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The polysaccharide composition of dried bulbs of Orchis mascula (L.) L. is reported. The obtained polysaccharides were studied as sulfate derivatives, were called SP-S, and were purified by ion-exchange chromatography over a column of DEAE 650M to afford four fractions. Homogeneous polysaccharides were obtained by purifying these fractions using a column of Sephadex G-150. The chemical characteristics were studied. The antioxidant properties of these fractions were determined.

This study aimed to investigate the anti-inflammatory activity of Prunus cerasifera Ehrhart (EHP). LC-MS/MS, network pharmacology, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis methods were used to investigate the chemical composition and the anti-inflammatory mechanism of EHP. The LC-MS/MS results showed that flavonoids and phenolic acids were the major compounds in EHP. The network pharmacology analysis results indicated that EHP was related to TNF, inflammatory cytokine, and MAPK signaling pathway. ELISA and Western blot results showed that EHP impeded the increase in inflammatory factors, inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), nuclear transcription factors κB (p65), MAPK pathway, pyrolytic relevant proteins nod-like receptor family pyrin domain-containing 3 (NLRP3), and interleukin-1β (IL-1β) induced by lipopolysaccharide (LPS) and activated the nuclear factor erythroid 2-related factor 2 (Nrf2)/hemeoxygenase-1 (HO-1) pathway. Therefore, this research highlighted the potential application of P. cerasifera in the development of anti-inflammatory foods that prevented inflammatory diseases. PRACTICAL APPLICATIONS: In recent years, many synthetic drugs with anti-inflammatory effect have the disadvantages of high price and side effects. Thus, the development of anti-inflammatory drugs from natural resources has its application value. In this study, LPS-stimulated RAW264.7 cells were used to establish inflammatory model to verify the anti-inflammatory effect of Prunus cerasifera (EHP). The results showed that P. cerasifera possessed anti-inflammatory activity through inhibiting pro-inflammatory cytokines secretion, NF-κB, MAPK pathway, and NLRP3 inflammasome activation. Therefore, P. cerasifera has the potential to develop into functional food to prevent the progress of various inflammatory-related diseases.

The chemical composition of hazelnut kernels (Corylus avellana L.) and their COX-2 inhibitory, antimicrobial, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical-scavenging activities were investigated. Six previously undescribed indoleacetic acid glycosides, hazelnutins A-F (1-6), and five known compounds (7-11) were isolated from the hazelnut kernels. The structures of compounds 1-6 were successfully identified by high-resolution-electrospray ionization-mass spectrometry and NMR data, and their absolute configurations were established by electron-capture detector spectroscopy analyses in corporation with quantum chemical calculations. Furthermore, the absolute configurations of compounds 7 and 8 were unambiguously confirmed for the first time. Compounds 8-11 were discovered in hazelnut kernels for the first time. Compounds 1-5 inhibited COX-2 expression with inhibition rates ranging from 36.10 to 64.08%. Compounds 3, 4, and 8 could inhibit the proliferation of Candida albicans. Compound 11 exhibited potent antioxidant activity against ABTS and DPPH with IC50 values of 11.22 and 13.21 μmol/L, respectively. Compounds 8 and 10 exhibited moderate antioxidant activity against ABTS.

Chamomile (Matricaria chamomilla L.) is a popular herbal tea for the treatment of hepatitis and cholecystitis in traditional Uygur medicines.To investigate the anti-inflammatory activity and chemical composition of M. chamomilla, and clarify its molecular mechanism.M. chamomilla was extracted with 75% ethanol and then extracted with different solvents to obtain five fractions, namely petroleum ether fraction (EOPE), dichloromethane fraction (EOD), ethyl acetate fraction (EOEA), n-butanol fraction (EOB), and water fraction (EOW). Cytotoxicity and the effect on the nitric oxide (NO) production of RAW264.7 cells induced by LPS of the five fractions were screened, and the most active one (EOD) was selected for further investigations. The components of EOD were identified by LC-MS/MS analysis in combination with comparison of retention time and UV absorption with authentic compounds by HPLC. In addition, five most abundant compounds of EOD were isolation by column chromatography and semi-preparative HPLC and their structures were further confirmed by HRMS and NMR data analysis and comparison with data in literatures. Then the underlying anti-inflammatory mechanism of EOD were predicted through Network pharmacology using the identified compounds from EOD, and further verified by Western Blot and ELISA experiments.EOD showed the most significant inhibition ratio against NO in RAW264.7 cells without toxicity among the tested five fractions. Thirty-seven compounds including flavonoid-O-glycoside, flavonoid aglycone, methylated flavonoid aglycone, phenolic acid, coumarin, sesquiterpene, and triterpene were identified from EOD by LC-MS/MS and comparison with authentic compounds. The five most abundant compounds in EOD were isolated and determined to be axillarin (26), tricin (30), chrysoeriol (31), centaureidin (33) and chrysosplenetin (35). IL-6, NF-κB, ERK1 and ERK2 cascade, TNF were the most important anti-inflammatory targets of EOD predicted by Network pharmacology. Western Blot and ELISA experiments revealed that EOD significantly decreased the protein expression levels of inflammatory factors (PGEM. chamomilla exerted anti-inflammatory effect via NF-κB, MAPK and Nrf2/HO-1 pathways. It could be further applied as a safe anti-inflammatory agent from natural source.

Plants of genus Cichorium are famous due to their therapeutic and medicinal properties. They are used as traditional medicine and edible food. To date, several scholars concentrated on compounds belonging to coumarins, flavonoids, sesquiterpenoids, triterpenoids, steroids, organic acids and other chemical constituents. Pharmacological effects such as photo-protective, hepatoprotective, anti-diabetic and lipid lowering, antioxidant, anti-inflammation, antifungal, antimalarial, increased bone mineral density, as well as vasorelaxant and antitumour activity were wildly reported. In this study, botanical resources, ethnopharmacological application, chemical constituents and bioactivities, as well as safety and toxicity of clinical applications of genus Cichorium were reviewed, which may provide a reliable basis for further development and utilization of Cichorium genetic resources.

In this study, the method for detection of chloramphenicol was investigated by electrochemical sensor; the sensor was constructed by biomass derived porous carbon. At first, porous carbon doped with hetroatoms (nitrogen, sulfur, phosphorus) was synthesized based on the use of pyrolysis and high temperature carbonization methods. Elaeagnusangustifolia L. gum was used as the carbon source in the facile template-free process. The biomass derived porous carbon was then used as the active electrode material for antibiotic sensing. The chemically modified electrodes properties were studied with the cyclic voltammetry and differential pulse voltammetry methods. The effects of the scan rate, accumulation time and pH, were carefully considered. Comparison with other working electrodes at the optimized conditions indicated that the N, S, P triple doped porous carbon modified glassy carbon electrode appeared a well-defined reduction peak towards chloramphenicol. The linear concentration response of chloramphenicol ranged from 1 to 40 μM (R=0.9903) and 50 to 500 μM (R=0.9923), and a low detection limit of 0.01 μM (S/N=3). Furthermore, the constructed novel electrochemical sensor was used for detection of chloramphenicol in real samples and achieved satisfactory recovers.

Anchusa italica Retz. (Boraginaceae) is an important medicinal plant for the treatment of meningitis and pneumonia in traditional Uygur medicines.To clarify the anti-inflammatory activity of A. italica, to reveal its molecular mechanisms, and to discover the anti-inflammatory active ingredients.Dried and crushed aerial parts of A. italica were extracted with 75% ethanol to yield crude extract (AICE) and AICE was fractionated to obtain petroleum ether extract (AIPE), dichloromethane extract (AIDE), ethyl acetate extract (AIEE), n-butanol extract (AIBE) and residues (AIW). By measuring the effects of AIPE, AIDE, AIEE, AIBE and AIW on cell viability and nitric oxide (NO) in Lipopolysaccharide (LPS) stimulated RAW264.7 cell lines, AIDE with the lowest cytotoxicity and NO contents was finally selected for further chemical and anti-inflammatory investigations. LC-MS/MS experiment was applied to analyze the chemical composition of AIDE. MTT and Griess methods were used to detect the cell viability and to quantify the nitrite levels in culture supernatants, respectively. Prostaglandin EIn preliminary anti-inflammatory screening, AIDE showed the lowest cytotoxicity and the most significant inhibitory effect on the production of NO (the inhibitory is 89%) induced by LPS among the tested five extracts. Thirty-three compounds including twenty-five triterpenoids were identified by LC-MS/MS analysis. AIDE could inhibit LPS-induced the over-expression of NO, IL-6, PGEAnchusa italica Retz. exerted its anti-inflammatory activity by inhibiting the mitogen-activated protein kinase (MAPK), nuclear transcription factors κB (NF-κB) and pyrolytic relevant proteins, down-regulating inflammatory factor levels, and activating the Nrf2/HO-1 pathway. Triterpenoids might be its major active anti-inflammatory ingredients.

Three new monoterpene glycosides, komarovins A–C (1–3), together with one known monoterpene glycoside (4) and two known phenolic compounds (5-6), were isolated and identified from the aerial parts of Dracocephalum komarovi. Their structures were established based on comprehensive spectroscopic data analysis and comparison with reported data. Compounds 2–4 were investigated for their inhibition against nitric oxide (NO) production in LPS-stimulated RAW264.7 macrophages, and all of them displayed inhibitory effects on NO production.

The pathogenesis of acute liver injury has been plagued by biologists and physicians. We know little about its therapeutic mechanism. Therefore, this study explored the mechanism of bifendate and muaddil sapra in the treatment of acute liver injury. Firstly, co-expression and cluster analysis of disease-related genes were carried out, and the Go function and KEGG pathway of modules and related genes were identified. Secondly, pivot analysis of modules can identify key regulators. On the other hand, based on the acute liver injury induced by CCl4, we use the combined analysis of proteomics and transcriptome to find therapeutic targets and related mechanisms of drugs. A total of 21 dysfunction modules were obtained, which were significantly involved in immune system, hepatitis and other related functions and pathways. Transcriptome analysis showed 117 targets for bifendate treatment, while 119 for muaddil sapra. Through exploring the mechanism, we found that the two drugs could modulate the module genes. Moreover, bifendate regulate the dysfunction module through ncRNA (SNORD43 and RNU11). Muaddil sapra can mediate dysfunction modules not only by regulating ncRNA (PRIM2 and PIP5K1B), but also by regulating TF (STAT1 and IRF8), thus having a wider therapeutic potential. On the other hand, proteome analysis showed that bifendate mainly regulated Rac2, Fermt3 and Plg, while muaddil sapra mainly regulated Sqle and Stat1. In addition, muaddil sapra regulates less metabolic related proteins to make them more effective. Overall, this study not only provides basic theory for further study of the complex pathogenesis of acute liver injury, but also provides valuable reference for clinical use of bifendate and muaddil sapra in the treatment of acute liver injury.

Kursi Wufarikun Ziyabit (KWZ) is a classic traditional medicine used for the prevention treatment of diabetes in China. It was widely used as healthcare tea in folk and can prevent and treat type 2 diabetes. However, the underlying mechanism of KWZ in type 2 diabetes has not been investigated extensively. Here, the weekly body weight and blood glucose level of KWZ in type 2 diabetes db/db male mice were observed. After 4 weeks of treatment, the physiological changes and pharmacological effects of KWZ were investigated. The results showed that KWZ can significantly decrease fasting blood glucose and improve glucose tolerance and insulin sensitivity in db/db mice. The serum/liver lipid profiles such as LDL-C, TC, TG, and serum-free fatty acid/Fructosamine levels were decreased, and the serum/liver HDL-C levels were increased. In addition, significant improvement in glucose metabolism enzymes and antioxidant enzymes in experimental mice’s livers was observed. Moreover, the expression of GRP78, p-IRE1α/IRE1α, p-eIF2α/eIF2α, and XBP1s was decreased. The expression of p-PERK/PERK, p-Akt/Akt, and p-GSK-3β/GSK-3β was markedly increased. These results suggested that KWZ is effective for type 2 diabetes by improving endoplasmic reticulum (ER) stress in the liver of db/db mice, and it might prevent the damage of insulin Beta cells and alleviate insulin resistance.

Hyssopus cuspidatus is a famous spice and an aromatic vegetable. Few information could be available concerning its non-volatile chemical composition and bioactivities. Preliminary bioactive evaluations on the crude ethanol extract and its four fractions disclosed that the ethyl acetate fraction (EAF) exhibited antioxidant and antimicrobial bioactivities. LC-MS/MS analysis of EAF helped to identify sixty-four compounds, and phenolic compounds were the dominant components. Systematic separation and purification of EAF led to the isolation of thirty-four compounds. Six compounds were identified to be new and eighteen compounds were discovered from H. cuspidatus for the first time. Rosmarinic acid, methyl rosmarinate, butyl rosmarinate and salvigenin were the major components of EAF and their contents were determined. Most of isolated compounds exhibited significant or moderate antioxidant and antimicrobial activities. This research supported the edible application of H. cuspidatus and disclosed the potency of it as a natural antioxidant and antimicrobial food additive.

The herbal medicine of Kursi Wufarikun Ziyabit contains two herbs (Geranium collinum Steph.ex Willd and Hypericum Scabrum Lnn) in the formula of ethnomedicine. It is usually used in the treatment of diabetes mellitus with a significant therapeutic efficacy. However, the molecular mechanism remains unknown for the action of medicine. In this study, we investigated the mechanism with a focus on an extract (GC30) of the medicine in the regulation of energy metabolism in hepatocytes. GC30 was prepared from a crude extract of the medicine through elution of an AB-8 macro porous resin column loaded with the medicine in 30% ethanol. GC30 exhibited an activity in the inhibition of triglyceride (TG) accumulation in the mouse hepatocytes through a suppression of SREBP1c activity. FGF21 (fibroblast growth factor 21) expression was induced by GC30 in a dosage-dependent manner at concentrations of 25 - 100 μg/ml. The induction was observed in mRNA and protein of FGF21, which were peaked at 2 hours and lasted for 8 hours in the response to GC30 (100 μg/ml). The transcription of FGF21 gene was induced by GC30 for an increase in the FGF21 gene promoter activity. AMPK and PKA activities were induced by GC30 with an elevation in their phosphorylation status, which were associated with a reduction in ATP abundance and an increase in CREB phosphorylation in cells treated with GC30. Oxygen consumption of mitochondria was inhibited in the hepatocytes by GC30. These activities of GC30 were similar to those of diabetes medicines including metformin and berberine. The data suggest that GC30 inhibited ATP production in mitochondria to activate AMPK and PKA in the hepatocytes to induce FGF21 expression. This study suggests a novel activity of the herbal medicine in the regulation of glucose and lipid metabolism in the hepatocytes.

Objective. To evaluate the hepatoprotective mechanism of Xwak granule (Xwak) in treatment of mice with alcoholic liver injury via activating ERK/NF-kappa B and Nrf/HO-1 signaling pathways.Methods. The chemical composition of Xwak was tested by liquid chromatography coupled with mass spectrometry (LC-MS). Herein, 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay and 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid (ABTS) radical tests were performedin vitro. The hepatoprotective effect of Xwak was assessed at different concentrations (1.5, 3, and 6 g/kg) in a mouse model of alcoholic liver injury.Results. Totally, 48 compounds, including 16 flavonoids, 8 tannins, 9 chlorogenic acids, and 15 other compounds, were identified from Xwak. Xwak showed to have a satisfactory antioxidant activityin vitro. In a group of Xwak-treated mice, the serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase (ALP) were decreased compared with a group of the mouse model of alcoholic liver injury. In addition, the levels of antioxidant enzymes, such as glutathione peroxidase (GSH-PX), total superoxide dismutase (T-SOD), and catalase (CAT), were noticeably increased and the levels of malondialdehyde (MDA), tumor necrosis factor-alpha(TNF-alpha), transforming growth factor-beta(TGF-beta), and interleukin-6 (IL-6) were markedly reduced in the liver of mice. The state of oxidative stress in the mouse model of alcoholic liver injury was improved after treatment with Xwak. The improvement of inflammation-mediated disruption may conducive to the Xwak activity in the control of liver injury. The signals of p-ERK1/2, p-NF-kappa B, COX-2, iNOS, CYP2E1, Nrf, and HO-1 were significantly induced in the liver of mice after treatment with Xwak.Conclusions. The abovementioned findings indicated that the hepatoprotective mechanism of Xwak could be achieved by activating ERK/NF-kappa B and Nrf/HO-1 signaling pathways to alleviate oxidative stress and inflammatory.

Nine undescribed lignanamides, limoniumins A−I, together with ten known lignanamides and two known phenolics were isolated from ethyl acetate extract of the roots of Limonium gmelinii (Plumbaginaceae). Their structures were determined by spectroscopic analysis including 1D and 2D NMR and HRESIMS experiments. Limoniumin A is the first hybrid lignanamide of phenylpropanoid and coumarin. All tested lignanamides showed significant inhibitory activity against α-glucosidase stronger than positive control and remarkable inhibitory effect to PTP1B with IC50 values less than 10 μM. In addition, some lignanamides exhibited moderate cytotoxic activity against HeLa and MCF-7 cells and anti-inflammatory activity against COX-2 in a dose-dependent way.

In this study, an iron-doped metal-organic framework (MOF) Fe/ZIF-8 was synthesized from ZIF-8 at room temperature. Direct carbonization of Fe/ZIF-8 under a nitrogen atmosphere produced nanoporous nitrogen doped carbon nanoparticles decorated with Fe component (Fe/NC). The Fe/NC exhibited a large surface area (1221.185 m2 g−1) and narrow pore-size distribution (3–5 nm). The nanoporous Fe/NC components along with Nafion were used to modify a glassy carbon electrode for the electrochemical determination of chloramphenicol and metronidazole via linear sweep voltammetry. Under optimal conditions, the reduction peak currents (observed at −0.237 V and −0.071 V vs. Ag/AgCl) of these analytes increased linearly with increasing chloramphenicol and metronidazole concentrations in the range of 0.1–100 μM and 0.5–30 μM, with the detection limits estimated to be 31 nM and 165 nM, respectively. This result was attributed to the large surface area, porous structure, high nitrogen content, and as well as the electrocatalytic effect of Fe atoms embeded in the carbon support. The proposed sensor was used for chloramphenicol and metronidazole analysis in samples, providing satisfactory results.

Background Dry skin is a common skin condition caused by reduction of water-holding capacity, which is regulated by skin barrier function. Dry skin can also be a symptom that indicates a more serious diagnosis. There are a number of moisturizers on the market, which play an important role in dermatologic and cosmetic therapies. However, the demand for these products with good and therapeutic efficiency is still growing. Aims It remains necessary to investigate the effects of Elaeagnus L gum polysaccharides (EAP), which are prepared from gum of Elaeagnus angustifolia L. on the epidermal permeability barrier function and their possible underlying mechanisms. Patients/methods EAP were purified, analyzed, and tested on human keratinocyte cell line (HaCaT) and then on the skin in vivo to evaluate their antiinflammatory activities and their impacts on impaired skin barrier function. Results Histological analyses revealed that topical administration with EAP effectively attenuated dryness-like skin condition, including less percutaneous water loss rate, less infiltrate inflammation cells, and less epidermal thickening. Moreover, EAP inhibited the production of various inflammatory mediators and increased AQP-3, FLG, and LOR expression. Conclusion Our results indicated that EAP enhances epidermal permeability barrier function, and they can be used as a promising adjuvant agent in skin care cosmetics and in treating some skin disorders characterized by cutaneous inflammation and abnormal barrier function.

Kursi Wufarikun Ziyabit (KWZ) is a traditional prescription that used in folk tea drinking for its health care effect in treatment of type 2 diabetes mellitus (T2DM) in central Asia. However, the underlying mechanism of KWZ in T2DM has not been investigated extensively. This study designed to observe the effect of KWZ on glucose consumption and assess the molecular mechanism on associated proteins in insulin signaling and ER stress pathway in L6 rat skeletal muscle cells. The results showed that, KWZ exhibited proteins of PTP-1B and α-glycosidase inhibitory activity in vitro. No cytotoxicity of KWZ was found on L6 cell line. The best effect of glucose consumption of cells was shown at 6.25 μg/mL after KWZ treatment for 12 h. Expression of PTP-1B protein was inhibited by KWZ in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by KWZ. Moreover, the insulin-mediated induction of IRS-1 and GSK-3 were also activated by KWZ. Western blot results indicated that KWZ significantly improved the levels of ER stress proteins, which reduced the expression of GRP78, enhanced the expression of the PERK, eIF2α and XBP1s. The activation of PERK/eIF2α was likely consequence of GRP78 inhibition, and this might be beneficial for improving the stability of ER and alleviating insulin resistance. These results suggest that KWZ might be serving as the potential drug for the prevention and treatment of T2DM. Keywords: Type 2 diabetes, Kursi Wufarikun Ziyabit, Anti-diabetic activity, Insulin signaling pathway, Endoplasmic reticulum stress

This study was designed to investigate the mechanism of polyphenol-enriched extract of Rosa rugosa Thunb (RPE) in the control of dyslipidemia in diabetic rats. RPE was tested at three dosages (37.5 mg/kg, 75 mg/kg and 150 mg/kg) in the rat dyslipidemia model established with high fat diet feeding in combination with STZ injection (30 mg/kg). The RPE effect was evaluated after 4 weeks of treatment. In the RPE-treated rats, hepatic total cholesterol (TC) and triglyceride (TG) were significantly reduced, lipoprotein lipase (LPL) and liver lipase (HL) were significantly increased. The levels of alanine transaminase (ALT) and aspartate transaminase (AST) were decreased in the serum. Those effects of RPE were observed primarily at the mediate and high dosages. Expression of FGF21 was increased in the liver tissue and hepatic cell line 1c1c7 by RPE. The signals of p-AMPK, p-ACC, ACC, p-SIRT, and PGC-1 alpha were significantly induced in the liver by RPE. The results suggest that RPE may improve hepatic steatosis and liver function by induction of AMPK signaling activity in the control of dyslipidemia.

A new fatty acid ester (1) and seven known phenolic compounds, i.e. salfredin B11 (2), nigephenol C (3), nigephenol B (4), acetovanillion (5), p-hydroxybenzoic acid (6), p-hydroxy-acetophenone (7) and p-hydroxybenzaldehyde (8), were isolated from the seeds of Nigella sativa var. hispidula. Among them, compounds 5, 7 and 8 were isolated from Nigella for the first time. Their structures were elucidated with HR-ESI-MS, 1D and 2D NMR spectra. Evaluation of the isolated compounds on protein tyrosine phosphatase (PTP1B) assay indicated that although compounds 2-8 show no promising anti-PTP1B activities, compound 1 possess anti-PTP1B activity with an IC50 value of 7.38±0.14muM in vitro.

Ethnopharmacological relevance: Rosa rugosa Thunb is a traditional Uygur medicine that has been used in the treatment of diabetes in Uygur ancient recipe for hundreds of years. However, the mechanism of Rosa rugosa Thunb activity is still unclear. This study was designed to address this issue by studying the polyphenols enriched extract (RPE) of Rosa rugosa Thunb in diabetic rats. Materials and methods: RPE were tested in the inhibition of a-glucosidase and oxidative stress in vitro. RPE was administrated at dosages of 37.5, 75 and 150 mg/kg body weight in the type 2 diabetic rats, which were made by high fat diet feeding plus a low dose of STZ injection (30 mg/kg). The therapeutic effect was evaluated four weeks later. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT) and insulin signal pathway (PI3K/AKT) were examined to determine insulin sensitivity. Blood glucose levels and body weight were measured weekly in the study. Results: In vitro, RPE exhibited an activity in the inhibition of a-glucosidase and had an excellent antioxidant activity in the liver of diabetic rats. RPE significantly decreased the fasting blood glucose, improved insulin sensitivity (HOMA-IR), OGTT, ITT and blood lipid profile. The glycogen synthesis and hexokinase activity were increased together with the improved signaling activity of insulin as indicated by p-IRS, p-IR, p-AKT, and p-GSK-3 beta. Conclusions: The results suggest that RPE reduced blood glucose in type 2 diabetic rats by improvement of insulin sensitivity. The effect is likely achieved by inhibition of oxidative stress and a-glucosidase.

Two new alkaloids, nigellisoquinomine (1) with a novel pyrrolo-isoquinoline skeleton, and nigellapyrrolidine (2) possessing a rare glycosylated pyrrolidine moiety, together with two known alkaloids, agrocybenine (3) and 4,6,6-trimethyl-3,4-epoxypiperidin-2-one (4), were isolated from the seeds of Nigella glandulifera Freyn. Their structures were identified by extensive NMR and HR-ESIMS analysis. Compound 1 exhibited potent protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with an IC50 value of 3.65 ± 0.08 μM.

Diabetes is a metabolic disease with the characteristic of high blood glucose (hyperglycemia). In our previous study, we found that nigelladines A – C (compounds A – C ), three norditerpenoid alkaloids from the seeds of Nigella glandulifera Freyn (Ranunculaceae) exhibited protein of tyrosine phosphatase 1B (PTP1B) inhibitory activity in vitro . In the present study, we further investigated their anti-diabetes activities in L6 moytubes and illuminated the mechanisms of action of compounds A – C . Several parameters of glucose metabolism such as glucose consumption, glycogen content and hexokinase activity were increased by compounds A – C . The results suggested that compounds A–C improved glucose metabolism through promoting synthesis of glycogen. Expression of PTP1B protein was inhibited by compounds A – C in L6 moytubes. PI3K-dependent Akt phosphorylation was found to be activated by compounds A - C and completely blocked by wortmannin (a PI3K inhibitor). Moreover, the insulin-mediated induction of insulin receptor substrate-1 (IRS-1) and glycogen synthase kinase-3β (GSK-3β) were also suppressed by wortmannin. Western blot results indicated that compounds A – C -induced IRS-1/Akt activation was likely a consequence of PTP1B inhibition. Compounds A – C promoted glycogen synthesis through Akt-mediated GSK3 phosphorylation. Therefore, activation of PI3 K/Akt insulin signaling pathway and suppression of PTP1B is the molecular mechanism that contributes to the anti-diabetic effect of compounds A–C in cellular models. The three alkaloids potentially serve as lead compounds for the development of antidiabetic drugs.

Asthma is a chronic immune disease that has become a serious public health problem. The currently available medications are not ideal because of their limitations and side effects; hence, new target proteins and signaling cascades for precise and safe therapy treatment are needed. This work established an ovalbumin-induced asthma rat model and treated it with total flavonoid extract from the Xinjiang chamomile. The proteins that were differentially expressed in the chamomile extract-treated asthmatic rats and the asthma and healthy rat groups were identified using isobaric tagging followed by LC-MS/MS. Kyoto encyclopedia of genes and genomes pathway analysis of the differentially expressed proteins was performed. Pathways involved in purine metabolism, herpes simplex infection, and JNK phosphorylation and activation mediated by activated human TAK1 were enriched, indicating the intrinsic links between the mechanism of asthma development and treatment effects. Furthermore, we constructed a protein–protein interaction network and identified KIF3A as a potential target protein of chamomile extract that affected the Hedgehog signaling pathway. This study may provide new insights into the pathogenesis of asthma and reveal several proteins and pathways that could be exploited to develop novel treatment approaches.

The edible and medicinal properties of Rosa rugosa Thunb are widely applied in the world. There are many including rose oil, rose sauce, rose cake, rose wine, rose tea, rose herbs, and other applications. In the medicinal application, R. rugosa Thunb is used in the treatment of diabetes mellitus and related complications in Korea, Japan, and Uyghur medicine in China. In addition, the active constituents of R. rugosa Thunb could act on some biological effects, such as antihyperglycemic, antiinflammatory, antioxidation, lipid lowing, antihepatotoxic, antihypertensive, cardioprotective, antihyperplasia, antistress, antibacterial, antiallergic, and so on. There are many reports about the bioactivities of R. rugosa Thunb. The aim of this work is to summarize the related research contents and provide a theoretical basis for the medicinal application of R. rugosa Thunb.

Rosa rugosa Thunb, a deciduous shrub of the genus Rosa, has been widely used to treat stomach aches, diarrhoea, pain, and chronic inflammatory disease in eastern Asia. In recent years, our research team has extensively studied the Rosa rugosa flower extract, and specifically undertook pharmacological experiments which have optimized the extraction process. Our methods have yielded a standard extract enriched in phenolic compounds, named PRE. Herein, we expand our efforts and evaluated the anti-inflammatory activity of PRE on lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages. PRE significantly inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF)-a, interleukin (IL)-6, and interleukin 1β (IL-1β), as well as expression of their synthesizing enzymes, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX-2). Furthermore, PRE inhibited activity of mitogen-activated protein kinases (MAPK) as well as nuclear factor-kappa B (NF-κB) signaling pathway. Our findings are the first to explain the anti-inflammatory mechanism by PRE in LPS-stimulated macrophages. Given these results, we propose that PRE has therapeutic potential in the prevention of inflammatory disorders.

Nigella glandulifera Freyn belongs to the Ranunculaceae family of plants. It is an annual herbaceous plant widely distributed in the southwest and western regions of China. The seeds and oil of N. glandulifera have been used as a medicine to treat a variety of diseases. Unfortunately, the extraction of bioactive components and their inherent phytochemical characterization is rarely investigated using optimum condition of emerging extraction. In the study, we compared the microwave-assisted method to traditional extraction methods, which has the shortest time, highest yield and greatest biological activity. We performed single factor experiments with comprehensive assessments and used Box-Behnken design with a response surface methodology to assess the optimal conditions. The optimal extraction method was as follows; solid-to-liquid ratio of 1:20 g/mL, ethanol concentration of 70%, extraction time of 35.00 min, and extraction temperature of 66 °C. Using these conditions, we further analyzed the spectrum–effect relationship using gray correlation and chemical composition using ultra-high-performance liquid chromatography coupled with high resolution hybrid quadruple-orbitrap mass spectrometry (UHPLC-Q-Orbitrap-HRMS). Therefore, the gray relationship of 17 compounds was analyzed greater than 0.95 which may have synergistic effects on the inhibiting of aldose reductase. In addition, thirty compounds were identified, including alkaloids, flavonoid glucosides, triterpenoid saponins and phenolic compounds, all of which may have a therapeutic effect on diabetic complications. The results of this study may offer a time-saving and convenient method to acquire bioactive components to improve and treat diabetic complications.

Fifteen new piperidine derivatives, pyracyclumines A-J (1-10), including five pairs of enantiomers, (+)-1/(-)-1 to (+)-5/(-)-5, together with three known compounds, agrocybenine (11), 4,6,6-trimethyl-5,6-dihydro-2(1 H)-pyridone (12), and 3,5,5-trimethyl-1,5-dihydro-2 H-pyrrol-2-one (13), were isolated from the roots of Anacyclus pyrethrum. Pyracyclumines A, B, and H (1, 2, and 8) possess a novel 6/5/6/6 dimeric piperidine skeleton, a unique 6/5/6 dimeric piperidine skeleton, and a 1,4,6-triazaindan skeleton, respectively. Pyracyclumine C (3) is based on a rare cyclopentane-piperidine framework. The structures of the isolated compounds were established by analysis of their NMR and HRESIMS data. The racemic pyracyclumines A-E (1-5) were further separated by chiral HPLC to give the enantiomers (+)-1/(-)-1 to (+)-5/(-)-5, for which the absolute configurations were determined by comparison of their experimental and calculated ECD spectra. The plausible biogenetic pathways of these piperidine alkaloids were proposed starting from the basic units of compounds 12 and 13. All of the isolated compounds were tested for their inhibitory effects on menin-mixed lineage leukemia 1 protein-protein interaction.

By using extraction yield, total polyphenolic content, antidiabetic activities (PTP-1B and α-glycosidase), and antioxidant activity (ABTS and DPPH) as indicated markers, the extraction conditions of the prescription Kursi Wufarikun Ziyabit (KWZ) were optimized by response surface methodology (RSM). Independent variables were ethanol concentration, extraction temperature, solid-to-solvent ratio, and extraction time. The result of RSM analysis showed that the four variables investigated have a significant effect (p<0.05) for Y1, Y2, Y3, Y4, and Y5 with R2 value of 0.9120, 0.9793, 0.9076, 0.9125, and 0.9709, respectively. Optimal conditions for the highest extraction yield of 39.28%, PTP-1B inhibition rate of 86.21%, α-glycosidase enzymes inhibition rate of 96.56%, and ABTS inhibition rate of 77.38% were derived at ethanol concentration 50.11%, extraction temperature 72.06°C, solid-to-solvent ratio 1 : 22.73 g/mL, and extraction time 2.93 h. On the basis of total polyphenol content of 48.44% in this optimal condition, the quantitative analysis of effective part of KWZ was characterized via UPLC method, 12 main components were identified by standard compounds, and all of them have shown good regression within the test ranges and the total content of them was 11.18%.

A novel ellipsoid column was designed for centrifugal counter-current chromatography . Performance of the ellipsoid column with a capacity of 3.4mL was examined with three different solvent systems composed of 1-butanol-acetic acid-water (4:1:5, v/v/v) (BAW), hexane-ethyl acetate-methanol-0.1M HCl (1:1:1:1, v/v/v/v) (HEMH), and 12.5% (w/w) PEG1000 and 12.5% (w/w) dibasic potassium phosphate in water (PEG-DPP) each with suitable test samples. In dipeptide separation with BAW system, both stationary phase retention (Sf) and peak resolution (Rs) of the ellipsoid column were much higher at 0 degrees column angle ( column axis parallel to the centrifugal force) than at 90 degrees column angle ( column axis perpendicular to the centrifugal force), where elution with the lower phase at a low flow rate produced the best separation yielding Rs at 2.02 with 27.8% Sf at a flow rate of 0.07mL/min. In the DNP-amino acid separation with HEMW system, the best results were obtained at a flow rate of 0.05ml/min with 31.6% Sf yielding high Rs values at 2.16 between DNP-DL-glu and DNP-beta-ala peaks and 1.81 between DNP-beta-ala and DNP-L-ala peaks. In protein separation with PEG-DPP system, lysozyme and myolobin were resolved at Rs of 1.08 at a flow rate of 0.03mL/min with 38.9% Sf. Most of those Rs values exceed those obtained from the figure-8 column under similar experimental conditions previously reported.

Ethnopharmacological relevance: Cichorum glandulosum Boiss. et Huet is a traditional Uygur herbal medicine that has been used as a cholagogic and diuretic agent to improve liver function. However, the mechanism is not known for the liver-protective function. We investigated the antioxidant effects of plant extraction (CGE60) in vitro and in vivo, and find the mechanism of liver protection in Bacille Calmette-Guerin vaccine (BCG)+Lipopolysaccharides (LPS) induced liver injury in mice. Materials and methods: CGE60 was made, and the antioxidant activity was investigated by comparing the ability of scavenging 1,1-diphenyl-2-picrylhydrazyl (DPPH), and 2,2-azinobis(3-ehtylbenzothiazolin-6-sulfnicAcid) diammonium salt (ABTS) free radicals in vitro. Then, CGE60 was administrated in mice of liver damage model which was induced in mice using the BCG+LPS protocol. The CGE 60 extract was tested at three dosages: 50 mg/kg, 100 mg/kg, and 200 mg/kg. Product of lipid peroxidation (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-PX,), nitric oxide (NO), nitric oxide synthetase (NOS), hydroxyproline and alkaline phosphatase (ALP) contents were evaluated in liver to determine the CGE60 activity in the hepatic injury model. Tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and transforming growth factor-beta (TGF-beta) proteins were determined in the liver tissues using ELSIA. The signaling activities were evaluated in Western blot. Results: CGE60 exhibited strong antioxidant ability in vitro. With oral administration, CGE60 significantly increased the activity of CAT, SOD, GSH-PX, and decreased the level of NO, NO synthase, hydroxyproline, ALP and lipid peroxidation liver of in the BDG+ LPS model. CGE60 attenuated hepatic inflammation via down- regulation of TNF-alpha, IL-6 and TGF-beta. CGE60 blocked protein expression of cytochrome P450 2E1 (CYP2E1), nuclear factor kappa-B (NF-kappa B), phosphorylation of extracellular signal-regulated kinase (p-ERK1/2), and cyclooxygenase-2 (COX-2),but activated the expression of p-P38 MAPK. Conclusion: This study suggests that CGE60 possesses antioxidant activity and this activity associates with hepatoprotective effect in the mice of BCG +LPS model, and the mechanisms underlying these effects may involve antioxidant actions and anti-inflammation activities.

IntroductionRosa rugosa flowers used as herbal medicine possess many activities. A fraction extracted by ethyl acetate exhibited strong inhibitive activity against protein tyrosine phosphatase 1B (PTP1B) in vitro. ObjectiveEstablish an efficient method of LC coupled to quadrupole time-of-flight (QTOF) with tandem MS/MS to investigate the compositions in the active fraction. MethodsChemical compositions were separated and investigated by LC/QTOF-MS/MS in negative electrospray ionisation (ESI) mode at different collision energy (CE) values. The maximal structural information was obtained for the identification of components. ResultsA total of 75 compounds including tannins, their related compounds and flavonoids were identified or partially characterised according to accurate mass and the characteristic fragments at low and high CE. Meanwhile, the fragmentation pathways of gallotannins and ellagitannins (hexahydroxydiphenoyl group and lactonised valoneoyl group) were studied and proposed and were used to trace tannins in crude extracts. ConclusionThe results suggest that this fraction is a source of PTP1B inhibitory activity with a potential for treating diabetes. Copyright (c) 2013 John Wiley & Sons, Ltd. As a traditional herbal medicine, Rosa rugosa flowers possess many activities. In this study, a LC-MS method was established for investigation of chemical compositions in a fraction with the PTP 1B inhibitory activity from Rosa rugosa. And 75 chemical compositions in this fraction were identified or tentatively characterized. The fragmentation pathways of gallotannins and ellagitannins were proposed. Knowing the phytochemical profiles of PTP 1B inhibitory activity fraction of this plant gives insights to its potential application to promote health.

A sample pretreatment method using acid-base extraction was established for pH-zone-refining counter-current chromatography (CCC) to increase the yield of the target compound. As the most important step, selection of two-phase solvent system for pH-zone-refining CCC should follow some rules. One of these rules is that when pH of two-phase solvent system is around 2 (for an acidic analyte) or 10 (for a basic analyte), partition coefficient values of K(acid) or K(base) should be much greater than 1. According to this rule, a new pretreatment method was developed that could substantially increase the yield of the target compound in pH-zone-refining CCC. The separation of the crude alkaloids extracted from the seeds of Sophora alopecuroides was selected as an example to show the advantage of this method. Before CCC separation, 20 g of crude sample was extracted 3 times with the selected two-phase solvent system composed of MtBE-CH₃CN-H₂O (2:2:3, v/v), where pH of the upper phase was adjusted with triethylamine to 10. A 10 g amount of the second basic extract thus obtained was subjected to pH-zone-refining CCC separation. As a result, 169 mg of sophoramin and 696 mg of sophoearpin were isolated from the second basic extract, where the yields have been doubled compared with those of the untreated sample (crude sample). Experimental results showed that the present method for pretreating the crude sample could produce substantially higher yields of target compounds in pH-zone-refining CCC.

The chemical compositions of essential oils extracted by n-hexane extract (HE), petroleum ether extract (PE), dichloromethane extract (DE), and hydrodistillation (HD) from Carthamus tinctorius L. (safflower) were analyzed by gas chromatography-mass spectrometry (GC-MS). A total of 86 compounds from four different extracts were identified, and the contents were 97.65%, 98.05%, 98.93%, and 99.68%, respectively. 6,10,14-Trimethyl-2-pentadecanone, hexadecanoic acid, methyl ester, hexadecanoic acid, 8,11-octadecadienoic acid, methyl ester, and 9,12,15-octadecatrien-1-ol were the major constituents of the extracts. The antidiabete activity was assayed in vitro by against protein tyrosine phosphatase 1B (PTP1B). The results showed that the HE exhibited the best in vitro inhibitory enzyme activity against PTP1B, which holds a good potential for treating diabetes and obesity.

An efficient method for bioassay-guided preparative isolation of antioxidants from the n-butanol extract of Astragalus altaicus Bunge was ingeniously developed by combination of silica gel column chromatography and high-speed counter-current chromatography. Under the bioassay-guidance of antioxidant activities, the antioxidants were gradually separated from the crude sample of Astragalus altaicus Bunge by silica gel column chromatography and high-speed counter-current chromatography. Silica gel column chromatography separation was performed with chloroform, chloroform-methanol (100:1∼5:1, v/v) and chloroform-methanol-water (5:1:0.1∼2:1:0.1, v/v/v). High-speed counter-current chromatography separation was performed with a two-phase solvent system composed of ethyl acetate-n-butanol-water (2:1:6, v/v/v), which was successfully selected by thin layer chromatography analysis, at a flow rate of 1.5 mL/min. As a result, isorhamnetin-3-gentiobioside (20.8 mg), rutin (82.0 mg), and narcissin (12.8 mg) were obtained for the first time from 200 mg of the crude sample, ABS-5 of Astragalus altaicus Bunge. The purities were all at over 95% by high-performance liquid chromatography analysis, and their structures were unambiguously identified by mass spectroscopy, 1H, and 13C nuclear magnetic resonance spectroscopy. Antioxidant activities of the three compounds were also assayed by in vitro ABTS [2,2'-azino-bis-(3- ethylbenzothiazoline-6-sulphonic acid) diamonium salt] radical cation scavenging activity. Among them, rutin possessed the highest antioxidant capacity with SC50 value of 22.15 μg/mL. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two new sesquiterpene lactones, namely 8-O-methylsenecioylaustricin (1) and epi-8 alpha-angeloyloxy-cichoralexin (2), as well as a new triterpene glycoside (taraxasterol 3-O-beta-D-glucoside, 3), together with the three known sesquiterpene lactones lactucin (4), lactucopicrin (5), and 11 beta,13-dihydrolactucin (6), were isolated from the stems of Cichorium glandulosum BOISS. FT HUET. The chemical structures were elucidated on the basis of spectroscopic methods.