Danggui­Sayuk­Ga­Osuyu­Senggang­Tang ameliorates cold­induced vasoconstriction in vitro and in vivo.

Danggui-Sayuk-Ga-Osuyu-Senggang-Tang (DSGOST), one of the traditional Chinese medicines, has long been prescribed for patients suffering from Raynaud phenomenon (RP) in Northeast Asian countries, including China, Japan and Korea. Although a previous in vitro study from our laboratory revealed that DSGOST prevents cold (25˚C)­induced RhoA activation and endothelin­1 (ET­1) production in endothelial cells (ECs), the mechanisms by which DSGOST is able to alleviate the symptoms of RP have yet to be fully elucidated. The present study aimed to demonstrate that DSGOST regulates RhoA­mediated pathways in cold­exposed pericytes. In pericytes, DSGOST amplified cold­induced RhoA activation, while markedly reducing ET­1­induced RhoA activation. Additionally, DSGOST­mediated regulation of RhoA was closely associated with Rho­associated, coiled­coil­containing protein kinase 1 (ROCK1)/testis­specific kinase 1 (TESK1)/PDXP, but not with LIM domain kinase 1/2 (LIMK1/2), cofilin and myosin light chain (MLC). Thus, DSGOST activation of RhoA/ROCK1/TESK1/PDXP in cold­exposed pericytes appeared to be crucial for treating vessel contraction. In addition, the DSGOST effect on the RhoA­mediated pathway in cold­induced human umbilical vein endothelial cells or human dermal microvascular endothelial cells was similar to that in ET­1­treated pericytes, but not in cold­induced pericytes. The results of the present study further confirmed that DSGOST inhibits cold­induced contraction of the mouse tail vein in vivo. Furthermore, DSGOST treatment reduced cold­induced expression of the α2c­adrenergic receptor in mouse tail vessels. Therefore, the data in the present study suggest that DSGOST may be useful for the treatment of RP­like disease.

Effects and safety of gyejibongnyeong-hwan on dysmenorrhea caused by blood stagnation: a randomized controlled trial.

Objective. This study was a multicenter, randomized, double-blind, and controlled trial with two parallel arms: the GJBNH group and the placebo group. This trial recruited 100 women aging 18 to 35 years with primary dysmenorrhea caused by blood stagnation. The investigational drugs, GJBNH or placebo, were administered for two menstrual periods (8 weeks) to the participants three times per day. The participants were followed up for two menstrual cycles after the administration. Results. The results were analyzed by the intention-to-treat (ITT) dataset and the per-protocol (PP) dataset. In the ITT dataset, the change of the average menstrual pain VAS score in the GJBNH group was statistically significantly lower than that in the control group. Significant difference was not observed in the SF-MPQ score change between the GJBNH group and the placebo group. No significant difference was observed in the PP analyses. In the follow-up phase, the VAS scores of the average menstrual pain and the maximum menstrual pain continually decreased in the placebo group, but they increased in the GJBNH group. Conclusion. GJBNH treatment for eight weeks improved the pain of the dysmenorrhea caused by blood stagnation, but it should be successively administered for more than two menstrual cycles. Trial Registration. This trial is registered with Current Controlled Trials no. ISRCTN30426947.

Antiinflammatory effects of Epimedium brevicornum water extract on lipopolysaccharide-activated RAW264.7 macrophages.

Epimedium brevicornum Maxim (Berberidaceae) possesses estrogenic properties. It is one of the most widespread herbal remedies used in Oriental medicine. The present study investigated the effects of Epimedium brevicornum water extract (EB) on proinflammatory mediators secreted from lipopolysaccharide (LPS)-induced RAW264.7 macrophages. EB significantly inhibited the production of nitric oxide (NO), interleukin (IL)-3, IL-10, IL-12p40, interferon-inducible protein-10, keratinocyte-derived chemokine, vascular endothelial growth factor, monocyte chemotactic protein-1 and granulocyte macrophage-colony stimulating factor in LPS-induced RAW264.7 cells at concentrations of 25, 50, 100 and 200 µg/mL (p < 0.05). These results suggest that EB has antiinflammatory activity related to its inhibition of NO, cytokine, chemokine and growth factor production in macrophages.

Antidepressant effects of Soyo-san on Immobilization stress in ovariectomized female rats.

Soyo-san is a traditional oriental medicinal formula, a mixture of 9 crude drugs, and it has been clinically used for treating mild depressive disorders. The purpose of the study was to examine the effect of Soyo-san on repeated stress-induced alterations of learning and memory on a Morris water maze (MWM) task and also the anxiety-related behavior on the elevated pulse maze (EPM) in ovariectomized female rats. We assessed the changes in the reactivity of the cholinergic system by measuring the immunoreactive neurons of choline acetyltransferase (ChAT) and reactivity of acetylcholinesterase (AChE) in the hippocampus, and the serum levels of corticosterone were assessed after behavioral testing. The female rats were randomly divided into three groups: the nonoperated and nonstressed group (normal), the ovariectomized and stressed group (control), and the ovariectomized, stressed and Soyo-san treated group (SOY). The rats were exposed to immobilization stress (IMO) for 14 d (2 h/d), and Soyo-san (400 mg/kg, i.p.) was administered 30 min before IMO stress. Treatments with SOY caused significant reversals of the stress-induced deficits in learning and memory on a spatial memory task, and it also produced an anxiolytic-like effect on the EPM, and increased the ChAT and AChE reactivities (p<0.05, respectively). The serum level of corticosterone in the SOY group was significantly lower than that in the control group (p<0.05). These results suggest that Soyo-san might prove to be an effective antidepressant agent.