Synthesis and in vitro anticancer activities of biotinylated derivatives of glaucocalyxin A and oridonin.

Fourteen glaucocalyxin A biotinylated derivatives, one glaucocalyxin C biotinylated derivative, and two oridonin biotinylated derivatives were designed and synthesized. Their structures were confirmed from 1H NMR, 13C NMR and HRMS data. The derivatives were evaluated for cytotoxic activities against lung (A549), cervical cancer cell line HeLa derivative (KB), multidrug-resistant KB subline (KB-VIN), triple-negative breast (MDA-MB-231), and estrogen receptor-positive breast (MCF-7) cancer cell lines.[Formula: see text].

1-O-tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-κB and JNK activation in microglia cells.

Overactivation of microglia may contribute to the pathogenesis of neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, and HIV dementia. Thus, regulating microglial activation has been an important therapeutic strategy for treating neurodegenerative diseases. In this research, we compared three limonoids compounds extracted from Melia toosendan by a cell-based assay to investigate their anti-inflammatory effects in lipopolysaccharide (LPS)-stimulated microglia cells. Our study indicated that 1-O-tigloyl-1-O-deacetyl-nimbolinin B (TNB) markedly suppressed the production of nitric oxide (NO) and tumor necrosis factor (TNF)-α in LPS-stimulated microglia cells. TNB also inhibited the gene expression of inducible nitric oxide synthase (iNOS), TNF-α, cyclooxygenase (COX-2), and interleukin (IL)-1ß. In addition, TNB inhibited generation of intracellular reactive oxygen species (ROS). We found that TNB significantly attenuated the nuclear translocation of NF-κB, inhibiting the activation of c-jun N-terminal kinase (JNK) in LPS-stimulated BV-2 cells. Furthermore, TNB reduced cytotoxicity of activated microglia toward HT-22 hippocampal cells in a co-culture system. Taken together, our experimental results reveal, for the first time, that TNB is a potent inhibitor of microglia-mediated inflammation, and it might be a potential candidate for the treatment of neurodegenerative diseases.

Antiinflammatory effects of orientin-2"-O-galactopyranoside on lipopolysaccharide-stimulated microglia.

Microglia activation-mediated neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, and human immunodeficiency virus (HIV)-associated dementia. Inhibition of microglia activation may alleviate neurodegeneration under neuroinflammatory conditions. In the present study, we compared three flavone C-glycosides extracted from Trollius chinensis BUNGE using a cell-based assay to evaluate their antiinflammatory effects on microglial cells. The results showed that orientin-2"-O-galactopyranoside (OGA) significantly inhibited the production of nitric oxide and tumor necrosis factor (TNF)-α in lipopolysaccharide (LPS)-stimulated microglial cells. OGA also markedly inhibited the LPS-induced expression of TNF-α, interleukin-1ß, inducible nitric oxide (NO) synthase, and cyclooxygenase-2, which was accompanied by suppression of the activation of nuclear factor (NF)-κB and the extracellular signal-regulated kinase (ERK) signal pathway. In addition, OGA decreased LPS-induced reactive oxygen species generation, which appears to be related to the activation of the NF-E2-related factor2 (NRF2)/ heme oxygenase-1 (HO-1) pathway in BV-2 microglial cells. Furthermore, OGA reduced the cytotoxicity of activated microglia toward HT-22 neuroblastoma cells in a co-culture system. Taken together, the present study demonstrated that the induction of HO-1-mediated inhibition of the NF-κB and ERK pathways contributes significantly to the antineuroinflammatory and neuroprotective effects elicited by OGA.

Flavone C-glycosides from the flowers of Trollius chinensis and their anti-complementary activity.

Phytochemical investigation of ethanol extract from the flowers of Trollius chinensis Bunge resulted in the isolation of two new flavone C-glycosides (1-2), along with 10 known compounds (3-12). The structures of the new compounds were established as 6‴-(3-hydroxy-3-methylglutaroyl)-2″-O-ß-d-galactopyranosyl orientin (1) and 6‴-(3-hydroxy-3-methylglutaroyl)-2″-O-ß-d-galactopyranosyl vitexin (2) on the basis of various spectroscopic analysis (including different 1D and 2D NMR spectroscopies, high-resolution electrospray ionization mass spectrometry) and chemical evidences. Bioassay showed that eight flavonoids inhibited complement activation on the classic pathway in vitro, with their IC50 values ranging from 0.88 to 4.02 mM, which may contribute to the applications of the herb in treatment of acute respiratory distress syndrome, etc.

New triterpenoid saponins from Patrinia scabiosifolia.

Phytochemical investigation of methanol extract from the whole plants of Patrinia scabiosifolia Fisch. resulted in the isolation of three new triterpenoid saponins (1-3) along with twelve known triterpenoids (4-15). The structures of the new compounds were established as 11α, 12α-epoxy-3-O-ß-D-xylopyranosyl-olean-28, 13ß-olide (1), 11α, 12α-epoxy-3-O-ß-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-xylopyranosyl-olean-28, 13ß-olide (2), and 3-O-ß-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-xylopyranosyl oleanolic acid 28-O-ß-D-glucopyranoside (3) on the basis of various spectroscopic analyses (including different 1D and 2D NMR spectroscopies and high-resolution electrospray ionization mass spectrometry) and chemical evidences.

Chantriolide C, a new withanolide glucoside and a new spirostanol saponin from the rhizomes of Tacca chantrieri.

A new withanolide, chantriolide C (1) and a new spirostanol saponin, chantrieroside A (2) were isolated from the rhizomes of Tacca chantrieri, together with another five known steroidal compounds. Their structures were established as (22R)-1alpha,12alpha-diacetoxy-2alpha,3alpha;6alpha,7alpha-diepoxy-27-[(beta-D-glucopyranosyl)oxy]-5alpha-hydroxywith-24-enolide (1) and (25R)-spirost-5-en-3-yl-O-alpha-L-rhamnopyranosyl-(1-->2)-O-[O-beta-D-glucopyranosyl-(1-->4)-alpha-L-rhamnopyranosyl-(1-->3)]-beta-D-glucopyranoside (2). The structures of the new saponins were determined by detailed analysis of their 1 dimensional (1D) and 2D NMR spectra, and chemical evidences.

[Effect of ultrasound-guided acupoint electrical stimulation on diaphragmatic dysfunction associated with mechanical ventilation].

OBJECTIVE: To observe the effect of ultrasound-guided acupoint electrical stimulation on the patients with diaphragmatic dysfunction associated with mechanical ventilation in ICU. METHODS: Fifty-two patients were randomly divided into an observation group (26 cases, 3 cases dropping) and a control group (26 cases). Conventional treatment was given to all patients. On the basis of conventional treatment, acupoint electrical stimulation therapy was applied at Zhangmen (LR 3), Dabao (SP 21), Pishu (BL 20), Shenshu (BL 23), etc. In the observation group, the treatment was given for 30 min each time, 3 times a day for 7 days. Diaphragm thickening fraction (TFdi) was used as an index to guide the individualized setting of stimulation intensity and judge the effect, and the difference of mechanical ventilation time, ICU time, total hospitalization time, hospital mortality and reintubation rate between the two groups were observed. RESULTS: The mechanical ventilation time in the observation group was shorter than that in the control group (P<0.05). There was no significant difference in the ICU time and total hospitalization time between the two groups (P>0.05). During hospitalization, 2 patients died in the observation group and 3 patients died in the control group, there was no significant difference in hospital mortality (P>0.05). One patient in the observation group was reintubated and 8 patients in the control group (P<0.05). The use of acupoint electrical stimulation was a factor in shortening the mechanical ventilation time and reducing the reintubation events (P<0.05). CONCLUSION: Ultrasound-guided acupoint electrical stimulation can relieve ventilator-induced diaphragmatic dysfunction, reduce ventilator support time and reintubation events.

Chemical characterization, anti-benign prostatic hyperplasia effect and subchronic toxicity study of total flavonoid extract of Pteris multifida.

The decoction of Pteris multifida had been applied to attenuate symptoms of benign prostatic hyperplasia in Chinese folk medicine. In this study, the total flavonoid extract of Pteris multifida was processed at first. High performance liquor chromatography and tandem mass spectrometer assay revealed 10 flavonoids as key constituents of this extract. After 60-day administration, the total flavonoid extract (180 mg/kg, i. g.) decreased the prostate index in mice of benign prostatic hyperplasia apparently. Immunohistochemical assay revealed inhibition of vascular endothelial growth factor expression, together with activation of transforming growth factor-beta 1 expression in the prostatic samples after administration of the extract. A 90-day subchronic toxicity test was further undertaken in male Sprague-Dawley rats, and the no-observed-adverse-effect level for the extract was 200 mg/kg body weight/day. These results revealed that the total flavonoid extract of Pteris multifida exhibited positive effect with safety, which might be applied in treatment of benign prostatic hyperplasia.

Synthesis and structure-activity relationships of guaiane-type sesquiterpene lactone derivatives with respect to inhibiting NO production in lipopolysaccharide-induced RAW 264.7 macrophages.

A guaiane framework was scaffolded by photochemical rearrangement reactions using α-santonin 1 as a starting material. Then, using a series of reactions, we synthesized the guaiane-type sesquiterpene lactone 5 in high yield. The inhibitory activities of compound 5 and of a series of derivatives on nitric oxide (NO) release were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Compounds 6g, 7h, 7i, 7k and 8g, exhibited significant inhibitory effects on NO production, with IC50 values of 14.8, 22.3, 18.3, 17.4 and 7.0 µM, respectively. Their cytotoxicities were also estimated using an MTT assay. The structure-activity relationships of these compounds were also discussed.

Controlled acetylation of water-soluble glucomannan from Bletilla striata.

Glucomannans from Bletilla striata (bletillan) were used as excipient for controlled deliveries of drugs, genes and tissue engineering. In the present study, a controlled acetylation method was developed to improve water solubility of bletillan 70 (BT) firstly, by reacting with acetic anhydride (AA) in N,N-dimethylformamide solvent. The preparation parameters, such as reaction temperature, reaction time and molar ratio of BT/AA, were optimized based on degrees of acetyl group in addition. IR and (1)H NMR spectra were applied to elucidate the reaction process and substitution pattern, which indicated that the acetylation took place at C-6 and C-2 of the hexose units in a ratio of 2:1, with DS up to 0.83. Relative viscosity analysis revealed that the resulted products had improved water solubilities. This novel method is simple, economic and easily controlled.

New triterpenoid saponins from Patrinia scabiosaefolia.

Phytochemical investigation of the methanol extract from the whole plants of Patrinia scabiosaefolia Fisch. resulted in the isolation of four new triterpenoid saponins (1-4) along with six known compounds (5-10). On the basis of spectroscopic and chemical methods, the structures of the new compounds were established as 3-O-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranosyl-12ß,30-dihydroxy-olean-28,13ß-olide (1), 3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranosyl-12ß,30-dihydroxy-olean-28,13ß-olide (2), 3-O-ß-D-xylopyranosyl-(1→2)-ß-D-glucopyranosyl-12ß, 30-dihydroxy-olean-28,13ß-olide (3), and 3-O-ß-D-glucopyranosyl-(1→4)-ß-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-ß-D-xylopyranosyl-oleanolic acid 28-O-ß-D-glucopyranoside (4), respectively. Compounds 1-3 possess a novel 12ß,30-dihydroxy-olean-28,13ß-lactone aglycone and a 12ß-hydroxy substituent that is rarely found in this kind of triterpenoid saponin.

A new minor triterpene saponin from kaixin-san prescription.

A new minor oleanane-type saponin, ginsenoside-R(OA) (1), has been isolated from the extract of Kaixin-San, a prescription composed of Panax ginseng and other medicinal herbs, together with 15 known ginsenosides. The structure of 1 was established as 3-O-beta-D-glucopyranosyl-(1-->2)-beta-D-glucuronopyranosyl oleanolic acid 28-O-beta-D-glucopyranosyl-(1-->6)-beta-D-glucopyranoside by chemical and spectroscopic evidence. In addition, the presence of ginsenoside-R(OA) in ginseng was confirmed by HPLC-ESI-MS.

[Studies on the separation and determination of natural phenolic acids by reversed-phase high performance liquid chromatography].

A new method using gradient elution of reversed-phase high performance liquid chromatography was set up for the separation and determination of 12 natural phenolic acids simultaneously. The separation conditions were studied with a Zorbax ODS (5 microns) column, and optimized conditions were suggested with the mobile phase gradient elution of CH3CN-H2O (with 0.5% HAc) (5:95-->35:65, V/V, in 40 min) at room temperature, flow rate at 1.0 mL/min and detection wavelength at 280 nm. And the effects of acidity on separations and the relationships between the phenolic acids structures and their retention behaviors were discussed. Qualitative and quantitative analysis of the 12 compounds were performed. The regression equation, correlation coefficient, linear range, detection limit and relative standard deviation (RSD) of each compound were obtained under the optimized conditions. The correlation coefficients of the 12 compounds were between 0.9980 and 0.9999. The detection limits ranged from 0.96 ng to 4.10 ng and RSDs were < or = 2.64%. These results demonstrate that the optimized determination method obtained is successful for the separation and determination of the 12 phenolic acids analysed.