, Bao-Jun Xu, Yoshiyuki Kimura, Yi-nan Zheng and Hiromichi Okuda,
   Platycodi Radix Affects Lipid Metabolism in Mice with High Fat Diet–Induced Obesity,
   American Society for Nutritional Sciences. 24 July 2000; 2760-2764


                                        VISHWESHWAR M DHARASHIVE

10.   REMARKS OF THE GUIDE                         RECOMMENDED


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      11.3 CO-GUIDE (IF ANY)                           ------

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                                              Mr. H.J.HRISHIKESHAVAN PhD
      11.5 HEAD OF THE
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                                                DEPT. OF PHARMACOLOGY
                                            NARGUND COLLEGE OF PHARMACY,

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