A high-resolution α-glucosidase inhibition profiling for targeted identification of natural antidiabetic products from Lycopodiella cernua (L.) Pic. Serm and their inhibitory mechanism study.

The targeted identification of α-glucosidase inhibitors from the crude ethyl acetate of Lycopodiella cernua (L.) Pic. Serm (L.cernua) was guided by high-resolution inhibition profiling. The α-glucosidase inhibition profiling and HPLC-QTOF-MS showed tannins and serratenes were the corresponding antidiabetic constituents. Two new serratenes named 3ß, 21ß-dihydroxyserra-14-en-24-oic acid-3ß-(4'-methoxy-5'-hydroxybenzoate) (4), 3ß, 21α-dihydroxyserra-14-en-24-oic acid-3ß-(4'-methoxy-5'-hydroxybenzoate) (7), together with two known compounds (5 and 6) were isolated. Their structures were elucidated by HR-ESI-MS and NMR. Compounds 5-7 inhibited the α-glucosidase activity in a non-competitive manner with Ki values ranging from 1.29 to 12.9 µM. The molecular docking result unveiled that 4-7 bound to the residues at the channel site, which enabled to block the substrate access. In addition, the molecular dynamics (MD) simulation of the most active compound 7 and α-glucosidase indicated the 4'-methoxy-5'-hydroxybenzoate group formed the stable hydrogen bonds and pi-pi T-shaped interactions with Arg312, Gln350 and Phe300 residues, while the rings D and E were stabilized by hydrophobic interaction.

Corrigendum to "Metabolic profiling of icaritin in rats using UHPLC-Q/TOF-MS" [Chinese Herbal Medicines 11 (2019) 185-191].

[This corrects the article DOI: 10.1016/j.chmed.2019.03.008.].

An integrated approach based on phytochemistry, network pharmacology and metabolomics reveals the mechanism of action of Xanthium strumarium L. for allergic rhinitis.

Xanthium strumarium L. (XS) is a traditional Chinese medicine (TCM) that has been widely used in Chinese medicine prescription for allergic rhinitis (AR). However, the action mechanisms of XS on the therapeutic effects on AR remain elusive. Herein, an integrated approach of phytochemistry, network pharmacology and metabolomics was first applied to uncover the action mechanisms of XS for AR. The therapeutic effect of XS extract on AR was evaluated in rat models of ovalbumin (OVA)-induced AR. The cytokine levels in rat serum and histopathological changes of nasal mucosa were assessed after oral treatment with XS. Chemical compositions of XS were elucidated by phytochemical methods, and active ingredients were identified via ADME-TOX screening in silico. Network pharmacology was performed to establish and analyze the compound-target-disease network so as to find the possible mechanism of XS in treating AR. In addition, metabolomics analysis was applied to investigate the changes in the endogenous metabolite levels that result from XS treatments. As result, the XS extract significantly increased the serum concentrations of IL-2 and reduced the levels of serum IL-4, while XS could ameliorate inflammation in the nasal sub-mucosal area, indicating that XS has significant therapeutic effects on AR model rats. Furthermore, a total of 119 compounds were isolated from XS, and 59 of these compounds were identified as active ingredients through ADME-TOX screening in silico. An in-depth analysis of the network pharmacology implied that the active ingredients of XS could regulate the inflammatory response via "multi-component, multi-target" patterns. In combination with the results of metabolomics, we found that the active ingredients of XS have a beneficial effect on AR through regulating the metabolism of arachidonic acid, which was reflected by medicating the Fc epsilon RI signaling pathway, and the neuroactive ligand-receptor interaction pathway, as well as the key proteins in arachidonic acid metabolism, such as PTGS2, PTGS1, PTGES and ALOX5. Additionally, molecular docking showed that multiple compounds have better binding with PTGS2 and ALOX5, which might be two crucial targets. Overall, these results suggest that the treatment of XS for AR is realized by regulating the metabolism of arachidonic acid via a combination form. This study provides the basis for clinical applications of XS.

Nine pairs of megastigmane enantiomers from the leaves of Eucommia ulmoides Oliver.

Nine pairs of megastigmane enantiomers (1a/1b-9a/9b), comprising two new compounds (6S,9R)-blumenol C (7b), (6S,9S)-blumenol C (8b), two pairs of enantiomers (+)-(6R)-eucomegastigmane A (1a), (-)-(6S)-eucomegastigmane A (1b), (+)-(3S,4S)-eucomegastigmane B (5a), (-)-(3R,4R)-eucomegastigmane B (5b) isolated by chiral resolution firstly, and twelve known compounds, were isolated from the leaves of Eucommia ulmoides Oliver. Their structures were elucidated based on extensive spectroscopic analysis. Absolute configurations of the megastigmane enantiomers were assigned by comparing experimental ECD and OR with calculated ECD and OR. Docking-based virtual screening of all compounds showed that megastigmane enantiomers have weak intermolecular interactions with the binding site residues of angiotensin-converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R).

Megastigmane glycosides from leaves of Eucommia ulmoides Oliver with ACE inhibitory activity.

Four new megastigmane glycosides, eucomegastigsides A-D (2, 3, 5 and 7), together with three known megastigmane glycosides, (6R, 7E, 9R)-9-hydroxy-4, 7-megastigmadien-3-one-9-O-[α-l-arabinopyranosyl-(l→6)-ß-d-glucopyranoside (1), foliasalacioside B1 (4) and eleganoside A (6), were isolated from the leaves of Eucommia ulmoides Oliver. Their anti-hypertensive effect was investigated in vitro based on the inhibition of Angiotensin Converting Enzyme (ACE) using HPLC. The results showed that the isolates (2, 3, 4, 5, 7) had moderate inhibitory effects on ACE in vitro compared with captopril.