Ascophyllum nodosum (Linnaeus) Le Jolis from Arctic: Its Biochemical Composition, Antiradical Potential, and Human Health Risk.

Ascophyllum nodosum is a brown seaweed common in Arctic tidal waters. We have collected A. nodosum samples from the Barents Sea (BS), Irminger Sea (IS), and Norwegian Sea (NS) in different reproductive stages and have evaluated their biochemical composition, radical scavenging potential, and health risks. The total content of dominating carbohydrates (fucoidan, mannitol, alginate, and laminaran) ranged from 347 mg/g DW in NS to 528 mg/g DW in BS. The proportion of two main structural monosaccharides of fucoidan (fucose and xylose) differed significantly between the seas and reproductive phase, reaching a maximum at the fertile phase in the BS sample. Polyphenols and flavonoids totals were highest in NS A. nodosum samples and increased on average in the following order: BS < IS < NS. A positive correlation of free radical scavenging activity for seaweed extracts with polyphenols content was observed. The concentration of elements in A. nodosum from the Arctic seas region was in the following order: Ca > Mg > Sr > Fe > Al > Zn > As total > Rb > Mn > Ba > Cu > Co. Seaweeds from BS had the lowest metal pollution index (MPI) of 38.4. A. nodosum from IS had the highest MPI of 83. According to the calculated target hazard quotient (THQ) and hazard index (HI) values, Arctic A. nodosum samples pose no carcinogenic risk to adult and child health and are safe for regular consumption. Our results suggest that the Arctic A. nodosum has a remarkable potential for food and pharmaceutical industries as an underestimated source of polysaccharides, polyphenols, and flavonoids.

Arctic Edible Brown Alga Fucus distichus L.: Biochemical Composition, Antiradical Potential and Human Health Risk.

Fucus distichus L. is the dominant canopy-forming macroalga in the rocky intertidal areas of the Arctic and Subarctic. In the present study, the impact of the geographic location of F. distichus collected in the Baffin Sea (BfS), Norwegian Sea (NS), White Sea (WS), and Barents Sea (BS) on the variations in biochemical composition, antiradical properties, and health risk was evaluated. The accumulation of main carbohydrates (fucoidan, mannitol, and alginic acid) varied from 335 mg/g dry weight (DW) in NS to 445 mg/g DW in BS. The highest level of the sum of polyphenols and flavonoids was found in samples of F. distichus from WS and was located in the following ranking order: BS < BfS < NS < WS. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity of seaweed is correlated with its phenolic content. It is notable that in most Arctic F. distichus samples, Cd, Cr, Pb, and Ni were not detected or their concentrations were below the limit of quantification. According to calculated targeted hazard quotient and hazard index values, all studied samples of Arctic F. distichus are safe for daily consumption as they do not pose a carcinogenic risk to the health of adults or children. The results of this study support the rationale for using Arctic F. distichus as a rich source of polysaccharides, polyphenols, and flavonoids with important antiradical activity. We believe that our data will help to effectively use the potential of F. distichus and expand the use of this algae as a promising and safe raw material for the food and pharmaceutical industries.

Optimization of Extraction of Phlorotannins from the Arctic Fucus vesiculosus Using Natural Deep Eutectic Solvents and Their HPLC Profiling with Tandem High-Resolution Mass Spectrometry.

Phlorotannins are secondary metabolites produced mainly by brown seaweeds (Phaeophyceae) and belong to the class of polyphenolic compounds with diverse bioactivities. The key factors in the extraction of polyphenols are the selection of a suitable solvent, method of extraction and selection of optimal conditions. Ultrasonic-assisted extraction (UAE) is one of the advanced energy-saving methods suitable for the extraction of labile compounds. Methanol, acetone, ethanol and ethyl acetate are the most commonly used solvents for polyphenol extraction. As alternatives to toxic organic solvents, a new class of green solvents, natural deep eutectic solvents (NADES), has been proposed for the efficient extraction of a wide range of natural compounds including polyphenols. Several NADES were screened previously for the extraction of phlorotannins; however, the extraction conditions were not optimized and chemical profiling of NADES extract was not performed. The purpose of this work was to study the effect of selected extraction parameters on the phlorotannin content in NADES extract from Fucus vesiculosus, optimization of extraction conditions and chemical profiling of phlorotannins in the NADES extract. A fast and green NADES-UAE procedure was developed for the extraction of phlorotannins. Optimization was performed through an experimental design and showed that NADES (lactic acid:choline chloride; 3:1) provides a high yield (137.3 mg phloroglucinol equivalents per g dry weight of algae) of phlorotannins under the following extraction conditions: extraction time 23 min, 30.0% water concentration and 1:12 sample to solvent ratio. The antioxidant activity of the optimized NADES extract was equal to that of EtOH extract. In total, 32 phlorotannins have been identified (one trimer, two tetramers, six pentamers, four hexamers, six heptamers, six octamers and seven nonamers) in NADES extracts from arctic F. vesiculosus using the HPLC-HRMS and MS/MS technique. It was noted that all the above-mentioned phlorotannins were identified in both EtOH and NADES extracts. Our results suggest that NADES could be considered as an alternative to the conventional techniques for the effective extraction of phlorotannins from F. vesiculosus with high antioxidant potential.

Flavonoids and saponins: What have we got or missed?

BACKGROUND: Flavonoids and saponins are important bioactive compounds that have attracted wide research interests. This review aims to summarise the state of the art of the pharmacology, toxicology and clinical efficacy of these compounds. METHODS: Data were retrieved from PubMed, Cochrane Library, Web of Science, Proquest, CNKI, Chongqing VIP, Wanfang, NPASS and HIT 2.0 databases. Meta-analysis and systematic reviews were evaluated following the PRISMA guideline. Statistical analyses were conducted using SPSS23.0. RESULTS: Rising research trends on flavonoids and saponins were observed since the 1990s and the 2000s, respectively. Studies on pharmacological targets and activities of flavonoids and saponins represent an important area of research advances over the past decade, and these important resources have been documented in open-access specialised databases and can be retrieved with ease. The rising research on flavonoids and saponins can be attributed, at least in part, to their links with some highly investigated fields of research, e.g., oxidative stress, inflammation and cancer; i.e., 6.88% and 3.03% of publications on oxidative stress cited by PubMed in 1990 - 2021 involved flavonoids and saponins, respectively, significantly higher than the percentage involving alkaloids (1.88%). The effects of flavonoids concern chronic venous insufficiency, cervical lesions, diabetes, rhinitis, dermatopathy, prostatitis, menopausal symptoms, angina pectoris, male pattern hair loss, lymphocytic leukaemia, gastrointestinal diseases and traumatic cerebral infarction, etc, while those of saponins may have impact on venous oedema in chronic deep vein incompetence, erectile dysfunction, acute impact injuries and systemic lupus erythematosus, etc. The volume of in vitro research appears way higher than in vivo and clinical studies, with only 10 meta-analyses and systematic reviews (involving 290 interventional and observational studies), and 36 clinical studies on flavonoids and saponins. Data are sorely needed on pharmacokinetics, in vitro pan-assay interferences, purity of tested compounds, interactions in complex herbal extracts, real impact of anti-oxidative strategies, and mid- and long-term toxicities. To fill these important gaps, further investigations are warranted. On the other hand, drug interactions may cause adverse effects but might also be useful for synergism, with the goals of enhancing effects or of detoxifying. Furthermore, the interactions between phytochemicals and the intestinal microbiota are worth investigating as the field may present a promising potential for novel drug development.

Potential of the Ethyl Acetate Fraction of Padina boergesenii as a Natural UV Filter in Sunscreen Cream Formulation

Brown seaweeds, due to their wide range of bioactive compounds, have a high ability to inhibit free radicals and protect against ultraviolet rays. In the present study, the ethyl acetate fraction (EF) was isolated from the Padina boergesenii brown seaweed. Antioxidant activity (by the DPPH scavenging activity method) and cytotoxicity against UVB-induced cytotoxicity in HaCaT human keratinocytes were evaluated. Then, this fraction was used as a bio-filter in the formulation of sunscreen, and the physical properties and stability were investigated. The results showed that the EF could inhibit DPPH radical scavenging (54 ± 1%) and cell viability of HaCaT keratinocytes exposed to UVB irradiation (81.2 ± 0.1%). The results of the stability study of the cream formulated with EF showed that at temperatures 4 °C and 25 °C it has high stability; and at 40 °C on the 28th day, a slight decrease in its stability was observed. The pH and Sun Protection Factor of the cream formulated with EF were reported at 5.8 and 20.55, respectively. Also, the DPPH scavenging activity of the cream was not altered for 28 days of storage at temperatures of 4-40 °C. According to our results, it was proved that the sunscreen formulated with EF of P. boergesenii brown seaweed has promising properties and characteristics that can create a new opportunity for the development of cosmetics and skin care products.

The Ability of Acid-Based Natural Deep Eutectic Solvents to Co-Extract Elements from the Roots of Glycyrrhiza glabra L. and Associated Health Risks.

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.

In Vitro Anti-Inflammatory Activities of Fucoidans from Five Species of Brown Seaweeds.

This study aimed to compare the anti-inflammatory effects of fucoidans from brown seaweeds (Saccharina japonica (SJ), Fucus vesiculosus (FV), Fucus distichus (FD), Fucus serratus (FS), and Ascophyllum nodosum (AN)), and determine the relationship between composition and biological activity. The anti-inflammatory activity was tested in vitro. It is believed that inflammation could be triggered by free radicals. Fucoidans from F. vesiculosus (FV1 and FV3) showed the strongest 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity with an IC50 = 0.05 mg/mL. In the total antioxidant capacity (TAC) test, the activity was concentration-dependent. Notable, the TAC of fucoidans except samples of FV2 and SJ (which have a lower phenolic content) was higher than that of phloroglucinol. The TAC of fucoidans strongly and positively correlated with polyphenol content. A weak correlation was associated with xylose content. The synergistic effect for fucoidans was calculated for the first time using carbohydrates and polyphenols as model mixtures. The synergy in the DPPH test was found only for FV1 and FV3 (mixture effect ME = 2.68 and 2.04, respectively). The ME strongly positively correlated with polyphenols. The relationship of ME with fucose content was positive but moderate. It was first established that the anti-inflammatory effects of fucoidan could be mediated via the inhibition of protein denaturation. The inhibition was concentration-dependent and strongly correlated with the fucose content and moderate with sulfate content. The purified fucoidan FV2 showed the most promising activity (IC50 = 0.20 mg/mL vs. IC50 = 0.37 mg/mL for diclofenac sodium). Similar relations were also observed in the membrane protection model. Fucoidans were able to stabilize the cell membrane integrity of human red blood corpuscles (HRBC). The results of our study support the rationality of fucoidan use as a promising agent for the treatment of inflammatory-related diseases via mechanisms of radical scavenging, antioxidant activity, inhibition of protein denaturation, and HRBC membrane stabilization.

The Impact of Natural Deep Eutectic Solvents and Extraction Method on the Co-Extraction of Trace Metals from Fucus vesiculosus.

In recent years, natural deep eutectic solvents (NADES) have been widely investigated for the extraction of food and medicinal plants as well as seaweeds. However, the ability of NADES for trace elements co-extraction from natural sources is not well investigated. The aim of this study was to investigate the ability of common NADES for trace elements co-extraction from Fucus vesiculosus. All of the tested NADES did not recover As and Co (concentration

The Biochemical Composition and Antioxidant Properties of Fucus vesiculosus from the Arctic Region.

Fucus vesiculosus is one of the most prominent brown algae in the shallow waters of the seas of the Arctic region (Barents (BS), White (WS), Norwegian (NS), and Irminger (IS)). The aim of this study was to determine the biochemical composition of F. vesiculosus from the Arctic at different reproductive phases, and to evaluate the antioxidant properties of F. vesiculosus extracts. The amounts of monosaccharides, phlorotannins, flavonoids, and ash and the mineral composition significantly varied in the algae. A strong correlation was established between monosaccharide, phlorotannin, and flavonoid accumulation and water salinity (Pearson's correlation coefficients r = −0.58, 0.83, and 0.44, respectively; p < 0.05). We noted a negative correlation between the antioxidant activity and the amount of the structural monosaccharides of fucoidan (r = −0.64). A positive correlation of phlorotannins and flavonoids with antioxidant power was confirmed for all samples. The ash accumulation was relatively lower in the sterile phase for the algae from the BS and WS. The correlation between the Metal Pollution Index (MPI) and the reproductive phases was medium with high fluctuation. Meanwhile, the MPI strongly correlated with the salinity and sampling site. The gradient of the MPI values across the sea was in the following ranking order: BS < WS < NS < IS. Taken together, and based on our data on the elemental contents of F. vesiculosus, we believe that this alga does not accumulate toxic doses of elements. Therefore, the Arctic F. vesiculosus could be safely used in food and drug development as a source of active biochemical compounds and as a source of dietary elements to cover the daily nutritional requirements of humans.

Formulation, Optimization and In Vivo Evaluation of Fucoidan-Based Cream with Anti-Inflammatory Properties.

Fucoidan is a polysaccharide found in brown alga with glorious potential for pharmacological activities, among which its anti-inflammatory properties have gained meaningful attention. Due to several advantages of formulations for topical application, this study aimed to develop and optimize a fucoidan-based cream formulation and to investigate its anti-inflammatory potential after topical application in vivo. Fucoidan from Fucus vesiculosus L. was used. The cream base consisting of olive oil and Kolliphor RH40 was optimized followed by in vitro agar diffusion and drug release studies. The fucoidan-based cream with 13% Kolliphor P 407, 1% Transcutol P, and 5% PEG400 showed good spreadability, washability, and colloidal stability, and it did not irritate the skin. The kinetics of fucoidan release from the optimized cream exhibited the best fit to the Korsmeyer-Peppas and Higuchi models with R2 > 0.99. Fucoidan release was controlled by drug diffusion and anomalous transport provided by the optimized cream base. The formulation was stable and provided high fucoidan release after storage for 1 year. Topical application of the fucoidan-based cream dose-dependently inhibited carrageenan-induced edema and ameliorated mechanical allodynia in rats. The efficacy of the fucoidan-based cream at a high dose was comparable with the efficacy of diclofenac gel. The fucoidan-based cream could be considered a promising anti-inflammatory formulation.

Medical Species Used in Russia for the Management of Diabetes and Related Disorders.

Background: Polyherbal mixtures called "medical species" are part of traditional and officinal medicine in Russia. This review aimed to analyze medical species used in Russia for the treatment of diabetes and related disorders. The information relevant to medical species, diabetes, and obesity was collected from local libraries, the online service E-library.ru, and Google Scholar. The prediction of the antidiabetic activity for the principal compounds identified in plants was performed using the free web resource PASS Online. Results: We collected and analyzed information about the compositions, specificities of use, and posology of 227 medical species. The medical species represent mixtures of 2-15 plants, while the most frequently mentioned in the literature are species comprising 3-6 plants. The top 10 plants among the 158 mentioned in the literature include Vaccinium myrtillus L., Phaseolus vulgaris L., Taraxacum campylodes G.E. Haglund., Urtica dioica L., Rosa spp., Hypericum spp., Galega officinalis L., Mentha × piperita L., Arctium spp, and Fragaria vesca L. The leading binary combination found in medical species comprises the leaves of V. myrtillus and pericarp of P. vulgaris; leaves of V. myrtillus and leaves of U. dioica; and leaves of V. myrtillus and aerial parts of G. officinalis. In triple combinations, in addition to the above-mentioned components, the roots of T. campylodes are often used. These combinations can be regarded as basic mixtures. Other plants are added to improve the efficacy, treat associated disorders, improve gastrointestinal function, prevent allergic reactions, etc. Meanwhile, an increase in plants in the mixture necessitates advanced techniques for quality control. A feature of medical species in Russia is the addition of fresh juices, birch sap, seaweeds, and adaptogenic plants. Modern studies of the mechanisms of action and predicted activities of the principal compounds from medicinal plants support the rationality of polyherbal mixtures. Nevertheless, the mechanisms are not well studied and reported due to the limited number of compounds. Further investigations with calculations of synergistic or additive indices are important for strengthening the scientific fundamentals for the wider use of medical species in the therapy of diabetes. Two medical species, "Arfazetin" (7 medicinal plants) and "Myrphasinum" (12 medicinal plants), are approved for use in officinal medicine. The efficacy of these species was confirmed in several in vivo experiments and clinical trials. According to modern regulatory rules, additional experiments and clinical trials are required for more detailed investigations of the mechanisms of action and confirmation of efficacy. Conclusion: We believe that the scientifically based utilization of rich plant resources and knowledge of Russian herbal medicine can significantly contribute to the local economy as well as to the sectors seeking natural healing products.

Efficacy of Natural Deep Eutectic Solvents for Extraction of Hydrophilic and Lipophilic Compounds from Fucus vesiculosus.

The impact of the composition of natural deep eutectic solvents (NADES) and extraction conditions on the simultaneous extraction of hydrophilic ascorbic acid (AA), phlorotannins (TPhC), and lipophilic fucoxanthin (FX) from Fucus vesiculosus was investigated for the first time. In biological tests, the NADES extracts showed the promising ability to scavenge DPPH radicals. A positive correlation was observed between DPPH scavenging activity and AA, TPhC, and FX contents. We calculate the synergistic effect of antioxidants extracted by NADES from F. vesiculosus based on the mixture effect (ME). The addition of 30% water to the NADES and the prolongation of sonication time from 20 min up to 60 min were favorable for the ME. The ME for extracts with the NADES was increased by two folds (ME > 2). In contrast, conventional extraction by maceration with steering at 60 °C does not lead to the synergistic effect (ME = 1). It is notable that the NADES provides high stability and preserves the antioxidant activity of the extracts from F. vesiculosus during storage.

Findings of Russian literature on the clinical application of Eleutherococcus senticosus (Rupr. & Maxim.): A narrative review.

ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus senticosus (Rupr. et Maxim.) Maxim (ES) (syn. Acanthopanax senticosus (Rupr. & Maxim.) Harms) is a medicinal plant used in traditional medicine of Russian Far East and East Asia and known as an adaptogen - a category of herbal medicinal products which have non-specific inter-system anti-stress effects throughout the human body. ES was first established as a medicinal plant officially in the pharmacopeia of the Union of Soviet Socialist Republics (USSR) in 1962, and is currently recommended by the European Medicines Agency (EMA) to be prescribed to treat symptoms of asthenia such as fatigue and weakness. AIM OF THE REVIEW: During the time of the USSR, a distinct research directive was undertaken on ES to examine substances which improve stamina and endurance, with over 1000 studies published. Due to security measures within the former USSR these papers were not accessible to the public and were never translated into English. This is the first study to make findings of the USSR studies on ES available to the international research and scientific community. METHODS: This study was an archival retrieval. References for studies were sought from printed journal and conference preceding's publications, then located within library catalogues of three libraries in St Petersburg Russia. Eligibility criteria included human clinical trials examining the efficacy of ES in any condition, published in the Russian language in the Soviet Union. RESULTS: A total of 46 studies published between 1962 and 1986 in the USSR were sourced. Of the retrieved articles, 29 were reported as placebo-controlled trials, 11 were reported as controlled trials and six studies did not report the study design. Trends in studies were those reporting on healthy volunteers (n=21) at a dose of 2 ml extract/day (n=14) examining outcomes such as physical and mental stamina under varying conditions, normal work conditions, high temperatures and high altitudes, incidence or prophylaxis of colds and influenza (n=5), effects on color perception and vision (n=2), work capacity (n=1), cognitive effects (n=1), prophylaxis of hearing loss (n=3), effects on blood cell counts (n=2) and sensitivity to UV radiation (n=1). CONCLUSIONS: ES appears to exhibit benefits for cognitive function and physical and mental endurance and its effect as a respiratory system infection prophylaxis treatment are promising. This study is the first to publish the findings of clinical trials on ES from the USSR, which supports the traditional use and offers a valuable contribution to the body of evidence on medicinal uses of ES when the data is applied within the context of its limitations.

Sceletium for Managing Anxiety, Depression and Cognitive Impairment: A Traditional Herbal Medicine in Modern-Day Regulatory Systems.

Modern-day regulatory systems governing conditions for how health products enter national markets constitute a barrier of access for traditional herbal medicines on an international level. Regulatory intentions are focused on ensuring that consumers are being provided with safe, efficacious and high-quality products that, however, collaterally limit opportunities for traditional herbal medicinal products, especially those that do not already have a long-standing tradition of use established in the respective national marketplaces. This case study investigates and compares how a Southern African herbal medicine with great potential as an anxiolytic and mild antidepressant - Mesembryanthemum tortuosum L. [syn. Sceletium tortuosum (L.) N.E.Br.] aerial parts - fares internationally in today's regulatory environments. It is argued that inadvertent regulatory favoritism combined with the lack of means for adequate protection of intellectual property may obstruct innovation by creating an almost insurmountable economical hurdle for successful product development and introduction of botanicals from developing countries into most of the world's health product markets.

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases.

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases.

Medicinal plants from the 14th edition of the Russian Pharmacopoeia, recent updates.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine in Russia has a long history starting with handwritten herbalist manuscripts from the Middle Ages to the officinal Pharmacopoeia of the 21st century. The "herbophilious" Russian population has accumulated a lot of knowledge about the beneficial effects of local medicinal plants. Yet, for a long time, Russian traditional and officinal herbal medicine was not well known to the international audience. In our previous comprehensive review, we discussed the pharmacological effects of specific plants included in the 11th edition of the Pharmacopoeia of the USSR, which was also for a while used in Russia. The 14th edition of the Russian Federation's State Pharmacopoeia was implemented in 2018. AIM OF THE REVIEW: The aims of the present review are: (i) to trace the evolution of medicinal plant handling from handwritten herbalist manuscripts to Pharmacopoeias; (ii) to describe the modern situation with regulatory documents for herbal medicinal products and their updated classification; (iii) to summarize and discuss the pharmacology, safety, and clinical data for new plants, which are included in the new edition of the Pharmacopoeia. METHODS: New medicinal plants included in the 14th edition of the Russian Federation's State Pharmacopoeia were selected. We carefully searched the scientific literature for data related to traditional use, pharmacological, clinical application, and safety. The information was collected from local libraries in Saint-Petersburg, the online databases E-library.ru, Scopus, Web of Science, and the search engine Google scholar. RESULTS: Investigating the evolution of all medicinal plants referred to in the Russian Pharmacopoeias led us to the identification of ten medicinal plants that were present in all editions of civilian Russian Pharmacopoeias starting from 1778. In the 14th edition of the modern Russian Pharmacopoeia, medicinal plants are described in 107 monographs. Altogether, 25 new monographs were included in the 14th edition, and one monograph was excluded in comparison to the 11th edition. Some of the included plants are not endemic to Russia and do not have a history of traditional use, or on the other hand, are widely used in Western medicine. For 15 plants, we described the specificity of their application in Russian traditional medicine along with the claimed dosages and indications in officinal medicine. The pharmacology, safety, and clinical data are summarized and assessed for nine plants, underlining their therapeutic potential and significance for global phytopharmacotherapy. CONCLUSIONS: In this review, we highlight the therapeutical potential of new plants included in the modern edition of the Russian Pharmacopoeia. We hope that these plants will play an imperative role in drug development and will have a priority for future detailed research.

Pharmacokinetics of Marine-Derived Drugs.

Marine organisms represent an excellent source of innovative compounds that have the potential for the development of new drugs. The pharmacokinetics of marine drugs has attracted increasing interest in recent decades due to its effective and potential contribution to the selection of rational dosage recommendations and the optimal use of the therapeutic arsenal. In general, pharmacokinetics studies how drugs change after administration via the processes of absorption, distribution, metabolism, and excretion (ADME). This review provides a summary of the pharmacokinetics studies of marine-derived active compounds, with a particular focus on their ADME. The pharmacokinetics of compounds derived from algae, crustaceans, sea cucumber, fungus, sea urchins, sponges, mollusks, tunicate, and bryozoan is discussed, and the pharmacokinetics data in human experiments are analyzed. In-depth characterization using pharmacokinetics is useful for obtaining information for understanding the molecular basis of pharmacological activity, for correct doses and treatment schemes selection, and for more effective drug application. Thus, an increase in pharmacokinetic research on marine-derived compounds is expected in the near future.

Variability of Major Phenyletanes and Phenylpropanoids in 16-Year-Old Rhodiola rosea L. Clones in Norway.

Rhodiola rosea L. (roseroot) is an adaptogen plant belonging to the Crassulaceae family. The broad spectrum of biological activity of R. rosea is attributed to its major phenyletanes and phenylpropanoids: rosavin, salidroside, rosin, cinnamyl alcohol, and tyrosol. In this study, we compared the content of phenyletanes and phenylpropanoids in rhizomes of R. rosea from the Norwegian germplasm collection collected in 2004 and in 2017. In general, the content of these bioactive compounds in 2017 was significantly higher than that observed in 2004. The freeze-drying method increased the concentration of all phenyletanes and phenylpropanoids in rhizomes compared with conventional drying at 70 °C. As far as we know, the content of salidroside (51.0 mg g-1) observed in this study is the highest ever detected in Rhodiola spp. Long-term vegetative propagation and high genetic diversity of R. rosea together with the freeze-drying method may have led to the high content of the bioactive compounds observed in the current study.

Mechanisms of Bioactivities of Fucoidan from the Brown Seaweed Fucus vesiculosus L. of the Barents Sea.

The aim of this study was to elucidate some mechanisms of radical scavenging and the anti-inflammatory, anti-hyperglycemic, and anti-coagulant bioactivities of high molecular weight fucoidan from Fucus vesiculosus in several in vitro models. Fucoidan has displayed potent 1, 1-diphenyl-2-picryl hydrazil radical scavenging and reduction power activities. It significantly inhibits the cyclooxygenase-2 (COX-2) enzyme (IC50 4.3 µg mL-1) with a greater selectivity index (lg(IC80 COX-2/IC80COX-1), -1.55) than the synthetic non-steroidal anti-inflammatory drug indomethacin (lg(IC80 COX-2/IC80COX-1), -0.09). A concentration-dependent inhibition of hyaluronidase enzyme with an IC50 of 2.9 µg mL-1 was observed. Fucoidan attenuated the lipopolysaccharide-induced expression of mitogen-activated protein kinase p38. Our findings suggest that the inhibition of dipeptidyl peptidase-IV (DPP-IV) (IC50 1.11 µg mL-1) is one of the possible mechanisms involved in the anti-hyperglycemic activity of fucoidan. At a concentration of 3.2 µg mL-1, fucoidan prolongs the activated partial thromboplastin time and thrombin time by 1.5-fold and 2.5-fold compared with a control, respectively. A significant increase of prothrombin time was observed after the concentration of fucoidan was increased above 80 µg mL-1. This evidenced that fucoidan may have an effect on intrinsic/common pathways and little effect on the extrinsic mechanism. This study sheds light on the multiple pathways of the bioactivities of fucoidan. As far as we know, the inhibition of hyaluronidase and DPP-IV by high molecular fucoidan was studied for the first time in this work. Our results and literature data suggest that molecular weight, sulfate content, fucose content, and polyphenols may contribute to these activities. It seems that high molecular weight fucoidan has promising therapeutic applications in different pharmacological settings. Anti-oxidant, anti-inflammatory and anti-coagulant drugs have been used for the management of complications of COVID19. Taken as a whole, fucoidan could be considered as a prospective candidate for the treatment of patients with COVID19; however, additional research in this field is required.

Natural Deep Eutectic Solvents for the Extraction of Phenyletanes and Phenylpropanoids of Rhodiola rosea L.

The extraction of Rhodiola rosea rhizomes using natural deep eutectic solvent (NADES) consisting of lactic acid, glucose, fructose, and water was investigated. A two-level Plackett-Burman design with five variables, followed by the steepest ascent method, was undertaken to determine the optimal extraction conditions. Among the five parameters tested, particle size, extraction modulus, and water content were found to have the highest impact on the extrability of phenyletanes and phenylpropanoids. The concentration of active compounds was analyzed by HPLC. The predicted results showed that the extraction yield of the total phenyletanes and phenylpropanoids (25.62 mg/g) could be obtained under the following conditions: extraction time of 154 min, extraction temperature of 22 °C, extraction modulus of 40, molar water content of 5:1:11 (L-lactic acid:fructose:water, mol/mol), and a particle size of rhizomes of 0.5-1 mm. These predicted values were further verified by validation experiments in predicted conditions. The experimental yields of salidroside, tyrosol, rosavin, rosin, cinnamyl alcohol and total markers (sum of phenyletanes and phenylpropanoids in mg/g) were 11.90 ± 0.02, 0.36 ± 0.02, 12.23 ± 0.21, 1.41 ± 0.01, 0.20 ± 0.01, and 26.10 ± 0.27 mg/g, respectively, which corresponded well with the predicted values from the models.