Inhibitory Activity of Compounds Isolated from Ligustrum robustum (Roxb.) Against HepG2 Liver Cancer Cells: Isocubein and 4-(2-Acetoxyethyl)phenol as Potential Candidates.

Many herbal species in the genus Ligustrum have been shown to contain compounds with anti-cancer biological activity. This study aimed to isolate some compounds from the leaves of Ligustrum robustum (Roxb.) Blume (L. robustum) and evaluate their effects against liver cancer cells. As a result, seven previously reported compounds (1-7) were isolated, including four lignans (1-4) and three phenolic derivatives (5-7). The structures of these compounds were determined using spectroscopic methods and comparison with reported data. All isolates were assessed for their inhibitory effects on HepG2 liver cancer cells. Screening results revealed that two compounds, isocubein (3) and 4-(2-acetoxyethyl)phenol (7), exhibited strong inhibitory activity against cell proliferation, with IC50 values of 3.1±0.9 and 4.5±14 µM, respectively. Further analyses demonstrated that both compounds could suppress the formation and development of 3D tumorspheres in terms of quantity and size. Additionally, isocubein (3) and 4-(2-acetoxyethyl)phenol (7) exhibited the ability to inhibit the migration of HepG2 cells. This study represents the first report on the inhibitory activity against HepG2 liver cancer cells of extracts and isolated compounds from L. robustum, providing valuable information for future research aiming to develop products for liver cancer treatment.

Integration of lornoxicam nanocrystals into hydroxypropyl methylcellulose-based sustained release matrix to form a novel biphasic release system.

The study aims to (a) enhance the solubility of a poorly soluble drug by optimization of nanocrystal formulation using the top-down approach and (b) modify the release profile of this drug, which exhibits a short elimination half-life, by the integration of a fast-release phase containing the optimized nanocrystals and a sustained-release phase in a compression-coated tablet. Nanocrystals of the model drug (lornoxicam; LNX) was prepared by simultaneous application of jet-milling and ball-milling techniques. Investigation of the precipitation inhibition capacity, thermal property, and interaction of different polymers with the drug revealed polyvinyl pyrrolidone K30 (PVP) as the most effective stabilizer for nanocrystals. The immediate-release layer containing the optimized nanocrystals (size of 279.5 ± 11.25 nm and polydispersity index of 0.204 ± 0.01) was then compressed on a zero-order sustained-release matrix core using different derivatives of hydroxypropyl methylcellulose (HPMC). Application of the Design of Experiment approach (DoE) was applied to optimize the formulation of tablet. Analysis of drug concentration in dog plasma by liquid chromatography-tandem mass spectrometry demonstrated an improvement in the release behavior of LNX from the optimal compression-coated tablet integrating a HPMC-based sustained release matrix core and a PVP-stabilized lornoxicam nanocrystals coating layer compared to the reference product.