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To develop potential agents for slowing the progression of Alzheimer's disease, two pairs of new enantiomeric lignans, including a couple of rarely 8',9'-dinor-3',7-epoxy-8,4'-oxyneolignanes named (7S, 8S)- and (7R, 8R)-pithecellobiumin A (1a/1b) and a pair of 2',9'-epoxy-arylnaphthalenes named (7R, 8R, 8'R)- and (7S, 8S, 8'S)-pithecellobiumin B (2a/2b) were separated by chiral high performance liquid chromatography (HPLC). Their planar structures were elucidated by spectroscopic data analyses. The absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The inhibitory activity on Aβ aggregation of all optical pure compounds was tested by ThT assay. Interestingly, enantiomeric inhibitors 1a (62.1%) and 1b (81.6%) exhibited different degrees of anti-Aβ aggregation activity. However, 2a (65.4%) and 2b (68.4%) showed similar inhibition rate. The different inhibition profiles were explained by molecular dynamics and docking simulation studies.

The twigs and leaves of Pithecellobium clypearia Benth have been used as a folk medicine for the treatment of diseases related to inflammation in southern China for many years. To search for novel bioactive constituents as lead structures for anti-inflammatory drug development, seven new 3, 3′-neolignans ( 1 – 7 ), together with four known ones ( 8 – 11 ) were isolated from the 70% EtOH extract of the twigs and leaves of P. clypearia . Their structures were determined by spectroscopic analyses, especially the 1D, 2D NMR and CD spectra. The antioxidant and anti-inflammatory activities of all the isolated compounds were investigated. Among them, compound 11 showed promising activity against nitric oxide (NO) and considerable antioxidant activity. These findings will help in the effective use of P. clypearia as a valuable source of novel compounds for the prevention and treatment of inflammation-related disorders.

The pharmacokinetic profile of gallocatechin-7-gallate (J10688) was studied in rats after intravenous administration. Male and female Sprague-Dawley (SD) rats received 1, 3, and 10 mg/kg (i.v.) of J10688 and plasma drug concentrations were determined by a high performance liquid chromatography-mass spectrometry (LC–MS) method. The pharmacokinetic software Data Analysis System (Version 3.0) was used to calculate the pharmacokinetic parameters. For different i.v. doses of J10688, the mean peak plasma concentration (C0) values ranged from 11.26 to 50.82 mg/L, and mean area under the concentration-time curve (AUC0–t) values ranged from 1.75 to 11.80 (mg·h/L). J10688 lacked dose-dependent pharmacokinetic properties within doses between 1 and 10 mg/kg, based on the power model. The method developed in this study was sensitive, precise, and stable. The pharmacokinetic properties of J10688 in SD rats were shown to have rapid distribution and clearance values. These pharmacokinetic results may contribute to an improved understanding of the pharmacological actions of J10688., Graphical abstract A simple, selective, and sensitive LC–MS method was developed and validated. Pharmacokinetic study of gallocatechin-7-gallate (J10688) in rats was carried out. The pharmacokinetic properties of J10688 in SD rats were characterized as quick distribution and clearance. fx1

To explore potential compounds with marked effect on Alzheimer’s disease (AD) in Pithecellobium clypearia Benth., nineteen compounds (1–19) were obtained, including two new flavonoid derivatives, named pithecellobiumol A (1) and pithecellobiumol B (2) and 17 flavonoids (3–19). Their structures were elucidated based on 1D and 2D-NMR spectra as well as HR-ESI-MS data. The absolute configurations of new compounds were assigned by comparing their experimental specific rotation or ECD curves with the calculated data. The inhibitory activity on Aβ aggregation was screened by ThT assay, and compounds 7 (70.7%), 9 (86.5%), 10 (88.4%), 15 (86.1%) and 16 (87.7%) showed outstanding inhibition rate at 20 μM compared to the positive control, curcumin (65.64%). In addition, docking study was performed to initially examine possible molecular mechanisms. Considering the important role of oxidative stress in AD, all the isolated compounds were tested for their H2O2-induced damage in human neuronblastoma SH-SY5Y cells. Among them, compound 16 (91.0%) was the most potent candidate in the treatment of AD.

Introduction Multidrug-resistant Acinetobacter baumannii (MDRAB) and Pseudomonas aeruginosa (MDRPsA) have attracted widespread attention. Antibiotic adjuvants can give a second life to antibiotics that bacteria have developed resistance to. Pithecellobium clypearia is a medicinal plant used in China for treating various diseases, including infections. Pithecellobium clypearia may have the potential as an antibiotic adjuvant to enhance the effect of antibiotics. Methods The antibacterial and synergistic activities of extract from Pithecellobium clypearia (S20b) and antibiotics, alone and in combination with MDRAB and MDRPsA, were evaluated in vitro against 20 clinic multidrug-resistant isolates by the micro-dilution and checkerboard dilution methods. The compounds in S20b were analysed by RRLC-MS/MS. The mechanism of S20b was confirmed by transmission electron microscopy (TEM). Results S20b demonstrated potential inhibitory activity against MDRAB and MDRPsA and showed a synergistic effect of interaction with the antibiotics in this experiment. The TEM results confirmed that S20b could damage the bacterial cell wall. Moreover, the effects of S20b on the reversion resistance of A. baumannii and P. aeruginosa against the corresponding antibacterial agents could possibly be associated with the increase in bacterial membrane permeability. Conclusions S20b increased the efficiency of antibiotics against MDRAB and MDRPsA. This study is the first to demonstrate that S20b from Pithecellobium clypearia may have potential use as a therapeutic agent to against MDRAB and MDRPsA.