Hallmarks of Alzheimer's disease (AD) pathology include acetylcholine (ACh) deficiency and plaque deposition. Emerging studies suggest that acetylcholinesterase (AChE) may interact with amyloid β (Aβ) to promote aggregation of insoluble Aβ plaques in brains of patients. Current therapeutic options available for AD patients, such as AChE inhibitors, provide only symptomatic relief. In this study, we screened four natural compounds believed to harbor cognitive benefits-curcumin, piperine, bacoside A, and chebulinic acid. In the first section, preliminary screening through computational molecular docking simulations gauged the suitability of the compounds as novel AChE inhibitors. From here, only compounds that met the in silico selection criteria were selected for the second section through in vitro investigations, including AChE enzyme inhibition assay, 3-(4,5-dimenthylthiazol-2-yl)-2,5-dimethyltetrazolium bromide (MTT) assay, Thioflavin T (ThT) assay, and biochemical analysis via a neuronal cell line model. Of the four compounds screened, only curcumin (-9.6 kcal/mol) and piperine (-10.5 kcal/mol) showed favorable binding affinities and interactions towards AChE and were hence selected. In vitro AChE inhibition demonstrated that combination of curcumin and piperine showed greater AChE inhibition with an IC50 of 62.81 ± 0.01 μg/ml as compared to individual compounds, i.e., IC50 of curcumin at 134.5 ± 0.06 μg/ml and IC50 of piperine at 76.6 ± 0.08 μg/ml. In the SH-SY5Y cell model, this combination preserved cell viability up to 85%, indicating that the compounds protect against Aβ-induced neuronal damage (p < 0.01). Interestingly, our results also showed that curcumin and piperine achieved a synergistic effect at 35 μM with an synergism quotient (SQ) value of 1.824. Synergistic behavior indicates that the combination of these two compounds at lower concentrations may provide a better outcome than singularly used for Aβ proteins. Combined curcumin and piperine managed to inhibit aggregation (reduced ThT intensity at 0.432 a.u.; p < 0.01) as well as disaggregation (reduced ThT intensity at 0.532 a.u.; p < 0.01) of fibrillar Aβ42. Furthermore, combined curcumin and piperine reversed the Aβ-induced up-regulation of neuronal oxidative stress (p < 0.01). In conclusion, curcumin and piperine demonstrated promising neuroprotective effects, whereas bacoside A and chebulinic acid may not be suitable lead compounds. These results are hoped to advance the field of natural products research as potentially therapeutic and curative AD agents.
The prevalence of vaping worldwide is showing an upward trend. This study aimed to determine the factors associated with motivation to quit vaping among vapers in the Federal Territory of Kuala Lumpur, Malaysia, through a cross-sectional, purposive sampling study. Respondents were required to complete a questionnaire consisting of vapers' sociodemographic questions, habitual behavioral pattern questions, the e-Fagerström Test of Nicotine Dependence, the Glover-Nilsson Smoking Behavioral Dependence Questionnaire, perception questions, motivation to quit questions, and withdrawal symptom questions. A total of 311 vapers participated in this study. The majority of the vapers were male (84.6%), younger (18-25 years) (55.3%), and with monthly income less than RM 4000 (USD 868; 83.9%). The level of motivation to quit vaping was found to have a significant association with the perception of vaping being as satisfying as cigarette smoking (p = 0.006) and mild to very strong nicotine dependence (p = 0.001). Participants who recorded moderate and strong habitual vaping behaviors had lower odds of having high motivation to quit vaping compared to those recording slight habitual behaviors (OR = 0.279, 95%CI(0.110-0.708), p = 0.007 and OR = 0.185, 95%CI(0.052-0.654), p = 0.009, respectively). Factors associated with higher motivation to quit vaping could be explored to gain better understanding of how to increase their motivation level for future quit attempts.