Hippocampal neurogenesis modulated by Quinic acid: A therapeutic strategy for the neurodegenerative disorders.

Neural progenitor cells (NPCs) reside in the brain and participate in the mechanism of neurogenesis that permits the brain to generate the building blocks for enhancement of cognitive abilities and acquisition of new skills. The existence of NPCs in brain has opened a novel dimension of research to explore their potential for treatment of various neurodegenerative disorders. The present study provides novel insights into the intracellular mechanisms in neuronal cells proliferation, maturation and differentiation regulated by Quinic acid (QA). Furthermore, this study might help in discovery and development of lead molecule that can overcome the challenges in the treatment of neurodegenerative diseases. The growth supporting effect of QA was studied using MTT assay. For that purpose, hippocampal cell cultures of neonatal rats were treated with different concentrations of QA and incubated for 24, 48 and 72 h. Gene and protein expressions of the selected molecular markers nestin, neuron-specific class III beta-tubulin (Tuj-1), neuronal nuclear protein (NeuN), neuronal differentiation 1 (NeuroD1), glial fibrillary acidic protein (GFAP), neuroligin (NLGN) and vimentin were analyzed. QA-induced cell proliferation and differentiation of hippocampal progenitor cells was also accompanied by significantly increased expression of progenitor and immature neuronal marker, mature neuronal marker and differentiating factor, that is, nestin, Tuj-1, NeuN and NeuroD1, respectively. On the other hand, vimentin downregulation and constant GFAP expression were observed following QA treatment. Additionally, the effects of QA on the recovery of stressed cells was studied using in vitro model of oxygen glucose deprivation (OGD). It was observed that hippocampal cells were able to recover from OGD following the treatment with QA. These findings suggest that QA treatment promotes hippocampal neurogenesis by proliferating and differentiating of NPCs and recovers neurons from stress caused by OGD. Thus, the neurogenic potential of QA can be explored for the treatment of neurodegenerative disorders.

Evaluation of the cytotoxic and antioxidant activities Buxus wallichiana Baill leaf extract against U 87 glioblastoma.

The scientific community has been drawn towards natural plant resources due to the rising success rates. This work aimed to explore the phytochemical, antioxidant and anti-cancer properties of an ethanolic extract derived from the leaves of Buxus wallichiana Baill. which is utilized in traditional medicine in the treatment of various disease such as respiratory disorders, GI disorders and inflammation. Chemical composition of the ethanolic extract of BW leaves was evaluated by using Gas chromatography-mass spectrometry and phytochemical analysis. Moreover, anti-oxidant and anticancer activity was carried out through 2,2-diphenyl-1-picryl hydrazyl scavenging activity method and 3-(4, 5-dimethyl thiazol-2-yl)-2, 5-diphenyl tetrazolium bromide assay against human glioblastoma cell line. ANOVA test was used to analyze the results followed by Bonferoni's post hoc. Results were significant at P <0.05 and demonstrated that, blocking the production of free radicals also caused tumor cell proliferation on the U 87 MG. Thus, the results show the same pattern of toxicity as indicated by the American National Cancer Institute. The minimum dose for cytotoxic activity of the crude extract was less than 30µg/mL. BW leave extract is considered to have promising anticancer potential as well as antioxidant due to the presence of potent compounds and could become a source of treatment with minimum side effects.

Urease and human glioblastoma (U87) cells growth inhibitory iridoid glycoside acetates from Nyctanthes arbor-tristis Linn.

The present study was undertaken on the chemical constituents of ethanol extract of aerial parts of Nyctanthes arbor-tristis Linn., and their determination of growth inhibitory activity against glioblastoma multiforme cell line (U87) and urease inhibitory activity. Six constituents were isolated including two new arbortristoside F tetraacetate (1) and arbortristoside G heptaacetate (2) and four known arborside A tetraacetate (3), arborside C pentaacetate (4), 6,7-di-O-acetyl-6ß-hydroxyloganin hexaacetate (5) and nyctanthoside heptaacetate (6) iridoid glycoside acetates. Their structures were elucidated using spectroscopic methods, including 1D and 2D NMR and mass analyses. Compounds 3 and 6 showed significant growth inhibition of U87 cell line (76.41 and 87.62% inhibition) respectively while 2, 4 and 5 showed moderate inhibition. 3 and 6 showed notable urease inhibition (IC50 = 17.2 ± 0.4 and 17.2 ± 0.7 µM) respectively, and IC50 of 2, 4 and 5 were 23.8 - 56.3 µM. Compound 1 was inactive.

Opuntiol Inhibits Growth and Induces Apoptosis in Human Glioblastoma Cells by Upregulating Active Caspase 3 Expression.

BACKGROUND: Glioblastoma Multiforme (GBM) is a deadly tumor with poor prognosis. Resistance to apoptosis considered as an important factor in treatment failure. Therefore, identification of new compounds that facilitates apoptosis is crucial. Natural Anti-inflammatory compounds have emerged as potential anti-cancer agents and should be explored for their apoptotic activity against GBM. Therefore, the present study aims to evaluate growth inhibitory and apoptotic activity of a natural anti-inflammatory compound "Opuntiol" against GBM cell line U87. METHODS: MTT assay was performed to determine the effect of Temozolomide and Opuntiol on growth inhibition of U87 cell. While, TUNEL assay was used to assess their apoptotic activity. To further assess apoptosis, nuclear condensation and nuclear area factor (NAF) was evaluated through DAPI staining. Whereas, active caspase-3 protein expression determined using immunocytochemistry. RESULTS: Significant growth inhibition was observed in U87 cells treated with Temozolomide (IC50 380 µM) and Opuntiol (IC50 357 µM). Temozolomide (p<0.001) and Opuntiol (p<0.001) significantly improved rate of apoptosis when compared to control group. A significant decrease in NAF was also observed in Temozolomide (p < 0.05) and Opuntiol (p < 0.05) treated cells. There was a significant increase in active caspase-3 expression when observed in Temozolomide (p<0.001) and Opuntiol (p<0.05) treated groups as compared to control. CONCLUSION: In conclusion our findings suggests, Opuntiol repress cell viability and possess strong apoptotic activity against GBM cell line U-87. However, further mechanistic studies will be required to confirm whether it can be develop as a potential drug against GBM.

Substance P: A neuropeptide involved in the psychopathology of anxiety disorders.

Substance P (SP) is the most widely distributed neuropeptide in central nervous system (CNS) where it participates in numerous physiological and pathophysiological processes including stress and anxiety related behaviors. In line with this notion, brain areas that are thought to be involved in anxiety regulation contains SP and its specific NK1 receptors. SP concentration in different brain regions alters with the exposure of stressful stimulus and affected NK1 receptor binding is observed. SP is released in response to a stressor, which produces anxiogenic effects via activation of hypothalamic-pituitary-adrenal (HPA) axis, resulting in the liberation of cortisol. Moreover, SP is also involved in the activation of the sympathetic nervous system via stimulation of locus coeruleus (LC). This sympathetic surge initiates cortisol discharge by activation of HPA axis, representing the indirect anxiogenic effect of SP. Besides the aforementioned regions, SP also has an impact on other brain regions known to be involved in stress and anxiety mechanisms, including amygdala, lateral septum (LS), periaqueductal gray (PAG), ventromedial nucleus of the hypothalamus (VMH), and bed nucleus of stria terminalis (BNST). Thus, SP acts as an important neuromodulator in various brain regions in stress and anxiety response. Consistent with the above statement, SP makes a robust link in the psychopathology of anxiety disorders. As SP concentration is found elevated in stressed conditions, several studies have reported that the pharmacological antagonism or genetic depletion of NK-1 receptors results in the anxiolytic response making them a suitable therapeutic target for the treatment of stress and anxiety related disorders.