New depside and rosmarinic acid derivatives from Perilla frutescens and their anti-inflammatory activity.

Two new depside derivatives 1 and 2 as well as a new pair of rosmarinic acid enantiomers 3a/b were isolated from the leaves of Perilla frutescens (L.) britt. The chemical structures of these compounds were identified based on detailed spectroscopic and physicochemical analyses (HR-ESI-MS, NMR) and comparison of literature data. Compounds 3a/b were obtained by chiral separation, and their absolute configurations were determined by comparison of experimental and calculated ECD spectra. Compounds 3a/b exhibited potential inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC50 values of 15.92 ± 3.32 µM and 48.72 ± 4.12 µM.

Research Progress on the Antioxidant Activity of Natural Diarylheptanoids: Mechanisms and Structure-activity Relationships.

Antioxidant research has recently become a popular topic. Medicinal plants are important sources of novel active compounds. Diarylheptanoids, a typical family of secondary plant metabolites, are of great interest owing to their extensive spectrum of biological activities. They possess a unique 1,7-diphenylmethane structural skeleton. Thus, this review summarizes the natural linear or macrocyclic diarylheptanoids with antioxidant activity in the last two decades. In addition, the relationships between the structural characteristics of natural diarylheptanoids and their antioxidant capacity were also discussed. All the available data highlight the potential of natural diarylheptanoids as novel antioxidants.

New verticillane-diterpenoid as potent NF-κB inhibitor isolated from the gum resin of Boswellia sacra.

Two new verticillane-diterpenoids (1 and 2) were isolated from the gum resin Boswellia sacra. Their structures were elucidated by physiochemical and spectroscopic analysis, as well as ECD calculation. In addition, the in vitro anti-inflammatory activities of the isolated compounds were evaluated by determining the inhibitory effects on lipopolysaccharide (LPS)-induced NO production in RAW 264.7 mouse monocyte-macrophages. The results showed that compound 1 exhibited significant inhibitory effect on NO generation with an IC50 value of 23.3 ± 1.7 µM suggesting that it might be a candidate for an anti-inflammatory agent. Furthermore, 1 potently inhibited the release of inflammatory cytokines IL-6 and TNF-α induced by LPS in a dose-dependent manner. Using Western blot and Immunofluorescence methods, compound 1 was found to inhibit inflammation mainly by restraining the activation of NF-κB pathway. And in the MAPK signaling pathway, it was found to have inhibitory effects on the phosphorylation of JNK and ERK proteins and have no effect on the phosphorylation of p38 protein.

Two new ent-kaurane glucosides from the fruits of Xanthium strumarium subsp. sibiricum.

The chemical investigation of the fruits of Xanthium strumarium (Asteraceae) led to the isolation of two new ent-kauranoid glucosides named 2-O-(6-O-isocaleryl-ß-D-glucopyranosyl) atractyligenin (1) and 2-O-(2-O-isovaleryl-ß-D-glucopyranosyl) atractyligenin (2), together with one known compound. Their structures were established by comprehensive spectroscopic analysis coupled with single-crystal X-ray diffraction and electronic circular dichroism data. All compounds and their aglycone were evaluated for their anti-proliferative activities in vitro against three human cancer cell lines.

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.

A New Triterpenoid from the Aerial Parts of Agrimonia pilosa.

(1S,3R,17R,18R,19R,20R,22R)-1,3,19,22-tetrahydroxy-28-norurs-12-en-2-one (1), along with 5 known triterpenoids (2-6), were isolated from the aerial parts of Agrimonia pilosa Ledeb. Their structures were established based on extensive spectroscopic and MS analysis. The absolute configuration of compound 1 was deduced by circular dichroism (CD). Compound 1 was the first example of a 28-norursene backbone isolated from the genus Agrimonia. Compounds 2-6 were tested for anti-inflammatory activities against RAW 264.7 macrophages. A plausible biosynthetic pathway for compound 1 in A. pilosa was also proposed.