Chamaiphorn Wongwan

Oxidative stress, caused by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, is a central contributor to aging and neurodegenerative disorders. Natural products that enhance cellular stress resistance therefore represent promising candidates for promoting healthy aging. Here, we investigated the anti-aging potential of the ethanol extract of Artocarpus thailandicus (ATE) using the Caenorhabditis elegans model. ATE significantly reduced intracellular ROS levels and improved multiple healthspan parameters, including lifespan, egg-laying capacity, pharyngeal pumping rate, and survival under juglone-induced oxidative stress. ATE also attenuated oxidative damage, as indicated by decreased expression of the stress-responsive marker HSP-16.2. Mechanistically, ATE suppressed daf-2 expression and promoted nuclear translocation of DAF-16 and SKN-1, leading to upregulation of antioxidant genes such as sod-3 and gst-4. Together, these findings identify A. thailandicus as a promising natural source of bioactive compounds with potential healthspan-promoting and anti-aging properties.

Angiogenesis inhibitor drugs have been explored as important pharmacological agents for cancer therapy, including hepatocellular carcinoma. These agents have several drawbacks, such as drug resistance, nonspecific toxicity, and systemic side effects. Therefore, combination therapy of the drug and small interfering RNA could be a promising option to achieve high therapeutic efficacy while allowing a lower systemic dose. Therefore, we studied adding an alpha-fetoprotein siRNA (AFP-siRNA) incorporated on polymeric nanoparticles (NPs) along with angiogenesis inhibitor drugs. The AFP siRNA-loaded NPs were successfully synthesized at an average size of 242.00 ± 2.54 nm. Combination treatment of AFP-siRNA NPs and a low dose of sunitinib produced a synergistic effect in decreasing cell viability in an in vitro hepatocellular carcinoma (HCC) model. AFP-siRNA NPs together with sorafenib or sunitinib greatly inhibited cell proliferation, showing only 39.29 ± 2.72 and 44.04 ± 3.05% cell viability, respectively. Moreover, quantitative reverse transcription PCR (qRT-PCR) demonstrated that AFP-siRNA incorporated with NPs could significantly silence AFP-mRNA expression compared to unloaded NPs. Interestingly, the expression level of AFP-mRNA was further decreased to 28.53 ± 5.10% when sunitinib was added. Therefore, this finding was considered a new promising candidate for HCC treatment in reducing cell proliferation and enhancing therapeutic outcomes.