In this modern era, in which interest in natural compounds is gaining more ground, Geranium robertianum L. (Gr), a species with long use in traditional medicine, stands out for its promising potential in managing a multitude of health issues. In this context, the present review aims to explore the main phytocompounds detected in various types of extracts, as well as the biological activity of Gr species. This review was conducted by analyzing data published up to February 2025 from peer-reviewed journals and databases including PubMed, Web of Science, and Google Scholar, using key words combinations such as Geranium robertianum L. and the searched phytocompound and biological effect. According to the literature the main phytochemical classes identified in different types of extracts include tannins, flavonoids, phenolic acids, and essential oils. The most important biological actions described in the literature are antioxidant, anti-inflammatory, antimicrobial, antiulcerative, neuroprotective, anti-cancer, and antidiabetic effects. However, knowledge about Gr is still relatively limited, requiring more detailed study regarding its pharmacological proprieties and the molecular mechanisms behind them.

Background and Objectives: Oropharyngeal squamous cell carcinoma (OPSCC) is a common type of head and neck cancer with a progressive incidence in recent years. The limitations and the side effects associated with the current treatments require new therapeutic alternatives. Silibinin (SIL) is a phytocompound with multifaceted properties that has demonstrated antitumor effects in several types of cancer. The aim of this study was to assess the potential anticancer effects of SIL in Detroit 562 human pharyngeal cancer cells, an ideal model for HPV-negative OPSCC. Materials and Methods: Detroit 562 cells and HGF-1- human gingival fibroblasts were used as experimental models. For the mechanistic investigations, different methods, such as MTT assay, bright field microscopy, immunofluorescence staining, and specific assays and kits were applied to quantify intracellular ROS production, activation of caspases, and the colony formation assay. Results: Treatment with SIL (25–200 µM) for 48 h induced a selective cytotoxic effect in Detroit 562 cancer cells, being minimally toxic to healthy cells. The cytotoxic mechanism of action was characterized by a decreased cell viability, morphological alterations, elevation of intracellular ROS, decreased mitochondrial potential, mitochondrial and nuclear dysmorphologies, activation of caspases 9 and 3/7 and apoptosis occurrence, and decreased long-term colony formation. Conclusions: These findings show that SIL could represent a potential alternative therapy for HPV-negative OPSCC by triggering mitochondrial apoptosis and exerting a decline in the colonogenicity of Detroit 562 cancer cells.

Background: Aristolochia clematitis L. (AC), a plant with diverse traditional uses, has gained increasing scientific interest due to its rich content of bioactive compounds such as flavonoids and polyphenols. However, its systemic use is limited by the presence of aristolochic acids, which are known for their nephrotoxic and carcinogenic potential. Methods: In this context, the present study investigates the therapeutic potential of A. clematitis extract by encapsulating it in liposomes with the aim of enhancing its topical efficacy. Results: The extract was characterized in terms of its flavonoid content (67.23 ± 0.33 mg QE/g DW (quercetin/dry plant material)) and polyphenols expressed as gallic acid equivalents (64.38 ± 0.16 mg GAE/g DW), as well as its antioxidant capacity using the reagents 1,1-diphenyl-2-picrylhydrazyl (DPPH − IC₅₀ = 0.1619 mg/mL extract) and diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS − IC₅₀ = 205.57 μg/mL extract). Four types of liposomes were synthesized (two loaded with extract and two empty), and their characterization was performed using Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS), Zeta Potential, polydispersity index, and in vitro release studies. Conclusions: The results demonstrated a high entrapment efficiency (over 82%), good stability over 30 days, and controlled release of flavonoids. Microbiological studies revealed relevant antimicrobial activity against Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and Pseudomonas aeruginosa strains. The evaluation on HaCaT skin-derived cells (at 10–100 µg/mL) proved that the samples displayed good overall tolerability, slightly decreasing cell viability (the most statistically significant being associated with AC treatment) and showing no structural, nuclear, or mitochondrial morphological changes.

Puerarin is a naturally occurring isoflavone with reported anticancer activity, yet its topical translation is constrained by limited stability and suboptimal dermal delivery. A Puerarin-loaded proniosomal gel was developed as a potential dermal delivery platform, and we performed an initial assessment of its antimelanoma activity and safety. The gel was produced by coacervation–phase separation using Span 60, Tween 80, phosphatidylcholine, and cholesterol. Physicochemical characterization included pH, entrapment efficiency, rheology, FTIR, DSC, and vesicle properties (DLS, PDI, ζ-potential). In silico geometry optimization and docking were carried out for melanoma-associated targets (MITF and DNMT3B). Biological effects were investigated in vitro on A375 melanoma cells using MTT, morphological analysis, and nuclear/mitochondrial staining, while irritation potential was evaluated in ovo by HET-CAM. The optimized formulation exhibited a skin-compatible pH and an entrapment efficiency of 62 ± 0.26%. DLS indicated a multimodal population, with a major number-weighted vesicle population in the 100–200 nm range, and a ζ-potential of −34.9 ± 0.14 mV. FTIR and DSC supported component incorporation without evidence of chemical incompatibility. The gel showed non-Newtonian, pseudoplastic, thixotropic flow, which is advantageous for topical use. Docking predicted meaningful affinities of Puerarin toward MITF and DNMT3B. The formulation reduced A375 viability in a dose-dependent manner (to 44.66% at 200 µg/mL) and, at higher concentrations, produced nuclear condensation and disruption of the mitochondrial network. HET-CAM classified the gel as non-irritant. The Puerarin-loaded proniosomal gel represents a promising topical platform with preliminary in vitro antimelanoma cytotoxic potential, warranting additional studies to validate skin delivery, efficacy, and safety.

Geranium robertianum L. is used in traditional medicine to treat different systemic disorders and holds great therapeutic potential but remains understudied. To this aim, an ethanolic extract obtained from the aerial parts of G. robertianum L. (GR) was investigated in terms of phytochemical composition and biological activity. GR extract exhibited high levels of phenolic compounds and flavonoids. The antioxidant activity was determined by means of three different colorimetric assays (DPPH, ABTS, and FRAP), and the results obtained indicate that the ABTS assay showed the highest antioxidant capacity. Metal analysis was also performed. Fe was found to be the most abundant element in the analyzed extract, with a concentration of 363.65 ± 4.18 μg/g, followed by Zn, Mn, Ni, and Cr. Four potentially hazardous heavy metals, As, Co, Pb, and Cd, were found to be under the detection limit. The GR extract exhibited moderate antibacterial activity against both Gram-positive and Gram-negative bacteria, with inhibition zones generally comparable to those of levofloxacin. However, the extract was significantly less effective against the P. aeruginosa strain. On A253 human salivary gland carcinoma cells, GR extract elicited a dose-dependent antiproliferative effect, produced morphological changes, and increased ROS and both caspase-3/7 and caspase-9 levels.

Background/Objectives: Magnetic iron oxide nanoparticles are investigated in cancer research; however, the direct biological effects of unloaded magnetic colloidal suspensions in renal cancer remain insufficiently characterized. This study compared two double-oleic-acid-coated formulations prepared from precursors: magnetite-based MCS 1 and maghemite-based MCS 2. Methods: The suspensions were characterized by vibrating-sample magnetometry, dynamic light scattering, bright-field scanning transmission electron microscopy, and energy-dispersive X-ray spectroscopy. Their effects on A704 renal adenocarcinoma cells were evaluated after 24 h of exposure to 1–5 µg/mL using MTT, neutral red uptake, JC-1, Hoechst 33342/MitoTracker Red CMXRos, acridine orange/propidium iodide staining, and a 7-day clonogenic assay. Results: MCS 2 showed higher volumetric saturation magnetization (1.541 vs. 1.059 Gs), a smaller Z-average hydrodynamic diameter (79.65 vs. 103.9 nm), and a more uniform volume-weighted distribution. Both formulations significantly reduced metabolic activity and neutral red uptake and induced mitochondrial depolarization, cell-death-associated morphological changes, and impaired clonogenic capacity. MCS 1 generally produced a moderate response with an apparent plateau, whereas MCS 2 showed a pronounced concentration-related effect at 4–5 µg/mL. At 5 µg/mL, MCS 2 reduced metabolic activity to approximately 49%, neutral red uptake to 50.04%, the JC-1 aggregate-to-monomer ratio to 46.02%, and colony formation to 31.44% of the control. Conclusions: The suspensions exhibited distinct physicochemical and biological profiles. MCS 2 produced greater effects at the highest concentrations, potentially related to its smaller hydrodynamic size and more uniform particle-size distribution. Further studies should establish tumor selectivity, cellular uptake, and the underlying molecular mechanisms.