Scientia Pharmaceutica

Hydrothermal vent communities are a source of bioactive compounds; some of these could be a potential anticancer therapy. Riftia pachyptila is a marine invertebrate endemic to hydrothermal vents. The dichloromethane–methanol (1:1) extracts were obtained from the wall (Pa), the trophosome (Tr), and the tube (Tu) of R. pachyptila. The cytotoxic effect of extracts was evaluated on human glioblastoma cell lines U373 and U87 and fibroblast BJ1 cell line by MTT and trypan blue assays. To detect DNA apoptotic fragmentation and tumoral p53 expression by Pa, the TUNEL and immunofluorescence assays were performed, respectively. The extracts were analyzed by gas chromatography–mass spectrometry. The Pa extract produced the most cytotoxicity on U87 and U373 cells, but not on BJ1 cells; furthermore, Pa extract produced apoptosis and cytosolic p53 stabilization. The chemical profile of extracts showed thirty-four natural compounds. This study identifies R. pachyptila extracts as potential source of drugs for glioblastoma.

Chronic and difficult-to-heal wounds require topical agents that combine reparative activity with favorable local disposition and an acceptable preliminary safety profile. This study evaluated three orotic acid–1,2,4-triazole hybrids (1–3) using an integrated computational and experimental workflow. Accelerated weight histogram simulations were performed in an atomistic human stratum corneum lipid model; acute toxicity was assessed by in silico rat LD₅₀ prediction, 96 h Danio rerio LC₅₀ testing, and OECD 425 oral testing in rats. Compounds selected on the basis of toxicity were incorporated into electrospun polyvinylpyrrolidone K-30 dressings and evaluated in a rat excisional wound model. Compound 1 showed pronounced lipid partitioning and potential intralamellar retention, whereas compounds 2 and 3 encountered broad membrane-interior free-energy barriers. Compound 2 had the least favorable acute-toxicity profile and was excluded. By day 8, wound area decreased by 89.0% with compound 1 and 78.6% with compound 3, versus 70.5% with the drug-free vehicle dressing (p < 0.001 for both comparisons). Neither treatment caused clinically evident deterioration or a consistent biochemical pattern of marked hepatic or renal dysfunction, although hematological and compound-specific biochemical changes were observed. The compound 1-loaded dressing therefore warrants further mechanistic, histological, and longer-term safety evaluation as the lead formulation.

Beta-amyloid peptide (Aβ), the key pathogenic factor of Alzheimer’s disease (AD), induces oxidative stress-mediated neuronal damage, eventually leading to death. Madecassic acid (MAD), a natural triterpenoid isolated from Centella asiatica, has been reported for many biological activities, including neuroprotective effects. The low solubility and poor bioavailability of MAD are major limitations; hence, the present study focused on formulating MAD in a nanostructured lipid carrier (NLC-MAD) and evaluating its protective effect against oxidative stress induced by Aβ (25–35) in Neuro-2A cells. NLC-MAD, made of 7.5% total lipid, 50% liquid oil, and 6% surfactant with desirable qualities, was selected for further studies. NLC-MAD exhibited potent free radical scavenging activity (IC₅₀ value 80.20 ± 0.05 μg/mL), reducing power, total antioxidant power, and metal chelating activity (IC₅₀ value 120.12 ± 0.02 µg/mL). NLC-MAD showed a dose-dependent inhibition of acetyl and butyrylcholinesterase with IC₅₀ values of 12.5 ± 0.001 and 30 ± 0.02 µg/mL, respectively. NLC-MAD attenuated Aβ peptide aggregation and disaggregated the preformed mature fibrils. NLC-MAD pretreated Neuro-2A cells attenuated Aβ-induced toxicity dose-dependently and attenuated oxidative stress-mediated toxicity. Safety evaluation studies revealed that NLC-MAD is neither cytotoxic nor hemolytic under in vitro conditions and exhibited no adverse effects under in vivo conditions, indicating a non-toxic nature. The results warrant further studies on the stability of NLC-MAD and preclinical studies before consideration to clinical trials.