Chlorhexidine (CHX) represents one of the most commonly used antiseptics in dentistry and other medical–pharmaceutical fields due to its broad-spectrum antimicrobial activity. However, the potential toxic events arising from its common use in practice has become a subject of increasing concern. Thus, the present study was designed to investigate the potential toxicity of CHX digluconate at concentrations covering its antibacterial properties (0.0002–0.2%) in HGF primary gingival fibroblasts, HaCaT immortalized human keratinocytes, and JB6 Cl 41-5a epidermal cells, as well as its irritant action in ovo. Our results indicate that CHX exerted a concentration- and time-dependent cytotoxicity in all cell lines, which was evidenced by the reduction in cell viability, number, and confluence, damaged cell membrane integrity, impaired cell morphology, and specific apoptotic nuclear shape. The highest cytotoxicity was caused by CHX digluconate 0.02% and 0.2%, concentrations, at which an irritant effect on the chorioallantoic membrane was also observed. The novel findings revealed in this research contribute to the overall safety profile of CHX and stand as a basis for further investigations in this regard.

Colorectal cancer (CRC) represents one of the most serious health issues and the third most commonly diagnosed cancer worldwide. However, the treatment options for CRC are associated with adverse reactions, and in some cases, resistance can develop. Flavonoids have emerged as promising alternatives for CRC prevention and therapy due to their multitude of biological properties and ability to target distinct processes involved in CRC pathogenesis. Their innate disadvantageous properties (e.g., low solubility and stability, reduced bioavailability, and lack of tumor specificity) have delayed the potential inclusion of flavonoids in CRC treatment regimens but have hastened the design of nanopharmaceuticals comprising a flavonoid agent entrapped in a nanosized delivery platform that not only counteract these inconveniences but also provide an augmented therapeutic effect and an elevated safety profile by conferring a targeted action. Starting with a brief presentation of the pathological features of CRC and an overview of flavonoid classes, the present study comprehensively reviews the anti-CRC activity of different flavonoids from a mechanistic perspective while also portraying the latest discoveries made in the area of flavonoid-containing nanocarriers that have proved efficient in CRC management. This review concludes by showcasing future perspectives for the advancement of flavonoids and flavonoid-based nanopharmaceuticals in CRC research.

Skin disorders constitute a persistent health problem, covering both acute and chronic conditions that manifest in patients of all ages. Betulinic acid (BA) is a triterpene previously studied as an efficient treatment of skin ailments due to its innate pharmacological properties. Nonetheless, due to its lipophilic nature and low bioavailability, topical delivery systems are necessary for its proper administration. Oleogels are efficient carriers for the incorporation of hydrophobic biomolecules; however, their use for the delivery of BA remains scarce. Therefore, this study was designed to develop, characterize, and evaluate a BA-containing oleogel (BA-O) regarding its cutaneous safety profile as a potential pharmaceutical formulation targeting dermatologic issues. The findings illustrated the efficient formulation of BA as oleogel, the product presenting the specific conditions of topical semi-solid formulations in terms of physico-chemical characteristics and high biocompatibility in vitro and in ovo, as BA-O lacked a cytotoxic effect in HaCaT and JB6 Cl 41-5a skin cells (cell viability percentages being > 70%) and was categorized as non-irritant in EpiDerm™ tissues (viability > 80%) and on the chorioallantoic membrane (Irritation Score = 0.186). These results present the preclinical biosafety profile of BA-O with prospective potential for cutaneous applications that should be investigated in future studies.

Lung cancer (LC) represents one of the most prevalent health issues globally and is a leading cause of tumor-related mortality. Despite being one the most attractive compounds of plant origin due to its numerous biological properties, the therapeutic applications of rutin (RUT) are limited by its disadvantageous pharmacokinetics. Thus, the present study aimed to evaluate in vitro the application of two RUT fatty acids bioconjugates, rutin oleate (RUT-O) and rutin linoleate (RUT-L), as potential improved RUT-based chemotherapeutics in non-small cell lung cancer (NSCLC) treatment. The results indicate that both compounds lacked cytotoxic potential in EpiAirway™ tissues at concentrations up to 125 µM. However, only RUT-L exerted anti-tumorigenic activity in NCI-H23 NSCLC cells after 24 h of treatment by reducing cell viability (up to 47%), proliferation, and neutral red uptake, causing cell membrane damage and lactate dehydrogenase (LDH) leakage, affecting cytoskeletal distribution, inducing cytoplasmic vacuolation, and increasing oxidative stress. The cytopathic effects triggered by RUT-L at 100 and 125 µM are indicators of a non-apoptotic cell death pathway that resembles the characteristics of paraptosis. The novel findings of this study stand as a basis for further investigations on the anti-cancer properties of RUT-L and their underlying mechanisms.

Cutaneous melanoma (CM) represents a severe skin cancer with a rising incidence at present and limited treatment options. 5-Fluorouracil (5-FU) is widely used, including for CM; however, the innate resistance of this cancer to conventional therapy remains problematic. Quercetin (QUE) is a flavonoid that can sensitize cancer cells to antitumor agents such as 5-FU. However, the potential sensitization capability of CM cells to 5-FU has scarcely been determined, and is investigated herein. Therefore, A375 CM cells were tested in terms of their cell viability, cell confluence, and morphological changes. Their nuclear and cytoskeletal aspects, clonogenic potential, and in ovo properties were also followed. The results showed that the 50% inhibitory concentrations (IC50s) of 5-FU and QUE determined by a cell proliferation assay were 11.56 and 11.08 µM, respectively. The addition of QUE (10 µM) to 5-FU (5–50 µM) increased the cytotoxic potential. A significant decline in cell viability (up to 43.51%), the loss of cell confluence, chromatin condensation and nuclear dysmorphology, tubulin and F-actin constriction, and a suppressed clonogenic ability were noted. The QUE + 5-FU association was non-irritating to the chorioallantoic membrane and showed an antiangiogenic effect in ovo. Thus, our results highlight that combining QUE with 5-FU can enhance the cytotoxic effect of 5-FU in A375 melanoma cells and present a safe profile in ovo.

The Rosaceae family, comprising over 3000 species, has been extensively investigated for its therapeutic potential, particularly in dermatological applications. Skin illnesses have become in recent years a serious burden worldwide, with more than 3 billion individuals of all ages affected by a skin condition. This review focuses on approximately 50 species from genera such as Rosa, Rubus, Prunus, Potentilla, and especially Eriobotrya japonica, which have shown promising biological effects due to their diverse bioactive compounds. This review provides a current perspective on the recent scientific literature that highlights the role of Rosaceae members in managing various skin disorders. Key dermatological conditions addressed include dermatitis, acne, skin aging, melanoma, and psoriasis. By summarizing both in vitro and in vivo findings, this review underscores the importance of Rosaceae species in the development of plant-based dermatological therapies and encourages further research into their mechanisms of action and clinical potential.