Modified Suanzaorentang Had the Treatment Effect for Generalized Anxiety Disorder for the First 4 Weeks of Paroxetine Medication: A Pragmatic Randomized Controlled Study.

Background. Paroxetine does not show satisfactory therapeutic effect for generalized anxiety disorder (GAD) patients for the first 2-4 weeks of medication. Diazepam is always concurrently used although it has some shortcomings such as physical dependence and withdrawal reactions. In this study, we aimed to identify whether modified Suanzaorentang (MSZRT), a combined Chinese formula including Suanzaorentang (SZRT) and Zhizichitang (ZZCT), could control the anxiety of GAD for the first 4 weeks of paroxetine medication. Methods. 156 GAD patients were randomized to the treatment of paroxetine, paroxetine-diazepam, or paroxetine-MSZRT for 4 weeks. Hamilton Anxiety Scale (HAMA) Test and Self-Rating Anxiety Scale (SAS) Test were determined each week as the evaluation of clinical efficacy. Adverse events (AEs) were also closely observed by performing the Treatment Emergent Symptom Scale (TESS) Test. Results. Both paroxetine-MSZRT and paroxetine-diazepam decreased more HAMA and SAS total scores than paroxetine from weeks 1 to 3. Paroxetine-MSZRT as well as paroxetine-diazepam had an obviously higher onset rate than paroxetine in each week. After 4 weeks' treatment, the overall effectiveness rate in the paroxetine-MSZRT group (90.00%) was obviously higher than those of the paroxetine group (74.42%) but did not significantly differ from the paroxetine-diazepam group (93.88%). Conclusion. MSZRT had the treatment effect for GAD when paroxetine was used for the first 4 weeks.

Sinomenine prevents metastasis of human osteosarcoma cells via S phase arrest and suppression of tumor-related neovascularization and osteolysis through the CXCR4-STAT3 pathway.

Osteosarcoma is the most common primary malignant tumor of the bone. The long-term survivals continue to be unsatisfactory for patients with metastatic and recurrent disease. Metastasis is still a severe challenge in osteosarcoma treatment. Sinomenine, an alkaloid from traditional Chinese medicine, has been proved to possess potent antitumor and anti-invasion effect on various cancers. However, the effect of sinomenine on human osteosarcoma and the underlying mechanisms remains unknown. We report here that sinomenine inhibited proliferation by inducing S phase arrest and suppressing the clone formation. Significant inhibitory effects were found in invasion and metastasis in osteosarcoma, but little cytotoxicity was observed in tested concentrations. Exposure to sinomenine resulted in suppression of invasion and migration in osteosarcoma cells as well as tube formation ability in the human umbilical vein endothelial cells (HUVEC) and U2OS cells. Furthermore, it demonstrated that CXCR4 played a key role contributing to invasion in osteosarcoma which is considered to be a core target site in sinomenine treatment. Sinomenine inhibited invasion by suppressing CXCR4 and STAT3 phosphorylation then downregulating the expression of MMP-2, MMP-9, RANKL, VEGF downstream. In addition, then RANKL-mediated bone destruction stimulated by osteoclastogenesis and VEGF-related neovascularization were restrained. Importantly, in vivo, sinomenine suppressed proliferation, osteoclastogenesis and bone destruction. Through these various comprehensive means, sinomenine inhibits metastasis in osteosarcoma. Taken together, our results revealed that sinomenine caused S phase arrest, inhibited invasion and metastasis via suppressing the CXCR4-STAT3 pathway and then osteoclastogenesis-mediated bone destruction and neovascularization in osteosarcoma. Sinomenine is therefore a promising adjuvant agent for metastasis control in osteosarcoma.

[Effect of acupuncture on early onset of SSRIs treating depressive disorder and related indicators of neuroimmunology].

OBJECTIVE: To observe the intervention effect of acupuncture on early onset of selec- tive serotonin reuptake inhibitors (SSRIs) in treating depressive disorder, and to study its effect on ser- um 5-HT and unbalanced inflammatory cytokines secreted by TH1/TH2. METHODS: Totally 90 patients with depressive disorder were randomly assigned to the drug control group (as the control group, 45 cases) and the acupuncture combined drug treatment group (as the treatment group, 45 cases). All patients were treated for 4 consecutive weeks. Another 45 healthy subjects were recruited as a healthy control group. The effect of acupuncture on early onset of SSRls in treating acute phase depressive disorder pa- tients was evaluated by HAMD score in the control group and the treatment group before treatment,and at weekends of the 1st, 2nd, and 4th week after treatment. Besides, their serum levels of 5-HT, IL-1ß and IL-6 (secreted by TH1), and IL-4 and IL-10 (secreted by TH2) were detected before treatment and after treatment at the weekend of the 4th week. RESULTS: Compared with the healthy control group,serum lev- els of 5-HT, IL-4, and IL-10 decreased in the two drug-treated groups before treatment (P < 0.01); serum levels of IL-1ß and IL-6 increased (P <0.01). Compared with before treatment in the same group, HAMD score decreased in the control group at weekends of the 2nd and the 4th week after treatment (P < 0.01); HAMD scores decreased in the treatment group at weekends of the 1st, 2nd, 3rd,and 4th week after treatment (P < 0.01); serum levels of 5-HT, IL-4, and IL-10 increased,serum levels of IL-1ß and IL- 6 decreased in the two drug-treated groups after treatment (all P < 0.01). Compared with the control group at the same time point,HAMD scores decreased in the treatment group at weekends of the 1st, 2nd,3rd,and 4th week after treatment (P < 0.01),serum levels of 5-HT, IL-4, and IL-10 increased (P < 0.05, P < 0.01), serum levels of IL-6 decreased (P < 0. 01). CONCLUSION: Acupuncture could accelerate early onset of SSRIs in treating acute phase depressive disorder, and effectively regulate serum 5-HT levels and inflammatory cytokines secreted by TH1/TH2.

Protective effect of panaxatriol saponins extracted from Panax notoginseng against MPTP-induced neurotoxicity in vivo.

AIM OF THE STUDY: Panaxatriol saponins (PTS), the main constituents extracted from Panax notoginseng, a Chinese herbal medicine, has been shown to be an effective agent on various diseases. Our previous study has demonstrated that PTS is an inducer of thioredoxin-1 (Trx-1) and has a possible potential as a therapeutic agent for Parkinson's disease (PD). However, the effect of PTS on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in vivo is unknown. MATERIALS AND METHODS: Using locomotor activity test and traction test, we detected the effect of PTS on MPTP-induced behavioral impairment. Tyrosine hydroxylase, Trx-1, cyclooxygenase-2, pro-caspase-9, pro-caspase-12 and caspase-3 expressions in the anatomical region of substantia nigra pars compacta (SNc) were tested by Western blot. RESULTS: PTS provided neuroprotection against the loss of dopaminergic neurons and behavioral impairment caused by MPTP. MPTP-induced neuronal death in the SNc was suppressed by PTS through increasing Trx-1 expression, suppressing cyclooxygenase-2 over-expression and inhibiting mitochondria-mediated apoptosis. CONCLUSIONS: PTS, an inducer of Trx-1, has pluripharmacological properties in the protection against PD including enhancing antioxidant activity, acting as neurotrophic factor, modulating inflammation and inhibiting mitochondria-mediated apoptosis.

Panaxatriol saponins extracted from Panax notoginseng induces thioredoxin-1 and prevents 1-methyl-4-phenylpyridinium ion-induced neurotoxicity.

AIM OF THE STUDY: Thioredoxin-1 has various biologic activities, including the control of redox balance and the inhibition of apoptosis. The current study was designed to examine the effects of panaxatriol saponins (PTS) extracted from Panax notoginseng on thioredoxin-1 expression and 1-methyl-4-phenylpyridinium ion-induced injury. MATERIALS AND METHODS: Using PC12 cells and Kunming mice, we test thioredoxin-1 expression after PTS treatment by Western blot. The protective effect of PTS against 1-methyl-4-phenylpyridinium ion-induced injury was assessed by MTT assay and LDH release assay. RESULTS: PTS induced thioredoxin-1 expression in vitro and in vivo, and attenuated 1-methyl-4-phenylpyridinium ion-induced cell death of PC12 cells. CONCLUSIONS: PTS is a new inducer of thioredoxin-1 and has a possible potential as a therapeutic agent for neurodegenerative diseases including Parkinson's disease.