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The purpose of this work is to study the features of the life cycle of Sanguisorba officinalis in various types of vegetation in the Republic of Tatarstan, Russia. We used traditional methods for studying the cenopopulation, analysis of the calendar age of plants of various ontogenetic states, and potential and actual seed productivity. Under broad‐leaved forest conditions, a young normal population was formed on the basis of slowly developing plants. In conditions of open communities, young cenopopulations were formed on the basis of intensive seed reproduction processes. The young cenopopulation can be recommended for further study in biomass exploitation. The predominance of long‐lived vegetative and immature plants in the conditions of a broad‐leaved forest is associated with difficulties in the transition of individuals to sexual reproduction. The maintenance of numbers is carried out through vegetative growth and reproduction. With deterioration of ecological and coenotic conditions, above‐ground shoots were not formed but regressive‐quasisenile coenopopulations were formed. Seed productivity was determined by ecological and cenotic conditions. On the steppe meadow of the Bugulma district, the lowest seed productivity index was 9 %. The lowest indicator of the trait “Number of full‐fledged seeds” (the average indicator was 7), low seed germination and germination energy were also noted there. The highest values of these indicators were noted n glades of the broad‐leaved areas of the same region. The realization of the reproductive system of Sanguisorba officinalis even under extreme conditions and the survival of the species in various types of vegetation suggest that the territory of the Republic of Tatarstan is included in the ceno‐area of the species. This will permit the creation of plantations in the republic.

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The Scarce Large Blue (Phengaris teleius) is a threatened butterfly throughout Europe due to its special life cycle and habitat loss. P. teleius butterflies tend to be very sedentary and move only a few hundred meters a day and rarely leave their home patches. In this paper, details are presented regarding the first mention of P. teleius in the region of Săcădat locality, Bihor County, Romania. This location meets all the environmental requirements of P. teleius (host plants for larvae and ants of the genus Myrmica). The area researched was about 3.16 ha, with about 25000 individuals of Sanguisorba officinalis L. flowers, on which we found an approximate number of 94 P. teleius butterflies. We hope that our initial study of P. teleius could have a positive impact on the conservation of this species in this new location. [ABSTRACT FROM AUTHOR]

Hypertension requires proper management because of the increased risk of cardiovascular disease and death. For this purpose, functional foods containing tannins have been considered an effective treatment. Sanguisorbae radix (SR) also contains various tannins; however, there have been no studies on its vasorelaxant or antihypertensive effects. In this study, the vasorelaxant effect of the ethanol extract of SR (SRE) was investigated in the thoracic aorta of Sprague Dawley rats. SRE (1, 3, 10, 30, and 100 μg/mL) showed this effect in a dose-dependent manner, and its mechanisms were related to the NO/cGMP pathway and voltage-gated K+ channels. Concentrations of 300 and 1000 μg/mL blocked the influx of extracellular Ca2+ and inhibited vasoconstriction. Moreover, 100 μg/mL of SRE showed a relaxing effect on blood vessels constricted by angiotensin II. The hypotensive effect of SRE was investigated in spontaneously hypertensive rats (SHR) using the tail-cuff method. Blood pressure significantly decreased 4 and 8 h after 1000 mg/kg of SRE administration. Considering these hypotensive effects and the vasorelaxant mechanisms of SRE, our findings suggests that SRE can be used as a functional food to prevent and treat hypertension. Further studies are needed for identifying the active components and determining the optimal dosage. [ABSTRACT FROM AUTHOR]

Aeromonas hydrophila , a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila , regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection. The dietary supplementation of lactic acid bacteria fermented herbal Sanguisorba officinalis preparation for crucian carp (Carassius auratus) could improve the growth performance, antioxidant capacity, immune parameters and protection against Aeromonas hydrophila. [Display omitted] • Three lactic acid bacteria fermented herbal Sanguisorba officinalis (DY) cultures as dietary supplements for crucian carp. • The Chinese herbal fermented cultures improved the growth performance and non-specific immunity of crucian carp. • The Chinese herbal fermented cultures enhanced the resistance of crucian carp against A. hydrophila. [ABSTRACT FROM AUTHOR]

Hypertension requires proper management because of the increased risk of cardiovascular disease and death. For this purpose, functional foods containing tannins have been considered an effective treatment. Sanguisorbae radix (SR) also contains various tannins; however, there have been no studies on its vasorelaxant or antihypertensive effects. In this study, the vasorelaxant effect of the ethanol extract of SR (SRE) was investigated in the thoracic aorta of Sprague Dawley rats. SRE (1, 3, 10, 30, and 100 μg/mL) showed this effect in a dose-dependent manner, and its mechanisms were related to the NO/cGMP pathway and voltage-gated K+ channels. Concentrations of 300 and 1000 μg/mL blocked the influx of extracellular Ca2+ and inhibited vasoconstriction. Moreover, 100 μg/mL of SRE showed a relaxing effect on blood vessels constricted by angiotensin II. The hypotensive effect of SRE was investigated in spontaneously hypertensive rats (SHR) using the tail-cuff method. Blood pressure significantly decreased 4 and 8 h after 1000 mg/kg of SRE administration. Considering these hypotensive effects and the vasorelaxant mechanisms of SRE, our findings suggests that SRE can be used as a functional food to prevent and treat hypertension. Further studies are needed for identifying the active components and determining the optimal dosage.

In Europe, 50%–70% of former natural grassland area has been destroyed during the past 30 years due to land use changes, losses are expected to increase in the future. Restoration is thought to reverse this situation by creating suitable abiotic conditions. In this paper, we investigate the effects of sod translocation with specific vegetation to facilitate the restoration of a former intensive agricultural field into a wet meadow. First, starting conditions were optimized including modification of the local hydrology, removal of the fertilized topsoil, application of liming, and translocation of fresh clippings as a seed source. The second part aimed at restoring the habitat for the butterfly species Phengaris (Maculinea) teleius, one of the species that was especially affected by the loss of wet meadows. This species engages in a complex myrmecophilous relationship with one host plant, Sanguisorba officinalis, and one obligate host ant, Myrmica scabrinodis. We used sod translocation to create islands of habitat to promote host plant and host ant colonization. After 4 years following the restoration, we observed that plants spread from the transplanted sods to the surroundings. The vegetation composition and structure of the transplanted sods attracted colonization of Myrmica ants into the restored areas. Following the increase in vegetation cover and height, Myrmica ant colonies further spread into the restored areas. Therefore, sod translocations can be considered an effective restoration method following topsoil removal in the process of restoring wet meadows to provide a starting point for ant colonization and plant dispersion. With these findings, this paper contributes to the evidence‐based restoration of wet meadows on former agricultural fields, including complex interactions between invertebrates and their required ecological relationships. [ABSTRACT FROM AUTHOR]

Rosaceae is one of the important families with a variety of diversified plant species which grows in the north temperate zone and occurs in a wide variety of habitats. Moreover, Sanguisorba spp. is very good frost tolerant. The aim of our study is to investigated total phenols content (using Folin-Ciocalteu method), and antioxidant capacity, (using two methods, i.e. DPPH and FRAP), of ethanolic extracts from stem, flowers, leaves, and roots of Sanguisorba officinalis and Sanguisorba minor. The total phenols content was higher in S. officinalis root (8.56 mg GAE/g dry weight (dw)), followed by S. officinalis leaves (2.80 mg GAE/g dw), S. officinalis stem (0.59 mg GAE/g dw), S. officinalis flowers (0.41 mg GAE/g dw) compared to S. minor root (3.89 mg GAE/g dw), followed by S. minor leaves (1.19 mg GAE/g dw), S. minor stem (0.19 mg GAE/g dw). The highest DPPH-scavenging capacity was recorded for root extracts, i.e. 94.61 % for S. officinalis and 92.93 % and S. minor roots respectively. The lowest Radical Scavenging Activity (RSA)% was recorded in descending order among S. officinalis leaves (71.83%), flowers (20.73%) and stem (18.22 %). The lowest RSA (%) for S. minor was recorded in descending order among stem (43.16 %) and leaves (0.32%). These results suggest that the roots of Sanguisorba species are likely to have high antioxidant capacity. Based on our results, Sanguisorba spp. can be used as medicinal plants with antioxidant properties.

Background: Colorectal cancer (CRC) is the most common malignant cancer worldwide. Sanguisorba officinalis has been shown to have anti-inflammatory, anti-bacterial, antioxidant, and anti-tumor effects, while its molecular mechanism against CRC remains unclear. The aim of this study is to explore the underlying mechanism of S. officinalis against CRC cell lines using network pharmacology and transcriptomic sequencing methods. Method: Firstly, the active ingredients and potential targets of S. officinalis against CRC were screened from databases. Secondly, the networks of ingredient–target, ingredient–target–CRC and protein–protein interaction were constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of network pharmacology and transcriptomic sequencing were performed. Finally, the effect of S. officinalis against CRC was verified by in vitro experiments. Results: In total, 14 active ingredients and 273 potential targets against CRC were identified in S. officinalis by network pharmacology. PI3K–Akt, HIF-1, and MAPK signaling pathways related to cell proliferation were regulated by S. officinalis in enrichment analyses and transcriptomic sequencing. In vitro , S. officinalis inhibited the proliferation and migration of CRC cells and arrested the cell cycle at the G0–G1 phase. The western blot showed that S. officinalis downregulated the expression of p-PI3K, p-Akt, HIF-1A, VEGFA, cyclin D1, c-Myc, and p-MAPK proteins in CRC cells. Conclusion: In conclusion, network pharmacology and transcriptomic sequencing analyses, in combination with in vitro studies, have been successfully applied to study the underlying mechanism of S. officinalis against CRC cells. Our results demonstrate that S. officinalis suppresses the proliferation, survival, and migration of CRC cells through regulating the PI3K–Akt, HIF-1, and MAPK signaling pathways. [ABSTRACT FROM AUTHOR]

Two new phenolic glycosides 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-(3''-α-L-arabinofuranosyl)-β-D-glucopyranoside. (1), 4-(4'-hydroxyphenyl)-2-butanone-4''-O-(6-β-D-xylosyl)-β-D-glucopyranoside (2), along with two known related analogues 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-3'-O-β-D-glucopyranoside (3), 4-(4'-hydroxyphenyl)-2-butanone-4'-O-β-D-glucopyranoside (4) were obtained from the roots of Sanguisorba officinalis. Combined with acid hydrolysis derivatization, the absolute configurations of these new compounds were elucidated by comprehensive analyses of spectroscopic data including nuclear magnetic resonance (NMR), electrospray ionization high resolution mass (HRESIMS) as well as circular dichroism (CD). Compounds 1-4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). [ABSTRACT FROM AUTHOR]

BackgroundColorectal cancer (CRC) is the most common malignant cancer worldwide. Sanguisorba officinalis has been shown to have anti-inflammatory, anti-bacterial, antioxidant, and anti-tumor effects, while its molecular mechanism against CRC remains unclear. The aim of this study is to explore the underlying mechanism of S. officinalis against CRC cell lines using network pharmacology and transcriptomic sequencing methods.MethodFirstly, the active ingredients and potential targets of S. officinalis against CRC were screened from databases. Secondly, the networks of ingredient–target, ingredient–target–CRC and protein–protein interaction were constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of network pharmacology and transcriptomic sequencing were performed. Finally, the effect of S. officinalis against CRC was verified by in vitro experiments.ResultsIn total, 14 active ingredients and 273 potential targets against CRC were identified in S. officinalis by network pharmacology. PI3K–Akt, HIF-1, and MAPK signaling pathways related to cell proliferation were regulated by S. officinalis in enrichment analyses and transcriptomic sequencing. In vitro, S. officinalis inhibited the proliferation and migration of CRC cells and arrested the cell cycle at the G0–G1 phase. The western blot showed that S. officinalis downregulated the expression of p-PI3K, p-Akt, HIF-1A, VEGFA, cyclin D1, c-Myc, and p-MAPK proteins in CRC cells.ConclusionIn conclusion, network pharmacology and transcriptomic sequencing analyses, in combination with in vitro studies, have been successfully applied to study the underlying mechanism of S. officinalis against CRC cells. Our results demonstrate that S. officinalis suppresses the proliferation, survival, and migration of CRC cells through regulating the PI3K–Akt, HIF-1, and MAPK signaling pathways.

Abstract Background Sanguisorba officinalis, a popular Chinese herb, called DiYu, has been shown to inhibit the growth of many human cancer cell lines, including colorectal cancer cells. The aims of this study were to discover the active compound and molecular mechanism of S. officinalis against Wnt/β-catenin signaling pathway and develop Wnt inhibitors from natural products as anti-colorectal cancer agents. Methods 1,4,6-Tri-O-galloyl-β-d-glucopyranose (TGG) was obtained by the preparative HPLC. The effect of DiYu on proliferation of NIH3T3 and HT29 was detected by MTT assay. Luciferase reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in NIH3T3. The expression levels of mRNA and protein were detected by RT-PCR and western blot. Immunofluorescence assay was used to measure the level of β-catenin in cytoplasm and nucleus. Transcriptomic profiling study was performed to investigate the molecular mechanism of DiYu on the Wnt/β-catenin signaling pathway. Results TGG significantly inhibited the Wnt/β-catenin signaling pathway, down-regulated the expression of β-catenin and Wnt target genes (Dkk1, c-Myc, FGF20, NKD1, Survivin), up-regulated the levels of cleaved caspase3, cleaved PARP and ratio of Bax/Bcl-2, which may explain the apoptosis of HT29. Conclusions Our study enhanced the discovery of the materials and elucidation of mechanisms that account for the anti-Wnt activity of natural inhibitor (DiYu) and identified the potential of TGG to be developed as anti-colorectal cancer drugs.

Sanguisorba officinalis is well known for its incredible performance on stopping bleeding in herbal remedies in China. The chloroplast genome sequence of Sanguisorba officinalis was 155,479 bp length as the circular structure and typical quadripartite structure. It contained a large single-copy (LSC) region of 85,548 bp, a small single-copy (SSC) region of 18,769 bp and separated by two inverted repeat (IR) regions of 25,581 bp. The overall G + C content of the chloroplast genome sequence is 37.2%. This chloroplast genome contained 131genes that included 86 protein-coding (PC) genes, 37 transfer RNA (tRNA) genes and 8 ribosomal RNA (rRNA) genes. In IR region, 18 genes was found, contained 7 PCGs species, 7 tRNA genes species and 4 rRNA genes species. In phylogenetic analysis, the result shown that Sanguisorba officinalis was closed relationship with Sanguisorba tenuifolia in the phylogenetic relationship using the Maximum-Likelihood (ML) method.

Three aryl-tetralin-type lignans, including 2 previously undescribed compounds, were isolated from the root of Sanguisorba officinalis. The structures of the new compounds were elucidated by 1D- and 2D-NMR spectroscopic analyses and mass spectrometry. Experimental and calculated ECD were used to determine the absolute configurations. The isolated compounds were evaluated for cytotoxicity against two cell lines (MV4-11 and MDA-MB-231) and compound 1 exhibited moderate growth inhibition against MDA-MB-231 cell line with IC50 value of 15.76 μM. [ABSTRACT FROM AUTHOR]

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Ulcerative colitis (UC) accounts for the untreatable illness nowadays. Bloody stools are the primary symptom of UC, and the first-line drugs used to treat UC are associated with several drawbacks and negative side effects. S. officinalis has long been used as a medicine to treat intestinal infections and bloody stools. However, what the precise molecular mechanism, the exact etiology, and the material basis of the disease remain unclear. This work aimed to comprehensively explore pharmacological effects as well as molecular mechanisms underlying the active fraction of S. officinalis , and to produce a comprehensive and brand-new guideline map of its chemical base and mechanism of action. First, different polarity S. officinalis extracts were orally administered to the DSS-induced UC model mice for the sake of investigating its active constituents. Using the UPLC-orbitrap high-resolution mass spectrometry (UPLC-Q-Orbitrap-HRMS) technique, the most active S. officinalis (S. officinalis ethyl acetate fraction, SOEA) extract was characterized. Subsequently, the effectiveness of its active fraction on UC was evaluated through phenotypic observation (such as weight loss, colon length, and stool characteristics), and histological examination of pathological injuries, mRNA and protein expression. Cell profile, cell-cell interactions and molecular mechanisms of SOEA in different cell types of the colon tissue from UC mice were described using single-cell RNA sequencing (scRNA-seq). As a final step, the molecular mechanisms were validated by appropriate molecular biological methods. For the first time, this study revealed the significant efficacy of SOEA in the treatment of UC. SOEA reduced DAI and body weight loss, recovered the colon length, and mitigated colonic pathological injuries along with mucosal barrier by promoting goblet cell proliferation. Following treatment with SOEA, inflammatory factors showed decreased mRNA and protein expression. SOEA restored the dynamic equilibrium of cell profile and cell-cell interactions in colon tissue. All of these results were attributed to the ability of SOEA to inhibit the PI3K-AKT/NF-κB/STATAT pathway. By integrating the chemical information of SOEA derived from UPLC-Q-Orbitrap-HRMS with single-cell transcriptomic data extracted from scRNA-seq, this study demonstrates that SOEA exerts the therapeutic effect through suppressing PI3K-AKT/NF-B/STAT3 pathway to improve clinical symptoms, inflammatory response, mucosal barrier, and intercellular interactions in UC, and effectively eliminates the interference of cellular heterogeneity. [Display omitted] [ABSTRACT FROM AUTHOR]

Thirteen undescribed ursane-type triterpenoids, named as sangosides A–M (1 – 13), including two nor-ursanes, one split ring-ursane and ten ursanes, along with thirty-six known triterpenoids (14 – 49) were isolated and identified from the roots of Sanguisorba officinalis (Rosaceae). Their structures and absolute configurations were elucidated through spectroscopic data, single-crystal X-ray crystallography and electronic circular dichroism analysis. Their Nrf2 activation activity was evaluated in 293 T cells in vitro. Compounds 2 , 5 – 7 , 9–13 , 19 , 25 , 26 , 28–39 , 41 and 46 showed significant Nrf2 agonistic effects compared with the control group at 25 μM, their cytotoxicity and dose-effect relationship were further studied in a dose-dependent manner. Their structure–activity relationships analysis suggested that the pentacyclic triterpenoids (10 , 11 , 30 – 34 and 41) contains two pairs of double bonds on the C & E rings and the ursane-type triterpenoids (25 and 26) with a carbonyl to C-2 and a hydroxyl group at C-3 all showed a considerably Nrf2 activation activity. These results suggested that S. officinalis was worthy of further investigation to find small molecule Nrf2 activators and facilitate their utilization as natural antioxidants. Thirteen undescribed triterpenoids (1–13) and thirty-six known triterpenoids (14–49) were isolated from the roots of S. officinalis with compounds 2 , 5 – 7 , 9–13 , 19 , 25 , 26 , 28–39 , 41 and 46 exhibiting significant Nrf2 agonist activity at 25 μM. [Display omitted] • Thirteen undescribed and thirty-six known triterpenoids were isolated from Sanguisorba officinalis. • The Nrf2 activation activity of the isolated compounds were evaluated in 293 T cells. • Compounds 2 , 5 – 7 , 9–13 , 19 , 25 , 26 , 28–39 , 41 and 46 showed remarkable Nrf2 agonist activity at 25 μM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is a metabolic disorder caused by abnormal carbohydrate metabolism, and closely associated with abnormal lipid metabolism and hepato-renal dysfunction. This study investigated the anti-diabetic and hepato-renal protective properties of ziyuglycoside I (ZG01) derivative on type 2 diabetes. ZG01 was isolated from roots of Sanguisorba officinalis and chemically modified by deglycosylation and esterification to obtained ziyuglycoside II methyl ester (ZG02-ME). Here, we showed that ZG02-ME has stronger anti-diabetic activity than the original compound (ZG01) through decreasing blood glucose, glycated hemoglobin (HbA1c), and insulin levels in a mouse model of type 2 diabetes (db/db mice). We further found that ZG02-ME treatment effectively ameliorated serum insulin, leptin and C-peptide levels, which are key metabolic hormones, in db/db mice. In addition, we showed that elevated basal blood lipid levels were decreased by ZG02-ME treatment in db/db mice. Furthermore, treatment of ZG02-ME significantly decreased serum AST, ALT, BUN, creatinine, and liver lipid peroxidation in db/db mice. These results demonstrated that compared to ZG01, chemically modified ZG02-ME possess improved anti-diabetic properties, and has hepato-renal protective activities in type 2 diabetes.

Sanguisorba officinalis L. is widely used in China to treat various wounds, particularly burns. The present study was carried to evaluate the healing efficacy of a purified polysaccharide (SOP) from the roots of S. officinalis L. on burn wound models in mice. The results indicated that oral administration of SOP (50 and 200 mg/kg) significantly stimulated wound contraction and reduced epithelialization time as compared to control group, which might be mediated by promoting collagen synthesis as evidenced by an increase of hydroxyproline content. Elevation of IL-1β and VEGF content was also observed in mice following SOP treatment, which in turn facilitate epithelization and angiogenesis. Besides, histopathological examination of the wound tissues in the SOP-treated animals showed collagen deposition and epidermal formation. It may be concluded that the enhancement of burn wound healing by SOP might be due to promotional collagen synthesis and angiogenesis during skin wound repair as a result of the stimulation of hydroxyproline, IL-1β and VEGF production. The excellent wound-healing activities of SOP provide a scientific rationale for the development of plant-based product in the management of wounds. [ABSTRACT FROM AUTHOR]

Introduction Sanguisorba officinalis (SO) has been commonly used to relieve dermatitis, burns, intestinal infections, hematemesis, and melena for a long time in China, Korea, and Japan. The aim of this study was to investigate the antiviral effects of 30% ethanol extract of SO (SOE) and its major compounds (ziyuglycoside I and II) against HBV in HepG2.2.15 cells and HepG2 cells transfected with HBV genotype C. Methods The antiviral activities of SOE were evaluated by ELISA and quantitative RT-PCR assay in in vitro models. In addition, its effect on HBsAg level was compared to entecavir (ETV), and its co-treatment with ETV was performed to observe combination efficacy. After HPLC analysis of ziyuglycoside I and II, the effects of those compounds on HBsAg levels were measured. Results SOE, ziyuglycoside I, and II significantly reduced HBsAg excretion and the pgRNA levels in HepG2.2.15 cells. In particular, SOE treatment of 100 μg/ml showed an inhibitory effect on HBsAg excretion similar to the levels found with ETV treatment of the same concentration. Additional use of 125 μg/ml of SOE in combination with 80 μM of ETV inhibited HBsAg production up to the level that is diminished by 320 μM ETV treatment in HepG2.2.15 cells. Among SOE, ziyuglycoside I, II, and ETV, ziyuglycoside II had the lowest inhibitory concentration of 50% against genotype D, and it was more potent against HBV genotype C than D in down-regulating HBsAg secretion. Conclusion Taken together, SOE noticeably inhibited replication and antigen secretion of HBV, which was at least in part attributed to ziyuglycoside II, thus presenting the possibility of developing therapeutic candidates for the treatment of HBV-related diseases. [ABSTRACT FROM AUTHOR]

Sanguisorba officinalis Linne ( S. officinalis, Rosaceae) has been used as a medicinal plant for the treatment of burns, hematemesis, melena, intestinal infections, and dermatitis for a long time in China, Korea, and Japan. The therapeutic efficacy of this herb is intimately associated with its anti-oxidant, anti-inflammatory, antiviral, antifungal, hemostatic, and anticancer activities. Its root contains triterpenoid saponins (zigyuglycoside I: CHO and ziyuglycoside II: CHO8) and tannins (sanguiin H-6: CHO). It has been recently revealed that these active constituents of S. officinalis possess antiwrinkle properties without cytotoxicity. They also have anticancer effects by inducing apoptosis and cell cycle arrest. Moreover, they can inhibit proliferative tumorigenesis. The underlying mechanism involved in the pharmacological actions of these active constituents is mainly related to p38 MAPK signaling. Although various studies have reported its therapeutic activities and major chemical components, review articles that extensively organize various properties of S. officinalis and its major constituents are still scarce. Taken together, the objective of this paper is to provide overall pharmacological and phytochemical profiles of S. officinalis and its constituents (including ziyuglycoside I, ziyuglycoside II, and sanguiin H-6), and their potential roles in clinical applications for the treatment of inflammatory diseases, bleeding disorders, and cancer. [ABSTRACT FROM AUTHOR]

Savytskiy I. V., Ostapets M. O., Znamerovskiy S. G. Efficiency of plant origin drugs in gastrointestinal bleeding ulcer genesis treatment = Ефективність застосування лікарського засобу рослинного походження для лікування шлунково-кишкових кровотеч виразкового генезу = Эффективность применения лекарственных средств растительного происхождения для лечения желудочно-кишечных кровотечений язвенного генеза. Journal of Education, Health and Sport. 2016;6(11):640-648. eISSN 2391-8306. DOI http://dx.doi.org/10.5281/zenodo.204936 http://ojs.ukw.edu.pl/index.php/johs/article/view/4072 The journal has had 7 points in Ministry of Science and Higher Education parametric evaluation. Part B item 755 (23.12.2015). 755 Journal of Education, Health and Sport eISSN 2391-8306 7 © The Author (s) 2016; This article is published with open access at Licensee Open Journal Systems of Kazimierz Wielki University in Bydgoszcz, Poland Open Access. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. This is an open access article licensed under the terms of the Creative Commons Attribution Non Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted, non commercial use, distribution and reproduction in any medium, provided the work is properly cited. The authors declare that there is no conflict of interests regarding the publication of this paper. Received: 02.11.2016. Revised 22.11.2016. Accepted: 30.11.2016. УДК 616.15-008.1:34-005.1;615.322 ЕФЕКТИВНІСТЬ ЗАСТОСУВАННЯ ЛІКАРСЬКОГО ЗАСОБУ РОСЛИННОГО ПОХОДЖЕННЯ ДЛЯ ЛІКУВАННЯ ШЛУНКОВО-КИШКОВИХ КРОВОТЕЧ ВИРАЗКОВОГО ГЕНЕЗУ І. В. Савицький1, М. О. Остапець2, С. Г. Знамеровський1 1Одеський національний медичний університет, Одеса, Україна 2Національний фармацевтичний університет, Харків, Україна marina.ostapets.22@mail.ru Реферат Стаття присвячена вивченню впливу біологічно активних речовин родовика лікарського на систему гемостазу та можливість його застосування з метою лікування та профілактики шлунково-кишкових кровотеч виразкового генезу. На моделі спиртово-преднізолонової виразки шлунку встановлено, що досліджуваний екстракт проявив виражений гемостатичний ефект відносно контрольної патології (неліковані тварини) та порівняно з референс-препаратом. Підтвердженням даної активності слугували показники вмісту азоту сечовини в сироватці крові та позитивний тест на приховану кров в калі. Одержані результати можна пояснити фітохімічним складом досліджуваного екстракту – поліфеноли (фенільні сполуки з великою кількістю гідроксилів) здатні утворювати зв’язки за донорно-акцепторним механізмом з гідроксилами плазмових факторів зсідання крові, таким чином вони впливають на коагуляційну фазу системи гемостазу. Ключові слова: шлунково-кишкові кровотечі, родовик лікарський, гемостаз, виразка шлунку. efficiency of plant origin drugs in gastrointestinal bleeding ulcer genesis treatment I. V. Savytskiy, M. O. Ostapets, S. G. Znamerovskiy Odessa national medical university National University of Pharmacy Abstract This article is dedicated to the influence of bio-active substances of Sanguisorba officinalis on hemostatic system and the possibility of its use in the treatment and prevention of ulcer genesis gastrointestinal bleeding. During the alcohol-prednisolone model experimental study of gastric ulcers the analyzed extract showed notable hemostatic effect comparatively with the control pathology (without treatment) and with the reference drug. This influence was indicated by the content of urea nitrogen in the blood and serum positive test for occult blood in the feces. The results can be explained by the composition of the researched extract: high levels of polyphenols were observed. Polyphenols (phenyl compounds with a large number of hydroxyl groups) are capable to form a donor-acceptor mechanism based connection with hydroxyl groups of plasma coagulation factors, thus, they affect the coagulation phase of the hemostatic system. Key words: gastrointestinal bleeding, Sanguisorba officinalis ,hemostatic effect, gastric ulcer. ЭФФЕКТИВНОСТЬ ПРИМЕНЕНИЯ ЛЕКАРСТВЕННЫХ СРЕДСТВ РАСТИТЕЛЬНОГО ПРОИСХОЖДЕНИЯ ДЛЯ ЛЕЧЕНИЯ ЖЕЛУДОЧНО-КИШЕЧНЫХ КРОВОТЕЧЕНИЙ ЯЗВЕННОГО ГЕНЕЗА И. В. Савицкий1, М. А. Остапец2, С. Г. Знамеровский1 1Одесский национальный медицинский университет 2 Национальный фармацевтический университет Реферат Статья посвящена изучению влияния биологически активных веществ кровохлебки лекарственной на систему гемостаза и возможность ее применения с целью лечения и профилактики желудочно-кишечных кровотечений язвенного генеза. На модели спиртово-преднизолоновой язвы желудка установлено, что исследуемый экстракт проявил выраженный гемостатический эффект относительно контрольной патологии (без лечения) и в сравнении с референс-препаратом. Подтверждением данной активности служили показатели содержания азота мочевины в сыворотке крови и положительный тест на скрытую кровь в кале. Полученные результаты можно объяснить фитохимическим составом исследуемого экстракта – полифенолы (фенильные соединения с большим количеством гидроксилов) способны образовывать связи по донорно-акцепторному механизму с гидроксилами плазменных факторов свертывания крови, таким образом они влияют на коагуляционную фазу системы гемостаза. Ключевые слова: желудочно-кишечные кровотечения, кровохлебка лекарственная, гемостаз, язва желудка.

Two new terpene glycosides (1−2) along with two known analogs (3−4) were obtained from the root of Sanguisorba officinalis, which is a common traditional Chinese medicine (TCM). Their structures were elucidated by nuclear magnetic resonance (NMR), electrospray ionization high resolution mass spectrometry (HRESIMS), and a hydrolysis reaction, as well as comparison of these data with the literature data. Compounds 1−4 exhibited anti-inflammatory properties in vitro by attenuating the production of inflammatory mediators, such as nitric oxide (NO) as well as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). An anti-inflammatory assay based on the zebrafish experimental platform indicated that compound 1 had good anti-inflammatory activity in vivo by not only regulating the distribution, but also by reducing the amount of the macrophages of the zebrafish exposed to copper sulfate.

Radioprotective potential of the polyphenolic glycoconjugates, isolated from flowers of Sanguisorba officinalis L. (So) and Erigeron canadensis L. (Ec), and from leaves of Fragaria vesca L. (Fv) and Rubus plicatus Whe. Et N. E. (Rp) as well as their aglycones (SoA, EcA, FvA and RpA, respectively), against γ-radiation-induced lipid peroxidation in human plasma and DNA damage in lymphocytes, were investigated in vitro. These properties were assessed by measuring the concentration of thiobarbituric acid reactive substances (TBARS) and using the alkaline comet assay, and were compared to the protective effects of rutin (R) and quercetin (Q). Cytotoxicity of the glycoconjugates/aglycones towards L929 mouse fibroblasts and human lymphocytes were also measured. Plant products from S. officinalis , similar to Q, were able to reduce the most radiation-induced lipid peroxidation as well as DNA damage and extent of oxidative damage to the DNA basis. Contrary to the pure flavonoids, where Q was shown to be significantly more effective than its glycoside R, the results did not show more benefit with application of SoA/EcA over So/Ec in terms of lipid peroxidation inhibition. Moreover, glycoconjugates Ec and So showed much higher capacity in protecting lymphocytes against radiation-induced genotoxicity which may suggest that between the polyphenolic and polysaccharide parts exist some synergistic effects. There were no significant differences between Fv versus FvA or Rp versus RpA in terms of the provided radioprotection. Summarizing, plant glycoconjugates isolated by the multi-step method offered sufficient radioprotection. In addition, they possess many advantages, compared to the synthetic polyphenolic compounds or the plant extracts, such as water-solubility and minor toxicity. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the healing effect of Sanguisorba officinalis L. extract (SOLE) on seconddegree burns in rats. Methods: Male Sprague Dawley rats, weighing 200 - 220 g, were subjected to deep second-degree skin burns by electrical scald instrument. The animals were divided into three groups as follows: (1) second-degree burns model (control), (2) burns model treated with 1 % silver sulfadiazine (SSD), and (3) burns model treated with SOLE. On days 3, 7 and 14, following administration of drug/extract, the wound area and histopathological changes of rat epidermis were evaluated in all the groups. Minimum inhibitory concentration (MIC) of SOLE on Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli was also assessed separately. Results: On day 14, the mean wound area of SOLE treatment group (0.22 ± 0.05 cm²) was significantly smaller than that of control rats (2.67 ± 0.18 cm², p < 0.01). Histological data indicate that inflammatory cells of burnt rats disappeared and were replaced by new granulation tissue by day 14 for the group treated with SOLE. The antibacterial results revealed that the MIC of SOLE for Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli was 3.5, 14.0 and 7.0 mg·mL-1, respectively. Conclusion: Sanguisorba officinalis L. appears to be an effective medicinal herb for the treatment of second-degree burns. [ABSTRACT FROM AUTHOR]

A macromolecular complex has been isolated from the dried flowering parts of medicinal plant Sanguisorba officinalis L. (So) by multi-step extraction procedure, including that with extraction by organic solvents to degrease the plant material, then with hot alkali, followed by neutralization, partitioning with organic solvents and dialysis. The complex was purified by size-exclusion chromatography into five fractions labeled as So1-So5. Individual fractions differed in the chemical composition and molecular weight distribution patterns. In vitro anticoagulant activity tests showed in all fractions more or less important inhibition of plasma clots, however, So3 and So4 were the most active. The anticoagulant activity of So3 was even more significant than that of the unfractionated complex So. These S. officinalis conjugates were able to inhibit mainly the activity of thrombin when they were mediated by heparin cofactor II, but what was unexpected they were the non-direct inhibitors of factor Xa, mediated by antitrombin, where such mechanism of action is typical for a highly sulphated glycosaminoglycans. [ABSTRACT FROM AUTHOR]

Larvae of the endangered Scarce Large Blue butterfly, Phengaris (Maculinea) teleius, are initially endophytic, feeding upon developing seeds of Sanguisorba officinalis, but complete their development as social parasites preying on the brood of Myrmica ants. Females show very specific preferences, laying eggs exclusively in young flower heads of the food plant. In the present contribution we report the results of a detailed study of female behaviour at three sites differing in size and abundance of S. officinalis. Tracked individuals switched between feeding on nectar (nectaring), flight and oviposition. They fed exclusively on flowers of reddish, pink or violet colouration, favouring Viccia cracca and S. officinalis. However, females spent about one fifth of the time they were active ovipositing and laid about 20 eggs per hour. Oviposition visits to flower heads were highly stereotyped and followed a specific ritual. Examination of accepted, rejected and randomly sampled flower heads showed that females avoided those containing conspecific eggs and at a site where this was difficult due to a shortage of suitable flower heads, they tended to distribute their eggs evenly among the available flower heads. Our results indirectly indicate the existence of an oviposition-deterring pheromone (ODP) in P. teleius. This hypothetical marking ensures a more even distribution of eggs and possibly increases the chances of survival of caterpillars by reducing competition during both the phytophagous and myrmecophagous stages of development. There are few reports of butterflies producing ODPs and to our knowledge this is the first evidence of their presence in the family Lycaenidae.

Four phenolic compounds were isolated from the roots of Sanguisorba officinalis L. by silica gel column chromatography and preparative HPLC. On the basis of chemical and spectroscopic methods, their structures were identified as methyl 4-O-β-D-glucopyranosy-5-hydroxy-3-methoxylbenzoate (1), 3,3′,4′-tri-O-methylellagic acid (2), fisetinidol-(4α-8)-catechin (3), and (+)-catechin (4). Compound 1 is a new phenolic glycoside and compounds 2 and 3 were isolated from the Sanguisorba genus for the first time. Compounds 1–4 were also assayed for their antioxidant activities using the DPPH free radical assay.

Guided by a hemostasis bioassay, seven terpene glycosides were isolated from the roots of Sanguisorba officinalis L. by silica gel column chromatography and preparative HPLC. On the grounds of chemical and spectroscopic methods, their structures were identified as citronellol-1-O-α-l-arabinofuranosyl-(1→6)-β-d-glucopyranoside (1), geraniol-1-O-α-l-arabinofuranosyl-(1→6)-β-d-glucopyranoside (2), geraniol-1-O-α-l-arabinopyranosyl-(1→6)-β-d-glucopyranoside (3), 3β-[(α-l-arabinopyranosyl)oxy]-19α-hydroxyolean-12-en-28-oic acid 28-β-d-glucopyranoside (4), 3β-[(α-l-arabinopyranosyl)-oxy]-19α-hydroxyurs-12-en-28-oic acid 28-β-d-glucopyranoside (ziyu-glycoside I, 5), 3β,19α-hydroxyolean-12-en-28-oic acid 28-β-d-glucopyranoside (6) and 3β,19α-di-hydroxyurs-12-en-28-oic acid 28-β-d-glucopyranoside (7). Compound 1 is a new mono-terpene glycoside and compounds 2, 3 and 5 were isolated from the Sanguisorba genus for the first time. Compounds 1–7 were assayed for their hemostatic activities with a Goat Anti-Human α2-plasmin inhibitor ELISA kit, and ziyu-glycoside I (5) showed the strongest hemostatic activity among the seven terpene glycosides. This is the first report that ziyu-glycoside Ι has strong hemostatic activity.

• Novel chemical-structure small molecule, TMEA, targets TPOR protein. • Megakaryocytes differentiation and thrombopoiesis are stimulated by TMEA through mTOR and ERK signalings downstream of TPOR signaling. • TMEA increases the platelet production in thrombocytopenia state but not triggers an unexpected excessive platelet in normal condition. Non-peptide thrombopoietin receptor (TPOR) agonists are promising therapies for the mitigation and treatment of thrombocytopenia. However, only few agents are available as safe and effective for stimulating platelet production for thrombocytopenic patients in the clinic. This study aimed to develop a novel small molecule TPOR agonist and investigate its underlying regulation of function in megakaryocytes (MKs) differentiation and thrombopoiesis. A potential active compound that promotes MKs differentiation and thrombopoiesis was obtained by machine learning (ML). Meanwhile, the effect was verified in zebrafish model, HEL and Meg-01 cells. Next, the key regulatory target was identified by Drug Affinity Responsive Target Stabilization Assay (DARTS), Cellular Thermal Shift Assay (CETSA), and molecular simulation experiments. After that, RNA-sequencing (RNA-seq) was used to further confirm the associated pathways and evaluate the gene expression induced during MK differentiation. In vivo, irradiation (IR) mice, C57BL/6N-TPORem1cyagen (Tpor -/-) mice were constructed by CRISPR/Cas9 technology to examine the therapeutic effect of TMEA on thrombocytopenia. A natural chemical-structure small molecule TMEA was predicted to be a potential active compound based on ML. Obvious phenotypes of MKs differentiation were observed by TMEA induction in zebrafish model and TMEA could increase co-expression of CD41/CD42b, DNA content, and promote polyploidization and maturation of MKs in HEL and Meg-01 cells. Mechanically, TMEA could bind with TPOR protein and further regulate the PI3K/AKT/mTOR/P70S6K and MEK/ERK signal pathways. In vivo , TMEA evidently promoted platelet regeneration in mice with radiation-induced thrombocytopenia but had no effect on Tpor -/- and C57BL/6 (WT) mice. TMEA could serve as a novel TPOR agonist to promote MKs differentiation and thrombopoiesis via mTOR and ERK signaling and could potentially be created as a promising new drug to treat thrombocytopenia. [Display omitted] [ABSTRACT FROM AUTHOR]