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The most widespread Sanguisorba species are Sanguisorba officinalis L. and Sanguisorba minor Scop. which are also found in the Romanian flora and classified as medicinal plants because of hemostatic, antibacterial, antitumor, antioxidant and antiviral activities. This study aimed to characterize and compare Sanguisorba species in order to highlight which species is more valuable according to phenolic profile and antimicrobial activity. Based on high-performance liquid chromatography equipped with photodiode array detection and mass spectrometry (electrospray ionization) (HPLC–DAD-MS (ESI+)) analysis, it was evident that the ethanol extract obtained from the leaves of S. minor Scop. contains the highest content of phenolic compounds at 160.96 mg/g p.s., followed by the flower and root extract (131.56 mg/g dw and 121.36 mg/g dw, respectively). While in S. officinalis, the highest amount of phenols was recorded in the root extract (127.06 mg/g), followed by the flower and leaves extract (102.31 mg/g and 81.09 mg/g dw, respectively). Our results show that among the two species, S. minor Scop. is richer in phenolic compounds compared with the S. officinalis L. sample. In addition, the antimicrobial potential of each plant organ of Sanguisorba species was investigated. The ethanol extract of S. minor Scop. leaves exhibited better antibacterial activity against all of the bacteria tested, especially on Staphylococcus aureus, with an inhibition zone of 15.33 ± 0.83 mm. Due to the chemical composition and antimicrobial effect, the Sanguisorba species can be used as food supplements with beneficial effects on human health.

A selective and rapid ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established and validated for the determination of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, and pomolic acid in rats after the oral administration of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, pomolic acid, and Sanguisorba officinalis L. extract. The separation was carried out on an ACQUITY UPLC®HSS T3 column (2.1 mm × 100 mm, 1.8 μm), using methanol and 5 mmol/L ammonium acetate water as the mobile phase. The three compounds were quantified using the multiple reaction monitoring mode with the electrospray ion source in both the positive and negative mode. Liquid-liquid extraction was applied to the plasma sample preparation. Bifendate was selected as the internal standard. The intra-day and inter-day precision and the accuracy of the method were all within receivable ranges. The lower limit of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, and pomolic acid were 6.50, 5.75, and 2.63 ng/mL, respectively. The extraction recoveries of analytes in rat plasma ranged from 83 to 94%. The three components could be rapidly absorbed into the blood (Tmax, 1.4–1.6 h) both in the single-administration group or S. officinalis extract group, but the first peak of PA occurred at 0.5 h and the second peak at 4–5 h in the S. officinalis extract. Three compounds were eliminated relatively slowly (t1/2, 7.3–11 h). The research was to establish a rapid, sensible, and sensitive UHPLC–MS/MS method using the multi-ion mode for multi-channel simultaneous mensuration pharmacokinetics parameters of three compounds in rats after oral administration of S. officinalis extract. This study found, for the first time, differences in the pharmacokinetic parameters of the three compounds in the monomer compounds and S. officinalis extract administration, which preliminarily revealed the transformation and metabolism of the three compounds in vivo.

BACKGROUND Many natural products confer health benefits against diverse diseases through their antioxidant activities. Carbon tetrachloride (CCl4) is often used in animal experiments to study the effects of substances on liver injury and the related mechanisms of action, among which oxidative stress is a major pathogenic factor. AIM To compare antioxidant and hepatoprotective activities of ten herbs and identify and quantify phytochemicals for the one with strongest hepatoprotection. METHODS The antioxidant activity of ten medicinal herbs was determined by both ferric-reducing antioxidant power and Trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin–Ciocalteu method and aluminum chloride colorimetry, respectively. Their effects on CCl4-induced oxidative liver injury were evaluated and compared in a mouse model by administrating each water extract (0.15 g/mL, 10 mL/kg) once per day for seven consecutive days and a dose of CCl4 solution in olive oil (8%, v/v, 10 mL/kg). The herb with the strongest hepatoprotective performance was analyzed for the detailed bioactive components by using high-performance liquid chromatography-electrospray ionization source-ion trap tandem mass spectrometry. RESULTS The results revealed that all tested herbs attenuated CCl4-induced oxidative liver injury; each resulted in significant decreases in levels of serum alanine transaminase, aspartate transaminase, alkaline phosphatase, and triacylglycerols. In addition, most herbs restored hepatic superoxide dismutase and catalase activities, glutathione levels, and reduced malondialdehyde levels. Sanguisorba officinalis (S. officinalis) L., Coptis chinensis Franch., and Pueraria lobata (Willd.) Ohwi root were the three most effective herbs, and S. officinalis L. exhibited the strongest hepatoprotective effect. Nine active components were identified in S. officinalis L. Gallic acid and (+)-catechin were quantified (7.86 ± 0.45 mg/g and 8.19 ± 0.57 mg/g dried weight, respectively). Furthermore, the tested herbs displayed a range of in vitro antioxidant activities proportional to their phenolic content; the strongest activities were also found for S. officinalis L. CONCLUSION This study is of value to assist the selection of more effective natural products for direct consumption and the development of nutraceuticals or therapeutics to manage oxidative stress-related diseases.

Sanguisorba officinalis L. (SO), a well-known herbal medicine, has been proven to show effect against thrombocytopenia. However, metabolites of SO in vivo are still unclear, and the underlying mechanism of SO against thrombocytopenia from the aspect of metabolites have not been well elucidated. In this study, an improved analytical method combined with UHPLC-QTOF MS and a molecular network was developed for the rapid characterization of metabolites in vivo based on fragmentation patterns. Then, network pharmacology (NP) was used to elucidate the potential mechanism of SO against thrombocytopenia. As a result, a total of 1678 exogenous metabolites were detected in urine, feces, plasma, and bone marrow, in which 104 metabolites were tentatively characterized. These characterized metabolites that originated from plasma, urine, and feces were then imported to the NP analysis. The results showed that the metabolites from plasma, urine, and feces could be responsible for the pharmacological activity against thrombocytopenia by regulating the PI3K-Akt, MAPK, JAK-STAT, VEGF, chemokine, actin cytoskeleton, HIF-1, and pluripotency of stem cells. This study provides a rapid method for metabolite characterization and a new perspective of underlying mechanism study from the aspect of active metabolites in vivo.

A novel analytical method involving high-performance liquid chromatography with evaporative light scattering detection (HPLC-ELSD) was developed for simultaneous determination of 11 phenolic acids and 12 triterpenes in Sanguisorba officinalis L. Chromatographic separation was conducted with gradient elution mode by using a DiamonsilTM C18 column (250 mm × 4.6 mm, 5 μm) with the mobile phase of 0.1% acetic acid water (A) and methanol (B). The drift tube temperature of ELSD was set at 70 °C and the nitrogen cumulative flow rate was 1.6 L/min. The method was fully validated to be linear over a wide concentration range (R2 ≥ 0.9991). The precisions (RSD) were less than 3.0% and the recoveries were between 97.7% and 101.4% for all compounds. The results indicated that this method is accurate and effective for the determination of 23 functional components in Sanguisorba officinalis L. and could also be successfully applied to study the influence of processing method on those functional components in Sanguisorba officinalis L.

Thrombocytopenia is closely linked with hemorrhagic diseases, for which induction of thrombopoiesis shows promise as an effective treatment. Polyphenols widely exist in plants and manifest antioxidation and antitumour activities. In this study, we investigated the thrombopoietic effect and mechanism of 3,3′,4′-trimethylellagic acid (TMEA, a polyphenol in Sanguisorba officinalis L.) using in silico prediction and experimental validation. A KEGG analysis indicated that PI3K/Akt signalling functioned as a crucial pathway. Furthermore, the virtual molecular docking results showed high-affinity binding (a docking score of 6.65) between TMEA and mTOR, suggesting that TMEA might target the mTOR protein to modulate signalling activity. After isolation of TMEA, in vitro and in vivo validation revealed that this compound could promote megakaryocyte differentiation/maturation and platelet formation. In addition, it enhanced the phosphorylation of PI3K, Akt, mTOR, and P70S6K and increased the expression of GATA-1 and NF-E2, which confirmed the mechanism prediction. In conclusion, our findings are the first to demonstrate that TMEA may provide a novel therapeutic strategy that relies on the PI3K/Akt/mTOR pathway to facilitate megakaryocyte differentiation and platelet production.

Background Helicobacter pylori (H. pylori) infection has become an international public health problem, and antibiotic-based triple or quadruple therapy is currently the mainstay of treatment. However, the effectiveness of these therapies decreases due to resistance to multiple commonly used antibiotics. Sanguisorba officinalis L. (S. officinalis), a traditional Chinese medicine clinically used for hemostasis and treatment of diarrhea, has various pharmacological activities. In this study, in vitro antimicrobial activity was used for the preliminary evaluation of S. officinalis against H. pylori. And a pharmacology analysis approach was also utilized to elucidate its underlying mechanisms against H. pylori infection. Methods Micro-broth dilution method, agar dilution method, checkerboard assay, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) were used for the assessment of anti-bacterial activity. Active ingredients screening, GO analysis, KEGG analysis, construction of PPI network, molecular docking, and RT-qPCR were used to elucidate the underlying pharmacological mechanisms of S. officinalis against H. pylori infection. Results The minimum inhibitory concentration (MIC) values of S. officinalis against multiple H. pylori strains including clinically isolated multi-drug resistant (MDR) strains were ranging from 160 to 320 µg/ml. These results showed that S. officinalis had additive interaction with four commonly used antibiotics and could exert antibacterial effect by changing the morphology of bacteria without developing drug resistance. Through network pharmacology analysis, 8 active ingredients in S. officinalis were screened out for subsequent studies. Among 222 putative targets of S. officinalis, 49 targets were identified as potential targets for treatment of H. pylori infection. And these 49 targets were significantly enriched in GO processes such as protein kinase B signaling, protein kinase activity, protein kinase binding, and KEGG pathways such as Pathways in cancer, MicroRNAs in cancer, and TNF signaling pathway. Protein-protein interaction analysis yielded 5 core targets (AKT1, VEGFA, EGFR, SRC, CCND1), which were validated by molecular docking and RT-qPCR. Conclusions Overall, this study confirmed the in vitro inhibitory activity of S. officinalis against H. pylori and explored the possible pharmacological mechanisms, laying the foundation for further research and clinical application.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is challenging to eradicate because of antibiotic resistance and biofilm formation. Novel antimicrobial agents and alternative therapies are urgently needed. This study aimed to evaluate the synergy of sanguisorbigenin (SGB) isolated from Sanguisorba officinalis L. with six conventional antibiotics to achieve broad-spectrum antibacterial action and prevent the development of resistance. A checkerboard dilution test and time-to-kill curve assay were used to determine the synergistic effect of SGB combined with antibiotics against MRSA. SGB showed significant synergy with antibiotics and reduced the minimum inhibitory concentration of antibiotics by 2–16-fold. Biofilm inhibition assay, quantitative RT-PCR, crystal violet absorption, and transmission electron microscopy were performed to evaluate the synergy mechanism. The results indicated that SGB could inhibit biofilm formation and alter cell membrane permeability in MRSA. In addition, SGB was found to exhibit quite low cytotoxicity and hemolysis. The discovery of the superiority of SGB suggests that SGB may be an antibiotic adjuvant for use in combination therapy and as a plant-derived antibacterial agent targeting biofilms.

Sanguisorba officinalis L. (SA) is a common herb for cancer treatment in the clinic, particularly during the consolidation phase to prevent occurrence or metastasis. Nevertheless, there are limited studies reporting the molecular mechanisms about its anti-metastatic function. It is well demonstrated that autophagy is one of the critical mechanisms accounting for metastasis and anti-cancer pharmacological actions of Chinese herbs. On the threshold, the regulatory effects and molecular mechanisms of SA in suppressing autophagy-related breast cancer metastasis were investigated in this study. In vitro findings demonstrated that SA potently suppressed the proliferation, colony formations well as metastasis process in triple-negative breast cancer. Network and biological analyses predicted that SA mainly targeted caveolin-1 (Cav-1) to induce anti-metastatic effects, and one of the core mechanisms was via regulation of autophagy. Further experiments—including western blotting, transmission electron microscopy, GFP-mRFP-LC3 immunofluorescence, and lysosomal-activity detection—validated SA as a potent late-stage autophagic inhibitor by increasing microtubule-associated light chain 3-II (LC3-II) conversion, decreasing acidic vesicular-organelle formation, and inducing lysosomal dysfunction even under conditions of either starvation or hypoxia. Furthermore, the anti-autophagic and anti-metastatic activity of SA was Cav-1-dependent. Specifically, Cav-1 knockdown significantly facilitated SA-mediated inhibition of autophagy and metastasis. Furthermore, hypoxia inducible factor-1α (Hif-1α) overexpression attenuated the SA-induced inhibitory activities on Cav-1, autophagy, and metastasis, indicating that SA may have inhibited autophagy-related metastasis via Hif-1α/Cav-1 signaling. In both mouse breast cancer xenograft and zebrafish xenotransplantation models, SA inhibited breast cancer growth and inhibited late-phase autophagy in vivo, which was accompanied by suppression of Hif-1α/Cav-1 signaling and the epithelial-mesenchymal transition. Overall, our findings not only indicate that SA acts as a novel late-phase autophagic inhibitor with anti-metastatic activities in triple-negative breast cancer, but also highlight Cav-1 as a regulator in controlling late-phase autophagic activity.

Ziyuglycoside I (ZgI), one of the main active ingredients in the popular Diyushengbai tablet made from Sanguisorba officinalis L., has been proven to relieve leukopenia clinically. However, to our knowledge, no studies have investigated the pharmacokinetics of either Diyushengbai tablet or ZgI in leukopenic vs. healthy individuals. In the present study, a rapid and sensitive UHPLC-MS/MS method was developed for detecting ZgI. On using this method on a novel cyclophosphamide-induced leukopenia model, we investigated differences in the pharmacokinetic characteristics of ZgI between leukopenic and normal rats. Chromatographic separation of ZgI and glycyrrhetinic acid (IS) was achieved via gradient elution in 0.5 min, and the total run time lasted for 5 min. Methodological validation results presented a good accuracy (102.6 %–110.8 %) and precision (% RSD ≤ 13.8) with a limit of quantitation of 0.5 ng/mL. Pharmacokinetic results showed a significantly shortened peak time (Tmax) (0.93 vs. 0.33 h) while a remarkably decreased maximum concentration (Cmax) (7.96 vs. 3.40 ng/L) in the 20 mg/kg leukopenia group in comparison with those in the 20 mg/kg normal group. In addition, a prolonged elimination half-life (t1/2β) was observed in the 20 mg/kg leukopenia group (5.02 vs. 18.51 h). We observed similar trends in the 5 mg/kg oral dosing treatment and control groups, except for Cmax, which did not differ between the groups. We did not find pharmacokinetic differences in ZgI between the two leukopenia groups. Thus, the pharmacokinetic parameters of ZgI (e.g., Tmax, Cmax, and T1/2β) changed based on the presence of a leukopenic state. This study may provide guidance for the development of ZgI as an agent for the treatment of leukopenia.

The subject of the investigation. 70 % water-ethanol extracts of Sanguisorba officinalis L. herb. The purpose of the investigation – a comparative research of antioxidant and antiradical activity of 70 % water-ethanol extracts of Sanguisorba officinalis L. herb, gathered during various development stages – beginning of growing, budding, blooming and fruit-bearing, was performed using in vitro methods. Methods of investigation. Antioxidant activity was evaluated by inhibiting lipid peroxidation reaction and adrenalin autoxidation. Antiradical activity of the extracts was determined by the ability to inactivate DPPH-, ABTS-radicals and by their ability to bind nitrogen oxide molecules, inhibiting of superoxide, hydroxyl radical and ions Fe+2chelate activity. Main results. It was determined that herb extracts, gathered during budding and blooming stages, had higher antioxidant and antiradical activity which is explained by high content of polyphenolic compounds, in particular flavonoids in these periods. Scope. The results can be used for creation of new medicinal products from medicinal plants possess antioxidant action. Conclusions. The results of these tests allow to consider Sanguisorba officinalis L. herb, gathered during budding and blooming stages, as perspective antioxidant medicinal herb.

The main purpose of the work was the phytochemical study of the herb of the blood burnet drug (Sanguisorba officinalis L.) from six regions of the Republic of Bashkortostan and the rationale for the prospect of expanding its use in medicine. The collection of herbs was carried out in the flowering phase. The analysis of raw materials was carried out on the basis of the Bashkir State Medical University. Qualitative and quantitative determination of biologically active substances was carried out according to standard and modified methods. Amino acid composition was determined by x-ray fluorescence method The quantitative characteristics of the following groups of biologically active substances were determined: ascorbic acid (0.307–0.521%), organic (1.46–2.27%) and hydroxycinnamic (1.13–1.30%) acids, carotenoids (31.17–35.89 mg%), polysaccharides (0.43–1.05%), saponins (0.56–0.88%), coumarins (0.285–0.326%), tannins (5.1–6.3%). A characteristic of the amino acid composition. The possibility of using the herb of burnet drug is shown along with the rhizomes and roots, which will solve the problem of waste-free processing of this plant., Основной целью работы являлось фитохимическое исследование травы кровохлебки лекарственной (Sanguisorba officinalis L.) из шести районов Республики Башкортостан и обоснование перспективы расширения ее использования в медицине. Сбор травы осуществляли в фазу цветения. Анализ сырья проводили на базе Башкирского государственного медицинского университета. Качественное и количественное определение биологически активных веществ осуществляли по общепринятым и модифицированным методикам. Аминокислотный состав определяли рентгенофлуоресцентным методом. Рассчитаны количественные характеристики следующих групп биологически активных веществ: аскорбиновая кислота (0.307–0.521%), органические (1.46–2.27%) и оксикоричные (1.13–1.30%) кислоты, каротиноиды (31.17–35.89 мг%), полисахариды (0.43–1.05%), сапонины (0.56–0.88%), кумарины (0.285–0.326%), дубильные вещества (5.1–6.3%). Дана характеристика аминокислотному составу. Показана возможность использования травы кровохлебки лекарственной наравне с корневищами и корнями, что позволит решить проблему безотходной переработки данного растения.

Muscle fatigue is induced by an acute or chronic physical performance inability after excessive physical activity often associated with lactate accumulation, the end-product of glycolysis. In this study, the water-extracted roots of Sanguisorba officinalis L., a herbal medicine traditionally used for inflammation and diarrhea, reduced the activities of lactate dehydrogenase A (LDHA) in in vitro enzyme assay myoblast C2C12 cells and murine muscle tissue. Physical performance measured by a treadmill test was improved in the S. officinalis-administrated group. The analysis of mouse serum and tissues showed significant changes in lactate levels. Among the proteins related to energy metabolism-related physical performance, phosphorylated-AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor-coactivator-1 alpha (PGC-1α) levels were enhanced, whereas the amount of LDHA was suppressed. Therefore, S. officinalis might be a candidate for improving physical performance via inhibiting LDHA and glycolysis.

Leukopenia is the most common hallmark of hematopoietic diseases in clinic. Sanguisorba Officinalis L., a traditional Chinese medicine, has long been used for alleviating leukopenia. However, its associated mechanism still remains unknown. In this study, a network pharmacology approach was used to elucidate the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia. Firstly, 12 active compounds of Sanguisorba Officinalis L. were identified through TCMSP database with absorption, distribution, metabolism, excretion (ADME) screening, and UHPLC-MS analysis. Then, 258 leukopenia related targets of the identified active compounds were predicted via the Swiss Target Prediction database, GeneCards database and DisGeNET database, respectively. After taking the intersection of two related targets, 72 common targets were selected. Among them, 8 core targets (VEGFA, HSP90AA1, EGFR, PTGS2, MTOR, ESR1, ERBB2, MDM2) of Sanguisorba Officinalis L. against leukopenia were obtained through the topological analysis. Meanwhile, both the GO and KEGG pathway analysis reveal that the core targets are mainly enriched in PI3K-Akt, HIF-1, VEGF and estrogen signaling pathways. In addition, molecular docking simulation was performed to explore the binding ability between the 12 active compounds of Sanguisorba Officinalis L. with 8 core targets. Furthermore, a myelosuppressive mice model was established to evaluate the protective effect of Sanguisorba Officinalis L. against leukopenia. The results showed that the ethanol extract of Sanguisorba Officinalis L. significantly raised the number of peripheral white blood cells. Overall, this study provides an insight into the underlying mechanisms of Sanguisorba Officinalis L. against leukopenia, which lays a theoretical foundation for the further experimental verification and clinical application.

Radix Sanguisorbae, the root of Sanguisorba officinalis L. is used as traditional Chinese medicine. In recent decades, it has been reported to be clinically effective against myelosuppression induced by chemotherapy and/ or radiotherapy. However, the underlining mechanism has not been well studied. In this work, we evaluated the hematopoietic effect of total saponins from S. officinalis L. on myelosuppressive mice induced by cyclophosphamide and by60Co-γ-irradiation and confirmed the therapeutic effect. Then, we found total saponins and their characteristic constituents Ziyuglycoside I and Ziyuglycoside II can inhibit apoptosis of TF-1 cells caused by cytokine deprivation, and promote survival of mouse bone marrow nuclear cells through focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (Erk1/2) activation in vitro. In addition, they can down-regulate macrophage inflammatory protein 2 (MIP-2), platelet factor 4 (PF4) and P-selectin secretion, which are reported to be suppressive to hematopoiesis, both in vitro and in vivo. These results suggest that promotion of survival through FAK and Erk1/2 activation and inhibition of suppressive cytokines in the bone marrow is likely to be the pharmacological mechanism underlying the hematopoietic effect of saponins from S. officinalis L.

An analysis of the fractions of free acids and phenolic acids liberated by way of hydrolysis in the rhizomes and herbaceous tissues of Sanguisorba officinalis L. was conducted through utilizing the 2D-TLC method. Fifteen phenolic acids were identified. Our work showed that ellagic, protocatechuic, gentisic, p-hydroxybenzoic, syringic, vannilic and ferulic acids were common in all tested fractions, and gallic and protocatechuic acids were dominant in fractions obtained from the rhizomes, while caffeic, p-coumaric, syringic, vannilic and ferulic acids were abundant in the herbaceous tissues. However, α and β - resorcylic acids were detected only in rhizome phenolic acid fractions liberated from their conjunction with sugars and alcohols. Furthermore, chlorogenic acid was present only in a free form in the herbaceous tissues, while p-hydroxyphenylacetic acid was liberated from conjunction from a herbaceous extract.

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3&beta, 19&alpha, dihydroxyurs-12-en-28-oic-acid 28-&beta, d-glucopyranosyl ester (II), 3&beta, [(&alpha, l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid &beta, d-glucopyranosyl ester (III), rosamultin (IV), 1&beta, hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3&beta, d-glucopyranosyl ester, 3&beta, d-glucopyranosyl ester, rosamultin, 1&beta, hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid&ndash, liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3&beta, hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from &minus, 9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58&ndash, 1.58 h), and then eliminated relatively slowly (t1/2, 6.86&ndash, 11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis.

Using a bioassay-directed chromatographic separation, two ellagic acids were obtained from the ethyl acetate extract of the roots of Sanguisorba officinalis L. On the basis of chemical and spectroscopic methods, the two ellagic acids were identified as 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside and 3,3',4-tri-O-methylellagic acid. Stimulation of cell proliferation was assayed in hematopoietic progenitor cells using the Cell Counting kit-8 method. The megakaryocyte differentiation was determined in human erythroleukemia (HEL) cells using Giemsa staining and flow cytometry analysis. The ellagic acids significantly stimulated the proliferation of Baf3/Mpl cells. Morphology analysis and megakaryocyte specific-marker CD41 staining confirmed that the ellagic acids induced megakaryocyte differentiation in HEL cells. This is the first time that 3,3',4-tri-O-methylellagic acid or 3,3',4-tri-O-methylellagic acid-4'-O-β-d-xyloside are reported to induce megakaryopoiesis, suggesting a class of small molecules which differ from others non-peptidyl, and appears to have potential for clinical development as a therapeutic agent for patients with blood platelet disorders.

The effect of chiyu extract on antioxidant defense alteration in senescence-accelerated mice (SAM) was examined. Comparison with AKR/N Slc mice, a strain consistent with SAM but exhibiting normal aging, showed a lower glutathione (GSH) level and glutathione/glutathione disulfide (GSH/ GSSG) ratio in the kidney and liver of SAM, whereas malondialdehyde (MDA), a lipid peroxidation product, was increased significantly. Administration of chiyu extract increased the GSH level and GSH/ GSSG ratio, and markedly suppressed MDA production. On the other hand, detection of renal enzymes related to the glutathione redox cycle showed that catalase and glutathione peroxidase activities were largely decreased in SAM, whereas chiyu extract reversed this tendency. The reduced activities of hepatic catalase and glutathione reductase were increased significantly by the extract. These findings suggest that a decline of the antioxidant defense system occurs in SAM, and that chiyu extract may have a beneficial effect in ameliorating oxidative stress or damage. 老化促進マウス(SAM)の抗酸化防御機構に対し,地楡エキスがいかなる影響を及ぼしているかについて,SAMと同じ系統ではあるが,通常の老化過程を辿るAKR/N Slcマウスと比較検討した。その結果,SAMの腎,肝グルタチオンレベルとグルクチオン/グルタチオンジスルフィド比は低下し,脂質過酸化物のマロンジアルデヒドは逆に有意に上昇していたが,地楡エキスを投与したSAMでは,これらパラメーターがいずれも改善していた。一方,グルタチオン酸化還元サイクルに関係している酵素のうち,腎ではカタラーゼとグルクチオンペルオキシダーゼ活性がSAMで著しく低下し,地楡エキス投与によってこれら酵素の活性が回復していた。肝においても低下していたカタラーゼとグルタチオンレダクターゼ活性がエキス投与により著しく回復していた。これら所見は,SAMで認められる抗酸化防御系の低下が,地楡エキスによって是正されることを示唆するものである。