A Randomized Double-Blind, Placebo-Controlled Study on Anti-Stress Effects of Nelumbinis Semen.

Introduction: Depression is a serious and common mental disease that causes low mood and loss of interest in activities. Nelumbinis semen (NS) has been widely used as a treatment for depression for hundreds of years in many Asian countries. Water extract of nelumbinis semen (WNS) is a standardized herbal medicine made from NS. Methods: The objective of the present research was to perform a randomized, double-blind, placebo-controlled trial to estimate the efficacy of WNS for improving depressive and stress symptoms using Beck depression inventory (BDI) and the stress response inventory (SRI) in 45 adults diagnosed with major depression or other forms of depressive disorders. They were randomized to either a placebo-treated group, a 2.4 g per day WNS-treated group, or a 4.8 g per day WNS-treated group. BDI and SRI were determined in order to evaluate changes in depression before and after two weeks of WNS treatment. Results: The average BDI and SRI of the 2.4 g WNS-treated group were significantly (p < 0.05) improved compared to those of the placebo-treated group. Their BDI subscale A (negative attitudes towards self) and subscale C (somatic disturbances), SRI E, and depression subscale of SRI were substantially shorter (p < 0.05). In addition, an analysis of collected EEG data of participants showed a significant increase in alpha/beta activity in the 4.8 g WNS-treated group, which might be explained as an advancement of their depression symptoms (p < 0.05). Conclusions: These results suggest that WNS treatment can decrease depression. Our study provides preliminary evidence for the safety of WNS and its potential to decrease depression.

Woohwangcheongsimwon Prevents High-Fat Diet-Induced Memory Deficits and Induces SIRT1 in Mice.

Woohwangcheongsimwon (WHC) is a mixture of herbal medicines that is widely prescribed in Korean traditional medicine. SIRT1 is known for its regulatory roles in energy metabolism, oxidative stress, and circadian rhythms. This study was designed to determine whether WHC can increase and mimic the biological reactions of SIRT1 activation. Ten-month-old male mice were divided into four groups: nontreated normal diet (ND), nontreated high-fat diet (HFD), WHC-treated ND, and WHC-treated HFD. Body weight and cognitive functions were evaluated after treatment. The hippocampal expressions of SIRT1 and PGC-1α were also measured. The components of WHC were identified by liquid chromatography. High-fat diet-fed mice gained more weight and demonstrated greater deficits in short-term and long-term cognitive functions. WHC suppressed the deleterious effects of a HFD on weight gain and cognitive decline, but showed no prominent effects on animals fed NDs. The herbal treatment also increased the expression of SIRT1 and PGC-1α in the hippocampus. Despite the induction of hippocampal SIRT1 expression by WHC, resveratrol was not present among the natural compounds identified. This expression might have contributed to the suppression of high-fat diet-induced memory deficits in mice treated with the herbal mixture.

Effect of an herbal mixture of Cinnamon Cortex, Persicae Semen, and Natril Sulfas on collagen-induced arthritis and lipopolysaccharides-induced nuclear factor-κ B signaling.

OBJECTIVE: To investigate the anti-arthritic and anti-inflammatory effects of the mixture of three herbal agents, Cinnamon Cortex, Persica Semen, and Natril Sulfas (CPN), the major ingredients of Taoren Chengqi Decoction (). METHODS: Collagen-induced arthritis (CIA) was induced by immunization with bovine type II collagen on day 1 and 21. DBA/1J mice were orally administered the water extract of CPN (100 and 500 mg/kg) and indomethacin (1 mg/kg) or vehicle (water) 3 times per week for 6 weeks. Arthritic symptoms were recorded on day 29, 31, 33, 36 and 38. On sacrififi ce, serum was obtained for inflammatory markers and anti-collagen antibodies as well as arthritic joints were obtained for histologic analysis. For the evaluation of in vitro anti-inflammatory mechanism of CPN, peritoneal macrophages were isolated from thioglycollate injected C57BL/6 mice and stimulated with lipopolysaccharides (LPS) for 15 min in the presence of CPN extract. Levels of inhibitor of NF-κB α isoform (IκBα), phospho-p38, phospho-C-Jun N-terminal kinases (JNK) and phospho-extracellular signal-regulated kinase 1/2 (ERK1/2) were detected by Western blot. RESULTS: Compared with mice in CIA group, oral administration of CPN signififi cantly reduced the clinical scores (P<0.05), histological analysis revealed the protective effect of CPN on inflamed joints. Serum levels of the pro-inflammatory markers tumor necrosis factor-α, interleukin-6 and prostaglandin E2, but not anti-collagen antibodies, were significantly reduced (P<0.05). CPN did not affect the activation of p38, JNK and ERK1/2 but inhibited LPS-induced IκBα degradation, a required event prior to the translocation of NF-κB to the nucleus. CONCLUSIONS: The ameliorating effect of CPN on arthritis progression seems to be mediated by its anti-inflammatory effect, without affecting antibody response. As a supplementary agent, CPN could be benefifi cial for treatment of CIA.

MicroRNA134 Mediated Upregulation of JNK and Downregulation of NFkB Signalings Are Critically Involved in Dieckol Induced Antihepatic Fibrosis.

Though Dieckol, a phlorotannin of Ecklonia cava, was known to have antioxidant, anticancer, antidiabetic, and anti-inflammatory effects, the underlying antifibrotic mechanism of Dieckol still remains unclear until now. Thus, in the current study, the inhibitory mechanism of Dieckol on liver fibrosis was elucidated mainly in hepatic stellate cells (HSCs). Dieckol exerted cytotoxicity in LX-2, HSC-T6, and HepG2 cells with the reduced fibrosis features of large, spread out, and flattened polygonal shapes in LX-2 cells compared to untreated control. Dieckol attenuated the expression of α-SMA and TGF-ß1, increased sub-G1 phase population, and induced caspase-3 activation and cleavages of PARP in HSCs. Furthermore, Dieckol decreased phosphorylation of ERK, p38, AKT, NF-kB, and IkB and activated the microRNA(miR)134 level and JNK phosphorylation in HSCs. Conversely, JNK inhbitor SP600125 reversed the effect of Dieckol on PARP, p-NF-kB, α -SMA, and p-JNK in LX-2 cells. Likewise, miR134 overexpression mimic enhanced phosphorylation of JNK and NF-kB and reduced the expression of α-SMA and PARP cleavage, while miR134 inhibitor reversed the ability of Dieckol to cleave PARP and attenuate the expression of α-SMA in LX-2 cells. Overall, our findings suggest that Dieckol suppresses liver fibrosis via caspase activation and miR134 mediated JNK activation and NF-kB inhibition.

Preclinical evidence of rapid-onset antidepressant-like effect in Radix Polygalae extract.

Radix Polygalae (the root of Polygala tenuifolia) is a herb widely used in traditional Asian medicine that is thought to exert a variety of neuropsychiatric effects. Radix Polygalae extract can protect against N-methyl D-aspartate (NMDA) neurotoxicity and induce brain-derived neurotrophic factor (BDNF) expression, suggesting modulatory roles at glutamatergic synapses and possible antidepressant action. In accordance with this hypothesis, Radix Polygalae extract demonstrated antidepressant-like effects in 8-week-old male C57Bl/6 mice by decreasing behavioral despair in the forced swim and tail suspension tasks and increasing hedonic-like behavior in the female urine sniffing test 30 minutes after a single oral administration of 0.1 mg/kg. Reduced latency to acquire a food pellet in the novely suppressed feeding paradigm, without change in anxiety-like behaviors suggested a rapid-onset nature of the antidepressant-like effect. In addition, it decreased the number of failed escapes in the learned helplessness paradigm after two oral administrations 24 hours and 30 minutes before the first test. Finally, it reversed anhedonia as measured by saccharin preference in mice exposed to the chronic stress model after two administrations of 0.1 mg/kg, in contrast to the repeated administration generally needed for similar effect by monoamergic antidepressants. Immobility reduction in tail suspension task was blocked by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist NBQX, a pattern previously demonstrated by ketamine and other ketamine-like rapid-onset antidepressants. Also similarly to ketamine, Radix Polygalae appeared to acutely decrease phosphorylation of GluR1 serine-845 in the hippocampus while leaving the phosphorylation of hippocampal mTOR serine 2448 unchanged. These findings serve as preclinical evidence that Radix Polygalae extract exerts rapid-onset antidepressant effects by modulating glutamatergic synapses in critical brain circuits of depression and may be worthy of further evaluation as a safe substitute to other rapid-onset antidepressants known to have unacceptable side effects.

Inhibition of Hypoxia Inducible Factor Alpha and Astrocyte-Elevated Gene-1 Mediates Cryptotanshinone Exerted Antitumor Activity in Hypoxic PC-3 Cells.

Although cryptotanshinone (CT) was known to exert antitumor activity in several cancers, its molecular mechanism under hypoxia still remains unclear. Here, the roles of AEG-1 and HIF-1α in CT-induced antitumor activity were investigated in hypoxic PC-3 cells. CT exerted cytotoxicity against prostate cancer cells and suppressed HIF-1α accumulation and AEG-1 expression in hypoxic PC-3 cells. Also, AEG-1 was overexpressed in prostate cancer cells. Interestingly, HIF-1α siRNA transfection enhanced the cleavages of caspase-9,3, and PAPR and decreased expression of Bcl-2 and AEG1 induced by CT in hypoxic PC-3 cells. Of note, DMOG enhanced the stability of AEG-1 and HIF-1α during hypoxia. Additionally, CT significantly reduced cellular level of VEGF in PC-3 cells and disturbed tube formation of HUVECs. Consistently, ChIP assay revealed that CT inhibited the binding of HIF-1α to VEGF promoter. Furthermore, CT at 10 mg/kg suppressed the growth of PC-3 cells in BALB/c athymic nude mice by 46.4% compared to untreated control. Consistently, immunohistochemistry revealed decreased expression of Ki-67, CD34, VEGF, carbonic anhydrase IX, and AEG-1 indices in CT-treated group compared to untreated control. Overall, our findings suggest that CT exerts antitumor activity via inhibition of HIF-1α, AEG1, and VEGF as a potent chemotherapeutic agent.

Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models.

BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols.

Protective effect of the methanol extract from Cryptotaenia japonica Hassk. against lipopolysaccharide-induced inflammation in vitro and in vivo.

BACKGROUND: In folk medicine, the aerial part of Crytotaenia japonica Hassk. (CJ), is applied for treatment of the common cold, cough, urinary problems, pneumonia, and skin rashes. In this paper, the in vitro and in vivo anti-inflammatory activity of CJ methanol extract was tested using lipopolysaccharide (LPS)-induced inflammatory models. METHODS: We measured nitric oxide (NO), inducible NO synthase (iNOS), and inflammatory cytokine levels from LPS-stimulated mouse peritoneal macrophages. Also, several cellular signaling molecules which regulate the expressions of these inflammatory markers were examined. Finally, we tested whether oral administration of CJ methanol extract might affect the serum cytokine levels in LPS-injected mice. RESULTS: CJ methanol extract reduced NO release via iNOS protein inhibition. The extract was also shown to decrease the secretions of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-12. Analysis of signaling molecules showed that CJ inhibited the phosphorylation of STAT1, p38, JNK and ERK1/2 as well as IκBα degradation. Finally, CJ decreased the serum levels of TNF-α and IL-6 in LPS-injected mice. CONCLUSIONS: Our results demonstrated the anti-inflammatory activity of CJ methanol extract and its possible underlying mechanisms that involve modulation of IκBα, MAPK, and STAT1 activities.

Acupressure for treating neurological disorders: a systematic review.

The objective of this review is to assess the clinical evidence for or against acupressure as a treatment for neurological disorders. We searched the literature from 12 databases from their inception to July 2010. We included any type of controlled clinical trial (CCT) in which patients with neurological disorders were treated with acupressure. The methodological quality of all clinical trials was assessed using the Cochrane risk of bias analysis. In total, two randomized clinical trials (RCTs) and four CCTs were included. Four studies (one RCT and three CCTs) compared the effects of acupressure with routine care or no treatment in patients with stroke and showed significant effects of acupressure on improving patient function and symptoms. One RCT, which compared acupressure with sham acupressure and no treatment in patients with headache, also showed that acupressure significantly reduced headache severity and pain. However, all trials were open to methodological limitations and a high risk of bias. In conclusion, current evidence showing that acupressure is an effective treatment for improving function and symptoms in patients with stroke is limited. However, the evidence is insufficient to draw conclusions concerning the effects of acupressure on other neurological disorders. More rigorous studies are warranted.

Antiplatelet effects of Spatholobus suberectus via inhibition of the glycoprotein IIb/IIIa receptor.

ETHNOPHARMACOLOGICAL RELEVANCE: The vine stem of Spatholobus suberectus is a widely used blood-activating and stasis-dispelling medicine for the treatment of diseases related to blood stasis syndrome in traditional medicine in Korea, Japan, and China. AIM OF THE STUDY: To demonstrate the clinical effects of Spatholobus suberectus against blood stasis syndromes using in vitro and in vivo platelet aggregation studies and to investigate its exact mechanisms. MATERIALS AND METHODS: We extracted vine stems of Spatholobus suberectus, using 95% EtOH (SSE) and investigated its antiplatelet activity on platelet aggregation induced by collagen and ADP in human platelet-rich plasma (PRP). For the mechanism study, a glycoprotein IIb/IIIa (GP IIb/IIIa) assay using flow cytometric analysis and a thromboxane A(2) (TXA(2)) assay were performed. In addition, we investigated the effects of SSE in a thromboembolic mouse model. RESULTS: SSE significantly inhibited ADP- and collagen-induced platelet aggregation in human PRP concentration-dependently without affecting plasma clotting time. It also significantly inhibited fibrinogen binding to the GP IIb/IIIa receptor and partly inhibited the formation of TXA(2). In the in vivo study, oral administration of SSE dose-dependently suppressed the death of thromboembolism model mice induced by intravenous injection of collagen plus epinephrine. CONCLUSIONS: SSE showed antiplatelet activity without anticoagulant effects mainly through the inhibition of fibrinogen binding to the GP IIb/IIIa receptor. Our current results support the clinical usage of SSE in the East Asian region treating atherothrombotic diseases and may represent a new natural source to develop antiplatelet agents.