In vitro Anti-aging Effect via Sirtuin-1 Modulation and Enhancement of Resveratrol Pharmacokinetics in Gnetum gnemon...

Gnetum gnemon L. (melinjo) contains resveratrol, a polyphenolic compound that activates Sirtuin-1, a key regulator of cellular aging. The plant's hard shell, often discarded as waste, contains resveratrol that is inefficiently utilized. However, its therapeutic potential is limited by poor solubility and low bioavailability.

The hard shell was processed using ball-milling nanotechnology to obtain a nanoextract. Human fibroblast CRL2522 cells were exposed to hydrogen peroxide-induced oxidative stress and treated with either the nanoextract or a conventional dry extract. SIRTUIN-1 expression was analyzed as an anti-aging marker. Pharmacokinetic studies were performed in male Wistar rats administered 144 mg/kg orally, with plasma resveratrol quantified using validated HPLC.

Both extracts significantly increased SIRTUIN-1 expression compared with controls (p < 0.05). The nanoextract exhibited a higher peak plasma concentration (Cmax = 0.064 ± 0.025 ppm) and prolonged Tmax (240 min), indicating enhanced solubility and extended bioavailability.

The improvement in pharmacokinetic parameters and SIRTUIN-1 expression suggests that nanonization effectively enhances cellular uptake and stability of resveratrol. The smaller particle size increases surface area and dissolution rate, allowing greater intestinal absorption and sustained plasma levels. These findings align with previous reports that nanoparticle formulations can improve polyphenol bioefficacy through enhanced permeability and metabolic resistance. Importantly, this approach valorizes melinjo by-products into high-value bioactive materials, offering both scientific and economic benefits. Nonetheless, further studies on long-term safety, biodistribution, and molecular targets are necessary to confirm therapeutic relevance.

Ball-milling nanotechnology improved the solubility, bioavailability, and biological activity of G. gnemon hard shell, supporting its potential as a natural anti-aging agent.