Carla Varela

Aromatic plants and essential oils have long been recognized for their useful properties and broad applicability across various industrial sectors, particularly in the realm of food applications. This article aims to comprehensively review the botanical, chemical and technological dimensions of aromatic plants and their essential oils, covering isolation techniques and exploring their applications in sectors such as in the food, biomedical, cosmetic and personal care, household and agricultural sectors. Beginning with an overview of the background and significance of these natural substances, the review delves into the properties of aromatic plants and essential oils, elucidating their chemical compositions and therapeutic effects. The isolation of essential oils and their analysis are discussed, providing insights into the developments in the field. Furthermore, encapsulation methods are examined for their role in enhancing stability and bioavailability for food, cosmetic and agriculture applications. The review also addresses regulatory frameworks and food and cosmetic safety considerations, governing their present and future use.

Plant-based extracts are rich sources of phenolic compounds, which may act as skin antiaging mediators. Herein, Cistus albidus L. (Ca), Cistus ladanifer L. subsp. ladanifer (Cl) and Cistus salviifolius L. (Cs) were selected to test whether their phytochemical profile and bioactive potential align to target human skin aging. Hydroethanolic extracts (HEs) were prepared and characterized using infrared vibrational spectroscopy (FTIR-ATR) and liquid chromatography–mass spectrometry (LC-MS). Non-toxic concentrations were screened, and cytoprotective and antioxidant effects were studied in tert-butyl hydroperoxide-stimulated normal human dermal fibroblasts (NHDFs). Lipopolysaccharide-stimulated RAW 264.7 macrophages were used to assess anti-inflammatory activity, the Organization for Economic Co-operation and Development (OECD) Test Guideline No. 439 was used to assess irritant effects, and the anti-senescence potential was assessed in etoposide-stimulated NHDFs. A series of enzymatic inhibition assays was performed. All extracts comprised ellagic acid derivatives, as well as myricetin and quercetin derivatives in Cs and Ca. The HE of Cs was also markedly composed of ligstroside. At non-toxic concentrations, cytoprotective effects were observed in NHDFs. However, only Cs and Cl exhibited significant antioxidant activity in these cells (p < 0.001 and p < 0.0001, respectively). In addition to that, Cl demonstrated highly significant anti-inflammatory (p < 0.0001) and anti-senescence (p < 0.0001) effects. Cs and Cl showed a remarkable potential to inhibit elastase; in addition, Cs also showed anti-hyaluronidase and anti-tyrosinase activities. Meaningfully, Cs and Cl extracts did not exhibit skin irritant effects. The unveiled potential of Cl in skin aging offset highlights the need to elucidate the detailed mechanisms of action, paving the way for the development of skin anti-aging formulations.

Background/Objectives: Plants inhabiting mediterranean-influenced climatic zones, like Helichrysum stoechas (L.) Moench subsp. stoechas, Lavandula pedunculata (Mill.) Cav., and Thymus mastichina (L.) L. subsp. mastichina, have been scarcely investigated regarding their richness in phenolic compounds, herein explored as sources of skin anti-aging compounds. Methods: In this investigation, Fourier transform infrared spectroscopy (FTIR) in attenuated total reflectance (ATR) mode and high-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry (HPLC-DAD-ESI/MSⁿ) were employed to chemically characterize the hydroethanolic extracts (HEs), and their cell-free antioxidant potential was screened. Thereafter, non-toxic concentrations of HEs were determined in human skin cells using Alamar blue^® and Sulforhodamine B assays. The cytoprotective and antioxidant effects of HEs were assessed in tert-butyl hydroperoxide-stimulated fibroblasts, their anti-inflammatory potential was studied in lipopolysaccharide-injured macrophages, and enzymatic inhibition assays were performed. Notably, the irritant effects of HEs were tested according to Test Guideline No. 439 of the Organization for Economic Co-operation and Development (OECD). Results: The major compounds identified in the T. mastichina and L. pedunculata HEs were rosmarinic and salvianolic acid derivatives, while H. stoechas HE was mainly composed of caffeoyl and feruloyl derivatives, and O-glycosylated flavonoids. T. mastichina (≤0.4 mg/mL) exhibited significant cytoprotective, anti-inflammatory, and antioxidant effects, as well as remarkable anti-hyaluronidase activity. Conclusions: Shedding light on the quantitative and qualitative chemical picture of these HEs highlighted T. mastichina as a promising candidate to target skin aging effects, which correlates with its phenolic content. Further investigation is warranted regarding its anti-aging pharmacological activity, which could lead to the development of plant-based skin anti-aging products.

Background/Objectives: Endocrine therapies that comprise anti-estrogens and aromatase inhibitors (AIs) are the standard treatment for estrogen receptor-positive (ER+) (Luminal A) breast cancer—the most prevalent subtype. However, the emergence of resistance restricts their success by causing tumor relapse and re-growth, which demands a switch towards other therapeutic approaches in order to minimize or overcome resistance. Indeed, this clinical limitation highlights the search for new molecules to improve cancer treatment. Recently, strategies that address multiple targets have been emerging, and multi-target drugs have the potential to become the future anti-cancer molecules. Our group has been searching for new multi-target compounds, and as part of this, our study aims to understand the anti-cancer and multi-target potential of three new steroidal aromatase inhibitors (AIs): 7α-methylandrost-4-en-17-one (6), 7α-methylandrost-4-ene-3,17-dione (10a) and androsta-4,9(11)-diene-3,17-dione (13). Methods: Their in vitro actions and molecular mechanisms were elucidated in a sensitive ER+ aromatase-overexpressing breast cancer cell line, MCF-7aro cells, as well as in an AI-resistant ER+ breast cancer cell line, LTEDaro cells. Results: All the new AIs (10 µM) prevented the proliferation of MCF-7aro cells by arresting cell cycle progression. Interestingly, all AIs (10 µM) act as androgen receptor (AR) agonists and modulate ER levels, synthesis and signaling to induce the apoptosis of ER+ breast cancer cells. Additionally, these new AIs (10 µM) also re-sensitize resistant cells by promoting apoptosis, offering a therapeutic benefit. Conclusions: Overall, new steroidal polypharmacological compounds have been discovered that, by acting as AIs, ER modulators and AR agonists, impair ER+ breast cancer cell growth. Overall, this study is a breakthrough on drug discovery as it presents new molecules with appealing anti-cancer properties and multi-target action for the treatment of ER+ breast cancer.

Background/Objectives: Côa Valley, located in the northeast of Portugal, harbors more than 500 medicinal plant species. Among them, four species stand out due to their traditional uses: Equisetum ramosissimum Desf. (hemorrhages, urethritis, hepatitis), Rumex scutatus L. subsp. induratus (Boiss. and Reut.) Malag. (inflammation, constipation), Geranium purpureum Vill., and Geranium lucidum L. (pain relief, gastric issues). Given their rich ethnomedicinal history, we evaluated their protective effects on an in vitro model of metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: Decoction (D) and hydroalcoholic (EtOH80%) extracts were prepared and chemically characterized. Their safety profile and effects on lipid accumulation were assessed in palmitic acid (PA)-treated HepG2 cells using resazurin, sulforhodamine B, and Nile Red assays. Results: Chemical analysis revealed diverse phenolic compounds, particularly kaempferol derivatives in E. ramosissimum. All extracts showed minimal cytotoxicity at 25–50 µg/mL. At 100 µg/mL, only E. ramosissimum extracts maintained high cell viability. In the lipotoxicity model, E. ramosissimum decoction demonstrated the most potent effect, significantly reducing PA-induced neutral lipid accumulation in a dose-dependent manner, while other extracts showed varying degrees of activity. Conclusions: These findings highlight E. ramosissimum’s decoction, rich in kaempferol derivatives, as particularly effective in reducing lipid accumulation in this MASLD cell model while also providing a comprehensive characterization of traditionally used plants from the Côa Valley region.

Background/Objectives: Côa Valley located in the northeast of Portugal, harbors more than 500 medicinal plant species. Among them, four species stand out: Equisetum ramosissimum Desf. used to treat hemorrhages, urethritis, hepatitis, and rheumatic diseases; Rumex scutatus L. subsp. induratus (Boiss. & Reut.) Malag. consumed in salads or with mashed potatoes and used to reduce inflammation and constipation; Geranium purpureum Vill. and Geranium lucidum L. used as antipyretic agents, for pain relief, to halt hemorrhages, and to address gastric and inflammatory diseases. Given the immense medicinal potential of these four species, we evaluated its protective effect on in vitro model for the lipotoxicity associated to Non-Alcoholic Fatty Liver Disease (MASLD). Methods: Cytotoxicity of decoction (D) and hydroalcoholic (EtOH80%) extracts from the four species was assessed through the resazurin and sulforhodamine B (SRB) assays. Lipoprotection potential was determined by incubating previously human HepG2 cells with the extracts and then incubated with palmitic acid (PA). Lipid accumulation was determined through the Nile Red assay. Results: The extracts induced minimal cell metabolic and cell mass decrease at 25 and 50 µg/mL concentrations, indicating their safety. At 100 µg/mL, the cell metabolic activity was moderately affected in all extracts, except for E. ramosissimum extracts. Pre-incubation with E. ramosissimum decoction, significantly decreased the neutral lipid accumulation measured after PA accumulation. Conclusions: These findings suggest that E. ramosissimum decoction, rich in kaempferol derivatives, exhibits a notable capacity reducing lipid accumulation in the cell model of metabolic dysfunction-associated steatotic liver disease (MASLD).

The wine industry is responsible for a considerable amount of waste produced by agricultural activities worldwide, which impacts both the economic sector and the environment through pollution and ecosystem imbalance. There are several examples of by-products generated during the winemaking process, such as grape pomace, vine leaves, grape stalks, or wine lees. These can be recovered and reused by the cosmetic industry, which is actively seeking natural and greener products. There are active ingredients that come from by-products that have relevant bioactive properties such as antioxidant, antiaging, anti-hyperpigmentation, or cellular protection. Therefore, the use of by-products from the wine industry as a source of active ingredients for topical application has attracted attention from the scientific community, overcoming some of the drawbacks of the winemaking process. Further research into extraction processes and methods is essential, as they directly influence the quality and quantity of recovered active ingredients. While current cosmetic products on the market undergo safety and cytotoxicity testing, it is important to evaluate the effects of pesticide treatments applied before pruning and the toxicity of the by-products to ensure the safety of future formulations. This review addresses a critical discussion on this subject, assessing the potential benefits of their use in topical formulations. Graphical Abstract

Atopic dermatitis (AD) is a chronic eczematous inflammatory disease that may arise from environmental, genetic, and immunological factors. Despite the efficacy of current treatment options such as corticosteroids, such approaches are mainly focused on symptom relief and may present certain undesirable side effects. In recent years, isolated natural compounds, oils, mixtures, and/or extracts have gained scientific attention because of their high efficiency and moderate to low toxicity. Despite their promising therapeutic effects, the applicability of such natural healthcare solutions is somewhat limited by their instability, poor solubility, and low bioavailability. Therefore, novel nanoformulation-based systems have been designed to overcome these limitations, thus enhancing the therapeutic potential, by promoting the capacity of these natural drugs to properly exert their action in AD-like skin lesions. To the best of our knowledge, this is the first literature review that has focused on summarizing recent nanoformulation-based solutions loaded with natural ingredients, specifically for the management of AD. We suggest that future studies should focus on robust clinical trials that may confirm the safety and effectiveness of such natural-based nanosystems, thus paving the way for more reliable AD treatments.