[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Secoiridoid glycosides from the fruits of Ligustrum lucidum and their in vitro anti-inflammatory activity.

Seven new secoiridoid glycosides (1-7), together with a known analogue (8), were isolated from the fruits of Ligustrum lucidum. Their structures with absolute configurations were determined by HR-ESI-MS, 1D and 2D NMR, and electronic circular dichroism (ECD) spectroscopic analysis, as well as biogenetic consideration. Compounds 1 and 2 are the first examples of secoiridoid glycoside dimers featuring a rare rearranged oleoside-type secoiridoid moiety, and compounds 3-7 represent a new class of oleoside-type secoiridoid glycosides with unusual stereochemistry at C-1 position. A plausible biosynthetic pathway for this group of unusual secoiridoid glycosides was also proposed herein. In addition, the isolates were evaluated for their in vitro anti-inflammatory activity, and all tested compounds exhibited modest inhibitory effects against nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages.

Quassinoids from the Roots of Eurycoma longifolia and Their Anti-Proliferation Activities.

A phytochemical investigation on the roots of medicinal plant Eurycoma longifolia resulted in the isolation of 10 new highly oxygenated C20 quassinoids longifolactones G‒P (1-10), along with four known ones (11-14). Their chemical structures and absolute configurations were unambiguously elucidated on the basis of comprehensive spectroscopic analysis and X-ray crystallographic data. Notably, compound 1 is a rare pentacyclic C20 quassinoid featuring a densely functionalized 2,5-dioxatricyclo[5.2.2.04,8]undecane core. Compound 4 represents the first example of quassinoids containing a 14,15-epoxy functionality, and 7 features an unusual α-oriented hydroxyl group at C-14. All isolated compounds were evaluated for their anti-proliferation activities on human leukemia cells. Among the isolates, compounds 5, 12, 13, and 14 potently inhibited the in vitro proliferation of K562 and HL-60 cells with IC50 values ranging from 2.90 to 8.20 µM.

Phloroglucinol-derived lipids from the leaves of Syzygium cumini and their neuroprotective activities.

Based on the typical HPLC-UV-MS profiles and characteristic 1H NMR signals, twelve new phloroglucinol-derived lipids (1-12), featuring a long linear aliphatic side chain, together with three known ones (13-15) were isolated from the ethanol extract of the leaves of Syzygium cumini. Their structures were elucidated on the basis of extensive NMR spectroscopic analyses and mass spectrometric data. Compounds 1-5 characterize an enolizable ß,ß'-tricarbonyl motif with a cyclohexa-3,5-dien-1-one core that is hitherto undescribed in phloroglucinol-derived lipids. Compounds 4 and 10-12 are novel phloroglucinol-derived lipids containing an uncommon methylene interrupted trans double bond in their polyunsaturated aliphatic side chains. A polyketide biogenetic pathway for those phloroglucinol-derived lipids was also proposed. In addition, the isolates were evaluated for their neuroprotective activities against oxygen-glucose deprivation and re­oxygenation (OGD/R)-induced Neuro-2a cell injury. Notably, compounds 1, 5, and 10-12 significantly improved viability of Neuro-2a cells after OGD/R damage.

Caffeic acid oligomers from Mesona chinensis and their In Vitro antiviral activities.

The phytochemical study of the aerial part of Mesona chinensis led to the isolation of five new caffeic acid oligomers (1-5), as well as four known analogues (6-9). The structures of the new compounds including their absolute configurations were elucidated by comprehensive spectroscopic analysis, chemical method, and quantum-chemical electronic circular dichroism (ECD) calculation. Among the isolates, compound 7 showed significant in vitro antiviral activity on respiratory syncytial virus (RSV).

Dosing-time contributes to chronotoxicity of clofarabine in mice via means other than pharmacokinetics.

To evaluate the time- and dose-dependent toxicity of clofarabine in mice and to further define the chronotherapy strategy of it in leukemia, we compared the mortality rates, LD50s, biochemical parameters, histological changes and organ indexes of mice treated with clofarabine at various doses and time points. Plasma clofarabine levels and pharmacokinetic parameters were monitored continuously for up to 8 hours after the single intravenous administration of 20 mg/kg at 12:00 noon and 12:00 midnight by high performance liquid chromatography (HPLC)-UV method. Clofarabine toxicity in all groups fluctuated in accordance with circadian rhythms in vivo. The toxicity of clofarabine in mice in the rest phase was more severe than the active one, indicated by more severe liver damage, immunodepression, higher mortality rate, and lower LD50. No significant pharmacokinetic parameter changes were observed between the night and daytime treatment groups. These findings suggest the dosing-time dependent toxicity of clofarabine synchronizes with the circadian rhythm of mice, which might provide new therapeutic strategies in further clinical application.

Investigation of the alterations in cellular electrophysiology underlying ventricular arrhythmia in dogs with the multiple organ dysfunction syndrome.

BACKGROUND: Multiple organ dysfunction syndrome (MODS)-specific cellular electrophysiological changes have so far not been reported and it seemed unlikely that they were related to arrhythmogenesis. METHODS AND RESULTS: Twelve dogs, weight 12 +/- 2 kg, were divided into a control group (n = 6) and an MODS group (n = 6). MODS lasting for 72 h was induced by the 'two-hit' method in 6 dogs. Ventricular myocytes were enzymatically isolated. Early afterdepolarizations (EADs), action potential duration (APD) and L-type calcium currents (ICa,L) were assessed. Sinus arrhythmias in all MODS dogs (100%; 6 of 6) and premature ventricular beats in 4 MODS dogs (66%; 4 of 6) were recorded, while no arrhythmias were found in the control animals. The prolongation of the APD was associated with a decreased ICa,L, and frequently provoked EADs were the typical electrophysiological alterations in the myocytes of MODS dogs. The action potential prolongation was shortened, the ICa,L blocked and EAD suppressed by using verapamil (100 micromol/l) in the myocytes of MODS dogs (66%; 4 of 6). CONCLUSION: The changes in cellular electrophysiology within 72 h in the heart of MODS dogs are APD prolongation, markedly decreased ICa,L as well as frequently provoked EAD, the most common types of arrhythmia being sinus arrhythmia and premature ventricular beats. This study suggests that verapamil appears to be an effective agent in reversing alterations in cellular electrophysiology at the early stage of MODS.