Beneficial effect of astragalosides on stroke condition using PC12 cells under oxygen glucose deprivation and reperfusion.

Astragalosides (AST) are reported to be neuroprotective in focal cerebral ischemic models in vivo. In this study, the direct effect of AST against oxygen and glucose deprivation (OGD) including neuronal injury and the underlying mechanisms in vitro were investigated. 5 h OGD followed by 24 h of reperfusion [adding back oxygen and glucose (OGD-R)] was used to induce in vitro ischemia reperfusion injury in differentiated rat pheochromocytoma PC12 cells. AST (1, 100, and 200 µg/mL) were added to the culture after 5 h of the OGD ischemic insult and was present during the reoxygenation phases. A key finding was that OGD-R decreased cell viability, increased lactate dehydrogenase, increased reactive oxygen species, apoptosis, autophagy, functional impairment of mitochondria, and endoplasmic reticulum stress in PC12 cells, all of which AST treatment significantly reduced. In addition, AST attenuated OGD-R-induced cell loss through P38 MAPK activation a neuroprotective effect blunted by SB203580, a specific inhibitor of P38 MAPK. Our data suggest that both apoptosis and autophagy are important characteristics of OGD-R-induced PC12 death and that treating PC12 cells with AST blocked OGD-R-induced apoptosis and autophagy by suppressing intracellular oxidative stress, functional impairment of mitochondria, and endoplasmic reticulum stress. Our data provide identification of AST that can concomitantly inhibit multiple cells death pathways following OGD injuries in neural cells.

Effects of electroacupuncture on benign prostate hyperplasia patients with lower urinary tract symptoms: a single-blinded, randomized controlled trial.

We tested the effect of electroacupuncture (EA) on lower urinary tract symptoms (LUTS) in benign prostatic hyperplasia (BPH) patients. A total of 42 BPH patients with LUTS were randomly assigned to either the EA group (EG), received 2 Hz EA for 20 min twice/week for a total of twelve treatments, or a sham EA group (CG), received sham EA. The increase of voiding volume, average flow rate, and maximal flow rate in the EG were 32.2 ± 104.4 mL, 1.2 ± 1.6 mL/sec, and 2.3 ± 3.7 mL/sec, respectively, from baseline value (before EA) using the measurement of an uroflowmetry. These increases were greater than -37.9 ± 120.4, -0.22 ± 2.7, and -0.3 ± 4.3, respectively, in the CG (P = .038, .026, and .030, resp.). The changes of prostate special antigen and international prostatic symptom score were not significantly different between two groups (P = .573, .175, resp.), suggesting the clinical improvement of 2 Hz EA was quite limited to the LUTS of patients with BPH.

Acupuncture on Renal Function in Patients with Chronic Kidney Disease: A Single-Blinded, Randomized, Preliminary Controlled Study.

OBJECTIVE: To evaluate the feasibility effect of acupuncture on renal function in patients with chronic kidney disease (CKD). METHODS: In total, 59 patients with CKD were randomized into acupuncture (AG; n = 30) and sham acupuncture (CG; n = 29) treatment groups. In the AG, acupuncture was applied to bilateral Hegu (LI4), Zusanli (ST36), and Taixi (KI3) to obtain qi, and electroacupuncture (2 Hz) was applied to two acupoint pairs (right Zusanli and Taixi and left Zusanli and Taixi) once per week for 12 weeks. In the CG, the acupuncture methods were identical to in the AG, and the acupuncture needle was applied to the subcutaneous layer at 1.5 cm lateral to the aforementioned acupoints, without electrical discharge. The levels of serum creatinine and estimated glomerular filtration rate (eGFR) were measured at 3 months (observation period; O), immediately before the acupuncture treatment (baseline; B), at 12 weeks (after treatment completion; T12), and at the 3-month follow-up (postacupuncture treatment; P). RESULTS: In total, 53 patients (AG, n = 28; CG, n = 25) with CKD completed the trial. The serum creatinine levels at baseline (B) were 1.45 mg/dL in the AG and 1.67 mg/dL in the CG (p = 0.1298). Furthermore, the change in serum creatinine levels after the acupuncture treatment (T12) was 1.41 mg/dL in the AG and 1.65 mg/dL in the CG (p = 0.0489). The eGFR at baseline was 51.85 mL/min/1.73 m2 in the AG and 42.50 mL/min/1.73 m2 in the CG (p = 0.0855). The change in the eGFR after the acupuncture treatment was 54.50 mL/min/1.73 m2 in the AG and 43.60 mL/min/1.73 m2 in the CG (p = 0.0470). CONCLUSION: Acupuncture at bilateral Hegu, Zusanli, and Taixi for 12 weeks reduced creatinine levels and increased eGFR levels. The study only provided a feasibility method for the treatment of patients with CKD. However, the results of this preliminary study warrant further investigation.

Celastrol inhibits dengue virus replication via up-regulating type I interferon and downstream interferon-stimulated responses.

ETHNOPHARMACOLOGICAL RELEVANCE AND AIM OF THE STUDY: Tripterygium wilfordii (lei gong teng; Thunder of God Vine), a member of the Celastraceae family, is a medicinal plant used to treat a range of illnesses. Celastrol is a quinone methide triterpene and the most abundant bioactive constituent isolated from the root extracts of T. wilfordii. Previous studies have shown that celastrol exhibits antiviral activity against HIV and SARS-CoV. To date, no investigations of the anti-DENV activity of celastrol have been reported. This work aimed to investigate the anti-DENV effect and possible mechanism of celastrol in vitro and in vivo. METHODS: A four-serotype DENV infection system was performed to determine the anti-DENV effect of celastrol by detecting DENV RNA replication and protein synthesis. The precise anti-DENV replication mechanism of celastrol was clarified using specific RNA silencing and specific inhibitor. In addition, the therapeutic efficacy of celastrol was evaluated by monitoring survival rates and clinical scores in a DENV-infected Institute of Cancer Research (ICR) suckling mouse model. RESULTS: Celastrol inhibited DENV-1, -2, -3, and -4 RNA replication with EC50 values of 0.19 ± 0.09, 0.12 ± 0.11, 0.16 ± 0.14, and 0.17 ± 0.08 µM, respectively. This antiviral effect of celastrol was associated with celastrol-induced interferon-α (IFN-α) expression and was attenuated by a specific inhibitor of the JAK-STAT signaling pathway downstream of IFN-α or specific shRNA. Furthermore, celastrol protected ICR suckling mice against life-threatening DENV infection. CONCLUSION: Celastrol represents a potential anti-DENV agent that induces IFN-α expression and stimulates a downstream antiviral response, making the therapy a promising drug or dietary supplement for the treatment of DENV-infected patients.

Schisandrin A inhibits dengue viral replication via upregulating antiviral interferon responses through STAT signaling pathway.

Dengue virus (DENV) infects 400 million people worldwide annually. Infection of more than one serotype of DENV highly corresponds to dengue hemorrhagic fever and dengue shock syndrome, which are the leading causes of high mortality. Due to lack of effective vaccines and unavailable therapies against DENV, discovery of anti-DENV agents is urgently needed. We first characterize that Schisandrin A can inhibit the replication of four serotypes of DENV in a concentration- and time-dependent manner, with an effective half-maximal effective concentration 50% (EC50) value of 28.1 ± 0.42 µM against DENV serotype type 2 without significant cytotoxicity. Furthermore, schisandrin A can effectively protect mice from DENV infection by reducing disease symptoms and mortality of DENV-infected mice. We demonstrate that STAT1/2-mediated antiviral interferon responses contribute to the action of schisandrin A against DENV replication. Schisandrin A represents a potential antiviral agent to block DENV replication in vitro and in vivo. In conclusion, stimulation of STAT1/2-mediated antiviral interferon responses is a promising strategy to develop antiviral drug.

Sulforaphane Suppresses Hepatitis C Virus Replication by Up-Regulating Heme Oxygenase-1 Expression through PI3K/Nrf2 Pathway.

Hepatitis C virus (HCV) infection-induced oxidative stress is a major risk factor for the development of HCV-associated liver disease. Sulforaphane (SFN) is an antioxidant phytocompound that acts against cellular oxidative stress and tumorigenesis. However, there is little known about its anti-viral activity. In this study, we demonstrated that SFN significantly suppressed HCV protein and RNA levels in HCV replicon cells and infectious system, with an IC50 value of 5.7 ± 0.2 µM. Moreover, combination of SFN with anti-viral drugs displayed synergistic effects in the suppression of HCV replication. In addition, we found nuclear factor erythroid 2-related factor 2 (Nrf2)/HO-1 induction in response to SFN and determined the signaling pathways involved in this process, including inhibition of NS3 protease activity and induction of IFN response. In contrast, the anti-viral activities were attenuated by knockdown of HO-1 with specific inhibitor (SnPP) and shRNA, suggesting that anti-HCV activity of SFN is dependent on HO-1 expression. Otherwise, SFN stimulated the phosphorylation of phosphoinositide 3-kinase (PI3K) leading Nrf2-mediated HO-1 expression against HCV replication. Overall, our results indicated that HO-1 is essential in SFN-mediated anti-HCV activity and provide new insights in the molecular mechanism of SFN in HCV replication.

Traditional Chinese medicine treatments for upper respiratory tract infections/common colds in Taiwan.

INTRODUCTION: Traditional Chinese medicine (TCM) has been used to treat upper respiratory tract infections/common colds (URTIs) in Asian countries for over 2000 years. However, Chinese medicine doctors (CMDs) follow the traditional treatment rules to select or administer these diverse Chinese medicine formulae. The main purpose of our study was to explore data on the frequency of medication and medication habits by CMDs for the treatment of URTIs with Chinese herbs and Chinese medicine formulae. METHODS: The TCM treatments for patients consulting with an URTIs were analyzed from the National Health Insurance Research Database using the appropriate codes from the International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses for Taiwan in 2009. A data mining and association rules, were used to analyze co-prescriptions of TCM for patients with URTIs. RESULTS: For 472,005 patients who sought the treatment of URTIs, a total of 46,805 patients with URTIs received TCM treatments, of these 29,052 patients sought both TCM and Western medication treatments. Of the URTIs patients who had received a TCM treatment, 79% presented with an acute common cold, 9% had influenza, and 9% had acute upper respiratory infections. Furthermore, 53.89% of the sample were aged between 20 and 49 years, and 62.84% were women, 3.56% of the patients used Yin-Qiao-San and 2.76% used Jie-Geng. Yin-Qiao-San and Ma-Xing-Gan-Shi-Tang were the most commonly combinations of prescriptions for patients with URTIs. CONCLUSIONS: The patients experiencing URTIs were more likely to request TCM treatment if their symptoms were mild and they were women. The Chinese medicine doctors treating URTIs generally followed TCM theory. A coding system for TCM diagnostic classifications could improve evaluations of TCM treatments.

Acupuncture stimulation and neuroendocrine regulation.

Acupuncture has been used to treat different conditions for at least 3000 years in China and has gained increasing acceptance worldwide. The acupuncture needle inserted into the muscle layer at the acupoint produces the so-called obtaining qi sensation that causes the excitation of A-δ and C-fibers of the muscle tissue, resulting in afferent signals. The afferent signals pass through the dorsal horn cells of the spinal cord ascending to the brain, such as the hypothalamus, enhancing the release of neuropeptides and hormones, and these afferent signals in the spinal segment may innervate the visceral organ, inducing effect on visceral function. Here, we reviewed the effect of acupuncture stimulation on neuropeptides and hormones, including ß-endorphin, serotonin, oxytocin, adrenocorticotropic hormone, gonadotropin-releasing hormone, corticotrophin-releasing hormone, cholecystokinin, and acetylcholine, as well as insulin sensitivity, immunomodulation (anti-inflammation), and autonomic nerve activity.

Intraocular pressure-lowering effect of auricular acupressure in patients with glaucoma: a prospective, single-blinded, randomized controlled trial.

OBJECTIVE: The objective of the study was to evaluate the effect of auricular acupressure in controlling intraocular pressure (IOP) in patients with glaucoma. DESIGN: Thirty-three (33) patients were recruited through advertisement at the clinic for glaucoma. These patients were divided into the auricular acupressure group (16 patients, 28 glaucoma eyes) and the sham group (17 patients, 32 glaucoma eyes). Patients in the acupressure group received auricular acupoint (kidney, liver, and eye) stimulator tapping and regular massage twice a day for 4 weeks. Patients in the sham group received tapping at sham auricular acupoints (wrist, shoulder, and jaw) without massage stimulation. The IOP and visual acuity (VA) were assessed before and after the treatment in the first 4 weeks and followed up, up to 8 weeks. RESULTS: After the treatment and at the 8-week follow-up, IOP and VA improved significantly in the acupressure group when compared with pretreatment (p < 0.05). The most significant IOP-lowering effect was seen at about 3-4 weeks after auricular acupressure. IOP returned to the initial level after acupressure had been discontinued for 4 weeks. Significant improvement of the uncorrected VA (UCVA) was noted at about 2-4 weeks in the acupressure group. UCVA improvement was also noted in the sham group. The difference was only significant in week 3. Improvement of the best-corrected VA was noted in both groups, but was only significant in week 2. CONCLUSIONS: Our data suggest that auricular acupressure can be used as a complementary treatment to ameliorate IOP and VA for patients with glaucoma.