Yujie Li

A new dicoumarinoid glycoside from Daphne giraldii.

A new dicoumarinoid glycoside, named giraldoid A (1), has been isolated from Daphne giraldii Nitsche. The structure of 1 was determined as 7-O-β-glucosyl-8-(7-hydroxy-2H-1-benzopyran-2-one-8-)yl-2H-1-benzopyran-2-one on the basis of chemical reactions and spectroscopic methods.

Flavonoids casticin and chrysosplenol D from Artemisia annua L. inhibit inflammation in vitro and in vivo.

BACKGROUND The aim of our experiments was to investigate the anti-inflammatory properties of casticin and chrysosplenol D, two flavonoids present in Artemisia annua L. METHODS Topical inflammation was induced in ICR mice using croton oil. Mice were then treated with casticin or chrysosplenol D. Cutaneous histological changes and edema were assessed. ICR mice were intragastrically administrated with casticin or chrysosplenol D followed by intraperitoneal injection of lipopolysaccharide (LPS). Mouse Raw264.7 macrophage cells were incubated with casticin or chrysosplenol D. Intracellular phosphorylation was detected, and migration was assessed by trans-well assay. HT-29/NFκB-luc cells were incubated with casticin or chrysosplenol D in the presence or absence of LPS, and NF-κB activation was quantified. RESULTS In mice, administration of casticin (0.5, 1 and 1.5μmol/cm(2)) and chrysosplenol D (1 and 1.5μmol/cm(2)) inhibited croton oil-induced ear edema (casticin: 29.39-64.95%; chrysosplenol D: 37.76-65.89%, all P<0.05) in a manner similar to indomethacin (0.5, 1 and 1.5μmol/cm(2); 55.63-84.58%). Casticin (0.07, 0.13 and 0.27mmol/kg) and chrysosplenol D (0.07, 0.14 and 0.28mmol/kg) protected against LPS-induced systemic inflammatory response syndrome (SIRS) in mice (all P<0.05), in a manner similar to dexamethasone (0.03mmol/kg). Casticin and chrysosplenol D suppressed LPS-induced release of IL-1 beta, IL-6 and MCP-1, inhibited cell migration, and reduced LPS-induced IκB and c-JUN phosphorylation in Raw264.7 cells. JNK inhibitor SP600125 blocked the inhibitory effect of chrysosplenol D on cytokine release. CONCLUSIONS The flavonoids casticin and chrysosplenol D from A. annua L. inhibited inflammation in vitro and in vivo.

Establishment of an interleukin‑1β‑induced inflammation‑activated endothelial cell‑smooth muscle cell‑mononuclear cell co‑culture model and evaluation of the anti‑inflammatory effects of tanshinone IIA on atherosclerosis

Increasing evidence supports the hypothesis that inflammatory reactions serves an important function in the formation, progression and plaque rupture of atherosclerosis. Interleukin (IL)-1 primarily induces inflammation and is closely associated with the inflammatory environment and the formation of atherosclerosis. The present study aimed to establish an in vitro model for the evaluation of drug efficacy in the intervention of atherosclerosis from the inflammatory perspective, and to observe the anti-inflammatory effects of tanshinone IIA and andrographolide on atherosclerosis. The IL-1β-induced inflammation-activated endothelial cell (EC)-smooth muscle cell (SMC)-mononuclear cell (MC) co-culture model was established, based on the changes in a series of atherosclerosis-associated inflammatory markers secreted by ECs and SMCs. The expression of connexin in ECs, adhesion of MCs and changes in inflammatory signalling molecules were selected as evaluation indices for the inflammatory microenvironment of atherosclerosis. The use of this model revealed that tanshinone IIA exhibited significant efficacy against atherosclerosis and its inflammatory reactions. Inflammatory reactions were regarded as the primary mechanism underlying atherosclerosis. The established model simulated a series of relevant changes in the arterial wall under the inflammatory cytokines with oxidized low-density lipoprotein during the atherosclerotic process. The present study presented a reliable method for the identification of drugs with potential anti-inflammatory activity in atherosclerosis, for investigating the mechanisms of action, considering the improvement of the inflammatory state and the increase in plaque stability observed.

Lonicerae Japonicae Flos and Lonicerae Flos: A Systematic Pharmacology Review

Lonicerae japonicae flos, a widely used traditional Chinese medicine (TCM), has been used for several thousand years in China. Chinese Pharmacopeia once included Lonicerae japonicae flos of Caprifoliaceae family and plants of the same species named Lonicerae flos in general in the same group. Chinese Pharmacopeia (2005 Edition) lists Lonicerae japonicae flos and Lonicerae flos under different categories, although they have the similar history of efficacy. In this study, we research ancient books of TCM, 4 main databases of Chinese academic journals, and MEDLINE/PubMed to verify the origins and effects of Lonicerae japonicae flos and Lonicerae flos in traditional medicine and systematically summarized the research data in light of modern pharmacology and toxicology. Our results show that Lonicerae japonicae flos and Lonicerae flos are similar pharmacologically, but they also differ significantly in certain aspects. A comprehensive systematic review and a standard comparative pharmacological study of Lonicerae japonicae flos and Lonicerae flos as well as other species of Lonicerae flos support their clinical safety and application. Our study provides evidence supporting separate listing of Lonicerae japonicae flos and Lonicerae flos in Chinese Pharmacopeia as well as references for revision of relevant pharmacopeial records dealing with traditional efficacy of Lonicerae japonicae flos and Lonicerae flos.

Anti-tumor pharmacological evaluation of extracts from stellera chamaejasme L based on hollow fiber assay

BackgroundStellera chamaejasme L, a traditional Chinese herb, has long been used for treatment of various tumors in the Chinese population. In our previous study, we paid an attention to the cytotoxic and proapoptotic effects of Stellera chamaejasme L extracts (ESC, ESC-1 and ESC-2, the latter two were isolated from ESC) on 4 various tumor cells (NCI-H157, NCI-H460, BEL-7402 and SK-HEP-1) in vitro. ESCs showed significantly inhibitory effects on the 4 tumor cells. ESC-2 had the strongest inhibitory effect and the broadest sensitive cell spectrum. ESC-2 and ESC acted in a similar way against tumor cells, which suggested anti-tumor active fraction of ESC might exist in ESC-2. Here, we further observe the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts in vivo.MethodsIn this study, we used hollow fiber tumor model to evaluate the inhibitory and proapoptotic effects of Stellera chamaejasme L extracts. Apoptotic rates of the cancer cells retrieved from the hollow fibers were measured with flow cytometric analysis, caspase 3, 8, 9 enzyme activities were detected by colorimetric assay, Fas, Fas-L, TNF-R1 and TNF-α expression were determined with elisa assay and radioimmunoassay respectively.ResultsThe results showed that ESC, ESC-2 all had inhibitory effects on 4 tumor cells. According to the effect strength, dose and antitumor spectrum, the order of antitumor effects of ESCs was: ESC-2 > ESC > ESC-1. NCI-H460 cells were the most sensitive to ESCs. ESC, ESC-2 increased greatly the apoptotic rate and caspase 3, 8 enzyme activities in NCI-H460. ESCs had no significant effects on expression of Fas, Fas-L protein, but TNF-α/TNFR1 protein expression in NCI-H460 cells changed significantly after ESC and ESC-2 treatment.ConclusionESC-2 had the similar antitumor effect to that of ESC in vivo and further confirmed that ESC-2 may be the main antitumor active fraction of ESC, which was consistent with our previous results in vitro.

Chamaejasmenin B, a novel candidate, inhibits breast tumor metastasis by rebalancing TGF-beta paradox

Metastasis is the leading lethal factor severely restraining the effectiveness of clinical treatment. TGF-beta is the key regulator for metastasis and influences paradoxically on cancer progression. The known TGF-beta blockers exert little selectivity on its functions, indiscriminately causing the anti-metastatic and pro-growth effects. Under such circumstances, specifically rebalancing the oncological function of TGF-beta provides a crucial oncotarget against metastasis. In our study, we established the screening platform targeting cell motility and identified a potential flavonoid, Chamaejasmenin B (ICJ), extracted from Stellera chamaejasme L. It suppressed the migration and invasion in breast cancer cells in vitro. Moreover, by dynamical quantification of breast cancer progression in small-animal imaging system, ICJ was proved to be a potent inhibitor of metastasis with minimal toxic side effects. Mechanism study further revealed that ICJ efficiently blocked TGF-beta induced EMT, disrupted the interaction between β3 integrin-TβRII complex and, consequently, resulted in the selective inhibition of FAK:Src:p38 pathway. Meanwhile, specific blockage of this pathway largely attenuated the anti-metastatic function of ICJ. Importantly, in contrast with the antagonistic effects on TGF-beta induced metastasis, ICJ obviously sensitized its cytostatic activity, suggesting that it was not a pan-blocker but a rebalancer for the functional output of TGF-beta. Collectively, by targeting TGF-beta Paradox, we experimentally provided a promising candidate for metastatic intervention.

Pharmacokinetics of Two Alkaloids after Oral Administration of Rhizoma Coptidis Extract in Normal Rats and Irritable Bowel Syndrome Rats

A comparative pharmacokinetic study of berberine and palmatine after oral administration of Rhizoma Coptidis extract (96 mg/kg, containing berberine 22 mg/kg and palmatine 5 mg/kg based on body weight) was performed in normal and postinflammation irritable bowel syndrome (PI-IBS) rats, induced by intracolonic instillation of acetic acid and restraint stress. Quantification of berberine and palmatine in rat plasma was achieved by using a sensitive and rapid UPLC-MS/MS method. Plasma samples were collected at 13 different time points and the pharmacokinetic parameters were analyzed by WinNonlin software. The significant differences in the pharmacokinetic behaviors, such as C max⁡, AUC(0–t), V d/F, and CL/F, of berberine and palmatine were found between normal and PI-IBS model rats. The results indicated that PI-IBS pathological conditions in rats could alter the pharmacokinetic behavior of drug. Preclinical pharmacokinetic studies are usually carried out on healthy animals. However, we should pay more attention to the fact that the change of pharmacokinetic behavior plays an important role on efficacy. It is essential to investigate the pharmacokinetics of the drug in disease status.

HPLC Quantitative Analysis of Main Stilbenes and Flavones in Different Parts of Matteuccia struthiopteris

A simple and accurate HPLC-UV method was developed for the simultaneous quantitative analysis of main stilbenes and flavones in different parts (fronds, rhizomes, and frond bases) of M. struthiopteris. The chromatographic separation was performed on a Kromasil C18 column (4.6 mm × 250 mm, 5 μm) with the mobile phase of MeOH-H2O (including 0.1% phosphoric acid) using a gradient elution at the flow rate of 1.0 mL min−1 and UV detection at 295 nm. The method was validated by specificity, linearity, accuracy (recovery), and precision tests (repeatability, intra- and interday). For all the six compounds, the linear regression coefficients ranged from 0.9958 to 0.9998 within the test ranges; intra- and interday precisions were 2% and the mean recoveries ranged from 98.09 to 103.56%. The amount of these compounds in the frond bases was almost the same as in the rhizomes but much higher than that in the fronds. The results indicate that the HPLC method developed was appropriate for the analysis of the six compounds in different parts (fronds, rhizomes, and frond bases) of M. struthiopteris.

Two new C-methyl flavanones from the rhizomes and frond bases of Matteuccia struthiopteris

Two new C-methyl flavanones, (2S)-5,7-dihydroxy-6,8-dimethyl-4′-methoxydihydroflavone-7-O-(6″-O-acetyl)-β-d-glucopyranoside (1) and (2S)-5,7-dihydroxy-6,8-dimethyldihydroflavone-7-O-(6″-O-acetyl)-β-d-glucopyranoside (2), together with five known compounds, demethoxymatteucinol-7-O-β-d-glucopyranoside (3), matteucinol-7-O-β-d-glucopyranoside (4), 5,7-dihydroxy-6-methyl-4′-methoxydihydroflavone (5), methoxymatteucin (6), and thunberginol C (7), were first isolated from the EtOH extract of the rhizomes and frond bases of Matteuccia struthiopteris. The structures were established by spectral analyses, mainly HR-ESI-MS and 1D and 2D NMR experiments (COSY, HSQC, and HMBC).

Divergent immunomodulatory effects of extracts and phenolic compounds from the fern Osmunda japonica Thunb.

ObjectiveTo study possible immunobiological potential of Osmunda japonica Thunb.MethodsImmunomodulatory effects of ethanol extracts prepared from rhizomes of O. japonica and phenolic compounds isolated from the extracts were investigated under the in vitro conditions using the rat peritoneal cells (2×106/mL; 24 h culture). Biosynthesis of nitric oxide (NO) was assayed by Griess reagent, production of prostaglandin E2 (PGE2) and secretion of cytokines were determined by enzyme-linked immunoabsorbent assay.ResultsThe extracts activated dose dependently, with the onset at 2.5–5 μmol/L concentrations, the high output NO production, and secretion of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Mild enhancement of NO was produced by the aldehyde-type phenolics 4-hydroxybenzaldehyde and 3,4-hydroxybenzaldehyde. In contrasts, the acetone-type phenolics 4-hydroxybenzalacetone and 3,4-hydroxybenzalacetone inhibited production of immune mediators including cytokines (TNF-α, IL-1β, IL-6), NO, and PGE2. The 3,4-hydroxybenzalacetone was more effective than 4-hydroxybenzaldehyde. The IC50s estimates ranged within the interval of 5–10 μmol/L. No signs of cytotoxicity were observed up to the 50 μmol/L concentration of the compounds.ConclusionPhenolic compounds contained in medicinal herb Osmunda japonica possess distinct immunomodulatory activity.