Osteogenic differentiation and mineralization potential of zinc oxide nanoparticles from Scutellaria baicalensis on human osteoblast-like MG-63 cells.

Development of biologically inspired green synthesis of silver nanoparticles has been extensively scrutinized owing to its uses in biomedical industry. In the last two decades, the demands of nanomaterial in bone remodelling have increased. Scutellaria baicalensis is a flowering plant usually used for many ailments. This work explores the zinc oxide nanoparticles (ZnO NPs) by green route method from S. baicalensis and the therapeutic potentials of Sb-ZnONPs on differentiation of osteoblast and osteoclast formation inhibition. The characterization of the fabricated ZnO-NPs from S. baicalensis was done via different spectroscopic and microscopic techniques; ultraviolet-visible spectroscopy (UV-Vis), Fourier transform-infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and dynamic light scattering (DLS). The Osteogenic-related tests (MTT, Mineralization assay and Real-time PCR) were used to evaluate the properties of SB-ZnONPs on the growth and proliferation of human osteoblast-like MG-63 cells. The characterization of SB-ZnONPs discovered the crystalline properties with high zinc content and the existence of bioactive mixtures from S. baicalensis extract. In addition, SB-ZnONPs showed insignificant cytotoxicity with enhanced differentiation, proliferation, and mineralization on MG-63 cells. Overall, these results denote that SB-ZnONPs is expected to be a natural source for the development of medical agents to in bone healing and remodelling.

Caspase dependent apoptotic activity of polycyclic cage-like heterocyclic hybrids.

A small library of cage-like heterocyclic hybrids encompassing pyrroloisoquinolines, pyridinone and acenaphthene structural moieties have been synthesized and tested for their potential as anticancer agents against HCT116 and JURKAT cell lines. The results revealed that these cell lines are more sensitive towards compound 1g and it showed dose dependent cytotoxic effect at 48 hrs of incubation. The IC50 values of compound 1g against HCT116 and JURKAT cell lines are 12.14 ± 1.53 and 10.68 ± 0.68 µM, respectively. Further studies on the determination of mechanism of action of compound 1g discovered that it brought the cell death by inducing Caspase 3 dependent apoptosis and also by arresting the cell cycle at S phase. These studies revealed that compound 1g can be recommended as a potential anti-cancer agent.

Molecular docking analysis of amyloid precursor protein with compounds from the Australian cowplant.

Amyloid precursor protein is linked with Alzheimer's disease (AD). The Australian cowplant Gymnema sylvestre is known in Indian and Chinese medicine. Therefore, it is of interest to screen the Amyloid precursor protein with compounds from the Australian cowplant. We report five compounds (Gymnemasaponin 5, Gymnemasin D, Gymnemoside A, Gymnemoside E, Gymnemoside F) derived from the Australian cowplant as the poteinal inhibitors of Amyloid precursor protein with optimal binding features for further consideration.

Molecular docking analysis of aspirin analogues with ß-catenin.

Canonical Wnt signaling pathway plays a crucial role in cancer cell proliferation, which links by the growth of ß-catenin in cell due to inactivation of glycogen synthetase kinase-3. Therefore, it is of interest to design novel candidates to bind with ß-catenin. Hence, we document the molecular docking analysis data of aspirin analogues with ß-catenin for further consideration.

Molecular docking analysis of COX-2 for potential inhibitors.

Cyclooxygenase-2 (COX-2) is liked with breast cancer. Therefore, it is of interest to design and develop new yet effective compounds against COX-2 from medicinal plants such as the natural alkaloid compounds. We document the optimal binding features of aristolochicacid with COX-2 protein for further consideration.

Molecular docking analysis of beta-catenin with compounds derived from Lycopersicon esculentum.

Beta-catenin is linked with colorectal cancer (CRC). Therefore, it is of interest to design and develop novel compounds to combat CRC. Hence, we document compounds (chlorogenic acid, gallic acid, protocatechuic acid, quercetin and vanillic acid) from Lycopersicon esculentum with optimal binding features for further consideration.

Effect of Litsea lancifolia Leaf Extract on Glucose Transporter 4 Translocation and Glucose Uptake in 3T3L1 Cell Line.

BACKGROUND: Numerous synthetic drugs have been recommended as a remedy for diabetes, but their role in hypoglycemic effects are diverse. The side effects associated with these drugs due to their extended use led scientists to find unconventional medicines with no or little side effects. AIM: This study was aimed at assessment of in vitro antidiabetic activities of methanolic extract of Litsea lancifolia leaves by using 3T3L1 cell line. MATERIALS AND METHODS: The cytotoxic effect of the leaf extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The glucose uptake-inducing capabilities and its correlation with glucose transporter 4 (GLUT4) translocation were measured by flow cytometry in 3T3L1 cells. In addition, the inhibitory effect of L. lancifolia leaf extract on α-amylase activity and α-glucosidase activity was determined by colorimetric methods. RESULTS: Different concentrations of L. lancifolia leaf extract did not show any toxicity on 3T3L1 cells, after the treatment for 24h. On stimulation with leaf extract, 60.22% and 86.26% of 3T3L1 cells showed glucose uptake and GLUT4 expression, respectively. The colorimetric assays showed that the methanolic leaf extract of L. lancifolia has a significant inhibitory effect on the activity of α-amylase enzyme and α-glucosidase enzyme with inhibitory concentration (IC50) value of 248.65 µg/mL and 229.61 µg/mL, respectively. CONCLUSION: On the basis of the results of this study, it is evident that L. lancifolia leaf extract showed promising anti-diabetic effect when compared to the standard drugs metformin and acarbose and was nontoxic to 3T3L1 cells. Thus, it can be further investigated to recommend as a possible alternative treatment in antidiabetic applications.

NOTCH Signaling Is Essential for Maturation, Self-Renewal, and Tri-Differentiation of In Vitro Derived Human Neural Stem Cells.

Although neural stem cells (NSCs) have potential applications in treating neurological disorders, much still needs to be understood about the differentiation biology for their successful clinical translation. In this study, we aimed at deriving NSCs from human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) and explored the role of Notch signaling in the differentiation process. The hUCB-MSCs were characterized as per guidelines of the International Society of Cellular Therapy. NSCs were successfully generated from hUCB-MSCs by using epidermal and fibroblast growth factors under serum-free conditions. The expression of NSC markers (Nestin and Musashi-1) in the neurospheres generated from hUCB-MSCs in the presence or absence of N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT; Notch inhibitor) was immuno-phenotypically characterized by using immunofluorescence. DAPT showed significant (*p < 0.05) downregulated expression of the NSC markers-Nestin and SOX2-at different time points (6 hours, 12 hours, 24 hours, 36 hours, and 5 days) post-treatment. In addition, Mushashi-1 (NSC marker) expression in NSCs was also inhibited after DAPT treatment, which signifies that the process is Notch dependent. These data were further correlated with formation of a reduced average number of neurospheres derived from hUCB-MSCs (2 colonies vs. 11 colonies/field of view) in the presence of DAPT compared with the control (without DAPT). The expression of Notch target genes in NSC cultures (Notch intracellular domain [NICD], HES1, and HES5) was also significantly downregulated after DAPT treatment. In the presence of DAPT, the markers for neuronal (MAP2, NEFH); and glial (GFAP, GLUL, and MBP) lineages were significantly downregulated as seen via immunofluorescence and quantitative polymerase chain reaction, indicating the role of Notch in the tri-differentiation mechanism of NSCs as well. In addition, Notch signaling inhibition induced higher cell death during the lineage commitment of NSCs as measured 3 days (16.9% vs. 8.9%) and 6 days (42.9% vs. 20.8%) postinduction. These results suggest that the efficient derivation of NSCs and their subsequent lineage commitment from hUCB-MSCs requires the Notch signaling pathway.