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A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X -ray diffraction analysis. The test results of EC 50 values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC 50 values of 236.8, 206.0 μg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 μg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (K d) value of 0.045 μM, which was superior to the ningnanmycin (0.700 μM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents. [Display omitted] • In this paper, 20 myricetin derivatives containing benzoxazinone were designed and synthesized. • Compound Y8 exhibited excellent antiviral against tobacco mosaic virus in vivo. • The binding ability of Y8 to TMV-CP were explored by microscale thermophoresis and molecular docking technology. • Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA and increasing SOD content. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a serious threat to human life and health. The α-glucosidase and protein tyrosine phosphatase 1B (PTP1B) were important targets for the treatment of type 2 diabetes mellitus. In this paper, euparin, a natural product from Eupatorium chinense possessed extensive pharmacological activities, was selected as the lead compound. It was derived into chalcone compounds with high efficiency, and the inhibitory activities of these 30 products on α-glucosidase and PTP1B were tested. The results showed that compounds 12 and 15 had good inhibitory activities against both enzymes. The IC 50 value of 12 to inhibit α-glucosidase and PTP1B was 39.77 and 39.31 μM, and the IC 50 value of 15 to inhibit α-glucosidase and PTP1B was 9.02 and 3.47 μ M , respectively. In addition, molecular docking results showed that compounds 12 and 15 exhibited good binding affinities toward both α -glucosidase and PTP1B with negative binding energies. The results of the present study demonstrate that compounds 12 and 15 might be beneficial in the treatment of type 2 diabetes. [Display omitted] • High yield, broad substrate, and mild conditions of the synthetic route. • Euparin, a natural product, had been derived into chalcone compounds. • Dual inhibitors of PTP1B and α-glucosidase to against diabetes. • A promising resources for novel antidiabetic drug discovery. [ABSTRACT FROM AUTHOR]

Apigenin and protoapigenone that both have the activities against various cancer cell lines co-exist in Macrothelypteris torresiana , while the extracts of M. torresiana couldn't achieve the fine anti-tumor effects for the existence of potent anti-tumor compounds. This study disclosed an antagonism between the two compounds on the protein level to elucidate the paradox. First, the study established the fingerprint for M. torresiana extract. The following anti-proliferation assay verified that the antagonism occurs between protoapigenone and apigenin. And then Western blot and qt-PCR were applied to evaluate the expression and transcription level of the Akt phosphorylation related targets to validate the antagonism at the protein level. Moreover, CETSA further validated the binding of PDK-1 with apigenin and protoapigenone, as well as the antagonism between the two compounds. Finally, the compound-protein complexes predicted by SYBYL-X gave the visual results for the antagonism. The results demonstrated that: Due to the structural similarity and close binding coefficients to the identical targets, when the cells were treated with apigenin and protoapigenone simultaneously, the Akt phosphorylation inhibition induced by protoapigenone would attenuate significantly. The antagonism disclosed in this paper could be a new explanation for the unsatisfied efficacy of M. torresiana extract. Unlabelled Image [ABSTRACT FROM AUTHOR]

Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. Reinvestigation of the n-BuOH extract of the roots of Clematis argentilucida led to the isolation of a new ursane-type triterpenoid saponin 1 and a new taraxerane-type saponin 2, four known saponins 3-6 first isolated from the species, together with seven saponins 7-13 reported in the previous papers. The structures of saponins 1-6 were elucidated by extensive spectroscopic analysis and chemical evidences. The ursane-type and taraxerane-type triterpenoid saponins were obtained from genus Clematis for the first time, and the aglycone of saponin 1, 3β,28-dihydroxy-18αH-ursan-20-en was first encountered. The cytotoxicity of all the saponins was evaluated against human glioblastoma U251MG cell lines. The monodesmosidic saponins 1, 2 and 4-8 exhibited cytotoxic activity against the cells with IC50 values ranging from 6.95 to 38.51 μM. [ABSTRACT FROM AUTHOR]

Cranberry procyanidins and quercetin derivatives are considered possible active compounds against urinary tract infections (UTIs). In this paper a small group (n = 6) of healthy subjects consumed a product containing 360 mg of cranberry extract (42.6% w/w of PAC-A and 14.6% w/w of PAC-B) and 200 mg of quercetin. Urine samples were collected after 2,4,6,8, and 24 h. The changes in antiadhesive properties against urophatogenic E . coli of the urinary output were determined in vitro and modification to urinary metabolome were studied by LC-MS. Significant antiadhesive properties of urine samples were observed, with the greatest effect 6–8 h after oral administration, confirming the possible usefulness of cranberry containing products in urinary tract infections (UTI). Metabolomic analysis revealed that valeric acid and valerolactone derivatives that were detected in 6 and 8 h sample, while 4-hydroxy-5-(phenyl)-valeric acid- O -glucuronide and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone at 6 h and 4-hydroxy-5-(phenyl)-valeric acid- O -sulphate, 3-hydroxyphenyl-valeric acid, 5-(4′-hydroxyphenyl)-gamma-valerolactone-4′- O -glucuronide and 4-hydroxy-5-(3′-hydroxyphenyl)-valeric acid-3′- O -sulphate were the most abundant at 8 h. The present study shows that the antiadhesive properties of urine sample after cranberry consumption are not ascribable to the direct effect of PAC-A, because their levels in urinary output are in the range of ng/mL. On the other hand, significant metabolites that were detected are mainly metabolites of intestinal action on polyphenols and PACs, as well as glucuronidated and sulphated quercetin, suggesting an important role of intestinal modification of phytoconstituents in the cranberry extract mechanism of action. [ABSTRACT FROM AUTHOR]

Aconitum karacolicum from northern Kyrgyzstan (Alatau area) contains about 0.8–1% aconitine as well as other aconite derivatives that have already been identified. In this paper, we compare several methods for the further purification of an Aconitum karacolicum extract initially containing 80% of aconitine. Reverse-phase flash chromatography, reverse-phase semi-preparative HPLC, centrifugal partition chromatography (CPC) and recrystallization techniques were evaluated regarding first their efficiency to get the highest purity of aconitine (over 96%) and secondly their applicability in a semi-industrial scale purification process (in our case, 150 g of plant extract). Even if the CPC technique shows the highest purification yield (63%), the recrystallization remains the method of choice to purify a large amount of aconitine as i) it can be easily carried out in safe conditions; ii) an aprotic solvent is used, avoiding aconitine degradation. Moreover, this study led us to the identification of lappaconitine in Aconitum karacolicum , a well-known alkaloid never found in this Aconitum species. [ABSTRACT FROM AUTHOR]

This paper utilized a quantitative 1 H nuclear magnetic resonance (qHNMR) method for assessing the purity of iridoids and secoiridoids. The method was fully validated, including specificity, linearity, accuracy, precision, reproducibility, and robustness. For optimization of experimental conditions, several experimental parameters were investigated, including relaxation delay (D1), scan numbers (NS) and power length (PL1). The quantification was based on the area ratios of H-3 from analytes relative to aromatic protons from 1,4-dinitrobenzene (internal standard) with methanol- d 4 as solvent. Five iridoids and secoiridoids (sweroside, swertiamarin, gentiopicroside, geniposide, genipin) were analyzed. Furthermore, the results were validated by the high performance liquid chromatography coupled with ultraviolet detection (HPLC-UV) method. It can be concluded that the qHNMR method was simple, rapid, and accurate, providing a reliable and superior method for assessing the purity of iridoids and secoiridoids. [ABSTRACT FROM AUTHOR]

Isorhynchophylline is one of the major alkaloids from the Uncaria hook possessing the effects of lowered blood pressure, vasodilatation and protection against ischemia-induced neuronal damage. However, the metabolic pathway of isorhynchophylline has not been fully reported yet. In this paper, the metabolism of isorhynchophylline was investigated in rats. Five metabolites were isolated by using solvent extraction and repeated chromatographic methods, and identified by spectroscopic methods including UV, MS, NMR and CD experiments. Three new compounds were identified as 5-oxoisorhynchophyllic acid-22-O-β-D-glucuronide (M1), 17-O-demethyl-16,17-dihydro isorhynchophylline (M2) and 5-oxoisorhynchophyllic acid (M4) together with two known compounds isorhynchophylline (M0) and rhynchophylline (M3). Possible metabolic pathways of isorhynchophylline are proposed. Furthermore, the activity assay for all the metabolites showed that isorhynchophylline (M0) exhibited potent neuroprotective effects against glutamate-induced HT22 cell death. However, little or weak neuroprotective activities were observed forM1-M4. Our present study is important to further understand its metabolic fate and disposition in humans. [ABSTRACT FROM AUTHOR]

In this paper, barbigerone (1a) and its twenty-seven related structural analogues were synthesized via complementary synthetic routes and their anti-inflammatory effects on the expression of TNF-α in LPS-stimulated splenocytes were evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably inhibit TNF-α production. Furthermore, 1g showed the most potent and dose-dependent manner inhibitory effect on TNF-α release, with better IC50 value (3.58 μM) than barbigerone (8.46 μM). Oral administration of 1g at 20 mg/kg/day for two weeks obviously demonstrated protective effect in adjuvant-induced arthritis models as evaluated by clinical score of paws, and histological examination of joint tissues from rats. Mechanism studies on mRNA and protein level suggested that 1g inhibited the TNF-α production via depressing TNF-α converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g with potential therapeutic effects as an anti-inflammatory agent. [ABSTRACT FROM AUTHOR]

Abstract: The fruits of Schisandra chinensis have been used for the treatment of insomnia in oriental countries for more than thousands of years. However, the pharmacological properties and the mechanism of sedative and hypnotic effects have not yet been studied. Gomisin N is one of the major bioactive constituents from the fruits of Schisandra chinensis, and in this paper we reported a detailed study on the effects and mechanisms of Gomisin N on its sedative and hypnotic activity for the first time. These results implied that Gomisin N possessed weak sedative effects on locomotion activity in normal mice, and produced a dose-dependent(5–45mg/kg, i.p.) increase in sleep duration in pentobarbital-treated mice, thus, itself did not induce sleep at higher dose which was used in this experiment (45mg/kg, i.p.). It also can reverse the rodent models of insomnia induced by p-chlorophenylalanine (PCPA) and caffeine, which could exhibit a synergistic effect with 5-hydroxytryptophan (5-HTP) as well; furthermore, the hypnotic effects of Gomisin N were inhibited by flumazenil (a specific GABAA-BZD receptor antagonist). Altogether, these results indicated that Gomisin N produced beneficial sedative and hypnotic bioactivity, which might be mediated by the modification of the serotonergic and GABAergic system. [Copyright &y& Elsevier]

Abstract: Five new sesquiterpenes (1–5) along with ten known ones were isolated from the heartwood of Dalbergia odorifrea T. Chen. Their structures were determined by spectroscopic techniques including MS, UV, IR, 1D and 2D NMR. Bioassay results showed that compounds 1 and 9 had inhibitory effect on Candida albicans, and compound 9 exhibited inhibitory effects on Staphylococcus aureus by paper disk diffusion method. [Copyright &y& Elsevier]

Abstract: Herbal medicine, especially traditional Chinese medicine and Ayurvedic medicine have played and still play an important role in fighting against various diseases. Emerging clinical studies regarding traditional Chinese medicine have provided convincing evidence for the first time to gain credibility and reputation outside China. Although synergistic therapeutic actions of herbal ingredients have been frequently reported, few reports have offered clear underlying mechanisms. This might be the main reason for the conflicting views with respect to the therapeutic efficacy of medicinal herbs. Therefore, this paper reviews the herb synergisms reported in the recent literature and discusses thoroughly the mechanisms underlying synergistic actions of herbal ingredients. The authors conducted an electronic literature search to detect articles published mainly in the last five years. Articles were included if they pertained to synergy research of ethnomedicines or the active compounds derived from them, included verification of synergy effects using modern analytical tools and molecular–biological methods. Results have revealed that the multi-component nature of medicinal herbs makes them particularly suitable for treating complex diseases and offers great potential for exhibiting synergistic actions. The mechanisms underlying synergistic therapeutic actions of herb medicines are (1): different agents may regulate either the same or different target in various pathways, and therefore cooperate in an agonistic, synergistic way; (2): regulate the enzymes and transporters that are involved in hepatic and intestinal metabolism to improve oral drug bioavailability; (3): overcome the drug resistance mechanisms of microbial and cancer cells; and (4): eliminate the adverse effects and enhance pharmacological potency of agents by “processing” or by drug–drug interaction. The exploration of synergistic mechanisms of herbal ingredients will not only help researchers to discover new phytomedicines or drug combinations but also help to avoid the possible negative synergy. Further clinical research is required for verifying these reported drug combinations and discovered synergistic mechanisms. [Copyright &y& Elsevier]

Abstract: Rhubarbs and their extractives have been used as cathartic for many years. There have been numerous breakthroughs in the pharmacological research of the drug. However, as the key point of the mechanism, the targets of the effective components still remain unclear. In this paper, with an in vitro system of isolated intestine, we found that both the rhubarb extractives and the anthraquinone derivatives can antagonize the adrenaline effectively. Furthermore, computer based docking provided the binding model of the anthraquinone derivatives and adrenergic receptor. Then, based on the results of the small intestinal promotion and purgative effect experiments in vivo, we built an “inhibitor–carrier” hypothesis to elucidate the mechanism of rhubarb. This work provided key massages for the pharmacological research of rhubarb, such a common and active medicinal plant, and might be of help for the development of new purgative drugs. [Copyright &y& Elsevier]

Abstract: Reliable methods to identify medicinal plant material are becoming more important in an increasingly regulated market place. DNA-based methods have been recognised as a valuable tool in this area with benefits such as being unaffected by the age of the plant material, growth conditions and harvesting techniques. It is possible that the methods of production used for medicinal plant products will degrade or remove DNA. So how applicable are these techniques to processed medicinal plant products? A simple PCR-based identification technique has been developed for St. John's Wort, Hypericum perforatum L. Thirteen St. John's Wort products were purchased including capsules, tablets and tinctures. DNA was extracted from each product, and the species specific PCR test conducted. DNA was successfully extracted from all thirteen products, using a fast and efficient modified method for extracting DNA from tinctures. Only four products yielded the full length ITS region (850bp) due to the quality of the DNA. All of the products tested positive for H. perforatum DNA. DNA-based identification methods can complement existing methods of authentication. This paper shows that these methods are applicable to a wide range of processed products, provided that they are designed to account for the possibility of DNA degradation. [Copyright &y& Elsevier]

Abstract: Arctiin, an important lignan compound in Fructus Arctii, has been reported to possess various kinds of bioactivities. Previous studies on the pharmacokinetic of arctiin after oral administration showed that it had a rapid absorption phase followed by a sharp but lasting disappearance. To gain deep insight into the action mechanism of arctiin, the excretion and metabolism of arctiin in vivo should be further studied. In this paper, three metabolites were isolated and identified in rat feces as (−)-enterolactone (M-1), (−)-arctigenin (M-2) and [(2R,3R)-2-(3′-hydroxybenzyl)-3-(3″,4″-dimethoxybenzyl)-butyrolactone] (M-3). Based on the structures of three metabolites, possible metabolic pathways of arctiin in rats are proposed. At the same time, the cumulative excretion rate of arctiin and its metabolites in rat urine and feces were determined, indicating that arctiin was excreted 19.84% in urine and 1.80% in feces, respectively, enterolactone, the most main metabolite, was excreted 35.80% in feces. These results provide very important information for understanding the metabolism and excretion of arctiin in vivo and speculating its action mechanism, they can provide useful information and reference for further metabolic investigations on arctiin in humans. [Copyright &y& Elsevier]

Abstract: In this paper, a novel approach using UPLC–MS (Ultra performance liquid chromatography tandem mass spectrometry) coupled with multivariate statistic analysis was established for the profiling and discrimination of raw and processed herb using Genkwa Flos as a model herb. A batch of raw and processed samples was analyzed, and the datasets of t R–m/z pairs, ion intensities and sample codes were subjected to the principal component analysis (PCA). Raw and processed herb showed a clear classification of the two groups on the score plot. Loading plot was performed, and the chemical markers having great contributions to the differentiation were screened out. The identities of the chemical markers were identified by comparing the mass spectra and retention times with those of reference compounds and/or tentatively assigned by matching empirical molecular formulae and mass fragments with those of the known compounds published in the literatures. Based on the proposed strategy, yuanhuacine, genkwadaphnin, genkwanin-5-O-β-d-primeveroside, genkwanine N, genkwanin, 3′-hydroxy-genkwanin and apigenin were explored as representative markers in distinguishing the raw from the processed herbs. The method has been successfully applied in the distinguishing raw from processed herbs. Furthermore, the underlying detoxification mechanism of traditional processing procedure on the herb was predicted, and was related to the changes in the metabolic profiling. This research could be valuable to explore the chemical markers, investigate the mechanism underlying the processing procedure, and promote the quality control and safety application of traditional Chinese herbs. [Copyright &y& Elsevier]

Abstract: Background: Studies indicate that extracts and purified components, including carnosic acid, from the herb rosemary display significant growth inhibitory activity on a variety of cancers. Purpose: This paper examines the ability of rosemary/carnosic acid to inhibit the growth of human breast cancer cells and to synergize with curcumin. Materials and methods: To do this, we treated human breast cancer cells with rosemary/carnosic acid and assessed effects on cell proliferation, cell cycle distribution, gene expression patterns, activity of the purified Na/K ATPase and combinations with curcumin. Results: Rosemary/carnosic acid potently inhibits proliferation of ER-negative human breast cancer cells and induces G1 cell cycle arrest. Further, carnosic acid is selective for MCF7 cells transfected for Her2, indicating that Her2 may function in its action. To reveal primary effects, we treated ER‐negative breast cancer cells with carnosic acid for 6h. At a low dose, 5μg/ml (15μM), carnosic acid activated the expression of 3 genes, induced through the presence of antioxidant response elements, including genes involved in glutathione biosynthesis (CYP4F3, GCLC) and transport (SLC7A11). At a higher dose, 20μg/ml, carnosic acid activated the expression of antioxidant (AKR1C2, TNXRD1, HMOX1) and apoptosis (GDF15, PHLDA1, DDIT3) genes and suppressed the expression of inhibitor of transcription (ID3) and cell cycle (CDKN2C) genes. Carnosic acid exhibits synergy with turmeric/curcumin. These compounds inhibited the activity of the purified Na-K-ATPase which may contribute to this synergy. Conclusion: Rosemary/carnosic acid, alone or combined with curcumin, may be useful to prevent and treat ER‐negative breast cancer. [Copyright &y& Elsevier]

Abstract: It is difficult to develop injectable sustained delivery systems for herbal medicines because of their composition complexity. Encapsulating various compounds with different physiochemical properties and achieving their synchronized and sustained release seem too hard to realize. In this paper, an injectable nanoparticulate system based on an mPEG–PLGA–mPEG (PELGE) platform was prepared for co-encapsulation and sustained release of four active components (ginkgolides A, B, C and bilobalide) in Ginkgo biloba extract. Different carriers were screened by macrophage uptake experiment for their ability to be long-circulation. Drug loaded nanoparticles were prepared with 10% PEG2000 modified PLGA by a co-precipitation method. The encapsulation efficiency of the total ginkgo terpenes (GT) in the optimal formulation was 78.84±2.06% with a loading dose of 11.90±0.31mg/150mg PELGE. The particles exhibited a spherical shape with a mean diameter of 123.3±44.0nm and zeta potential of −30.86±2.49mV. Sustained and synchronized release of the four components from PELGE nanoparticles was observed both in vitro and in vivo, which was mainly contributed to the long circulation of PEGylated nanoparticles and the slow degradation of PLGA. The half-life time of the four terpenoid compounds were also significantly improved by incorporation into PELGE nanoparticles. The results indicate that a PELGE nanoparticle is a promising carrier system for sustained and synchronized release of herbal medicines containing multiple components. [Copyright &y& Elsevier]

Symphytum officinale (comfrey), Tussilago farfara (coltsfoot) and Borago officinalis (borage) have long histories of therapeutic use, but their safety has been questioned due to the presence of unsaturated pyrrolizidine alkaloids (PAs). The evidence base underlying these concerns relies in part on case reports. This systematic review assesses these case reports for their reliability to inform this debate. Study selection was restricted to case reports describing possible pyrrolizidine alkaloid related harm and ingestion of comfrey, coltsfoot or borage. An extensive search of academic databases was conducted. Papers meeting the criteria were critically appraised. The search resulted in 11 appropriate case reports, none of which involved borage. Nine reports were assessed for causality and indicated some degree of association between the material ingested and the adverse event. Lack of unequivocal identification of the species ingested compromised attribution and was a significant source of uncertainty. Three levels of identity confusions were found; misidentification or substitution at the level of the whole herb; omission of appropriate botanical identification and attribution of a specific PA to either comfrey or coltsfoot when it is a constituent found in other plants of established toxicity. These cases are an unreliable body of evidence on which to draw conclusions about the safety of the oral consumption of Symphytum officinale and Tussilago farfara. Toxicological studies based on oral ingestion of phytochemically-complex preparations of these herbs may be the most accurate methodology for assessing clinical risk. Unlabelled Image [ABSTRACT FROM AUTHOR]