Sinomenine inhibits the inflammatory responses of human fibroblast-like synoviocytes via the TLR4/MyD88/NF-κB signaling pathway in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder mainly characterized by inflammation of the synovial tissue that can lead to destruction of bone and cartilage. Sinomenine is an alkaloid extracted from the stem of the Chinese medicinal plant Sinomenium acutum. It has been reported that sinomenine has immunosuppressive and anti-inflammatory properties. However, the molecular mechanism underlying the effect of sinominine on IL-1ß-induced human RA fibroblast-like synoviocytes (RAFLS) is poorly understood. Therefore, in this study, we investigated the effect of sinomenine on the expression of inflammatory cytokines in IL-1ß-treated human RAFLS in vitro and the underlying mechanism. RAFLS viability was evaluated using the MTS assay after sinomenine treatment. The levels of inflammatory cytokines were measured with ELISA, RT-PCR and western blot, respectively. The levels of TLR4 and its downstream signaling targets were determined by western blot analysis. We found that sinomenine suppressed not only NO and PGE2 production but also iNOS and COX-2 expression in IL-1ß-induced RAFLS. It also inhibited the expression of TNF-α and IL-6 in IL-1ß-stimulated RAFLS. Furthermore, sinomenine prevented IL-1ß-induced TLR4, MyD88 and p-NF-κB p65 expression. Taken together, these results demonstrated that sinomenine prevented IL-1ß-induced inflammation in human RAFLS at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway, suggesting that sinomenine could be a potential agent in the treatment of RA.

Curcumin inhibits osteoclastogenic potential in PBMCs from rheumatoid arthritis patients via the suppression of MAPK/RANK/c-Fos/NFATc1 signaling pathways.

The aim of the present study was to determine the effects of curcumin on the osteoclastogenic potential of peripheral blood mononuclear cells (PBMCs) obtained from patients with rheumatoid arthritis (RA), and to investigate the underlying molecular mechanisms. PBMCs from patients with RA (n=12) and healthy controls (n=10) were cultured to assess osteoclastogenic potential. The number of tartrate­resistant acid phosphatase­positive osteoclasts differentiated from PBMCs isolated from patients with RA was significantly increased compared with that of the healthy controls. In addition, the osteoclast number in patients with RA was correlated with the clinical indicators, Sharp score (r=0.810; P=0.001) and lumbar T­score (r=­0.685; P=0.014). Furthermore, the resorption area was increased in the RA group compared with the healthy controls. The mRNA and protein expression levels in PBMC­derived osteoclasts treated with curcumin were measured by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. Curcumin inhibited the osteoclastogenic potential of PBMCs, potentially by suppressing activation of extracellular signal­regulated kinases 1 and 2, p38 and c­Jun N­terminal kinase, and inhibiting receptor activator of nuclear factor κB (RANK), c­Fos and nuclear factor of activated T cells (NFATc1) expression. The results of the present study demonstrated that curcumin may inhibit the osteoclastogenic potential of PBMCs from patients with RA through the suppression of the mitogen­activated protein kinase/RANK/c­Fos/NFATc1 signaling pathways, and that curcumin may be a potential novel therapeutic agent for the treatment of bone deterioration in inflammatory diseases such as RA.

Synthesis and anti-BVDV activity of novel δ-sultones in vitro: implications for HCV therapies.

In this study we report the synthesis and activity against bovine viral diarrhea virus (BVDV) of a novel series of bicycle δ-sultones containing γ-lactones. BVDV is responsible for major losses in cattle. Some of the synthesized δ-sultones showed pronounced anti-BVDV activity with EC50 values of 0.12-1.0µM and no significant cytotoxicity. Among them, the ortho bromosubstituted derivative 4f (EC50=0.12µM) showed better antiviral activity than other derivatives and was 10 fold more that of than positive control ribavirin (EC50=1.3µM). BVDV is also considered to be a valuable surrogate for the hepatitis C virus (HCV) in antiviral drug studies. The above results provided a novel candidate for the development of anti-HCV agents.

Sinomenine decreases MyD88 expression and improves inflammation-induced joint damage progression and symptoms in rat adjuvant-induced arthritis.

Sinomenine (SIN) is the active principle of the Chinese medical plant Sinomenium acutum which is widely used for the treatment of rheumatoid arthritis (RA) in China. Recently, several groups indicated that myeloid differentiation primary response protein 88 (MyD88) might be associated with disease progression of RA. Here, we observed the effect of SIN on MyD88 expression and showed its therapeutic role in RA. First, immunohistochemical staining in clinical specimens showed that MyD88 was mainly located in characteristic pathological structures of RA synovial tissues. Second, we found that MyD88 was overexpressed in the synovial tissues of the rats with adjuvant-induced arthritis (AIA). Treatment with SIN markedly decreased the expression of MyD88 in AIA rats. Finally, we provided evidences that SIN suppressed inflammation response and inflammation-induced joint destructive progression and arthritis symptoms in AIA rats. Therefore, SIN is an effective therapeutic agent for RA. Targeting MyD88 signaling may provide new methods for the treatment of RA.

A facile synthesis, antibacterial activity of pulvinone and its derivatives.

Pulvinone and several 3-fluoro-4-morpholino substituted pulvinone derivatives were synthesized in five steps from a common precursor, phenyl acetic acid. Most of synthetic morpholine substituted pulvinones showed inhibitory activity against Esherichia coli. For the first time, the inhibition of pulvinone and its derivatives against Gram-negative bacteria was reported.

[Effect of acupuncture on serum leptin level in patients with type II diabetes mellitus].

OBJECTIVE: To study the relationship between serum leptin and insulin resistance, and to analyze the effect of acupuncture on serum leptin level in patients with type-II diabetes mellitus (DM). METHODS: A total of 80 type-II DM patients were randomized into acupuncture and medication groups. Acupuncture was applied to Yishu (EX), Feishu (BL13), Pishu (BL 20), etc. according to syndrome identification. The treatment was given once every other day for 12 weeks. For patients in the medication group, Glibenclamide (2.5-7.5 mg/time, 1-2 times/d according to blood sugar level) was given for 12 weeks. Fasting blood glucose (FBG), fasting insulin (FINS) and fasting leptin (FLP) were detected by using glucose oxidase method, radioimmunoassay and ELISA, respectively. Insulin sensitivity index (ISI) and homeostasis model assessment-insulin resistance (HOMA-IR) were calculated. RESULTS: In comparison with pre-treatment, FBG levels and HOMA-IR in both acupuncture and medication groups, and FINS and FLP levels in the acupuncture group were decreased significantly (P < 0.01), while ISI in both acupuncture and medication groups, and FINS level in the medication group were increased remarkably after the treatment (P < 0.01). Comparison between two groups showed that after the treatment, FINS and FLP levels, and HOMA-IR of the acupuncture group were considerably lower than those of the medication group (P < 0.01), while ISI of the acupuncture group was significantly higher than that of the medication group (P < 0.01). CONCLUSION: Acupuncture therapy is effective in lowering FLP level, which may contribute to its clinical effect in improving type-II DM.

[Relationship between lupus headache and headache due to internal injury in traditional Chinese medicine].

In 1999, the nomenclature and case definitions for neuropsychiatric lupus syndromes were published by American College of Rheumatology (ACR), and the cognition of neuropsychiatric damage of systemic lupus erythematosus (SLE) was gradually unified and standardized. Lupus headache is an intractable problem in SLE, especially in SLE patients complicated with multiple organ injury. In general, vascular headache is common in most SLE patients, and a small number of SLE patients complicated with nervous headache are found in clinic. Moreover, its pathophysiological mechanism is far from being understood. Although early diagnosis is essential for good outcomes, the diagnosis method is rather confused in the world. There still exist some limitations in the proposal of clinical classification of headache from ACR and International Headache Society (IHS), and the proposal does not mention the classification of headache related to psychiatric damage. Current therapeutic regimens are almost exclusively based on empirical evidence. Treatment approaches include symptomatic treatment, immunosuppressive, anticoagulant and anti-aggregant therapies. It provides enormous and hopeful space in research of combined therapy strategy, especially in the field of traditional Chinese medicine. The authors discussed the relationship between lupus headache and headache due to internal injury in the view of integrated traditional Chinese and Western medicine, and suggested that the treatment strategy for lupus headache should be made in argument with the headache due to internal injury. Syndrome differentiation treatment according to deficiency in the root and excess in the branch and the therapy for activating blood to dredge collaterals maybe have great advantages in treatment of the headache in SLE.