Introduction: 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. materials and methods: Materials Nanoextract G.gnemon (GNE) as the main ingredient is melinjo hard shell dry extract that has been ballmilled 120 minutes, has been measured using PSA and SEM to have a size of less than 1 micrometer measured around 300 to 600 nm with a polydispersity index below 0.5 which means it has a good distribution and is known to be quite stable with the ballmilling process based on FTIR characterization analysis. It has been shown to have higher total phenol content and antioxidant power than regular dry extract without ballmilling (GDE). Method Methods of Anti-aging activity test against CRL2522 cell line: The in vitro anti-aging activity was evaluated in several stages, including a concentration determination viability test, incubation time optimization, further viability test using the optimal concentration and incubation time, and finally the comparison of SIRT1 levels. In this study, group 1 cells examined for SIRT1 expression consisted of control, GNE 125, GNE 250, GDE 125, and GDE 250. Group 2 tested for aging induction included control, GNE125 + H2O2, GNE250 + H2O2, GDE 125 + H2O2, and GDE 125 + H2O2. Both 125 and 250 represented the concentration used for all treatments measured in units of ppm. Methods of Pharmacokinetic test: The pharmacokinetic test design used a crossover method consisting of two sessions. In Session I, the test animals were divided into two treatment groups. The first group (n=5) received GNE preparation at a single dose of 144 mg/KgBB, while the second (n=5) was given GDE at the same dose. The pharmacokinetic profile of resveratrol in the plasma of rats was evaluated using a validated HPLC analysis method including ensuring accuracy, precision, linearity of measurement results, detection limit (LoD), and quantitation limit (LoQ) Methods: 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. Results: 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. Discussion: 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. conclusion: Nanotechnology-based processing of G. gnemon hard shell improves resveratrol solubility and bioavailability, supporting its potential as a natural anti-aging agent and promoting the valorization of plant-derived by-products in health applications Conclusion: Ball-milling nanotechnology improved the solubility, bioavailability, and biological activity of G. gnemon hard shell, supporting its potential as a natural anti-aging agent.
Indriastuti et al. (Wed,) studied this question.