dc.contributor.advisor |
Madyastha, K.M. |
|
dc.contributor.author |
Bhat, B. Vadiraja |
|
dc.date.accessioned |
2021-11-12T09:40:12Z |
|
dc.date.available |
2021-11-12T09:40:12Z |
|
dc.date.issued |
2001 |
|
dc.identifier.citation |
Bhat, B. Vadiraja. 2001, Bio- Modulatory Properties of : (i) C-phycocyanin, a biliprotein from spirulina platensis (ii) Novel analogues of uric acid, Ph.D thesis, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru |
en_US |
dc.identifier.uri |
https://libjncir.jncasr.ac.in/xmlui/handle/123456789/3212 |
|
dc.description |
Open access |
en_US |
dc.description.abstract |
Spirulina platensis, a blue-green algae is very well known for its nutritional and
therapeutic properties. This algae has preventive effect on the fatty liver induced by a
fructose-rich diet in the rat. C-phycocyanin, a water soluble protein pigment is one of the
major constituents of Spirulina platensis. The chromophore of phycocyanin is
phycocyanobilin (PCB), a linear tetrapyrrole which is structurally similar to the natural
antioxidant bilirubin, a heme degradation product. Although anti-cancer and antiinflammatory properties of phycocyanin have been reported, its mechanism of action is not
clearly understood. In the present study we have made an attempt to understand the
biochemical basis for some of the observed pharmacological properties of phycocyanin.
C-phycocyanin was isolated from fresh and spray dried spirulina, purified to
homogeneity (Amax/A280 > 4.0) and fully characterized (ESI-MS, 37,468 Da, monomer, aP
subunits). Detailed studies on the effect of phycocyanin on CCI4 and R-(-i-)-pulegoneinduced hepatotoxicity in rats were carried out. These studies have established: (a)
phycocyanin significantly prevents CCI4 and R-(+)-pulegone-mediated hepatotoxicity in
rats, (b) phycocyanin inhibits the formation of reactive metabolites from R-(-f-)-pulegone
responsible for the observed hepatotoxicity, (c) phycocyanin effectively inhibits CCI4-
induced lipid peroxidation in rat liver in vivo.
We have also studied the radical scavenging property of phycocyanin both in vivo
and in vitro. Native and reduced phycocyanin significantly inhibits peroxyl radical-induced
lipid peroxidation in rat liver microsomes with an IC50 of 11.35 and 12.7 |iM, respectively.
The radical scavenging property of phycocyanin was established by studying its reactivity
with peroxyl and hydroxyl radicals and also by competition kinetics of crocin bleaching.
Our studies suggest that the chromophore, phycocyanobilin (PCB) is involved in the
antioxidant and radical scavenging activity and provides an explanation for the antiinflammatory property of phycocyanin. We have also demonstrated that phycocyanin is a
selective inhibitor of cyclooxygenase-2 activity (COX-2) with potency comparable to
celecoxib and rofecoxib, the known selective COX-2 inhibitors. Phycocyanin also has the ability to efficiently scavenge peroxynitrite (ONNO"), a potent physiological toxin and its
chromophore, PCB significantly inhibits the ONOO'-mediated single strand breaks in
supercoiled plasmid DNA in a dose dependent manner with an IC50 value of 2.9 ± 0.6 ^iM.
This suggests that phycocyanin inhibits the ONOO-mediated deleterious biological effects.
Studies have also been carried out on the antioxidant, radical scavenging and iron chelating
properties of PCB. Our studies suggest that phycocyanin has the potential to be used as a
therapeutic agent.
The second part of the thesis deals with the preparation and bio-modulatory
properties of 8-0x0 derivatives of various xanthine analogues and xanthine drugs. We have
isolated a bacterial consortium consisting of strains belonging to the genus Klebsiella and
Rhodococcus which quantitatively converts various analogues of 1,3,7-trimethylxanthine
with N-1 methyl groups replaced by alkyl, hydroxethyl, benzyl, 2-oxopropyl, allyl,
propargyl and butenyl groups to their corresponding 8-0x0 compounds. The enzyme
responsible for this novel transformation, caffeine oxidase has been purified to
homogeneity. Many of the uric acids prepared by this method are hitherto not known.
These uric acids were used as test compounds to evaluate their protective potential against
lipid peroxidation and ability to scavenge oxygen free radicals. These properties are
compared with that observed from known methyluric acids and thus these studies provide
information on structure-activity relationship. Our studies clearly indicated that 8-
oxopentoxifylline and 8-oxolisofylline are significantly better hydroxyl, peroxyl and
superoxide radical scavengers and more potent inhibitors of lipid peroxidation than the
parent drugs. These results indicated that anti-inflammatory property of pentoxifylline and
lisofylline is exerted more through their 8-0x0 derivatives than the parent drugs. We have
also demonstrated that the 8-0x0 derivatives of pentoxifylline and lisofylline specifically
inhibit rabbit reticulocyte 15-lipoxygenase whereas the parent drugs failed to do that
suggesting that the anti-atherogenic property of pentoxifylline and lisofylline is exerted
through their 8-0x0 derivatives. All these studies will be discussed in detail. |
en_US |
dc.language |
English |
en |
dc.language.iso |
en |
en_US |
dc.publisher |
Jawaharlal Nehru Centre for Advanced Scientific Research |
en_US |
dc.rights |
JNCASR theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. |
en |
dc.subject |
Biological chemistry |
en_US |
dc.subject |
C-Phycocyanin |
en_US |
dc.subject |
Bio-modulatory properties |
en_US |
dc.subject |
Uric acid |
en_US |
dc.subject |
Novel analogues |
en_US |
dc.subject |
Bio-modulatory properties |
en_US |
dc.title |
Bio- Modulatory Properties of : (i) C-phycocyanin, a biliprotein from spirulina platensis (ii) Novel analogues of uric acid |
en_US |
dc.type |
Thesis |
en_US |
dc.type.qualificationlevel |
Doctoral |
en_US |
dc.type.qualificationname |
PhD |
en_US |
dc.publisher.department |
CPMU |
en_US |