Methods: Anti-cholinesterase, anti-oxidant, and total phenolic and flavonoid contents were established using standard procedures.
Results: The three polyherbal extracts exhibited significant concentration dependent acetylcholinesterase (AChE) inhibitory activity (P = 0.001). The highest AChE inhibition was observed with the Neocare Herbal Tea (NHT) with 99.7% (IC50 = 324 μg/mL); whereas the Herbalin Complex Tea (HCT) and Phytoblis Herbal Tea (PHT) exhibited 73.8% (IC50 = 0.2 μg/mL) and 60.6% (IC50 = 0.7 μg/mL) inhibition, respectively, relative to eserine at 100% inhibition (IC50 = 0.9 μg/mL) at 200 μg/mL. The order of percentage increase in inhibition of AChE was NHT > HCT > PHT; while the order of decrease in potency was HCT > PHT > NHT.Radical scavenging activities of HCT, NHT and PHT were 82.13% (IC50 = 0.08 μg/mL), 77.43% (IC50 = 0.01 μg/mL) and 76.28% (IC50 = 0.3 μg/mL), respectively, at 1 mg/mL concentrations. The reducing power revealed a dose-dependent effect, with NHT > PHT > HCT. The order of total phenolics content in the extracts were PHT > HCT > NHT, and for total flavonoids content: PHT > NHT > HCT.
Conclusion: The three polyherbal standardised products possess significant acetylcholinesterase inhibitory activity and secondary metabolites that could collectively contribute to their memory-enhancing effects.
OBJECTIVE: This study investigates the chemical constituents, anti-proliferative, and apoptotic properties of C. nutans root extracts.
MATERIALS AND METHODS: The roots were subjected to solvent extraction using methanol and ethyl acetate. The anti-proliferative effects of root extracts were tested at the concentrations of 10 to 50 μg/mL on MCF-7 and HeLa by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for 72 h. Morphological changes were observed under light microscope. Pro-apoptotic effects of root extracts were examined using flow cytometric analysis and RT-PCR. The chemical compositions of root extracts were detected using GC-MS.
RESULTS: The proliferation of MCF-7 cells was inhibited with the IC50 values of 35 and 30 μg/mL, respectively, for methanol and ethyl acetate root extracts. The average inhibition of HeLa cells was ∼25%. Induction of apoptosis in MCF-7 was supported by chromatin condensation, down-regulation of BCL2 and unaltered expression of BAX. However, only ethyl acetate extract caused the loss of mitochondrial membrane potential. GC-MS analysis revealed the roots extracts were rich with terpenoids and phytosterols.
DISCUSSION AND CONCLUSIONS: The results demonstrated that root extracts promote apoptosis by suppressing BCL2 via mitochondria-dependent or independent manner. The identified compounds might work solely or cooperatively in regulating apoptosis. However, further studies are required to address this.
RESULTS: We developed DeSigN, a web-based tool for predicting drug efficacy against cancer cell lines using gene expression patterns. The algorithm correlates phenotype-specific gene signatures derived from differentially expressed genes with pre-defined gene expression profiles associated with drug response data (IC50) from 140 drugs. DeSigN successfully predicted the right drug sensitivity outcome in four published GEO studies. Additionally, it predicted bosutinib, a Src/Abl kinase inhibitor, as a sensitive inhibitor for oral squamous cell carcinoma (OSCC) cell lines. In vitro validation of bosutinib in OSCC cell lines demonstrated that indeed, these cell lines were sensitive to bosutinib with IC50 of 0.8-1.2 μM. As further confirmation, we demonstrated experimentally that bosutinib has anti-proliferative activity in OSCC cell lines, demonstrating that DeSigN was able to robustly predict drug that could be beneficial for tumour control.
CONCLUSIONS: DeSigN is a robust method that is useful for the identification of candidate drugs using an input gene signature obtained from gene expression analysis. This user-friendly platform could be used to identify drugs with unanticipated efficacy against cancer cell lines of interest, and therefore could be used for the repurposing of drugs, thus improving the efficiency of drug development.