Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis.

BACKGROUND: The relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy. METHODS: We searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events. RESULTS: Nine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant. CONCLUSIONS: Our results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

The Prognostic Significance of Vitamin D Deficiency in Korean Patients With Multiple Myeloma.

BACKGROUND: Vitamin D deficiency is relatively common among patients with multiple myeloma. The prognostic significance of vitamin D deficiency in Asian patients with multiple myeloma remains unevaluated. This study aimed to assess the prognostic value of vitamin D levels in this Korean patient population. METHODS: From September 2017 to May 2020, 98 patients were enrolled in the study. Vitamin D deficiency was defined as 25-hydroxyvitamin D level of less than 10 ng/mL. RESULTS: Thirty-six patients (36.7%) had vitamin D deficiency. These patients had significantly lower 2-year progression-free survival rates (44.8% vs. 66.9%, P = .008) and overall survival (OS) rates (2-year OS 47.2% vs. 74.2%, P = .024) compared with those without deficiency. Furthermore, patients who received vitamin D supplementation showed a trend towards improved OS compared with those who did not, with a 2-year OS rate of 51.9% vs. 33.3% (P = .14). CONCLUSION: These findings suggest that vitamin D levels are a significant prognostic factor in patients with multiple myeloma.

Effectiveness of the Shugan Jieyu Capsule against Psychiatric Symptoms in Epilepsy: a protocol for systematic review and meta-analysis.

Objectives: Psychiatric symptoms in epilepsy are very common, and the most common symptoms are depression, insomnia, and anxiety. These symptoms not only lower the quality of life of epilepsy patients, but also elevate the risk of epileptic seizures. There are no specific criteria for the available antiepileptic drugs to ameliorate these symptoms in patients with epilepsy, and there is a lack of evidence to support the efficacy and safety of existing drugs. The Shugan Jieyu capsule (SJC) is a traditional herbal medicine composed of Acanthopanax senticosus and Hypericum perforatum and is reported to be effective in relieving psychiatric symptoms. The purpose of this study was to assess the efficacy of SJC as a treatment for psychiatric symptoms in epilepsy patients. Methods: Electronic databases will be investigated for publications in English, Korean, Japanese, and Chinese. The participants of the study are epilepsy patients with psychiatric symptoms diagnosed using any validated criteria. All types of controls will be compared-placebo, conventional treatments, and no treatment-to groups treated with SJC or modified SJC. We will measure the degree of improvement in psychiatric symptoms and check epileptic symptoms, such as the frequency of seizures. The study selection and data extraction will be performed by two independent reviewers, who will also assess methodological quality using the risk-of-bias tool by Cochrane. We will use Review Manager software (RevMan) to carry out all statistical analyses. Results: This systematic review and meta-analysis will be performed in accordance with the PRISMA-P statement. Conclusion: This systematic review is the first study to assess the efficacy and safety of SJC for the treatment of psychiatric symptoms in epilepsy. We expect that this study will provide clinically applicable evidence for patients with epilepsy when selecting drug treatments.

Effect of Korean Red Ginseng extracts on drug-drug interactions.

BACKGROUND: Ginseng has been the subject of many experimental and clinical studies to uncover the diverse biological activities of its constituent compounds. It is a traditional medicine that has been used for its immunostimulatory, antithrombotic, antioxidative, anti-inflammatory, and anticancer effects. Ginseng may interact with concomitant medications and alter metabolism and/or drug transport, which may alter the known efficacy and safety of a drug; thus, the role of ginseng may be controversial when taken with other medications. METHODS: We extensively assessed the effects of Korean Red Ginseng (KRG) in rats on the expression of enzymes responsible for drug metabolism [cytochrome p450 (CYP)] and transporters [multiple drug resistance (MDR) and organic anion transporter (OAT)] in vitro and on the pharmacokinetics of two probe drugs, midazolam and fexofenadine, after a 2-wk repeated administration of KRG at different doses. RESULTS: The results showed that 30 mg/kg KRG significantly increased the expression level of CYP3A11 protein in the liver and 100 mg/kg KRG increased both the mRNA and protein expression of OAT1 in the kidney. Additionally, KRG significantly increased the mRNA and protein expression of OAT1, OAT3, and MDR1 in the liver. Although there were no significant changes in the metabolism of midazolam to its major metabolite, 1'-hydroxymidazolam, KRG significantly decreased the systemic exposure of fexofenadine in a dose-dependent manner. CONCLUSION: Because KRG is used as a health supplement, there is a risk of KRG overdose; thus, a clinical trial of high doses would be useful. The use of KRG in combination with P-glycoprotein substrate drugs should also be carefully monitored.

Prevalence of treated epilepsy in Korea based on national health insurance data.

The Korean national health security system covers the entire population and all medical facilities. We aimed to estimate epilepsy prevalence, anticonvulsant utilization pattern and the cost. We identified prevalent epilepsy patients by the prescription of anticonvulsants under the diagnostic codes suggesting seizure or epilepsy from 2007 Korean National Health Insurance databases. The information of demography, residential area, the kind of medical security service reflecting economic status, anticonvulsants, and the costs was extracted. The overall prevalence of treated epilepsy patients was 2.41/1,000, and higher for men than women. The age-specific prevalence was the lowest in those in their thirties and forties. Epilepsy was more prevalent among lower-income individuals receiving medical aid. The regional prevalence was the highest in Jeju Island and lowest in Ulsan city. New anticonvulsants were more frequently used than old anticonvulsants in the younger age group. The total annual cost of epilepsy or seizure reached 0.46% of total medical expenditure and 0.27% of total expenditure on health. This is the first nationwide epidemiological report issued on epilepsy in Korea. Epilepsy prevalence in Korea is comparable to those in developed countries. Economic status and geography affect the prevalence of epilepsy.

TANK-binding kinase 1 (TBK1) controls cell survival through PAI-2/serpinB2 and transglutaminase 2.

The decision between survival and death in cells exposed to TNF relies on a highly regulated equilibrium between proapoptotic and antiapoptotic factors. The TNF-activated antiapoptotic response depends on several transcription factors, including NF-κB and its RelA/p65 subunit, that are activated through phosphorylation-mediated degradation of IκB inhibitors, a process controlled by the IκB kinase complex. Genetic studies in mice have identified the IκB kinase-related kinase TANK-binding kinase 1 (TBK1; also called NAK or T2K) as an additional regulatory molecule that promotes survival downstream of TNF, but the mechanism through which TBK1 exerts its survival function has remained elusive. Here we show that TBK1 triggers an antiapoptotic response by controlling a specific RelA/p65 phosphorylation event. TBK1-induced RelA phosphorylation results in inducible expression of plasminogen activator inhibitor-2 (PAI-2), a member of the serpin family with known antiapoptotic activity. PAI-2 limits caspase-3 activation through stabilization of transglutaminase 2 (TG2), which cross-links and inactivates procaspase-3. Importantly, Tg2(-/-) mice were found to be more susceptible to apoptotic cell death in two models of TNF-dependent acute liver injury. Our results establish PAI-2 and TG2 as downstream mediators in the antiapoptotic response triggered upon TBK1 activation.

Ebselen attenuates cisplatin-induced ROS generation through Nrf2 activation in auditory cells.

Ebselen, an organoselenium compound that acts as a glutathione peroxidase mimetic, has been demonstrated to possess antioxidant and anti-inflammatory activities. However, the molecular mechanism underlying this effect is not fully understood in auditory cells. The purpose of the present study is to investigate the protective effect of ebselen against cisplatin-induced toxicity in HEI-OC1 auditory cells, organotypic cultures of cochlear explants from two-day postnatal rats (P(2)) and adult Balb/C mice. Pretreatment with ebselen ameliorated apoptotic death induced by cisplatin in HEI-OC1 cells and organotypic cultures of Corti's organ. Ebselen pretreatment also significantly suppressed cisplatin-induced increases in intracellular reactive oxygen species (ROS), intracellular reactive nitrogen species (RNS) and lipid peroxidation levels. Ebselen dose-dependently increased the expression level of an antioxidant response element (ARE)-luciferase reporter in HEI-OC1 cells through the translocation of Nrf2 into the nucleus. Furthermore, we found that pretreatment with ebselen significantly restored Nrf2 function, whereas it ameliorated the cytotoxicity of cisplatin in cells transfectants with either a pcDNA3.1 (control) or a DN-Nrf2 (dominant-negative) plasmid. We also observed that Nrf2 activation by ebselen increased the expression of phase II antioxidant genes, including heme oxygenase (HO-1), NAD(P)H:quinine oxidoreductase, and gamma-glutamylcysteine synthetase (gamma-GCS). Treatment with ebselen resulted in an increased expression of HO-1 and intranuclear Nrf2 in hair cells of organotypic cultured cochlea. After intraperitoneal injection with cisplatin, auditory brainstem responses (ABRs) threshold was measured on 8th day in Balb/C mice. ABR threshold shift was marked occurred in mice injected with cisplatin (16 mg/kg, n=5; Click and 8-kHz stimuli, p<0.05; 4, 16 and 32 kHz, p<0.01), whereas that of animal group which was treated with cisplatin and ebselen was not significantly changed. These results suggest that ebselen activates the Nrf2-ARE signaling pathway, which ultimately prevents free radical stresses from cisplatin and further contributes to protect auditory sensory hair cells from free radicals produced by cisplatin.

Antiinflammatory effect of Daesiho, a Korean traditional prescription for cerebral infarct patients.

Daesiho, a prescription composed of eight herbal mixtures, has been widely used in the treatment of cerebral infarct in Oriental medicine. However, the mechanisms by which the formula affects the production of pro-inflammatory cytokines in cerebral infarct patients remains unknown. The levels of secretory protein pro-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6, were significantly increased in both lipopolysaccharide (LPS) and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from cerebral infarct patients and LPS-stimulated THP-1 differentiated macrophage-like cells (THP-1/M). However, pretreatment with Daesiho significantly inhibited the secretion of pro-inflammatory cytokines, including TNF-alpha, IL-1beta, and IL-6, in stimulated PBMCs and THP-1/M cells. In addition, Daesiho significantly suppressed mRNA expression of pro-inflammatory cytokines. Therefore, these data indicate that Daesiho may be beneficial in the cessation of inflammatory processes of cerebral infarction through suppression of the production of pro-inflammatory cytokines via inhibition of mRNA expression.

Chaga mushroom (Inonotus obliquus) induces G0/G1 arrest and apoptosis in human hepatoma HepG2 cells.

AIM: To investigate the anti-proliferative and apoptotic effects of Chaga mushroom (Inonotus obliquus) water extract on human hepatoma cell lines, HepG2 and Hep3B cells. METHODS: The cytotoxicity of Chaga extract was screened by 3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide (MTT) assay. Morphological observation, flow cytometry analysis, Western blot were employed to elucidate the cytotoxic mechanism of Chaga extract. RESULTS: HepG2 cells were more sensitive to Chaga extract than Hep3B cells, as demonstrated by markedly reduced cell viability. Chaga extract inhibited the cell growth in a dose-dependent manner, which was accompanied with G0/G1-phase arrest and apoptotic cell death. In addition, G0/G1 arrest in the cell cycle was closely associated with down-regulation of p53, pRb, p27, cyclins D1, D2, E, cyclin-dependent kinase (Cdk) 2, Cdk4, and Cdk6 expression. CONCLUSION: Chaga mushroom may provide a new therapeutic option, as a potential anticancer agent, in the treatment of hepatoma.

Hibiscus sabdariffa L. water extract inhibits the adipocyte differentiation through the PI3-K and MAPK pathway.

Hibiscus sabdariffa L., a tropical beverage material and medical herb, is used commonly as in folk medicines against hypertension, pyrexia, inflammation, liver disorders, and obesity. This report was designed to investigate the inhibitory mechanisms of hibiscus extract on adipocyte differentiation in 3T3-L1 preadipocytes. The possible inhibitory pathways that regulate the adipocyte differentiation contain the adipogenic transcription factors, C/EBPalpha and PPARgamma, PI3-kinase, and MAPK pathway. In this study, we examined whether hibiscus extract affected the adipogenesis via these three pathways. To differentiate preadipocyte in adipocyte, confluent 3T3-L1 preadipocytes were treated with the hormone mixture including isobutylmethylxanthine, dexamethasone, and insulin (MDI). Hibiscus extract inhibited significantly the lipid droplet accumulation by MDI in a dose-dependent manner and attenuated dramatically the protein and mRNA expressions of adipogenic transcriptional factors, C/EBPalpha and PPARgamma, during adipogenesis. The increase of phosphorylation and expression of PI3-K/Akt during adipocytic differentiation was markedly inhibited by treatment with hibiscus extract or PI3-K inhibitors. Furthermore, the phosphorylation and expression of MEK-1/ERK known to regulate the early phase of adipogenesis were clearly decreased with the addition of hibiscus extract. Taken together, this report suggests that hibiscus extract inhibits the adipocyte differentiation through the modulation of PI3-K/Akt and ERK pathway that play pivotal roles during adipogenesis.

Antidiabetic effect of a prodrug of cysteine, L-2-oxothiazolidine-4-carboxylic acid, through CD38 dimerization and internalization.

CD38 is a bifunctional enzyme synthesizing (ADP-ribosyl cyclase) and degrading (cyclic ADP-ribose (cADPR) hydrolase) cADPR, a potent Ca(2+) mobilizer from intracellular pools. CD38 internalization has been proposed as a mechanism by which the ectoenzyme produced intracellular cADPR, and thiol compounds have been shown to induce the internalization of CD38. Here, we show that the disulfide bond between Cys-119 and Cys-201 in CD38 may be involved in CD38 dimerization and internalization. We tested the effect of a reducing agent, l-2-oxothiazolidine-4-carboxylic acid (OTC), a prodrug of cysteine, on CD38 internalization in pancreatic islets. OTC enhanced insulin release from isolated islets as well as CD38 internalization and cytoplasmic Ca(2+) level. Furthermore, islet cells treated with antisense CD38 oligonucleotide showed inhibition of OTC-induced insulin secretion. Intake of OTC in db/db mice ameliorated glucose tolerance, insulin secretion, and morphology of islets when compared with control mice. These data indicate that OTC improves glucose tolerance by enhancing insulin secretion via CD38/cADPR/Ca(2+) signaling machinery. Thus, OTC may represent a novel class of antidiabetic drug.