Studies On The Synthesis And Pharmacological Effect Of Derivatives Of Gentiopicroside

Gentiopicroside as a secoiridoid glycoside commonly existing in the gentianaceous plants, especially in the genera Gentiana and Swertia, was isolated from the methanol extract of Gentiana macrophylla (Qinjiao). Antibacterial, free radical scavenging cholagogic activities of Gentiopicroside have been reported. It was also found to have the capability of protecting against many kinds of chemical and immunological liver injuries.In our study, four derivates of Gentiopicroside were synthesized. Gentiopicroside was esterified with acetic anhydride in the presence of perchloric acid to give tetraacetate- Gentiopicroside. Gentiopicroside was reacted with ammonia water to obtain gentianine. The product ofβ-glucosidase enzymatic hydrolusis of Gentiopicroside was Gentiogenal .Gentiopicroside was hydrogenated Pd-C as catalyst to give a derivative. Their structures were characterized by IR, UV, ~1H-NMR, and Mass spectra. The anti-inflammatory and analgesic effects of the four derivates were contrasted by writhing and xylen-induced ear edema tests, respectively. The tumor inhibiting capabilities in vitro were conducted by MTT assay.Rheumatoid arthritis (RA) is a kind of autoimmune disease characterized by chronic and symmetrical multijoint inflammation,which result in joint malformation even lead to sever disability. The major damaged-target is synovial membrane. The therapeutics of arthritis was mainly about analgesic, anti-inflammatory effects, immunological regulation. In this article, analgesic, anti-inflammatory effects, immunological regulation of Gentiopicroside were studied, and its demulcent mechanism was lucubrated.To study the analgesic effects of Gentiopicroside one chemical and two thermal nociceptive models were used. Gentiopicroside given by s.c.route, (50, 100, and 150mg/kg) dose-dependently reduced the number of writhing induced by acetic acid and increased the reaction time in hot-plate test and tail-flick test. The writhing test allowed us to identify peripheral analgesic compounds. The thermal model of the tail flick test was considered to be a spinal reflex and the hot-plate test was commonly used to assess narcotic analgesics. The fact that Gentiopicroside at the doses tested produced analgesia in all nociceptive models is indicative that they possess both central and peripheral antinociceptionIn the anti-inflammatory test, Gentiopicroside inhibited significantly the formation of the albumin-induced rat paw oedema and xylene-induced mouse ear edema. It also suppressed markedly the formation of cotton pellet-induced rat granuloma. All results of the study have clearly demonstrated that Gentiopicroside possessed significant antinociceptive and anti-inflammatory activities.The immunoregulatory effect of Gentiopicroside on rat with adjuvant arthritis (AA) induced by Freund's complete adjuvant (FCA) showed that the productions of Interleukin-1 (IL-1), Tumor necrosis factor alpha (TNF-α) in serum remarkably were higher than in control group but remarkably lower in in AA model group. Its mechanism might suppresse activity of IL-1 and TNF-α.We studied the analgesic mechanism of Gentiopicroside. The anterior cingulate cortex (ACC) is a forebrain structure known for its roles in pain transmission and modulation. Painful stimuli potentiate the prefrontal synaptic transmission and induce glutamate NMDA NR2B receptor expression in the ACCWhole-cell patch-clamp recordings revealed that Gentiopicroside significantly reduced NR2B receptors mediated postsynaptic currents but had no effects on the basal excitatory or inhibitory synaptic transmission in the ACC. This is demonstrated by unchanged paired-pulse, mEPSCs or mIPSCs frequency and amplitude in vitro slice incubation. Western blot results showed that the expression level of NR2B receptor, but not' NR2A receptor was increased in the ACC after CFA injection. Gentiopicroside reversed expression level of NR2B receptor. Our findings provided strong evidences that analgesic effect of Gentiopicroside involving modulation of NR2B receptors in the ACC to persistent inflammatory pain.Coxsackievirus is an important pathogen in human, for its inducing serious pancreatition or myocarditis, which often leads the death of young individual, inetiology, recent research revealed that coxsackievirus was responsible for the acute chronic viral myocarditis with its end stage scenario--myocardial failure or dilated myocardiopathy.and by heart biopsy and molecular blot, CVB3 serological form was the most seen form in allcvb infection.Antiviral activities of Gentiopicroside were determined by in vitro experiments. When primarily cultured myocardial cells infected with CVB3 were treated with Gentiopicroside, virus titers decreased significantly and apoptosis of myocardial cells induced by CVB3 reduced obviously. This observation indicated that Gentiopicroside had excellent antiviral activity in vitro and had protective effect on myocardial cells from CVB3 infection.The inhibitory action of Gentiopicroside to Simian immunodeficiency virus (SIV) and human lung cancer cellsA549 were slight even in high density. Therefore, it was worthless of application.