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1.  Design and evaluation of herbal hepatoprotective formulation against paracetamol induced liver toxicity 
Aim
To isolate and identify the quercetin from polyherbal hepatoprotective formulation. Polyherbal formulations were developed by using five bioactive fractionated extracts of Butea monosperma, Bauhinia variegata and Ocimum gratissimum for treatment of liver disorders by exploiting the knowledge of traditional system of medicine and evaluated for hepatoprotective activity using acute liver toxicity model of paracetamol induced liver damage in rats.
Methods
Major active fractions were isolated by solvent fractionation and quantified by HPTLC method. Two polyherbal tablet formulations were developed by the wet granulation method using microcrystalline cellulose, aerosil and other excipients and subjected for physicochemical evaluation to assess physical stability followed by pharmacological screening. The prepared tablets were finally subjected to stability testing to assess its shelf-life. The rats were monitored for change in liver morphology, biochemical parameters like serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT), alkaline phosphatase (ALP) and total bilirubin for polyherbal tablet formulation at 50 mg/kg and polyherbal tablet formulation at 100 mg/kg.
Results
Active principle was isolated, quantified by HPTLC and characterized with IR. Both formulations showed significant hepatoprotective activity. The histological studies were also support the biochemical parameters. From the results of biochemical analysis and histopathological studies, it can be accomplished that polyherbal tablet formulation at 100 mg/kg can be effectively formulated into a suitable dosage form with added benefit of no side effects for control and cure of chronic ailments like liver disorders. A comparative histopathological study of liver exhibited almost normal architecture as compared to toxicant group.
Conclusion
Biochemical marker showed improved results for polyherbal tablet formulation at 100 mg/kg. Polyherbal tablet formulation contains a potent hepatoprotective agent suggested to be a flavone concentrated in polyherbal formulation which may find clinical application in amelioration of paracetamol induced liver damage.
doi:10.1016/j.jyp.2013.12.003
PMCID: PMC3930109  PMID: 24563599
Butea monosperma; Bauhinia variegata; Ocimum gratissimum; Polyherbal formulation; Hepatoprotective activity
2.  Chitosan–pectin polyelectrolyte complex as a carrier for colon targeted drug delivery 
Objective
The objective of present work was to prepare a polyelectrolyte complex (PEC) between chitosan (polycation) & pectin (polyanion) and to develop enteric coated tablets for colon delivery using the PEC.
Methodology
The PECs were prepared using different concentrations of chitosan and pectin. Drug loaded enteric coated tablets were prepared by wet granulation method using PEC to sustain the release at colon and coating was done with Eudragit S 100 to prevent the early release of the drug in stomach and intestine. Two independent variable, % PEC (chitosan/pectin) and % coating were optimized by 32 full factorial design. Statistical model were also used to supplement the optimization. DSC was performed to confirm the interaction between the polyions. Developed formulations were evaluated for physical appearance, weight variation, thickness, hardness, friability, % swelling, assay, in-vitro and ex-vivo drug release studies to investigate the PEC's ability to deliver the drug to colon. Ex-vivo release study using rat caecal content was also carried out on optimized formulation.
Results and discussion
DSC results confirmed chitosan/pectin interaction and subsequent formation of PEC. The optimized formulation containing 1.1% of PEC and 3% of coating showed highest swelling and release in alkaline pH mechanism of which was found to be microbial enzyme dependent degradation established by ex-vivo study using rat caecal content.
doi:10.1016/j.jyp.2013.11.002
PMCID: PMC3930120  PMID: 24563596
Polyelectrolyte complex (PEC); Chitosan; Pectin; Colon targeted drug delivery
3.  Genetic divergence in natural populations of bronze featherback, Notopterus notopterus (Osteoglossiformes: Notopteridae) from five Indian rivers, analyzed through mtDNA ATPase6/8 regions☆ 
Meta Gene  2013;1:50-57.
The present study characterized 842 bp fragment of mitochondrial ATP synthase 6 and 8 (ATPase6/8) genes in Notopterus notopterus. In all, 97 samples of N. notopterus were collected from five distant rivers; viz Satluj, Gomti, Yamuna, Brahmaputra and Mahanadi representing 4 river basins in India. The analysis of variation revealed presence of 23 haplotypes in ATPase6/8 gene with haplotype diversity (Hd) of 0.899 and nucleotide diversity (π) of 0.00336. The within population variation which was 41.78% of the total variation of 58.22% was found among population. The Fst value of 0.582 (P < 0.05) of the total population was found significant. The results concluded that the polymorphism in ATPase6/8 gene is a potential marker that is important for determining genetic divergence of wild N. notopterus populations. The findings reveal common ancestry of mahanadi population with the populations in rivers of Indo-Gangetic region. However, long evolutionary isolation must be responsible for the high genetic divergence between N. notopterus in Mahanadi and other regions.
Highlights
•The present study analyzed 842 bp fragment of mitochondrial ATPase6/8 genes in N. notopterus.•Analysis indicated high genetic diversity with 23 haplotypes.•The Fst value of 0.582 for total population was found significant (P < 0.05).•Five genetically distinct stocks of N. notopterus found in rivers of India.
doi:10.1016/j.mgene.2013.10.007
PMCID: PMC4205040  PMID: 25606374
ATPase, adenosine tri phosphates; DNA, deoxyribonucleic acid; dent, deoxyribonucleoside triphosphate; mtDNA, mitochondrial DNA; FAO, Food and Agriculture Organization; IUCN Red List, International Union for Conservation of Nature; CAMP, Conservation Assessment and Management Plan; Notopterus; ATPase6/8; Mitochondrial DNA; Polymorphism; Population genetic
5.  Inhibition and structure of Trichomonas vaginalis purine nucleoside phosphorylase with picomolar transition state analogues† 
Biochemistry  2007;46(3):659-668.
Trichomonas vaginalis is a parasitic protozoan purine auxotroph possessing a unique purine salvage pathway consisting of a bacterial type purine nucleoside phosphorylase (PNP) and a purine nucleoside kinase. Thus, T. vaginalis PNP (TvPNP) functions in the reverse direction relative to PNPs in other organisms. Immucillin-A (ImmA) and DADMe-Immucillin-A (DADMe-ImmA) are transition state mimics of adenosine with geometric and electrostatic features that resemble early and late transition states of adenosine at the transition state stabilized by TvPNP. ImmA demonstrates slow-onset tight-binding inhibition with TvPNP, to give an equilibrium dissociation constant of 87 pM, an inhibitor release half-time of 17.2 min and a Km/Kd ratio of 70,100. DADMe-ImmA resembles a late ribooxacarbenium ion transition state for TvPNP to give a dissociation constant of 30 pM, an inhibitor release half-time of 64 min and a Km/Kd ratio of 203,300. Tight binding of DADMe-ImmA supports a late SN1 transition state. Despite their tight binding to TvPNP, ImmA and DADMe-ImmA are weak inhibitors of human and P. falciparum PNPs. The crystal structures of the TvPNP•ImmA•PO4 and TvPNP•DADMe-ImmA•PO4 ternary complexes differ from previous structures with substrate analogues. The tight binding with DADMe-ImmA is in part due to a 2.7 Å ionic interaction between a PO4 oxygen and the N1’ cation of the hydroxypyrrolidine and is weaker in the TvPNP•ImmA•PO4 structure at 3.5 Å. However, the TvPNP•ImmA•PO4 structure includes hydrogen bonds between the 2’-hydroxyl and the protein that are not present in TvPNP•DADMe-ImmA•PO4. These structures explain why DADMe-ImmA binds tighter than ImmA. Immucillin-H is a 12 nM inhibitor of TvPNP but a 56 pM inhibitor of human PNP. And this difference is explained by isotope-edited difference infrared spectroscopy with [6-18O]ImmH to establish that O6 is the keto tautomer in TvPNP•ImmH•PO4, causing an unfavorable leaving-group interaction.
doi:10.1021/bi061515r
PMCID: PMC2517847  PMID: 17223688
6.  Draft Genome Sequence of the Sexually Transmitted Pathogen Trichomonas vaginalis 
Science (New York, N.Y.)  2007;315(5809):207-212.
We describe the genome sequence of the protist Trichomonas vaginalis, a sexually transmitted human pathogen. Repeats and transposable elements comprise about two-thirds of the ~160-megabase genome, reflecting a recent massive expansion of genetic material. This expansion, in conjunction with the shaping of metabolic pathways that likely transpired through lateral gene transfer from bacteria, and amplification of specific gene families implicated in pathogenesis and phagocytosis of host proteins may exemplify adaptations of the parasite during its transition to a urogenital environment. The genome sequence predicts previously unknown functions for the hydrogenosome, which support a common evolutionary origin of this unusual organelle with mitochondria.
doi:10.1126/science.1132894
PMCID: PMC2080659  PMID: 17218520

Results 1-6 (6)