Wound healing is a tightly regulated biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. When these phases are disrupted, wound repair can be delayed or become chronic. Key signaling pathways, including NF-κB, JAK/STAT, and MAPK, coordinate immune activation, cytokine expression, cell proliferation, and tissue repair. Medicinal plants and their bioactive compounds, such as flavonoids, alkaloids, tannins, and other phytoconstituents, have demonstrated significant anti-inflammatory, antioxidant, and immunomodulatory effects that modulate these pathways. Tannins contribute to repair through neutralization of reactive oxygen species (ROS), activation of antioxidant enzymes, and metal-chelating activity. Alkaloids, including tetrandrine, oxymatrine, and berberine, inhibit NF-κB signaling, thereby reducing pro-inflammatory cytokines such as IL-1β and TNF-α. Flavonoids regulate inflammatory mediators and enzymes, including COX and phospholipase A2, while also protecting against oxidative stress and stimulating fibroblast and keratinocyte proliferation—key steps in tissue regeneration. Collectively, these compounds accelerate wound closure by reducing oxidative stress and promoting cellular proliferation and migration. Thus, medicinal plants represent promising complementary approaches to wound management. Future research should focus on developing advanced drug delivery systems to enhance the stability, bioavailability, and targeted action of plant-derived compounds. Localized and biomaterial-based strategies show promise for sustained release at the wound site, and further preclinical and clinical studies are required to ensure their safety, reproducibility, and efficacy.

Wounds are among the most common skin diseases. They are formed after tissue injury and result in severe damage to the epidermis. The application of plants for wound healing is not only a cheap and accessible way of treatment, but also provides a reliable natural resource of medicinal substances with fewer side effects. Biologically active substances such as alkaloids, essential oils, flavonoids, tannins and phenolic compounds demonstrate a wide spectrum of action: wound healing, anti-inflammatory, antibacterial and antioxidant effects. This review article examines the chemical composition of three plants - Calendula officinalis, Marrubium vulgare, Vitis vinifera and the signal transduction in skin wound healing. Studies have shown that they have a strong antioxidant effect, hemostatic activity, powerful vasoconstrictor effect, pro-angiogenic and cell-protective effects. Because of the mentioned benefits of these plants, more scientific research and well-designed clinical trials are needed to establish their wider use in wound treating medicaments.

Achillea clypeolata Sibth. & Sm. is an endemic Balkan species traditionally used in Bulgarian folk medicine. The present study aimed to conduct untargeted metabolomic profiling and characterization of 70% methanol, 70% ethanol, and water A. clypeolata extracts via the UHPLC-ESI-Orbitrap-MS/MS method. Furthermore, the in vitro antioxidant and antibacterial activities were determined. The putative analysis led to the identification of 62 compounds: 41 in positive and 21 in negative ionization mode. Predominant classes included flavonoids, organic acids, terpenes, fatty acids, sugars, and amino acids. The antiradical tests revealed the greatest antioxidant potential for the methanol extract, followed by the ethanol one, consistent with the findings for the total polyphenol and flavonoid contents. The antibacterial assays revealed the lowest minimum inhibitory concentration against the studied Gram-positive bacteria for the methanol extract, while the ethanol one better suppressed the Gram-negative ones’ growth. Additionally, the ethanol extract had the lowest minimum bactericidal concentration (MBC) against S. aureus while the hydroalcoholic extracts’s MBC was equal for the rest of the studied bacterial strains. The present findings provide additional insights into the phytochemical contents and in vitro biological activity of Achillea clypeolata, and serve as a basis for future investigations associated with its pharmacological application.

Background: Betonica bulgarica Degen et Neič is an endemic Balkan species with reported antioxidant, antimicrobial, antitumor, immunomodulatory, and hypoglycemic effects. Despite its promising biological potential, its phytochemical composition remains incompletely characterized, and its application in advanced wound-healing medications has not been investigated. Therefore, the aim of the present study is to develop hydroxypropyl methylcellulose (HPMC)-based wound dressings incorporating B. bulgarica bioactive compounds as a biocompatible delivery platform with promising physical and chemical properties suitable for further biological evaluation in wound-care applications. Methods: The phytochemical composition of the extract was investigated using Ultra-High-Performance Liquid Chromatography–Mass Spectrometry (UHPLC–MS). Results: The putative analysis led to the identification of 81 compounds in positive and negative ionization mode. Predominant classes included flavonoids, phenolic acids, terpenes, organic acids, fatty acids, sugars, nucleobases and amino acids. HPMC-based films containing B. bulgarica extract were prepared and characterized with key physicochemical and mechanical properties. Mechanical evaluation demonstrated that high-molecular-weight HPMC films exhibited higher tensile strength (73 ± 9 MPa) than low-molecular-weight formulations (44 ± 8 MPa). Increasing the Betonica bulgarica extract loading up to 8.8 mg/cm² was associated with concentration-dependent decreases in tensile strength, elongation at break, and Young’s modulus across all film types. These changes indicate an alteration of the mechanical behavior of the films, although the individual contributions of the extract and the varying PEG-to-HPMC ratio cannot be distinguished. Incorporation of Betonica bulgarica extract reduced the water vapor transmission rate (WVTR) of the HPMC films, promoting a denser polymer matrix structure. Additionally, high-molecular-weight HPMC films displayed higher WVTR values than low-molecular-weight formulations due to increased free volume within the entangled matrix. The release profiles of Betonica bulgarica extract from the HPMC films were fitted to the Korsmeyer–Peppas model using data from the first 8 h of the release study (R² = 0.9811–0.9989). The release exponent values indicated anomalous transport behaviour for the low-MW HPMC films (n = 0.68–0.70), whereas the values obtained for the high-MW HPMC films (n = 0.404–0.438) were closer to the range commonly associated with Fickian diffusion in planar matrices. The high-MW HPMC films showed more gradual release profiles, supporting their further investigation as matrices for the delivery of plant-derived extracts. Conclusions: The findings provide further insight into the phytochemical profile of the endemic species B. bulgarica and demonstrate the feasibility of incorporating its bioactive compounds into HPMC-based wound-dressing film for future biological evaluation. The developed formulations represent a promising natural-based platform for wound-healing applications, although further studies are required to establish their therapeutic efficacy and mechanism of action.