Synthesis, and anti-inflammatory activities of gentiopicroside derivatives.

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine, Gentiana macrophylla Pall have been prescribed for the treatment of pain and inflammatory conditions. In addition, it is a common Tibetan medicinal herb used for the treatment of tonsillitis, urticaria, and rheumatoid arthritis (RA), while the flowers of G. macrophylla Pall have been traditionally treated as an anti-inflammatory agent to clear heat in Mongolian medicine. The secoiridoid glycosides and their derivatives are the primary active components of G. macrophylla and have been demonstrated to be effective as anti-inflammatory agents. MATERIALS AND METHODS: Solvent extraction and D101 macroporous resin columns were employed to concentratethe gentiopicroside. Gentiopicroside cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; the toxicity of gentiopicroside in chondrocytes was reconfirmed using Hoechst staining. Western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were utilized to explore the protective effects and mechanisms of gentiopicroside prevents interleukin-1 beta induced inflammation response in rat articular chondrocyte. RESULTS: The MTT assay demonstrated that 50, 500, and 1,500 µg/mL of gentiopicroside exhibited no significant toxicity to chondrocytes (P>0.05) after 24h. Using immunohistochemistry, ELISA, RT-PCR, Western blot method to explore the protective effect and mechanism of gentiopicroside on chondrocytes induced by IL-1ß. The results showed some pathways of IL-1ß signal transduction were inhibited by gentiopicroside in rat chondrocytes: p38, ERK and JNK. Meanwhile, gentiopicroside showed inhibition in the IL-1ß-induced release of MMPs while increasing Collagen type II expression. CONCLUSIONS: The current study demonstrated that gentiopicroside exhibited a potent protective effect on IL-1ß induced inflammation response in rat articular chondrocyte. Thus, gentiopicroside could be a potential therapeutic strategy for treatment of OA.

[Study on the chemical constituents of Buddleja davidii].

OBJECTIVE: To study the chemical constituents of Buddleja davidii. METHODS: The constituents were isolated and purified by silica gel column chromatography, polyamide column chromatography and macroporous adsorption resin and their structures were identified by spectroscopic analysis. RESULTS: Eight compounds were elucidated as : Cranioside A (1), Eutigoside A (2), 1-O-4-Dimethoxyphenylethyl-4-O-3,4-dimethoxyphenylethy-beta-D-glucopyranoside (3), Isomartynoside (4'), 4"-O-Acetylmartynoside (5), Stigmasterol glueoside (6), beta-Sitosterol (7), Daucosterol (8). CONCLUSION: All these compounds are obtained from this plant for the first time.

[Study on the flavanone constitutes of Buddleja davidii].

OBJECTIVE: To study the chemical constitutes of Buddleja davidii. METHODS: The constitutes were isolated and purified by silica gel column chromatography, polyamide column chromatography and macroporous absorption resin and their structures were elucidated by spectroscopic analysis. RESULTS: Seven compounds including Apigenin (1), Apigenin-7-O-beta-D-glucoside (2), Acacetin (3), Acacetin-7-O-beta-D-glucoside(4), Acacetin-7-O-alpha-L-rhamnopyranosyl-(1-6)-beta-D-glucopyranoside (5), Luteolin (6), Luteolin-7-O-beta-D-glueoside (7). CONCLUSION: All these compounds are obtained from this plant for the first time.