Biomedical subjects
Publications and source records attributed to Preeti Sharma.
In a program to identify new anti-ulcer compounds, a series of N-acyl derivatives of alpha-amino acids were screened for their in vitro H(+)/K(+) ATPase inhibitory activity, and in vivo efficacy in Pylorus ligation model. 3D-QSAR studies were carried out and a representative compound 13 was studied for the nature of its proton pump inhibition.
Larvicidal potential of petroleum ether (Pee), carbon tetrachloride (Cte) and methanol extract (Mee) of Artemisia annua, Chenopodium album and Sonchus oleraceus was observed against malaria vector, Anopheles stephensi Liston. The Pee of A. annua with LC50 16.85 ppm after 24 h and 11.45 ppm after 48 h of treatment was found most effective, followed by Cte of A. annua and Ch. album, Pee of Ch. album and Mee of A. annua. However, no significant larvicidal activity was observed in Mee of Ch. album and all the three extracts of S. oleraceous. The Pee of A. annua was further investigated for its effect on the metamorphosis and the development of the malaria vector. It influenced the early life cycle of An. stephensi by reducing the percentage of hatching, larval, pupal and adult emergence and also lengthening the larval and pupal periods. The growth index was also reduced significantly. As the extract has remarkable effect on the metamorphosis and high larvicidal potential, it could, therefore, be used as an effective biocontrol agent against the highly nuisant malaria vector.
Mosquito larvicidal activity of crude carbon-tetra-chloride, methanol and petroleum ether extracts of Solanum xanthocarpum fruits was examined against Anopheles stephensi and Culex quinquefasciatus. Among the extracts tested, carbon-tetra-chloride extract was the most effective with LC50 values of 5.11 ppm after 24 hours and 1.27 ppm after 48 hours of treatment against An. stephensi. In the case of Cx. quinquefasciatus the petroleum ether extract was observed as most toxic with LC50 values of 62.62 ppm after 24 hours and 59.45 ppm after 48 hours of exposure period respectively. It is, therefore, suggested that S. xanthocarpum can be applied as an ideal potential larvicide against An. stephensi and Cx. quinquefasciatus.
Ethanolic and acetone extracts of Nerium indicum and Thuja orientelis have been studied against III instar larvae of Anopheles stephensi and Culex quinquefasciatus. Ethanolic extract of N. indicum is found more effective than its acetone extract against anopheline larvae with LC50 values of 185.99 and 148.05 ppm for former and 229.28 and 149.43 ppm for the later after 24 and 48 hrs of exposure. The acetone extract with LC50 values of 209.00 and 155.97 ppm is more effective in case of culicine larvae than its ethanolic extract with LC50 494.07 and 194.49 ppm after 24 and 48 hours of treatment. Ethanolic extract of T. orientelis is more effective against both the larval species with LC50 values of 13.10 and 9.02 ppm after 24 and 48 hours for anopheline and 22.74 and 16.72 ppm against culicine larvae. The acetone extract showed LC50 values of 200.87 and 127.53 ppm against anopheline and 69.03 and 51.14 ppm against culicine larvae. Thus ethanolic extract of T. orientelis is an ideal potential larvicide for both types of mosquito larvae.
The effect of ABA on reserve accumulation in maturing somatic embryos of tea was compared with and without ABA treatment. Changes in the levels of starch, total soluble sugars (TSS), proteins, and phenols were studied in the somatic embryos at different stages of development (globular, heart, torpedo and germinating embryos) in order to investigate whether ABA could trigger accumulation of storage reserves and thereby overcome the problem of poor germination. After ABA treatment (5.0 mg l(-1)) for 14 days, the starch and protein contents that were negligible in the untreated embryos increased by several fold with a simultaneous increase in TSS. When ABA treatment occurred at the heart stage, the germination of the embryos also improved, relative to untreated controls, after ABA treatment. ABA treatment prior to or after heart stage did not improve somatic embryo germination.
The characteristic feature of visceral leishmaniasis (VL) is the profound impairment of immune system of the infected host, which contributes significantly to the partial success of antileishmanial chemotherapy. Since in VL, cure is the combinatorial effect of drug and immune status of the host, the rationale approach towards antileishmanial chemotherapy would be to potentiate the immune functioning of the host to extract desired results. Towards this direction several rationally designed analogues of human beta-casein fragment (54-59) were evaluated for their ability to stimulate the non-specific resistance in hamsters against Leishmania donovani infection. By virtue of being derived from the food protein casein derivatives may be devoid of unwanted side effects associated with the substances of microbial origin, e.g. muramyl dipeptide (MDP). Out of this one peptide Val-Glu-Gly-Ile-Pro-Tyr (compound 89/215) had been reported to have such activity. In this communication, the prophylactic and therapeutic efficacy of the peptide along with its natural sequence has been evaluated in detail against experimental VL in hamsters. Their use as an adjunct to chemotherapy was also explored. Human beta-casein fragment, compound 89/215 and MDP were tested in vivo at various dose levels wherein compound 89/215 showed superiority over MDP at 3 mg/kg x 2 given intraperitoneally (i.p.). Compound 89/215 sensitized peritoneal macrophages acquired considerable resistance and only 24% of the cells were found infected in comparison to control peritoneal macrophages where 76.4% of the cells were found infected. Similarly, the efficacy of sodium antimony gluconate (SAG) in hamsters pretreated with compound 89/215 enhanced significantly (P < 0.001). This peptide also exhibited considerably good therapeutic efficacy when evaluated either alone or in combination with SAG in established infection of L. donovani.
CDRI 85/92, an anti-ulcer drug, is a new proton pump inhibitor, currently in an advanced stage of drug development. To know more about the drug it was our objective to delineate/identify the metabolic pathway as well as the enzymes responsible for the formation of metabolites. Metabolism of CDRI-85/92 (cis-5-styryl-2-oxazolidinone-4-carboxylic acid) was investigated in rat liver cellular fractions (S9, microsomes and cytosol) using reverse-phase HPLC and mass spectrometry techniques. Two major metabolites were produced by rat liver S9 fractions and reducing factor generating system from either untreated rats or phenobarbitone (PB)-pretreated rats. Incubation of CDRI-85/92 with postmitochondrial fraction (S9) for 24 h resulted in a cis to trans conversion (metabolite M2). Further cis-trans metabolizing capacity was measured separately in the cytosolic and microsomal fractions. Incubation with the cytosolic fraction resulted in an increased rate of cis-trans conversion, while the microsomal fraction showed no cis to trans conversion, thereby restricting the cis to trans conversion to Phase II enzymes, which are mainly located in the cytosol. Studies with PB-pretreated rat liver S9 fractions resulted in an increased rate of cis to trans conversion. Another metabolite was also present (M1) which was identified as an oxygenated metabolite by mass spectrometry. The major urinary metabolite from CDRI-85/92-treated Sprague-Dawley rats (20 mg/kg p.o.) was identified as M2. Studies using sulfobromophthalein and N-ethylmaleimide, as specific inhibitors of GST, showed a complete absence of metabolism, thus indicating the involvement of GST in the metabolism of CDRI-85/92. This study will be helpful in providing clues about factors influencing the bioavailability of CDRI-85/92 as well as drug-drug interactions.
The objective of the present study is to determine the bioefficacy of different crude extracts of Ajuga remota against anopheline and culicine larvae. Larval susceptibility of crude carbon-tetrachloride, methanol and petroleum-ether extracts of Ajuga remota leaves was observed against the malaria vector, Anopheles stephensi and the filariasis vector, Culex quinquefasciatus. Among the extracts tested, petroleum-ether extract was the most effective with LC50 values of 0.033% after 24 hours and 0.029% after 48 hours of treatment against the larvae of Anopheles stephensi. In the case of the larvae of Culex quinquefasciatus, the carbon-tetra-chloride extract exhibited maximum efficacy with LC50 values of 0.043% after 24 hours and 0.026% after 48 hours of exposure, respectively. It is, therefore, concluded that Ajuga remota can be applied as an ideal larvicide against An. stephensi and Cx. quinquefasciatus.
Lens epithelium-cell derived growth factor (LEDGF) is a transcriptional activator. It protects the cells by binding to cis-stress response ((A/T)GGGG(T/A)), and heat shock (HSE; nGAAn) elements in the stress genes and activating their transcription. Transforming growth factor-beta (TGF-beta) has been implicated in the control of tissue homeostasis, terminal differentiation, and apoptosis. Here we provide evidence that TGF-beta1 down-regulates LEDGF expression and diminishes its affinity for DNA during TGF-beta1-induced phenotypic changes and apoptosis in human lens epithelial cells. Surprisingly, TGF-beta1 treatment for 48 h markedly decreased the LEDGF, Hsp27, and alphaB-crystallin promoter activities with the decrease of abundance of LEDGF mRNA and protein. Deletion mutants of the LEDGF promoter showed that one TGF-beta1 inhibitory element (TIE) like sequence nnnTTGGnnn (-444 to -433) contributed to this negative regulation. Mutation of TIE (TTGG to TATT) abolished the down-regulation of the LEDGF promoter. Gel mobility and supershift assays showed that LEDGF in the nuclear extracts of TGF-beta1-treated human lens epithelial cells did not bind to stress-response elements and HSE. The TGF-beta1-induced down-regulation of LEDGF, Hsp27, and alphaB-crystallin promoters activity was reversed by cotransfection with a plasmid expressing LEDGF. Because overexpression of LEDGF was able to relieve TGF-beta1 and/or stress-induced changes, it would be a candidate molecule to postpone age-related degenerating disorders.