The interest in natural deep eutectic solvents (NADESs) in green technology as an alternative to organic solvents has grown over the past decades. In this work, for the first time, the effect of dilution with water on the physicochemical and antimicrobial properties of lactic acid-based NADES with choline chloride (NADES1), sorbitol (NADES2), and glucose (NADES3) was systematically studied. According to FTIR data, after the dilution of NADESs with water, the strong hydrogen bonds weakened, however, were not destroyed after dilution of up to 40% water. The dilution of NADES with water resulted in a linear decrease in density and refractive index and in a linear increase in pH. The equations for the prediction of NADES density, pH, and refractive index as a function of water content were calculated. The viscosity decreased by half after adding approximately 10% water. The initial viscosity of NADES2 and NADES3 was significantly different. However, after adding 20% of the water, the viscosity was almost the same. The most pronounced decrease in surface tension (by 46.7%) was found for NADES1. The water activity was decreased in the following order: NADES3 > NADES1 > NADES2. The dilution of NADES with water caused a gradual increase in water activity. NADES1 showed the lowest minimal inhibitory concentrations (MIC) (7.8, 3.9, and 0.98 mg/mL) and minimum bactericidal concentrations (MBC) (15.6, 7.8, and 1.95 mg/mL) for Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, respectively. The antimicrobial activity was decreased by 2–8 times after the addition of 40% water. The water activity for all tested NADES together with low pH could explain the antimicrobial effect. The revealed regularity can be useful for the prediction of NADES properties and for the selection of green solvents on a laboratory and industrial scale.

The roots of licorice (Glycyrrhiza glabra L.) have been widely used in traditional and officinal medicines for the treatment of different diseases. Natural deep eutectic solvents (NADES) have become popular for the extraction of active principles from medicinal plants. However, the ability of NADES to co-extract trace elements during the isolation of target active compounds is rarely investigated. The aim of this study was to analyze the content of trace elements in acid-based NADES extracts from the roots of G. glabra and the health risks associated with them. In this study, we have tested for the first time the ability of several acid-based NADES to co-extract glycyrrhizic acid (GA) and trace elements from the roots of G. glabra. GA has been identified as the dominant phytochemical in G. glabra NADES extracts (0.145–0.495 mg/g). Due to the close pKa of lactic acid and GA, the yield of GA in lactic acid-based NADES was higher in comparison with other tested NADES. The yield of GA in NADES3-NADES5 was statistically significant and surpassed the yield of GA in water. The recovery of all elements (except Li) by all tested NADES was low (less than 6%). According to an ANOVA test, the hydrogen bond donor type plays a decisive role in the extraction of elements. A strong positive correlation between the recovery of GA and MPI was noted. The metal pollution index, hazard quotient, hazard index, and chronic daily intake were calculated and suggest that all tested NADES extracts of G. glabra roots were nontoxic and possess no health risk for both ingestion and topical application.

Natural deep eutectic solvents (NADES) have been extensively used for the extraction of a wide spectrum of plant materials. However, limited data about the in vivo toxicity of NADES extracts restrict their future practical application. In this study, we are aiming to assess the safety of a Sorbitol–lactic acid (3:1 mol./mol.; 30% water) NADES extract of Glycyrrhiza roots (GR) in mice. LC-MS/MS analysis revealed the presence of 17 metabolites, including phenolic acids, flavonoids, their glycosides, chalcones, terpene saponins, and coumarins. Interestingly, most of the identified compounds were found in higher amounts in NADES extract compared to water and EtOH extracts. No skin edema, inflammation, or erythema was observed in mice after topical application of NADES extract of GR and NADES at the doses of 50, 100, and 150 µL/mice in comparison with the control group. The calculated primary irritation index was about 0.45 both for NADES and NADES extract of GR only in high doses and falls into mild irritant categories. The individual Draize scores indicate that erythema was evident in the first three days and that all signs had disappeared by day five. No acute toxic signs or mortality of animals was observed in mice following oral administration of single doses of 4, 6, and 20 g/kg of NADES or NADES extract of GR. The NADES and extract seem to be safe at doses of up to 20 g/kg, and the LD50 was considered to be >20 g/kg. Our results open prospects for the use of NADES extract of GR for the development of transdermal and peroral formulations in the cosmetic, food, and pharmaceutical industries.

Background/Objectives: The pharmacological management of inflammation remains a clinical challenge, driving the demand for advanced topical formulations. This study utilizes a “smart-NADES” (natural deep eutectic solvent) paradigm to develop an innovative anti-inflammatory topical system. The aim was to evaluate the integrated antioxidant potential, alongside the in vitro and in vivo anti-inflammatory activities, of a novel smart-NADES licorice root extract and its hydrogel formulation. Methods: A NADES system composed of D-sorbitol and L-lactic acid (3:1) was employed for licorice root extraction. The antioxidant capacity was assessed using three independent assays and integrated via the Relative Antioxidant Capacity Index (RACI), while phytochemical interactions were quantified using the Chou–Talalai Combination Index (CI). In vitro anti-inflammatory activity was evaluated via protein stabilization capacity, and in vivo efficacy was validated using a formalin-induced paw edema model in mice. Results: The NADES extract contained glycyrrhizic acid levels of 6.3 ± 0.3 mg/g and showed strong antioxidant synergism in the DPPH assay (CI = 0.49 ± 0.07). The extract exhibited potent total antioxidant capacity (IC₅₀ = 11.9 ± 0.6 μg/mL) with a superior RACI score (1.23). In vitro protein stabilization (IC₅₀ = 63 ± 5 μg/mL) was comparable to diclofenac sodium. The 5% hydrogel numerically surpassed the commercial 2% diclofenac Emulgel (67.5% vs. 32.9% inhibition, respectively) at 24 h, although the direct pairwise comparison did not reach statistical significance (p = 0.186). Conclusions: The developed smart-NADES licorice hydrogel represents an effective, green formulation with pronounced topical anti-inflammatory properties, establishing a robust pharmacological rationale for advanced topical drug delivery.

Introduction. Phytomedicines (PM) are medicinal products that contain at least one plant-based component with established pharmacological activity. The global PM market has demonstrated steady growth for many years. Despite growing demand, the Russian PM market remains understudied. Aim. To assess the current state and structure of the Russian PM market over the period 2020–2025. Materials and methods. The data from the analytical agency DSM Group (2020–2025) were used for the market assessment. PM containing at least one herbal-based component were included in our analysis. A modified Boston Consulting Group (BCG) matrix was used for the strategic assessment of the PM market segments. Results and discussion. In 2025, the total Russian PM reached 152.6 bln rubles ($1.9 bln) and 393.4 mln packs. PM account for 6.2 % of the total pharmaceutical market in value and 8.6 % in volume terms, respectively. Domestic manufacturers lead the sales structure in volume (up to 80 %), while imported PM dominate in value (up to 57 %). The top 3 medicinal plants most frequently included in PM (in 2025) are Valeriana officinalis L., Mentha piperita L., and Glycyrrhiza spp. The herbal medicinal products (HMP) with individual compounds (IC) isolated from plant materials are widely presented on the market. Of these, more than 14 % are PM with alkaloids (morphine from Papaver somniferum L., pilocarpine from Pilocarpus pennatifolius Lem., atropine from Atropa belladonna L., platyphylline from Porella biedermannii Frank Müll., vinpocetine from Vinca minor L., and paclitaxel from Taxus spp.). By 2025, the average annual growth rate exceeded 8 % in monetary terms and 2 % in packages for alkaloid-based drugs. Considering classification by pharmacotherapeutic groups, bioflavonoids (HMP) based on diosmin, hesperidin, rutin, and their combinations) lead the market in monetary terms for 2025. Sleeping and sedatives PM are leaders in unit sales. Expectorants and respiratory medications hold second place in both monetary and packages terms. The promising niche of brown algae-based medicines (kelp) is also showing dynamic growth, with sales reaching 8.9 bln rubles. Among tonic PM, phytoadaptogens hold a significant position, with sales totaling 3.4 bln rubles in value and 38.7 mln packs in volume for the 2020–2025 period. The Compound Annual Growth Rate (CAGR) for the PM market is +6 %. The category of homeopathic medicines, despite its minimal market share (1.6 %), is the most dynamic (CAGR +9 %). The category of combination drugs with PM ranks second in terms of sales (24.8 %) and 32.6 % of packages). The CAGR for this category is +3 % and the drivers with a CAGR of +12 % are PM with medicinal plant materials (MPM). The category of herbal medicines is growing by 8 % and is the clear leader in terms of packages sales (35.3 %). The herbal medicines category, while leading in terms of sales value (54.3 %), is showing moderate growth (CAGR +5 %). According to the BCG matrix estimate for 2020–2025, the only segment that occupies the "Star" position in the PM market structure is the HMP with IC (the segment accumulates 31.0 % of the total sales volume (RUB 249.2 bln) with a CAGR of 6 %). The "Cash Cows" category encompasses the largest number of segments, but the dominant positions are held by galenic HMP (tinctures, extracts, elixirs, juices, and syrups) with a CAGR of 5 % and HMP (CAGR of 8 %). Solid dosage forms predominate in the PM market, accounting for approximately 63 % by value and 44.1 % by packages. The share of tinctures and drops accounts for 13.1 % and 12.2 % in monetary terms and in packages, respectively. Conclusion. A key direction for PM Industry development is to increase the share of locally produced drugs with high added value. The strategic priority for the development of the PMs market is to support the segments of HMPs with IC, galenic HMPs and plant-based medicines (PbM), as well as scaling the segments of combinations of combined medicine (CM) with MPM as the fastest growing.

Ethnopharmacological relevance: Traditional medicine (TM) is used worldwide, yet its global footprint, in terms of both scientific research and public engagement, remains poorly quantified. While thousands of medicinal plant species have been documented, it is unclear which ones receive the most academic attention, which ones are most sought after by the general public, and how these two dimensions relate to each other. This lack of integrated understanding limits the evidence-based integration of TM into modern healthcare systems and may leave widely used but under-investigated remedies neglected.This study is firmly grounded in ethnopharmacological theory by systematically documenting and quantifying the global landscape of TM uses. Rather than treating TM as a mere source of bioactive compounds, our work engages directly with the cultural, historical, and practical dimensions of medicinal plant knowledge as it exists across diverse societies. The identification of "orphan" traditional medicines, widely used in community practice but severely under-investigated scientifically, represents a direct contribution to evidence-based integration of TM into healthcare systems, which is a core objective of ethnopharmacological research. Furthermore, by mapping the gap between academic prioritization and public engagement across 11 languages representing approximately 5.6 billion people, this study provides a global empirical foundation for understanding how traditional medical knowledge is preserved, transmitted, and transformed in the digital era, a question of fundamental importance to the ethnopharmacological community, including academics and enterprise.Aim of the review: To quantitatively map the global patterns of research focus and public interest for a large set of traditional medicines, identify the most extensively studied species, compare them with those most frequently searched online, and characterize the gaps between academic prioritization and real-world community use.Materials and methods: A panel of global TM experts compiled an initial list of 3,212 medicinal substances from major pharmacopoeias and authoritative sources across 34 countries. After taxonomic standardization, 2,567 distinct species were retained. Bibliometric analysis was performed using PubMed to retrieve citation counts for each species, with attention to geographical origin, disease associations, and temporal trends (2015-2024). Public interest was assessed by querying the dominant search engines in 11 languages representing the ten most populous countries (total population approximately 5.6 billion). Search volumes were collected, validated for consistency, and normalized by population. Hierarchical clustering and comparative analyses were used to stratify species by growth trajectories and to identify overlap between high-citation and high-search species.Results: Academic output was heavily concentrated: the top 20 most studied species (e.g., Panax ginseng C.A.Mey., Salvia miltiorrhiza Bunge, Withania somnifera (L.) Dunal) accounted for nearly 20% of the total literature, despite representing less than 1% of the analyzed species. China and India dominated research contributions, followed by several European and Middle Eastern countries.Temporal analysis revealed four distinct citation growth clusters; C. sativa and M. oleifera showed the steepest increase (mean +362.4%) during the COVID-19 pandemic. In contrast, public searches across the 11 languages totaled over 6.4 billion (average 1.13 searches per capita), with English showing the highest per-capita activity (4.57) and Hindi the lowest (0.01).Only five species, including N. sativa, A. sativum, C. sativa, C. longa, and A. vera, ranked highly in both academic and public domains. Widely searched but low-citation remedies included staple crops (maize, rice, wheat) and common spices (peppermint, olive, rosemary), identifying a class of "orphan" traditional medicines.Conclusions: This first large-scale quantification reveals a pronounced divergence between academically studied and publicly used traditional medicines. While research is concentrated on a few species with historical medical importance, public interest is dominated by accessible, everyday items. The identified "orphan" remedies, namely those highly utilized yet under-investigated, represent critical opportunities for future research. Aligning scientific inquiry with public practice is essential to support evidence-based integration of TM into healthcare systems and to preserve the cultural and medicinal heritage embedded in traditional pharmacopeias.