Saroj Arora

Anti-free radical activities of kaempferol isolated from Acacia nilotica (L.) Willd. Ex. Del.

In the present study the polyphenolic compound has been isolated from methanol extract of Acacia nilotica Willd. Ex. Del. which has been identified as kaempferol (AN-5) by NMR and mass spectroscopy. The antioxidant potential of the AN-5 was demonstrated in several in vitro assays: measuring the proton radical scavenging activity (DPPH scavenging assay), hydroxyl radical scavenging activity (deoxyribose degradation assay), metal chelating activity, reducing power and inhibition of lipid peroxidation. It was found that the effect of the compound AN-5 was strongly dose dependent up to the concentrations 1-50 microg/ml in DPPH assay and 1-100 microg/ml in deoxyribose degradation assay but did not show further change above the highest concentrations.

Antimutagenic activities of acetone and methanol fractions of Terminalia arjuna

The antimutagenic effect of benzene, chloroform, acetone and methanol fractions from Terminalia arjuna, a well-known medicinal plant, was determined against Acid Black dye, 2-aminofluorene (2AF) and 4-nitro-o-phenylenediamine (NPD) in TA98 Frameshift mutagen tester strain of Salmonella typhimurium. Among the different fractions, the antimutagenic effect of acetone and methanol fractions was more than that observed with other fractions. Co-incubation and pre-incubation modes of experimentation did not show much difference in the antimutagenic activity of the extracts. Moreover, these fractions inhibited the S9-dependent mutagens, 2AF and Acid Black dye more effectively than the direct-acting mutagens. Studies are under way to isolate and elucidate the nature of the antimutagenic factor in acetone and methanol fractions.

Oxidative stress—implications, source and its prevention

Oxidative stress has been a major predicament of present day living. It has been the product of imbalance between the processes involved in free radical generation and their neutralization by enzymatic and non-enzymatic defence mechanisms. The oxidative stress has been contributed by numerous factors including heavy metals, organic compound-rich industrial effluents, air pollutants and changing lifestyle pattern focussing mainly on alcohol consumption, dietary habits, sun exposure, nuclear emissions, etc. The most common outcome of oxidative stress is the increased damage of lipid, DNA and proteins that resulted in the development of different pathologies. Among these pathologies, cancer is the most devastating and linked to multiple mutations arising due to oxidative DNA and protein damage that ultimately affect the integrity of the genome. The chemopreventive agents particularly nutraceuticals are found to be effective in reducing cancer incidences as these components have immense antioxidative, antimutagenic and antiproliferative potentials and are an important part of our dietary components. These secondary metabolites, due to their unique chemical structure, facilitate cell-to-cell communication, repair DNA damage by the downregulation of transcription factors and inhibit the activity of protein kinases and cytochrome P450-dependent mixed function oxidases. These phytochemicals, therefore, are most appropriate in combating oxidative stress-related disorders due to their tendency to exert better protective effect without having any distinct side effect.

A CORRELATIVE STUDY ON ANTIMUTAGENIC AND CHEMOPREVENTIVE ACTIVITY OF ACACIA AURICULIFORMIS A. CUNN. AND ACACIA NILOTICA (L.) WILLD. EX DEL

The present study provides a correlation of the antimutagenic and chemopreventive activity of the barks of two commonly observed plants viz. Acacia auriculiformis and Acacia nilotica. We used the Ames antimutagenicity assay and the mouse mammary gland organ culture (MMOC) model. The plants were extracted with organic solvents to obtain chloroform fractions and acetone extracts. The antimutagenic activity was determined in two different strains using both direct-acting [4-nitro-o-phenylenediamine (NPD) or sodium azide] and indirect-acting [2-aminofluorene (2AF)] mutagens. The anticarcinogenic activity was evaluated based on the development of preneoplastic lesions in response to the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The results showed that the activity resulting from the 2AF mutagen was selectively greater than the activity from the direct-acting mutagens. Moreover, in general, acetone extracts were more potent in suppressing mutagenesis than the chloroform extracts. The antimutagenicity results obtained with extracts using the 2AF – TA100 system were comparable to the chemopreventive results with DMBA-induced mammary lesions. The order of activity in both tests was A. nilotica > A. auriculiformis. These results exhibited a good correlation between the antimutagenesis assay and the MMOC model, suggesting that these plants may contain active chemopreventive agents.

Free radical scavenging potential of some Indian medicinal plants

Indian medicinal herbs and plants are used since ancient times to treat different diseases and ailments as these natural products exert broad-spectrum actions. The present study was aimed to explore the hydrogen donating and hydroxyl radical scavenging potential of methanol extract of 10 medicinal plants belonging to six families including mimosaceae, Apocynaceae, moraceae, sapindaceae, rutaceae and meliaceae using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and plasmid nicking assay, respectively. The total phenol and flavonoid content of these extracts was also estimated using Folin-Ciocalteu and colorimetric assay respectively. It was found that methanol leaf extract of Koelreutaria paniculata, Acacia catechu and Mimusops hexandra showed strong inhibitory activity whereas that of Hamelia patens exhibited moderate DPPH radical scavenging activity at concentration of 200 µg/ml. However, methanol extract of Swietenia mahogoni, Murraya exotica, Murraya koenigii, Alstonia scholaris, Ficus benjamina and Sapindus trifoliatus exhibited weak hydrogen donating potential in DPPH assay. The methanol extract of these plants was effective in plasmid nicking assay and the activity was found to be correlated to the phenolic and flavonoid content in these fractions. These results emphasized the benefit of the phenolic compounds rich plant extracts and thus augmented the urge of in vivo studies to further confirm the beneficial effect of these extracts.

Interactions of betulinic acid with xenobiotic metabolizing and antioxidative enzymes in DMBA-treated Sprague Dawley female rats

Cancer chemoprevention is related to classical epidemiology and involves the use of agents that inhibit, delay, or reverse the carcinogenesis that occurs as a result of accumulation of mutations and increased proliferation. Betulinic acid is known for its cytotoxic effects against a panel of cancer cell lines. In the present study, interactions of betulinic acid (BA) with xenobiotic metabolizing enzymes including mixed function oxidases (cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase), phase II enzymes (GST, DT-diaphorase, γ-glutamyl transpeptidase), LDH, antioxidative enzymes (glutathione reductase, SOD, catalase, ascorbate peroxidase, and guaiacol peroxidase), and lipid peroxidation are studied alone as well as in the presence of 7,12 dimethylbenzanthracene (DMBA)--a potent carcinogen using Sprague Dawley female rats. The effect of BA on reduced glutathione content and protein content is also taken into consideration. It has been found that administration of BA decreased the level of mixed function oxidases that are involved in the conversion of carcinogen to electrophile, elevated the level of phase II enzymes which participated in the removal of electrophiles by sulfation, conjugation etc. It has been found that BA effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was reflected from the specific activities of antioxidative enzymes which were found to be lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. BA was also found to have a pronounced effect in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. This study highlights the role of BA in modulating the activities of xenobiotic and antioxidative enzymes that have putative roles in cancer initiation and proliferation.

Overexpression of hypoxia-inducible factor and metabolic pathways: possible targets of cancer

Cancer, the main cause of human deaths in the modern world is a group of diseases. Anticancer drug discovery is a challenge for scientists because of involvement of multiple survival pathways of cancer cells. An extensive study on the regulation of each step of these pathways may help find a potential cancer target. Up-regulated HIF-1 expression and altered metabolic pathways are two classical characteristics of cancer. Oxygen-dependent (through pVHL, PHDs, calcium-mediated) and independent (through growth factor signaling pathway, mdm2 pathway, HSP90) regulation of HIF-1α leads to angiogenesis, metastasis, and cell survival. The two subunits of HIF-1 regulates in the same fashion through different mechanisms. HIF-1α translation upregulates via mammalian target of rapamycin and mitogen-activated protein kinase signaling pathways, whereas HIF-1β through calmodulin kinase. Further, the stabilized interactions of these two subunits are important for proper functioning. Also, metabolic pathways crucial for the formation of building blocks (pentose phosphate pathway) and energy generation (glycolysis, TCA cycle and catabolism of glutamine) are altered in cancer cells to protect them from oxidative stress and to meet the reduced oxygen and nutrient supply. Up-regulated anaerobic metabolism occurs through enhanced expression of hexokinase, phosphofructokinase, triosephosphate isomerase, glucose 6-phosphate dehydrogenase and down-regulation of aerobic metabolism via pyruvate dehydrogenase kinase and lactate dehydrogenase which compensate energy requirements along with high glucose intake. Controlled expression of these two pathways through their common intermediate may serve as potent cancer target in future.

Free radical scavenging, antiproliferative activities and profiling of variations in the level of phytochemicals in different parts of broccoli (Brassica oleracea italica).

In the present study, the seeds of Broccoli (cultivar Palam samridhi) at different stages of development were being analysed for their antioxidant and antiproliferative properties. Among the antioxidant assays performed, a remarkable inhibition of superoxide radicals i.e. 94.25% observed with extracts of five days old sprout (PS5) at 2 mg/ml concentration. Although, all the extracts showed high cytotoxicity but the floret extract (PSF) found to be most effective with IC₅₀ value of 25.94 μg/ml while leaves extract (PSL) was least effective. The cell cycle analysis showed increased G₀/G₁ phase population as compare to positive control camptothecin. Profiling of various phytochemicals executed by using gas chromatography-mass spectroscopy in order to correlate the bioactivities of the extracts. A wide variation observed in the profile of GLS hydrolytic products of different extracts obtained from the seeds, sprouts (three, five and seven days), leaves and florets.

Anticancer potential of Himalayan plants

Plants used in traditional medicine have stood up to the test of time and contributed many novel compounds for preventive and curative medicine to modern science. India is sitting on a gold mine of well recorded and traditionally well practiced knowledge of herbal medicine. Specially, plants growing at high altitude in Himalayan pastures are time-honored sources of health and general well being of local inhabitants. As of today, Himalayan plants are a major contributor to the herbal pharmaceutical industry both of India and other countries. Plants growing at higher altitudes are subjected to an assault of diverse testing situations including higher doses of mutagenic UV-radiation, physiological drought, desiccation and strong winds. Plants interact with stressful environments by physiological adaptation and altering the biochemical profile of plant tissues and producing a spectrum of secondary metabolites. Secondary metabolites are of special interest to scientists because of their unique pharmacophores and medicinal properties. Secondary metabolites like polyphenols, terpenes and alkaloids have been reported to possess antimutagenic and anticancer properties in many studies. The fundamental aspiration of the current review is to divulge the antimutagenic/anticancer potential of five alpine plants used as food or medicine by the populations living at high altitudes.

Direct Rhizogenesis from in vitro Leaves of Withania somnifera (L.) Dunal

ABSTRACT Direct rooting was induced in Withania somnifera leaf segments using an IBA dip treatment. The segments dipped in IBA formed roots along the midrib region of the abaxial surface when placed on Murashige and Skoogs (MS) basal medium containing no plant growth regulators. The length of the dip treatments (10, 20 and 30 min) and strength of the MS media (¼, ½, and full-strength) treatments had no apparent effect on rooting, although maximum rooting (85.3 percent of the cultures) occurred when the leaf segments were placed on ½-strength MS medium after a dip treatment with 100 mg/liter IBA solution for 20 min. The average number and length of roots were 32.3 per culture and 5.6 cm, respectively. Only 20 percent of the cultures produced roots if explants were grown on full-strength MS medium supplemented with IBA.