NO Release Inhibitory Activity of Flavonoids from Aesculus Wilsonii Seeds through MAPK (P38), NF-κB, and STAT3 Cross-Talk Signaling Pathways.

The flavonoid constituents of Aesculus wilsonii, a source of the Chinese medicinal drug Suo Luo Zi, and their in vitro anti-inflammatory effects were investigated. Fifteen flavonoids, including aeswilflavonosides IA-IC (1:  - 3: ) and aeswilflavonosides IIA-IIE (4:  - 8: ), along with seven known derivatives were isolated from a seed extract. Their structures were elucidated by extensive spectroscopic methods, acid and alkaline hydrolysis, and calculated electronic circular dichroism spectra. Among them, compounds 3: and 7: possess a 5-[2-(carboxymethyl)-5-oxocyclopent-yl]pent-3-enylate or oleuropeoylate substituent, respectively, which are rarely reported in flavonoids. Compounds 2, 3, 7: , and 12:  - 15: were found to inhibit lipopolysaccharide-induced nitric oxide production in RAW 264.7 cell lines. In a mechanistic assay, the flavonoid glycosides 2, 3: , and 7: reduced the expressions of interleukin-6 and tumor necrosis factor-alpha induced by lipopolysaccharide. Further investigations suggest that 2: and 3: downregulated the protein expression of tumor necrosis factor-alpha and interleukin-6 by inhibiting the phosphorylation of p38. Compound 7: was found to reduce the production of inducible nitric oxide synthase, and the secretion of tumor necrosis factor-alpha and interleukin-6 through inhibiting nuclear factor kappa-light-chain-enhancer of activated B signaling pathway. Compounds 2, 3: , and 7: possessed moderate inhibitory activity on the expression of signal transducer and activator of transcription-3. Taken together, the data indicate that the flavonoid glycosides of A. wilsonii seeds exhibit nitric oxide release inhibitory activity through mitogen-activated protein kinase (p38), nuclear factor kappa-light-chain-enhancer of activated B, and signal transducer and activator of transcription-3 cross-talk signaling pathways.

Structural characterization of phenolic constituents from the rhizome of Imperata cylindrica var. major and their anti-inflammatory activity.

As one of raw materials, the rhizome of Imperata cylindrica var. major (Nees) C.E. Hubb. is used in kinds of preparations curing inflammation related diseases, while its effective substances are not yet clear. In this paper, its chemical constituents and their anti-inflammatory activities were investigated. As results, ten compounds, named as imperphenoside A (1), imperphenols B (2) and C (3), imperphenosides D-F (4-6), and imperlignanosides A-D (7-10), along with previously reported thirty-seven known ones (11-47) were obtained from it. Their structures were ascertained basing on the extensive spectroscopic methods and electronic circular dichroism data analysis. Meanwhile, compounds 4, 11, 12, 24, 27, 31, 32, 37, 43, 45, and 47 exhibited nitric oxide inhibitory effects in concentration dependent at 3, 10, and 30 µM on lipopolysaccharides induced RAW 264.7 cells. Moreover, the western blot analysis indicated that compounds 4, 11, 43, and 47 could restrain the phosphorylation of nuclear factor kappa-B kinase to down-regulate the protein expression of inflammatory cytokines such as inducible nitric oxide synthase, interleukin-6 and tumor necrosis factor-α. In conclusion, they might play the anti-inflammatory effects through regulating NF-κB signaling pathway.