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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: 20 July 2026 | Viewed by 12332

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Dr. Octavia Gligor

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Guest Editor

Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania
Interests: bioactive compounds; plant extracts; natural dermatocosmetic products; skincare; cutaneous applications

Dr. Ana-Maria Vlase

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Department of Pharmaceutical Botany, Faculty of Pharmacy, Iuliu Hațieganu University of Medicine and Pharmacy, 8 Victor Babeș Street, 400012 Cluj-Napoca, Romania
Interests: modern extraction techniques; optimized/standardized extracts; phytochemical analysis; health outcomes of plant extracts; bioaccessability of compounds from various vegetal matrices; drug–vegetal extract interactions at metabolic level
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Dear Colleagues,

In recent decades, the interest in natural products has grown significantly, particularly in the fields of dermatology and cosmetology. Medicinal plants and their extracted bioactive compounds are increasingly incorporated into skincare formulations due to their therapeutic potential, biocompatibility, and lower risk of adverse effects compared to synthetic alternatives.

Numerous plant-derived compounds—such as those from Matricaria recutita, Calendula officinalis, or Melaleuca alternifolia—have demonstrated antioxidant, anti-inflammatory, antimicrobial, and photoprotective properties, making them suitable for various dermatological applications. These include anti-acne and anti-aging treatments, care for sensitive skin, sun protection, and even adjunctive use in skin cancer therapies. Examples range from green tea and witch hazel in acne care to pomegranate extract and Coenzyme Q10 in anti-aging formulations and raspberry seed and carrot oils in natural sun protection.

However, challenges remain, such as the instability of certain natural compounds, risk of allergic reactions, and the need for standardization of extract purity and dosage. Addressing these limitations requires continued scientific validation, particularly through well-designed in vitro and in vivo studies.

This Special Issue invites original research articles and reviews focused on the characterization, biological activity, and dermatological application of natural bioactive compounds. Emphasis will be placed on mechanistic studies, innovative formulation strategies, and preclinical models supporting the safe and effective integration of natural compounds into modern dermatocosmetic products.

Dr. Octavia Gligor
Dr. Ana-Maria Vlase
Guest Editors

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Keywords

bioactive compounds
plant extracts
topic preparations
skincare
cutaneous applications
skin cancer
medicinal plants
modern extraction techniques
optimized/standardized extracts
phytochemical analysis
health outcomes of plant extracts
bioaccessability of compounds from various vegetal matrices
drug–vegetal extract interactions at metabolic level

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Published Papers (8 papers)

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Research

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28 pages, 14202 KB

Open AccessArticle

In Situ Thai Apis mellifera Propolis Film as Potential Protective Phytopharmaceuticals Against UVB-Induced HaCaT Keratinocyte Damage

by Takron Chantadee, Anyamanee Chatsirisupachai, Ampai Phrutivorapongkul, Sunee Chansakaow, Sasithorn Sirilun and Onusa Thamsermsang

Pharmaceuticals 2026, 19(5), 680; https://doi.org/10.3390/ph19050680 - 27 Apr 2026

Viewed by 245

Abstract

Background/Objectives: Propolis is well recognized for its antioxidant, anti-inflammatory, and wound-healing properties, supporting its cutaneous application in phytopharmaceuticals for the management of ultraviolet B (UVB)-induced skin damage. However, the application of propolis is limited by its intense coloration, stickiness, and poor user convenience. In situ film-forming systems (FFS) represent a novel dosage form designed to overcome these challenges, although efficacy data for using FFS remains limited. Consequently, this study aimed to develop a propolis-based FFS and evaluate its efficacy in mitigating UVB-irradiated HaCaT keratinocytes. Methods: Apis mellifera propolis was macerated and analyzed for total phenolic content (TPC) and total flavonoid content (TFC), radical scavenging activity (DPPH assay), and nitric oxide scavenging capability. Bioactive compounds were identified using high-performance liquid chromatography analysis (HPLC). The propolis extract was formulated into FFS and investigated on UVB-damaged HaCaT keratinocytes. An MTT viability assay, propidium iodide flow cytometry for cell cycle analysis, and a scratch wound healing assay were used to evaluate the therapeutic effects of the FFS. Results: The 72 h macerated propolis extract contained high levels of TPC, TFC, and targeted phytochemicals. The propolis extract exhibited free radical scavenging and nitric oxide inhibitory activities. Seven formulations exhibited suitable performance, with formulation F7 (FFS-F7) demonstrating superior drying time and dose-dependent free radical scavenging. Notably, FFS-F7 (≥12.5 µg/mL) significantly enhanced HaCaT proliferation, mitigated UVB-induced cell cycle arrest, reduced cellular damage, and accelerated wound closure. Conclusions: This study successfully developed an FFS that not only overcomes these physical drawbacks but also preserves the biological activity of the extract. The significant protective and restorative effects against UVB-induced HaCaT damage demonstrate the therapeutic potential of Thai Apis mellifera propolis and establish the FFS as a versatile base with the potential for delivering other bioactive compounds. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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16 pages, 4218 KB

Open AccessArticle

Quercus acuta Acorn Bran Extract Enhances Wound Healing by Promoting Human Dermal Fibroblast Migration and Antioxidant Activity

by So-An Lim, Tae Hyun Son, Hye-Lim Shin, Dongsoo Kim, Jun-Hyuck Yoon, Hwan-Gyu Kim, Hyunmo Choi, Shin-Hye Kim and Sik-Won Choi

Pharmaceuticals 2026, 19(3), 481; https://doi.org/10.3390/ph19030481 - 15 Mar 2026

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Abstract

Background/Objectives: Wound repair-associated processes and the antioxidant properties of natural products play critical roles in skin wound healing and barrier restoration. Wound healing is a complex process characterized by a series of interconnected events that facilitate the self-repair of the skin following injury. Methods: This study aimed to evaluate the effects of Quercus acuta acorn bran extract (QAABE) on wound healing using human dermal fibroblast (HDF) cell cultures treated with QAABE. Additionally, in vivo experiments were conducted using a mouse model of skin injury to assess the wound-healing potential of the extract. Results: The results indicated that QAABE enhanced wound healing in vitro by upregulating extracellular matrix-related markers, including vimentin, Col1a1, Col3a1, endothelin, fibronectin, and VEGF at the mRNA level, and increasing the protein expression of vimentin, COL1A1, endothelin, and α-SMA. QAABE also exhibited reactive oxygen species (ROS)-scavenging activity. In the mouse skin injury model, QAABE treatment accelerated wound closure and was associated with reduced inflammatory responses. Conclusions: These findings suggest that QAABE may promote wound-healing-related responses in both in vitro and in vivo models, supporting its potential as a candidate for further investigation in wound-healing research. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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27 pages, 3106 KB

Open AccessArticle

Preparation and Investigation of Artemisia annua L.-Loaded Alginate Hydrogels with Excipients

by Boglárka Papp, Zsolt Szűcs, Sándor Gonda, Zoltán Cziáky, Richárd Kajtár, István Lekli, Ádám Haimhoffer, Ágnes Klusóczki, Liza Józsa, Ágota Pető, Nodirali S. Normakhamatov, Zoltán Ujhelyi, Ildikó Bácskay and Pálma Fehér

Pharmaceuticals 2026, 19(3), 424; https://doi.org/10.3390/ph19030424 - 5 Mar 2026

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Abstract

Background: Artemisia annua L. is a medicinal plant with documented antimicrobial, antioxidant, and anti-inflammatory properties. Although widely studied for internal therapeutic applications, its topical use—especially in hydrogel-based systems—has not been thoroughly investigated. The aim of this study was to develop sodium alginate hydrogels containing Artemisia annua extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. Methods: Select bioactive constituents of the Artemisia annua extract were quantified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS). Hydrogels were prepared by cross-linking sodium alginate with a calcium carbonate–glucono-delta-lactone system and were formulated with or without hyaluronic acid and dexpanthenol. Physicochemical evaluations included measurements of moisture content, water-retention capacity, gelation time, and pH. The hydrogel microstructure was examined by scanning electron microscopy (SEM). Antioxidant activity was assessed using three methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and the cupric reducing antioxidant capacity (CUPRAC) assay. Biocompatibility and regenerative effects were analyzed using cell viability assays and an in vitro scratch wound model on human keratinocyte cells. In vivo wound-healing efficacy was examined in rats with full-thickness skin excisions. Results: The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of Artemisia annua. Hydrogels supplemented with hyaluronic acid and dexpanthenol exhibited improved hydration stability and higher porosity. All formulations demonstrated measurable antioxidant activity, and those containing hyaluronic acid showed the strongest effects. The preparations were biocompatible and enhanced keratinocyte migration in vitro, with the combined hyaluronic acid–dexpanthenol formulation promoting the fastest wound closure. In vivo, Artemisia annua hydrogels accelerated wound healing by two to three days compared with untreated wounds. Conclusions: These results confirm the promise of Artemisia annua hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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20 pages, 2705 KB

Open AccessArticle

Instrumental In Vivo Assessment of Cosmetic Emulsions Containing Platelet-Rich Fibrin (PRF) or Recombinant Epidermal Growth Factor (EGF): A Pilot Compatibility Study

by Marzena Liliana Wyganowska, Filip Tyliszczak, Marta Marzec, Sylwia Klewin-Steinböck and Izabela Nowak

Pharmaceuticals 2026, 19(3), 394; https://doi.org/10.3390/ph19030394 - 28 Feb 2026

Viewed by 549

Abstract

Background: This study evaluates short-term skin compatibility and biophysical changes in new cosmetic preparations containing PRF and EGF, conducted through in vivo studies. Material and Methods: The study involved 20 healthy volunteers (aged 20–40) who received three identically packaged creams to be applied for a period of four weeks to specific facial areas: formulation 1: base formulation (control); formulation 2: base formulation human epidermal growth factor (EGF) loaded; and formulation 3: base formulation platelet-rich fibrin (PRF) loaded. Skin assessments were conducted at baseline (week 0) and at weeks 1, 2, and 4. Transepidermal water loss (TEWL), skin hydration using corneometry to determine the moisture content of the stratum corneum, skin elasticity using a cutometer to measure the skin’s ability to return to its original state after deformation, and dermal bioavailability were measured. EGF concentration in the stratum corneum will be measured using the tape-stripping method followed by HPLC (high-performance liquid chromatography) analysis. Results: A significant decrease in TEWL was observed for all tested formulations (24%, 37%, and 34%, for formulations 1, 2, and 3, respectively), indicating improved skin barrier function. Formulation 3 showed the highest increase in skin hydration (by 95%), followed by formulation 2. Both formulations 2 and 3 demonstrated improvements in skin elasticity, with formulation 3 showing the greatest enhancement. EGF concentration in the stratum corneum increased over the four-week period, reaching equilibrium with the product concentration by week four. Conclusions: The in vivo instrumental compatibility studies confirmed that the new cosmetic formulations were well tolerated and associated with short-term improvement in selected skin parameters. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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17 pages, 4572 KB

Open AccessArticle

Rosemary Aqueous Extract as a Natural Alternative to Retinol for Skin Aging Intervention

by Ping Gao, Hong Zhang and Xuelan Gu

Pharmaceuticals 2026, 19(3), 378; https://doi.org/10.3390/ph19030378 - 27 Feb 2026

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Abstract

Background/Objectives: Retinoids are the gold standard for topical anti-aging treatments; however, their application is frequently limited by skin irritation and poor tolerability, particularly in sensitive or aged populations. Consequently, there is a growing demand for plant-based alternatives that offer comparable efficacy with an improved safety profile. The present study aims to explore the effects of rosemary aqueous extract (RE) on skin aging and its potential as a safe and effective alternative to retinol. Methods: Comparative RNA sequencing was employed to analyze the transcriptomic profiles of RE and retinol in human dermal fibroblasts (HDFs). Efficacy of collagen synthesis was evaluated using in vitro 2D and 3D skin models. As aging is associated with chronic inflammation, the responses of HDFs from young versus elderly donors under chronic IL-1β stimulation were compared, and a novel inflammaging model combining repetitive UVA irradiation with chronic cytokine (IL-1β and TNF-α) stimulation was utilized. Potential for neurogenic irritation was assessed by measuring transient receptor potential vanilloid subtype 1 (TRPV1) expression in SH-SY5Y neuronal cells. Results: RE was revealed to regulate gene expression in a pattern analogous to retinol, while also modulating distinct pathways related to wound healing and oxidative stress. RE not only enhanced collagen I synthesis but also protected against UVA-induced damage by preserving epidermal thickness, restoring the dermal-epidermal junction (DEJ), and reducing inflammation. Furthermore, RE demonstrated protective effects in the inflammaging model, effectively countering the synergistic damage caused by combined intrinsic and extrinsic stressors. Notably, RE downregulated TRPV1 expression in SH-SY5Y cells, suggesting a potential of reducing skin itching sensation. Conclusions: These findings position RE as a multifaceted anti-aging ingredient that not only represents a promising candidate for a retinol alternative, but also in the context of inflammaging and sensitive skin conditions, highlighting its potential impact on the future of anti-aging skincare. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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14 pages, 777 KB

Open AccessArticle

Rheological Characterization of Lemon Oil-Loaded Eucerin Cream and Aquaphor Ointment

by Shorouq Alzahrani and Jinsong Hao

Pharmaceuticals 2025, 18(12), 1838; https://doi.org/10.3390/ph18121838 - 2 Dec 2025

Viewed by 767

Abstract

Background/Objectives: Lemon oil has demonstrated its therapeutic effects in various dermatological diseases, and different dosage forms have been investigated to incorporate lemon oil. Using the existing ointment bases to prepare drug-loaded formulations is a common practice in formulation development. Eucerin and Aquaphor are commonly used ointment bases in pharmacy for compounding preparations to meet patient needs. The maximum drug-loading capacity is an important consideration in order not to compromise desired properties of the ointment bases. The objective of this research was to determine the maximum lemon oil loading capacities by understanding the effects of loading lemon oil into Eucerin and Aquaphor on the rheological properties of the lemon oil-loaded formulations. Methods: Lemon oil was incorporated into Eucerin and Aquaphor at different concentrations. The rheological properties of the formulations were determined in flow and oscillation modes. Creep and recover tests were performed to determine the viscoelastic properties of the formulations. Results: The results showed that addition of lemon oil impacted rheological properties, including viscosity, elastic modulus, viscous modulus, compliance, and strain%, but the overall rheological behaviors remained consistent with the control for both bases. Conclusions: The maximum loading capacity of lemon oil could be determined from rheological testing. The rheological studies provided an important tool to determine the desired formulations for topical applications, without affecting the performance characteristics of the commercial products. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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27 pages, 2069 KB

Open AccessEditor’s ChoiceArticle

In Vitro and in Vivo Efficacy of Different Ointment Formulations Containing Centaurium erythraea Rafn. Aerial Extract

by Anett Jolán Karetka, Boglárka Papp, István Lekli, Ana-Maria Vlase, Annamária Pallag, Laura Grațiela Vicaș, Antonia-Maria Lestyán, Liza Józsa, Dóra Kósa, Ágota Pető, Zoltán Ujhelyi, Fruzsina Nacsa, Ildikó Bácskay, Pálma Fehér and Tünde Jurca

Pharmaceuticals 2025, 18(11), 1681; https://doi.org/10.3390/ph18111681 - 6 Nov 2025

Viewed by 2381

Abstract

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol^® P (diethylene glycol monoethyl ether), Capryol^® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol^® P and Capryol^® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10⁻⁵ cm²/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol^® P and Capryol^® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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Review

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23 pages, 2247 KB

Open AccessReview

Comparison of the Effectiveness Differences between Western and Chinese Medicinal Ointments against Eczema

by Siu Kan Law, Yanping Wang and Xiao Xiao Wu

Pharmaceuticals 2025, 18(9), 1248; https://doi.org/10.3390/ph18091248 - 22 Aug 2025

Cited by 2 | Viewed by 5309

Abstract

Eczema is the most common skin disease among Hong Kong’s adults and children, affecting an estimated 30% of the total population. Western and Chinese medicinal ointments are the usual treatment for eczema. Conventional Western medicinal ointments are topical corticosteroids and non-steroidal agents. Eczema skin products include “Aveeno Parabens Lotion”, “Cerave Moisturizing Cream”, and “Cetaphil Lotion”. However, these are not a long-term solution for managing significant erythema. Chinese medicinal ointments are based on adjusting the formula, including the ingredients and amount, to address an individual’s skin condition and other factors that may be worsening symptoms. This approach aims to regulate the immune system and make it less reactive to environmental and food allergies. This approach is mainly for local topical use. The ingredients of eczema skin products should include Coptis chinensis Franch, Phellodendron chinense Schneid, Angelica sinensis (Oliv.) Diels, Rehmannia glutinosa Libosch, Curcuma longa L., and sesame oil. Chinese medicinal ointments are natural ingredients, personalized formulas, and concerned with holistic healing, while Western medicinal ointments provide fast-acting relief, targeted action, and a standardized dosage. Methods: Nine electronic databases, such as WanFang Data, PubMed, Science Direct, Scopus, Web of Science, Springer Link, SciFinder, and the China National Knowledge Infrastructure (CNKI), were searched mainly within the past twenty years and without any language restrictions. The inclusion criteria were the keywords “Western medicine and ointment”, “Chinese medicine and ointment”, and “Western and Chinese medicines and ointment”. Differences in effectiveness between Western and Chinese ointments were evaluated to determine if they had functions against eczema. This review included an analysis and summary of all relevant papers. Results: Western medicinal ointments are topical corticosteroids, and they exert their pharmacological activities via many mechanisms, including anti-inflammatory, immunosuppressive, antiproliferative, and vasoconstrictive effects on eczema. Similarly, Chinese medicinal ointments have the same pharmacological functions, but they may focus on the immune system for the treatment of inflammatory and skin conditions, including erythema, edema, dryness, desquamation, and callus exfoliation. Conclusion: Based on the clinical research, the effectiveness rate of integrated Chinese and Western medicines was 88%, which was greater than the 70% rate for using Western medicine alone to treat eczema. Western and Chinese medicinal ointments have different active ingredients with advantages and disadvantages for eczema or when acting as skin care products. The most important thing is knowing “How” to use Western and Chinese medicinal ointments properly, especially for some formulations of Chinese ointments. It may be beneficial to consider the pharmacokinetic studies of herbal ingredients, which offer personalized formulas tailored to individual body constitutions and conditions, as well as to emphasize holistic healing, addressing both symptoms and underlying imbalances in the body. Much more work needs to be carried out, such as safety assessments of these ointments for use as skin care products for eczema. Full article

(This article belongs to the Special Issue Natural Products for Skin Applications)

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