Anti-Rheumatic Properties of Gentiopicroside Are Associated With Suppression of ROS-NF-κB-NLRP3 Axis in Fibroblast-Like Synoviocytes and NF-κB Pathway in Adjuvant-Induced Arthritis.

Rheumatoid arthritis (RA) is among the most prevalent forms of autoimmunity. Gentiopicroside (Gent) is an iridoid glucoside derived from the Gentiana Macrophylla Pall which is used in traditional Chinese medicine to treat RA. The present study was designed to explore the ability of Gent to combat RA and to explore the molecular basis for such anti-RA activity both in vitro using tumor necrosis factor alpha (TNF-α)-stimulated human RA fibroblast-like synoviocytes (RA-FLS) and in vivo using a rat adjuvant-induced arthritis (AIA) model. We found that Gent was able to significantly reduce the swelling of joints and arthritic index scores, with corresponding reductions in synovial inflammatory cell infiltration, synovial hyperplasia, and bone erosion in treated AIA rats. Importantly, Gent 200 mg/kg reduced thymus index in AIA rats, but had no effect on spleen index and body weight, it revealed that Gent was relatively safe at the dose we chose. We further found that Gent was able to suppress the TNF-α-induced proliferation and migration of RA-FLS cells. This suppression was attributed to the ability of Gent to block NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), and caspase-1, thereby disrupting the activation of the NLRP3 inflammasome. Consistent with such suppression, Gent led to a significant decrease in IL-1ß secretion by treated cells. Furthermore, this reduction in NLRP3 inflammasome activation was also associated with decreases in the activation of nuclear factor (NF-κB), the production of reactive oxygen species (ROS), and the expression of inflammatory IL-6. Together these findings indicate that Gent can suppress the ROS-NF-κB-NLRP3 axis to alleviate RA symptoms. CHEMICAL COMPOUNDS STUDIED IN THIS ARTICLE: Gentiopicroside (PubChem CID: 88708).

Effects of rotigotine and rotigotine extended-release microsphere therapy on myocardial ischemic injury in mice.

Rotigotine is a dopamine receptor agonist that can improve motor function in Parkinson's disease (PD) patients. Rotigotine extended-release microsphere (RoMS) is an extended-release intramuscular formulation that exhibits a sustained release of rotigotine over a 14-day period. The clinical trials of RoMS has been carried out in USA and China. The purpose of this study is to observe the effects of RoMS therapy on myocardial ischemic injury in mice, to know whether RoMS alleviate or deteriorate the myocardial ischemic injury while PD patient has onset of myocardial ischemia concurrent after administered with RoMS. A mouse model of myocardial ischemia was established using isoproterenol, and mice were pretreated with rotigotine or RoMS before inducing myocardial ischemic injury. The effects of rotigotine or RoMS therapy on the degree of myocardial ischemic injury were studied by evaluating troponin I level, creatine kinase-MB (CK-MB) activity, and histopathological changes in cardiomyocytes. The dopamine receptor blocker chlorpromazine was used to further investigate the effects of rotigotine or RoMS on myocardial ischemic injury. Furthermore, serum rotigotine concentrations were also assayed. When myocardial ischemia occurred during rotigotine or RoMS administration, troponin I level and CK-MB activity were decreased, and ischemia-induced histopathological changes in cardiomyocytes were alleviated. The effects of rotigotine were maintained only 12 h and after that no protective effect was observed. RoMS releases continuously into the circulation after intramuscular injection. The cardioprotective effects of RoMS were maintained 14 days after a single RoMS administration. When combined with chlorpromazine, the protective effects of rotigotine on myocardial ischemic injury were eliminated, and the protective effects of RoMS were also partially abolished. In the animal model of myocardial ischemia, pretreatment with rotigotine or RoMS does not deteriorate, but can alleviate cardiomyocyte injury. Furthermore, RoMS pretreatment show long-term and continuous protective effects on cardiomyocyte injury. RoMS therapy in PD patients at high risk for cardiovascular diseases may attenuate the degree of cardiomyocyte injury caused by ischemia.

Ginsenoside Rg1 attenuates adjuvant-induced arthritis in rats via modulation of PPAR-γ/NF-κB signal pathway.

Ginsenoside Rg1, the main active compound in Panax ginseng, has already been shown to have anti-inflammatory effects. However, the protective effects of Rg1 on rheumatoid arthritis (RA) remain unclear. The aim of the present study was to investigate the effects and mechanisms of Rg1 on adjuvant-induced arthritis (AIA) in rats. AIA rats were given Rg1 at doses of 5, 10, and 20 mg/kg intraperitoneally for 14 days to observe the anti-arthritic effects. The results showed that Rg1 significantly alleviated joint swelling and injuries. Rg1 can also significantly reduce the level of TNF-α and IL-6, increase PPAR-γ protein expression, inhibit IκBα phosphorylation and NF-κB nuclear translocation in the inflammatory joints of AIA rats and RAW264.7 cells stimulated by lipopolysaccharide (LPS). The results indicate that Rg1 has therapeutic effects on AIA rats, and the mechanism might be associated with its anti-inflammatory effects by up-regulating PPAR-γ and subsequent inhibition of NF-κB signal pathway.

[Improved laparoscopic Vechitti procedure for constructing a functioning vagina].

OBJECTIVE: To investigate the clinical effect of improved laparoscopic Vechitti procedure for constructing a functioning vagina. METHODS: By using the method of raising vestibular mucosa, 18 patients with congenital absence of vagina and uterus underwent surgery in our hospital. No cave was made between bladder and rectum. The procedure involved puncturing the vulvar vestibulum pit with an epidural paracentetic needle or specially-made needle into abdominal cavity through rectovesical interspace, two drag-lines was introduced through anterior abdominal wall, using the line to tie a clothes button of 2.0-2.5 cm diameter to the vulva, rasing the lines day by day, the vestibule go upward along with the button, then the vagina was formed. RESULTS: After the procedures, the artificial vagina of all 18 patients could hold a speculum and the mucosa appeared soft and smooth with normal lubrication. The vulvar tissues appeared uninjured and normal in all cases. The married patients were satisfactory to the intercourse. One case of vagino-rectal fistula was observed in a patient after she rode a bicycle with the vaginal mould. CONCLUSION: The improved laparoscopic Vechitti procedure for constructing a functioning vagina has less trauma than conventional operation and is easy to operate. Therefore, the new improved procedure is a preferred way in constructing vagina for treating those patients.